Clinical Molecular Diagnostics

Foreword
Coordinators
Preface
Acknowledgments
Contents
About the Editors and Contributors
About the Editors
Editorial Board
Contributors
Part I: Principles of Clinical Molecular Diagnostics
	1: Molecules of Disease and Their Detection Methods
		1.1	 Overview
		1.2	 Molecular Mechanism of Diseases
		1.3	 Nucleic Acid Detection Methods
			1.3.1	 Nucleic Acid Amplification Technology
			1.3.2	 Sequencing Technology
			1.3.3	 Nucleic Acid Hybridization Technology
			1.3.4	 Chip Technology
			1.3.5	 Biosensing Technology
		1.4	 Protein Detection Methods
			1.4.1	 Spectrum Technology
			1.4.2	 Protein Chip Technology
			1.4.3	 Labeled Immunoassay
			1.4.4	 Mass Spectrometric Technique
		1.5	 Future Trends
		References
	2: Assay Performance Evaluation
		2.1	 Precision
			2.1.1	 Terminology and Definitions
			2.1.2	 Overview of the Precision Evaluation Process (Fig. 2.1)
			2.1.3	 Features of the EP5-A2 Program
			2.1.4	 EP5-A2 Experimental Protocol and Requirements
				2.1.4.1	 Experimental Preparation
					Experimental Sample
				2.1.4.2	 Experimental Method
				2.1.4.3	 Quality Control
			2.1.5	 Data Collection, Processing, and Statistical Analysis
				2.1.5.1	 Experimental Data Record
				2.1.5.2	 Outlier Test
				2.1.5.3	 Repeatability Estimate
		2.2	 Accuracy
			2.2.1	 Definitions
			2.2.2	 Features of the EP9-A2 Program
			2.2.3	 EP9-A2 Experimental Protocol and Requirements
				2.2.3.1	 Experimental Preparation
					Sample Preparation
					Comparison Method Selection
				2.2.3.2	 Experimental Method
				2.2.3.3	 Quality Control
			2.2.4	 Simple Accuracy Evaluation Plan
				2.2.4.1	 Comparison of Patient Sample Results to Those of Another Procedure
				2.2.4.2	 Method of Setting Reference Materials
					Sources of Reference Materials
					Procedure for Demonstration of Accuracy with Reference Materials
		2.3	 Sensitivity
			2.3.1	 Definitions
			2.3.2	 Discussion of Several Common Terms
			2.3.3	 Lower Limit of Linear Range (LLR), Biological Limit of Detection (BLD), and Functional Sensitivity (FS)
				2.3.3.1	 Lower Limit of Linear Range (LLR)
				2.3.3.2	 Biological Limit of Detection (BLD)
				2.3.3.3	 Functional Sensitivity (FS)
				2.3.3.4	 Experimental Precautions
					Blank Sample
					Detection Limit Sample
					Time Required for the Experiment
			2.3.4	 Limits of Blank, Limits of Detection, and Limits of Quantitation
				2.3.4.1	 Overview
				2.3.4.2	 General Method for Determining the Limits of Blank (LoB)
		2.4	 Analytical Measurement Range
			2.4.1	 Definitions
			2.4.2	 EP6-A Protocol and Requirements
				2.4.2.1	 Experimental Requirements
					Device Familiarization Period
					Duration of the Experiment
					Specimen of the Experiment
						Number of Samples
						Matrix Effects
						Selection of Materials Used to Supplement Samples
						Analyte Range
						Sample Preparation and Value Assignment
				2.4.2.2	 Analytical Sequence
				2.4.2.3	 Preliminary Data Check
					Outlier Inspection
					Determination of the Linear Range
						Degree of Nonlinearity
						Considerations for Random Error
		2.5	 Variation Factors of Pre-analysis
			2.5.1	 Collection, Transport, and Preservation of Nucleic Acid Test Specimens
				2.5.1.1	 Preparation of Specimen Collection Site
				2.5.1.2	 Type and Collection of Specimens
				2.5.1.3	 Sampling and Transport Containers
				2.5.1.4	 Anti-pollution in Specimen Collection
				2.5.1.5	 Evaluation of Sampling Quality
		References
	3: Establishment of Biological Reference Interval
		3.1	 Biological Reference
			3.1.1	 Definitions and Terms
			3.1.2	 Clarifications
		3.2	 Establishment of Biological Reference Interval
			3.2.1	 Protocol Outline for Obtaining Reference Values and Establishing Reference Intervals
				3.2.1.1	 New Analyte or Analytical Method
				3.2.1.2	 Previously Measured Analyte
			3.2.2	 Selection of Reference Individuals
				3.2.2.1	 Exclusion Criteria
				3.2.2.2	 Partitioning Criteria
				3.2.2.3	 Selection of Reference Individuals
				3.2.2.4	 Sample Questionnaire
			3.2.3	 Pre-analytical and Analytical Considerations
			3.2.4	 Analysis of Reference Values
				3.2.4.1	 Minimum Number of Reference Values
				3.2.4.2	 Treatment of Outlying Observations
				3.2.4.3	 Partitioning of Reference Values
		3.3	 Verification of Biological Reference Interval
		3.4	 Description of Biological Reference Interval
			3.4.1	 Laboratory Presentation
			3.4.2	 Manufacturer Presentation
		References
	4: Ethics: Informed Consent, Patient Privacy
		4.1	 Overview
		4.2	 Informed Consent
			4.2.1	 Challenges
			4.2.2	 Regulations and Recommendations
			4.2.3	 What Should Be Included in the Informed Consent?
		4.3	 Patient Privacy and Confidentiality
			4.3.1	 Challenges
			4.3.2	 Regulations and Recommendations
			4.3.3	 How to Protect Patient Privacy?
		4.4	 Conclusion
		References
	5: Bioinformatics
		5.1	 Overview
			5.1.1	 Concept and Background
			5.1.2	 Research Categories
			5.1.3	 Common International Bioinformatics Centers
			5.1.4	 Common Bioinformatics Database
		5.2	 Biological Sequence Analysis
			5.2.1	 Sequence Analysis
			5.2.2	 Multiple Sequence Analysis
			5.2.3	 Molecular Polygenetic Tree
			5.2.4	 Comparative Genomics
		5.3	 Transcriptomics Data Analysis
			5.3.1	 Gene Expression Profile Analysis
			5.3.2	 Functional Enrichment Analysis
			5.3.3	 Timing Analysis
			5.3.4	 Gene Co-expression Network Analysis
			5.3.5	 Analysis of Transcriptional Regulation
		5.4	 Protein Structure Analysis
			5.4.1	 Protein Structure Prediction
			5.4.2	 Protein-Protein Interaction
			5.4.3	 Protein Function Prediction
		5.5	 Bioinformatics and Precision Medicine
			5.5.1	 Bioinformatics and Precision Medical Diagnosis
				5.5.1.1	 Genetic Testing
				5.5.1.2	 Detection of Pathogenic Microorganisms
			5.5.2	 Bioinformatics and Precision Medical Prevention and Treatment
			5.5.3	 Bioinformatics and the Future of Precision Medicine
		References
	6: Report and Consultation
		6.1	 Overview
		6.2	 Genetic Variation and Description
			6.2.1	 The Level of Sequence Variation
			6.2.2	 Content of the Variant Description
			6.2.3	 Types of Variant Sequences
			6.2.4	 Expression of Variant Types Specific Abbreviations Are Used to Describe Different Types of Sequence Variations
			6.2.5	 Reference Sequence
		6.3	 Naming Rules
			6.3.1	 Specific Rules for DNA Levels
			6.3.2	 Detailed Rules for RNA Levels
			6.3.3	 Detailed Rules of Protein Levels
				6.3.3.1	 Amino Acid Coding
				6.3.3.2	 Silent Changes
				6.3.3.3	 Substitutions, Missense Changes
				6.3.3.4	 Amino Acid Deletion
				6.3.3.5	 Frameshift Mutation
				6.3.3.6	 Amino Acid Insertion, Repeat
			6.3.4	 Gene Pharmacology Genotype Terminology
			6.3.5	 Other
		6.4	 Application of Gene Mutation in Disease Diagnosis
			6.4.1	 Genetic Variation and Genetic Diagnosis
			6.4.2	 Application of Genetic Variation Detection in Disease Diagnosis
				6.4.2.1	 Molecular Diagnosis of Mendelian Genetic Disease
				6.4.2.2	 Prenatal Diagnosis and Prenatal and Postnatal Care
				6.4.2.3	 Molecular Genetic Testing of Complex Diseases
				6.4.2.4	 Diagnosis and Treatment of Tumors
				6.4.2.5	 Detection of Pathogenic Microorganisms
		6.5	 What Is Involved Before the Clinical Report
			6.5.1	 Content Covered by the Clinical Report
				6.5.1.1	 The Test Report Should Include the Following
				6.5.1.2	 DNA Sequencing Reports and Explanations Should Include
				6.5.1.3	 Reports and Interpretations of Whole-Exon or Whole-Genome Next-Generation Sequencing Should also Include the Following
			6.5.2	 Clinical Interpretation of the Data
			6.5.3	 Clinical Molecular Diagnostic Testing Process and Precautions
				6.5.3.1	 Clinical Molecular Diagnostic Testing Process
				6.5.3.2	 Precautions for Clinical Reports
		6.6	 Reporting Model and Case Analysis
			6.6.1	 Tumor Molecular Diagnosis Report
				6.6.1.1	 Introduction to Non-small Cell Lung Cancer
				6.6.1.2	 Methods and Test Items for Clinical Molecular Diagnosis of Non-small Cell Lung Cancer
					Source of NSCLC Target Molecule Detection Project
					Detection Method of NSCLC Target Molecule
					For Example
			6.6.2	 Molecular Diagnosis Report of Infectious Diseases
				6.6.2.1	 Introduction to Hepatitis B
				6.6.2.2	 Method and Test Item for Clinical Molecular Diagnosis of Hepatitis B Virus
					Project Source
					Detection Method
					For Example
			6.6.3	 Noninvasive Prenatal Screening Results Report
				6.6.3.1	 Introduction to Noninvasive Prenatal Screening
				6.6.3.2	 Noninvasive Prenatal Screening Method and Test Project for Clinical Molecular Diagnosis
				6.6.3.3	 High Throughput Sequencing
					For Example
			6.6.4	 Genetic Disease Diagnosis Report
				6.6.4.1	 Clinical Molecular Diagnosis of G6PD Deficiency
					Introduction to G6PD Deficiency
					Methods and Test Items for Clinical Molecular Diagnosis of G6PD Deficiency
					Source of G6PD Deficiency Molecular Testing Project
					For Example
		References
	7: Factors Associated with Variation
		7.1	 The Concept
		7.2	 Sampling
			7.2.1	 Specimen Collection
				7.2.1.1	 Time of Collection
				7.2.1.2	 Method of Collection
					Body Position and Part in Blood Collection
					Cuff
					Infusion
				7.2.1.3	 Volume of Specimen
				7.2.1.4	 Precautions for Sample Collection
					Collect Representative Specimens
					Proper Use of Anticoagulant
					Avoid Specimen Hemolysis and Container Contamination
					Avoid Collecting Blood During Infusion
			7.2.2	 Sample Delivery and Preservation
				7.2.2.1	 Sample Delivery
					Delivery Principle
					Specially Assigned People
					Receiving
				7.2.2.2	 Specimen Preservation
		7.3	 Biological Factors
			7.3.1	 Age
				7.3.1.1	 Neonatal
				7.3.1.2	 Children
				7.3.1.3	 The Elderly
			7.3.2	 Gender
			7.3.3	 Season
			7.3.4	 Altitude
			7.3.5	 Biological Cycle
			7.3.6	 Pregnancy
			7.3.7	 Lifestyle
		7.4	 Drugs
			7.4.1	 Interference of Drugs on Routine Inspection in Clinic
				7.4.1.1	 The Impact on Routine Blood Tests Results
				7.4.1.2	 The Impact on Routine Urine Test Results
				7.4.1.3	 The Impact on Routine Stool Test Results
			7.4.2	 Interference of Drugs on Clinical Biochemical Tests
				7.4.2.1	 Drugs Affecting Enzyme Assay
				7.4.2.2	 Drugs Affecting Blood Sugar Assay
				7.4.2.3	 Drugs Affecting Protein Assay
				7.4.2.4	 Drugs Affecting Lipid Assay
				7.4.2.5	 Drugs Affecting Electrolyte Assay
		References
	8: Quality Control and Quality Assurance
		8.1	 Overview
		8.2	 Laboratory Setting and Contamination Control
			8.2.1	 Laboratory Setting
			8.2.2	 Facilities
			8.2.3	 Laboratory Practices
			8.2.4	 Chemical and Enzymatic Controls
		8.3	 Internal Quality Control
			8.3.1	 Quantitative Tests
			8.3.2	 Qualitative Tests
		8.4	 Quality Assessments
			8.4.1	 Quality Indicators
			8.4.2	 External Quality Assessment
			8.4.3	 Auditing Program
		8.5	 Quality Control Material
		8.6	 Verification and Validation
		8.7	 The Process of Detection and Quality Control
			8.7.1	 Pre-analytic Phase
			8.7.2	 Analytic Phase
			8.7.3	 Post-analytical Phase
		8.8	 Personnel
		8.9	 Quality Control of Laboratory Equipment
		8.10	 Reagents and Consumables Quality Control
		8.11	 Quality Improvement
		8.12	 Document Control
		8.13	 Conclusion
		References
	9: Precision Medicine
		9.1	 Evidence-Based Laboratory Medicine
		9.2	 Translational Medicine of Molecular Diagnostic Tests
		9.3	 Molecular Diagnostic Tests in Personalized Medicine
		9.4	 The Application of Pharmacogenomics
		9.5	 Companion Diagnostics
		References
Part II: Molecular Biomarkers and Signals from Diseased Functional Organ
	10: Molecules in Body Systems
		10.1	 Overview
		10.2	 Four Major Families of Small Organic Molecules
			10.2.1	 Sugars Provide an Energy Source for Cells and Are the Subunits of Polysaccharides
			10.2.2	 Fatty Acids Are Precursors for Phospholipids and Other Membrane Components
			10.2.3	 Amino Acids Are the Subunits of Proteins
			10.2.4	 Nucleotides Are the Subunits of DNA and RNA
		10.3	 The Chemistry of Cells Is Dominated by Macromolecules with Remarkable Properties
			10.3.1	 Carbohydrates
			10.3.2	 Lipids
			10.3.3	 Nucleic Acids
			10.3.4	 Proteins
		References
	11: Molecules in Signal Pathways
		11.1	 Overview
		11.2	 Functions
			11.2.1	 The Change of Signal Transduction Molecules Is the Basis of Signal Transduction
				11.2.1.1	 Signal Transduction Molecules Constitute the Network of Signal Transduction Pathways
				11.2.1.2	 The Change in the Conformation and Activity of Signal Transduction Molecules Is the Basis of Signal Transduction
				11.2.1.3	 Changes of Intracellular Signal Transduction Molecule Content and Translocation Are Important Ways of Signal Transduction Regulation
			11.2.2	 Signal Transduction Molecules Are Important Targets for Drug Action
		11.3	 Signal Pathways
			11.3.1	 Apoptosis
				11.3.1.1	 The BCL-2 Family
				11.3.1.2	 Caspases
				11.3.1.3	 Inhibitors of Apoptotic Proteins
			11.3.2	 PI3K/AKT/mTOR Signal Pathway
				11.3.2.1	 Phosphatidylinositide 3 Kinase
				11.3.2.2	 Akt
				11.3.2.3	 Mammalian Target of Rapamycin
			11.3.3	 Wnt Signal Pathway
				11.3.3.1	 Wnt
				11.3.3.2	 Adenomatous Polyposis Coli
				11.3.3.3	 β-Catenin
				11.3.3.4	 c-Myc
			11.3.4	 Mitogen-Activated Protein Kinase Signal Pathway
				11.3.4.1	 Extracellular Signal-Regulated Kinase 1/2
				11.3.4.2	 c-Jun Terminal Kinases
				11.3.4.3	 p38
			11.3.5	 JAK/STAT Signal Pathway
				11.3.5.1	 JAKs
				11.3.5.2	 STATs
			11.3.6	 Angiogenesis
			11.3.7	 Notch Signal Pathway
		11.4	 Important Molecules
			11.4.1	 PD-1/PD-L1
			11.4.2	 HIF-1
			11.4.3	 p53
			11.4.4	 Tumor Specific Protein 70
		References
	12: Endocrine and Metabolism
		12.1	 Overview
		12.2	 Insulin
			12.2.1	 Sources and Characteristic
			12.2.2	 Methods
			12.2.3	 Reference Interval for Healthy Persons
			12.2.4	 Clinical Significance
				12.2.4.1	 The Application in the Diagnosis and Treatment of Diabetes
				12.2.4.2	 The Application in the Hypoglycemia Syndrome
				12.2.4.3	 The Application in the Diagnosis of Insulin Beta Cell Tumor
				12.2.4.4	 The Application of Other Diseases in the Diagnosis and Treatment
		12.3	 C-Peptide
			12.3.1	 Source and Characteristics
			12.3.2	 Methods
			12.3.3	 Reference Interval for Healthy Persons
			12.3.4	 Clinical Significance
		12.4	 Glycosylated Hemoglobin (HbA1c)
			12.4.1	 Sources and Characteristics
			12.4.2	 Methods
			12.4.3	 Reference Interval for Healthy Persons
			12.4.4	 Clinical Significance
			12.4.5	 Conclusions and Prospects
		12.5	 IGFBP-2
			12.5.1	 Sources and Characteristics
			12.5.2	 Methods
			12.5.3	 Reference Interval for Healthy Persons
			12.5.4	 Clinical Significance
			12.5.5	 Conclusions and Prospects
		12.6	 Thyroid Markers
			12.6.1	 The Function of Thyroid
			12.6.2	 Laboratory Evaluation of Thyroid
				12.6.2.1	 Tests That Asses the Hypothalamic-Pituitary-Thyroid Axis
					T3 and T4
					TSH and TRH
					FT4 and FT3
				12.6.2.2	 Tests for Evaluation of Thyroid Autoimmunity
					TG-Ab and TPO-Ab
					TR-Ab
			12.6.3	 Conclusions and Prospects
		12.7	 Adrenal Gland Markers
			12.7.1	 Structure of Adrenal Gland
			12.7.2	 Function of Adrenal Gland
			12.7.3	 Laboratory Examination of Adrenal Gland
				12.7.3.1	 Tests That Assess the Level of Adrenal Medullary Hormone
				12.7.3.2	 Tests That Asses the Level of Adrenocortical Hormone
					Examinations of Glucocorticoids and Their Metabolites in Blood, Urine, and Saliva
					Examination of ATCH and N-POMC in Plasma
					Dynamic Functional Test
					Dexamethasone Inhibition Test
				12.7.3.3	 Genetic Testing
			12.7.4	 Conclusion
		12.8	 The Relevant Progress
		References
	13: Immune System
		13.1	 Overview
			13.1.1	 Autoimmune Diseases
			13.1.2	 Hypersensitive Diseases
				13.1.2.1	 Markers of Type I Hypersensitivity Diseases
				13.1.2.2	 Markers of Type II Hypersensitivity Diseases
				13.1.2.3	 Markers of Type III Hypersensitivity Diseases
				13.1.2.4	 Markers of Type IV Hypersensitivity Diseases
		13.2	 Tissue-specific Autoantibodies
			13.2.1	 Anti-intrinsic Factor Antibody (AIFA)
			13.2.2	 Anti-parietal Cell Antibody
			13.2.3	 Anti-smooth Muscle Antibody
			13.2.4	 Anti-liver/Kidney Microsome Antibody
			13.2.5	 Anti-pituitary Antibody
			13.2.6	 Anti-thyroid Antibody
			13.2.7	 Anti-glutamic Acid Decarboxylase Antibody
			13.2.8	 Anti-islet Cell Antibody
			13.2.9	 Anti-insulin Antibody
			13.2.10 Anti-adrenocortical Antibody
			13.2.11 Anti-glomerular Basement Membrane Antibody
		13.3	 Systemic Autoantibodies
			13.3.1	 Anti-mitochondrial Antibody
			13.3.2	 Human Anti-globulin Antibody
			13.3.3	 Anti-cold Agglutinin Antibody
			13.3.4	 Anti-nuclear Antibody
			13.3.5	 Anti-extractable Nuclear Antibody
				13.3.5.1	 Anti-Smith Antibody
				13.3.5.2	 Anti-SSA/Ro Antibody and Anti-SSB/La Antibody
				13.3.5.3	 Anti-RNP Antibody
				13.3.5.4	 Anti-topoisomerase Antibody (ATA)/Anti-Scl-70 Antibody
			13.3.6	 Anti-cardiolipin Antibody
			13.3.7	 Anti-DNA Antibody
				13.3.7.1	 Anti-dsDNA Antibody
				13.3.7.2	 Anti-ssDNA Antibody
			13.3.8	 Anti-histone Antibody
			13.3.9	 Anti-centromere Antibody
			13.3.10 Anti-p62 Antibody (AP62A)/Anti-sp100 Antibody/Anti-glycoprotein-210 Antibody (AGPA, Anti-gp210, Anti-nup210, Anti-np210)
			13.3.11 Rheumatoid Factor
			13.3.12 Anti-citrullinated Peptide Antibody (Anti-CCP Antibody)
			13.3.13 Anti-glucose-6-Phosphate Isomerase (Anti-G6PI)
			13.3.14 Antineutrophil Cytoplasmic Antibody
			13.3.15 Rh Antibody
			13.3.16 Anti-erythrocyte Antibody
			13.3.17 Anti-HLA Antibody
			13.3.18 Prospects for Autoantibodies
		13.4	 Immunoglobulin E
		13.5	 Relevant Activated Cell Markers
			13.5.1	 Mast Cells
			13.5.2	 Eosinophil Activation Marker
			13.5.3	 The Activation Markers of Basophil and Neutrophil
			13.5.4	 T Lymphocyte Immunophenotype
		13.6	 Complement System
		13.7	 Circulation Immune Complex
		13.8	 Other Markers
			13.8.1	 Cytokines
			13.8.2	 Proteins and Enzymes
		13.9	 The Relevant Progress
		References
	14: Lipoproteins
		14.1	 Overview
			14.1.1	 Basic Concepts
			14.1.2	 Functions and Metabolic Pathways of Various Lipoproteins
				14.1.2.1	 Chylomicrons Transport Exogenous Triglycerides and Cholesterol
				14.1.2.2	 Very Low-Density Lipoproteins Transport Endogenous Triglycerides
				14.1.2.3	 Low-Density Lipoprotein Transports Endogenous Cholesterol
				14.1.2.4	 High-Density Lipoprotein Transports Cholesterol in Reverse Fashion
			14.1.3	 Lipoprotein Metabolic Disturbances
				14.1.3.1	 Hyperlipoproteinemia
					Primary Hyperlipoproteinemia
					Hyperlipoproteinemia
					Secondary Hyperlipoproteinemia
					Clinical Manifestations of Hyperlipoproteinemia
					Diagnostic Criteria for Hyperlipoproteinemia
				14.1.3.2	 Hypolipoproteinemia
				14.1.3.3	 Lipoprotein Metabolic Disturbance and Atherosis
					Factors Leading to Atherosis
						Lipoprotein Remnants
						Modified LDL
						Type B LDL
						LP(a)
		14.2	 Total Cholesterol
			14.2.1	 Sources and Characteristics
			14.2.2	 Detection Methods and Reference Values of Healthy People
				14.2.2.1	 Detection Methods
				14.2.2.2	 Reference Values of Healthy Individuals
				14.2.2.3	 Clinical Significance
				14.2.2.4	 Related Progress
		14.3	 Triglycerides
			14.3.1	 Sources and Characteristics
			14.3.2	 Detection Methods and Reference Values of Healthy Individuals
				14.3.2.1	 Detection Methods
				14.3.2.2	 Reference Values of Healthy Individuals
				14.3.2.3	 Clinical Significance
				14.3.2.4	 Related Progress
		14.4	 Free Fatty Acids
			14.4.1	 Sources and Characteristics
			14.4.2	 Detection Methods and Reference Values of Healthy Individuals
				14.4.2.1	 Detection Methods
				14.4.2.2	 Reference Values of Healthy Individuals
				14.4.2.3	 Clinical Significance
		14.5	 Phospholipids
			14.5.1	 Sources and Characteristics
			14.5.2	 Detection Methods and Reference Values of Healthy People
				14.5.2.1	 Detection Methods
				14.5.2.2	 Reference Values of Healthy Individuals
				14.5.2.3	 Clinical Significance
		14.6	 Lipoprotein
			14.6.1	 High-Density Lipoprotein
				14.6.1.1	 Sources and Characteristics
				14.6.1.2	 Detection Methods and Reference Values of Healthy Individuals
					Detection Methods
				14.6.1.3	 Reference Values of Healthy Individuals
				14.6.1.4	 Clinical Significance
				14.6.1.5	 Related Progress
			14.6.2	 Low-Density Lipoprotein
				14.6.2.1	 Sources and Characteristics
				14.6.2.2	 Detection Methods and Reference Values of Healthy Individuals
					Detection Methods
					Reference Values of Healthy Individuals
				14.6.2.3	 Clinical Significance
				14.6.2.4	 Related Progress
			14.6.3	 Small and Dense Low-Density Lipoprotein
				14.6.3.1	 Sources and Characteristics
				14.6.3.2	 Detection Methods and Reference Values of Healthy Individuals
					Detection Methods
					Reference Values of Healthy Individuals
				14.6.3.3	 Clinical Significance
				14.6.3.4	 Related Progress
			14.6.4	 Lipoprotein (a)
				14.6.4.1	 Sources and Characteristics
				14.6.4.2	 Detection Methods and Reference Values of Healthy Individuals
					Detection Methods
					Reference Values of Healthy Individuals
				14.6.4.3	 Clinical Significance
				14.6.4.4	 Related Progress
		References
	15: Transport and Carrier Proteins
		15.1	 Overview
		15.2	 Apolipoprotein AI (AI, ApoAI)
			15.2.1	 Sources and Characteristics
			15.2.2	 Detection Methods and Reference Values of Healthy Individuals
				15.2.2.1	 Detection Methods
				15.2.2.2	 Reference Values of Healthy Individuals
			15.2.3	 Clinical Significance
			15.2.4	 Related Progression
		15.3	 Apolipoprotein B
			15.3.1	 Sources and Characteristics
			15.3.2	 Detection Methods and Reference Values of Healthy Individuals
				15.3.2.1	 Detection Methods
				15.3.2.2	 Reference Values of Healthy Individuals
			15.3.3	 Clinical Significance
			15.3.4	 Related Progress
		15.4	 Apolipoprotein B/Apolipoprotein AI Ratio (ApoB/ApoAI Ratio)
			15.4.1	 Sources and Characteristics
			15.4.2	 Detection Methods and Reference Values of Healthy Individuals
				15.4.2.1	 Detection Methods
				15.4.2.2	 Reference Values of Healthy Individuals
			15.4.3	 Clinical Significance
			15.4.4	 Related Progress
		15.5	 Apolipoprotein CII and CIII
			15.5.1	 Sources and Characteristics
			15.5.2	 Detection Methods and Reference Values of Healthy Individuals
				15.5.2.1	 Detection Method
				15.5.2.2	 Reference Values of Healthy Individuals
			15.5.3	 Clinical Significance
			15.5.4	 Related Progress
		15.6	 Apolipoprotein E
			15.6.1	 Sources and Characteristics
			15.6.2	 Detection Methods and Reference Values of Healthy Individuals
				15.6.2.1	 Detection Methods
				15.6.2.2	 Reference Values of Healthy Individuals
			15.6.3	 Clinical Significance
			15.6.4	 Related Progress
		15.7	 Apolipoprotein H
			15.7.1	 Sources and Characteristics
			15.7.2	 Detection Methods
				15.7.2.1	 Detection Methods
				15.7.2.2	 Reference Value of Healthy Individuals
			15.7.3	 Clinical Significance
			15.7.4	 Research Progress
		15.8	 Apolipoprotein M
			15.8.1	 Sources and Characteristics
			15.8.2	 Detection Methods and Reference Values of Healthy Individuals
				15.8.2.1	 Detection Methods
				15.8.2.2	 Reference Values of Healthy Individuals
			15.8.3	 Clinical Significance
			15.8.4	 Research Progress
		References
	16: Coagulation and Fibrinolysis
		16.1	 Overview
		16.2	 Fibrinogen
			16.2.1 Sources and Characteristics
			16.2.2 Detection Method and Reference Range
			16.2.3 Clinical Significance
		16.3	 D-Dimer
			16.3.1 Sources and Characteristics
			16.3.2 Detection Method
			16.3.3 Healthy Person Reference Range
			16.3.4 Clinical Significance
		16.4	 Fibrinogen/Fibrin Degradation Product
			16.4.1 Sources and Characteristics
			16.4.2 Detection Method
			16.4.3 Healthy Person Reference Range
			16.4.4 Clinical Significance
		16.5	 Protein C
			16.5.1 Sources and Characteristics
			16.5.2 Detection Method
			16.5.3 Healthy Person Reference Range
			16.5.4 Clinical Significance
		16.6	 Protein S
			16.6.1 Sources and Characteristics
			16.6.2 Detection Method
			16.6.3 Healthy Person Reference Range
			16.6.4 Clinical Significance
		16.7	 Antithrombin
			16.7.1 Sources and Characteristics
			16.7.2 Detection Method
			16.7.3 Healthy Person Reference Range
			16.7.4 Clinical Significance
		16.8	 Plasminogen
			16.8.1 Sources and Characteristics
			16.8.2 Detection Method
			16.8.3 Healthy Person Reference Range
			16.8.4 Clinical Significance
		16.9	 α2-Plasmin Inhibitor
			16.9.1 Sources and Characteristics
			16.9.2 Detection Method
			16.9.3 Healthy Person Reference Range
			16.9.4 Clinical Significance
		16.10	 Von Willebrand Factor
			16.10.1 Sources and Characteristics
			16.10.2 Detection Method
			16.10.3 Healthy Person Reference Range
			16.10.4 Clinical Significance
		16.11	 Thrombomodulin
			16.11.1 Sources and Characteristics
			16.11.2 Detection Method and Healthy Person Reference Range
			16.11.3 Clinical Significance
		16.12	 Plasminogen Activator Inhibitor Type 1
			16.12.1 Sources and Characteristics
			16.12.2 Detection Method
			16.12.3 Healthy Person Reference Range
			16.12.4 Clinical Significance
		16.13	 Tissue Factor Pathway Inhibitor
			16.13.1 Sources and Characteristics
			16.13.2 Detection Method
			16.13.3 Healthy Person Reference Range
			16.13.4 Clinical Significance
		16.14	 Laboratory Tests for Clotting Factor Deficiency Screening
			16.14.1 Prothrombin Time
				16.14.1.1	 Sources and Characteristics
				16.14.1.2	 Detection Method
				16.14.1.3	 Healthy Person Reference Range
				16.14.1.4	 Clinical Significance
			16.14.2 Activated Partial Thromboplastin Time
				16.14.2.1	 Sources and Characteristics
				16.14.2.2	 Detection Method
				16.14.2.3	 Healthy Person Reference Range
				16.14.2.4	 Clinical Significance
			16.14.3 Thrombin Time
				16.14.3.1	 Sources and Characteristics
				16.14.3.2	 Detection Method
				16.14.3.3	 Healthy Person Reference Range
				16.14.3.4	 Clinical Significance
			16.14.4 Coagulation Factor Assay
				16.14.4.1	 Sources and Characteristics
				16.14.4.2	 Detection Method
				16.14.4.3	 Healthy Person Reference Range
				16.14.4.4	 Clinical Significance
		16.15	 Molecular Diagnosis of Inherited Bleeding Disorders
			16.15.1 Molecular Diagnosis of Hemophilia A and Hemophilia B
			16.15.2 Molecular Diagnosis of Von Willebrand Disease
			16.15.3 Molecular Diagnosis of Rare Bleeding Disorders
		16.16	 Related Progress
		References
	17: Cardiovascular System
		17.1	 Overview
		17.2	 Myocardial Damage Markers
			17.2.1	 Cardiac Troponin (cTn)
			17.2.2	 Myoglobin (Mb)
			17.2.3	 Creatine Kinase Isoenzyme MB (CK-MB)
			17.2.4	 Heart Type-Fatty Acid Binding Protein (H-FABP)
			17.2.5	 Copeptin
		17.3	 Myocardial Ischemia Markers
			17.3.1	 Ischemic Modified Albumin (IMA)
		17.4	 Heart Function Markers
			17.4.1	 Brain Natriuretic Peptide (BNP) or NT-proBNP
			17.4.2	 Soluble Suppression of Tumorigenicity-2 (sST2)
			17.4.3	 Adrenomedullin (ADM)
		17.5	 Inflammatory Markers
			17.5.1	 C-Reactive Protein (CRP)
			17.5.2	 Interleukin-6 (IL-6)
		17.6	 Markers That Predict Heart-Risk Events
			17.6.1	 Homocysteine (Hcy)
			17.6.2	 Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)
			17.6.3	 Myeloperoxidase (MPO)
		17.7	 Other Markers
			17.7.1	 MicroRNAs
			17.7.2	 KCNQ1
			17.7.3	 SCN5A
			17.7.4	 RYR2
			17.7.5	 KCNE1
			17.7.6	 KCNH2
		References
	18: Pregnancy
		18.1	 Overview
		18.2	 Human Chorionic Gonadotropin (hCG)
			18.2.1	 Resource and Characteristics
			18.2.2	 Detection Methods
			18.2.3	 Reference Range
			18.2.4	 Clinical Application
				18.2.4.1	 Diagnosis and Monitor Normal/Abnormal Pregnancy
				18.2.4.2	 Diagnosis of Gestational Trophoblastic Disease (GTD)
				18.2.4.3	 Marker for Down’s Syndrome Screening
		18.3	 Alpha-Fetoprotein (AFP)
			18.3.1	 Resource and Characteristics
			18.3.2	 Detection Methods
			18.3.3	 Reference Range
			18.3.4	 Clinical Applications
				18.3.4.1	 Prenatal Diagnosis
				18.3.4.2	 Diagnosis and Monitoring of Hepatocellular Carcinoma and Other Germ Cell Tumors
		18.4	 Pregnancy-Associated Plasma Protein-A (PAPP-A)
			18.4.1	 Resource and Characteristics
			18.4.2	 Detection Methods
			18.4.3	 Reference Range
			18.4.4	 Clinical Applications
		18.5	 Inhibin
			18.5.1	 Resource and Characteristics
			18.5.2	 Detection Methods
			18.5.3	 Reference Range
			18.5.4	 Clinical Application
				18.5.4.1	 A Marker of Trophoblast Viability and Placental Dysfunction
				18.5.4.2	 Prenatal Serum Screening for Down’s Syndrome
				18.5.4.3	 Prenatal Serum Screening for Other Chromosome Abnormalities
				18.5.4.4	 A Marker to Evaluate the Development of Hypertensive Disorders of Pregnancy
		18.6	 Unconjugated Estriol
			18.6.1	 Resource and Characteristics
			18.6.2	 Detection Method
			18.6.3	 Reference Range
			18.6.4	 Clinical Application
				18.6.4.1	 Prenatal Serum Screening for Down’s Syndrome
				18.6.4.2	 Monitor Placental Function and Fetal Development
		18.7	 Cell-Free DNA (cfDNA)
			18.7.1	 Resource and Characteristics
			18.7.2	 Detection Method
			18.7.3	 Clinical Application
				18.7.3.1	 Trisomy 21 (Down’s Syndrome)
				18.7.3.2	 Trisomy 18 (Edwards Syndrome)
				18.7.3.3	 Trisomy 13
		References
	19: Urine
		19.1	 Overview
		19.2	 Urea
			19.2.1 Sources and Characteristics
			19.2.2 Detection Methods
			19.2.3 Normal Reference Interval
			19.2.4 Clinical Significance
		19.3	 Creatinine
			19.3.1 Sources and Characteristics
			19.3.2 Detection Methods
			19.3.3 Normal Reference Interval
			19.3.4 Clinical Significance
		19.4	 Urinary Microalbumin
			19.4.1 Sources and Characteristics
			19.4.2 Detection Methods
			19.4.3 Normal Reference Interval
			19.4.4 Clinical Significance
		19.5	 Cystatin C
			19.5.1 Sources and Characteristics
			19.5.2 Detection Methods
			19.5.3 Normal Reference Interval
			19.5.4 Clinical Significance
		19.6	 Transferrin
			19.6.1 Sources and Characteristics
			19.6.2 Detection Methods
			19.6.3 Normal Reference Interval
			19.6.4 Clinical Significance
		19.7	 Uric Acid
			19.7.1 Sources and Characteristics
			19.7.2 Detection Methods
			19.7.3 Normal Reference Interval
			19.7.4 Clinical Significance
		19.8	 α1-Microglobulin
			19.8.1 Sources and Characteristics
			19.8.2 Detection Methods
			19.8.3 Normal Reference Interval
			19.8.4 Clinical Significance
		19.9	 β2-Microglobulin
			19.9.1 Sources and Characteristics
			19.9.2 Detection Methods
			19.9.3 Normal Reference Interval
			19.9.4 Clinical Significance
		19.10	 Neutrophil Gelatinase-Associated Lipocalin
			19.10.1 Sources and Characteristics
			19.10.2 Detection Methods
			19.10.3 Normal Reference Interval
			19.10.4 Clinical Significance
		19.11	 N-Acetyl-β-d Glucosamine Glycosaminase
			19.11.1 Sources and Characteristics
			19.11.2 Detection Methods
			19.11.3 Normal Reference Interval
			19.11.4 Clinical Significance
		19.12	 Retinol Binding Protein
			19.12.1 Sources and Characteristics
			19.12.2 Detection Methods
			19.12.3 Normal Reference Interval
			19.12.4 Clinical Significance
		References
	20: Bone
		20.1	 Overview
		20.2	 BAP
			20.2.1	 Sources and Characteristics
			20.2.2	 Methods
			20.2.3	 Reference Interval for Healthy Persons
			20.2.4	 Clinical Significance
			20.2.5	 Conclusions and Prospects
		20.3	 N-MID Osteocalcin
			20.3.1	 Sources and Characteristics
			20.3.2	 Methods
			20.3.3	 Reference Interval for Healthy Persons
			20.3.4	 Clinical Significance
			20.3.5	 Conclusions and Prospects
		20.4	 Total PINP
			20.4.1	 Sources and Characteristics
			20.4.2	 Methods
			20.4.3	 Reference Interval for Healthy Persons
			20.4.4	 Clinical Significance
			20.4.5	 Conclusions and Prospects
		20.5	 PINP
			20.5.1	 Sources and Characteristics
			20.5.2	 Methods
			20.5.3	 Reference Interval for Healthy Persons
			20.5.4	 Clinical Significance
			20.5.5	 Conclusions and Prospects
		20.6	 PICP
			20.6.1	 Sources and Characteristics
			20.6.2	 Methods
			20.6.3	 Reference Interval for Healthy Persons
			20.6.4	 Clinical Significance
			20.6.5	 Conclusions and Prospects
		20.7	 β-Crosslaps
			20.7.1	 Sources and Characteristics
			20.7.2	 Methods
			20.7.3	 Reference Interval for Healthy Persons
			20.7.4	 Clinical Significance
		20.8	 Conclusions and Prospects
		References
	21: Cancer
		21.1	 Overview
			21.1.1	 The Ideal Biomarker for Cancer
			21.1.2	 Classification of Tumor Biomarkers
				21.1.2.1	 Classification by Biochemical Properties
				21.1.2.2	 Classification by Sources
				21.1.2.3	 Classification by Oncogenesis and Development of Tumors
		21.2	 Tumor Markers with Different Biochemical Properties
			21.2.1	 Oncofetal Protein
				21.2.1.1	 AFP
				21.2.1.2	 AFP-L3
				21.2.1.3	 CEA
			21.2.2	 Protein
				21.2.2.1	 TPA and TPS
				21.2.2.2	 CYFRA21-1
				21.2.2.3	 PIVKA-II
			21.2.3	 Enzymes
				21.2.3.1	 PSA
				21.2.3.2	 NSE
				21.2.3.3	 LDH
			21.2.4	 Sugar Esters or Glycoproteins
				21.2.4.1	 CA125
				21.2.4.2	 CA15–3
				21.2.4.3	 CA19–9
			21.2.5	 Hormone
				21.2.5.1	 HCG
				21.2.5.2	 CA
		21.3	 Multistage Biomarkers of Tumorigenesis and Development
			21.3.1	 Molecular Biomarkers for Early Diagnosis
				21.3.1.1	 SPLUNC1
				21.3.1.2	 APC
				21.3.1.3	 RASSF1A
				21.3.1.4	 EBERs
				21.3.1.5	 DAPK
				21.3.1.6	 NES1
				21.3.1.7	 DCC
			21.3.2	 Molecular Biomarkers for Invasion and Metastasis
				21.3.2.1	 Adhesion Molecules
					E-Cadherins
					Integrins
					CD44
				21.3.2.2	 Proteolytic Enzymes and Their Inhibitors
					MMP
					uPA
					Cathepsin
				21.3.2.3	 Tumor Microangiogenesis-Related Molecules
					Promoting Microangiogenesis Factors
					VEGF
					MVD
					Inhibitory Microangiogenesis Factors
					Angiostatin and Endostatin
				21.3.2.4	 Autocrine Motility Factor
					AMF
					Gp78
			21.3.3	 Molecular Biomarkers for Prognosis
				21.3.3.1	 Survivin
				21.3.3.2	 Cyclin D1
				21.3.3.3	 P53
				21.3.3.4	 TSLC1
				21.3.3.5	 BAG-1
				21.3.3.6	 Bmi-1
		21.4	 Molecular Biomarkers for Precision Medicine
			21.4.1	 Breast Cancer
				21.4.1.1	 HER2
				21.4.1.2	 ER and PR
				21.4.1.3	 BRCA1/BRCA2
			21.4.2	 Lung Cancer
				21.4.2.1	 EGFR
				21.4.2.2	 ALK
				21.4.2.3	 ROS-1
			21.4.3	 Colorectal Cancer
				21.4.3.1	 CIN
				21.4.3.2	 MSI
				21.4.3.3	 CIMP
		21.5	 Novel Molecular Biomarkers of Tumor
			21.5.1	 Tumor Specific Protein 70 (SP70)
				21.5.1.1	 Sources and Characteristics
				21.5.1.2	 Clinical Detection Methods
				21.5.1.3	 Clinical Application
			21.5.2	 CTC
			21.5.3	 ctDNA
			21.5.4	 DNA Methylation in Peripheral Blood
			21.5.5	 Circulating miRNAs
			21.5.6	 LncRNA
			21.5.7	 CircRNA
			21.5.8	 Exosome
			21.5.9	 Endosome
		21.6	 Future Prospects for Cancer Biomarkers
		References
	22: Translation Research of Novel Biomarker
		22.1	 Overview
		22.2	 Discovery
			22.2.1	 Characteristics of Molecular Biomarkers
			22.2.2	 Biomarker Classification and Samples
			22.2.3	 Existing Detection Techniques for Clinical Application
			22.2.4	 Biomarker Discovery Approaches
				22.2.4.1	 Strategy of Biomarker Discovery
					Research Subjects
					Omics Technologies
				22.2.4.2	 Biomarker Function Identification
					Role Transformation of P53
					Current Novel Tumor Biomarkers
					Pro-Gastrin-Releasing Peptide (ProGRP)
					Protein Induced by Vitamin K Absence/Antagonist-II (PIVKA-II)
			22.2.5	 Artificial Intelligence and Big Data
			22.2.6	 Monoclonal Antibody Library Technique
				22.2.6.1	 Usage of Monoclonal Antibody Library
					Research on Diagnostic Tumor Biomarker
					Cancer Target Therapy
					Advantages of the Monoclonal Antibody Library
			22.2.7	 Transformation Determinants
		22.3	 Qualification and Verification
			22.3.1	 Samples from Clinical Cohort
			22.3.2	 Platforms for Qualification/Verification
				22.3.2.1	 Enzyme-Linked Immunosorbent Assay (ELISA)
				22.3.2.2	 Mass Spectrometry
				22.3.2.3	 Selection of Assays
		22.4	 Assay Optimization
			22.4.1	 Development of Clinical Diagnostic Monoclonal Antibodies
			22.4.2	 Preanalytical Variation
				22.4.2.1	 Sample Collection and Processing
				22.4.2.2	 Physiological Factors
			22.4.3	 Analytical Evaluation
				22.4.3.1	 Indicators of Accuracy
				22.4.3.2	 Indicators of Precision
				22.4.3.3	 Analytical Measurement Range (AMR)
			22.4.4	 Reference Intervals
			22.4.5	 Cut-off Value
		22.5	 Clinical Evaluation
		22.6	 Progress
		References
Part III: Advanced Molecular Diagnostic Techniques
	23: Next-Generation Sequencing (NGS)
		23.1	 Overview
		23.2	 Basic Principle
			23.2.1	 Library Construction Principle and Characteristics
				23.2.1.1	 Construction of DNA Library
				23.2.1.2	 Construction of RNA Library
			23.2.2	 High-Throughput Sequencing Principles and Features
				23.2.2.1	 Illumina Sequencing
				23.2.2.2	 Ion Torrent Semiconductor Sequencing
				23.2.2.3	 Complete Genomics Sequencing Platform
				23.2.2.4	 Single-Molecule Sequencing
		23.3	 Technology Development
			23.3.1	 Summary of Technology Development
			23.3.2	 First-Generation Sequencing Technology
				23.3.2.1	 Maxam-Gilbert Chemical Degradation Sequencing
				23.3.2.2	 Deoxygenation Chain Termination Sequencing
				23.3.2.3	 DNA Automated Sequencing
			23.3.3	 Next-Generation Sequencing
				23.3.3.1	 Pyrosequencing
				23.3.3.2	 454/Roche Sequencing System
				23.3.3.3	 Ion Torrent/Life Technologies Sequencing System
				23.3.3.4	 Solexa/Illumina Sequencing System
				23.3.3.5	 SOLiD/Life Technologies Sequencing System
				23.3.3.6	 Complete Genomics/BGI Sequencing System
			23.3.4	 Third Generation of Sequencing Technology
				23.3.4.1	 Pacific Bioscience SMRT Sequencing Technology
				23.3.4.2	 Oxford Nanopore Technologies Nanopore Sequencing Technology
			23.3.5	 Development and Prospect of Sequencing Technology
		23.4	 Clinical Application
			23.4.1	 Application of NGS in Noninvasive Prenatal Screening for Chromosome Aneuploidy
			23.4.2	 Application of NGS in Preimplantation Genetic Screening
			23.4.3	 Application of NGS in the Detection of Single-Gene Genetic Diseases
			23.4.4	 Application in the Detection of Tumors
			23.4.5	 Application of NGS in Tumor-Targeted Therapy
			23.4.6	 Application of NGS in the Detection of Pathogenic Microorganisms
			23.4.7	 Application of NGS in Epigenetic Detection
			23.4.8	 Application of NGS in Sequencing of Immune Repertoire (IR)
			23.4.9	 Application of NGS in Transcriptomics
		References
	24: Digital PCR
		24.1	 Overview
		24.2	 Basic Principle
			24.2.1	 Statistics and Quantitative Principles of Digital PCR
				24.2.1.1	 Confidence Interval in Absolute Quantification
			24.2.2	 Experimental Principle of Digital PCR
			24.2.3	 Technology Development
				24.2.3.1	 The Germination of Digital PCR
				24.2.3.2	 Proposal of Digital PCR Concept
				24.2.3.3	 BEAMing Digital PCR
				24.2.3.4	 Microfluidic Digital PCR
			24.2.4	 Clinical Application
				24.2.4.1	 Application Characteristics of Digital PCR
				24.2.4.2	 Application of Digital PCR on Genomics
				24.2.4.3	 Application of Digital PCR on Translational Medicine and Precision Medicine
					Individualized Medicine and Liquid Biopsy Technique
					Application of Digital PCR on Drug Resistance Surveillance
					Prenatal Examination
				24.2.4.4	 Application of Digital PCR on Food Safety
				24.2.4.5	 Application of Digital PCR on Environmental Microorganisms
				24.2.4.6	 Other Applications on Digital PCR
					Quality Control of Sequencing Library and Verification of Sequencing Result
					Gene Editing
				24.2.4.7	 The Trend of Development of Digital PCR
		References
	25: Biosensor
		25.1	 Overview
			25.1.1	 Characteristics
				25.1.1.1	 Low Cost and High Speed
				25.1.1.2	 High Precision and Stability
				25.1.1.3	 High Specificities
				25.1.1.4	 Wide Range of Applications
				25.1.1.5	 Simple Operation and Automatic Analysis
			25.1.2	 Classifications
		25.2	 Basic Principle
			25.2.1	 Principles of Electrochemical Biosensor
				25.2.1.1	 Electrochemical Immunosensor
				25.2.1.2	 Electrochemical Enzyme Electrode Sensor
				25.2.1.3	 Electrochemical DNA Sensor
				25.2.1.4	 Electrochemical Cell Sensor
				25.2.1.5	 Cell Receptor-Based Cell Sensor
				25.2.1.6	 Cellular Lesion-Based Cell Sensor
				25.2.1.7	 Cell Sensor Integrating Optical Measurement Technology and Electronic Measurement Technology
			25.2.2	 Principles of Optical Biosensor
				25.2.2.1	 Passive Optical Sensor
				25.2.2.2	 Photoinduced Optical Biosensor
				25.2.2.3	 Electro-optical Biosensor
			25.2.3	 Principles of Piezoelectric Biosensor
		25.3	 Technology Development
			25.3.1	 Wearable Biosensor
			25.3.2	 Molecular Biosensor and Imaging
			25.3.3	 Biological Function Simulation Sensor
				25.3.3.1	 Odor Sensor
				25.3.3.2	 Taste Sensor
			25.3.4	 Biosensor Chips
		25.4	 Clinical Application
		References
	26: Microfluidic Chip
		26.1	 Overview
		26.2	 Basic Principle
			26.2.1	 Separation
			26.2.2	 Detection
		26.3	 Technology Development
			26.3.1	 Silica and Glass
			26.3.2	 Polymers
			26.3.3	 Hydrogel
			26.3.4	 Paper
			26.3.5	 Droplet
		26.4	 Clinical Application
			26.4.1	 Capillary Electrophoresis
			26.4.2	 Detection of Nucleic Acid
				26.4.2.1	 Polymerase Chain Reaction
				26.4.2.2	 Detection of Gene Mutation
				26.4.2.3	 Genotyping Detection
				26.4.2.4	 DNA Sequencing
			26.4.3	 Amino Acid Analysis
			26.4.4	 Peptide and Protein Analysis
				26.4.4.1	 Sample Manipulation and Detection
				26.4.4.2	 Protein-Ligand Interaction Analysis
				26.4.4.3	 Mass Spectrometry-Based Proteomics
			26.4.5	 Immunoassay
			26.4.6	 Cell Culture and Analysis
				26.4.6.1	 Cell Manipulation
				26.4.6.2	 Cell Culture and Cell-to-Cell Interaction Analysis
				26.4.6.3	 Single-Cell Analysis
			26.4.7	 Drug Assay and Screening
				26.4.7.1	 Drug Delivery System
				26.4.7.2	 Drug Screening
			26.4.8	 Enzymatic Analysis
			26.4.9	 Mono-molecular Detection
		References
	27: Liquid Biopsy
		27.1	 Overview
		27.2	 Basic Principle
			27.2.1	 Circulating Tumor DNA
				27.2.1.1	 Sample Collection and DNA Extraction
				27.2.1.2	 ctDNA Detection
					PCR-Based Gene Analysis
					Sequencing-Based Gene Mutation Analysis
					Whole Genome Sequencing Analysis
			27.2.2	 Circulating Tumor Cells
				27.2.2.1	 CTC Detection Technologies Without Enrichment
				27.2.2.2	 CTC Detection Technologies with Enrichment
					Molecular Marker-Based Cell Enrichment
						Negative Enrichment
						Positive Enrichment
					Physical Property and Non-affinity-Based Microfluidic Cell Enrichment
			27.2.3	 Exosomes
				27.2.3.1	 Isolation
				27.2.3.2	 Analysis of Exosomes
		27.3	 Technology Development
			27.3.1	 Circulating Tumor DNA
				27.3.1.1	 PCR-Based Techniques
				27.3.1.2	 Sequencing Techniques
					NGS in Liquid Biopsy
			27.3.2	 Circulating Tumor Cells
				27.3.2.1	 CellSearch System
				27.3.2.2	 MagSweeper
				27.3.2.3	 ISET
				27.3.2.4	 MEMS
				27.3.2.5	 FMSA
				27.3.2.6	 Vortex
				27.3.2.7	 SP70-Targeted Tumor Cell Enrichment
				27.3.2.8	 SP70-Targeted Flow Cytometry
			27.3.3	 Exosomes
				27.3.3.1	 Isolation of Exosomes
					Ultracentrifugation Techniques
					Size-Based Techniques
					Immunoaffinity Capture-Based Techniques
					Precipitation
					Microfluidic-Based Isolation Techniques
				27.3.3.2	 Analysis of Exosomes
					Physical Analysis
					Chemical, Biochemical, and Compositional Analysis
		27.4	 Clinical Application
			27.4.1	 Circulating Tumor DNA
			27.4.2	 CTCs
			27.4.3	 Exosome
			27.4.4	 Comparison Between CTCs, ctDNA, and Exosome Tests in Cancer Detection
			27.4.5	 Challenges and Outlook
		References
	28: Molecular-Targeted Imaging
		28.1	 Overview
		28.2	 Basic Principle
			28.2.1	 Probes
			28.2.2	 Molecular-Targeted Imaging Strategy
			28.2.3	 Molecular-Targeted Imaging Type
		28.3	 Technology Development
			28.3.1	 PET/CT
			28.3.2	 SPECT
			28.3.3	 PET/MR
			28.3.4	 CT
			28.3.5	 Ultrasound
			28.3.6	 Optical Imaging
		28.4	 Clinical Application
			28.4.1	 Cancer
			28.4.2	 Cardiovascular Diseases
			28.4.3	 Central Nervous System Diseases
			28.4.4	 Autoimmune Diseases
			28.4.5	 Drug Development
		References
	29: Fluorescence In Situ Hybridization
		29.1	 Overview
		29.2	 Basic Principle
			29.2.1	 Preparation of the Slides
			29.2.2	 Preparation of the Probes
			29.2.3	 Fluorescence In Situ Hybridization
			29.2.4	 FISH Quality Control
		29.3	 Technology Development
			29.3.1	 Immuno-FISH
			29.3.2	 Multiplex-FISH (M-FISH), Spectral Karyotyping (SKY) and RxFISH
			29.3.3	 RNA-FISH
			29.3.4	 Three-Dimensional FISH (3D-FISH)
			29.3.5	 Fiber-FISH
			29.3.6	 CGH (Comparative Genomic Hybridization)
			29.3.7	 Array-CGH
			29.3.8	 Flow-FISH
		29.4	 Clinical Application
			29.4.1	 Prenatal Diagnosis
			29.4.2	 Hematopoietic Diseases and Lymphoma Related Tests
			29.4.3	 Application of FISH in Pathogen Detection
			29.4.4	 FISH for Detection of Circulating Tumor Cells (CTC)
			29.4.5	 Application of FISH in Solid Oncology
		References
	30: Circulating DNA Quantification
		30.1	 Overview
		30.2	 Basic Principle
			30.2.1	 Sample Selection of Circulating DNA Testing
			30.2.2	 Isolation of Circulating DNA
			30.2.3	 Analysis Platform of Circulating DNA
				30.2.3.1	 Massive Parallel Sequencing
				30.2.3.2	 Quantitative Polymerase Chain Reaction, PCR
		30.3	 Technology Development
			30.3.1	 Duplex Real-Time PCR for Total Plasma DNA Quantitation
			30.3.2	 Candidate Gene Approach
				30.3.2.1	 Allele-Specific PCR (AS PCR)
				30.3.2.2	 Competitive Allele-Specific TaqMan PCR (CAST PCR)
				30.3.2.3	 Coamplification at Lower Denaturation Temperature PCR (COLD-PCR)
				30.3.2.4	 Peptide Nucleic Acid-Locked Nucleic Acid PCR (PNA-LNA PCR)
				30.3.2.5	 Droplet Digital PCR (ddPCR)
				30.3.2.6	 Microfluidic Digital PCR
				30.3.2.7	 “Beads, Emulsion, Amplification, Magnetics Digital PCR” (BEAMing)
			30.3.3	 Whole-Genome Sequencing Methods
			30.3.4	 Targeted Deep Sequencing
				30.3.4.1	 Tagged AMplicon Deep Sequencing (TAM-Seq)
				30.3.4.2	 Safe-Sequencing System (Safe-SeqS)
				30.3.4.3	 Duplex Sequencing
				30.3.4.4	 Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq)
		30.4	 Clinical Application
			30.4.1	 Prognostic Value
			30.4.2	 Diagnosis Value
			30.4.3	 Detecting Resistance Mechanisms
			30.4.4	 Detecting Minimal Residual Disease
			30.4.5	 Noninvasive Prenatal Testing (NIPT)
			30.4.6	 Injury Assessment
		References
	31: DNA Methylation Detection Techniques
		31.1	 Overview
		31.2	 Basic Principle
			31.2.1	 DNA Enrichment Methods
			31.2.2	 ChIP-Seq
			31.2.3	 Mapping Open Chromatin
			31.2.4	 Chromosome Conformation Capture
		31.3	 Technology Development
			31.3.1	 Genome-Wide Methylation Analysis
				31.3.1.1	 High-performance Liquid Chromatography
				31.3.1.2	 High-performance Capillary Electrophoresis
			31.3.2	 Methylation Detection of Specific Sites
				31.3.2.1	 Bisulfite Sequencing (BSP)
				31.3.2.2	 Methylation Specificity PCR
				31.3.2.3	 Methylight
				31.3.2.4	 High-resolution Melting (HRM)
				31.3.2.5	 Combined Bisulfite Restriction Analysis (COBRA)
				31.3.2.6	 Pyrosequencing
				31.3.2.7	 Analysis of DNA Methylation Map Based on Chip
				31.3.2.8	 Single Molecule Real-Time (SMRT) Sequencing Technology
				31.3.2.9	 Flight Mass Spectrometry
		31.4	 Clinical Application
		References
Part IV: Disease Presentation and Clinical Laboratory Procedures
	32: Immunological Disorders
		32.1	 Allergic Disease
			32.1.1	 Overview
			32.1.2	 Pathogenesis
				32.1.2.1	 Immune Cells in Allergy
				32.1.2.2	 Inflammatory Molecules in Allergy
			32.1.3	 Atopic Dermatitis
				32.1.3.1	 Overview
				32.1.3.2	 Clinical Appearance
				32.1.3.3	 Laboratory Diagnosis
					Serum Total IgE
					Detection of Eosinophils in Peripheral Blood
					Serum Eosinophil Cationic Protein (ECP)
					Allergen Skin Patch Test or Prick Test
					Basophil Activation Test (BAT)
			32.1.4	 Allergic Asthma
				32.1.4.1	 Overview
				32.1.4.2	 Clinical Appearance
				32.1.4.3	 Laboratory Diagnosis
					Allergic Skin Prick Test and Serum IgE Test
					Induced Sputum Test
					Fractional Exhaled Nitric Oxide (FeNO) Measurement
					BAT
					Gene Detection
			32.1.5	 Allergic Rhinitis
				32.1.5.1	 Overview
				32.1.5.2	 Clinical Appearance
				32.1.5.3	 Laboratory Diagnosis
					Supportive Methods for the Diagnosis of AR Include Skin Prick Test (SPT) and Serum Specific IgE
					Inhalation Allergen Screening Test (Phadiatop)
					ECP Detection
			32.1.6	 Food Allergy
				32.1.6.1	 Overview
				32.1.6.2	 Clinical Appearance
					IgE-Mediated Food Allergy
					Non-lgE-Mediated Food Allergy
					Mixed IgE and Non-IgE-Related Food Allergies
					Laboratory Diagnosis
					Component Resolution Diagnosis (CRD)
					Gene Detection
			32.1.7	 Drug Allergy
				32.1.7.1	 Overview
				32.1.7.2	 Clinical Appearance
				32.1.7.3	 Laboratory Diagnosis
					General Laboratory Examination
					Gene Detection
			32.1.8	 Typical Medical Case
		32.2	 Autoimmune Diseases
			32.2.1	 Overview
				32.2.1.1	 Classification of Autoimmune Diseases
				32.2.1.2	 Common Characteristics of Autoimmune Diseases
				32.2.1.3	 Pathogenesis of Autoimmune Diseases (Fig. 32.2)
				32.2.1.4	 The Appearance of Autoantigens
				32.2.1.5	 Abnormal Immune Regulation
				32.2.1.6	 Abnormal Expression of Fas/FasL
				32.2.1.7	 Genetic Factors
			32.2.2	 The Mechanism of Immune Injury in Autoimmune Diseases (Fig. 32.3)
				32.2.2.1	 Type II Hypersensitivity
				32.2.2.2	 Type III Hypersensitivity
				32.2.2.3	 Type IV Hypersensitivity
			32.2.3	 Common Autoimmune Diseases
				32.2.3.1	 Autoimmune Hemolytic Anemia (AIHA)
					Case 1, Primary WAIHA
				32.2.3.2	 Immune Thrombocytopenic Purpura (ITP)
				32.2.3.3	 Systemic Lupus Erythematosus (SLE)
					Experimental Diagnosis of SLE
					Case 2, SLE
				32.2.3.4	 Rheumatoid Arthritis (RA)
					Case 3, RA
				32.2.3.5	 Sjögren’s Syndrome (SS)
				32.2.3.6	 Myasthenia Gravis (MG)
				32.2.3.7	 Pulmonary Hemorrhagic Nephritis Syndrome
			32.2.4	 Major Immunological Detection of Autoimmune Diseases
				32.2.4.1	 Detection of Autoantibodies and Its Clinical Significance
					Systemic Lupus Erythematosus (SLE)
					Rheumatoid Arthritis (RA): Detection of Autoantibodies to RA
					Autoimmune Hemolytic Anemia
					Sjögren’s Syndrome (SS)
				32.2.4.2	 Clinical Significance of Immunoglobulin and Complement Examination
				32.2.4.3	 Lymphocyte Detection
				32.2.4.4	 Detection of Cytokines
				32.2.4.5	 Application Principles of Immunoassay for Autoimmune Diseases
		32.3	 Acquired Immune Deficiency Syndrome
			32.3.1	 Overview
				32.3.1.1	 HIV Morphology
				32.3.1.2	 HIV Gene Structure
				32.3.1.3	 Virus Characteristics
				32.3.1.4	 Route of Transmission of AIDS
			32.3.2	 Clinical Appearance
				32.3.2.1	 General Symptoms
				32.3.2.2	 Respiratory Symptoms
				32.3.2.3	 Digestive Symptoms
				32.3.2.4	 Nervous System Symptoms
				32.3.2.5	 Skin and Mucous Membrane Damage
				32.3.2.6	 Tumor
			32.3.3	 Detection Method
				32.3.3.1	 Antibody Detection
					Screening Test
					Confirmatory Reagent
				32.3.3.2	 Antigen Detection
				32.3.3.3	 Nucleic Acid Detection
					Qualitative Detection
					Quantitative Detection
				32.3.3.4	 CD4+ and CD8+ T Lymphocyte Detection
				32.3.3.5	 Virus Isolation and Culture
				32.3.3.6	 HIV-1 Genotype Resistance Detection
			32.3.4	 Therapy
				32.3.4.1	 General Treatment
				32.3.4.2	 Antiviral Therapy
				32.3.4.3	 Drug Resistance
		References
	33: Liver Diseases
		33.1	 Viral Hepatitis
			33.1.1	 Overview
			33.1.2	 Hepatitis A
				33.1.2.1	 Overview
				33.1.2.2	 Clinical Appearance
				33.1.2.3	 Laboratory Diagnosis
					Immunological Detection
					Molecular Biological Detection
						Nucleic Acid Molecular Hybridization
						RT-PCR
				33.1.2.4	 Management
				33.1.2.5	 Typical Medical Case
			33.1.3	 Hepatitis B
				33.1.3.1	 Overview
				33.1.3.2	 Clinical Appearance
				33.1.3.3	 Laboratory Diagnosis
					Immunological Detection
						HBsAg
						Anti-HBs Antibodies
						HBeAg
						Anti-HBe Antibodies
						HBcAg
						Anti-HBc Antibodies
					Molecular Biological Detection
						Quantitative Analysis of HBV DNA
						Quantitative Analysis of HBV RNA
						HBV Typing
						Analysis of Drug Resistance of HBV
				33.1.3.4	 Management
				33.1.3.5	 Typical Medical Case
			33.1.4	 Hepatitis C
				33.1.4.1	 Overview
				33.1.4.2	 Clinical Appearance
				33.1.4.3	 Laboratory Diagnosis
					Immunological Detection
						Screening Test
						Confirmatory
					Molecular Biological Detection
						Detection of HCV Nucleic Acid
						Genotyping of HCV
				33.1.4.4	 Management
				33.1.4.5	 Typical Medical Case
					Results with Interpretation Guideline
					Final Diagnosis
			33.1.5	 Hepatitis D
				33.1.5.1	 Overview
				33.1.5.2	 Clinical Appearance
					Co-Infection
					Superinfection
				33.1.5.3	 Laboratory Diagnosis
					Immunological Detection
					Molecular Biological Detection
				33.1.5.4	 Management
			33.1.6	 Hepatitis E
				33.1.6.1	 Overview
				33.1.6.2	 Clinical Appearance
				33.1.6.3	 Laboratory Diagnosis
				33.1.6.4	 Management
				33.1.6.5	 Typical Medical Case
					Final Diagnosis
		33.2	 Autoimmune Hepatitis
			33.2.1	 Overview
			33.2.2	 Clinical Appearance
			33.2.3	 Laboratory Diagnosis
				33.2.3.1	 Serum Biochemical Indicators
				33.2.3.2	 Autoantibody
					ANA
					Anti-Smooth Muscle Antibodies (ASMA)
					Anti-Liver/Kidney Microsomal Antibodies (ALKM)
					Anti-Liver Cytosol Type 1 (LC-1) Antibodies
					Antibodies Against Soluble Liver Antigens/Antibodies Against Liver Pancreas (SLA/LP)
				33.2.3.3	 Serum Immunoglobulin
				33.2.3.4	 Histopathology
				33.2.3.5	 Conclusion
		33.3	 Hepatocellular Carcinoma
			33.3.1	 Overview
			33.3.2	 Surveillance and Diagnosis
				33.3.2.1	 Surveillance
				33.3.2.2	 Diagnosis
			33.3.3	 Biomarkers
				33.3.3.1	 Alpha-Fetoprotein (AFP)
				33.3.3.2	 Glypican-3 (GPC3)
				33.3.3.3	 Golgi Protein-73 (GP73)
				33.3.3.4	 Alpha-l-Fucosidase (AFU)
				33.3.3.5	 Protein Induced by Vitamin K Absence/Antagonist-II (PIVKA-II)
				33.3.3.6	 Squamous Cell Carcinoma Antigen (SCCA)
				33.3.3.7	 MicroRNAs
				33.3.3.8	 Other Biomarkers
					Tumor Specific Protein 70 (SP70)
					Long Non-coding RNAs (LncRNAs)
					Circular RNAs (CircRNAs)
					Contents in Exosome
			33.3.4	 Genetic Variations
			33.3.5	 Treatment
			33.3.6	 Typical Medical Case
		33.4	 Wilson Disease
			33.4.1	 Clinical Appearance
				33.4.1.1	 Clinical Manifestations
				33.4.1.2	 Neurological and Psychiatric Manifestations
				33.4.1.3	 Ophthalmic Manifestations
			33.4.2	 Diagnosis
				33.4.2.1	 Liver Function Tests
				33.4.2.2	 Biochemical Investigations
					Ceruloplasmin
					Total Serum Copper
					Urinary Copper Excretion
				33.4.2.3	 Liver Biopsy and Liver Copper Content
				33.4.2.4	 Imaging
				33.4.2.5	 Genetic Testing
			33.4.3	 Correlation Between Phenotype and Genotype
			33.4.4	 Genetic Counselling
			33.4.5	 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
			33.4.6	 Typical Clinical Case
		References
	34: Pancreatic Diseases
		34.1	 Pancreatic Ductal Adenocarcinoma
			34.1.1	 Overview
			34.1.2	 Clinical Appearance
			34.1.3	 Laboratory Diagnosis
				34.1.3.1	 Mucin Tumor Markers
					CA19-9
					CA50
					CA242
					DU-PAN-2
					CAM17.1/Wheat-Germ Agglutinin (WGA)
				34.1.3.2	 Other Markers
					Tumor-Specific Protein (SP70)
					Carcinoembryonic Antigen
					Membrane Antigens
					PAM4
					MicroRNAs
				34.1.3.3	 Proteomics
				34.1.3.4	 Genetic Testing
			34.1.4	 Management
			34.1.5	 Treatment
			34.1.6	 Typical Medical Case
		34.2	 Chronic Pancreatitis
			34.2.1	 Overview
			34.2.2	 Clinical Appearance
			34.2.3	 Laboratory Diagnosis
				34.2.3.1	 Exocrine Pancreatic Enzymes or Hormones
				34.2.3.2	 Human Pancreatic Polypeptide (PP)
				34.2.3.3	 Pancreatic Function Tests
					Indirect Pancreatic Function Tests
					Direct Pancreatic Function Tests
				34.2.3.4	 Genetic Testing
			34.2.4	 Management
			34.2.5	 Treatment
			34.2.6	 Typical Medical Case
		34.3	 Insulinoma
			34.3.1	 Overview
			34.3.2	 Clinical Appearance
			34.3.3	 Laboratory Diagnosis
				34.3.3.1	 C-Peptide Inhibition Test with Hog Insulin
				34.3.3.2	 Intravenous Secretin Test for Insulinoma
				34.3.3.3	 The 72-h Fast Test
				34.3.3.4	 Genetic Testing
			34.3.4	 Management
			34.3.5	 Treatment
		34.4	 Intraductal Papillary Mucinous Neoplasms
			34.4.1	 Overview
			34.4.2	 Clinical Appearance
			34.4.3	 Laboratory Diagnosis
				34.4.3.1	 Mucin Tumor Markers and Oncofetal Antigens
					CEA
					CA19-9
				34.4.3.2	 Other Tumor Markers
					CF protein
					S100 Protein
					mAb Das-1
					MicroRNAs
				34.4.3.3	 Genetic Testing
			34.4.4	 Management
			34.4.5	 Typical Medical Case
		References
	35: Digestive Tract Disease
		35.1	 Gastritis
			35.1.1 Classification
				35.1.1.1	 Based on the Course of Disease
				35.1.1.2	 Based on Etiology
					Helicobacter pylori Gastritis
					Chemical Gastritis
					Autoimmune Gastritis
			35.1.2 Clinical Manifestation
			35.1.3 Laboratory Diagnosis
				35.1.3.1	 Endoscopy
				35.1.3.2	 Histology
				35.1.3.3	 Helicobacter pylori
			35.1.4 Biomarker
				35.1.4.1	 Pepsinogens
				35.1.4.2	 Gastrin 17
				35.1.4.3	 HOX Transcript Antisense RNA
			35.1.5 Typical Medical Case
		35.2	 Diarrhea
			35.2.1 Overview
			35.2.2 Acute Diarrhea
				35.2.2.1	 Infections
				35.2.2.2	 Poisoning
				35.2.2.3	 Medications
				35.2.2.4	 Other Diseases
			35.2.3 Chronic Diarrhea
			35.2.4 Laboratory Examination
				35.2.4.1	 Stool Tests
					Fecal Bacterial Culture
					Stool Routine
					Detection of Virus, Virus Antigen, and Virus Nucleic Acid in Feces
				35.2.4.2	 Blood Tests
				35.2.4.3	 Serological Tests
				35.2.4.4	 Others Tests
			35.2.5 Biomarkers
				35.2.5.1	 Calprotectin
				35.2.5.2	 Lactoferrin
				35.2.5.3	 Anti-Saccharomyces cerevisiae Antibodies (ASCA)
				35.2.5.4	 Antineutrophil Cytoplasmic Antibody (ANCAs)
				35.2.5.5	 C-Reactive Protein (CRP)
				35.2.5.6	 Anti-Vinculin and Anti-Cytolethal Distending Toxin B Antibodies (CdtB)
				35.2.5.7	 Angiotensin-Converting Enzyme 2 (ACE 2)
			35.2.6 Conclusion
			35.2.7 Typical Medical Case
		35.3	 Crohn’s Disease
			35.3.1 Overview
			35.3.2 Clinical Manifestation
			35.3.3 Laboratory Diagnosis
				35.3.3.1	 CRP and ESR
				35.3.3.2	 Hematologic Tests
				35.3.3.3	 Fecal Calprotectin and Other Fecal Marker
				35.3.3.4	 Other Serological Markers
				35.3.3.5	 Microbiology
				35.3.3.6	 Genetic Testing
				35.3.3.7	 Endoscopy
				35.3.3.8	 Imaging
			35.3.4 Conclusions
			35.3.5 Typical Medical Case
		35.4	 Esophageal Cancer
			35.4.1 Overview
			35.4.2 Epidemiology
			35.4.3 Etiology
				35.4.3.1	 Squamous Cell Carcinoma
				35.4.3.2	 Adenocarcinoma
			35.4.4 Screening
			35.4.5 Clinical Diagnosis
			35.4.6 Molecular Diagnosis
				35.4.6.1	 Genetic and Epigenetic Alterations Detection and Its Implications
				35.4.6.2	 Molecular Diagnosis of Micrometastasis and CTCs
				35.4.6.3	 miRNA-Based Molecular Diagnosis
				35.4.6.4	 Genetic Polymorphism
				35.4.6.5	 Novel Molecular Markers
					ADAMTS16
					Tumor Specific Protein (SP70)
			35.4.7 Therapy
				35.4.7.1	 Ablation
				35.4.7.2	 Cryotherapy
				35.4.7.3	 Endoscopic Mucosal Resection
				35.4.7.4	 Esophagectomy
			35.4.8 Treatment Modalities Used in Locally Advanced Esophageal Cancer
				35.4.8.1	 Radiation Therapy
				35.4.8.2	 Chemotherapy
				35.4.8.3	 Chemoradiation Alone
				35.4.8.4	 Chemoradiation and Surgery
				35.4.8.5	 Surveillance
				35.4.8.6	 Palliative Options for Esophageal Carcinoma
			35.4.9 Molecules of Companion Diagnosis
				35.4.9.1	 Targeting the EGFR Signaling Pathway
				35.4.9.2	 Targeting the HER2 Signaling Pathway
				35.4.9.3	 Angiogenesis Inhibitors
				35.4.9.4	 Others
			35.4.10 Typical Medical Case
		35.5	 Gastric Cancer
			35.5.1 Overview
			35.5.2 Clinical Appearance
			35.5.3 Risk Factors for Gastric Cancer
			35.5.4 Historical Classification of GC
			35.5.5 Laboratory Diagnosis
				35.5.5.1	 Principles of Biomarker Testing by NCCN Guidelines for GC
				35.5.5.2	 Traditional Biomarkers of GC
				35.5.5.3	 Molecular Biomarkers of GC
					Tumor Specific Protein 70 (SP70)
					HER2/neu
					MSI
					PD-L1
					Circulating Nucleic Acids
					The Other Genetic Susceptibility Genes
			35.5.6 Typical Medical Case
			35.5.7 Conclusion
		35.6	 Colorectal Cancer
			35.6.1 Overview
			35.6.2 Epidemiology
			35.6.3 Aetiology
				35.6.3.1	 Environmental Factors
				35.6.3.2	 Genetic Factors
				35.6.3.3	 Other Risk Factors
					Colorectal Polyps (Adenomatous Polyps)
					Inflammatory Bowel Disease
					Cholecystectomy
			35.6.4 Screening
				35.6.4.1	 Screening Object
				35.6.4.2	 Screening Test
					Questionnaire Survey Based on High-Risk Factors
					Fecal Occult Blood Test (FOBT)
					Fecal DNA Testing
					Endoscopy
			35.6.5 Clinical Diagnosis
				35.6.5.1	 Clinical Manifestation
					Changes in Bowel Habits and Fecal Traits
					Abdominal Pain
					Abdominal Mass
				35.6.5.2	 Digital Rectal Examination
				35.6.5.3	 Imaging Examination
				35.6.5.4	 Histopathology
			35.6.6 Molecular Diagnosis
				35.6.6.1	 Broad-Spectrum Tumor Serum Markers
					CEA
					CA19-9
					CA242 and CA50
				35.6.6.2	 Tumor Specific Protein (SP70)
				35.6.6.3	 Liquid Biopsy
					CTCs
					CfDNA
				35.6.6.4	 Genetic Biomarkers
					Microsatellite Instability (MSI)
					KRAS and BRAF Mutations
					SMAD4 Mutation
				35.6.6.5	 Proteomics
					P53
					CDX2
					MutT-Related Proteins
					C-Met
				35.6.6.6	 Epigenetics
					MicroRNA (miRNA)
					Methylation
						CpG island Methylator Phenotype (CIMP)
						ZNF331
						LINE-1
			35.6.7 Therapy
			35.6.8 Typical Medical Case
		References
	36: Kidney Diseases
		36.1	 Polycystic Kidney Disease
			36.1.1	 Overview
			36.1.2	 Diagnosis
			36.1.3	 Genetic Testing Algorithm
			36.1.4	 Correlation Between Phenotype and Genotype
			36.1.5	 Genetic Counselling
			36.1.6	 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
			36.1.7	 Typical Clinical Case
		36.2	 Nephropathy
			36.2.1	 Overview
			36.2.2	 Classification
				36.2.2.1	 Glomerular Diseases
					Acute Glomerulonephritis
						Signs and Symptoms
						Causes and Pathogenesis
					Molecular Markers
						Serum Glomerular Filtration Markers
						Urinary Glomerular Cell Injury Markers
						Treatment
					Chronic Glomerulonephritis
						Signs and Symptoms
						Causes and Pathogenesis
						Molecular Markers
						Treatment
					Nephrotic Syndrome
						Signs and Symptoms
						Causes
						Pathogenesis
						Complications
						Laboratory Diagnosis
						Treatment
					IgA Nephropathy
						Signs and Symptoms
						Causes
						Pathogenesis
						Laboratory Diagnosis
						Treatment
				36.2.2.2	 Tubular Injury
					Signs and Symptoms
					Causes and Pathogenesis
					Molecular Markers
		36.3	 Kidney Cancer
			36.3.1	 Overview
				36.3.1.1	 Summary of Renal Tumors
				36.3.1.2	 The Classification of Malignant Kidney Diseases
			36.3.2	 Renal Cell Carcinoma
				36.3.2.1	 Serological Markers of Renal Cell Carcinoma
					Traditional Biomarkers for Renal Cell Carcinoma
					Novel Molecular Markers for Renal Cell Carcinoma
						Transforming Growth Factor β (TGF-β)
						Carbonic Anhydrase IX
						PTEN
						B7-H1
						Insulin-Like Growth Factor II mRNA Binding Protein 3 (IMP3)
					Other Laboratory Diagnostic Testings
				36.3.2.2	 Typical Case
			36.3.3	 Renal Pelvis Carcinoma
				36.3.3.1	 Biomarkers of Renal Pelvic Carcinoma
					Traditional Biomarkers for Renal Pelvic Carcinoma
						β2 Microglobulin
						Neuro-Specific Enolase
					Novel Molecular Biomarkers for Renal Pelvic Carcinoma
						Oncogene Marker
						Tamm–Horsfall Protein Antibody
				36.3.3.2	 Typical Case
		36.4	 Hantavirus Hemorrhagic Fever with Renal Syndrome
			36.4.1	 Overview
			36.4.2	 Pathogenesis
				36.4.2.1	 Pathogenesis
					Direct Action of the Virus
					Immunity
					The Role of Various Cytokines and Mediators
				36.4.2.2	 Pathology and Physiology
					Shock
					Bleeding
					Acute Renal Failure
			36.4.3	 Course of Disease
				36.4.3.1	 Fever Period
				36.4.3.2	 Hypotension Shock Period
				36.4.3.3	 Oliguria
				36.4.3.4	 Polyuria
				36.4.3.5	 Recovery Period
			36.4.4	 Diagnosis
				36.4.4.1	 Blood Routine
				36.4.4.2	 Urine Routine
				36.4.4.3	 Biochemical Tests
				36.4.4.4	 Special Inspections
				36.4.4.5	 Other Auxiliary Inspections
				36.4.4.6	 Differential Diagnosis
			36.4.5	 Treatment
			36.4.6	 Typical Medical Case
		References
	37: Cardiovascular Disease
		37.1	 Acute Myocardial Infarction
			37.1.1	 Overview
			37.1.2	 Clinical Appearance
			37.1.3	 Laboratory Diagnosis
			37.1.4	 Management
			37.1.5	 Conclusion
		37.2	 Heart Failure
			37.2.1	 Overview
			37.2.2	 Clinical Appearance
			37.2.3	 Laboratory Diagnosis
			37.2.4	 Management
			37.2.5	 Conclusion
		37.3	 Myocarditis
			37.3.1	 Overview
			37.3.2	 Clinical Appearance
			37.3.3	 Laboratory Diagnosis
				37.3.3.1	 Endomyocardial Biopsy
				37.3.3.2	 Cardiac Biomarkers
				37.3.3.3	 Inflammation Biomarkers
				37.3.3.4	 Pathogenetic Diagnosis
			37.3.4	 Management
			37.3.5	 Conclusion
		37.4	 Congenital Heart Disease (CHD)
			37.4.1	 Overview
			37.4.2	 Clinical Appearance
				37.4.2.1	 Excessive Sweating
				37.4.2.2	 Poor Feeding
				37.4.2.3	 Acyanotic and Cyanotic Congenital Heart Diseases
				37.4.2.4	 Heart Murmurs
			37.4.3	 Laboratory Diagnosis
				37.4.3.1	 Karyotyping
				37.4.3.2	 Array CGH
				37.4.3.3	 Whole-Exome Sequencing
				37.4.3.4	 Whole-Genome Sequencing
			37.4.4	 Management
			37.4.5	 Conclusion
		37.5	 Arrhythmia
			37.5.1	 Overview
			37.5.2	 Clinical Appearance
			37.5.3	 Laboratory Diagnosis
				37.5.3.1	 LQTS
				37.5.3.2	 SQTS
				37.5.3.3	 Brugada Syndrome
				37.5.3.4	 Catecholaminergic Polymorphic Ventricular Tachycardia
			37.5.4	 Management
			37.5.5	 Conclusion
		References
	38: Lung Disease
		38.1	 Lung Cancer
			38.1.1	 Overview
			38.1.2	 Etiology and Pathogenesis
			38.1.3	 Clinical Appearance
			38.1.4	 Routine Diagnosis (Fig. 38.3)
				38.1.4.1	 Imaging Tests
					Chest X-Ray
					CT Scan
					Magnetic Resonance Imaging
				38.1.4.2	 Endoscopic and Histopathological Examination
					Sputum Cytology
					Bronchoscopy
					Mediastinoscopy
					Needle Biopsy
			38.1.5	 Molecular Diagnosis
				38.1.5.1	 Routine Biomarkers
				38.1.5.2	 Companion Diagnostic Biomarker (Fig. 38.5) (Table 38.1)
					EGFR
					ALK and ROS1
					KRAS
					BRAF
					MET
					HER2
					PD-1/PD-L1
					Others
				38.1.5.3	 Other Biomarkers
					Tumor Specific Protein 70
						Auxiliary Diagnosis
						Therapy Efficacy Monitoring
						Predict Prognosis
					DNA Methylation
					Potential Biomarkers
				38.1.5.4	 Liquid Biopsy
			38.1.6	 Treatments and Therapies
			38.1.7	 Conclusion
			38.1.8	 Typical Medical Case
		38.2	 Cystic Fibrosis
			38.2.1	 Overview
			38.2.2	 Clinical Appearance
				38.2.2.1	 Respiratory System
				38.2.2.2	 Digestive System
				38.2.2.3	 Other
			38.2.3	 Laboratory Diagnosis
			38.2.4	 Conclusion
		38.3	 Pneumonia
			38.3.1	 Overview
			38.3.2	 Clinical Appearance
			38.3.3	 Laboratory Diagnosis
				38.3.3.1	 Pathogenic Diagnosis
				38.3.3.2	 Key Points for the Laboratory Diagnosis of Respiratory Infections
			38.3.4	 Management
			38.3.5	 Conclusion
		38.4	 Tuberculosis
			38.4.1	 Overview
			38.4.2	 Clinical Appearance
			38.4.3	 Laboratory Diagnosis
			38.4.4	 Typical Medical Case
			38.4.5	 Management
			38.4.6	 Conclusion
		38.5	 Influenza
			38.5.1	 Overview
			38.5.2	 Pathogenesis
				38.5.2.1	 Transmission
				38.5.2.2	 Pathology and physiology
			38.5.3	 Epidemiology
				38.5.3.1	 Seasonal Variations
				38.5.3.2	 Epidemic and Pandemic Spread
			38.5.4	 Course of the Disease
			38.5.5	 Diagnosis
				38.5.5.1	 Virus Isolation and Identification
				38.5.5.2	 Serological Testing and Typing Methods
				38.5.5.3	 Quick Diagnosis
					Loop-Mediated Isothermal Amplification
					Gene Chip Technology
					Pyrosequencing Technology
					Nuclear Acid Sequence-Based Amplification
			38.5.6	 Prevention and Treatment
				38.5.6.1	 Prevention
					Influenza Vaccination
					Improve Your Own Immunity
					Other
				38.5.6.2	 Treatment
					NA Inhibitors
					M2 Inhibitors
			38.5.7	 Typical Medical Case
		38.6	 COVID-19
			38.6.1	 Overview
			38.6.2	 Pathogenesis
				38.6.2.1	 Transmission
				38.6.2.2	 Pathology and Physiology
			38.6.3	 Epidemic and Pandemic Spread
			38.6.4	 Course of the Disease
				38.6.4.1	 Clinical Classification
			38.6.5	 Diagnosis
				38.6.5.1	 Blood Routine and Biochemical Indicators
				38.6.5.2	 Serological Detection of 2019-nCoV
				38.6.5.3	 Molecular Diagnostic Methods
					Specimen Collection and Storage
					Biosafety Considerations
					Detection of 2019-nCoV by Real-Time RT-PCR
					Assay Control Addition
					Interpretation of Results
					Detection of 2019-nCoV by Genetic Sequencing
				38.6.5.4	 Chest CT for COVID-19
				38.6.5.5	 Clinically Diagnosis
			38.6.6	 Prevention and Treatment
				38.6.6.1	 Prevention
					Diagnosis and Isolation
					Improve Your Immunity
					Others
				38.6.6.2	 Treatment
			38.6.7	 Typical Medical Case
		References
	39: Blood Disorders
		39.1	 Blood Cancer
			39.1.1	 Overview
			39.1.2	 Myeloid Neoplasms
				39.1.2.1	 Myelodysplastic Syndromes
				39.1.2.2	 Acute Myeloid Leukemia
				39.1.2.3	 Chronic Myeloid Leukemia
				39.1.2.4	 Myeloproliferative Neoplasms
				39.1.2.5	 Myelodysplastic/Myeloproliferative Neoplasms
			39.1.3	 Lymphoid Neoplasms
				39.1.3.1	 Lymphoid Leukemia
				39.1.3.2	 Lymphoma
				39.1.3.3	 Myeloma
			39.1.4	 Conclusion
		39.2	 Coagulation Disorders
			39.2.1	 Hemophilia
				39.2.1.1	 Introduction
					Hemophilia A
						Mutations in the F8 Gene
					Hemophilia B
						Mutations in the F9 Gene
				39.2.1.2	 Clinical Manifestation
				39.2.1.3	 Laboratory Diagnosis
					Hemophilia A
					Hemophilia B
				39.2.1.4	 Management
				39.2.1.5	 Conclusions
			39.2.2	 Von Willebrand Disease
				39.2.2.1	 Introduction
					Molecular Basis of Disease
					Type 1 Von Willebrand Disease
					Type 3 Von Willebrand Disease
					Type 2 Von Willebrand Disease
						Type 2A Von Willebrand Disease
						Type 2B Von Willebrand Disease
						Type 2M Von Willebrand Disease
						Type 2N (Normandy) Von Willebrand Disease
				39.2.2.2	 Clinical Manifestation
				39.2.2.3	 Laboratory Diagnosis
				39.2.2.4	 Management
				39.2.2.5	 Conclusions
			39.2.3	 Hereditary Thrombocytopenia
			39.2.4	 Typical Medical Case
		39.3	 Hematologic Disorders
			39.3.1	 Hemoglobinopathies
				39.3.1.1	 Sickle Cell Disease
					Overview
					Clinical Manifestation
					Laboratory Diagnosis
					Management
					Conclusions
			39.3.2	 Thalassemia
				39.3.2.1	 Overview
					α-Thalassemia
					β-Thalassemia
				39.3.2.2	 Clinical Manifestation
				39.3.2.3	 Laboratory Diagnosis
				39.3.2.4	 Management
				39.3.2.5	 Conclusions
			39.3.3	 Typical Medical Case
		References
	40: Endocrine and Metabolic Diseases
		40.1	 Diabetes
			40.1.1	 Overview
			40.1.2	 Classification and Clinical Appearance
				40.1.2.1	 Categories of Increased Risk for Diabetes (Prediabetes)
				40.1.2.2	 Type 1 Diabetes Mellitus
				40.1.2.3	 Type 2 Diabetes Mellitus
				40.1.2.4	 Gestational Diabetes Mellitus
				40.1.2.5	 Monogenic Diabetes Syndromes
			40.1.3	 Diagnosis
				40.1.3.1	 Prediabetes
				40.1.3.2	 Diagnostic Criteria for Diabetes Mellitus
				40.1.3.3	 Gestational Diabetes Mellitus
				40.1.3.4	 Monogenic Diabetes
			40.1.4	 Laboratory Diagnosis
				40.1.4.1	 Blood Glucose
				40.1.4.2	 Urinary Glucose
				40.1.4.3	 Glucose Tolerance Test
				40.1.4.4	 Glycated Hemoglobin (HbA1c)
				40.1.4.5	 Ketone Body
				40.1.4.6	 Lactic Acid and Pyruvic Acid
				40.1.4.7	 Blood Glucose Regulator
				40.1.4.8	 Urinary Microalbumin
				40.1.4.9	 Genetic Test
				40.1.4.10	 Autoimmune Markers
				40.1.4.11	 Other
			40.1.5	 Management
			40.1.6	 Conclusion
			40.1.7	 Typical Medical Case
		40.2	 Thyroid Disease
			40.2.1	 Overview
			40.2.2	 Thyroid Carcinoma
				40.2.2.1	 Classification of Thyroid Carcinoma
				40.2.2.2	 Differentiated Thyroid Carcinoma
				40.2.2.3	 Medullary Thyroid Carcinoma
				40.2.2.4	 Typical Case
			40.2.3	 Nontoxic Goiter
				40.2.3.1	 Etiology and Epidemiology
				40.2.3.2	 Classification of Goiter
				40.2.3.3	 Laboratory Diagnosis of Nontoxic Goiter
				40.2.3.4	 Typical Case
			40.2.4	 Thyroid Nodule
				40.2.4.1	 Definition and Clinical Manifestations
				40.2.4.2	 Laboratory Diagnosis
				40.2.4.3	 Typical Case
			40.2.5	 Thyroiditis
				40.2.5.1	 Introduction
				40.2.5.2	 Classification and Laboratory Diagnosis of Thyroiditis
				40.2.5.3	 Typical Case
			40.2.6	 Hypothyroidism
				40.2.6.1	 Definition and Classification of Hypothyroidism
				40.2.6.2	 Diagnosis of Hypothyroidism
				40.2.6.3	 Typical Case
			40.2.7	 Hyperthyroidism and Thyrotoxicosis
				40.2.7.1	 Graves’ Disease
				40.2.7.2	 Toxic Adenoma and Multinodular Toxic Goiter
				40.2.7.3	 Typical Case
		40.3	 Dwarfism
			40.3.1	 Clinical Appearance
				40.3.1.1	 Disproportionate Dwarfism
				40.3.1.2	 Proportionate Dwarfism
				40.3.1.3	 Others
			40.3.2	 Diagnosis
				40.3.2.1	 Disproportionate Dwarfism
				40.3.2.2	 Proportionate Dwarfism
				40.3.2.3	 Others
			40.3.3	 Correlation Between Phenotype and Genotype
				40.3.3.1	 Achondroplasia
				40.3.3.2	 Spondyloepiphyseal Dysplasia Congenita
				40.3.3.3	 Growth Hormone Deficiency
				40.3.3.4	 Others
			40.3.4	 Genetic Counseling
				40.3.4.1	 Achondroplasia
				40.3.4.2	 Spondyloepiphyseal Dysplasia Congenita
				40.3.4.3	 Combined Pituitary Hormone Deficiency
				40.3.4.4	 Others
			40.3.5	 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
				40.3.5.1	 Achondroplasia
				40.3.5.2	 Others
			40.3.6	 Typical Clinical Case
		40.4	 Adrenopathy
			40.4.1	 Overview
				40.4.1.1	 Structure of Adrenal Gland
			40.4.2	 Cushing’s Syndrome
				40.4.2.1	 Pathogeny and Clinical Manifestation
				40.4.2.2	 Laboratory Diagnosis of Cushing’s Syndrome
				40.4.2.3	 Typical Medical Case
			40.4.3	 Primary Aldosteronism
				40.4.3.1	 Pathogeny and Clinical Appearance
				40.4.3.2	 Laboratory Diagnosis of Primary Aldosteronism
				40.4.3.3	 Genetic Testing
				40.4.3.4	 Typical Medical Case
			40.4.4	 Addison’s Disease
				40.4.4.1	 Epidemiology and Clinical Appearance
				40.4.4.2	 Laboratory Diagnosis of Addison’s Disease
				40.4.4.3	 Typical Medical Case
			40.4.5	 Pheochromocytoma
				40.4.5.1	 Overview
				40.4.5.2	 Laboratory Diagnosis of Pheochromocytoma
				40.4.5.3	 Genetic Testing
				40.4.5.4	 Typical Medical Case
			40.4.6	 Congenital Adrenocortical Hyperplasia
				40.4.6.1	 Overview
				40.4.6.2	 Laboratory Examination
				40.4.6.3	 Genetic Testing
				40.4.6.4	 Typical Medical Case
		40.5	 Gout
			40.5.1	 Overview
			40.5.2	 Clinical Appearance
			40.5.3	 Laboratory Diagnosis
				40.5.3.1	 Blood Uric Acid
				40.5.3.2	 Urine Uric Acid
				40.5.3.3	 Synovial Fluid Analysis
				40.5.3.4	 Other Blood Tests
				40.5.3.5	 Gene Testing
				40.5.3.6	 Others
			40.5.4	 Management
			40.5.5	 Conclusion
			40.5.6	 Typical Medical Case
		References
	41: Neurological Disease
		41.1	 Alzheimer’s Disease
			41.1.1	 Overview
			41.1.2	 Etiology
			41.1.3	 Clinical Appearance
			41.1.4	 Clinical Diagnosis
				41.1.4.1	 Diagnostic Criteria
				41.1.4.2	 Laboratory Diagnosis
					Cerebrospinal Fluid (CSF) Biomarkers
						Amyloid-β
						Tau Protein
					Blood-Based Biomarker Candidates
						Aβ1–42:Aβ1–40 Ratio
						Phosphorylated Tau Protein (P-Tau)
						Neurofilament Light (NFL)
					Classical Genetic Testing
						Genes Implicated in EOAD
						Genes Implicated in LOAD
						Other Potential Genetic Risk Genes of AD
					Candidate Epigenetics Biomarkers
						DNA Methylation
						Histone Modifications
						MicroRNAs
					Imaging Diagnosis
			41.1.5	 Management
			41.1.6	 Conclusion
			41.1.7	 Typical Medical Case
		41.2	 Glioma
			41.2.1	 Overview
			41.2.2	 Classification
				41.2.2.1	 By Type of Cell
				41.2.2.2	 By Grade
				41.2.2.3	 By Location
			41.2.3	 Signs and Symptoms
			41.2.4	 Causes and Pathogenesis
				41.2.4.1	 Genetic Factors
				41.2.4.2	 Adult Stature and Body Weight
				41.2.4.3	 Allergies and Other Medical Conditions
				41.2.4.4	 Dietary Factors
				41.2.4.5	 Ionizing Radiation
			41.2.5	 Molecular Markers in Gliomas
				41.2.5.1	 Loss of Heterozygosity (LOH) of 1p19q
				41.2.5.2	 IDH1 and IDH2 Mutations
				41.2.5.3	 MGMT Promotor Methylation
				41.2.5.4	 Germline Mutation of TP53
				41.2.5.5	 Important Factors in Glioma Biology
					RTK/RAS/PI(3K), P53
					IDH Mutation
					Hypoxia, Pseudohypoxia, and Angiogenesis
			41.2.6	 Treatment
				41.2.6.1	 Surgical Resection
				41.2.6.2	 Radiation Therapy
				41.2.6.3	 Chemotherapy
			41.2.7	 Typical Medical Case
		41.3	 Muscular Dystrophy/Muscular Atrophy
			41.3.1	 Overview
			41.3.2	 Clinical Appearance
				41.3.2.1	 Muscular Dystrophy
					Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)
					Congenital Muscular Dystrophy
					Myotonic Dystrophy
					Facioscapulohumeral Muscular Dystrophy
					Limb-Girdle Muscular Dystrophy
					Oculopharyngeal Muscular Dystrophy
					Distal Myopathy
					Emery-Dreifuss Muscular Dystrophy
				41.3.2.2	 Muscular Atrophy
					Spinal Muscular Atrophy
					Amyotrophic Lateral Sclerosis
			41.3.3	 Diagnosis
				41.3.3.1	 Muscular Dystrophy
					DMD and BMD
					CMD
					DM
					FSHD
					LGMD
					OPMD
					Distal Myopathy
					EDMD
				41.3.3.2	 Muscular Atrophy
					SMA
					ALS
			41.3.4	 Correlation between Phenotype and Genotype
				41.3.4.1	 Muscular Dystrophy
					DMD/BMD
					CMD
					DM
					FSHD
					OPMD
					Distal Myopathy
					EDMD
				41.3.4.2	 Muscular Atrophy
					SMA
					ALS
			41.3.5	 Genetic Counseling
			41.3.6	 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
			41.3.7	 Typical Clinical Case
		41.4	 Epilepsy
			41.4.1	 Overview
			41.4.2	 Diagnosis
			41.4.3	 Genetic Testing Algorithm
				41.4.3.1	 Exclude Nongenetic Disorders
				41.4.3.2	 Family History
				41.4.3.3	 General Physical and Neurologic Evaluations
				41.4.3.4	 Inherited Metabolic Disorders
			41.4.4	 Correlation between Phenotype and Genotype
			41.4.5	 Genetic Counseling
			41.4.6	 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
			41.4.7	 Typical Clinical Case
		References
	42: Reproductive Organ Cancer
		42.1	 Breast Cancer
			42.1.1	 Overview
			42.1.2	 Anatomy of the Breast
			42.1.3	 Histological Classification
			42.1.4	 Surveillance and Diagnosis
				42.1.4.1	 Imaging Technologies and Applications in Early Diagnosis and Prognosis for Breast Cancer
				42.1.4.2	 Mammography
				42.1.4.3	 Ultrasound
				42.1.4.4	 Magnetic Resonance Imaging
				42.1.4.5	 Breast Cancer Biomarkers for Risk Assessment, Screening, Detection, Diagnosis, and Prognosis
				42.1.4.6	 Genomic Biomarkers
				42.1.4.7	 Epigenomic Biomarkers and Methylation Biomarkers
				42.1.4.8	 miR Biomarkers
				42.1.4.9	 Breast Circulating Tumor Cells Potential Biomarkers for Breast Cancer Diagnosis and Prognosis Evaluation
				42.1.4.10	 Tumor-Specific Protein 70 (SP70)
				42.1.4.11	 Other Protein Markers
			42.1.5	 Typical Medical Case
		42.2	 Ovarian Cancer
			42.2.1	 Overview
			42.2.2	 Clinical Appearance
			42.2.3	 Laboratory Diagnosis
				42.2.3.1	 Tumor Markers
					CA125
					Human Epididymis 4 (HE4)
					Mesothelin
					Osteopontin
					Kallikreins
					B7-H4
					Interleukins
					Vascular Endothelial Growth Factor (VEGF)
					MicroRNAs
					Exosomes
					Circulating Cell-Free DNA
				42.2.3.2	 Genetic Test
					Genetic Mutation
					Epigenetic Regulation
			42.2.4	 Management
			42.2.5	 Conclusion
			42.2.6	 Typical Medical Case
		42.3	 Cervical Cancer
			42.3.1	 Overview
				42.3.1.1	 Staging and Classification
				42.3.1.2	 HPV Introduction
					HPV Infection Procedure in the Cervix
					Ingestion of the Virus and Delivery of the Genome to Nucleus
					Virus Transcription and Life Cycle
					Self-limiting and Persistent Infection of the Virus
			42.3.2	 Clinical Appearance
			42.3.3	 Laboratory Diagnosis
				42.3.3.1	 Papanicolaou Test (Pap Test)
				42.3.3.2	 Molecular Marker
					Squamous Cell Carcinoma Antigen (SCCA)
					Serum Fragments of Cytokeratin (CYFRA)
			42.3.4	 Management
			42.3.5	 Conclusion
			42.3.6	 Typical Medical Case
		References
	43: Prenatal Diagnosis and Preimplantation Genetic Diagnosis
		43.1	 Noninvasive Prenatal Testing
			43.1.1	 Overview
			43.1.2	 Laboratory Examination
				43.1.2.1	 Cell-Free Fetus DNA(cffDNA) and Its Detection in Maternal Plasma
				43.1.2.2	 Fetal Nucleated Red Blood Cells
			43.1.3	 Clinical Application
				43.1.3.1	 Chromosomal Aneuploidy
				43.1.3.2	 Subchromosomal Abnormalities
				43.1.3.3	 Single Gene Mutations
				43.1.3.4	 Fetal Sex Determination
				43.1.3.5	 Hemolytic Disease of the Newborn
				43.1.3.6	 Other Applications
			43.1.4	 Summary
			43.1.5	 Typical Medical Case
		43.2	 Mitochondrial Deafness
			43.2.1	 Introduction
				43.2.1.1	 Mitochondria and Mitochondrial Genome
				43.2.1.2	 Mitochondrial Diseases
				43.2.1.3	 Deafness and Mitochondrial Deafness
			43.2.2	 Clinical Appearance
				43.2.2.1	 Mitochondrial Syndromic Hearing Loss
					Kearn-Sayre Syndrome
					Mitochondrial Encephalopathy with Lactic Acidosis, and Stroke-like episodes
					Myoclonic Epilepsy with Ragged Red Fibers
				43.2.2.2	 Mitochondrial Non-Syndromic Hearing Loss
					MT-RNR1 Related Mitochondrial Hearing Loss
						Sensorineural Hearing Impairment Induced by Aminoglycosides
						Sensorineural hearing impairment without aminoglycosides exposure
						MT-TS1 Related Mitochondrial Hearing Loss
			43.2.3	 Diagnosis
				43.2.3.1	 Mitochondrial Sensorineural Hearing Loss
					Initial Diagnosis
					Establishing the Diagnosis
				43.2.3.2	 Differential Diagnosis
					Aminoglycosides-Induced Ototoxicity
			43.2.4	 Management
				43.2.4.1	 Treatment of Manifestations
				43.2.4.2	 Prevention of Primary Manifestations
				43.2.4.3	 Prevention of Secondary Complications
				43.2.4.4	 Surveillance
				43.2.4.5	 Agents and Circumstances to Avoid
				43.2.4.6	 Evaluation of Relatives at Risk
			43.2.5	 Prenatal Diagnosis and Preimplantation Genetic Diagnosis in Mitochondrial Deafness
				43.2.5.1	 Prenatal Diagnosis in Mitochondrial Deafness
				43.2.5.2	 Preimplantation Genetic Diagnosis in Mitochondrial Deafness
			43.2.6	 Conclusion
			43.2.7	 Internet Resources
		43.3	 Hereditary Vascular Retinopathy
			43.3.1	 Overview
				43.3.1.1	 The Anatomy of the Retina
				43.3.1.2	 The Physiology of the Retinal Vessels
				43.3.1.3	 The Examination of the Retina
			43.3.2	 von Hippel-Lindau Syndrome
				43.3.2.1	 Overview
				43.3.2.2	 Clinical Appearance
				43.3.2.3	 Examination
				43.3.2.4	 Diagnosis
				43.3.2.5	 Genotype–Phenotype Correlations
				43.3.2.6	 Differential Diagnosis
					Isolated Hemangioblastoma or RCC
					Pheochromocytoma
					RCC
				43.3.2.7	 Management
				43.3.2.8	 Genetic Counseling
			43.3.3	 Retinal Vasculopathy with Cerebral Leukodystrophy
				43.3.3.1	 Overview
				43.3.3.2	 Clinical Appearance
				43.3.3.3	 Examination
				43.3.3.4	 Diagnosis
				43.3.3.5	 Genotype–Phenotype Correlations
				43.3.3.6	 Differential Diagnosis
				43.3.3.7	 Management
				43.3.3.8	 Genetic Counseling
			43.3.4	 Familial Exudative Vitreoretinopathy
				43.3.4.1	 Overview
				43.3.4.2	 Clinical Appearance
				43.3.4.3	 Examination
				43.3.4.4	 Diagnosis
				43.3.4.5	 Genotype–Phenotype Correlations
				43.3.4.6	 Differential Diagnosis
					Retinopathy of Prematurity
					Coats Disease
					Persistent Hyperplastic Primary Vitreous
					Norrie Disease
					Toxocariasis
				43.3.4.7	 Management
				43.3.4.8	 Genetic Counseling
			43.3.5	 Typical Medical Case
		References
	44: Transplant Matching
		44.1	 Overview
			44.1.1	 Hyperacute Rejection
			44.1.2	 Acute Rejection
			44.1.3	 Chronic Rejection
		44.2	 HLA and Transplantation Matching
			44.2.1	 Overview
			44.2.2	 Genetic Characteristics of HLA
				44.2.2.1	 Phenotype, Monotype, and Genotype
				44.2.2.2	 HLA Genetic Model
					Monotype Inheritance
					Codominant Inheritance
					Linkage Disequilibrium
		44.3	 Tissue Matching Technology and Related Experiments
			44.3.1	 HLA Typing
				44.3.1.1	 HLA Serological Typing Technology
				44.3.1.2	 HLA Genotyping Technology
				44.3.1.3	 The Basis of HLA Genotyping–Polymerase Chain Reaction
				44.3.1.4	 Restriction Fragment Length Polymorphism Typing
				44.3.1.5	 Single Strand Conformation Polymorphism Typing
				44.3.1.6	 Sequence-Specific Primers Typing
				44.3.1.7	 PCR-Sequence Specific Oligonucleotide Probe Hybridization
					The Basic Principle of PCR-SSO
					PCR-SSO Reverse Hybridization Typing
					Flow Cytometry-SSO Typing Method
				44.3.1.8	 Gene Chip Typing
					Basic Principle
					Advantages of Gene Chip
				44.3.1.9	 HLA Typing Based on Sequence-Based Typing
			44.3.2	 HLA Antibody Detection
				44.3.2.1	 Complement Dependent Cytotoxicity
				44.3.2.2	 ELISA
				44.3.2.3	 Flow Fluorescent Microsphere Method
			44.3.3	 MICA Antibody Analysis
			44.3.4	 Non-HLA Antibodies
			44.3.5	 Cross-Matching Experiment of Donor and Recipient
			44.3.6	 Monitoring of Drug Concentration After Transplantation
			44.3.7	 Detection of Pathogens Associated with Infection After Transplantation
			44.3.8	 Routine Blood Cell Analysis and Biochemical Index Detection
		44.4	 Clinical Significance of HLA Matching in Organ Transplantation
			44.4.1	 HLA and Kidney Transplantation
			44.4.2	 HLA and Liver Transplantation
			44.4.3	 HLA and Heart Transplantation
			44.4.4	 HLA and Lung Transplantation
		References
	45: Paternity Testing
		45.1	 Overview
			45.1.1	 Alleged Father (AF) /Alleged Mother (AM)
			45.1.2	 Genetic Marker
			45.1.3	 Genetic Law
			45.1.4	 Basic Principles of Paternity Testing
		45.2	 Several Common Paternity Testing Techniques
			45.2.1	 Paternity Exclusion by Red Blood Cell Type
			45.2.2	 Paternity and Family Relationship Identification by DNA Fingerprint Techniques
		45.3	 Judgement and Analysis of Paternity Testing Results
			45.3.1	 Parent-Child Relationship Exclusion
				45.3.1.1	 Excluding Probability of Paternity (EP)
				45.3.1.2	 Calculation of Excluding Probability of Paternity (EP)
				45.3.1.3	 Cumulative Excluding Probability of Paternity (CEP)
				45.3.1.4	 Errors in Excluding Parent-Child Relationship and Its Solutions
			45.3.2	 Affirmation of Parent-Child Relationship
				45.3.2.1	 Paternity Index
				45.3.2.2	 Relative Chance of Paternity
			45.3.3	 Forensic Criteria of Paternity Testing
				45.3.3.1	 The Standard of Paternity Exclusion
				45.3.3.2	 The Standard of Paternity Affirmation
			45.3.4	 Laboratory Standards of Paternity Testing
		45.4	 Collection and Preservation of Paternity Test Samples
			45.4.1	 Collection of Paternity Test Samples
				45.4.1.1	 Blood/Bloodstain
				45.4.1.2	 Hair
				45.4.1.3	 Oral Swab
				45.4.1.4	 Saliva and Saliva Spots
				45.4.1.5	 Amniotic Fluid Samples
			45.4.2	 Preservation of Paternity Test Samples
		References
Appendixes
	Appendix A: Tests of Infectious Disease
	Appendix B: Cancer Tests
	Appendix C: Tests of Genetic Disease
	Appendix D: Pharmacogenomics
		D.1 Anticoagulation Therapy
		D.2 Antihypertensive Therapy
		D.3 Anticardiac Insufficiency
		D.4 Antiangina Pectoris Treatment
		D.5 Anti-inflammatory Treatment
		D.6 Antigout Treatment
		D.7 Antipeptic Ulcer Treatment
		D.8 Antidepressant Therapy
		D.9 Antipsychotic Treatment
		D.10 Antiepileptic Treatment
		D.11Antileukemia Treatment
		D.12 Antineoplaston
		D.13 Antifungal Therapy
		D.14 Anti-hyperthyroidism
		D.15 Anti-tuberculosis Treatment
		D.16 Antiasthma treatment
		D.17 Anesthetic Treatment of Paroxysmal Pain
		D.18 Disease Prevention
		D.19 Erectile Dysfunction
		D.20 Hypoglycemic Therapy
		D.21 Immunosuppressive Therapy
		D.22 Lipid Control Therapy
		D.23 Risk Profile