Coal-burning Type of Endemic Fluorosis : Pathophysiology and Clinical Treatments

Endemic fluorosis is caused by excessive intake of fluorine in drinking water, air, food, tea and other media in a specific natural environment for a long time, which involves at least 25 countries, such as China, India, Vietnam, Iran, Egypt, Mexico, Argentina and influences more than 200 million of population. China and India are the countries with the most extensive endemic fluorosis and the most serious damages. There are three main intake sources of endemic fluorosis, e.g., drinking water, coal-burning pollution and drinking tea. Coal-burning type of endemic fluorosis was established in Guizhou Province of China in 1970’s. The residents in the areas used indoor stoves with no flue to burn coals with high content of fluoride to bake grains in the autumn and heat in the winter. This results in excessive intake of fluorine and then leads chronic poisoning. It has been confirmed that 13 provinces of China with 34.3 million of population are influenced by this type of fluorosis with severe injuries to most organs of human body. The content of this book covers the epidemiology, pathological changes, molecular pathogenesis and clinical treatments of the disease. This book is a suitable reference for the researchers and graduate students in this field, which is helpful to improve the understanding of this disease and to take preventive measures. Preface Acknowledgments Contents Contributors Part I: Discovery and Epidemiology of Endemic Fluorosis Chapter 1: Discovery and Concept of Endemic Fluorosis General Background about Fluorine The Discovery of Endemic Fluorosis Types of Endemic Fluorosis Drinking Water Type of Endemic Fluorosis Coal-Burning Type of Endemic Fluorosis Brick-Tea Type of Endemic Fluorosis Effect of Coal-Burning Type of Endemic Fluorosis on the Human Body Molecular Mechanisms underlying the Pathological Changes Caused by Chronic Fluorosis Clinical Treatments of Coal-Burning Type of Endemic Fluorosis Conclusion References Chapter 2: Epidemic Status of Coal-burning Type of Endemic Fluorosis Introduction Fluoride Metabolism Fluoride Ingestion Fluoride Excretion Physiological Function of Fluoride Epidemic Types and Features of Endemic Fluorosis Drinking Water Type of Endemic Fluorosis Coal-Burning Type of Endemic Fluorosis Brick-Tea Type of Endemic Fluorosis National Standards for Division of Endemic Fluorosis Area and Control of Endemic Fluorosis in China Division Standard of Endemic Fluorosis Areas Control Criteria for Endemic Fluorosis A History of Discovering Coal-Burning Type of Endemic Fluorosis Prevention and Control Measures of Coal-Burning Type of Endemic Fluorosis Improving Stoves Health Education Clinical Treatments Personalized Treatment of Dental Fluorosis Surgical Treatment of Skeletal Fluorosis Pharmaceutical Study on Targeting Endemic Fluorosis Other Measures Conclusion References Part II: Pathological Changes of Endemic (Chronic) Fluorosis Chapter 3: Skeletal Fluorosis Introduction Clinical Manifestations and Pathological Features of Skeletal Fluorosis Fluoride Metabolism and Its Correlation with Bone Tissue Clinical Manifestations of Skeletal Fluorosis Pathological Features of Skeletal Fluorosis Imbalance of Bone Turnover in Chronic Fluorosis Dynamic Imbalance of Bone Turnover Important Factors and Signal Pathways Associated with Imbalance in Bone Turnover Disorder of Calcium Low Ca2+ in External Environment Increased Intracellular Ca2+ Oxidative Stress and Endoplasmic Reticulum Stress Correlated with Skeletal Fluorosis Hormonal Regulatory Mechanism in the Procedure of Skeletal Fluorosis Genetic Susceptibility and Epigenetics Conclusions References Chapter 4: Medical Imaging Manifestation of Skeletal Fluorosis Introduction Manifestation and Epidemic Characteristic of Skeletal Fluorosis Prevalence of Skeletal Fluorosis Etiology, Pathology, and Pathogenesis of Skeletal Fluorosis Clinical Manifestation of Skeletal Fluorosis Medical Imaging Check X-ray Results Computerized Tomography (CT) Manifestation Magnetic Resonance Imaging (MRI) Manifestation Single Photon Emission CT (SPECT) Manifestation Diagnosis Criteria of Endemic Skeletal Fluorosis in China Scope Terminology and Definition Evidence of Diagnosis Principle of Diagnosis Division Criteria of Diagnosis Clinical Diagnosis and Division X-ray Results of Diagnosis and Division Prerequisites of Bone and Articular X-ray Check Differential Diagnosis Imaging Changes of Skeletal Fluorosis Correlation Among All Types of Endemic Fluorosis Mechanism of Endemic Skeletal Fluorosis Imaging Manifestation Medical Imaging Characteristics of Endemic Skeletal Fluorosis Diagnostic Value of Olecranarthropathy for Skeletal Fluorosis Differentiating Diagnosis Value of Digital Radiography in Skeletal Fluorosis by X-ray Check and Screening Conclusion References Chapter 5: Epidemic Characteristic and Pathogenesis of Dental Fluorosis Introduction General Epidemiological Characteristics of Dental Fluorosis Age Distribution Deciduous Teeth Gender Distribution Geographical Distribution Urban and Rural Distribution Epidemiological Significance and Medical Application of Dental Fluorosis Morbidity Rate Morbidity Rate of 8- to 12-Year-Old Children Dean ́s Index for Dental Fluorosis and Epidemic Grading Dental Fluorosis Morbidity Rate Served as Major Index for Determining and Classifying Endemic Areas Dental Fluorosis Morbidity Rate Served as Major Index to Evaluate Prevention and Control Efficacy Dental Fluorosis Morbidity Rate Mirrored the Severe Damage of Fluorosis on Children Relationship Between Prevalence of Dental Fluorosis and Urinary Fluoride Levels Physiological Effect of Fluoride on Teeth Biological Effects of Fluoride on Teeth Effect of Fluoride on Tooth Development Promoting Re-mineralization of Teeth by Fluoride Pathological Changes of Dental Fluorosis Changes in Tooth Enamel with Chronic Fluorosis Dentin Changes Cementum Changes Pathogenesis of Dental Fluorosis Damage of Fluoride to Enamel Damage of Fluoride on Amelogenin Damage of Fluoride on Dentin Conclusions References Chapter 6: Damage in Nervous System Introduction Clinical Changes of Nervous System in Patients with Endemic Fluorosis Histopathological Changes of Nervous System in Patients with Chronic Fluorosis Changes of Learning and Memory Capacity in Experimental Fluorosis Cases Effects of Chronic Fluorosis on the Development of Nervous System Changes of Fetal Development in Endemic Fluorosis Area Experimental Study on the Effect of Chronic Fluorosis on Fetal Development Changes of IQ of Children in Endemic Fluorosis Areas Molecular Mechanism of Nerve Injury in Chronic Fluorosis Mechanism of Free Radical Damage Mechanism of Structural Changes of Cellular Biofilm Lipids Mechanism of Neurotransmitter Receptor Alteration Mechanism of Neuronal Apoptosis Mechanism of Nitric Oxide Mechanism of Signal Transduction Pathway Alteration in Nervous System Mechanism of Developing Damage of Nervous System Caused by Chronic Fluorosis Conclusion References Chapter 7: Modification of Digestive System Introduction Influence of Chronic Fluorosis on Liver Normal Function and Metabolism of Liver Effects of Chronic Fluorosis on Liver Morphology, Function, and Metabolism Mechanism of Liver Changes Caused by Chronic Fluorosis The Increased Oxidative Damages in Liver Aggravated Inflammation The Elevating Level of Apoptosis Proteins and Genes Related to Changes in Liver Metabolism and Function Effect of Fluorosis on Gastrointestinal Tract Function and Metabolism of Gastrointestinal Tract Effect of Chronic Fluorosis on Gastrointestinal Function Mechanism of Gastrointestinal Dysfunction Caused by Fluoride Exposure Effect of Fluorosis on Pancreas Function and Metabolism of Pancreas Effects of Excessive Fluoride on the Morphology and Function of Pancreas Conclusion References Chapter 8: Modification of Urinary System Introduction Effect of Chronic Fluorosis on Kidney Renal Pathohistological Changes by Chronic Fluorosis Effect of Chronic Fluorosis on Renal Function and Metabolism Mechanism of Renal Damage Caused by Chronic Fluorosis Change of Renal Cell Cycle Disorder of Renal Calcium Balance High Level of Oxidative Stress Excessive Autophagy of Renal Cells Modification of the Related Cytokines Apoptosis of Renal Cells Correlative Detection Indexes for Judging Renal Function Changes in Chronic Fluorosis Serological Detection Index Urine Test Index Oxidative Stress Related Indicators Conclusion References Chapter 9: Modification of Cardiovascular System Introduction Population-Based Study Experiment The Cultivation of Cardiomyocyte Potential Pathogenesis of Fluoride Triggered Cardiovascular System Impairment Oxidative Stress Apoptosis Energy Metabolism Conclusion References Chapter 10: Damage of Endocrine System Introduction Influences of Fluoride Exposure on the Thyroid Gland Iodine Metabolism and Thyroid Function Influences of Fluoride Exposure on Function of Thyroid Mechanisms of Thyroid Damage Induced by Excessive Fluoride Influences of Fluoride Exposure on the Activity of TPO Parathyroid Function and Calcium Homeostasis Metabolism and Effect of Parathyroid Hormone (PTH) Possible Influences of Fluoride Exposure on the Body through PTH (Including Changes in Serum Free PTH Content, Abnormal Calciu... Influences of Fluoride Exposure on Insulin Metabolism and Diabetes Influences of Fluoride Exposure on the Reproductive System Conclusion References Chapter 11: Damages to Reproductive System by Coal-burning Type of Endemic Fluorosis Introduction Effect of Fluorosis on Sperm and Semen Quality Effects of Fluorosis on Sperm Morphology and Structure Effect of Fluorosis on Sperm Acrosome Effects of Fluorosis on the Testis Effect of Fluorosis on Testis Weight Effect of Fluorosis on Testicular Tissue Structure Effect of Fluorosis on Testicular Ultrastructure Effect of Fluorosis on Testicular Blood-Testis Barrier Impairment of Testicular Spermatogenic Function by Fluorosis Effect of Fluorosis on Apoptosis of Spermatogenic Cells in Testis Effect of Fluorosis on Oxidative Stress in Testicular Tissue Effect of Fluorosis on Testicular Cellular Immune Privilege/Autophagy Effects of Fluorosis on Epididymis and Vas Deferens Effects of Fluorosis on the Prostate and Seminal Vesicles Effects of Fluorosis on Male Reproductive Endocrine Levels Effects of Fluorosis on Sex Hormone Levels Effect of Fluoride on Serum Inhibin b (Inhb) in Adult Men Therapeutic Agents and Prognosis Testosterone Vitamin E and Lycopene Choline Taurine Extracts of Ginseng and Panama Leaf Insulin-like Growth Factor-I (IGF-I) and Human Chorionic Gonadotropin (hCG) Damage to the Female Reproductive System Due to Coal-Burning Type of Endemic Fluorosis Effects of Fluorosis on the Uterus Effects of Fluorosis on the Ovary Effects of Fluorosis on Ovarian Granulosa Cells Effects of Fluorosis on the Placenta and Fetus Effects of Fluorosis on Female Sex Hormone Levels Oxidative Stress Damage to the Female Reproductive System by Fluorosis Conclusion References Part III: Molecular Pathogenesis of Endemic (Chronic) Fluorosis Chapter 12: Enhanced Oxidative Stress Introduction Elevated Level of Oxidative Stress Induced by Chronic Fluorosis Free Radicals and Reactive Oxygen Species (ROS) Antioxidant Systems Imbalance Between Oxidative and Antioxidant Systems Chronic Fluorosis is Associated with an Elevated Level of Oxidative Stress Chronic Fluorosis is Associated with Modifications in the Structures of Lipids in Cellular Membranes Effects of the Oxidative Stress Induced by Chronic Fluorosis on Mitogen-Activated Protein Kinase (MAPK) Effects of the Oxidative Stress Induced by Chronic Fluorosis on Receptors Acetylcholine Receptors Advanced Glycation End Products (AGEs)/the Receptor for Advanced Glycation End Products (RAGE) Receptors for N-methyl-D-Aspartic Acid Receptors (NMDARs) Effects of the Oxidative Stress Induced by Chronic Fluorosis on Various Enzymes Changes in Mitochondria Correlated to the Oxidative Stress Induced by Chronic Fluorosis Apoptosis Resulting from the Oxidative Stress Induced by Chronic Fluorosis Prevention and Treatment of Chronic Fluorosis by Antioxidants Conclusions References Chapter 13: High Level of Inflammation Introduction An Overview of Chronic Inflammatory Response Chronic Inflammatory Response Proinflammatory Cytokines Inflammatory Cytokines Inflammatory Cytokine Regulator Anti-inflammatory Cytokines Basic Pathological Changes of Inflammatory Response Inflammatory Responses in Endemic Skeletal Fluorosis Inflammatory Responses of Non-bone Systems in Endemic Fluorosis Central Nervous System Damage Liver Damage Renal Damage Damage on Heart and Blood Vessels Thyroid Damage Reproductive System Damage Conclusion References Chapter 14: Effect of Fluoride on Signal Transduction Pathways Introduction Effect of Fluoride on G-protein Coupled Receptor (GPCR) Signal Transduction Pathway cAMP Signal Transduction Pathway Protein Kinase C (PKC) Signal Transduction Pathway Effect of Fluoride on Mitogen-Activated Protein Kinases (MAPKs) Signal Transduction Pathway Effect of Fluoride on Apoptosis Signal Transduction Pathway Death Receptor Mediated Apoptosis Signal Transduction Pathway Mitochondrial Mediated Apoptosis Signal Transduction Pathway ER Stress Mediated Apoptosis Signal Transduction Pathway Phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/PKB) Signal Transduction Pathway NF-κB Signal Transduction Pathway Effect of Fluoride on TGF-β/Smad Signal Transduction Pathway Effect of Fluoride on Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Signal Transduction Pathway Effect of Fluoride on Wnt/β-catenin Signal Transduction Pathway Effect of Fluoride on Autophagy Signal Transduction Pathway Conclusion References Chapter 15: Changes of Receptors Introduction Classification and Function of Cell Membrane Receptors Ligand-Gate Ion Channel Receptors G-protein Coupled Receptors Single Transmembrane α-helical Receptor Classification and Function of Intracellular Receptors The Cytoplasmic Receptor The Nuclear Receptor The Impact of Chronic Fluorosis on Acetylcholine Receptors The Structure, Function, and Distribution of nAChRs The Effect of Fluoride on nAChRs Structure, function, and Distribution of mAChRs The Effect of Fluoride on mAChRs The Impact of Chronic Fluorosis on N-methyl-D-Aspartate Receptors (NMDARs) Structure, Function, and Distribution of NMDARs The Effect of Fluoride on NMDARs The Impact of Chronic Fluorosis on Advanced Glycation End Products (AGEs) and Their Receptors Structure, Function, and Distribution of AGEs The Impact of Fluoride on AGEs and Their Receptors The Impact of Chronic Fluorosis on Vit D Receptor Structure, Function, and Distribution of Vit D The Impact of Fluoride on VDR The Impact of Chronic Fluorosis on Peroxisome Proliferators-Activated Receptors (PPARs) Structure, Function, and Distribution of PPARs The Impact of Fluoride on PPAR Conclusion References Chapter 16: Alteration of Endoplasmic Reticulum Stress Endoplasmic Reticulum Stress and Unfolded Protein Response (UPR) Endoplasmic Reticulum Stress Binding immunoglobulin Protein (BiP) UPR Signal Pathway PERK Pathway Inositol-Requiring Kinase 1 (IRE-1) Pathway ATF6 Pathway ER-Related Protein Degradation Relationship between Endoplasmic Reticulum Stress and Oxidative Stress Role of ERS in the Mechanism Underlying Fluoride-Induced Non-bone Damage Role of ERS in the Mechanism Underlying Fluoride-Induced Bone Damage ERS and Dental Fluorosis ER and Skeletal Fluorosis Conclusion References Chapter 17: Mitochondrial Changes Introduction Mitochondrial Structure and Function of Mitochondrial DNA (mtDNA) Mitochondrial Respiratory Chain Function in Oxidative Phosphorylation Mitochondrial Spatial Structure and Regulatory Mechanism Mitochondrial Changes in Chronic Fluorosis Morphological Changes of Various Organs Caused by Chronic Fluorosis Ultramorphological Changes Induced by Fluorosis Changes of Dynamic Equilibrium of Mitochondrial Fusion and Fission Conclusion References Chapter 18: Calcium Metabolism Disorder in Chronic Fluorosis Biological Effect of Calcium Effects of Endemic Fluorosis on Calcium Metabolism Effects of Endemic Fluorosis on Ca2+ Metabolism of Skeletal Organs Effects of Endemic Fluorosis on Ca2+ Metabolism of Brain Mechanism of Endemic Fluorosis Caused by Ca2+ Metabolism Disorder Problems and Prospects Conclusion References Chapter 19: Altering of Carbohydrate Metabolism Introduction Carbohydrate Metabolism Synthesis of Glucose Decomposition of Glucose Glycoprotein Collagen Osteocalcin (OCN) P-glycoprotein (P-gp) Advanced Glycation End Products Chronic Fluorosis and Disorder of Carbohydrate Metabolism Chronic Fluorosis Caused Carbohydrate Metabolism Disorder Chronic Fluorosis and Hyperglycemia Chronic Fluorosis and Altering of Glycoprotein Collagen Osteocalcin P-gp and Advanced Glycation End Products (AGEs) Conclusion References Chapter 20: Changes in Gene Expression Introduction Genes Associated with Enhanced Susceptibility to Chronic Fluorosis Genes Related to the Metabolism of Free Radicals Osteocalcin (OCN), Calcitonin (CT), and Calcitonin Receptors (CTR) Collagen Type I Estrogen Vitamin D Receptor (VDR) Catechol-O-Methyltransferase (COMT) Parathyroid Hormone (PTH) The Epigenetics of Chronic Fluorosis The Relationship between Epigenetics and Environmental Factors Correlation of Choric Fluorosis with Epigenetic Change Fluoride and Histone Modifications Fluoride and miRNA Alteration of Imprinted Genes by Fluoride Conclusions References Part IV: Clinical Diagnosis and Treatments of Coal-Burning Type of Endemic Fluorosis Chapter 21: Biological Indicators for Early Diagnosis of Endemic Fluorosis Introduction Clinical Indicators Closely Related to Diagnosing Endemic Fluorosis Epidemiology Skeletal Fluorosis Dental Fluorosis Fluoride Content in Different Organs or Tissues Fluoride Content in Blood Fluoride Content in Urine Fluoride Levels in Bone, Nail, Hair, and Others Biological Parameters Correlated to Chronic Fluorosis Serum Enzymology Mineral Content in Blood Changed Genetic Polymorphisms and Epigenetics Oxidative Stress Indicators Related to Chronic Fluorosis Conclusion References Chapter 22: Comprehensive Prevention and Control of Coal-burning Type of Endemic Fluorosis Introduction A National Measure Proposed by Government and Implemented by Medical Staff and the General Public Education on Prevention of Chronic Fluorosis Selected Tips of Fluorosis Prevention Preparation and Make of Fluorosis Prevention Education Materials Tips of Publicizing Fluorosis Prevention Publicity of Fluorosis Prevention via Media and Giveaways Education on Fluorosis Prevention Taken by Housewives in the Endemic Areas Education on Fluorosis Prevention Carried Out at School Education on Fluorosis Prevention Undertaken by Healthcare and Medical Institutions Improvement of Stoves Improvement of Stoves for Fluorosis Prevention Tailor-Made Fluorosis Prevention Equipment for Project Families Standard of Fluorosis Prevention Stove Instructing the Operation and Maintenance of Improved Stoves in Families of Endemic Areas The Construction and Application of Clean Energy Behavioral Intervention Promotion of Corn and Pepper Dehydration by Soot-Free Thermal Flux Technology Adopting the Habit of Rinsing Before Cooking Free Lunch in Rural Schools to Reduce the Overall Intake of Fluoride for Students National Ban on Small Scale and Illegal Coal Mines to Reduce the Use of Coal A Combined Practice of Poverty Alleviation Project to Promote the Prevention and Control of Coal-Burning Type of Fluorosis Official Measures of Prevention and Control on Coal-Burning Type of Endemic Fluorosis Prevention and Control Area Identification Budget, Funds, and Management for the Elimination of Fluorosis Hazards Prevention and Control Aim Specific Aim Personnel Management Mobilization Training Fluorosis Prevention Approach Prevention and Control Progress Schedule Procedures and Evaluation Standards of Prevention Effects Procedures and Standards of Evaluation Application The Manner of Acceptance and Evaluation Level by Level Evaluation and Acceptance Announcement Control Standard of Endemic Fluorosis Elimination Standards of Endemic Fluorosis Assessment of Prevention and Control Effect on Coal-Burning Endemic Fluorosis Monitoring of Dental Fluorosis Status Evaluation for the Typical Area of Coal-Burning Type of Endemic Fluorosis in Liupanshui City of Guizhou Province Effective Control to the Disease The Changes in Incidence Rate of Dental Fluorosis and the Urinary Fluoride Load Manifestation of Skeletal Fluorosis Conclusion References Chapter 23: Surgical Treatment of Joint Damage in Skeletal Fluorosis Introduction THA Treatment for Severe Hip Osteoarthritis Induced by Fluorosis Clinical Manifestation Imaging Examination Laboratory Examination Diagnostic Criteria and Characteristics Differential Diagnosis on Severe Hip Osteoarthritis Induced by Chronic Fluorosis Rheumatic Arthritis Femoral Head Necrosis Primary Hip Osteoarthritis Secondary Hip Osteoarthritis Ankylosing Spondylitis Surgical Treatment Operative Indication Preoperative Preparation and Evaluation Prosthesis Selection Anesthesia Methods Incision Surgical Operation Postoperative Management Operative Complications TKA for the Treatment of Severe Knee Osteoarthritis Induced by Skeletal Fluorosis Clinical Manifestation Medical Imaging Results Diagnostic Criteria and Characteristics Differential Diagnosis to Severe Knee Osteoarthritis Induced by Chronic Fluorosis Rheumatoid Arthritis Osteoarthritis Surgical Treatment of Knee Osteoarthritis Induced by Severe Fluorosis Operation Indication Preoperative Preparation and Evaluation Prosthesis Selection Surgical Operation Postoperative Management Surgical Treatment of Spinal Stenosis Induced by Chronic Fluorosis Clinical Manifestations Medical Imaging Check Laboratory Examination Diagnosis and Differential Diagnosis Surgical Indication Anesthesia Surgical Incision Choice of Surgical Method PCEML for Cervical Spinal Stenosis Induced by Chronic Fluorosis Total Laminectomy for Decompression and Partial Facetectomy for Decompression for Chest and Lumbar Spinal Stenosis Induced by ... Postoperative Management Prevention and Treatment of Surgical Complications Cerebrospinal Fluid Leakage Epidural Hematoma Spinal Cord and Nerve Root Injuries Infection Conclusion References Chapter 24: Clinical Prevention and Treatment of Coal-burning Type of Endemic Fluorosis Introduction Index, Clinical and Differential Diagnosis of Dental Fluorosis Index of Dental Fluorosis Clinical Diagnosis Differential Diagnosis Treatments of Dental Fluorosis Tooth Whitening Composite Resin Porcelain Veneer Full Crown Glass Ionomer Cement Notices During Treatment Dental Fluorosis Color Shade Selection of Dental Fluorosis Conventional Shade Guide Instrument Measurement Development and Application of Customized Fluorosis Teeth Shade Guide Color Modification of Restoration Special Dyeing Tooth Preparation is the Foundation of Restoration Prevention of Dental Fluorosis Conclusion References Chapter 25: Drug Development Introduction Chemical Elements Commonly Used to Treat Endemic Fluorosis Boron Magnesium Calcium Aluminum Selenium Zinc Molybdenum Copper Traditional Chinese Medicine (TCM) Prescription for the Treatment of Endemic Fluorosis ``Dan-Lan-Xian Boron ́ ́ Therapy Fluoride Capsule ``Guling-Tongbi ́ ́ Pill Development Trend of Antioxidant Drugs Current Situation and Problems in the Study of Endemic Fluorosis Drugs Conclusion References Chapter 26: Improvement of the Health Condition of Local Residents After Comprehensive Treatments of Coal-Burning Type of Ende... Introduction Research Subjects Effect of Comprehensive Treatments on Children with Dental Fluorosis Effect of Comprehensive Treatments on Intelligence of Children Effect of Comprehensive Measures on Skeletal Fluorosis Changes in Common Blood Biochemistry Parameters Routine Measurement of Blood Biochemistry Activity of GPT and GOT Level of Blood Lipids Level of Blood Glucose Changes of Blood Biochemistry Parameters in Elder Population Changes of Cardiac Function Changes of Oxidative Stress Related Indexes Activities of Enzymes Expressions of GST and MPO mRNAs Changes of Gene Polymorphism of Antioxidant Enzymes Quality of Life and Its Influence Factors of the Residents Living in the Areas of Coal-Burning Fluorosis with Comprehensive In... Conclusion References List of Abbreviations A B C D E F G H I K L M N O P R S T U V W X