Research on Q-markers of Polygoni Perfoliati Herba based on analytic hierarchy process-entropy weight method and fingerprints / 中国中药杂志

The potential quality markers(Q-markers) of Polygoni Perfoliati Herba were studied based on analytic hierarchy process(AHP)-entropy weight method(EWM), network pharmacology, and spectrum-effect relationship analysis. The AHP-EWM was used for quantitative identification of the Q-markers. To be specific, AHP was applied for the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM for the analysis of the second-level indexes supported by literature and experimental data. Based on literature and network pharmacology, the validity analysis was to study the component-target-disease-efficacy network, and select the components with the strongest correlation with the efficacy of clearing heat and removing toxin, diuresis and alleviating edema, and relieving cough. For the testability analysis, the high performance liquid chromatography(HPLC) and literature research were used to determine the 10 components in Polygoni Perfoliati Herba, and the fingerprints of Polygoni Perfoliati Herba were established at the same time. The specificity analysis was based on the statistics of the number of plants in which the components existed. Thereby, the 11 compounds: quercetin, oleanolic acid, ellagic acid, gallic acid, kaempferol, rutin, esculetin, quercetin-3-O-glucuronide, ursolic acid, protocatechuic acid, and ferulic acid, were identified as potential Q-markers. The 11 compounds were identified to have high anti-inflammatory activity, indicating that the 11 Q-markers may be the functional material basis. The result in this study is expected to serve as a reference for the quality control of Polygoni Perfoliati Herba.

Modern research thoughts and methods on bio-active components of TCM formulae / 中国天然药物

TCM formulae are the important guidances for clinical application of traditional Chinese medicines, which follow the principles of diagnosis and treatment in TCM. Elucidating the bio-active components of TCM formulae is the key to the modernization and internationalization of traditional Chinese medicines. With the rapid development of modern instruments and technology, many new theories, methods and strategies are emerging, which upgrade the research of TCM formulae into a higher level. Only when the medicinal efficacy, bio-active components, function mechanism of TCM formulae are understood, we can guarantee TCM safety and quality control. In this paper, we summarized the latest modern research thoughts and methods on bio-active components of TCM formulae including formula decomposition study, serum pharmacology and serum pharmacochemistry, association analysis, biochromatography, network pharmacology, metabolomics and proteomics, so as to provide reference for the research and development of TCM in the future.

Research Progress on Compatibility Mechanism of Coptidis Rhizoma-Euodiae Fructus： A Review / 中国实验方剂学杂志

Herb pair， a common form of compounding in Chinese medicinal prescriptions， reflects the experience of pharmacists in clinical medication in the past. It is characterized by simple composition while has the basic characteristics of Chinese medicine compounding. The combination of two medicinal herbs can enhance effect or reduce toxicity. Coptidis Rhizoma （CR） has the effects of clearing heat， drying dampness， purging fire， and removing toxin. Euodiae Fructus （EF） is acrid， bitter， and hot-natured， which can not only warm the Yang Qi in spleen and stomach to dissipate cold and relieve pain， but also descend stomach Qi and prevent vomiting. Furthermore， it can warm the liver and kidney. CR and EF form a typical cold-heat herb pair， which oppose and yet also complement each other. Specifically， their cold and heat natures interact with each other to clear liver fire， harmonize stomach for descending adverse Qi， relieve depression， and dissipate mass. CR clears the intestine and stops dysentery， while EF warms the middle and promotes the circulation of Qi. The combination of them can thus clear heat， dry dampness， and relieve pain. Modern pharmacological studies have demonstrated that CR-EF has not only significant efficacy against digestive system diseases but also good anti-cancer， anti-inflammatory， anti-ulcer， and lipid-lowering activities. Therefore， the article summarized the effect enhancement and toxicity reduction of the herb pair at the levels of cellular molecule， isolated organ， and whole animal， and clarified the mechanism of its pharmacological action. It will provide a theoretical basis for further development and clinical use of the herb pair.

Research on Q-markers of Eupatorium lindleyanum based on analytic hierarchy process-entropy weight method and network pharmacology / 中国中药杂志

The potential quality markers( Q-markers) of Eupatorium lindleyanum were studied with analytic hierarchy process(AHP)-entropy weight method(EWM) and network pharmacological method. Based on the concept of Q-markers of traditional Chinese medicine, AHP-EWM was employed to quantitatively identify the Q-markers of E. lindleyanum. AHP method was applied to the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM method was used to analyze the secondlevel indexes supported by literature and experimental data. At the same time, based on the theory and method of network pharmacology, the component-target-disease-efficacy network of E. lindleyanum was built, and the components most closely related to the efficacy of resolving phlegm and relieving cough and asthma were screened out. Through the integrated analysis of the results obtained with AHP-EWM and network pharmacological method, 13 compounds including rutin, quercetin, nepetin, cirsiliol, luteolin, hyperoside,isoquercitrin, kaempferol, caffeic acid, eupalinolide K, eupalinolide A, eupalinolide B, and eupalinolide C were comprehensively identified as the potential Q-markers of E. lindleyanum. The results provide a basis for the quality control of E. lindleyanum.

Identification of quality markers of Qixuehe Capsules based on analytic hierarchy process and entropy weight methods / 中国中药杂志

Qixuehe Capsules is a compound Chinese patent medicine developed for treating the disorder of Qi and blood(a common etiology of gynecological disease), which has remarkable effects on smoothing liver and regulating Qi, activating blood circulation, and relieving pain. However, due to its complex prescriptions(15 herbs) and multiple effects, the quality control of Qixuehe Capsules has always been a bottleneck problem limiting its sustainable development. Therefore, this study adopted the traditional Chinese medicine Q-markers quantitative identification system established previously by our research group based on the combination of analytic hierarchy process and entropy weight methods. With the different effects of Qixuehe Capsules as the entry point, the comprehensive scores of chemical ingre-dients in Qixuehe Capsules under the items of effectiveness(smoothing liver and regulating qi, activating blood circulation, and relieving pain), testability and specificity were calculated and integrated, respectively. Subsequently, through the analysis of compatibility relationship of Qixuehe Capsules, 15 active ingredients with high comprehensive scores were found to be the top Q-mar-kers of Qixuehe Capsules, including ferulic acid, quercetin, caffeic acid, kaempferol, rutin, Z-ligustilide, senkyunolide Ⅰ, vanillic acid, protocatechuic acid, chlorogenic acid, rosmarinic acid, senkyunolide A, gallic acid, tetrahydropalmatine and eugenol. Collectively, this study not only provided scientific evidence for further research on the improvement and standardization of quality standards of Qixuehe Capsules but also provided methodological references for the quantitative identification of Q-markers of multi-effect traditional Chinese medicine formulae.

Quantitative identification of TCM Q-markers based on analytical hierarchy and the entropy weight comprehensive method by taking Shaoyao Gancao decoction as an example / 药学学报

The quality markers (Q-markers) of traditional Chinese medicine (TCM) have become a topic of interest in TCM research in recent years. Nonetheless, there is still no consensus on how to scientifically characterize TCM Q-markers. Our study establishes an identification method for TCM Q-markers based on the analytical hierarchy process (AHP) and the entropy weight comprehensive method. By constructing an evaluation system encompassing the target layer, the factor layer and the control layer, AHP can be used to analyze the weight of three core TCM quality attributes, including effectiveness, testability and specificity. Following that, the entropy weight method is employed to analyze the specific indicators for each attribute based on the literature and experimental data. Finally, the comprehensive weight of each index is obtained by combining the two weights, and the comprehensive weight and the specific value of each component is multiplied and summed to obtain the integrated score ranking, and thereby identify the TCM Q-markers. Taking Shaoyao Gancao decoction as an example, the analysis revealed that the top 8 components are as follows: paeoniflorin > quercetin > albiflorin > glycyrrhizic acid > naringenin > liquiritin > oxypaeoniflorin > benzoylpaeoniflorin, and can be identified as Q-markers of Shaoyao Gancao decoction. This study not only provides support for the establishment of quality standards and process quality control of TCM formulae, but also provides innovative ideas and methods for quantitative evaluation and accurate identification of TCM Q-markers.

Studies on blood enrichment and anti-tumor effects of combined Danggui Buxue Decoction, Fe and rhEPO based on colon cancer-related anemia model and gut microbiota modulation / 中国天然药物

Colon cancer-related anemia (CCRA) is mainly caused by systemic inflammation, intestinal bleeding, iron deficiency and chemotherapy-induced myelosuppression in colon cancer. However, the best therapeutic schedule and related mechanism on CCRA were still uncertain. Studies on blood enrichment and anti-tumor effects of combined Danggui Buxue Decoction (DBD), Fe and rhEPO based on CCRA and gut microbiota modulation were conducted in this paper. Here, CCRA model was successfully induced by subcutaneous inoculation of CT-26 and i.p. oxaliplatin, rhEPO + DBD high dosage + Fe (EDF) and rhEPO + DBD high dosage (ED) groups had the best blood enrichment effect. Attractively, EDF group also showed antitumor activity. The sequencing results of gut microbiota showed that compared to P group, the relative abundances of Lachnospiraceae and opportunistic pathogen (Odoribacter) in ED and EDF groups were decreased. Interestingly, EDF also decreased the relative abundances of cancer-related bacteria (Helicobacter, Lactococcus, Alloprevotella) and imbalance-inducing bacteria (Escherichia-Shigella and Parabacteroides) and increased the relative abundances of butyrate-producing bacteria (Ruminococcaceae_UCG-014), however, ED showed the opposite effects to EDF, this might be the reason of the smaller tumor volume in EDF group. Our findings proposed the best treatment combination of DBD, rhEPO and Fe in CCRA and provided theoretical basis and literature reference for CCRA-induced intestinal flora disorder and the regulatory mechanism of EDF.

Research progress on processing history evolution as well as effect on chemical compositions and traditional pharmacological effects of Rhei Radix et Rhizoma / 中国中药杂志

Rhei Radix et Rhizoma(RRR) is a commonly used traditional Chinese medicine, with extensive pharmacological effects and clinical applications. This paper summarized processing history evolution of RRR and its effect on chemical compositions and pharmacological effects, and provided feasible insights for further studies on the chemical compositions and pharmacological effects of RRR before and after processing. Relevant information demonstrated that RRR has a long history of processing and various methods. At pre-sent, Chinese Pharmacopoeia mainly records four processing methods: cleaning(raw RRR), wine processing(RRR stir-fried with wine), steaming processing(RRR wine steaming), fried charcoal(RRR charring). RRR has a good effect in clearing heat effect, hemostatic effect and blood promoting effect, and its main chemical components are anthraquinone/anthrones, stilbene, phenylbutanone, chromogens, flavonoids and tannin compounds. This paper reviewed the history evolution of RRR and its effect on chemical composition and pharmacological changes, and put forward further study ideas, with the aim to provide a basic reference for processing mechanism, effective material basis and clinical application of RRR.

Dose-toxicity-effect relationship between licorice combined with rhubarb in purgation / 中国中药杂志

The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.

Research thoughts and methods on grading identification and transmission change law of traditional Chinese medicine(TCM) Q-marker / 中国中药杂志

The quality marker( Q-maker) of traditional Chinese medicine( TCM) has been the core concept of TCM quality evaluation and control in recent years. Based on the knowledge and long-term practice of the researches on TCM quality,we put forward that " Taking the effectiveness as the core,the measurability and peculiarity as necessary conditions,and considering compatibility for TCM formulae,TCM Q-makers are selected and confirmed,and then the transmission and traceability should be investigated as its functional attributes". Selecting the commonly used representative TCM as the research object,based on the score of TCM effectiveness,measurability and peculiarity,a layered three-dimensional integrated technology was adopted for the quantitative evaluation and grading identification of the Q-markers for TCM. And after Q-markers for TCM are selected and confirmed,the transmission variation of the Q-markers is studied in the whole process from the formation of TCM to its function representation. Based on TCM chemical and biological characteristics as well as effectiveness,and integrating multidisciplinary techniques and methods,researches on innovative methods for system identification and confirmation of the TCM Q-makers are developed emphatically to form representative and exemplary extensive application,which will provide significant theoretical and methodological support for effectively improving the quality control level of TCM.

Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change / 药物分析学报

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate com-bination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM"Eighteen Incompatible Medicaments", are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphin-ganine were screened out as the principal alternative biomarkers of compatibility group; sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of in-compatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM"Eighteen Incompatible Medicaments".

Modern research approaches and strategies for compatibility effects and efficacy components of herbal pairs / 药学学报

The herb pair is the simple and exquisite experience summary accumulated by generations of traditional Chinese medicine (TCM) experts in the process of long-term herbal prescription for curing diseases. Although it is only a combination of two herbs, it is cleverly matched and properly proportioned, which can well interpret TCM characteristics of "great combination and artful application". Moreover, the herb pair is an intermediate point between single herb and several TCM formulae, which implicates certain regularity and some connotation of many TCM formulae for diagnosis and treatment based on an overall analysis of the illness and the patient's condition. Our team has long been focusing on the complexity of drug interactions and the diversity of TCM components to carry out systematic research on herb pair by using modern scientific and technological knowledge and approaches. As results, a series of modern research approaches and strategies formed for the compatibility effect and bio-active components of the herb pair. By representing the principles and application characteristics of these approaches, this paper provides important support for elucidating scientific connotation of compatibility regularity of herb pairs and application of formulae optimization, as well as explorative ideas and approaches for modern research on other herb pairs.

Incompatible mechanism of compatibility of Chinese medicines based on Qianjinzi and Gancao effect on intestinal flora/barrier system / 中国中药杂志

The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function. It improved the degradation functions of mucus and aromatic amino acids on intestinal bacteria, which may increase the risk of disease and derived from intestinal urotoxin and other toxic substances. This study considered intestinal bacteria as an important target to study the interactions of traditional Chinese medicine. The "drug-intestinal bacteria-metabolism-toxicity" was applied in the experiment. Meanwhile, it provides ideas for exploring incompatible mechanism of traditional Chinese medicines.

Fumigation treatment of Four Yellow Qing Ling Water with artificial tears for dry eyes / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To observe the clinical efficacy of fumigation treatment of traditional Chinese medicine(Four Yellow Qing Ling Water) for dry eye, and to provide the reference for clinical treatment of dry eye. · METHODS: Totally 82 patients (164 eyes) were randomly divided into two groups from June 2016 to December 2016 in Ophthalmology Department of our hospital. The patients in control group were given artificial tears;the patients in the observation group were given artificial tears and fumigation treatment of traditional Chinese(Four Yellow Qing Ling Water) once a day. After treatment for 14d, the SchirmerⅠtest (SⅠt), break-up time (BUT), cornea fluorescein staining (FL) and clinical efficacy of two groups were compared. ·RESULTS:The efficiency rate of observation group was significantly better than the control group (87. 8% vs 70.7%,P<0.5). The SⅠt and BUT in the observation group were significantly higher than those in the control group (8.43 ± 2.51mm/5min vs 6.38 ± 2.52mm/5min, P<0.05;8.60±2.47s vs 6.35±2.29s, P<0.05); the FL in the observation group (0.84 ± 0.75 vs 1.26 ± 0.84, P<0.05) significantly lower than those in the control group. ·CONCLUSION: The fumigation treatment of traditional Chinese medicine (Four Yellow Qing Ling Water) combined with artificial tears for dry eyes can improve the clinical symptoms of dry eye syndrome.

Preparation and optimization of zhitong micro-emulsion formula / 中国中药杂志

To prepare Zhitong micro-emulsion in this study, with the empirical formula of Zhitong preparation as the model medicine, the essential oil in the formula as the oil phase, and the water decoction as the water phase. The types of surfactant and co-surfactant were investigated. The changes in micro-emulsion conductivity and construction, the water percentage in the micro-emulsion system, the changing curve of conductivity and the fine pseudo-ternary phase diagram of micro-emulsion were drawn to determine the surfactant-co-surfactant mass ratio (K(m)). Subsequently, the D-mixture design was used to optimize Zhitong Micro-emulsion formula, with particle size and surface tension of micro-emulsion as the indexes. Finally, efforts were made to determine part of physical parameters of Zhitong micro-emulsion and preliminarily detect its stability. The results showed that the micro-emulsion was optimal with the EL-35-tween 20 ratio of 4:1 in surfactant, whereas the absolute ethyl alcohol was recommended as the co-surfactant. The ratio between surfactant and co-surfactant (K(m)) was 1.5. The finalized micro-emulsion formula contains 12% surfactant, 8% co-surfactant, 70% 1 g x mL(-1) water decoction and 8% oil. The results of the preliminary stability experiment showed a better stability of Zhitong micro-emulsion.

The incompatibility mechanism based on the interaction of multiple-components for Flos Genkwa and Radix et Rhizoma Glycyrrhizae / 药学学报

By investigating the interaction between components from Flos Genkwa (FG) and Radix et Rhizoma Glycyrrhizae (RRG) and the dissolution profile of toxic components in co-decoction, the characteristics and possible mechanism of incompatibility were revealed. Ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and ultra-high performance liquid chromatography triple-quadrupole mass spectrometry (UPLC-TQ/MS) were used to analyze multi-components in different herb extractions prepared by different ratios of FG/FG processed by vinegar (FGV) and RRG, which reflect the interaction and characteristics of multiple components in incompatibility combinations. The results showed that the components dissolution was influenced by compatibility ratio with certain regularity. Whether FG processed by vinegar or not, with the increase of RRG in co-decoction, the dissolution of diterpenes, especially for yuanhuacine, yuanhuadine and yuanhuajine, the toxic ingredients of FG, increased significantly. From these results, the material basis and one possible mechanism of incompatibility between FG and RRG is the increasing dissolution of diterpenes, toxic components of FG in co-decoction process, which caused by interaction between multi-components in these two herbs.

A five-year follow-up study of hypothyroidism in areas with different iodine intakes / 中华内分泌代谢杂志

Objective To investigate epidemiologieal characteristics of hypothyroidism and factors influencing its outcome in the areas with different iodine intakes.Methods An epidemiologic follow-up study of thyroid diseases was performed in Panshan (iodine deficient),Zhangwu [mild iodine deficiency before universal salt iodination (USI) and more than adequate iodine intakes after USI ] and Huanghua ( iodine excessive) in China.A total of 3 761 subjects were investigated in 1999,and 3 018 (80.2% ) of them were followed up in 2004.FT_4,FT_3,TSH,thyroid autoantibodies and urinary iodine concentration were determined and thyroid B ultrasound was performed in all participants.Results Five-year cumulative incidence of overt hypothyroidism was 0.23%,0.47% and 0.35% in Panshan,Zhangwu and Huanghua,respectively.Twenty patients with autoimmune- induced overt hypothyroidism did not comply with the physician's orders to take thyroxine.Thyroid function spontaneously turned to normal in 55% of them,turned to subclinical hypothyroidism in 20% and maintained overt hypothyroidism in 25%.Five-year cumulative incidence of subclinical hypothyroidism in Zhangwu (2.60%) and Huanghua (2.89%) were significantly higher than that in Panshan(0.23% ) (both P＜0.01 ).One hundred patients with subclinical hypothyroidism were followed up,and 5% of them developed overt hypothyroidism,66% turned to euthyroidism and 29% maintained subclinical hypothyroidism.Raised serum TSH (＞6 mU/L) in the original survey ( OR = 3.4),positive thyroid autoantibodies in the follow-up study ( OR = 5.3 ) and more than adequate iodine supplementation in the mild iodine-deficient population ( OR = 8.0) were risk factors influencing outcome of subclinical hypothyroidism.Conclusion More than adequate iodine supplementation among a population in the mildly iodine-deficient area may increase the incidence of overt and subolinical hypothyroidism, and also influence outcome of subclinical hypothyroidism.

Incidences of hyperthyroidism in communities with different iodine intake levels:a five-year prospective and comparative epidemiological survey / 中华内分泌代谢杂志

Objective To analyze the relationship between different iodine intakes and epidemiological features of hyperthyroidism in 3 communities with different iodine intake levels,as well as to explore the risk factor for the pathogenesis of hyperthyroidism.Methods A cohort study was performed in 3 Chinese rural communities with long-term stable iodine nutrition status defined as mild deficient (Panshan),more than adequate (Zhangwu, previously mild iodine deficiency and salt iodization lasting 8 years until 2004) and excessive (Huanghua).A total of 3 761 (934 males,2 827 females) inhabitants aged above 13 participated in the original investigation in 1999 and 3 018(709 males,2 309 females) of them received identical examinations after 5 years.Results Median urinary iodine concentration of school-aged children was 87.61zg/L in Panshan,213.9?g/L in Zhangwu and 633.5?/L in Huanghua (P＜0.05) at fallowing up,and no statistic significance was found when comparing the corresponding data from original survey (83.5?g/L,242.9?g/L and 650.9?g/L).The accumulative incidence of hyperthyroidism was 13.6/1 000,9.4/1 000 and 8.1/1 000 (P＞0.05),being 16.4/1 000,11.2/1 000 and 9.1/1 000 (P＞0.05) in female,respectively in Panshan,Zhangwu and Huanghua.In original healthy subjects (without history of thyroid disease and overt thyroid dysfunction) merely with either positive thyroid peroxidase antibody (TPOAb＞50 IU/ml) or thyroglobulin antibody (TgAb＞40 IU/ml),the accumulative incidence of newly diagnosed hyperthyroidism was not significantly different among 3 communities in follow-up survey.TSH＜0.3 mIU/L,positive TPOAb or goiter in original healthy participants were associated with the occurrence of overt hyperthyroidism in 5 years [ Logistic Regression,OR = 5.7 (95% CI 2.1-15 ),OR = 3.8 (95% CI 1.7-8.7 ) and OR = 3.1 (95% CI 1.4-6.8) respectively].Conclusion Iodine supplementation in mild iodine deficient area does not increase the incidence of overt hyperthyroidism ultimately.Long-term excessive iodine intake does not affect the incidence and pattern of hyperthyroidism.TSH＜0.3 mIU/L,positive TPOAb and goiter in healthy individuals are the risk factors for hyperthyroidism.