[Clinical characteristics and risk factors of programmed death-1 inhibitors associated with thyroid gland injury].

Objective: To investigate the clinical characteristics and related risk factors of thyroid gland injury (TGI) in patients with a malignant tumor treated with a programmed death-1 (PD-1) inhibitor. Methods: A Retrospective case-control study. Data from 198 patients with a malignant tumor who received treatment with a PD-1 inhibitor in Chinese PLA General Hospital from October 2019 to October 2021 were collected and analyzed retrospectively. According to the TGI incurred after receiving treatment with a PD-1 inhibitor, patients were divided into a thyroid gland normal (TGN) group and TGI group. The prevalence, type, time of occurrence, and outcome of TGI were analyzed. The risk factors that may contribute to TGI were analyzed further by logistic regression. Results: TGI prevalence was 29.8% (59/198 cases) after treatment with a PD-1 inhibitor. There were significant differences with respect to previous radiotherapy and targeted therapy between the TGN group and TGI group (P<0.01 for both), but there were no significant differences with regard to sex, age, tumor type, previous surgery, previous chemotherapy, tumor metastasis, or type of PD-1 inhibitor (P>0.05 for all). Patients in the TGI group included those with subclinical hypothyroidism (32.2%, n=19), hypothyroidism (27.1%, n=16), thyrotoxicosis (23.7%, n=14), subclinical thyrotoxicosis (10.2%, n=6), and thyroiditis with normal thyroid function (6.8%, n=4), and the median time of occurrence (months) was 3.00, 3.00, 1.50, 1.50, and 0.80 after treatment with a PD-1 inhibitor, respectively. Among 20 patients who presented initially with thyrotoxicosis or subclinical thyrotoxicosis, 12 cases developed hypothyroidism or subclinical hypothyroidism subsequently. Logistic regression analysis suggested that previous radiotherapy (OR=3.737, 95%CI 1.390-10.046), targeted therapy (OR=3.763, 95%CI 1.553-9.117), thyroglobulin antibodies at baseline (OR=12.082, 95%CI 1.199-121.775), and thyroid-peroxidase antibodies at baseline (OR=10.874, 95%CI 1.010-117.047) were risk factors associated with the TGI caused by treatment with a PD-1 inhibitor. Conclusions: After treatment with a PD-1 inhibitor, TGI prevalence was high, especially in those with hypothyroidism or subclinical hypothyroidism. Some patients had a transition from thyrotoxicosis to hypothyroidism. Patients who underwent radiotherapy previously, had targeted therapy, or were thyroid autoantibody-positive at baseline may carry an increased risk of TGI following treatment with a PD-1 inhibitor.

[Analysis of correlation of community management index of essential hypertension and type 2 diabetes with probability of premature mortality caused by major non-communicable diseases in Zhejiang Province].

Objective: To evaluate the correlation of community management index of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases. Methods: From 2016 to 2018, the management of essential hypertension and type 2 diabetes were obtained from annual report of comprehensive prevention and control of chronic diseases in communities of Zhejiang province. The death data of chronic diseases were obtained from Information Management System of Chronic Diseases of Zhejiang province and annual population data were obtained from Public Security Bureau of Zhejiang Province. The management of essential hypertension and type 2 diabetes in communities of Zhejiang Province from 2016 to 2018 was described. The death status of major chronic diseases, including cardiovascular diseases, malignant tumors, diabetes and chronic respiratory diseases, in the same period was also described. Spearman correlation analysis and linear regression model were used to explore the correlation of community management of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases. Results: The number of essential hypertension patients under standardized management, blood pressure control and regular medication increased from 3.127 3, 2.811 5 and 3.569 7 million in 2016 to 3.355 9, 3.151 8 and 4.010 6 million in 2018, respectively. The number of type 2 diabetes patients with standardized management, blood glucose control and regular medication increased from 0.805 5, 0.687 5 and 0.913 4 million in 2016 to 0.912 6, 0.798 7 and 1.064 8 million in 2018, respectively. The standardized mortality rate of chronic diseases decreased from 403.07/100 000 in 2016 to 380.07/100 000 in 2018. The proportion of premature deaths of chronic diseases decreased from 28.39% in 2016 to 26.90% in 2018. The proportion of deaths from major chronic diseases in all chronic diseases decreased from 90.96% in 2016 to 90.69% in 2018.The probability of premature mortality decreased from 10.68% in 2016 to 9.67% in 2018. The spearman correlation analysis showed that the blood pressure control and regular drug use were negatively correlated with the probability of premature death of major chronic diseases (r values were -0.367 and -0.392; P values were 0.035 and 0.024). According to the linear regression model analysis, with increase of 100 000 of essential hypertension control cases or regular medication use cases of type 2 diabetes, the probability of premature death of major chronic diseases decreased by 0.47% (95%CI: 0.39%, 0.54%) or 1.31% (95%CI: 1.12%, 1.50%), respectively. Conclusion: From 2016 to 2018, the community management of essential hypertension and type 2 diabetes was negatively correlated with probability of premature death of major chronic diseases in Zhejiang province.

[Evaluation on the effect of comprehensive intervention combined with clinical preventive services and lifestyle adjustment among high-risk populations of cardiovascular disease in Tongxiang City].

Objective: To evaluate the effect of comprehensive intervention combined with clinical preventive services and lifestyle adjustment on high-risk populations of cardiovascular disease. Methods: In 2015, 4 towns (streets) in Tongxiang City, of Zhejiang Province including Heshan Town, Longxiang Street, Wutong Street, and Fengming Street, were selected by using the typical sampling. The towns (streets) were allocated to the intervention group (Heshan Town and Longxiang Street) and the control group (Wutong Street and Fengming Street) by using the cluster random sampling. In each town (street), hypertension patients aged 50 to 74 years old who were taking community medicine management and with a 10-year cardiovascular disease risk ≥10% were recruited as subjects. There were 1 823 subjects in the intervention group and 1 883 in the control group. The intervention group was given a 1-year comprehensive intervention combining clinical preventive services and lifestyle adjustment, while the control group received routine chronic disease management. After the intervention, the final questionnaire investigation was conducted and health physical examination data were obtained. The death, acute coronary heart disease events and stroke incidence were the primary outcomes, and cardiovascular disease-related knowledge and behavior, clinical preventive services utilization, physical changes, blood fat index and 10-year cardiovascular disease risk were the secondary outcomes. The difference-in-difference model was used to evaluate the effects of interventions. Results: The age of subjects in the intervention and control group was (68.76±3.75) and (67.90±4.56) years old, respectively. After 1-year intervention, the incidence of mortality, acute coronary events and stroke in intervention group was 1.65% (30 cases), 0.27% (5 cases) and 2.69% (49 cases), respectively, which showed no statistical difference compared to the control group [1.33% (25 cases), 0.32% (6 cases) and 2.07% (39 cases)]. After adjusting for the age, gender, education, marital status, self-assessed family income level and situation of taking antihypertensive drugs, the difference-in-difference model showed that the body mass index and diastolic blood pressure in the intervention group decreased by 0.33 kg/m(2) and 1.49 mmHg (1 mmHg=0.133 kPa). Compared with the control group, daily vegetable consumption proportion, the awareness rates of aspirin, stains, salt intake, and oil intake increased by 4.76%, 26.22%, 29.56%, 10.80%, and 15.17%, respectively (P<0.05). Conclusion: After the 1-year comprehensive intervention, there was no significant change in primary outcomes among high-risk populations of cardiovascular disease. In secondary outcomes, body mass index and diastolic blood pressure declined and cardiovascular disease-related knowledge awareness increased.

Rapidly rising incidence of Type 1 diabetes in children and adolescents aged 0-19 years in Zhejiang, China, 2007 to 2013.

AIMS: To investigate the incidence rates and trends in Type 1 diabetes in children and adolescents aged 0-19 years in the registered Zhejiang population over the period 2007-2013 by age, sex and calendar year. METHODS: In total, 611 individuals with newly diagnosed Type 1 diabetes were identified from 30 districts in Zhejiang province over the study period. Annual incidence and 95% confidence intervals (CI) by age group and sex were calculated per 100 000 person-years. Trends in diabetes incidence and the associations of age and sex with Type 1 diabetes were assessed using Poisson regression models. RESULTS: The mean annual age-standardized incidence of diabetes was 2.02/100 000 person-years (95% CI: 1.92-2.12), with an average annual increase of 12.0% (95% CI: 7.6-16.6%) over the study period. The risk for Type 1 diabetes in girls was estimated to be 1.25 (95% CI: 1.07-1.47) times higher than that in boys. Compared with those aged 0-4 years, the 5-9, 10-14 and 15-19 years age groups were at significantly greater risk, with adjusting incidence rate ratios of 3.54, 6.58 and 5.39, respectively. The mean age at diagnosis decreased significantly from 12.85 years in 2007 to 11.21 years in 2013. A steep rise in diabetes incidence was observed in the under 5 years age group, which showed the greatest increase at 33.61%. CONCLUSIONS: The incidence of diabetes in Zhejiang was relatively low, although rapidly rising trends have been found in recent years, particularly in younger children. Further monitoring and research are urgently required to better understand possible environmental risk factors and formulate preventive strategies.

EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the literature.

Ectodermal dysplasia (ED) represents a collection of rare disorders that result from a failure of development of the tissues derived from the embryonic ectoderm. ED is often associated with hair, teeth, and skin abnormalities, which are serious conditions affecting the quality of life of the patient. To date, a large number of genes have been found to be associated with this syndrome. Here, we report a patient with hypohidrotic ED (HED) without family history. We identified that this patient's disorder arises from an X-linked HED with a mutation in the EDA gene (G299D) found by whole-exome sequencing. In addition, in this paper we summarize the disease-causing mutations based on current literature. Overall, recent clinical and genetic research involving patients with HED have uncovered a large number of pathogenic mutations in EDA, which might contribute to a full understanding of the function of EDA and the underlying mechanisms of HED caused by EDA mutations.

[Spatial autocorrelation and related factors of stroke mortality in Zhejiang Province based on spatial panel model in 2015-2020].

Objective: To explore the spatial autocorrelation and macro influencing factors of stroke mortality in Zhejiang Province in 2015-2020 and provide a scientific basis for stroke prevention and control strategy. Methods: The data on stroke death were obtained from Zhejiang Chronic Disease Surveillance System. The spatial distribution of stroke mortality was explored by mapping and spatial autocorrelation analysis. The spatial panel model analyzed the correlation between stroke mortality and socioeconomic and healthcare factors. Results: From 2015 to 2020, the average stroke mortality was 68.38/100 thousand. The standard mortality of stroke was high in the areas of east and low in the west, high in the south and low in the north. Moreover, positive spatial autocorrelation was observed (Moran's I=0.274-0.390, P<0.001). Standard mortality of stroke was negatively associated with per capita gross domestic product (GDP) (ß=-0.370, P<0.001), per capita health expenditure (ß=-0.116, P=0.021), number of beds per thousand population (ß=-0.161, P=0.030). Standard mortality of ischemic stroke was negatively associated with per capita GDP (ß=-0.310, P=0.002) and standard management rate of hypertension (ß=-0.462, P=0.011). Standard mortality of hemorrhagic stroke was negatively associated with per capita GDP (ß=-0.481, P<0.001), per capita health expenditure (ß=-0.184, P=0.001), number of beds per thousand population (ß=-0.288, P=0.001) and standard management rate of hypertension (ß=-0.336, P=0.029). Conclusions: A positive spatial correlation existed between stroke mortality in Zhejiang Province in 2015-2020. We must focus more on preventing and controlling strokes in relatively backward economic areas. Moreover, to reduce the mortality of stroke, increasing the investment of government medical and health funds, optimizing the allocation of medical resources, and improving the standard management rate of hypertension are important measures.

[Construction and application of comprehensive system of chronic diseases surveillance in Zhejiang province].

To construct a non-communicable disease system recommended by WHO, develop the key techniques and promote their applications, obtain the main health indicators and understand the prevalence of chronic diseases, and provide support for the prevention, control and research of chronic diseases. Based on factor analysis, K-means clustering and multi-cluster random sampling, 30 typical sampling areas at provincial level were designed and constructed; By referring to WHO's Non-communicable Disease Surveillance Framework and the American behavioral risk factor sampling and questionnaire and combined with China's actual needs, a comprehensive surveillance system for chronic diseases, covering morbidity and mortality, risk factor exposure and community management and control of chronic diseases, was established, a "5+12+1" quality control system for surveillance data collection, management, analysis and feedback was formed and a three-level surveillance information management platform and information technology construction standards in the province were established, resulting the integration of life registration, chronic disease case reporting and community chronic disease management. Using these key techniques, we have obtained high-quality surveillance data of the whole province, produced the main health indicators, carried out research of chronic diseases, and analyze the prevalence and changing trend of the main chronic diseases and related risk factors to boost the government's practical projects for the reform of the people's livelihood and facilitate the construction of "Healthy Zhejiang". The successful experiences and key techniques have been applied in the construction of chronic disease surveillance system in some provinces in China.

[Interpretation for the group standards in technical specification of management for field survey in large population-based cohort study].

Large population-based cohort study is an important resource for population disease prevention and control, the results of which provide scientific basis for individualized treatment and precise prevention, and it is also the key strategic content of precision medicine. The Chinese Preventive Medicine Association coordinated experienced researchers from the Chinese Academy of Medical Sciences and other professional institutes to write up the group standard entitled Technical specification of management for field investigation in large population-based cohort study (T/CPMA 001-2019). Based on the research of large population-based cohort study in China and the principle of scientific, normative, applicable, and feasible, the standard proposed six aspects of management requirements including institutional arrangement, personnel composition, equipment, materials, documents and finance, as well as the basic requirements of the on-site investigation, the requirements of each position and the overall quality control requirements, etc.. The standard aims to guide the large population-based cohorts that have been or intended to be established in China, including national cohorts, regional population cohorts, and special population cohorts, hence to improve scientific research level, accelerate scientific research output and provide localization basis for disease prevention and control in China.

[Interpretation for the group standards in technical specification of long-term follow-up for end point in large population-based cohort study].

Long-term follow-up for end point is an extremely important and arduous task in large population-based cohort studies, which is also the key to the success of large cohort studies. Thus, the fundamental question of the achievements above is how to construct a large population- based cohort in a standardized way. The Chinese Preventive Medicine Association coordinated experienced researchers from Zhejiang Provincial Center for Disease Control and Prevention and other professional institutes to write up the group standard entitled Technical specification of long-term follow-up for end point in large population-based cohort study (T/CPMA 002-2019). The standard is drafted with principles of emphasizing the scientific, normative, applicability, and feasible nature. This group standard recommended the follow-up target population, time, content, methods, quality control, and indicators assessment. The standard aims to guide the large population-based cohorts that have been or intended to be established in China, including national cohorts, regional population cohorts, and special population cohorts, hence, to improve domestic scientific research level and the international influence, and to support decision-making and practice of disease prevention and control.

[Estimation on the health life expectancy of adults in Zhejiang province, 2016].

Objective: To estimate the health-adjusted life expectancy (HALE) of adults in Zhejiang province and evaluate the health status of the adults. Methods: This study was based on the mortality data collected from Zhejiang Chronic Disease Surveillance Information and Management System, and mortality rates from the underreporting survey and self-reported health data in 2016. Hierarchical Ordered Probit (HOPIT) model was used to estimate the severity-weighted prevalence of disability. Sullivan's method was used to calculate the HALE. Results: After adjustment by HOPIT model, the severity-weighted prevalence of disability increased significantly with age (χ(2)=5 795.81,P<0.001), and it was higher in females than in males (χ(2)=5 353.27, P<0.001). The life expectancy and self-evaluated HALE were 59.08 years and 48.68 years, respectively, in those aged ≥20 years, the difference was 10.40 years due to disability. The proportion of HALE loss due to disability in the total life expectancy was 17.61%, and it increased with age. HALE was higher in males than in females (49.21 years vs. 48.14 years), and in urban residents than in rural residents (49.92 years vs. 47.43 years). Conclusion: The proportion of loss of HALE in the total life expectancy in adults was high in Zhejiang, and it higher in males than in females, in urban residents than rural residents. Programs on improving health care in women and rural residents should be promoted.

[Factors related to thyroid carcinoma in Zhejiang province: a matched case-control study].

Objective: To explore the influencing factors related to thyroid carcinoma. Methods: Matched by sex, age and original residential areas, 659 pairs of cases and controls were recruited and studied. Methods including both single factor analysis and multivariate conditional logistic regression analysis were carried out to identify the influencing factors. Results: Multivariate conditional logistic regression analysis showed that higher education, being diabetic, alcohol intake, tea drinking, occupational physical activity and the frequency of eating fishes/eggs etc., were potentially protective to thyroid carcinoma. Depression, personal history of CT examination and less salt intake seemed to be risk factors on thyroid carcinoma. For males, factors as alcohol intake, tea drinking, occupational physical activity and frequent egg-eating appeared protective. For females, higher education, diabetes, tea drinking, occupational physical activity, frequent consumption of fishes/eggs, short duration of menstruation appeared as possibly protective. Conclusion: Higher education, diabetes, alcohol intake, tea drinking, occupational physical activity, frequent consumption of fishes/eggs, depression, personal history of CT examination and less salt intake served as potential influencing factors to thyroid carcinoma.

[Progress in research of thyroid carcinoma related gene mutation and epigenetics].

Thyroid cancer is one of the most common endocrine malignant tumors, and its molecular pathogenesis is also a process of multiple genes involved in many steps of carcinogenesis. With the development of molecular biology technology, a variety of related gene mutations and epigenetic phenomena have been found in thyroid cancer tissues. It is helpful to understand the latest progress in the research of the gene mutation and epigenetics of thyroid cancer for its early diagnosis, prevention and the development of targeted drugs.

[Impact of diabetes prevalence and mortality on health life expectancy among residents in Zhejiang province].

Objective: To evaluate the impact of diabetes prevalence and mortality on health life expectancy (HLE). Methods: A cause-excluded health adjusted life expectancy method was used to quantitatively analyze the impact of diabetes on HLE and the composition of health life losses (HLL), using the integrated data on population mortality, self-assessed health status and diabetes prevalence. Results: The HLE for people aged 15 was 55.80 in Zhejiang, in 2013. After removing the diabetes morbidity and mortality, the HLE for men aged 15 increased by 0.86 and 1.13, respectively, with an increase of 1.04 and 0.66 for urban and rural residents. Substantial increase of HLE was observed in women and urban residents than those for men and rural residents. HLL caused by diabetes mortality and morbidity appeared as 0.10 and 0.79, with a ratio of 7.92. Conclusion: HLL caused by diabetes mortality was much greater than those caused by diabetes mortality, suggesting the most effective measure in reducing the diabetes-related HLL is to promote the healthy lifestyle in urban areas and especially for women.

[Morbidity and mortality of malignant tumor in Zhejiang province, 2014].

OBJECTIVE: To analyze the morbidity and mortality of malignant tumor in Zhejiang province in 2014. METHODS: The data were collected from Zhejiang provincial chronic disease surveillance system in 2014. The crude rate, age-standardized rate, cumulative rate(0-74 years old), cut rate(35-64 years old), age-specific and area-specific morbidity/mortality as well as the constitution of top 10 leading cancers were then calculated and analyzed. The age-standardized rate was calculated according to the standard population in China in 1982 and the Segi' s world standard population. RESULTS: The crude morbidity was 348.80/100 000(370.74/100 000 in males and 326.51/100 000 in females). The age-standardized morbidity according to the standard population in China and according to world standard population were 168.84/100 000 and 217.23/100 000 respectively, the cumulative morbidity was 24.66% and the cut morbidity was 376.40/100 000. Age-specific morbidity in age group 0-34 years remained low; however, the morbidity increased obviously in age group ≥35 years, increased more rapidly in age group ≥50 years and finally reached the peak in age group 80-84 years(1 618.20/100 000). The morbidity of malignant tumor, age-standardized morbidity(China standard)and age-standardized morbidity(world standard)were 381.81/100 000, 185.15/100 000 and 236.27/100 000 respectively in urban area, and 330.23/100 000 , 159.47/100 000 and 206.29/100 000, respectively in rural area. The crude mortality was 189.08/100 000(248.57/100 000 in males, 128.72/100 000 in females), and the age-standardized mortality according to China population and world population were 97.56/100 000 and 135.54/100 000 respectively. The cumulative mortality was 15.08%, and the cut mortality was 162.75/100 000. Age-specific mortality increased in age group 45-49 years(92.29/1000 000)and reached the peak in age group ≥85 years(2 263.70/100 000). The mortality was higher in rural area(190.60/100 000)than in urban area(186.38/100 000). The leading cancers were lung cancer, colorectum cancer, thyroid cancer, stomach cancer and liver cancer, accounting for 58.64% of the total. Lung cancer, liver cancer, stomach cancer, colorectum cancer and esophagus cancer were the major cancers causing deaths, accounting for 70.72% of all the total. CONCLUSION: The leading cancers were lung cancer, colorectum cancer, thyroid cancer, stomach cancer and liver cancer in Zhejiang in 2014, close attention should be paid to thyroid cancer in women. The disease burden of malignant tumor is increasing,it is necessary for health department to take effective measures to reduce the disease burden caused by malignant tumor.