Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Cholangiocarcinoma/pathology* ; Carcinoma, Squamous Cell ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

Humans ; Carcinoma, Verrucous/pathology* ; Carcinoma, Squamous Cell/pathology* ; Bone Neoplasms ; Toes/pathology* ; Skin Neoplasms/pathology*

Objective: To investigate the clinicopathological features of perivascular epithelioid cell tumor (PEComa) of the lung. Methods: Eight PEComa cases of the lung diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China from July 2008 to December 2021 were collected and subject to immunohistochemical staining, fluorescence in situ hybridization and next generation sequencing. The relevant literature was reviewed and the clinicopathological features were analyzed. Results: There were 5 males and 3 females, aged from 18 to 70 years (mean 39 years). There were 3 cases of the right upper lung, 3 cases of the left lower lung, 1 case of the left upper lung and 1 case of the right middle lung. Seven cases were solitary and 1 case was multifocal (4 lesions). Seven cases were benign while one was malignant. The tumors were all located in the peripheral part of the lung, with a maximum diameter of 0.2-4.0 cm. Grossly, they were oval and well circumscribed. Microscopically, the tumor cells were oval, short spindle-shaped, arranged in solid nests, acinar or hemangiopericytoma-like patterns, with clear or eosinophilic cytoplasm. The stroma was rich in blood vessels with hyalinization. Coagulated necrosis and high-grade nuclei were seen in the malignant case, and calcification was seen in 2 cases. Immunohistochemically, the tumor cells were positive for Melan A (8/8), HMB45 (7/8), CD34 (6/8), TFE3 (4/7), and SMA (3/8). All cases were negative for CKpan and S-100. TFE3 (Xp11.2) gene fusion was examined using the TFE3 break-apart fluorescence in situ hybridization in 5 cases, in which only the malignant case was positive. The next generation sequencing revealed the SFPQ-TFE3 [t(X;1)(p11.2;p34)] fusion. Follow-up of the patients ranged from 12 to 173 months while one patient was lost to the follow-up. The malignant case had tumor metastasis to the brain 4 years after the operation and then received radiotherapy. Other 6 cases had no recurrence and metastasis, and all the 7 patients survived. Conclusions: Most of the PEComas of the lung are benign. When there are malignant morphological features such as necrosis, high-grade nuclei or SFPQ-TFE3 gene fusion, close follow-up seems necessary.
Male ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Perivascular Epithelioid Cell Neoplasms/pathology* ; Lung/pathology* ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Necrosis ; Biomarkers, Tumor/analysis*

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl₂ and hypoxia (1%O₂) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl₂ and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.
Humans ; Carcinoma, Renal Cell/pathology* ; Kidney Neoplasms/pathology* ; HeLa Cells ; Von Hippel-Lindau Tumor Suppressor Protein/genetics* ; Mutation ; Signal Transduction ; Luciferases/therapeutic use* ; Hypoxia/genetics* ; RNA, Messenger ; Lipids/therapeutic use* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

OBJECTIVE: To establish a snail control approach for spraying chemicals with drones against Oncomelania hupensis in complex snail habitats in hilly regions, and to evaluate its molluscicidal effect. METHODS: The protocol for evaluating the activity of spraying chemical molluscicides with drones against O. hupensis snails was formulated based on expert consultation and literature review. In August 2022, a pretest was conducted in a hillside field environment (12 000 m²) north of Dafengji Village, Dacang Township, Weishan County, Yunnan Province, which was assigned into four groups, of no less than 3 000 m² in each group. In Group A, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with drones at a dose of 40 g/m², and in Group B, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with drones at a dose of 40 g/m², while in Group C, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with knapsack sprayers at a dose of 40 g/m², and in Group D, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with knapsack sprayers at a dose of 40 g/m². Then, each group was equally divided into six sections according to land area, with Section 1 for baseline surveys and sections 2 to 6 for snail surveys after chemical treatment. Snail surveys were conducted prior to chemical treatment and 1, 3, 5, 7 days post-treatment, and the mortality and corrected mortality of snails, density of living snails and costs of molluscicidal treatment were calculated in each group. RESULTS: The mortality and corrected mortality of snails were 69.49%, 69.09%, 53.57% and 83.48%, and 68.58%, 68.17%, 52.19% and 82.99% in groups A, B, C and D 14 days post-treatment, and the density of living snails reduced by 58.40%, 63.94%, 68.91% and 83.25% 14 days post-treatment relative to pre-treatment in four groups, respectively. The median concentrations of chemical molluscicides were 37.08, 35.42, 42.50 g/m² and 56.25 g/m² in groups A, B, C and D, and the gross costs of chemical treatment were 0.93, 1.50, 0.46 Yuan per m² and 1.03 Yuan per m² in groups A, B, C and D, respectively. CONCLUSIONS The molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against O. hupensis snails is superior to manual chemical treatment without environmental cleaning, and chemical treatment with drones and manual chemical treatment show comparable molluscicidal effects following environmental cleaning in hilly regions. The cost of chemical treatment with drones is slightly higher than manual chemical treatment regardless of environmental cleaning. Spraying 5% niclosamide ethanolamine salt granules with drones is recommended in complex settings with difficulty in environmental cleaning to improve the molluscicidal activity and efficiency against O. hupensis snails.
Niclosamide/pharmacology* ; Ethanolamine/pharmacology* ; Unmanned Aerial Devices ; China ; Molluscacides/pharmacology* ; Ethanolamines

Precision medicine became the key strategy in development priority of science and technology in China. The large population-based cohorts become valuable resources in preventing and treating major diseases in the population, which can contribute scientific evidence for personalized treatment and precise prevention. The fundamental question of the achievements above, therefore, is how to construct a large population-based cohort in a standardized way. The Chinese Preventive Medicine Association co-ordinated experienced researchers from Peking University and other well-known institutes to write up two group standards Technical specification of data processing for large population-based cohort study (T/CPMA 001-2018) and Technical specification of data security for large population-based cohort study (T/CPMA 002-2018), on data management. The standards are drafted with principles of emphasizing their scientific, normative, feasible, and generalizable nature. In these two standards, the key principles are proposed, and technical specifications are recommended in data standardization, cleansing, quality control, data integration, data privacy protection, and database security and stability management in large cohort studies. The standards aim 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.
China ; Cohort Studies ; Delivery of Health Care ; Humans ; Population Surveillance ; Quality Control ; Reference Standards

Objective: To describe the genetic structure of populations in different areas of China, and explore the effects of different strategies to control the confounding factors of the genetic structure in cohort studies. Methods: By using the genome-wide association study (GWAS) on data of 4 500 samples from 10 areas of the China Kadoorie Biobank (CKB), we performed principal components analysis to extract the first and second principal components of the samples for the component two-dimensional diagram generation, and then compared them with the source of sample area to analyze the characteristics of genetic structure of the samples from different areas of China. Based on the CKB cohort data, a simulation data set with cluster sample characteristics such as genetic structure differences and extensive kinship was generated; and the effects of different analysis strategies including traditional analysis scheme and mixed linear model on the inflation factor (λ) were evaluated. Results: There were significant genetic structure differences in different areas of China. Distribution of the principal components of the population genetic structure was basically consistent with the geographical distribution of the project area. The first principal component corresponds to the latitude of different areas, and the second principal component corresponds to the longitude of different areas. The generated simulation data showed high false positive rate (λ=1.16), even if the principal components of the genetic structure was adjusted or the area specific subgroup analysis was performed, λ could not be effectively controlled (λ>1.05); while, by using a mixed linear model adjusting for the kinship matrix, λ was effectively controlled regardless of whether the genetic structure principal component was further adjusted (λ=0.99). Conclusions: There were large differences in genetic structure among populations in different areas of China. In molecular epidemiology studies, bias caused by population genetic structure needs to be carefully treated. For large cohort data with complex genetic structure and extensive kinship, it is necessary to use a mixed linear model for association analysis.
China ; Genetic Structures ; Genome-Wide Association Study ; Humans ; Linear Models ; Principal Component Analysis

Objective: To evaluate the association of educational level with anthropometric measurements at different adult stages and their long-term changes in adults who participated in the second re-survey of China Kadoorie Biobank (CKB). Methods: The present study excluded participants who were aged >65 years, with incomplete or extreme measurement values, or with major chronic diseases at baseline survey or re-survey. The weight at age 25 years was self-reported. Body height, body weight and waist circumference at baseline survey (2004-2008) and re-survey (2013-2014) were analyzed. Results: The present study included 3 427 men and 6 320 women. Both body weight and waist circumference (WC) increased with age. From age 25 years to baseline survey (mean age 45.2±6.5), the mean weight change per 5-year was (1.70±2.63) kg for men and (1.27±2.10) kg for women. From baseline survey to re-survey (53.2±6.5), the mean changes per 5-year for body weight were (1.12±2.61) kg for men and (0.90±2.54) kg for women; and that for WC was (3.20±3.79) cm for men and (3.83±3.85) cm for women. Among women, low educational level was consistently associated with higher body mass index (BMI) and WC at age 25 years, baseline survey and re-survey. Among men, low educational level was associated with higher BMI at age 25 years. At baseline survey and re-survey, the educational level in men was not statistically associated with BMI; but men who completed junior or senior high school showed slight higher WC and increase of WC from baseline survey to re-survey than other male participants. Conclusions: Body weight and WC increased with age for both men and women. The associations of educational level with BMI and WC were different between men and women.
Adult ; Asian People/statistics & numerical data* ; Body Height ; Body Mass Index ; Body Weight ; China/epidemiology* ; Educational Status ; Female ; Humans ; Male ; Middle Aged ; Obesity/ethnology* ; Risk Factors ; Sex Distribution ; Waist Circumference/ethnology*

Objective: To examine the prevalence of 'healthy lifestyle' from data extracted from the China Kadoorie Biobank (CKB) of 0.5 million adults from ten areas across China. Methods: After excluding participants with self-reported histories of coronary heart disease, stroke or cancer, a total of 487 198 participants at baseline (2004-2008) and 22 604 participants at second survey (2013- 2014), were included for analysis. 'Healthy lifestyle' was defined as haing the following characteristics: a) never smoking or having stopped smoking for reasons other than illness; b) alcohol drinking <25 g/day (men)/<15 g/day (women); c) diet rich in vegetables, fruits, legumes and fish, but low in red meat; d) upper quarter of the physical activity level; e) body mass index of 18.5-23.9 kg/m(2) and waist circumstance <85 cm (men)/80 cm (women). We calculated the healthy lifestyle scores (HLS) by counting the number of all the healthy lifestyle factors, with a range from 0 to 6. Results: At baseline, prevalence rates of the above five healthy lifestyles (except physical activity) were 70.6%, 92.6%, 8.7%, 52.6% and 59.0%, respectively, with the mean HLS being 3.1±1.2. Most participants (81.4%) had2-4 healthy components, while only 0.7% (0.2% in men and 1.0% in women) of all the participants had all six healthy lifestyles. Participants who were women, at younger age, with more schooling and rural residents, were more likely to adhere to the healthy lifestyle. After ten years, the mean HLS showed a slight decrease. Conclusion: The prevalence of optimal lifestyles in Chinese adults appeared extremely low. Levels of 'healthy lifestyle' varied greatly among those populations with different socio-demographic characteristics across the ten areas in China.
Adult ; Asian People/statistics & numerical data* ; China ; Female ; Healthy Lifestyle ; Humans ; Life Style ; Male ; Prevalence ; Risk Factors

Objective: To evaluate the association of family history with risk of major coronary events (MCE) and ischemic heart disease (IHD). Methods: After excluding participants with heart disease, stroke or cancer at baseline survey, a total of 485 784 participants from the China Kadoorie Biobank, who had no missing data on critical variables, were included in the analysis. Cox regression analysis was used to estimate the hazard ratios (HR) and 95% CI. Subgroup analyses were performed according to the baseline characteristics. Results: During a median of 7.2 years of follow-up, we documented 3 934 incident cases of MCE and 24 537 cases of IHD. In multivariable-adjusted models, family history was significantly associated with risk of MCE and IHD. The adjusted HRs (95%CI) were 1.41 (1.19-1.65) and 1.25 (1.18-1.33), respectively. History of disease among siblings was more strongly associated with early-onset MCE than parental history (HR=2.97, 95%CI: 1.80-4.88). Moreover, the association of family history with MCE and IHD was stronger in persons who were overweight or obesive, and the association between family history and MEC was stronger in smokers. Conclusion: This large-scale, prospective study indicated that family history was an independent risk factor for MCE and IHD in China. The intervention targeting major known lifestyle risk factors and the management of chronic diseases should be strengthened for Chinese population, especially for the individuals with family history were at high risk.
Asian People/statistics & numerical data* ; China/epidemiology* ; Coronary Disease/genetics* ; Humans ; Incidence ; Myocardial Ischemia/genetics* ; Overweight/ethnology* ; Proportional Hazards Models ; Prospective Studies ; Risk Assessment ; Risk Factors ; Smoking/ethnology*