This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Objective:To analyze the changes in T lymphocyte subsets, B lymphocytes and NK cells in children with active tuberculosis (TB) and their clinical significance.Methods:T lymphocyte subsets, B lymphocytes and NK cells in peripheral blood samples of 106 patients with acute TB (TB group) and 106 healthy children (healthy control group) were detected by flow cytometry and compared between different groups.Results:The percentages of CD3 + T, CD4 + T and NK cells as well as the CD4 +/CD8 + T cell ratio were significantly lower in the TB group than in the healthy control group ( Z=-3.783, P=0.000; Z=-5.401, P=0.000; Z=-3.434, P=0.001; Z=-2.014, P=0.044). The percentages of double negative T (DNT) and B cells in the TB group were significantly higher than those in the healthy control group ( Z=2.765, P=0.006; Z=6.880, P=0.000). No significant difference in the percentage of CD8 + T or double positive T (DPT) cells was observed between the two groups ( P>0.05). The expression of peripheral lymphocyte subsets varied in TB children of different age groups (0-<3, 3-<6, 6-<10 and 10-<16 years old). There were significant differences in CD3 + T, DNT and B cells among the four age groups ( H=10.081, P=0.018; H=14.583, P=0.002; H=8.498, P=0.037). The percentage of CD4 + T cells was significantly lower in children with extrapulmonary TB than in those with pulmonary TB ( Z=-3.068, P=0.002). No statistically significant difference in other lymphocyte subsets was found between children with extrapulmonary and pulmonary TB ( P>0.05). Conclusions:Tuberculosis could lead to immune dysfunction in children. Dynamic monitoring of the changes in peripheral lymphocyte subsets in children with TB could be conducive to better assessment of immune status and providing personalized treatment.

Objective:To analyze the epidemiological characteristics of respiratory syncytial virus (RSV)-caused respiratory diseases in children in Hebei Province and the changes in peripheral blood lymphocyte subsets and inflammatory indexes.Methods:A total of 9 491 sputum specimens and 9 491 paired peripheral blood specimens were collected from children admitted to Hebei Children′s Hospital for respiratory infection in 2018. RSV-positive sputum specimens were screened by multiple detection reagents for 13 kinds of respiratory pathogens. Flow cytometry was uses to detect T and B lymphocytes and NK cells in peripheral blood samples of randomly screened RSV-positive children. Procalcitonin (PCT) was measured by Roche E411 luminescence analyzer. Hypersensitive C-reactive protein (hs-CRP) was detected by Roche Cobas 8000 C701 biochemical analyzer. White blood cells (WBC) were measured by Sysmex XN-BN3 hematometer.Results:The positive rate of RSV in children with respiratory diseases was 13.08% in Hebei Province in 2018. There were significant differences in RSV-positive rates among different age groups (χ 2=479.297 6, P<0.000 1). The positive rate of RSV decreased gradually with age (χ 2=-20.282 7, P<0.000 1) and was higher in male than in female (χ 2=34.552 7, P<0.000 1). The incidence of co-infection of RSV with other respiratory pathogens was 29.49% (366/1 241), mainly caused by human rhinovirus (HRV, 150/1 241) and adenovirus (ADV, 40/1 241). The main epidemic seasons of RSV infection were winter and spring. The epidemic trends of simple RSV infection and co-infection were consistent. There were significant differences in inflammatory indexes, WBC ( P<0.01), CD4 + ( P=0.015) and CD4 + /CD8 + cells ( P=0.016) between simple RSV infection and co-infection groups. Conclusions:RSV was a common pathogen causing respiratory diseases in children in Hebei Province. The younger the children were, the more likely they were to be infected with RSV. RSV infection was easily complicated by HRV or ADV infection. The epidemic seasons of RSV infection in Hebei were winter and spring. Both simple infection and co-infection of RSV might result in immune dysfunction.

Objective The aims of this study were to investigate the expression of DKK2,a WNT signaling pathway regula-tor,in nephroblastoma cells and tissues of children,the effect on the proliferation of nephroblastoma SK-NEP-1 cells,and to explore its mechanism. Methods The relative expression of DKK2 in nephroblastoma cells and tissues was analyzed by qRT-PCR and im-munoblotting assays. Overexpressing DKK2 SK-NEP-1 cells were set as the experimental group( DKK2 group);the blank control plasmid group was set as a control group( Vector group),transfected with pcDNA3. 1 ( +) -Flag-DKK2 plasmid( Experimental group)and pcDNA3. 1( +) -Flag-Vector plasmid(Control group). The over-expression of DKK2 was confirmed in SK-NEP-1 cells by RT-PCR and immunoblotting. CCK-8 and cell cloning assays were used to determine the effect of DKK2 on cell prolifera-tion;flow cell cycle and apoptosis assays were used to confirm the effect on cell proliferation in overexpressed DKK2 cells. The xen-graft formation assay in nude mice was to verify the effect of DKK2 on proliferation in overexpressed DKK2 cells;the mechanism of DKK2 in inhibitory proliferation was analyzed by qRT-PCR,Western blotting and immunohistochemistry. Results Compared with normal renal epithelial tissues,DKK2 mRNA was down-regulated in children with nephroblastoma,and the difference was statistically significant(P<0. 001). Compared with the control group,transfected DKK2 cell viability was significantly inhibited after treatment for 24,48 and 72 h( P<0. 05),cell clone formation in the experimental group was significantly inhibited(31. 11% ± 2. 14% ) ( P<0. 05),the cell cycle in the experimental group was significantly arrested at the G1 phase(P<0. 001),and the apoptosis rate in the experimental group was significantly increased(P<0. 001). Compared with the control group,the tumor weight and volume in nude mice were significantly low in the experimental mice which were injected DKK2 overexpression cells(P<0. 001). Active-β-cate-nin and downstream genes were significantly inhibited in over-expressed DKK2 SK-NEP-1 cells. Conclusion DKK2 is down-regulated in human cutaneous nephroblastoma and participates in the mechanism of nephroblastoma by antagonizing Wnt/β-catenin signaling pathway.