Objective:To investigate the prospective association between lifestyle and the risk for all-cause mortality in middle-aged and elderly residents in China.Methods:The data from China Health and Retirement Longitudinal Study were used. Baseline information about the lifestyle were collected through questionnaire survey and physical measurements, and the mortality data were obtained through surveys conducted at 2-3 year intervals. A total of 5 436 study participants were included. A comprehensive lifestyle including smoking, alcohol consumption, sleep, BMI and physical activity was constructed, and a multivariate-adjusted Cox proportional hazards regression model was used to estimate the association between lifestyle and the risk for all-cause mortality.Results:During the follow-up of average 8.2 years, 695 deaths were recorded. The comprehensive lifestyle score was linearly associated with the risk for all-cause mortality. Compared with the study participants with comprehensive lifestyle score of 0-1, those with score of 2-5 all had lower risk for all-cause mortality, with HRs of 0.78 (95% CI: 0.62-0.98), 0.56 (95% CI: 0.44-0.72), 0.36 (95% CI:0.27-0.48), and 0.33 (95% CI: 0.21-0.52), respectively. The results of Cox proportional hazards regression model analysis of single lifestyle showed that compared with those with unhealthy lifestyles, the HRs of all-cause mortality for study participants who never smoked, had moderate alcohol consumption, had appropriate night sleep, maintained healthy body weight and kept active physical activity were 0.70 (95% CI: 0.57-0.84), 0.76 (95% CI: 0.64-0.90), 0.79 (95% CI: 0.67-0.94), 0.73 (95% CI: 0.62-0.87), and 0.68 (95% CI: 0.58-0.80), respectively. Conclusions:Keeping healthy lifestyles can significantly reduce the risk for all-cause mortality in middle-aged and elderly residents China. The higher the healthy lifestyle level, the lower the risk for all-cause mortality.

Objective:To investigate the pathogen of an acute gastroenteritis outbreak in a school in Taizhou, and to understand the epidemiological characteristics and patterns of the outbreak and the etiology of the pathogen.Methods:Twelve anal swab samples from patients who met the suspected case definition during the outbreak in March 2024 were collected. FilmArray GI was used to screen 22 common pathogens in the 12 samples, and the real-time fluorescent RT-PCR was performed for verification. Nested RT-PCR was used to amplify and sequence the nucleotide sequence of the viral capsid region VP1, and the variability of the sequence sites was analyzed. Based on the sequence relationship, a molecular phylogenetic tree was constructed and the viral genotypes were determined. Molecular transmission network analysis was conducted by integrating field epidemiological information.Results:The VP1 gene sequences were obtained from 8 of the 12 specimens. Systematic evolution showed that the molecular typing of the 8 strains of Sapoviuses (SaV) was all GI.6 genotype, and there was a C/T mutation at position 1236 in the VP1 gene. The inferred molecular transmission network was largely consistent with the information from the field epidemiological investigation, such as the initial infected person being the earliest case of the outbreak, and there was a closer transmission link between the two teachers.Conclusions:This article reported a school outbreak caused by a SaV GI.6 type. We speculated a more reliable molecular transmission network, estimated the rate of gene mutation and provided a reasonable elaboration for the C/T mutation at position 1236 of the VP1 gene.

Objective To compare ovulation recovery rate and metabolic indicators between ethinyl-estradiol/drospirenone(EE/DRSP)combined with orlistat and EE/DRSP alone in overweight/obese patients with polycystic ovary syndrome(PCOS).Methods This study was a randomized controlled clinical trial conducted based on the 2004 Rotterdam criteria.From October 2020 to December 2023,180 overweight/obese PCOS patients aged 20-40 were recruited from the Department of Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University.The patients were randomly divided into two groups in a 1∶2 ratio.Among them,60 patients received treatment with EE/DRSP(EE20 μg,DRSP 3 mg),while 120 patients received a combination treatment of EE/DRSP and orlistat(360 mg/d).The height,weight,waist circumference,hip circumference,and blood pressure of the patients were measured before treatment and after 12 weeks of treatment.Laboratory tests included measurements of follicle-stimulating hormone(FSH),luteinizing hormone(LH),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),free androgen index(FAI),alanine transaminase(ALT),aspartate transaminase(AST),gamma-glutamyl transferase(GGT),fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C),lipoprotein(a)[Lp(a)],sex hormone-binding globulin(SHBG),total testosterone(T),and free testosterone(FT).After 12 weeks of treatment,the medication was discontinued,and natural ovulation was observed.Results After 12 weeks of treatment,the ovulation rate of the EE/DRSP combined with orlistat group reached 70.8%,while the natural ovulation rate of the EE/DRSP group alone was only 35%,indicating that the ovulation rate was significantly increased after EE/DRSP combined with orlistat treatment.After 12 weeks of treatment,both groups showed a significant decrease in total testosterone,free testosterone,and low-density lipoprotein levels(all P<0.05),and the decrease in BMI,waist circumference,fasting insulin,and HOMA-IR in the EE/DRSP combined with orlistat group was greater than that in the EE/DRSP group alone(P<0.05).After treatment,both groups showed a significant increase in high-density lipoprotein and triglyceride levels(all P<0.05),with no significant changes in total cholesterol and fasting blood glucose(all P>0.05).Conclusion After 12 weeks of treatment,EE/DRSP combined with orlistat can significantly improve the ovulation rate of PCOS patients.It is superior to EE/DRSP alone in reducing androgen levels,body weight,insulin resistance,and low-density lipoprotein levels.

Objective To compare ovulation recovery rate and metabolic indicators between ethinyl-estradiol/drospirenone(EE/DRSP)combined with orlistat and EE/DRSP alone in overweight/obese patients with polycystic ovary syndrome(PCOS).Methods This study was a randomized controlled clinical trial conducted based on the 2004 Rotterdam criteria.From October 2020 to December 2023,180 overweight/obese PCOS patients aged 20-40 were recruited from the Department of Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University.The patients were randomly divided into two groups in a 1∶2 ratio.Among them,60 patients received treatment with EE/DRSP(EE20 μg,DRSP 3 mg),while 120 patients received a combination treatment of EE/DRSP and orlistat(360 mg/d).The height,weight,waist circumference,hip circumference,and blood pressure of the patients were measured before treatment and after 12 weeks of treatment.Laboratory tests included measurements of follicle-stimulating hormone(FSH),luteinizing hormone(LH),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),free androgen index(FAI),alanine transaminase(ALT),aspartate transaminase(AST),gamma-glutamyl transferase(GGT),fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C),lipoprotein(a)[Lp(a)],sex hormone-binding globulin(SHBG),total testosterone(T),and free testosterone(FT).After 12 weeks of treatment,the medication was discontinued,and natural ovulation was observed.Results After 12 weeks of treatment,the ovulation rate of the EE/DRSP combined with orlistat group reached 70.8%,while the natural ovulation rate of the EE/DRSP group alone was only 35%,indicating that the ovulation rate was significantly increased after EE/DRSP combined with orlistat treatment.After 12 weeks of treatment,both groups showed a significant decrease in total testosterone,free testosterone,and low-density lipoprotein levels(all P<0.05),and the decrease in BMI,waist circumference,fasting insulin,and HOMA-IR in the EE/DRSP combined with orlistat group was greater than that in the EE/DRSP group alone(P<0.05).After treatment,both groups showed a significant increase in high-density lipoprotein and triglyceride levels(all P<0.05),with no significant changes in total cholesterol and fasting blood glucose(all P>0.05).Conclusion After 12 weeks of treatment,EE/DRSP combined with orlistat can significantly improve the ovulation rate of PCOS patients.It is superior to EE/DRSP alone in reducing androgen levels,body weight,insulin resistance,and low-density lipoprotein levels.

Objective:To investigate the prospective association between lifestyle and the risk for all-cause mortality in middle-aged and elderly residents in China.Methods:The data from China Health and Retirement Longitudinal Study were used. Baseline information about the lifestyle were collected through questionnaire survey and physical measurements, and the mortality data were obtained through surveys conducted at 2-3 year intervals. A total of 5 436 study participants were included. A comprehensive lifestyle including smoking, alcohol consumption, sleep, BMI and physical activity was constructed, and a multivariate-adjusted Cox proportional hazards regression model was used to estimate the association between lifestyle and the risk for all-cause mortality.Results:During the follow-up of average 8.2 years, 695 deaths were recorded. The comprehensive lifestyle score was linearly associated with the risk for all-cause mortality. Compared with the study participants with comprehensive lifestyle score of 0-1, those with score of 2-5 all had lower risk for all-cause mortality, with HRs of 0.78 (95% CI: 0.62-0.98), 0.56 (95% CI: 0.44-0.72), 0.36 (95% CI:0.27-0.48), and 0.33 (95% CI: 0.21-0.52), respectively. The results of Cox proportional hazards regression model analysis of single lifestyle showed that compared with those with unhealthy lifestyles, the HRs of all-cause mortality for study participants who never smoked, had moderate alcohol consumption, had appropriate night sleep, maintained healthy body weight and kept active physical activity were 0.70 (95% CI: 0.57-0.84), 0.76 (95% CI: 0.64-0.90), 0.79 (95% CI: 0.67-0.94), 0.73 (95% CI: 0.62-0.87), and 0.68 (95% CI: 0.58-0.80), respectively. Conclusions:Keeping healthy lifestyles can significantly reduce the risk for all-cause mortality in middle-aged and elderly residents China. The higher the healthy lifestyle level, the lower the risk for all-cause mortality.

Objective:To investigate the pathogen of an acute gastroenteritis outbreak in a school in Taizhou, and to understand the epidemiological characteristics and patterns of the outbreak and the etiology of the pathogen.Methods:Twelve anal swab samples from patients who met the suspected case definition during the outbreak in March 2024 were collected. FilmArray GI was used to screen 22 common pathogens in the 12 samples, and the real-time fluorescent RT-PCR was performed for verification. Nested RT-PCR was used to amplify and sequence the nucleotide sequence of the viral capsid region VP1, and the variability of the sequence sites was analyzed. Based on the sequence relationship, a molecular phylogenetic tree was constructed and the viral genotypes were determined. Molecular transmission network analysis was conducted by integrating field epidemiological information.Results:The VP1 gene sequences were obtained from 8 of the 12 specimens. Systematic evolution showed that the molecular typing of the 8 strains of Sapoviuses (SaV) was all GI.6 genotype, and there was a C/T mutation at position 1236 in the VP1 gene. The inferred molecular transmission network was largely consistent with the information from the field epidemiological investigation, such as the initial infected person being the earliest case of the outbreak, and there was a closer transmission link between the two teachers.Conclusions:This article reported a school outbreak caused by a SaV GI.6 type. We speculated a more reliable molecular transmission network, estimated the rate of gene mutation and provided a reasonable elaboration for the C/T mutation at position 1236 of the VP1 gene.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To explore whether the food additive sodium benzoate(NAB) induces pancreatic inflammation and β cell apoptosis through the benzoylation(Kbz) modification pathway.Methods:In vivo experiments: C57BL/6J male mice(8 weeks old, 18-20 g) were randomly divided into normal control group(double distilled water feeding) and NAB feeding group(1 g/kg NAB feeding). Blood glucose were measured. After 20 weeks, fasting serum insulin, interleukin(IL)-18, IL-1β, and benzoyl-CoA levels were detected by ELISA method. Bax, IL-18, Pan-Kbz and Pan-Kac were detected by immunohistochemistry staining. In vitro experiments: β-TC-6 cells were cultured with NAB(6 mmol/L) or benzoyl-CoA(100 μmol/L) as stimulator and acyltransferase P300 inhibitor A485(10 μmol/L) as intervention factor. 24 hours later, inflammation, apoptosis, insulin secretion and Pan-Kbz level were detected by qRT-PCR, ELISA and Western blotting.Results:In the in vivo experiments, compared to the NC group, mice in the NAB group exhibited impaired glucose tolerance, decreased fasting insulin levels, significantly increased serum benzoyl coenzyme A concentrations, relatively elevated pancreatic IL-1β, IL-18, and Bax protein expressions, increased levels of Pan-Kbz, while Pan-Kac levels were downregulated(all P<0.05); In vitro experiments, NAB dose-dependently inhibited insulin secretion, promoted the release of Pan-Kbz and inflammatory factors IL-18 and TNF- α, inhibited Bcl-2 expression and up-regulated Bax expression, A485 reversed NAB-induced Pan-Kbz modification, improved NAB-induced inflammation and apoptosis, and promoted insulin secretion(all P<0.05). Conclusion:NAB may induce pancreatic inflammation, β-cell apoptosis, and impair insulin secretion through Kbz modification pathway.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.