Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Objective: To examine the relationship between self-management behaviors and time perspective among patients with comorbid diabetes, so as to provide the evidence for improving self-management behaviors among patients with comorbid diabetes. Methods: The patients with comorbid diabetes who were registered in the chronic disease health management system of Minhang District, Shanghai Municipality in 2021, followed up regularly, and lived in Meilong Town were recruited. Demographic information and family history of diabetes were collected through questionnaire surveys. Time perspective and self-management behaviors were assessed using the Zimbardo Time Perspective Inventory and Diabetes Self-Management Behavior Scale, respectively. The relationship between self-management behaviors and time perspective was analyzed using a multivariable ordinal logistic regression model. Results: A total of 907 patients with comorbid diabetes were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged 65 years and above, accounting for 71.89%. In terms of the types of time perspective, 280 patients were future-oriented (30.87%), 236 were balanced (26.02%), 162 were sensation-seeking (17.86%), 123 were fatalistic (13.56%), and 106 were negative (11.69%). In terms of the self-management behaviors, 46 patients were good (5.07%), 643 were moderate (70.89%), and 218 were poor (24.04%). Multivariable ordinal logistic regression analysis showed that after adjusting for age, gender, educational level, marital status, occupation status, monthly income, and family history of diabetes, the patients with comorbid diabetes who had a future-oriented time perspective had better self-management behaviors (OR=1.874, 95%CI: 1.204-2.915). Conclusion The self-management behaviors among patients with comorbid diabetes are moderate to poor, and patients with a future-oriented time perspective can better engage in self-management behaviors.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Objective To explore the mechanism by which Pulsatilla saponin D(PSD)inhibits invasion and metastasis of triple-negative breast cancer(TNBC).Methods The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC.The"PSD-target-disease"interaction network was constructed and protein-protein interaction(PPI)analysis was performed to obtain the core targets,which were analyzed for KEGG pathway and GO functional enrichment.Molecular docking study of the core targets and PSD was performed,and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells.Results Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets.GO analysis yielded 175 entries related to the binding of biomolecules(protein,DNA and RNA),enzyme activities,and regulation of gene transcription.KEGG analysis yielded 46 entries involving pathways in cancer,chemical carcinogenesis-receptor activation,microRNAs in cancer,chemical carcinogenesis-reactive oxygen species,PD-L1 expression and PD-1 checkpoint pathway in cancer.Molecular docking showed high binding affinities of PSD to MTOR,HDAC2,ABL1,CDK1,TLR4,TERT,PIK3R1,NFE2L2 and PTPN1.In cultured TNBC cells,treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2,MMP9,N-cadherin and the core proteins p-mTOR,ABL1,TERT,PTPN1,HDAC2,PIK3R1,CDK1,TLR4 as well as NFE2L2 expressionin the cell nuclei.Conclusion The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.

Objective:To investigate the value of nomogram model based on CT features in differentiating ectopic pancreas (EP) from gastrointestinal stromal tumors (GIST) with a long diameter less than 3 cm.Methods:This study was a case-control study. The clinical and imaging data of 43 patients with EP and 90 patients with GIST confirmed by pathology in the Affiliated Hospital of Guizhou Medical University from August 2013 to March 2024 were retrospectively analyzed. Preoperative CT images were analyzed to obtain qualitative features (number of lesions, location, morphology, growth pattern, borders, cystic degeneration, calcification, ulceration, catheter sign, central umbilication) and quantitative features (lesion long diameter, short diameter, long/short diameter, lesion and normal pancreas arterial-phase and venous-phase CT values, and enhancement ratio). Statistical analyses, including independent sample t-tests, Mann-Whitney U tests, χ2 tests, and Fisher exact tests, were performed to compare CT characteristics between the two groups. Binary logistic regression analysis was used to obtain independent predictors to identify the two groups, to establish a joint model, and to draw a nomogram. The discriminative performance of the independent predictors and the combined model was assessed using receiver operating characteristic (ROC) curves, while calibration curves were used to evaluate model fit. Results:The differences in age, location, morphology, border, catheter sign, central umbilication, short diameter, long/short diameter, arteriovenous phase enhancement CT value and arteriovenous phase enhancement ratio were statistically significant between the EP group and the GIST group (all P<0.05). The logistic analysis showed that the differences in age ( OR=0.920, 95% CI 0.885-0.956, P<0.001), border ( OR=5.994, 95% CI 2.111-17.022, P=0.001), long/short diameter ( OR=7.820, 95% CI 1.841-33.224, P=0.005), and venous phase enhancement ratio ( OR=8.847, 95% CI 1.103-70.972, P=0.040) were the independent predictors for distinguishing EP from GIST, and the area under the ROC curve (AUC) were 0.782 (95% CI 0.698-0.866), 0.684 (95% CI 0.600-0.767), 0.705 (95% CI 0.607-0.803), and 0.693 (95% CI 0.605-0.781), respectively. Combined age, border, long diameter/short diameter and venous phase enhancement ratio were plotted in a nomogram with an AUC of 0.881 (95% CI 0.817-0.945), sensitivity and specificity of 74.4% and 93.3%, respectively. The calibration curve demonstrated a strong agreement between predicted and actual probabilities (Hosmer-Lemeschow test, P=0.267). Conclusions:CT imaging reveals significant differences between EP and small GISTs (<3 cm). EP is more likely when patients are younger and lesions exhibit indistinct borders, a higher long-to-short diameter ratio, and greater venous-phase enhancement. The nomogram derived from CT features provides a valuable tool for differentiating EP from GIST.

Objective To explore the impact of seasonal and temperature variations on fasting blood glucose(FPG)in patients with type 2 diabetes(T2DM).Methods A retrospective analysis was conducted on clinical data of 31 994 T2DM patients managed by community health service center in Minhang District,Shanghai,from January 1,2020 to October 31,2023.The effect of seasonal and temperature variations on FPG levels and blood glucose control was investigated in T2DM patients.Results A total of 72 334 FPG tests were conducted in 31 994 T2DM patients,with an average of 2.26 tests per person.The number of tests conducted in spring,summer,autumn and winter were 15 558,34 018,21 929 and 829,respectively.The FPG levels of T2DM patients were lower in summer and autumn compared to those of winter and spring(P<0.05),while the FPG control rates were higher in summer and autumn compared to those of winter and spring(Bonferroni-corrected,P<0.008).There were no significant differences in FPG levels and blood glucose control rates between spring and winter,or between summer and autumn.The results of the multilevel mixed-effect Logistic model analysis with FPG control status as the dependent variable revealed that the risk of uncontrolled FPG in T2DM patients during winter and spring was 47%(aOR=1.465,95%CI:1.156-1.855)and 51%(aOR=1.510,95%CI:1.384-1.645),respectively,which was higher than that of autumn.The levels of FPG and the incidence of FPG abnormalities reached peak in February and reached the trough in September.Both the FPG levels and the incidence of FPG abnormal exhibited a trend of increasing with the decrease of temperature,and with a lag effect observed.Spearman rank correlation test indicated that there was a negative correlation between FPG levels and incidence of abnormal FPG and the monthly average daily temperature one month lagged(rs=-0.951,P＜0.001 and rs=-0.944,P＜0.001).Conclusion FPG levels of T2DM patients exhibit a pronounced seasonal pattern of elevation during winter and spring,accompanied by a reduction in blood glucose control rates.FPG levels and the prevalence of abnormal FPG exhibit a negative correlation with the monthly average daily temperature,and there is a lag effect.

Background and Aims:Obesity is often accompanied by symptoms of disordered eating.Although bariatric metabolic surgery can alleviate these symptoms,there are significant individual differences in postoperative outcomes,and effective predictive indicators are lacking.Liver and kidney function,along with lipid profiles,are closely related to metabolic status and may serve as useful markers for preoperative risk stratification and prognosis prediction.This study was conducted to explore the relationship between preoperative metabolic indicators and symptoms of disordered eating,thereby identifying postoperative recovery patterns among obese patients to support individualized management strategies.Methods:A total of 41 obese patients who underwent sleeve gastrectomy at Shanghai Sixth People's Hospital between September 2020 and June 2023 were enrolled,along with 36 healthy volunteers recruited during the same period.Participants completed the Eating Disorder Inventory-2(EDI-2)questionnaire,and serum samples were collected to assess liver function,kidney function,and lipid levels prior to surgery.The Mantel test was used to analyze correlations between metabolic indicators and EDI-2 scores.Latent profile analysis(LPA)was conducted using the indicators significantly correlated with EDI-2 scores to identify subgroups within the obese cohort.Linear mixed models were then applied to examine the trajectories of postoperative symptom changes across subgroups.Results:Levels of cystatin C,cholinesterase,gamma-glutamyl transferase,triglycerides,and apolipoprotein E were significantly higher in the obese group compared to the healthy group(all P＜0.05),and EDI-2 total score was also significantly elevated(P＜0.05);the prealbumin level in the healthy group was significantly higher than that in the obese group(P＜0.05).These six indicators were positively correlated with EDI-2 score(all r＞0.20,P＜0.05).Based on these markers,the LPA classified the obese group into two subgroups,with subgroup 2 exhibiting higher levels of most metabolic indicators than subgroup 1.During the 18-month postoperative follow-up,both subgroups showed reductions in EDI-2 score,but symptom improvement in subgroup 2 occurred later(month 6)compared to subgroup 1(month 4).Conclusion:Preoperative levels of cholinesterase,gamma-glutamyl transferase,prealbumin,triglycerides,and apolipoprotein E may serve as predictive indicators for improvement in disordered eating symptoms.Recovery patterns after bariatric surgery vary among obese patients with different metabolic profiles,highlighting the need for tailored intervention strategies.

ObjectiveTo analyze the impact of diabetes-related deaths on the probability of premature mortality and life expectancy in Minhang District of Shanghai from 2004 to 2023, and to provide reference data for the optimization of targeted prevention and control strategies. MethodsAll death cases involving diabetes among the registered residents of Minhang District from 2004 to 2023 were collected. The probability of premature mortality and life expectancy was computed using the abridged life table method. The average annual percent change (AAPC) was calculated with Joinpoint 4.9.0.0. The Arriaga decomposition method was employed for statistical analyses of the influence of cause-specific and age-specific mortality related to diabetes on life expectancy. ResultsThe total number of diabetes-related mortality, crude mortality, and standardized mortality for both males and females in Minhang District from 2004 to 2023 exhibited an increasing trend (P<0.001). The primary causes of death among diabetes-related cases were cardiovascular disease (37.68%), diabetes mellitus (31.95%), and malignant tumor (17.80%). From 2004 to 2023, probability of premature mortality to diabetes-related diseases demonstrated a rising trend (P<0.001), contrasting with the declining trend observed in the overall population (P=0.001). Males showed a significant upward trajectory (P<0.001), while females displayed a stable pattern. Among the diseases exerting considerable influence, cardiovascular disease and malignant tumor revealed a marked increase over time (P<0.001), whereas diabetes mellitus maintained a stable trend; both factors negatively impacted the reduction in probability of premature mortality. From 2004 to 2023, diabetes-related mortality reduced life expectancy among residents by an average of 1.22 years (-49.89%), indicating a negative impact; the reduction was 1.41 years in males and 0.90 years in females. The age groups exhibiting greater negative contributions differed by genders, namely males aged 50‒54 years and females aged 70‒74 years. Cardiovascular disease, diabetes mellitus, and malignant tumor contributed significantly to this decline (-0.46 years, -0.42 years, -0.20 years, respectively), with male experiencing higher negative contributions than females. ConclusionIn Minhang District, the rising mortality associated with diabetes-related diseases negatively impact both the reduction of the probability of premature mortality and the increase in life expectancy. This trend is primarily attributed to the rapid escalation of mortality and younger age demographic of male residents, which warrants significant attention. It is recommended that, based on the enhancement of case management, efforts should be directed towards the targeted prevention and control of risk factors and high-risk populations.