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*

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective:To design a new type of intelligent power-assisted hip disarticulation prosthesis and to use experiments to verify its kinematic performance.Methods:The main body of the prosthesis was designed using a double parallel four-link configuration based on a remote motion center mechanism. A series elastic actuator was used to provide external power for the prosthesis, and an antagonistic torsion spring structure was used to achieve bidirectional energy storage assistance in hip flexion and extension. A control system based on impedance control was established. By setting up an auxiliary force field to compensate for the difference between the actual angle of the prosthesis and the target angle, the prosthesis assist function was realized. Finally, the traditional hip disarticulation prosthesis was used as a comparison to test the overall performance of the new intelligent power-assisted hip disarticulation prosthesis worn by normal people.Results:For the new smart-assisted hip-disarticulation prosthesis, the goodness-of-fit of its hip joint angle curve to that of a normal person was 86%, which was 14% higher than that of the traditional hip-disarticulation prosthesis (72%). The goodness-of-fit of the healthy-side angle of the new smart-assisted hip disarticulation prosthesis to the normal human was 94%, which was the same as that of the traditional hip disarticulation prosthesis.Conclusions:A new type of intelligent power-assisted hip disarticulation prosthesis is designed to realize the function of prosthesis-assisted movement.

The paper summarizes the imaging evaluation methods for assessing the degree of carotid artery stenosis and analyzes the unique advantages and limitations of various imaging techniques in vascular imaging based on existing guidelines and consensus.The paper focuses on reviewing the clinical applications of several novel ultrasound technologies,including the use of advanced hemodynamic parameters such as blood flow dispersion(Tur index)and wall shear stress(WSS).Carotid artery stenosis is closely associated with cardiovascular disease.Although non-invasive and radiation-free ultrasound technology has certain limitations in diagnostic accuracy to a certain extent,with the continuous emergence of advanced functions such as ultrasound hemodynamics and vascular elasticity,the combination of multi-modality and multi-parameter ultrasound is expected to become an important method for efficient diagnosis of arterial stenosis in the future.

Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P＜0.001),while MAP was not significantly correlated with gestational week(P＞0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.

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.

Objective:This study aimed to analyze cytomegalovirus (CMV) reactivation and its influencing factors in patients with B-lymphocyte malignancy who received chimeric antigen receptor T (CAR-T) cell therapy.Methods:This study retrospectively reviewed patients with B-lymphocyte malignancy who received CAR-T cell therapy in the First Affiliated Hospital of Soochow University from January 2021 to December 2023. The data of patients who underwent CMV-DNA detection and/or pathogen metagenomic sequencing twice or more within 100 days after CAR-T cell therapy were analyzed. The clinical characteristics of the CMV reactivation and non-activation groups were compared. The factors related to CMV reactivation were analyzed with the Chi-square test and nonparametric rank sum test, and the risk factors were examined with Logistic regression.Results:This study included 86 patients, among whom 18 (20.9%) had CMV reactivation, and the median time of reactivation was 20 (1-95) days. All of the 18 patients had CMV viremia, and no CMV disease was observed. Seven patients turned to the latent state after continuing acyclovir antiviral therapy, and 11 patients returned to the latent state after upgrading the antiviral therapy to first-line drugs, including ganciclovir and foscarnet sodium. Six or more courses of anti-tumor treatment before CAR-T cell therapy, allogeneic hematopoietic stem cell transplantation within 2 years before CAR-T cell therapy, non-remission before treatment, and the use of high-dose glucocorticoids and/or tocilizumab were related to CMV reactivation, among which allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and the use of high-dose glucocorticoids and/or tocilizumab treatment were independent risk factors for CMV reactivation.Conclusion:Patients with B-lymphocyte malignancy who received CAR-T cell therapy have the risk of CMV reactivation, especially for those who received allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and those who received high-dose glucocorticoids and/or tocilizumab treatment.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.