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 review the current development of artificial intelligence (AI) technology in the field of transfusion medicine. Methods: A systematic search was conducted in the Clarivate Web of Science Database from inception to December 2024 for literature related to AI and transfusion. A total of 4 775 publications were identified. Based on inclusion and exclusion criteria, 133 original studies were ultimately included and analyzed using a narrative synthesis approach. Results: Research on AI in transfusion has surged since 2020 (accounting for 77% of all publications), with China ranking second globally in publication volume. Among the included studies, 69.2% focused on predicting individual transfusion needs, followed by inventory management (8.3%), diagnosis and prediction of adverse transfusion reactions (6.0%), factors influencing transfusion outcomes (5.3%), blood group identification (5.3%), blood quality testing (4.5%), and precise blood volume measurement (1.5%). Additionally, 4.5% of the studies were published in journals with an impact factor greater than 10; 19.5% developed software or applications; 31.5% were multi-center studies; 48.1% utilized decision tree methods, while 31.5% employed neural network approaches; and 14.2% conducted external validation of the algorithms. Conclusion: AI demonstrates significant potential in transfusion risk prediction, decision support, and blood management. However, challenges remain, including limited model generalizability, insufficient algorithm interpretability, and barriers to clinical translation. The deep integration of AI with transfusion medicine will accelerate the advent of precision transfusion era, maximizing blood resource utilization, reducing waste, and ensuring transfusion safety.

Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective:To evaluate the association between N-acylsphingosine amide hydrolase 1 (ASAH1) and pyroptosis during acute lung injury (ALI) in septic mice.Methods:Forty SPF-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-23 g, were divided into 4 groups ( n=10 each) by a random number table method: sham operation group (Sham group), ALI group, HCFU solvent+ ALI group (HA group) and ASAH1 inhibitor HCFU+ ALI group (AA group). The abdominal cavity was only opened in Sham group, and cecal ligation puncture was performed in ALI, HA and AA groups. HCFU solvent 0.2 ml was intraperitoneally injected at 2 h before operation in HA group, and HCFU 10 mg/kg was intraperitoneally injected at 2 h before operation in AA group. The mice were sacrificed at 24 h under deep anesthesia, the eyeballs were removed to collect the blood, the bronchoalveolar lavage fluid (BALF) was collected, and lung tissues and blood samples were collected for microscopic examination of the pathological changes (using HE staining) which were scored and for determination of concentrations of protein in BALF (by BCA method), concentrations of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in BALF (by enzyme-linked immunosorbent assay), and expression of NOD-like receptor thermoprotein structural domain-related protein 3 (NLRP3) in lung tissues (by Western blot), gasdermin D protein (GSDMD), ASAH1 and cysteine protease-1 (caspase-1) (by Western blot). The wet/dry lung weight (W/D) ratio was calculated. Results:Compared with Sham group, the lung injury score, W/D ratio and concentrations of protein in BALF, IL-1β, IL-6 and TNF-α in serum were significantly increased, and the expression of NLRP3, GSDMD and caspase-1 in lung tissues was up-regulated in ALI, HA and AA groups, and the expression of ASAH1 was significantly up-regulated in ALI and HA groups ( P<0.05). Compared with ALI and HA groups, the lung injury score, W/D ratio, and concentrations of protein in BALF, IL-1β, IL-6 and TNF-α in serum were significantly increased, the expression of NLRP3, GSDMD and caspase-1 in lung tissues was up-regulated, and the expression of ASAH1 was down-regulated in AA group ( P<0.05 or 0.01). Conclusions:ASAH1 is involved in the endogenous protective mechanism underlying ALI in septic mice, which may be related to the inhibition of cell pyroptosis.

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 To investigate the effect of galectin-1 preconditioning on pyroptosis of venti-lator-induced lung injury(VILI)in mice.Methods Thirty clean grade healthy male C57BL/6 mice,aged 6-8 weeks,weighing 22-30 g,were divided into three groups by random number table method:control group(group C),VILI group(group V),and galectin-1+VILI group(group G),10 mice in each group.After endotracheal intubation,group C kept spontaneous breathing for 4 hours,groups V and G kept me-chanical ventilation for 4 hours.One hour before endotracheal intubation,groups C and V were intraperito-neally injected with normal saline 0.75 ml,and group G was intraperitoneally injected with galectin-1 3 μg.Arterial blood was collected before endotracheal intubation and after spontaneous respiration or ventilation to detect PaO2.Then mice were sacrificed and bronchoalveolar lavage fluid(BALF)was collected.Concentra-tions of IL-1β and IL-18 in BALF were detected by ELISA.Lung tissue was collected for determination of the wet weight/dry weight ratio(W/D).The expression of GSDMD,caspase-1,and caspase-11 mRNA and protein in lung tissues were detected by qRT-PCR and Western blot.Pathological changes of the lungs were observed and scored by HE staining.Results Compared with group C,PaO2 were significantly decreased,W/D,concentrations of IL-1β and IL-18 in BALF,mRNA and protein expressions of GSDMD,caspase-1 and caspase-11,and lung injury score were significantly increased in groups V and G(P＜0.05).Com-pared with group V,PaO2 was significantly increased,W/D,concentrations of IL-1β and IL-18 in BALF,mRNA and protein expressions of GSDMD,caspase-1,and caspase-11,and lung injury score were signifi-cantly decreased in group G(P＜0.05).Conclusion Galectin-1 can increase PaO2 in mice and reduce IL-1β and IL-18 concentration,mRNA expression and protein content of classical non-classical pyroptosis pathway related genes,and reduce VILI in mice.

This study summarizes the construction background, rules and regulations and institutional settings of the MOOC and Micro-course Club in the Second Hospital of Jilin University, discusses the means of teacher training for clinical teachers, and shows the application effect of the club. At the same time, the related problems encountered in the process of club construction are summarized and reflected. The construction of MOOC and micro-course clubs is conducive to improving the information-based teaching level of clinical teachers, and also provides new inspiration and ideas for the construction of medical clubs.

Objective:To evaluate the effect of sitagliptin on the expression of airway mucin 5AC (MUC5AC) in mice with endotoxin-induced lung injury.Methods:Thirty-six healthy male SPF C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), endotoxin-induced lung injury group (group L), and endotoxin-induced lung injury+ sitagliptin group (group S). Lipopolysaccharide (LPS) 3 mg/kg was intratracheally infused to prepare endotoxin-induced lung injury model in L and S groups, while the equal volume of normal saline was given instead in group C. Sitagliptin 100 mg/kg was intraperitoneally injected at 1 h before LPS infusion in group S, and normal saline was intraperitoneally injected at 1 h before endotracheal infusion in C and L groups. The arterial blood samples from femoral artery were taken at 24 h of LPS or normal saline infusion for measurement of PaO 2 and glucose levels.The mice were then sacrificed, and broncho-alveolar lavage fluid (BALF) and lung tissues were collected for determination of the concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)in serum and BALF (by enzyme-linked immunosorbent assay), wet/dry weight ratio (W/D ratio), expression of MUC5AC (by immunohistochemistry and immunohistochemical comprehensive score), and expression of MUC5AC mRNA in lung tissues (by quantitative real-time polymerase chain reaction) and for examination of the pathological changes of lung tissues (using haematoxylin and eosin staining) which were scored. Results:Compared with group C, PaO 2 was significantly decreased, the glucose levels, W/D ratio and lung injury score were increased, the concentrations of IL-6, IL-1β and TNF-α in serum and BALF were increased, and the expression of MUC5AC mRNA in lung tissues was up-regulated in L and S groups( P<0.05). Compared with group L, PaO 2 was significantly increased, the glucose levels, W/D ratio and lung injury score were decreased, the concentrations of IL-6, IL-1β and TNF-α in serum and BALF were decreased, and the expression of MUC5AC mRNA in lung tissues was down-regulated in group S( P<0.05). Conclusions:The mechanism by which sitagliptin alleviates endotoxin-induced lung injury is related to down-regulation of MUC5AC expression in mice.