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*

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

A combined epidemic prediction method based on multi-source data fusion is presented to address the common problems of low accuracy,weak generalization,single structure,poor nonlinear processing ability,and long prediction time in traditional epidemic prediction models.The collected multi-source epidemic data are normalized and subjected to feature selection using principal component analysis.An ARIMA-GM-BPNN model for pandemic prediction is constructed by combining ARIMA model,grey GM model and BPNN.The fitting values of the first two prediction models are used as inputs to BPNN for model training.After sufficiently integrating the data and combining the advantages of different prediction models,the optimal combined model is obtained and used for forecasting the incidence and trend of epidemics.Experimental results show that the combined model exhibits excellent fitting performance,with predicted incidences and trends consistent with the real conditions.The proposed approach improves prediction accuracy and generalization capabilities,and it can provide reliable data support for epidemic prediction and control.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

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.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

Objective:To analyze the proportions of innate lymphoid cells (ILCs) subgroups during the process of Mycobacterium tuberculosis (MTB) infection, and to explore the molecular mechanism regulating the differentiation of ILCs during MTB infection. Methods:From March to October 2022, 31 patients with active pulmonary tuberculosis (ATB) and 17 patients who had recovered from pulmonary tuberculosis were enrolled from Shenzhen Third People′s Hospital. Additionally, 30 healthy controls were recruited from the physical examination department. Peripheral blood mononuclear cells (PBMCs) were extracted from all subjects, and the proportions of ILC, ILC1, ILC2 and ILC3 in lymphocytes of PBMCs from different populations were analyzed using flow cytometry. PBMCs from 18 healthy controls were induced in vitro with MTB H37Rv lysate or live Bacillus Calmette-Guérin (BCG) bacteria, and the differentiation of ILC subgroups was analyzed using flow cytometry. CD14 + cells from PBMCs of 29 healthy controls were isolated using magnetic bead sorting technology, and the cells were divided into three groups, including control group, CD14 - group, and CD14 + complement group. The CD14 + complement group was supplemented with CD14 + cells into CD14 - PBMCs through a Transwell chamber, and induced in vitro with H37Rv lysate. The differentiation of ILC subgroups was analyzed using flow cytometry. Statistical analyses were performed using Mann-Whitney U test, Kruskal-Wallis test, and Wilcoxon signed-rank test. Results:The proportions of ILCs in lymphocytes in healthy controls, ATB and recovered tuberculosis groups showed no statistically significant differences ( H=0.07, P=0.965). The proportion of ILC1 in lymphocytes in the peripheral blood of patients with ATB was lower than that in the healthy control group ( U=271.00), and the proportion of ILC2 was higher than that in the healthy control group ( U=299.00). The proportion of ILC1 in the peripheral blood of recovered tuberculosis patients was lower than that in the healthy control group ( U=123.00), and the proportion of ILC3 in the recovered tuberculosis group was higher than those in ATB and healthy control groups ( U=78.00 and 102.50, respectively). All differences were statistically significant (all P<0.05). Compared with the control group, the proportions of ILC ( W=-116.00 and -145.00, respectively) and ILC2 ( W=-149.00 and -155.00, respectively) in lymphocytes decreased after PBMCs induced by H37Rv lysate or BCG live bacteria (all P<0.05). The proportion of ILC1 showed no significant change after induction by H37Rv lysate ( W=-67.00, P=0.154), but decreased after induction by BCG ( W=-121.00, P=0.007) with statistical significance. There was no significant difference in the proportions of ILC1 in lymphocytes among control group, CD14 - group, and CD14 + complement group before and after induction by H37Rv lysate ( W=-159.00, 43.00 and -37.00, respectively, all P>0.05). The proportions of ILC2 in lymphocytes decreased after induction ( W=-435.00, -383.00 and -405.00, respectively) among the three groups, and the differences were all statistically significant (all P<0.001). The proportions of ILC3 in lymphocytes in the control group and CD14 + complement group decreased ( W=-250.00 and -262.00, respectively), and the differences were statistically significant (all P<0.05), while the proportion of ILC3 in lymphocytes in the CD14 - group did not change before and after induction, and the difference was not statistically significant ( W=-172.00, P=0.051). Conclusions:MTB infection induces an imbalance in the differentiation of ILCs subgroups, and the removal of CD14 + cells inhibits MTB-induced ILC3 differentiation without significantly affecting the differentiation of ILC1 and ILC2.

Objective:To analyze the proportions of innate lymphoid cells (ILCs) subgroups during the process of Mycobacterium tuberculosis (MTB) infection, and to explore the molecular mechanism regulating the differentiation of ILCs during MTB infection. Methods:From March to October 2022, 31 patients with active pulmonary tuberculosis (ATB) and 17 patients who had recovered from pulmonary tuberculosis were enrolled from Shenzhen Third People′s Hospital. Additionally, 30 healthy controls were recruited from the physical examination department. Peripheral blood mononuclear cells (PBMCs) were extracted from all subjects, and the proportions of ILC, ILC1, ILC2 and ILC3 in lymphocytes of PBMCs from different populations were analyzed using flow cytometry. PBMCs from 18 healthy controls were induced in vitro with MTB H37Rv lysate or live Bacillus Calmette-Guérin (BCG) bacteria, and the differentiation of ILC subgroups was analyzed using flow cytometry. CD14 + cells from PBMCs of 29 healthy controls were isolated using magnetic bead sorting technology, and the cells were divided into three groups, including control group, CD14 - group, and CD14 + complement group. The CD14 + complement group was supplemented with CD14 + cells into CD14 - PBMCs through a Transwell chamber, and induced in vitro with H37Rv lysate. The differentiation of ILC subgroups was analyzed using flow cytometry. Statistical analyses were performed using Mann-Whitney U test, Kruskal-Wallis test, and Wilcoxon signed-rank test. Results:The proportions of ILCs in lymphocytes in healthy controls, ATB and recovered tuberculosis groups showed no statistically significant differences ( H=0.07, P=0.965). The proportion of ILC1 in lymphocytes in the peripheral blood of patients with ATB was lower than that in the healthy control group ( U=271.00), and the proportion of ILC2 was higher than that in the healthy control group ( U=299.00). The proportion of ILC1 in the peripheral blood of recovered tuberculosis patients was lower than that in the healthy control group ( U=123.00), and the proportion of ILC3 in the recovered tuberculosis group was higher than those in ATB and healthy control groups ( U=78.00 and 102.50, respectively). All differences were statistically significant (all P<0.05). Compared with the control group, the proportions of ILC ( W=-116.00 and -145.00, respectively) and ILC2 ( W=-149.00 and -155.00, respectively) in lymphocytes decreased after PBMCs induced by H37Rv lysate or BCG live bacteria (all P<0.05). The proportion of ILC1 showed no significant change after induction by H37Rv lysate ( W=-67.00, P=0.154), but decreased after induction by BCG ( W=-121.00, P=0.007) with statistical significance. There was no significant difference in the proportions of ILC1 in lymphocytes among control group, CD14 - group, and CD14 + complement group before and after induction by H37Rv lysate ( W=-159.00, 43.00 and -37.00, respectively, all P>0.05). The proportions of ILC2 in lymphocytes decreased after induction ( W=-435.00, -383.00 and -405.00, respectively) among the three groups, and the differences were all statistically significant (all P<0.001). The proportions of ILC3 in lymphocytes in the control group and CD14 + complement group decreased ( W=-250.00 and -262.00, respectively), and the differences were statistically significant (all P<0.05), while the proportion of ILC3 in lymphocytes in the CD14 - group did not change before and after induction, and the difference was not statistically significant ( W=-172.00, P=0.051). Conclusions:MTB infection induces an imbalance in the differentiation of ILCs subgroups, and the removal of CD14 + cells inhibits MTB-induced ILC3 differentiation without significantly affecting the differentiation of ILC1 and ILC2.