OBJECTIVE: This study aimed to explore the interplay between the life-course body mass index (BMI) trajectories and insulin resistance (IR) on incident diabetes. METHODS: This longitudinal cohort included 2,336 participants who had BMI repeatedly measured 3-8 times between 1989 and 2009, as well as glucose and insulin measured in 2009. BMI trajectories were identified using a latent class growth mixed model. The interplay between BMI trajectories and IR on diabetes was explored using the four-way effect decomposition method. Logistic regression and mediation models were used to estimate the interaction and mediation effects, respectively. RESULTS: Three distinct BMI trajectory groups were identified: low-stable ( n = 1,625), medium-increasing ( n = 613), and high-increasing ( n = 98). Both interaction and mediation effects of BMI trajectories and IR on incident diabetes were significant ( P < 0.05). The proportion of incident diabetes was higher in the IR-obesity than in the insulin-sensitivity (IS) obesity group (18.9% vs. 5.8%, P < 0.001). After adjusting for covariates, the odds ratios (95% confidence intervals) of the IR, IS-obesity, and IR-obesity groups vs. the normal group were 3.22 (2.05, 5.16), 2.05 (1.00, 3.97), and 7.98 (5.19, 12.62), respectively. IR mediated 10.7% of the total effect of BMI trajectories on incident diabetes ( P < 0.001). CONCLUSION We found strong interactions and weak mediation effects of IR on the relationship between life-course BMI trajectories and incident diabetes. IS-obesity is associated with a lower risk of incident diabetes than IR-obesity.
Humans ; Insulin Resistance ; Body Mass Index ; Male ; Female ; Middle Aged ; China/epidemiology* ; Adult ; Longitudinal Studies ; Incidence ; Diabetes Mellitus/epidemiology* ; Aged ; Obesity/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; East Asian People

ObjectiveTo investigate the inhibitory effect of Huoluo Xiaolingdan on triple negative breast cancer （TNBC） in mice through its regulation of TCF1⁺CD8⁺ stem cell-like T cells infiltration. MethodsA mouse model of TNBC was established and the mice were randomly divided into the model group， low-dose （3.9 g·kg^-1）， medium-dose （7.8 g·kg^-1） and high-dose （15.6 g·kg^-1） Huoluo Xiaolingdan groups， and anti-PD-1 antibody treatment group. Each group was given a dose of 0.01 mL·g^-1， while the model group and the anti-PD-1 treatment group were also given an equivalent volume of normal saline. The drug was administered for 21 days. In the anti-PD-1 antibody group， mice were intraperitoneally injected with 100 μg of mouse anti-PD-1 antibody twice a week， for a total of five injections. The tumor volume， survival time and tumor mass were measured at different time points. Hematoxylin-eosin （HE） staining was used to observe the histological changes of the tumor. The expression of CD8⁺T cells and TCF1⁺CD8⁺ stem-like T cells in tumor tissues was detected by immunohistochemistry and immunofluorescence staining. Flow cytometry was used to detect the difference of immune cell subsets in tumors and the expression difference of TCF1⁺CD8⁺ stem cell-like T cells in tumors and peripheral blood. The expression level of PD-L1 in tumor tissues was detected by Western blot. ResultsCompared with model group， the tumor volume and mass of in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group were decreased （P<0.05， P<0.01）. The median survival time of mice in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was as follows： 27.00 days （95%CI， 0.45-2.65）， 31.00 days （95%CI， 0.32-1.89）， 34.00 days （95%CI， 0.40-2.33）， and 35.00 days （95%CI， 0.42-2.47）. All of them were higher than that of the model group ［24.50 days （95%CI， 0.37-10.5）］. Flow cytometry showed that compared with the model group， the proportion and number of infiltrating CD8⁺ T cells in tumor were increased in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group （P<0.05， P<0.01）， while the proportion of tumor regulatory T cells （Treg） and M2 macrophages decreased （P<0.05）. Compared with the model group， the proportion of IFN-γ⁺CD8⁺ T and GrzB⁺CD8⁺ T cells in tumors in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was increased （P<0.01）， and the proportion of TCF1⁺CD8⁺ T cells in tumor and peripheral blood was also increased. Immunofluorescence staining further showed that the number of TCF1⁺CD8⁺ T cells in tumor tissues increased in low-， medium- and high-dose Huoluo Xiaolingdan groups. Western blot analysis showed no significant decrease in the PD-L1 protein expression in tumor tissues between the Huoluo Xiaolingdan groups and the model group. ConclusionHuoluo Xiaolingdan can inhibit TNBC in mice by increasing tumor infiltration of TCF1⁺CD8⁺ stem-like T cells， enhancing CD8⁺ T cell activity， and regulating immune cell subgroups such as M2 macrophages and Treg cells to enhance anti-tumor immunity. This study provides a theoretical basis for the clinical application of Huoluo Xiaolingdan in breast cancer treatment and combination therapy.

OBJECTIVE Aimed to comprehensively evaluate various immunological changes in a mouse model of eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP)induced by ovalbumin(OVA)combined with Aspergillus protease(AP),including nasal polyps-like lesions,subepithelial collagen deposition,inflammatory cell infiltration,epithelial barrier function,and olfactory neuron damage.METHODS C57BL/6 mice were challenged with OVA and AP for 12 weeks.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe the changes of nasal polyps-like lesions,goblet cell hyperplasia,and subepithelial collagen deposition.Immunohistochemistry staining(IHC)was employed to detect the changes of various inflammatory cells,olfactory neurons,and the expression of epithelial tight junction proteins in the nasal and sinus mucosa.RESULTS Compared to the control group,the OVA and AP group showed significantly increased epithelial thickness,noticeable nasal polyps-like lesions,marked subepithelial collagen deposition,and goblet cell hyperplasia in the nasal and sinus mucosa.IHC results revealed a significant increase in eosinophils,along with higher numbers of neutrophils,mast cells,and CD4+T cells in the OVA and AP group.Additionally,the expression of tight junction proteins ZO-1 and E-cadherin in the nasal and sinus mucosa and the area of OMP+olfactory neurons in the olfactory epithelium were significantly lower in the OVA and AP group compared to the control.CONCLUSION Continuous exposure to OVA combined with AP successfully induces ECRSwNP.The establishment of this model provides a foundation for further research into the pathogenesis and the evaluation of new therapeutic strategies for ECRSwNP.

Chronic sinusitis with nasal polyps(CRSwNP)is a highly heterogeneous chronic inflammatory disease,that persistently impacts patients'quality of life.To date,its etiology and pathogenesis remain incompletely unclear.Animal models serve as crucial tools for exploration of CRSwNP pathogenesis However,there is still a lack of a recognized mature and stable mouse model of CRSwNP in basic research.The stable mouse model of CRSwNP has become a key bottleneck in the analysis of the pathogenesis.This paper systematically reviews existing construction methodologies,inflammatory phenotypes,and applicability of murine CRSwNP models.By comparing their advantages and limitations,we will explore future optimization directions.This review will provide a theoretical basis and foundation for the basic research and clinical precision treatment of CRSwNP.

Objective:To investigate the expression relationship of Survivin,Bad,Bax and Bcl-2 genes in esophageal squamous cell carcinoma patients and to explore their correlation with clinicopathological markers,moreover,compare with GEPIA cancer database.Methods:48 ESCC specimens were taken from patients and used in the study.Matched adjacent normal tissues were used as controls.The expression of Survivin,Bad,Bax,and Bcl-2 genes were detected by RT-PCR.Meanwile,genes expressions were analyzed with clinicopathological factors,including tumor differentiation degree,TNM classification,clinical stage and lymph node metastasis.GEPIA analyzes the correlation between Survivin,Bad,Bax and Bcl-2 online.Results:In 48 cases of cancer tissues,Survivin expression was detected in 85.4％(41/48)of cancer tissues and in 62.5％(30/48)of adjacent normal tissues,and Bad was 45.8％(22/48)and 25％(12/48)respectively.Survivin and Bad were both highly expressed in cancer tissues,and the difference was statistically significant(P＜0.05),but Bax and Bcl-2 genes had no statical significance(P＞0.05).The mRNA expression rates of Bad,Bax,and Bcl-2 increased with higher differentiation degree(P＜0.05),while the high expression rate of Survivin mRNA was correlated with lymph node metastasis(P＜0.05).However,none of these markers showed associations with TNM staging or clinical stage.The expression of Bad had a negative correlation with the expression of Survivin(r=-0.449,P＜0.05),but a positive correlation with the expression of Bcl-2(r=0.348,P＜0.05).The expressions of Bax,Bcl-2 and survivin were positively correlated(r=0.552,0.331,respectively,both P＜0.05).The results of the GEPIA cancer database show that Survivin was highly expressed in cancer tissues(P＜0.05),and the expressions of Bad,Bax and Survivin were negatively correlated(r=-0.19,-0.16,respectively,both P＜0.01).Conclusions:Survivin and Bad may synergistically promote esophageal squamous cell carcinogenesis,while Bad,Bax,and Bcl-2 are implicated in malignant transformation.

Objective To explore the effect and mechanism of Sechang Zhixie Powder(SCZXS)on mice with acute diarrhea caused by castor oil.Methods The mice were randomly divided into blank control group,model control group,montmorillonite powder group(1.4 g·kg-1),SCZXS-L group(0.9 g·kg-1),SCZXS-M group(1.8 g·kg-1)and SCZXS-H group(3.6 g·kg-1),10 mice in each group.After continuous administration of 7 days,the acute diarrhea model of mice was prepared by oral administration of castor oil(0.01 mL·g-1).The diarrhea of mice was observed within 4 hours of castor oil administration,and the rate of loose stool,degree of loose stool,and diarrhea index were calculated;the levels of DAO,D-LDH,VIP,and SS in the colon were determined by enzyme-linked immunosorbent assay;The morphological changes in the colon tissue of mice were observed after HE staining and the thicknesses of the mucosal and muscular layers of the colon were quantified;AB-PAS staining was performed to observe the effect on mucin in the colon;and the expression of AQP3,Occludin,and ZO-1 in the colon were quantified by immunohistochemistry.Results Compared with the model control group,the rate of loose stool,degree of loose stool,and diarrhea index of the mice in the SCZXS groups tended to decrease,but the difference was not statistically significant.Compared with the model control group,the flat luminal surface of the mice in the SCZXS-M and SCZXS-H group were significantly thickened(P<0.01),and the amount of VIP in the colon was significantly decreased(P<0.05,P<0.01),and that of DAO in the colon was significantly decreased(P<0.01),Occludin and ZO-1 expression were significantly increased(P<0.01),the mucin area ratio was significantly increased(P<0.05)in the SCZXS-M group,and AQP3 expression was significantly increased(P<0.05)in the SCZXS groups.Conclusions SCZXS can improve acute diarrhea induced by castor oil in mice.and its mechanism may be related to the regulation of gastrointestinal hormones and AQP3.In addition,SCZXS improves intestinal damage caused by diarrhea and protects the intestinal barrier.

Objective:To investigate the expression relationship of Survivin,Bad,Bax and Bcl-2 genes in esophageal squamous cell carcinoma patients and to explore their correlation with clinicopathological markers,moreover,compare with GEPIA cancer database.Methods:48 ESCC specimens were taken from patients and used in the study.Matched adjacent normal tissues were used as controls.The expression of Survivin,Bad,Bax,and Bcl-2 genes were detected by RT-PCR.Meanwile,genes expressions were analyzed with clinicopathological factors,including tumor differentiation degree,TNM classification,clinical stage and lymph node metastasis.GEPIA analyzes the correlation between Survivin,Bad,Bax and Bcl-2 online.Results:In 48 cases of cancer tissues,Survivin expression was detected in 85.4％(41/48)of cancer tissues and in 62.5％(30/48)of adjacent normal tissues,and Bad was 45.8％(22/48)and 25％(12/48)respectively.Survivin and Bad were both highly expressed in cancer tissues,and the difference was statistically significant(P＜0.05),but Bax and Bcl-2 genes had no statical significance(P＞0.05).The mRNA expression rates of Bad,Bax,and Bcl-2 increased with higher differentiation degree(P＜0.05),while the high expression rate of Survivin mRNA was correlated with lymph node metastasis(P＜0.05).However,none of these markers showed associations with TNM staging or clinical stage.The expression of Bad had a negative correlation with the expression of Survivin(r=-0.449,P＜0.05),but a positive correlation with the expression of Bcl-2(r=0.348,P＜0.05).The expressions of Bax,Bcl-2 and survivin were positively correlated(r=0.552,0.331,respectively,both P＜0.05).The results of the GEPIA cancer database show that Survivin was highly expressed in cancer tissues(P＜0.05),and the expressions of Bad,Bax and Survivin were negatively correlated(r=-0.19,-0.16,respectively,both P＜0.01).Conclusions:Survivin and Bad may synergistically promote esophageal squamous cell carcinogenesis,while Bad,Bax,and Bcl-2 are implicated in malignant transformation.

Objective:To explore the research hotspots and developmental trends in the application of artificial intelligence (AI) in the health management of chronic obstructive pulmonary disease (COPD) .Methods:Literature related to the application of AI in COPD health management published between 1999 and 2024 was retrieved from the Web of Science Core Collection database. Visualization analyses were performed using Scimago Graphica, VOSviewer, and CiteSpace software. National geographic maps, author and institutional collaboration networks, keyword co-occurrence graph, keyword clustering views, and burst detection analysis were constructed to identify research hotspots and trends in this field.Results:A total of 192 publications were included, with an overall increasing trend in annual publication volume. The United States ranked first in publication count. Collaboration among authors and research teams was relatively dispersed. Current research hotspots focus on COPD risk assessment and prediction, health promotion interventions for COPD patients, and improving diagnostic accuracy. Future research trends are expected to emphasize the broader application of AI algorithms, the development of predictive models to improve forecasting performance, integration of diverse technical approaches for differential diagnosis, and enhancement of patient adherence.Conclusions:The application of AI in COPD health management is expanding, yet international and inter-author collaboration remains insufficient. There is a need to broaden and deepen research in this field. Future work may focus more on optimizing and applying algorithmic technologies and improving system construction to enhance patient adherence.

Objective To explore the effect and mechanism of Sechang Zhixie Powder(SCZXS)on mice with acute diarrhea caused by castor oil.Methods The mice were randomly divided into blank control group,model control group,montmorillonite powder group(1.4 g·kg-1),SCZXS-L group(0.9 g·kg-1),SCZXS-M group(1.8 g·kg-1)and SCZXS-H group(3.6 g·kg-1),10 mice in each group.After continuous administration of 7 days,the acute diarrhea model of mice was prepared by oral administration of castor oil(0.01 mL·g-1).The diarrhea of mice was observed within 4 hours of castor oil administration,and the rate of loose stool,degree of loose stool,and diarrhea index were calculated;the levels of DAO,D-LDH,VIP,and SS in the colon were determined by enzyme-linked immunosorbent assay;The morphological changes in the colon tissue of mice were observed after HE staining and the thicknesses of the mucosal and muscular layers of the colon were quantified;AB-PAS staining was performed to observe the effect on mucin in the colon;and the expression of AQP3,Occludin,and ZO-1 in the colon were quantified by immunohistochemistry.Results Compared with the model control group,the rate of loose stool,degree of loose stool,and diarrhea index of the mice in the SCZXS groups tended to decrease,but the difference was not statistically significant.Compared with the model control group,the flat luminal surface of the mice in the SCZXS-M and SCZXS-H group were significantly thickened(P<0.01),and the amount of VIP in the colon was significantly decreased(P<0.05,P<0.01),and that of DAO in the colon was significantly decreased(P<0.01),Occludin and ZO-1 expression were significantly increased(P<0.01),the mucin area ratio was significantly increased(P<0.05)in the SCZXS-M group,and AQP3 expression was significantly increased(P<0.05)in the SCZXS groups.Conclusions SCZXS can improve acute diarrhea induced by castor oil in mice.and its mechanism may be related to the regulation of gastrointestinal hormones and AQP3.In addition,SCZXS improves intestinal damage caused by diarrhea and protects the intestinal barrier.

Objective:To explore the research hotspots and developmental trends in the application of artificial intelligence (AI) in the health management of chronic obstructive pulmonary disease (COPD) .Methods:Literature related to the application of AI in COPD health management published between 1999 and 2024 was retrieved from the Web of Science Core Collection database. Visualization analyses were performed using Scimago Graphica, VOSviewer, and CiteSpace software. National geographic maps, author and institutional collaboration networks, keyword co-occurrence graph, keyword clustering views, and burst detection analysis were constructed to identify research hotspots and trends in this field.Results:A total of 192 publications were included, with an overall increasing trend in annual publication volume. The United States ranked first in publication count. Collaboration among authors and research teams was relatively dispersed. Current research hotspots focus on COPD risk assessment and prediction, health promotion interventions for COPD patients, and improving diagnostic accuracy. Future research trends are expected to emphasize the broader application of AI algorithms, the development of predictive models to improve forecasting performance, integration of diverse technical approaches for differential diagnosis, and enhancement of patient adherence.Conclusions:The application of AI in COPD health management is expanding, yet international and inter-author collaboration remains insufficient. There is a need to broaden and deepen research in this field. Future work may focus more on optimizing and applying algorithmic technologies and improving system construction to enhance patient adherence.