Thalidomide(THA)is renowned for its potent anti-inflammatory properties.This study aimed to eluci-date its underlying mechanisms in the context of Crohn's disease(CD)development.Mouse colitis models were established by dextran sulfate sodium(DSS)treatment.Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry,respectively.Antibiotic-treated mice served as models for microbiota depletion and transplantation.The expression of forkhead box P3+(FOXP3+)regulatory T cells(Tregs)was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort.THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile,with an increased abundance of probiotics Bacteroides fragilis,while pathogenic bacteria were depleted.In addition,THA increased beneficial metabolites bile acids and significantly restored gut barrier function.Transcriptomic profiling revealed that THA inhibited interleukin-17(IL-17),IL-1β and cell cycle signaling.Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA.Specifically,increased level of gut commensal B.fragilis was observed,correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid(7-ketolithocholic acid,7-KA)following THA treatment.This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1(FXR1)to inhibit auto-phagy.An interaction between FOXP3 and FXR1 was identified,with binding regions localized to the FOXP3 domain(aa238-335)and the FXR1 domain(aa82-222),respectively.Conclusively,THA modu-lates the gut microbiota and metabolite profiles towards a more beneficial composition,enhances gut barrier function,promotes the differentiation of FOXP3+Tregs and curbs pro-inflammatory pathways.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

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*

Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3⁺ (FOXP3⁺) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3⁺ Tregs and curbs pro-inflammatory pathways.

Objective:To examine the manifestations and causes of administrative burden among primary healthcare professionals,and to explore its impact on job burnout through the mediating role of role conflict,providing theoretical and empirical support for governance-level burden-reduction strategies.Methods:An exploratory sequential mixed-methods design was employed,focusing on primary healthcare professionals in Shandong Province.In the first phase,in-depth interviews were conducted with 175 participants;in the second phase,a questionnaire survey of 1,096 participants and follow-up interviews with 107 participants were carried out.Results:The proportions of respondents who reported"heavy"or"very heavy"burdens were 62.7%for inspection,54.8%for documentation,51.8%for reporting,and 24.4%for meetings.Structural equation modeling showed that administrative burden had a direct effect on job burnout(0.150)and an indirect effect through role conflict(0.093).Qualitative findings further indicated that administrative burden largely stemmed from public health traceability requirements and medical insurance policies,and operated through both resource-based and value-based conflicts.Conclusions:Primary healthcare professionals face considerable administrative burdens,which may heighten job burnout through role conflict.Governance reforms should optimize inspection and assessment,streamline data reporting,refine record-keeping,and promote collaborative governance to break the chain of institutional pressure leading to burnout.

Objective:To examine the manifestations and causes of administrative burden among primary healthcare professionals,and to explore its impact on job burnout through the mediating role of role conflict,providing theoretical and empirical support for governance-level burden-reduction strategies.Methods:An exploratory sequential mixed-methods design was employed,focusing on primary healthcare professionals in Shandong Province.In the first phase,in-depth interviews were conducted with 175 participants;in the second phase,a questionnaire survey of 1,096 participants and follow-up interviews with 107 participants were carried out.Results:The proportions of respondents who reported"heavy"or"very heavy"burdens were 62.7%for inspection,54.8%for documentation,51.8%for reporting,and 24.4%for meetings.Structural equation modeling showed that administrative burden had a direct effect on job burnout(0.150)and an indirect effect through role conflict(0.093).Qualitative findings further indicated that administrative burden largely stemmed from public health traceability requirements and medical insurance policies,and operated through both resource-based and value-based conflicts.Conclusions:Primary healthcare professionals face considerable administrative burdens,which may heighten job burnout through role conflict.Governance reforms should optimize inspection and assessment,streamline data reporting,refine record-keeping,and promote collaborative governance to break the chain of institutional pressure leading to burnout.

Objective: To explore the moderating role of estradiol in the relationship between parenting styles and preschool children's behavioral problems, so as to provide a theoretical basis for improving the development of human s emotional health development in early life stage. Methods: During September to November in 2022, 354 children aged 3-6 years and their parents from two kindergartens in Bengbu City were chosen by using stratified cluster sampling method for the questionnaire survey. The Parenting Style Scale and the Child Behavior Checklist (CBCL) were used to collect information on parenting style and child behavioral problems. Salivary estradiol of children was collected and tested. Independent samples t test was applied to compare the scores of the scale for parental up bringing and children s behavioral problems, and Pearson correlation analysis was conducted to explore the relationship among parental upbringing, estradiol and children s behavioral problems. Results: Parents doting, laissez faire, autocratic, and inconsistent parenting styles were positive associated with child behavior problems( r =0.14-0.70); fathers democratic parenting style was negatively associated with child behavior problems( r =-0.14，-0.22，-0.21，-0.17，-0.27，-0.20); mothers democratic parenting styles was negatively correlated with scores on all five dimensions of child behavior problems except the withdrawal dimension ( r =-0.14，-0.12，-0.13，-0.21，-0.12)( P <0.05). Estradiol levels had significant moderating effects on maternal doting parenting style and children s withdrawal ( β =0.68) as well as social problems ( β =-1.00), also moderating laissez faire parenting styles and children s withdrawal problems ( β =0.75)( P <0.05). For children with low levels of estradiol, withdrawal problem scores were negatively associated with mother s doting parenting style and positively associated with laissez faire parenting style, and socialization problem scores were associated with mother s doting parenting style; for children with high levels of estradiol, withdrawal problem scores were positively associated with mother s doting parenting style, and socialization problem scores were associated with mother s doting parenting style ( t=2.84, 6.24, 3.16 , 2.37, 4.49, P <0.05). Conclusions Parenting styles are strongly associated with child behavioral problems; estradiol levels play a moderating role in mothers doting, laissez faire parenting styles and children s withdrawal problems and social problems.Parents should adopt more positive parenting styles and focus on the role of estradiol levels in maternal education to reduce the occurrence of behavioral problems in children.

Objective:To investigate the mid-and long-term clinical efficacy of modified Colonna arthroplasty in the treatment of unilateral dislocation type developmental dysplasia of hip (DDH) in adolescents.Methods:A total of 28 adolescent DDH patients with unilateral dislocation who underwent modified Colonna capsular arthroplasty from January 2016 to January 2018 in the 920th Hospital of Joint Logistics Support Force of People's Liberation Army were retrospectively analyzed. There were 4 males and 24 females, aged 16.5±5.0 years (range, 10-25 years). The mean body mass index was 21.2±1.1 kg/m 2 (range, 18.7-24.1 kg/m 2). According to DDH classification, 10 cases were Tonnis type III and 18 cases were Tonnis type IV. The postoperative lateral center-edge angle, acetabular coverage, femoral anteversion angle and leg length discrepancy were measured. The operation time, intraoperative blood loss, visual analogue scale (VAS) of hip pain, Harris hip score (HHS) and congenital dislocation of the hip score were recorded. Results:All patients successfully completed the operation and were followed up for 72.1±5.2 months (range, 60-84 months). The operation time was 81.6±4.3 min (range, 70-90 min), the intraoperative blood loss was 177.5±12.6 ml (range, 160-200 ml), and the hospital stay was 6.8±0.7 days (range, 6-9 days). The VAS score of the hip joint was 1.8±0.6 before operation and 2.3±0.6 at the last follow-up, and the difference was not statistically significant ( t=2.845, P=0.224). The preoperative HHS score was 57.1±5.9, and it increased to 87.3±4.0 at the last follow-up, and the difference was statistically significant ( t=-22.141, P=0.001). At the last follow-up, the femoral anteversion angle was 17.0°±1.5°, which was lower than that before operation 41.6°±2.4°, with a statistically significant difference ( t=-44.868, P=0.008). The leg length discrepancy was 10.2±2.3 mm, which was lower than that before operation (26.4±6.1 mm), with a statistically significant difference ( t=-12.892, P<0.001). The lateral center-edge angle was 28° (26°, 30°), and the acetabular coverage rate was 78% (76%, 79%). The curative effect evaluation standard score of congenital dislocation of the hip was 24 (16.7, 25.7) points, including 7 excellent cases, 14 good cases, 4 fair cases, and 3 poor cases. The excellent and good rate was 75% (21/28). Conclusion:The modified Colonna arthroplasty for the treatment of unilateral dislocation DDH in adolescents has good mid-and long-term hip function recovery and radiographic improvement.

Objective To evaluate the process risk of the implementation of prevention and control measures for surgical site infection(SSI)after colorectal surgery,and explore the application effect of failure mode and effects analysis(FMEA)based on action priority.Methods FMEA based on action priority was adopted to evaluate the whole process of the implementation of prevention and control measures for SSI after colorectal surgery.Prioritiza-tion ranking was conducted according to whether optimized measures were taken.Standard-reaching rate of comp-liance to SSI prevention and control measures as well as SSI incidence before and after the implementation of FMEA were compared.Results After evaluation,there were 7 high-priority and 22 medium-priority prevention and control measures for SSI.The control of medium-priority measures was strengthened,with a focus on developing further preventive and detectable measures for high-priority measures.The re-evaluation results after improvement showed that 7 high-priority measures have been downgraded to medium priority,and 16 medium-priority measures have been downgraded to low priority.Standard-reaching rate of compliance to SSI prevention and control measures in-creased from 77.15％(2 566/3 326)to 92.47％(3 096/3 348),and SSI incidence decreased from 6.04％(58/960)to 2.54％(60/2 364).Conclusion Application of FMEA based on action priority can effectively evaluate the risk of prevention and control process of SSI after colorectal surgery,and adopting preventive risk control measures accord-ing to the current situation can reduce the incidence of SSI after colorectal surgery.

BACKGROUND:This study aims to explore whether Xuebijing(XBJ)can improve intestinal microcirculation dysfunction in sepsis and its mechanism. METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ+axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate)were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(P13K),phosphorylated P13K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt)in the small intestine was analyzed via Western blotting. RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total P13K,and p-Akt/total Akt in the rat small intestine. CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.