Cornelia de Lange syndrome （CdLS） is a rare genetic disorder characterized by multisystem developmental abnormalities， with its core pathogenic mechanism closely linked to dysfunction of the cohesin complex. Integrated multi‑omics evidence revealed that cohesin dysfunction disrupted three‑dimensional chromatin architecture and epigenetic homeostasis， triggered genome‑wide transcriptional dysregulation， and perturbed the regulatory networks of signaling pathways such as Wnt/β‑catenin， TGF‑β/BMP， and Sonic Hedgehog （SHH）. These disturbances collectively drove multisystem phenotypes involving the neurological， cardiovascular and skeletal systems， and laid a theoretical foundation for further understanding of the pathological mechanisms of CdLS and optimizing molecular diagnosis. This review summarized the genetic basis （including epigenetic dysregulation mechanisms） and disruption of key developmental signaling pathways in CdLS，and discussed strategies for optimizing molecular diagnosis.

Objective To explore the mechanism of electroacupuncture in inhibiting peripheral sensitization of visceral pain in mice with irritable bowel syndrome(IBS)based on TRPV1/Ras/p38MAPK signaling pathway.Methods Totally 28 male SPF-grade C57BL/6 mice were randomly divided into normal group,model group,electroacupuncture group and inhibitor group.The IBS visceral hypersensitivity model was induced by trinitrobenzene sulfonic acid enema.Four weeks post-modeling,electroacupuncture group and inhibitor group were given electroacupuncture at bilateral"Zusanli"and intraperitoneal injection of the TRPV1 receptor inhibitor respectively for consecutive 7 d.Abdominal withdrawal reflex(AWR)score was used to evaluate visceral pain in mice,HE staining was used to observe the morphology of colonic tissue,Western blot was used to detect the protein expressions of TRPV1,p-p38,tumor necrosis factor(TNF)-α and interleukin(IL)-6 in colonic tissue,ELISA was used to detect the Ras-GTP content in colonic tissue,and RT-qPCR was used to detect the mRNA expression of TRPV1 and p38 in colonic tissue.Results Compared with the normal group,AWR score under different pressure were significantly increased in the model group(P<0.05,P<0.01),the expression of TRPV1,p-p38,TNF-α and IL-6 protein in colonic tissue significantly increased(P<0.05,P<0.01,P<0.001),the content of Ras-GTP significantly increased(P<0.001),the expression of TRPV1 and p38 mRNA significantly increased(P<0.001).Compared with the model group,AWR score under different pressure were significantly decreased in electroacupuncture group and inhibitor group(P<0.05,P<0.01),the expression of TRPV1,p-p38,TNF-α and IL-6 protein in colonic tissue significantly decreased(P<0.05,P<0.01,P<0.001),the content of Ras-GTP significantly decreased(P<0.01,P<0.001),and the expressions of TRPV1 and p38 mRNA significantly decreased(P<0.05,P<0.01,P<0.001).There was no significant change in the morphology of colonic tissue in each group of mice.Conclusion Electroacupuncture can effectively alleviate visceral hypersensitivity in IBS mice,and its analgesic effect may be related to the inhibition of the TRPV1/Ras/p38MAPK signaling pathway in colonic tissue.

Background High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker for cardiovascular disease (CVD) and can independently predict the risk of cardiovascular events. Although the association between per- and polyfluoroalkyl substances (PFAS) exposure and CVD risk has been widely reported, studies on the association between hs-CRP and PFAS remain limited. Objective To investigate the association between PFAS and hs-CRP levels, to provide a scientific basis for early identification and prevention of environment-related cardiovascular events. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018). Based on predefined inclusion and exclusion criteria, a total of 3219 participants were included for subsequent analysis. Five PFAS with detection rates exceeding 90% were selected as exposure factors and log-transformed (lnPFAS) for subsequent analysis, including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA). After selecting potential confounders through a change-in-estimate approach, logistic regression was employed to examine the effects of individual PFAS on serum hs-CRP level. Additionally, quantile g-computation and Bayesian kernel machine regression (BKMR) were applied to assess the combined effects of PFAS mixtures on hs-CRP. Results The study included 3219 participants with a mean age of (50.4±17.6) years, of whom 1554 (48.28%) were male. The median concentrations of the five PFAS compounds were: 1.20 ng·mL⁻¹ (PFHxS), 0.50 ng·mL⁻¹ (PFNA), 1.50 ng·mL⁻¹ (PFOA), 5.20 ng·mL⁻¹ (PFOS), and 0.20 ng·mL⁻¹ (PFDA). The Wilcoxon rank-sum tests revealed statistically significant differences between the elevated serum hs-CRP (≥2 mg·L⁻¹) and normal (<2 mg·L⁻¹) groups for all five PFAS compounds (PFHxS: P=0.005; PFNA: P=0.009; PFOA: P<0.001; PFOS: P<0.001; PFDA: P<0.001). After adjusting for potential confounders, the analysis of individual PFAS exposure demonstrated significant negative associations between serum hs-CRP levels and both ln-PFOS (OR: 0.87; 95%CI: 0.79, 0.96; P=0.0036) and lnPFDA (OR: 0.78; 95%CI: 0.71, 0.86; P < 0.001). The joint effect analysis using quantile g-computation revealed an overall inverse association between PFAS mixtures and hs-CRP, with lnPFDA emerging as a primary contributor; an similar association was observed in males, but not significant in females. Further evaluation through BKMR showed that when PFAS mixture concentrations reached or exceeded P₇₀, their combined effect on hs-CRP became significantly lower than when all PFAS concentrations were at P₅₀, establishing a clear negative dose-response relationship. Conclusion The mixed exposure to PFAS showed a significant negative joint effect on serum hs-CRP levels, with PFDA being the key component contributing to this combined effect. Future prospective cohort studies are warranted to further validate these findings and elucidate the underlying mechanisms involved.

Objective To explore the mechanism of electroacupuncture in inhibiting peripheral sensitization of visceral pain in mice with irritable bowel syndrome(IBS)based on TRPV1/Ras/p38MAPK signaling pathway.Methods Totally 28 male SPF-grade C57BL/6 mice were randomly divided into normal group,model group,electroacupuncture group and inhibitor group.The IBS visceral hypersensitivity model was induced by trinitrobenzene sulfonic acid enema.Four weeks post-modeling,electroacupuncture group and inhibitor group were given electroacupuncture at bilateral"Zusanli"and intraperitoneal injection of the TRPV1 receptor inhibitor respectively for consecutive 7 d.Abdominal withdrawal reflex(AWR)score was used to evaluate visceral pain in mice,HE staining was used to observe the morphology of colonic tissue,Western blot was used to detect the protein expressions of TRPV1,p-p38,tumor necrosis factor(TNF)-α and interleukin(IL)-6 in colonic tissue,ELISA was used to detect the Ras-GTP content in colonic tissue,and RT-qPCR was used to detect the mRNA expression of TRPV1 and p38 in colonic tissue.Results Compared with the normal group,AWR score under different pressure were significantly increased in the model group(P<0.05,P<0.01),the expression of TRPV1,p-p38,TNF-α and IL-6 protein in colonic tissue significantly increased(P<0.05,P<0.01,P<0.001),the content of Ras-GTP significantly increased(P<0.001),the expression of TRPV1 and p38 mRNA significantly increased(P<0.001).Compared with the model group,AWR score under different pressure were significantly decreased in electroacupuncture group and inhibitor group(P<0.05,P<0.01),the expression of TRPV1,p-p38,TNF-α and IL-6 protein in colonic tissue significantly decreased(P<0.05,P<0.01,P<0.001),the content of Ras-GTP significantly decreased(P<0.01,P<0.001),and the expressions of TRPV1 and p38 mRNA significantly decreased(P<0.05,P<0.01,P<0.001).There was no significant change in the morphology of colonic tissue in each group of mice.Conclusion Electroacupuncture can effectively alleviate visceral hypersensitivity in IBS mice,and its analgesic effect may be related to the inhibition of the TRPV1/Ras/p38MAPK signaling pathway in colonic tissue.

Objective:It aims to explore the advantages,disadvantages,opportunities and challenges of Chinese medicine practitioners participating in the"three-division co-management"service model in diabetes management,analyze its performance in policy support,resource matching and patient satisfaction,and put forward optimization strategies to enhance the role of Chinese medicine practitioners in chronic disease management.Methods:Through literature analysis,questionnaire survey and semi-structured interview,the data of six pilot units of"three divisions co-management"in Jinjiang were collected,and the internal and external environment of Chinese medicine practitioners participating in the"three divisions co-management"model was systematically evaluated by the Strengths,Weaknesses,Opportunities,Threats(SWOT)and the Politics,Economic,Society,Technology(PEST).Results:Chinese medicine practitioners' participation in the"three-division co-management"model has obvious advantages in policy support,resource matching and patient satisfaction,but it also faces key obstacles such as lack of incentive mechanism,shortage of Chinese medicine practitioners' resources and limitation of medical insurance reimbursement.The survey shows that 99.7％of the respondents are willing to choose this mode again,and 96.43％of the respondents said that the medical experience has improved significantly.However,43.92％of the subjects think that the professional knowledge and skills of doctors need to be improved,and 32.2％of the subjects think that the effect of Chinese medicine treatment on reducing the dependence and side effects of western medicine is limited.Conclusion:It is feasible and practical for Chinese medicine practitioners to participate in the"three divisions co-management"model,but it is necessary to further improve its service effect and sustainability by improving the performance appraisal mechanism,expanding the scope of medical insurance reimbursement,and strengthening the training for Chinese medicine practitioners' resources.

Objective:It aims to explore the advantages,disadvantages,opportunities and challenges of Chinese medicine practitioners participating in the"three-division co-management"service model in diabetes management,analyze its performance in policy support,resource matching and patient satisfaction,and put forward optimization strategies to enhance the role of Chinese medicine practitioners in chronic disease management.Methods:Through literature analysis,questionnaire survey and semi-structured interview,the data of six pilot units of"three divisions co-management"in Jinjiang were collected,and the internal and external environment of Chinese medicine practitioners participating in the"three divisions co-management"model was systematically evaluated by the Strengths,Weaknesses,Opportunities,Threats(SWOT)and the Politics,Economic,Society,Technology(PEST).Results:Chinese medicine practitioners' participation in the"three-division co-management"model has obvious advantages in policy support,resource matching and patient satisfaction,but it also faces key obstacles such as lack of incentive mechanism,shortage of Chinese medicine practitioners' resources and limitation of medical insurance reimbursement.The survey shows that 99.7％of the respondents are willing to choose this mode again,and 96.43％of the respondents said that the medical experience has improved significantly.However,43.92％of the subjects think that the professional knowledge and skills of doctors need to be improved,and 32.2％of the subjects think that the effect of Chinese medicine treatment on reducing the dependence and side effects of western medicine is limited.Conclusion:It is feasible and practical for Chinese medicine practitioners to participate in the"three divisions co-management"model,but it is necessary to further improve its service effect and sustainability by improving the performance appraisal mechanism,expanding the scope of medical insurance reimbursement,and strengthening the training for Chinese medicine practitioners' resources.

To promote the primary Traditional Chinese Medicine(TCM)service capacity,promote the high development of TCM in County Medical Communities,it takes Jinjiang as the subject to explore the construction path of TCM service system in County Medical Communities based on"healthcare,medical insurance and medicine"linkage reform.A tertiary TCM service network of"city-town-village"is constructed through implementing"three projects"and"six enhancements".The mode significantly improved the service accessibility of TCM,and formed the innovation mechanism,including differentiation appraisal system and"pharmacy sharing online",etc.It explores the practical challenges of human resources weakness and insufficient information exchange,promotes the improvement strategies of enhancing talent group construction and promoting information platform,so as to provide practical references for contructing the TCM service system of County Medical Communities in China.

Objective To investigate the impact of chronic observational social defeat stress on multidimensional behaviors in female mice,including social interaction,emotion,and cognition,as well as the underlying molecular mechanisms.Methods Adult female C57BL6N mice were divided into a stress group and a control group.Behavioral assessment were conducted through social interaction tests,anxiety-like behavior tests,and cognitive tests(novel object recognition and spatial memory).Synaptic plasticity-related proteins in the hippocampus were detected using Western blot.Results Behavioral tests revealed that the stress group showed reduced social interaction time compared to the control group[(106.2±9.31)s vs.(156.5±14.81)s,P<0.05].In a novel environment,the stress group consumed less food than the control group[(0.10±0.01)g vs.(0.16±0.02)g,P<0.05].Cognitive tests demonstrated that the stress group exhibited impaired novel object recognition[(52.17%%±2.67%)vs.(65.91%±5.23%)]and spatial memory[(61.84%±3.14%)vs.(74.13%±1.94%)]compared to the control group(P<0.05).Western blot analysis showed that the expression of hippocampal synaptic plasticity-related proteins,including the glutamate ionotropic receptor N-methyl-D-aspartate(NMDA)receptor subunit NR2A[(0.66±0.05)vs.(0.89±0.08)]and brain-derived neurotrophic factor(BDNF)[(0.81±0.05)vs.(1.14±0.06)],was significantly decreased in the stress group(P<0.05).Conclusion Chronic observational social defeat stress induces social withdrawal,anxiety-like behaviors,and cognitive deficits in female mice.These effects may be associated with reduced expression of NR2A and BDNF in the hippocampus.

To promote the primary Traditional Chinese Medicine(TCM)service capacity,promote the high development of TCM in County Medical Communities,it takes Jinjiang as the subject to explore the construction path of TCM service system in County Medical Communities based on"healthcare,medical insurance and medicine"linkage reform.A tertiary TCM service network of"city-town-village"is constructed through implementing"three projects"and"six enhancements".The mode significantly improved the service accessibility of TCM,and formed the innovation mechanism,including differentiation appraisal system and"pharmacy sharing online",etc.It explores the practical challenges of human resources weakness and insufficient information exchange,promotes the improvement strategies of enhancing talent group construction and promoting information platform,so as to provide practical references for contructing the TCM service system of County Medical Communities in China.