Objective: To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.

ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences. An effective way to obtain a single enantiomer is through racemates resolution. Recent literature shows that chiral metal-organic frameworks (CMOFs) have many applications in various fields because of their diverse topologies and functionalities. This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs. It highlights key advances and issues in the separation domain. In conclusion, the review provides perspectives on the challenges and prospective advancements of CMOFs materials and CMOFs-based separation technologies.

To investigate the effect of isthmin-1 (ISM1) on the invasion and metastasis of pancreatic cancer and its underlying mechanism, this study analyzed the expression of ISM1 in pancreatic cancer patients and normal pancreatic tissues using The Cancer Genome Atlas (TCGA) database. Western blot was employed to detect differences in ISM1 protein expression between pancreatic cancer cell lines (Aspc1, Bxpc3, PANC1, SW1990) and the pancreatic epithelial cell line (hPNE). Cell models with stable ISM1 overexpression and knockdown were constructed, and changes in cell migration and invasion capabilities were assessed via Transwell invasion assays and wound healing assays. Meanwhile, Western blot was used to detect the expression levels of key markers of epithelial-mesenchymal transition (EMT). Furthermore, TCGA and the Gene Expression Omnibus (GEO) database were utilized to analyze pathways regulated downstream of ISM1 and the mechanisms promoting pancreatic cancer invasion and metastasis. Immunoprecipitation combined with mass spectrometry (IP-MS) was used to screen for vimentin as an ISM1-binding protein, and the interaction between ISM1 and vimentin was verified by immunofluorescence and co-immunoprecipitation (Co-IP). Bxpc3 cells overexpressing ISM1 were treated with the protein synthesis inhibitor cycloheximide (CHX) to detect vimentin protein stability. The results indicate that ISM1 promotes the EMT process by inhibiting vimentin degradation, thereby enhancing the invasion and metastasis of pancreatic cancer. This study provides new experimental evidence for elucidating the mechanism of pancreatic cancer metastasis.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Vascular cognitive impairment (VCI) denotes a wide range of cognitive deficiencies resulting from cerebrovascular risk factors and cerebrovascular diseases. Sirtuin 1 (SIRT1), as a deacetylase, can mediate the deacetylation of histones and non-histone proteins. It is involved in regulating multiple pathophysiological processes of VCI, including neuroinflammation reduction, oxidative stress inhibition, cell apoptosis decrease, and blood-brain barrier protection, serving as a target for VCI treatment. This paper summarizes SIRT1 and the molecular mechanisms of targeting SIRT1 in order to provide a reference for the clinical treatment of VCI.

Objective To investigate the association of sleep disorders with the development and progression of nonalcoholic fatty liver disease(NAFLD).Methods A total of 1 868 participants from the health examination cohort and fatty liver cohort of Beijing Friendship Hospital from June 2022 to June 2023 were enrolled as subjects.Related data were collected from all subjects,including age,sex,education level,chronic medical history,and biochemical parameters,and all subjects completed Pittsburgh Sleep Quality Index(PSQI)scale independently.According to the diagnostic criteria,the subjects were divided into non-NAFLD group with 1 122 subjects and NAFLD group with 746 subjects,and according to the stage of progression,the patients in the NAFLD group were further divided into simple fatty liver group(SFL group with 624 subjects)and nonalcoholic steatohepatitis(NASH)group with 122 subjects.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between three groups.The chi-square test was used for comparison of categorical data between the three groups.The binary Logistic regression analysis was used to investigate the association between sleep factors and NAFLD,and the multinomial Logistic regression analysis was used to investigate the association between sleep factors and the different stages of NAFLD;two multivariate models were constructed for adjustment of potential confounding factors,i.e.,an age-sex adjustment model and a multivariate adjustment model,and the multivariate adjustment model adjusted the factors of age,sex,education level,smoking,diabetes,hypertension,body mass index(BMI),triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C).Results There were significant differences in age,sex,BMI,education level,smoking,diabetes,hypertension,alanine aminotransferase,TG,and HDL-C between the non-NAFLD,SFL,and NASH groups(all P<0.05).There were also significant differences between the three groups in the total score of PSQI scale and the proportion of subjects with a score of 0—3 points for the 7 sleep components(all P<0.05).The multivariate adjustment model showed no significant association between sleep disorders and SFL,while long sleep latency(odds ratio[OR]=4.04,95%confidence interval[CI]:2.33—7.03,P<0.001),short sleep duration(OR=3.53,95%CI:1.83—6.82,P<0.001),and severe sleep disorders(OR=2.96,95%CI:1.48—5.93,P=0.002)were closely associated with the risk of NASH.Conclusion Overall sleep condition and its components of sleep disorders are not significantly associated with the simple fatty liver;however,long sleep latency,short sleep duration,and severe sleep disorders can increase the risk of NASH,which should be taken seriously in clinical practice.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.