19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

OBJECTIVE: To review the application and progress of unilateral biportal endoscopy (UBE) technology in the treatment of cervical degenerative diseases, and to provide reference for clinical treatment decisions. METHODS: The literature related to UBE technology in the treatment of cervical spondylotic radiculopathy (CSR) and cervical spondylotic myelopathy (CSM) at home and abroad was extensively reviewed, and the surgical methods, indications, effectiveness, and safety were analyzed and summarized. RESULTS: UBE technology is effective in the treatment of CSR and CSM, and has the advantages of good surgical field, reducing the injury of the posterior structure of the cervical spine, and protecting the facet joint process, but in general, the indications are relatively narrow, limited to single-segment or adjacent double-segment lesions, and the requirements for the operator are relatively high, and the learning curve is long. CONCLUSION UBE technology can be applied to the treatment of CSR and CSM, but it needs to be carried out by experienced UBE surgeons for specific cases.
Humans ; Cervical Vertebrae/surgery* ; Endoscopy/methods* ; Radiculopathy/surgery* ; Spondylosis/surgery* ; Decompression, Surgical/methods* ; Spinal Cord Diseases/surgery* ; Treatment Outcome

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

Purpose To investigate the clinical significance of Gasdermin B(GSDMB)in ovarian cancer and its relationship with immune infiltration,aiming to explore novel biomarkers for immunotherapy.Methods Gene expres-sion matrix,somatic mutations,somatic copy number alterations(SCNA),and clinical data were obtained from the The Cancer Genome Atlas(TCGA)database.Copy number variation(CNV)analysis was performed using the GISTIC algorithm,and the CIBERSORT algorithm was applied to quantify the relative abundance of 22 immune cell types in the tumor microenvironment.Protein-protein interaction(PPI)network analysis was conducted to identify GSDMB-associ-ated interacting proteins.Additionally,multiplex immunofluorescence was used to verify the spatial distribution differ-ences of GSDMB protein in clinical ovarian cancer samples with different immune phenotypes and its interaction with immune cells.Results The expression level of the GSDMB gene was significantly higher in adjacent non-cancerous tissues than in tumor tissues(P＜0.001).Patients with high GSDMB expression exhibited elevated levels of immune chemokines(such as CXCL9 and CXCL10,P＜0.01)and tumor-killing lymphocytes(the proportion of CD8+T cell was significantly higher in the high-expression group than in the low-expression group,P＜0.001).CNV analysis re-vealed that GSDMB copy number alterations significantly influenced immune cell infiltration:patients with GSDMB cop-y number amplification had decreased infiltration levels of CD4+T cells and dendritic cells(P＜0.05),while those with deep deletion of GSDMB had significantly reduced infiltration levels of CD8+T cells and neutrophils(P＜0.01).PPI network analysis indicated that GSDMB might interact with key immune molecules,including IL-37,IL-18BP,IL-33,and IL-2(Pearson correlation coefficient r＞0.6,P＜0.001).Multiplex immunofluorescence analysis demonstra-ted that tumors with high GSDMB expression were more likely to exhibit an immune-inflamed phenotype(52.6％),while tumors in the low-expression group were predominantly immune-desert type(47.3％).Immunotherapy cohort a-nalysis suggested that GSDMB could serve as a potential predictive biomarker for immunotherapy responsiveness,with high predictive efficacy in multiple immune checkpoint inhibitor therapy cohorts targeting PD-1,PD-L1,and CTLA4(AUC＞0.8).Conclusion GSDMB plays a crucial role in reshaping the tumor microenvironment in ovarian cancer and may serve as a novel sensitizing target for immunotherapy.

Objective To investigate the relationship between serum levels of micro RNA(miR)-497-5p,fibroblast growth factor-2(FGF2)and brain-derived neurotrophic factor(BDNF),with cognitive dysfunction in Parkinson's disease(PD)patients.Methods From April 2022 to April 2024,86 PD patients(study group)treated in Wuhan Xinzhou District People's Hospital and 60 healthy individuals(control group)who underwent physical examination in Wuhan Xinzhou District People's Hospital were selected.Serum miR-497-5p levels were determined by real-time quantitative polymerase chain reaction(RT-qPCR),and serum FGF2 and BDNF levels were measured by enzyme linked immunosorbent assay(ELISA).Spearman was applied to analyze the correlation between serum miR-497-5p,FGF2,BDNF levels and montreal cognitive assessment(MoCA score).Logistic analysis was applied to analyze the factors influencing cognitive dysfunction in PD patients.Receiver operating characteristic(ROC)was applied to analyze the diagnostic value of serum miR-497-5p,FGF2 and BDNF for cognitive dysfunction in PD patients.Results The serum miR-497-5p(2.73±0.67)expression level in the study group was obviously increased than that in the control group(1.04±0.34),while the expression levels of FGF2(1.94±0.45ng/ml)and BDNF(8.31±2.44ng/ml)were obviously reduced than those in the control group(2.71±0.69ng/ml,12.81±3.07ng/ml),with significate differences(t=17.977,8.161,9.850,all P<0.05).Serum miR-497-5p was negatively correlated with MoCA score(r=-0.331,P<0.05),while FGF2 and BDNF levels were positively correlated with MoCA score(r=0.404,0.361,all P<0.05).Cognitive dysfunction group had significantly higher disease duration,FGF2,BDNF levels,and MoCA scores than the cognitively normal group.The course of disease and miR-497-5p levels in the cognitive dysfunction group were obviously higher than that in the normal cognitive function group,FGF2,BDNF levels,and MoCA scores in the cognitive dysfunction group were obviously lower than that in the normal cognitive function group(t=2.350～11.792,all P<0.05).The course of disease and serum miR-497-5p were risk factors for cognitive dysfunction in PD patients(Wald χ2=4.712,5.704,all P<0.05),while MoCA score,serum FGF2,and BDNF were protective factors for cognitive dysfunction in PD patients(Wald χ2=4.499,5.556,5.217,all P<0.05).The AUC and sensitivity of the combination of serum miR-497-5p,FGF2,and BDNF in PD patients with cognitive impairment were higher than those of individual diagnosis.The diagnostic effect of the combination of miR-497-5p,FGF2,and BDNF in PD patients with cognitive dysfunction was better than that of individual diagnosis,and the differences were statistically significant(Z=2.279,2.236,2.123,all P<0.05).Conclusion Elevated serum miR-497-5p level and decreased FGF2 and BDNF levels can increase the risk of cognitive dysfunction in PD patients,and the combination of the three has good diagnostic value for cognitive dysfunction in PD patients.

Objective:To investigate the diagnostic value of gastroenteroscopic narrow band imaging(NBI)combine with serum amyloid A(SAA),C-reactive protein(CRP),D-Dimer(D-D)in children with abdominal henoch schonlein purpura(HSP).Methods:90 children with HSP who were admitted to our hospital from September 2022 to September 2024 were prospectively selected as the research objects,of which 50 children with abdominal HSP were included in the observation group and 40 children with other types of HSP were included in the control group.All children underwent gastroenteroscopic NBI examination and serum CRP,SAA and D-D levels were detected,and serum CRP,SAA and D-D levels were compared between the two groups,and the results of gastroenteroscopic NBI examination were analyzed in the two groups.Then the receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of gastroenteroscopic NBI and serum CRP,SAA,D-D alone or in combination in children with abdominal HSP.Results:Serum CRP,SAA and D-D levels in the observation group were significantly higher than those in the control group(P＜0.05);The results of gastroenteroscopic NBI showed that most of the children with abdominal HSP had some degree of changes in the gastric and duodenal mucosa,with mucosal congestion,edema,erosion,ulceration,and scattered bright or dark red bleeding spots as the main manifestations.Under gastroenteroscopic NBI,41 of 50 children with abdominal HSP were diagnosed as abdominal HSP,and 11 of 40 children with other types of HSP were diagnosed as abdominal HSP;the area under curve(AUC)of serum CRP,SAA,and D-D in the diagnosis of children with abdominal HSP were 0.668,0.720 and 0.771,respectively,and the AUC of the combination diagnosis of serum CRP,SAA and D-D in the diagnosis of children with abdominal HSP was 0.815;The AUC of the diagnosis of gastroenteroscopic NBI and serum CRP,SAA and D-D in children with abdominal HSP was 0.801 and 0.815,respectively,and the AUC of the combination diagnosis of gastroenteroscopic NBI in children with abdominal HSP was 0.867.Conclusion:Serum CRP,SAA and D-D in children with abdominal HSP were significantly increased,and the main manifestations under gastroenteroscopic NBI were mucosal congestion,edema,erosion,ulceration and scattered bright or dark red bleeding spots as the main manifestations.Gastroenteroscopic NBI combine with serum CRP,SAA and D-D could significantly improve the diagnostic efficiency of children with abdominal HSP.

Objective·To explore the efficacy of the XP-Endo Shaper(XPS)and Reciproc(RC)engine-driven nickel-titanium file systems in removing root canal fillings,and to provide evidence for clinical application.Methods·The maxillary first permanent molars were obtained from patients who visited the Department of General Dentistry,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,between March and September 2022,which required tooth extraction due to periodontal disease.A total of 30 mesiobuccal or distobuccal root canals with moderate curvature were selected and randomly divided into the RC file group(control group,n=15)and the XPS file group(experimental group,n=15).All root canals were first negotiated and shaped using M3-PRO nickel-titanium files,followed by root canal obturation with bioceramic paste using the single-cone technique.Then,RC files(R25)were used in the control group,while XPS files were used in the experimental group to remove the root canal obturation.Cone Beam Computed Tomography(CBCT)scans were performed before and after the removal procedures.The time required for obturation removal,the percentage of residual obturation volume,the amount of apical debris extrusion,and the degree of instrument deformation were recorded.Independent-sample t-tests and chi-square test were used to compare the differences between the two groups.Results·The XPS group required slightly more time(118.87±18.58)s than the RC group(107.93±14.79)s,but the difference between two groups was not statistically significant.The XPS group had a lower percentage of residual obturation volume(7.51±8.06)%compared to the RC group(15.02±14.63)%,but the difference was not statistically significant.The XPS group had significantly less apical debris extrusion(6.15±1.42)mg than the RC group(8.29±2.01)mg,with a statistically significant difference(P=0.002).Both groups exhibited varying degrees of instrument deformation,but yet no instrument separation occurred in either group.Conclusion·The RC engine-driven nickel-titanium files were slightly more time-efficient in removing root canal fillings,whereas the XPS files achieved a higher canal cleanliness and produced less apical debris extrusion.As there was no significant difference in removal time,and considering the superior cleaning performance and reduced risk of postoperative complications,the XPS file system appears more suitable for removing root canal fillings in moderately curved root canals.

Objective To construct a prognostic model for patients with in-hospital cardiac arrest(CA)to evaluate their short-term and long-term prognosis and provide a reference for clinical decision-making.Methods Data of in-hospital CA patients were extracted from the Medical Information Mart for Intensive Care Ⅳ 2.2 database,and randomly divided into training set and validation set at a 7∶3 ratio.A predictive nomogram model was constructed in the training set via multivariate COX regression analysis,and internally validated using the validation set.Results A total of 1787 patients were included(1250 in training set and 537 in validation set).Univariate regression,LASSO regression,and multivariate COX regression analyses identified age,body weight,base excess,red cell volume distribution width,model for end-stage liver disease,acute physiology and chronic health evaluation,systemic inflammatory response index,dopamine,norepinephrine,congestive heart failure,diabetes with complications,and metastatic solid tumor were all independent risk factors affecting the prognosis of patients with CA.The receiver operating characteristic curve of the constructed nomogram showed good discrimination,and the decision curve analysis indicated that it had good clinical applicability.Conclusion The constructed nomogram model has certain clinical application value in identifying populations with good and poor prognosis,providing an auxiliary reference for the termination of resuscitation and post-resuscitation treatment.

Objective:To investigate the inhibitory effect of tripartite motif-containing 25 (TRIM25) on the replication of Japanese encephalitis virus (JEV) in cells and its molecular mechanism.Methods:Human glioma cells (U251 cells) and Kunming mice were infected with JEV, and then the cells and brain tissue samples were collected. The transcription levels of six TRIM genes were detected by real-time PCR, and the expression of TRIM25 in cells was detected by Western blot. U251 and A549 cells overexpressed with TRIM25 and U251 cells knocked out with TRIM25 gene were constructed. Cells were infected with JEV, and the replication of JEV was detected by viral plaque assay, real-time PCR and Western blot. The interaction of TRIM25 with viral proteins was investigated by co-immunoprecipitation (Co-IP) and indirect immunofluorescence assay. The expression of IFN-β in overexpressed TRIM25 cells was detected by real-time PCR and ELISA.Results:JEV infection promoted the expression of TRIM25 in cells and mouse brain tissues. TRIM25 overexpression restricted JEV replication in U251 and A549 cells, while TRIM25 knockout enhanced JEV replication. TRIM25 overexpression upregulated the level of IFN-β in cells. TRIM25 interacted with JEV capsid protein and promoted the degradation of capsid protein.Conclusion:TRIM25 can inhibit the replication of JEV in cells by upregulating IFN-β and promoting the degradation of JEV C protein.