To summarize the clinical characteristics, antibody spectrum and neuroelectrophysiological features of autoimmune nodopathy(AN), and to explore the phenotypic differences among different antibody-positive subgroups.

ObjectiveTo analyze the composition of respiratory virus pathogen spectrum and epidemiological characteristics among adult influenza-like illness (ILI) cases in Putuo District of Shanghai from 2015 to 2024, to summarize the epidemic patterns of respiratory viruses across different time periods and populations, and to provide scientific evidence for the prevention and control of adult respiratory virus infections in Putuo District of Shanghai. MethodsSurveillance data of 2 273 adult ILI cases from sentinel hospitals under the comprehensive surveillance system for acute respiratory infections in Putuo District of Shanghai from 2015 to 2024 were retrospectively collected. Descriptive epidemiological methods were adopted to analyze the temporal and population distribution characteristics of respiratory viruses, including influenza virus (IFV), respiratory syncytial virus (RSV), adenovirus (ADV), and human metapneumovirus (HMPV). The mixed infection status among different age groups was compared, and the distribution of influenza virus subtypes was described. SPSS 22.0 and WPS Office software were used for statistical analyses. ResultsThe overall detection rate of respiratory viruses in 2 273 adult ILI cases was 43.51%. The detection rate in females (45.48%) was significantly higher than that in males (41.25%), with statistical significance (χ²=4.113, P=0.043). Individuals aged 60 years old and above had the highest detection rate (47.41%) (χ²=8.430, P=0.014). The detection rates in winter (50.41%) and summer (48.42%) were higher than those in other seasons (χ²=47.028, P<0.001). The overall viral detection rate decreased after 2020 (χ²=208.411, P<0.001). Detection rates of various viruses varied by year, with IFV and ADV showing high rates from 2015 to 2019 (all P<0.001), while human coronavirus (HCoV) and rhinovirus/enterovirus (HRV/EV) exhibited higher rates from 2020 to 2022 (all P<0.001). Co-infection with IFV and HCoV was the most common, followed by co-infection with IFV and ADV, together accounting for 50.00% of all mixed infections. During the surveillance period, the detection rate of IFV was significantly higher than that of other respiratory viruses. Influenza B/Victoria lineage predominated in 2021, followed by successive predominance of influenza A(H1N1), A(H3N2), and the co-circulation of the two subtypes from 2022 to 2023. Influenza A(H1N1) re-emerged as the predominant subtype in the first half of 2024. ConclusionFrom 2015 to 2024, respiratory virus infections in adults prevailed in winter and summer, and people aged 60 years old and above were the key high-risk population. The detection rates of respiratory viruses declined after 2020. IFV was the predominant pathogen detected, and different influenza virus subtypes circulated alternately each year.

OBJECTIVE To provide data support and theoretical reference for drug-regulatory authorities to implement targeted supervision over internet-based pharmaceutical sales.METHODS Using keywords such as “internet-based pharmaceutical sales” and “online drug sales”， the official websites of the People’s Government， drug-regulatory authorities and databases including PKULaw and others were searched， so as to collect typical cases and public disclosure information of administrative penalties related to internet-based pharmaceutical sales from January 2014 to June 2024. Guided by accident-causation theory， the text-mining method was adopted to identify risk factors from four dimensions： human unsafe behaviors， unsafe state of substances， environmental factors and safety management. Grey relational analysis was performed to quantitatively evaluate and screen key risk factors， and targeted governance suggestions were subsequently put forward.RESULTS A total of 617 administrative penalty cases were included. The number of cases increased significantly since 2018. The regional distribution of cases presented a characteristic of “high in the east and low in the west”. Violations were mainly concentrated in the business qualification examination link， and online pharmaceutical retail enterprises were the dominant law-breaking subjects. A risk identification system for internet-based pharmaceutical sales was constructed， covering 4 primary-level， 17 secondary-level and 56 tertiary-level risk factors. Through grey relational analysis， 37 key tertiary-level risk factors （most of which belonged to the safety-management dimension） including inadequate bill management and illegal drug-advertising content， as well as 12 key secondary-level risk factors such as drug-advertising violations and non-standard drug storage， were screened out.CONCLUSIONS Inadequate capabilities and weak compliance awareness of practitioners， illegal drug advertising， non-standard drug storage and transportation， and imperfect quality-management systems of online-drug-sales enterprises and third-party platforms are prominent safety risk factors for internet-based pharmaceutical sales. It is recommended to strengthen qualification examination and competency training for practitioners， standardize drug-information display and drug advertising， improve the management system of drug warehousing and logistics， and refine institutional requirements for key links， so as to improve the supervision efficiency of internet-based pharmaceutical sales.

Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

Objective To investigate the effect of inhibiting stearoyl-CoA desaturase 1(SCD1)activity on the biological behavior of cervical cancer cells and elucidate the molecular mechanisms related to fatty acid metabolism.Methods Cancer tissues were collected from 48 patients with cervical cancer,whereas normal cervical tissues were obtained from 48 patients with uterine fibroids.Immunohisto-chemical SP staining and real-time quantitative PCR were performed to assess differences in SCD1 expression.The MTS assay was used to determine cell viability,and EdU staining was conducted to evaluate cell proliferation.Cell migration and invasion abilities were analyzed using in vitro scratch assay and Transwell chamber assay.Immunofluorescence staining was performed to detect E-cadherin and vimentin expression.Real-time quantitative PCR was used to measure the mRNA expression levels of SREBP1,ACLY,ACC,and FAS.Nile red fluorescence staining was applied to observe intracellular lipid droplet content.Results The positive expression rate of SCD1 and the relative expression level of SCD1 mRNA were significantly higher in cervical cancer tissues than in normal cervical tissues(P＜0.05).Treatment of HeLa cells with varying concentrations of MF-438 led to significant reductions in cell viability,EdU-positive cell rate,scratch closure rate,and the number of migrating and invading cells.Additionally,the fluorescence intensity of E-cadherin increased,whereas that of vimentin decreased.The relative expression levels of SREBP1,A CL Y,ACC,and FAS mRNA were downregulated,and intracellular lipid droplet content decreased in a concentration-dependent manner(P＜0.05).Conclusion Inhibition of SCD1 activity significantly reduced lipid metabolism in HeLa cells and suppressed malignant biological behaviors,including proliferation,migration,invasion,and epithelial-mesenchymal transition.

Objective:To investigate the effects of curcumin,berberine,and puerarin combination therapy on lipid levels in hyperlipidemic mice.Methods:A total of 40 male C57BL/6J mice were randomly divided into eight groups:normal control group(A),high-fat control group(B),curcumin group(C),berberine group(D),puerarin group(E),low-dose combination group of curcumin,berberine,and puerarin(F),high-dose combination group of curcumin,berberine,and puerarin(G),and positive control group(H),with 5 mice in each group.The normal control group was fed a standard diet,while the other groups were given a high-fat diet.After establishing the hyperlipidemic model,the mice were administered with physiological saline,curcumin(200 mg/kg),berberine(200 mg/kg),puerarin(300 mg/kg),low-dose combination of curcumin(50 mg/kg),berberine(50 mg/kg),and puerarin(100 mg/kg),high-dose combination of curcumin(200 mg/kg),berberine(200 mg/kg),and puerarin(300 mg/kg),or simvastatin(6 mg/kg)via gavage for three weeks.After treatment,serum was collected from the mice for biochemical analysis of lipid levels and liver function.Liver tissues were subjected to HE staining,Western blot analysis and real-time quantitative PCR.Results:Curcumin,berberine,and puerarin,whether administered individually or in combination,can reduce the body weight of hyperlipidemic mice(P＜0.01).Treatment with curcumin,berberine,and puerarin individually significantly reduced lipid levels in hyperlipidemic mice(P＜0.05)and alleviated liver damage caused by hyperlipidemia(P＜0.05).Furthermore,the high-dose combination of curcumin,berberine,and puerarin exhibited a more pronounced effect on improving lipid levels(P＜0.01)and provided greater protective effects on the liver compared to the positive control group(P＜0.05).Additionally,curcumin,berberine,and puerarin administered individually can each promote the expression of the LDLR gene in high-fat diet mice(increased by 90％,85％,and 98％,respectively)and reduce the expression of the ACC gene(decreased by 42％,45％,and 43％,respectively).The combination of all three compounds enhances the expression of the LDLR gene in high-fat diet mice(increased by 90％with low-dose combination and 169％with high-dose combination)and reduces the expression of the ACC gene(decreased by 38％with low-dose combination and 42％with high-dose combination).Conclusion:The combination of curcumin,berberine,and puerarin significantly improves lipid levels in hyperlipidemic mice and mitigates liver damage associated with hyperlipidemia.

Objective To explore the anti-intestinal fibrosis mechanism of Dahuang Zhechong pill.Methods Based on the network pharmacology method,the traditional Chinese medicine systems pharmacology database and analysis platform,SwissTargetPrediction database and metabolomics technology was used.OmicsNet 2.0 platform combined with the findings of network pharmacology and metabolomics,and molecular simulation docking and molecular biology methods were used to study the mechanism of anti-intestinal fibrosis of Dahuang Zhechong pill.Results Dahuang Zhechong pill contains 142 potential active ingredients and 855 anti-intestinal fibrosis targets.The 10 core ingredients(quercetin,acacetin,oroxylin a,kaempferol,moslosooflavone,panicolin,etc.)may play a role in regulating lipid metabolism and atherosclerosis,EGFR tyrosine kinase inhibitor resistance,HIF-1 signaling pathway,TNF signaling pathway and IL-17 signaling pathway.Metabolomics results showed that 59 endogenous substances(oxaloacetic acid,ethylthioisonicamide,6-benzylaminopurine,tyrosine and cortisol,etc.)may be the key metabolites of this drug against intestinal fibrosis.Central carbon metabolism,TCA cycle and amino acid metabolism were the key mechanisms,EGFR,AKT1,MAPK1,PTPN11,CASP3,PPARG,MET and PDGFRB may be the core targets.Dahuang Zhechong pill could significantly improve the levels of colorectal edema,inflammatory factors,inflammatory cell infiltration,collagen fiber deposition and α-SMA expression in mice with intestinal fibrosis,reduce the expression levels of pro-inflammatory factors IL-17 and IL-23 in serum,and increase the level of anti-inflammatory factor IL-10.Molecular dynamics simulations demonstrated stable conformational binding between core active ingredients and key targets.Conclusion Dahuang Zhechong pill may regulate EGFR/AKT1/MAPK mediated metabolism-inflammation interaction network through flavonoid components,and can improve intestinal fibrosis in multiple dimensions through molecular validation.

Objective:To investigate the accuracy and clinical utility of a newly designed acetabular bone defect classification system based on the ischial-gluteal pillar in assessing the severity of acetabular bone defects and guiding hip revision surgery.Methods:A retrospective analysis was conducted on 474 patients who underwent hip revision surgery for prosthetic loosening after total hip arthroplasty at our institution from January 2010 to December 2020, including 296 males and 178 females with a mean age of 70.4±8.9 years (range: 52-86 years). The accuracy of our classification system in guiding surgical procedures was evaluated by comparing preoperative defect classifications with intraoperative findings. Clinical outcomes were evaluated using preoperative and final follow-up Harris hip scores (HHS) and Oxford hip scores (OHS), as well as the incidence of complications.Results:Preoperative classifications included 143 Type I, 192 Type II (Type IIa: 86 cases, Type IIb: 59 cases, Type IIc: 47 cases), 93 Type III (Type IIIa: 54 cases, Type IIIb: 27 cases, Type IIIc: 12 cases), and 46 Type IV cases (Type IVa: 32 cases, Type IVb: 9 cases, Type IVc: 5 cases). Compared with intraoperative findings, classification accuracy was 99.3% for Type I (1 errors), 98.4% for Type II (3 errors), 97.8% for Type III (2 errors), and 97.8% for Type IV (1 misclassified as Type III). The mean follow-up was 5.8±4.4 years (range: 2-12 years). At final follow-up, mean HHS improved from 36.65±10.27 to 91.36±7.53, and mean OHS increased from 11.35±4.36 to 44.6±5.27 with significant difference ( P<0.001). Complications included one Type IV periprosthetic infection, one Type II hip dislocation, one Type I and two Type IV re-revisions (due to femoral loosening or graft resorption), one Type II and one Type III death unrelated to surgery, and one Type I postoperative thigh hematoma. No neurovascular injuries occurred. Conclusions:This novel 3D acetabular bone defect classification system, based on ischial-gluteal pillar integrity, provides accurate preoperative assessment and effectively guides surgical planning. Its application demonstrates favorable mid-term outcomes in hip revision surgery.

Objective:To construct a job competence evaluation index system for venous thromboembolism (VTE) control liaison nurses.Methods:Based on the "Iceberg Theory Model" of job competence, a preliminary version of the job competence evaluation index system for VTE control liaison nurses was developed from August to September 2023 through a literature review and qualitative interviews. Using the convenience sampling method, 18 experts were selected for two rounds of expert correspondence from October to December 2023, and the final evaluation index system was determined based on the correspondence.Results:In the two rounds of expert correspondence, the effective recovery rates of the questionnaires were 100.00% (18/18) and 88.89% (16/18), respectively, the expert authority coefficients were 0.97 and 0.97, and the Kendall's harmony coefficients were 0.15 and 0.24, respectively (all P<0.01). The job competence evaluation index system for VTE control liaison nurses contained six primary indicators, 18 secondary indicators, and 55 tertiary indicators. Conclusions:The job competence evaluation index system for VTE control liaison nurses constructed in this study is set up scientifically and reasonably, and the evaluation content is comprehensive and practical, which can provide reference for the training and assessment of hospital VTE control liaison nurses.

Objective:To observe the clinical effect of Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type polycystic ovary syndrome(PCOS)accompanied by insulin resistance.Methods:80 patients with PCOS accompanied by insulin resistance who were admitted to our hospital from June 2023 to June 2024 were included.The patients were divided into control group(treated with ethinylestradiol and cyproterone acetate,metformin)and study group(treated with modified Cangfu Daotan Decoction combine with ethinylestradiol and cyproterone acetate,metformin)by the random number table method,with 40 cases in each group.The total clinical effective rate,TCM syndrome score,sex hormone levels[prolactin(PRL),estradiol(E2),follicle-stimulating hormone(FSH),testosterone(T),and luteinizing hormone(LH)],insulin resistance indicators[fasting insulin(FINS),fasting blood glucose(FBG),homeostatic model assessment of insulin resistance(HOMA-IR)],and endometrial receptivity[pulsatile index(PI),resistance index(RI),endometrial thickness(ET),ovulation rate]and the occurrence of adverse reactions were compared between the two groups.Results:Compared with the control group after treatment,the total clinical effective rate,PRL,E2,FSH level,ET and the ovulation ratein the study group were higher,while the main symptoms,secondary symptoms,total score,T,LH levels,FBG,FINS levels,HOMA-IR,PI and RI were lower(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type PCOS accompanied by insulin resistance,can improve the clinical symptoms,increase the total clinical effective rate,it may be related to the regulation of insulin resistance,sex hormone levels,and endometrial receptivity,it is safe and reliable.