To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

ObjectiveTo investigate the mechanism underlying the weight loss effect of electrothermal acupuncture （ETA） in diet-induced obese （DIO） model mice based on the hypoxia-inducible factor-1α （HIF-1α）/sphingosine-1-phosphate （S1P）sphingosine-1-phosphate receptor 3 （S1PR3） signaling pathway-mediated macrophage polarization. MethodsAn obesity mouse model was established by continuously feeding at a high-fat diet （HFD） for 8 weeks. Twenty successfully modeled obese mice were randomly divided into a model group and an electrothermal acupuncture （ETA） group with 10 mice per group， both of which continued to receive the HFD till week 12. Another 10 mice were assigned to the normal group and fed a standard chow diet continuously for 12 weeks. Starting from week 9 of the experiment， mice in the ETA group received electrothermal acupuncture stimulation at Zhongwan （CV12）， bilateral Tianshu （ST25）， and bilateral Zusanli （ST36） for 30 minutes per session， with the instrument current set at （40±0.5）mA and a constant temperature of （40±0.5）℃. Mice in the normal group and the model group were restrained in the same manner for 30 minutes without acupuncture. All interventions were performed once every other day for a total of 4 weeks. Ten hours after the final intervention， the body weight， waist circumference， and body length of mice in each group were measured， and Lee's index was calculated. Serum biochemical analysis was performed to assess fasting blood glucose （FBG）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （Cr）. Serum leptin （LEP） and adiponectin （ADPN） levels， as well as sphingosine-1-phosphate （S1P） levels in epididymal white adipose tissue （eWAT）， were detected by ELISA. Histomorphological changes in eWAT were monitored via HE staining. Flow cytometry was used to analyze macrophage subtype-related indexes in eWAT， including the total proportion of macrophages， the proportion of M1 macrophages， the proportion of M2 macrophages， and the M1/M2 ratio. Antibody array technology was used to determine the levels of differentially expressed inflammatory factors in eWAT between the model and blank groups， as well as between the ETA and model groups. Western blot and qPCR were used to detect the protein and mRNA expression levels of HIF-1α and S1PR3 in the eWAT， respectively. ResultsCompared to the normal group， the model group showed significantly increased body weight， Lee's index， waist circumference， and FBG， TC， TG， HDL-C， LDL-C， AST， and ALT levels， upgraded LEP and S1P levels， decreased ADPN level and ADPN/LEP ratio， elevated proportion of M1 macrophages and the M1/M2 ratio， reduced proportion of M2 macrophages， and upregulated protein and mRNA expression levels of HIF-1α and S1PR3 （P＜0.05 or P＜0.01）. With the exception of HDL-C， all the abovementioned indicators in the ETA group were significantly improved compared to the model group （P＜0.05 or P＜0.01）. Analysis of differentially expressed inflammatory cytokines revealed that， compared to the normal group， the levels of interleukin-1β （IL-1β）， interferon-γ （IFN-γ）， interleukin-6 （IL-6）， and interleukin-12p70 （IL-12p70） in the eWAT of the model group were elevated； conversely， the levels of interleukin-17 （IL-17）， interleukin-5 （IL-5）， IL-6， and interleukin-23 （IL-23） in the eWAT of the ETA group decreased compared to the model group （P＜0.05 or P＜0.01）. ConclusionETA exerts a weight-reducing effect in obese model mice， and the mechanism may involve inhibition of the HIF-1α/S1P/S1PR3 signaling pathway activation， which shifts macrophage polarization from the M1 to M2 phenotype， thereby alleviating chronic inflammation.

ObjectiveFrozen shoulder (FS) is a debilitating musculoskeletal disorder characterized by persistent inflammation and progressive fibrosis of the glenohumeral joint capsule, leading to pain and severely restricted range of motion. Given the limited efficacy of current pharmacotherapies, there is an urgent need for novel anti-fibrotic agents. Guyanxiao Tincture (GYX), a traditional Chinese herbal formula, has shown clinical benefits in alleviating FS symptoms. However, its bioactive constituents and the molecular mechanisms underlying its therapeutic effects remain poorly defined. This study aimed to systematically evaluate the therapeutic efficacy of GYX against FS and to elucidate the mechanisms by which GYX attenuates capsular fibrosis. MethodsA Sprague-Dawley (SD) rat model of FS was established by immobilizing the unilateral shoulder with a plaster cast for 21 d. Following model induction, animals were administered with GYX or its serum-identified bioactive component, icariside F2. The absorbed prototype compounds of GYX in FS rat serum were profiled using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Therapeutic effects were assessed by measuring shoulder range of motion (ROM), histopathological evaluation of the capsule via hematoxylin-eosin staining, and quantification of transforming growth factor‑β1 (TGF-β1) content by ELISA. To explore the underlying mechanisms, transcriptomic profiling of the shoulder capsule was performed using RNA sequencing, and differentially expressed genes were validated by real-time quantitative PCR. Protein expression and localization were examined through immunohistochemistry, immunofluorescence, and Western blot. Protein-protein interaction networks were constructed to identify key regulatory hubs. In vitro, primary shoulder capsule fibroblasts were stimulated with TGF‑β1 to induce a fibrotic phenotype and then treated with icariside F2. The expression of alpha cardiac muscle 1 (ACTC1), α‑smooth muscle actin, and collagen I was subsequently measured. ResultsSerum pharmacochemistry analysis identified icariside F2 as the predominant circulating bioactive component of GYX in FS rats. Both GYX and icariside F2 treatment significantly improved the ROM and ameliorated histopathological lesions, including the attenuation of synovial hyperplasia, inflammatory infiltration, and excessive collagen deposition in the shoulder capsule. Consistently, elevated TGF‑β1 levels in the model group were markedly reduced after the interventions. RNA sequencing revealed that actin ACTC1 was dramatically upregulated in the fibrotic capsule, accompanied by the enrichment of fibrosis-associated pathways such as TGF‑β signaling, focal adhesion, and ECM-receptor interaction. Protein-protein interaction network analysis demonstrated that ACTC1 directly interacts with core fibrotic genes, including Col1a1, Col1a2, Thbs2, and Fn1. Critically, icariside F2 administration significantly reversed the aberrant overexpression of ACTC1 and suppressed the activation of the aforementioned fibrosis-related pathways in vivo. In TGF‑β1-stimulated fibroblasts, icariside F2 dose-dependently downregulated ACTC1 at both the mRNA and protein levels and concurrently decreased the expression of the fibrotic markers α‑smooth muscle actin and collagen I. Immunofluorescence and Western blot further confirmed that icariside F2 attenuated stress fiber formation and collagen production in vitro. ConclusionGYX and its bioactive component icariside F2 effectively alleviate the progression of frozen shoulder by inhibiting capsular fibrosis. Mechanistically, the therapeutic action is functionally linked to the suppression of ACTC1 and its downstream profibrotic signaling cascade, highlighting ACTC1 as a promising therapeutic target for the management of frozen shoulder.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

In recent years,organs-on-chips(OOCs)technology has gradually matured and been recognized by regulatory agencies,playing a key role in the construction of pathophysiological models,pharmacodynamic screening,toxicological evaluation and other fields,providing guidance for the research and development of innovative drugs of Chinese materia medica and the clinical application of classic prescriptions.This article reviewed the application progress of OOCs technology in the research of Chinese materia medica from four dimensions:pharmacodynamic and toxicological evaluation,quality control,active component analysis and innovative drug research and development,in order to provide a reference for the precise application of this technology in the field of Chinese materia medica.

Objective:To explore the therapeutic effect of drug-coated balloon(DCB)combined drug-eluting stent(DES)on coronary bifurcation lesions.Methods:A total of 108 patients with coronary bifurcation lesions admitted in Shanghai Ninth People's Hospital Huangpu Branch,Shanghai Jiaotong University School of Medicine between February 2021 and March 2023 were enrolled in this randomized controlled study.Patients were randomly divided into combined treatment group(n=54,DCB was implanted in the sub-branch,and DES was implanted in the main branch)and DES group(n=54,DES were implanted in both main branch and sub-branch).Clinical therapeutic effect,coronary angiography quantitative parameters before,instant and 9 months after operation and clinical out-comes during 1-year follow-up after operation were compared between two groups.Results:The total effective rate of combined treatment group was significantly higher than that of DES group(96.30％vs.87.04％,P=0.030).Compared to those in DES group,instant and 9 months after operation,patients in the combined treatment group had significant higher diameters of main branch vessel[(3.13±0.31)mm vs.(3.01±0.25)mm,(2.99±0.33)mm vs.(2.84±0.23)mm],sub-branch vessel[(2.51±0.26)mm vs.(2.42±0.13)mm,(2.44±0.24)mm vs.(2.29±0.36)mm],and significant lower main branch stenosis rate[(6.05±0.21)％vs.(6.24±0.31)％,(9.06±0.23)％vs.(10.12±0.12)％]and sub-branch stenosis rate[(7.38±0.42)％vs.(7.63±0.18)％,(8.07±0.39)％vs.(11.25±0.22)％](P＜0.05 or＜0.01).There were no significant difference in incidence of target lesion revascularization,cardiogenic death and major adverse cardiovascular events between two groups(P＞0.05 all).Conclusion:Drug-eluting stent combined drug-coated balloon may promote vascular branch dilation of coro-nary artery lesions,increase the minimum lumen diameter of sub-branch vessels,and reduce the occurrence of ste-nosis in the treatment of coronary bifurcation lesion,which had similar effectiveness and safety with drug-eluting stent technique.

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.

A 52-year-old male patient with recurrent Hodgkin′s lymphoma was treated with a combination therapy of gemcitabine, oxaliplatin, and sintilimab for 6 cycles, and sintilimab monotherapy for 15 cycles. Because of disease progression, the therapy was switched to decitabine (10 mg intravenous infusion on day 1-5) and penpulimab (200 mg intravenous infusion on day 8), with 21 days as one cycle. On the 5th day after the last administration of the 10th cycle, the patient experienced discomfort such as headache and poor appetite; on the 7th day, he suddenly developed unconscious and faint. The patient had a body temperature of 38.1 ℃ and mild yellowish skin and mucous membranes throughout the body. Laboratory tests showed platelet count 9×10 9/L, red blood cell count 4.1×10 12/L, hemoglobin 113 g/L, prothrombin time 15.6 s, blood creatinine 101.6 μmol/L, total bilirubin 61.1 μmol/L, and creatine kinase isoenzyme 43 U/L. Based on laboratory and imaging examinations, immune checkpoint inhibitors causing acquired thrombotic thrombocytopenic purpura was considered. The patient underwent 3 times of plasma exchanges, and received intravenous infusion of methylprednisolone 80 mg once daily and other symptomatic treatments for 5 days. The patient′s yellowish skin and mucous membranes throughout the body disappeared. The glucocorticoid was decreased gradually. Two months later, the patient′s laboratory test indicators such as platelet count and total bilirubin returned to normal.

A 61-year-old female patient was treated with sintilimab (200 mg by intravenous infusion on the first day, 21 days as a cycle) for lung adenocarcinoma and multiple lymph node metastases in the left hilum and mediastinum (10 cycles in total). Headache and dizziness in the patient occurred about 1 month after the last medication. Cerebrospinal fluid examination showed white blood cell count 14×10 6/L, total protein 799.8 mg/L, Pandy′s test (+), immunoglobulin G 70.8 mg/L, and glucose and chloride within the reference value range. The antibodies against N-methyl-D-aspartate receptor in cerebrospinal fluid and serum were all positive. The patient was diagnosed as having sintilimab-induced autoimmune encephalitis. After receiving methylprednisolone sodium succinate by intravenous infusion for 7 days, the patient′s headache and dizziness were alleviated. After that, the methylprednisolone sodium succinate was switched to oral prednisone acetate tablets. At a 2-month follow-up, no symptoms of headache or dizziness recurred in the patient.

Purpose This study aims to investigate the clinicopathological features of diffuse pulmonary menin-gotheliomatosis(DPM).Methods The clinical data of 10 patients with DPM undergoing video-assisted thoracic sur-gery(VATS)were collected,and their clinical and pathological characteristics were analyzed using immunohistochem-istry.Results The detection rate of DPM was 1.19‰,with 90％of the patients being female.DPM predominantly occurred in the age range of 40-60 years,with an average age at diagnosis of 50.7 years.Most patients had no smok-ing history.Pathological diagnosis combined with imaging findings was the main method for diagnosing DPM.80％of the patients were prone to concurrent early-stage invasive pulmonary adenocarcinoma.Laboratory indicators,including pulmonary function,were generally normal.Chest CT showed diffuse multiple ground-glass opacity or cystic nodules in both lungs,with the number of nodules in both lungs ranging from dozens to hundreds,and the maximum diameter of the nodules was 2-6 mm.The median volume and CT value of the pulmonary nodules were 35.32 mm3 and-566 HU,respectively.Pathological features mainly included multiple meningothelial-like nodules observed under the micro-scope.Immunophenotypically,CD56,EMA,PR,and vimentin were often positive.Conclusion DPM is a rare lung disease with no obvious clinical symptoms,and is more common in middle-aged and elderly women.Diffuse multiple nodules in both lungs are its main imaging features.Most DPM patients are complicated with lung adenocarcinoma,and regular follow-up is recommended.