ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

ObjectiveTo compare the effect of diaphragmatic and abdominal breathing training on the morphology and function of deep trunk muscles in patients with chronic nonspecific low back pain. MethodsFrom March to May, 2025, a total of 37 patients with chronic nonspecific low back pain recruited at Xi 'an Physical Education University, were randomly divided into control group (n = 12), abdominal breathing group (n = 12) and diaphragmatic breathing group (n = 13). All groups received transcutaneous electrical nerve stimulation and core stability training. On this basis, the abdominal breathing group was added with abdominal breathing training, and the diaphragmatic breathing group was added with diaphragmatic breathing training, for six weeks. The degree of pain was evaluated with Visual Analogue Scale (VAS) before and after intervention, while the activation levels of multifidus and transversus abdominis were evaluated with the root mean square value (RMS) of surface electromyography, and the thickness of the multifidus muscle, transverse abdominis muscle, diaphragm and diaphragm mobility were evaluated with musculoskeletal ultrasound. ResultsAfter intervention, all the indicators improved in all the groups (P < 0.001), except for the diaphragm thickness and mobility in the control group. All the effects (F > 4.634, P < 0.016) of VAS score were significant, and were better in the diaphragmatic/abdominal breathing groups than in the control group (P < 0.01). The intra-group effects (F > 64.869, P < 0.001) and interaction effects (F > 12.379, P < 0.001) of muscle morphology and function indexes were significant, and the RMS of multifidus and transversus abdominis, left multifidus thickness, bilateral transversus abdominis thickness, diaphragm thickness, and diaphragm excursion was better in the diaphragmatic breathing group than in the control group and the abdominal breathing group (P < 0.001), while bilateral transversus abdominis RMS, diaphragm excursion, and right multifidus thickness were better in the abdominal breathing group than in the control group (P < 0.037). ConclusionThe combination of diaphragmatic/abdominal breathing exercises can further improve the morphology and function of the deep muscles of trunk in patients with chronic nonspecific low back pain, and diaphragmatic breathing may be superior to abdominal breathing.

Objective To measure the urethral meatus circumference in middle-aged and elderly males to undergo surgery for benign prostatic hyperplasia (BPH), and to collect data for developing endoscopic equipment suitable for the male urethra in China. Methods Clinical data were collected from patients (aged ≥50 years) who underwent transurethral resection of prostate in the First Affiliated Hospital of Xi'an Jiaotong University during Jan. and Dec. 2024. All patients had the urethral meatus circumference measured with a metal urethral probe before surgery, followed by the use of a F26.5 endoscopic sheath for surgery. The passage of urethral meatus using different types of metal urethral probes were observed. Results For the 183 patients, the types of endoscopic sheath smoothly passing through the urethral meatus were distributed as follows:42 cases (22.95%) with F26 or above, 66 cases (36.07%) with F25-26, 27 cases (14.75%) with F23-24, 26 cases (14.21%) with F21-22, 22 cases (12.02%) with F20 or below, and the smallest was F17 (1 case). Of all patients, 59.02% (108/183) were able to insert the F26.5 endoscopic sheath smoothly into the urethral meatus (≥F25), 28.96% (53/183) required force or urethral dilation before inserting (F21-F24), and 12.02% (22/183) needed to open the urethral meatus before inserting the endoscopic sheath (≤F20). Conclusion When the most common F26.5 endoscopic sheath is used, 40.98% of the patients have the possibility of urethral injury, which is significantly too big for male transurethral surgery. For patients undergoing transurethral BPH surgery, a thinner sheath should be used to reduce the possibility of urethral injury and secondary iatrogenic urethral stricture.

ObjectiveTo develop and preliminarily validate a prediction model for brace treatment failure risk in patients with adolescent idiopathic scoliosis (AIS), based on information obtained before brace treatment and during initial brace fitting. MethodsA total of 191 patients with AIS who initiated thoracolumbosacral orthosis treatment at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March, 2015 to August, 2024 and had determinable outcomes were retrospectively included. Patients were divided according to a prespecified scheme into a training set (n = 133) and a validation set (n = 58). Brace treatment failure was defined as progression of the major-curve Cobb angle by ≥ 5° from baseline during follow-up or at brace weaning, or a final major-curve Cobb angle > 45°. Logistic regression, random forest, support vector machine with radial basis function kernel, and extreme gradient boosting (XGBoost) models were developed using routinely available clinical and radiographic variables before brace treatment and during initial brace fitting. Stratified five-fold cross-validation was used for hyperparameter tuning in the training set. Model performance was evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), Brier score, calibration curves, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) was used to interpret the main explanatory model. ResultsIn cross-validation of the training set, both random forest and XGBoost showed good discriminative performance, with cross-validation-AUC values of 0.871 and 0.880, respectively. In the validation set, the AUC values of random forest and XGBoost were 0.888 and 0.899, the AUPRC values were 0.678 and 0.830, and the Brier scores were 0.086 and 0.076, respectively. Random forest was selected as the primary model for interpretation, with a calibration intercept of 0.091 and a calibration slope of 0.995. SHAP analysis indicated that the in-brace correction rate and the major-curve Cobb angle measured in the brace contributed most to the model predictions. ConclusionThe random forest model developed using routinely available pretreatment and initial-fitting variables shows preliminary predictive value for brace treatment failure risk in AIS, and may provide quantitative support for follow-up scheduling, brace-fit reassessment and early adherence-oriented management.

AIM:To elucidate the pharmacody-namic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L.,to ex-plore their key targets and related pathways,and to clarify their mechanism of action against hepatic fibrosis.METHODS:The total flavonoids of Cartha-mus tinctorius L.were determined by LC-MS/MS and analysed for their compositions;the active in-gredients were screened by TCMSP database,SWISS ADME database and literature search;the targets related to total flavonoids of Carthamus tinctorius L.were screened by Swiss Target Predic-tion database;and the targets related to hepatic fi-brosis were screened by GeneCards database;the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained by taking the intersection of Venny.2.1.0;the protein interac-tions were analysed by STRING database;the visu-alization analysis was carried out by Cytoscape soft-ware;the GO function and KEGG pathway analysis was carried out by Metascape platform;and molec-ular docking was verified by using AutoDock soft-ware for the core targets and active ingredients.The mechanism of anti-hepatic fibrosis of total fla-vonoids of Carthamus tinctorius L.was verified by animal model and in vitro cell experiments.RE-SULTS:A total of 41 flavonoid components were identified in Carthamus tinctorius L.Through the network pharmacological analysis,149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained,including 23 core tar-gets.The GO enrichment analyses involved a total of three aspects,namely,biological process(BP),cellular component(CC),and molecular function(MF).KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the devel-opment of hepatic fibrosis.Molecular docking veri-fied that the active ingredients Quercetin,Acacetin and Glabridin were tightly bound to Akt1 and HI-FIA,respectively.In animal model experiments,it was observed by HE and Masson staining that fibro-plasia was reduced,collagen deposition was re-duced,inflammatory cell infiltration was reduced,and fibrotic liver tissues were improved in total fla-vonoids of Carthamus tinctorius L.administration group.In isolated cell experiments:Western blot-ting results suggested that total flavonoids of Car-thamus tinctorius L.could decrease the hepatic fi-brosis marker factor α-SMA,Collagen1(P＜0.01)and PI3K,Akt protein expression(P＜0.01).CONCLU-SION:Total flavonoids of Carthamus tinctorius L.ex-erted anti-hepatic fibrosis effects through multi-components,multi-targets and multi-pathways,and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway.

Objective To analyze the potential biological relationship between Alzheimer disease(AD)and chronic periodontitis(CP)by bioinformatics.Methods We analyzed two datasets of AD and CP from the Gene Expression Omnibus database,and differentially expressed genes(DEGs)were identified from these datasets.Weighted gene co-expression network analysis(WGCNA)was used to identify the most relevant modules.Functional enrichment analysis of shared genes was performed,and a protein-protein interaction(PPI)network was constructed.MCODE was used to identify key modules,and machine learning was used to discover key genes.In addition,Gene Set Enrichment Analysis(GSEA)and CIBERSORT were used to investigate KLRB1-related molecular pathways and immune cell distribu-tion.Results The study identified 18 genes common to both AD and CP.MCODE analysis revealed five pivotal genes,machine learning identified 13 genes for AD,eight for CP,and KLRB1 was determined as a common gene for AD and CP.GSEA demonstrated the intricate involvement of these genes in disease-related pathways.Immunocellular analysis underscored a significant association between KLRB1 and γδT cells.Conclusion This research highlighted KLRB1 as a key gene for AD and CP,providing new insights into their molecular linkages.

Objective:To study the comparative genomic characteristics of Marmota himalayana-derived (referred to as marmota-derived) Brucella abortus (B.ab). Methods:The species and types of one strain of marmota-derived Brucella and one strain of human-derived Brucella isolated from the brucellosis epidemic area in Qinghai Province in the same year were identified. Meanwhile, DNA was extracted for whole genome sequencing and comparative genomics analysis (including phylogenetic tree construction, gene family clustering analysis, common/specific gene analysis, and genomic structural variation analysis, etc.). Results:Two Brucella strains from different hosts were identified as B.ab. By constructing a phylogenetic tree, the marmota-derived B.ab strain was grouped with strains from Heilongjiang Province and showed genetic correlation with strains from Russia. Human-derived B.ab strain was classified as a strain in Inner Mongolia Autonomous Region, Hebei Province, Beijing City, and Gansu Province. The multilocus sequence typing (MLST) of the two strains belonged to the ST2 type. Multiple locus variable-number tandem repeat analysis (MLVA) belonged to two new MLVA-8 and MLVA-11 genotypes, which were clustered in two subclusters of the same cluster and clustered with the strains from Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, and Hebei Province. The pan-genome numbers of the marmota-derived B.ab and human-derived B.ab were 283 and 8, respectively; the number of core genes (common genes) was 68 and 2, respectively; and the number of unique genes was 3 and 4, respectively. The unique gene encoded proteins were inconsistent. In marmota-derived B.ab, the main ones were the ABC transporter ATP-binding protein, N-terminal acetyltransferase, and glucose/galactose transporter. The number of homologous genes of the marmota-derived B.ab and human-derived B.ab was 16 and 20, respectively; the number of translocation and inversion genes was 13 and 8, respectively; the number of deletion mutation genes was 11 and 14, respectively. Pathogenicity analysis showed that both strains had the mprF resistance gene, and the marmota-derived B.ab strain also carried bacitracin and macrolide resistance genes. Conclusions:Brucella exhibits cross-species genetic diversity. The proteins encoded by the unique genes of the marmota-derived B.ab mainly play a role in metabolic and epigenetic regulation. The strains cluster with B.ab strains from northern China, providing a reference for molecular epidemiology and pathogen tracing of B.ab infection.