ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

ObjectiveTo explore the association between marital/living status and cognitive domains （memory， language， visuospatial， executive， and attention domains） in older adults， and to examine the influencing factors underlying urban-rural differences. MethodsBased on baseline data from the dynamic enrollment cohort （2016—2025） of the Hubei Memory and Aging Cohort Study， 10 825 older adults aged 60 years and above who met the study criteria were included， comprising 3 788 rural residents and 7 037 urban residents. The cohort collected information on marital and living status via questionnaires. Cognitive domains were assessed using standardized neuropsychological tests， with scores converted to z-scores ［（raw score - mean score of the domain in the study population）/standard deviation of the domain in the study population］. Multiple linear regression models were used to analyze the associations between marital/living status and cognitive domains， as well as global cognition. ResultsRural older adults scored significantly lower than their urban counterparts in terms of socioeconomic status， healthy lifestyle indicators， and multiple cognitive domains （all P＜0.001）. Living away from family was significantly associated with lower scores across cognitive domains ［memory： b =-0.217， 95%CI （-0.276， -0.159）； attention： b =-0.213， 95%CI （-0.262， -0.163）， all P＜0.001］， with this association being stronger and involving a broader range of cognitive domains in the urban sample. Moreover， compared to married and living with family， married but living away from family was associated with poorer cognitive performance， an effect that was more pronounced in the urban sample ［memory： b =-0.521， 95%CI （-0.621， -0.422）； attention： b =-0.443， 95%CI （-0.533， -0.354）， all P＜0.001］. ConclusionUnmarried status and living away from family were each significantly associated with poorer performance in cognitive domains among older adults. The combined status of being married but living away from family was also associated with poorer cognitive performance， with these associations being more pronounced among urban-dwelling older adults.

This article introduces Professor Zhou Peng's clinical experience in treating generalized anxiety disorder(GAD)using spirit-regulating and root-strengthening integrated acupuncture.Based on the pathological characteristics of GAD,Professor Zhou Peng summarizes its pathogenesis as"disharmony of qi,blood,yin,and yang,"pointing out that"deficiency"is the essence of its onset,with spleen and kidney deficiency being the root cause.He advocates treating GAD from the perspective of"deficiency and decline,"focusing on strengthening the spleen and kidneys,consolidating the root,and nourishing the source,while also regulating the mind.The integrated acupuncture therapy includes needling,refined moxibustion,and intradermal needle embedding.Needling is used to harmonize qi and blood,refined moxibustion to regulate and supplement yin and yang to consolidate the root,and intradermal needle embedding to regulate the mind and consolidate the therapeutic effects of acupuncture.Starting from improving patients'compliance with treatment and ensuring sustained therapeutic effects,Professor Zhou emphasizes that acupuncture manipulation should be fast,gentle,and soft,with needle insertion resembling a swift crane touching the waves and needle manipulation like a deer drinking from a clear spring.He places great importance on patients'sensations and aims to holistically regulate the body's qi,blood,yin,and yang,restoring the balance of body and mind,thereby effectively treating generalized anxiety disorder.

Addressing the challenge of traditional physical/semi physical simulation methods being difficult to achieve full process and full element simulation of extravehicular activities,virtual reality technology is utilized to break through the limitations of physical environments and establish a virtual reality simulation system for extravehicular activities.Based on the application characteristics of space station extravehicular activity engineering,with the goal of improving system practicality and usability,integrating the visual immersion of virtual images,the ontology of real operation,and the consistency of virtual and real space perception,a three-dimensional scene simulation,multi-mode joystick interaction paradigm,continuous operation actions simulation of extravehicular operations,and interactive operation virtual/real space consistency method that were proposed and designed for the realistic visual perception and extravehicular operation.The system has been successfully applied to astronaut training,program validation,joint exercise,and flight control support for sixteen extravehicular activities from SZ-12 to SZ-18.The results showed that the complete reproduction of the static/dynamic realistic comprehensive scene was achieved on the ground for the human-machine operation in the entire process of extravehicular activity,and the system is an essential and important means of ground simulation for extravehicular activity.

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8(NEDD8)to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme(NAE)(E1),E2 NEDD8-conjugating enzyme(E2),and E3 NEDD8-ligase(E3).The most extensively studied substrates of neddylation are members of the cullin family,which act as scaffold components for cullin ring E3 ubiquitin ligases(CRLs).Since cullin neddylation activates CRLs,which are frequently overactive in tumors,inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies.This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions(PPIs)within the neddylation enzymatic cascade.

Objective To explore the potential profile characteristics and influencing factors of social participation in young and middle-aged stroke patients based on the theoretical framework of international classification of functioning,disability and health,so as to provide a basis for formulating personalized intervention measures.Methods From May to October 2024,convenience sampling was used to select young and middle-aged stroke patients in the First Affiliated Hospital of Jinan University as research objects.The data were collected through the general information questionnaire,impact on participation and autonomy questionaire and stroke stigma scale.The potential profile analysis was used to classify the patients' social participation level,and the disordered multinomial Logistic regression was used to analyze its influencing factors.Results The social participation of young and middle-aged stroke patients could be divided into three types:independent social life type(47.87％),limited social interaction type(28.20％)and weakened family responsibility type(23.93％).Stigma,stroke type and personal history of stroke were the influencing factors of different types of social participation(P＜0.05).Conclusion There is heterogeneity in the level of social participation in young and middle-aged stroke patients.Medical staff should provide personalized rehabilitation guidance according to different potential categories to improve the level of social participation and quality of life of patients.

Objective:To investigate influence of different phantoms on the results of quality control for the images of cone beam computed tomography(CBCT)for breast on the basis of quality control for breast CBCT.Methods:Five different manufacturers'phantoms were selected,and they were placed at the position of testing breast in clinical examination to conduct position for phantom according to the method of the national health industry standard WS 818-2023.The analysis focused on the differences of evaluation results of using different phantoms for image quality on the basis of a series of parameters included uniformity,resolution of high contrast,resolution of low contrast,and CT value of water in scanning images of different phantoms.Data collection and image reconstruction were performed respectively by using commonly clinical procedures.Corresponding module images were selected from the reconstructed images of standard breast phantom.The common layer thickness and projection method of the system were set to record and analyze data.Results:The image uniformity of measured results of the five phantoms were respectively 42.37±2.01,-5.83±0.15,3.76±0.15,2.16±0.06,3.60±0.10.The differences of the image uniformities among the five phantoms were statistically significant(F=1310.02,P<0.001),and the differences of the CT values of the measured water among the five phantoms were statistically significant(F=9 846.46,P<0.001).The differences in the resolution of low contrast among them were also statistically significant(F=27.50,P<0.001).However,the results of the resolution of high contrast were stability,and there was no significant difference in that among the five phantoms.Conclusion:The measured results of quality control of different phantoms are different.

Objective:To explore the clinical efficacy of the sixth generation CyberKnife (M6) in treating patients with brain metastases, and analyze clinical characteristics and dosimetric factors.Methods:Clinical data of patients with brain metastases who received CyberKnife treatment at Sichuan Cancer Hospital from April 2023 to March 2024 were retrospectively analyzed. All patients were treated with CyberKnife with 6 MV X-ray. According to the maximum diameter of brain metastases, the radiation prescription dose of brain metastases was adjusted. The tumor remission, recurrence, 6-month and 1-year overall survival (OS), local control (LC) of intracranial target lesions, progression-free survival (PFS), distant metastasis-free survival (DMFS) of intracranial brain metastases and adverse reactions were evaluated. According to the median biological dose, the survival difference between the groups was compared. Survival analysis was conducted by Kaplan-Meier method. Survival differences among different groups were analyzed by log-rank test.Results:A total of 63 eligible patients with brain metastases were enrolled, with a median age of 59 years (rang: 36-80 years). Among them, 47 patients were diagnosed with primary tumors originating from the lungs, 16 patients with primary tumors originating from other organs; 44 patients with single brain metastases, and 19 patients with 2-3 lesions, respectively. The median biological dose was 67.2 Gy (rang: 47.4-86.4 Gy), and the median single dose was 8 Gy/F (rang: 4-24 Gy/F). The follow-up was conducted until July 15, 2024. The median follow-up time for the entire group was 9 months (rang: 2-15 months). Among the 87 target lesions treated with CyberKnife, 11 patients corresponding to 14 target lesions experienced local recurrence. And the 6-month and 1-year LC rates were 92.5% and 70.9%, respectively. Ten patients corresponding to 16 target lesions died. And the 6-month and 1-year OS rates were 92.7% and 74.8%, respectively. Thirty-five patients corresponding to 50 target lesions experienced disease progression. And the 6-month and 1-year PFS rates were 64.3% and 25.5%, respectively. Thirty-three patients corresponding to 48 target lesions showed distant metastasis outside the target lesions, with a 6-month DMFS of 67.0% and a 1-year DMFS of 33.9%. Group comparison showed that 43 target lesions in the group receiving ≤67.2 Gy irradiation and 44 in the group receiving >67.2 Gy irradiation. The 6-month LC, OS, PFS, and DMFS rates between two groups were 89.8% vs. 97.7% ( P=0.127), 89.8% vs. 95.4% ( P=0.305), 65.4% vs. 68.5% ( P=0.514), 65.4% vs. 68.5% ( P=0.516), respectively. The 1-year LC, OS, PFS, and DMFS rates between two groups were 54.1% vs. 89.5% ( P=0.003), 67.3% vs. 82.9% ( P=0.219), 19.2% vs. 32.7% ( P=0.370) and 23.3% vs. 33.0% ( P=0.533). During the follow-up, only 2 patients (3.2%) were found to have grade 1-2 radiation-induced brain injury (asymptomatic brain injury) by MRI examination, and there were no other radiotherapy related adverse reactions. Conclusions:CyberKnife therapy is clinically effective for brain metastases, with mild adverse reactions. Increasing the tumor irradiation dose can improve local tumor control and is expected to further improve the OS of patients.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP