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.

Objective: To develop QingNangTCM, a specialized large language model (LLM) tailored for expert-level traditional Chinese medicine (TCM) question-answering and clinical reasoning, addressing the scarcity of domain-specific corpora and specialized alignment. Methods: We constructed QnTCM_Dataset, a corpus of 100 000 entries, by integrating data from ShenNong_TCM_Dataset and SymMap v2.0, and synthesizing additional samples via retrieval-augmented generation (RAG) and persona-driven generation. The dataset comprehensively covers diagnostic inquiries, prescriptions, and herbal knowledge. Utilizing P-Tuning v2, we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM. A multi-dimensional evaluation framework, assessing accuracy, coverage, consistency, safety, professionalism, and fluency, was established using metrics such as bilingual evaluation understudy (BLEU), recall-oriented understudy for gisting evaluation (ROUGE), metric for evaluation of translation with explicit ordering (METEOR), and LLM-as-a-Judge with expert review. Qualitative analysis was conducted across four simulated clinical scenarios: symptom analysis, disease treatment, herb inquiry, and failure cases. Baseline models included GLM-4-9B-Chat, DeepSeek-V2, HuatuoGPT-II (7B), and GLM-4-9B-Chat (freeze-tuning). Results: QingNangTCM achieved the highest scores in BLEU-1/2/3/4 (0.425/0.298/0.137/0.064), ROUGE-1/2 (0.368/0.157), and METEOR (0.218), demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy, coverage, and consistency. Although its ROUGE-L score (0.299) was lower than that of HuatuoGPT-II (7B) (0.351), it significantly outperformed domain-specific models in expert-validated win rates for professionalism (86%) and safety (73%). Qualitative analysis confirmed that the model strictly adheres to the “symptom-syndrome-pathogenesis-treatment” reasoning chain, though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes. Conclusion Combining domain-specific corpus construction with parameter-efficient prompt tuning enhances the reasoning behavior and domain adaptation of LLMs for TCM-related tasks. This work provides a technical framework for the digital organization and intelligent utilization of TCM knowledge, with potential value for supporting diagnostic reasoning and medical education.

OBJECTIVE To evaluate the performance of commonly used molecular biological identification methods in differential identification of Citrobacter freundii complex(Cfc)and find out the differences in the mass spectra among the prevalent species of Cfc so as to facilitate the rapid and accurate identification.METHODS Totally 150 clinical strains were isolated from The First Medical Center of Chinese PLA General Hospital from 2015 to 2020 and were identified as Cfc by means of matrix assisted laser desorption ionization-time-of-flight mass spectrometry(MALDI-TOF MS),the genome data were obtained by the next generation sequencing and were compared with reference genome of Citrobacter species from National Center of Biotechnology Information(NCBI)based on aver-age nucleotide identity(ANI),phylogenetic analyses of rec N gene,concatenated alignments of four housekeeping genes(fusA,pyrG,leuS and rpoB as well as gyrB,rplB,fusA and leuS),core genome single nucleotide poly-morphism(coreSNP)and whole genome(WG),digital DNA-DNA hybridization(dDDH)analysis,ribosomal multilocus sequence typing(rMLST)and typical(strain)genome service(TYGS)analysis.ANI was set as the'gold standard' for the identification of the Cfc strains,and the capabilities of the various methods were evaluated.A certain number of strains of Citrobacter freundii(Cfr),Citrobacter braakii(Cbr)and Citrobacter portucalen-sis(Cpo)were randomly selected to obtain and compare the mass spectra so as to find out the differences in the mass spectra.RESULTS The identification capability of the Cfc strains is limited based on the available database for MALDI-TOF MS,Cpo was prone to be misidentified as Cfr or Cbr.The mass spectrum between Cpo and Cfr ranged between 2600 and 2660 m/z,the mass spectrum between Cpo and Cbr ranged between 5200 and 5300 m/z,showing significant difference.The concatenated alignments of four housekeeping genes gyrB,rplB,fusA and leuS,CoreSNP and WG phylogenetic analysis had high accurate rate of identification.CONCLUSIONS The meth-ods have certain limitations in identification of Cfc.The joint application of ANI with the methods such as WG phylogenetic analysis,update of mass spectrum database and timely establishment of database can achieve the ac-curate identification of the species of Cfc.

To explore the cultivation path of excellent physicians in regional medical universities, a horizontal integration of clinical courses was performed to construct a curriculum centered on systemic diseases. Clinical courses adopted bedside rotation teaching with small class (30-40 students, 3-4 students/group). A comprehensive approach was designed and implemented, covering overall framework, organizational guarantee, teaching arrangement, teaching method, and assessment system. The effectiveness of the reform was evaluated through the comprehensive exams during the basic stage and national clinical medicine proficiency test. Despite no significant differences in the basic stage, the national clinical medicine proficiency test scores of the C2E class with teaching reform increased continuously from 2017 to 2020. The theoretical examination score of the C2E class was higher than that of regular classes 1 in 2017, 2019, and 2020. With continuous optimization, the skill examination score of the C2E class was significantly higher than that of regular class 1 in 2020. These findings highlight the effectiveness of the teaching reform and provide a foundation for the teaching reform of large class in five-year clinical medicine programs.

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

OBJECTIVE To observe the characteristics of outer membrane vesicles(OMVs)of 1 strain of hypervir-ulent Klebsiella pneumoniae(hvKp)11492.METHODS The hvKp11492,one of major clones of hvKp that were i-solated from patients with bloodstream infection in the First Medical Center of Chinese PLA General Hospital,was chosen as the research subject.The strain was identified by means of matrix-assisted laser desorption/ioniza-tion time of flight mass spectrometry and whole genome sequencing.The hvKp1 1492-OMVs were separated and purified by high speed centrifugation in combination with polymer precipitation,the morphology and particle size of the hvKp11492-OMVs were identified by transmission electron microscopy(TEM)and nanoparticle tracking a-nalysis(NTA),the proteomic characteristics were analyzed through bicinchoninic acid assay(BCA)and liquid chromatography-mass spectrometry(LC-MS)series technique,and the virulence genes were detected by PCR.RESULTS The hvKp11492-OMVs were displayed differently in size,round or oval,and complete double-layer membrane vesicles on TEM.The result of NTA showed that the average particle size of the hvKp1 1492-OMVs was 270 nm.The protein content of hvKp11492-OMVs was(2.448±0.975)μg/μl.The result of subcellular lo-calization indicated that the protein included plasmosin,intracellular membrane protein,periplasmic protein,ex-tracellular membrane protein and nuclear region protein,which were found,by the annotation of GO database,to participate in the biological processes such as oxidation-reduction,interpretation,and metabolism.The hvKp11492-OMVs contained various proteins such as GDP-L-fucose synthetase,iron ion transporter protein and ferritin that were associated with pathogenicity.In addition,the hvKp1 1492-OMVs carried with iutA,iroN,iucA and rmpA virulence genes.CONCLUSIONS The morphologic characteristics,size and proteomic characteris-tics of the hvKp11492-OMVs are identified in the study.It is concluded that the hvKp11492-OMVs carry with va-rious proteins and genes that are association with the virulence and pathogenicity.

OBJECTIVE To evaluate the performance of commonly used molecular biological identification methods in differential identification of Citrobacter freundii complex(Cfc)and find out the differences in the mass spectra among the prevalent species of Cfc so as to facilitate the rapid and accurate identification.METHODS Totally 150 clinical strains were isolated from The First Medical Center of Chinese PLA General Hospital from 2015 to 2020 and were identified as Cfc by means of matrix assisted laser desorption ionization-time-of-flight mass spectrometry(MALDI-TOF MS),the genome data were obtained by the next generation sequencing and were compared with reference genome of Citrobacter species from National Center of Biotechnology Information(NCBI)based on aver-age nucleotide identity(ANI),phylogenetic analyses of rec N gene,concatenated alignments of four housekeeping genes(fusA,pyrG,leuS and rpoB as well as gyrB,rplB,fusA and leuS),core genome single nucleotide poly-morphism(coreSNP)and whole genome(WG),digital DNA-DNA hybridization(dDDH)analysis,ribosomal multilocus sequence typing(rMLST)and typical(strain)genome service(TYGS)analysis.ANI was set as the'gold standard' for the identification of the Cfc strains,and the capabilities of the various methods were evaluated.A certain number of strains of Citrobacter freundii(Cfr),Citrobacter braakii(Cbr)and Citrobacter portucalen-sis(Cpo)were randomly selected to obtain and compare the mass spectra so as to find out the differences in the mass spectra.RESULTS The identification capability of the Cfc strains is limited based on the available database for MALDI-TOF MS,Cpo was prone to be misidentified as Cfr or Cbr.The mass spectrum between Cpo and Cfr ranged between 2600 and 2660 m/z,the mass spectrum between Cpo and Cbr ranged between 5200 and 5300 m/z,showing significant difference.The concatenated alignments of four housekeeping genes gyrB,rplB,fusA and leuS,CoreSNP and WG phylogenetic analysis had high accurate rate of identification.CONCLUSIONS The meth-ods have certain limitations in identification of Cfc.The joint application of ANI with the methods such as WG phylogenetic analysis,update of mass spectrum database and timely establishment of database can achieve the ac-curate identification of the species of Cfc.

AIM:This study aimed to establish a model of functional impairment in INS-1 cells(rat insulino-ma cells)induced by prolonged exposure to a low level of interleukin-1β(IL-1β),and to investigate the underlying mech-anisms.METHODS:INS-1 cells were treated with different concentrations of IL-1β for 10 d.The cells were divided into control,0.05 μg/L IL-1β,0.1 μg/L IL-1β,and 0.2 μg/L IL-1β groups(n=3).Flow cytometry was employed to assess cell apoptosis,facilitating the identification of IL-1β concentrations that did not significantly induce apoptosis.Subse-quently,INS-1 cells were divided into control and IL-1β groups(n=3)and treated with 0.1 μg/L IL-1β for 10 days.The intracellular insulin content and glucose-stimulated insulin secretion level were detected by immunofluorescence and en-zyme-linked immunosorbent assay(ELISA).Differential proteins and associated signaling pathways were screened using 4D label-free proteomics technology.Moreover,fluorescent probes were used to detect glucose-stimulated calcium ion in-flux,and Western blot was conducted to verify the expression changes of relevant proteins in the nuclear factor kappa-B(NF-κB)signaling pathway and calcium signaling pathway.RESULTS:Treatment with 0.1 μg/L IL-1β for 10 days ex-hibited minimal impact on the survival of INS-1 cells but significantly reduced the intracellular insulin content and glucose-stimulated insulin secretion(P<0.01).Therefore,0.1 μg/L IL-1β was chosen for in vitro induction of functional impair-ment in INS-1 cells.Proteomic analysis showed no significant differences in the expression of apoptosis-related factors,such as caspase-3,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and Bcl-2-associated death promoter(Bad),compared with the control(P>0.05).However,the expression of insulin,v-maf avian musculoaponeurotic fibro-sarcoma oncogene family protein A(Mafa),calcium/calmodulin-dependent protein kinase II(CaMKII),inositol 1,4,5-triphosphate receptor(IP3R),and NF-kappa-B inhibitor alpha(IκBα)was significantly reduced(P<0.01),while the protein expression levels of NF-κB and inducible nitric oxide synthase(iNOS)were significantly increased(P<0.05,P<0.01).Fluorescence probe results showed that,compared to the control,the calcium ion influx induced by glucose stimu-lation in the IL-1β group was significantly reduced(P<0.01).Western blot results demonstrated that the expression lev-els of IP3R,CaMKII,and IκBα in the IL-1β group were significantly reduced(P<0.05,P<0.01),while the expression levels of NF-κB and iNOS were significantly increased(P<0.01).CONCLUSION:A model of functional impairment in rat INS-1 cells induced by prolonged exposure to low levels of IL-1β has been successfully established,and it has been pre-liminarily confirmed that this impairment may be related to the activation of the NF-κB signaling pathway and dysfunction of the calcium signaling pathway.

Objective To analyze the distribution characteristics of infectious respiratory particles(IRPs)in hospi-tal waiting rooms,and explore the impact of indoor air environmental on the distribution characteristics of bacterial IRPs.Methods In the summer and winter of 2024,nine waiting rooms in non-infectious departments of three ter-tiary hospitals in a district of Beijing were selected for on-site investigation on basic conditions.Concentration and distribution of particle diameter of cultivable bacteria from 36 air specimens collected by the impacting method were analyzed.Cyclone method was employed to collect 36 IRPs specimens.Major respiratory pathogens were analyzed by fluorescence polymerase chain reaction(PCR).Results The median of the total bacterial count in IRPs in the waiting rooms in summer was 1 035 CFU/m3,which was higher than that in winter(295 CFU/m3),with statisti-cally significant difference(P＜0.05).The orders of medians of the total bacterial count from IRPs of different types in the waiting rooms in both summer and winter were as follows:emergency department waiting room＜re-spiratory department waiting room＜pediatric waiting room＜general outpatient waiting room.There was no sta-tistically significant difference in the total bacterial count among different waiting rooms(P＞0.05).Particle diame-ter of bacterial IRPs in the waiting rooms in summer and winter mainly distributed in the range of＜4.7 μm,ac-counting for 73.77％and 69.44％,respectively.The total number of bacteria in IRPs in the waiting rooms was positively correlated with indoor air temperature,relative humidity,PM10,and PM2.5(all P＜0.01),while nega-tively correlated with indoor wind speed(all P＜0.01).The types of respiratory infectious and non-infectious pathogens detected from IRPs in different types of waiting rooms were different between summer and winter.The pathogens detected in summer were mainly concentrated in respiratory non-infectious pathogens(Escherichia coli,Klebsiella pneumoniae,Staphylococcus aureus).In winter,respiratory infectious pathogens(virus and Mycoplas-ma pneumoniae)were detected.The types of detected pathogens in different types of waiting rooms were different.Non-infectious respiratory pathogens detected from IRPs in winter were mainly Escherichia coli,Klebsiella pneumoniae,and Staphylococcus aureus.Conclusion Particle diameter of bacterial IRPs in the waiting room is mainly＜4.7 μm.These particles can enter the lower respiratory tract of human body,and pose potential risk to health.The detection of main infectious and non-infectious respiratory pathogens from IRPs in waiting rooms suggests risk of exposure to infection for patients and healthcare workers.