Objective To assess the current status of microbial and parasitic quality control for laboratory animals in Jiangxi Province by analyzing microbiological and parasitic test results from production facilities between 2020 and 2024, and to provide a basis for enhancing quality control measures. MethodsIn accordance with the current national standards for laboratory animals at the time of testing, the Jiangxi Provincial Laboratory Animal Quality Inspection Station (affiliated to Institute of Occupational Medicine of Jiangxi) conducted microbial and parasitic testing on 451 laboratory animals of 4 species from 6 laboratory animal production units in Jiangxi Province between 2020 and 2024, and analyzed the quality status of laboratory animals in the province. ResultsPasteurella pneumotropica was detected in one mouse sample in 2020, with a detection rate of 5.00%. Pseudomonas aeruginosa was detected in one mouse sample and mouse hepatitis virus antibody was detected in another mouse sample in 2023, with a detection rate of 2.78%, respectively. No microorganisms or parasites that should be excluded from SPF grade mice as specified in the national standards were detected in 2021, 2022, or 2024, with a qualification rate of 100.00%. Pasteurella pneumotropica was detected in four rat samples in 2020, with a detection rate of 20.00%. Pseudomonas aeruginosa was detected in two rat samples in 2021, with a detection rate of 10.00%, and Tyzzer's disease agent antibody was detected in four rat samples in 2024, with a detection rate of 10.00%. No microorganisms or parasites that should be excluded from SPF grade rats as specified in the national standards were detected in 2022 or 2023, with a qualification rate of 100.00%. For rabbits and guinea pigs, no microorganisms or parasites required to be tested for conventional grade rabbits and guinea pigs as specified in the national standards were detected from 2020 to 2024, with the qualification rate of both species reaching 100.00%. ConclusionBased on the microbial and parasitic testing results, the quality of rabbits and guinea pigs in Jiangxi Province is satisfactory. However, some issues persist with rats and mice. It is recommended to enhance the quality of experimental animals in Jiangxi Province by increasing the frequency of random inspections by quality testing units or by improving the self-inspection capabilities of production and user facilities.

OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group， model group， dexamethasone group （positive control）， and Ephedrae Herba-Armeniacae Semen Amarum 2∶1， 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g （crude drug）/kg]， dexamethasone suspension （0.5 mg/kg）， or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration， medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration， the nucleus tractus solitarius （NTS） was located using a stereotaxic apparatus. Histamine phosphate （1 μL） was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats； the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor （NGF）， substance P （SP）， norepinephrine （NA）， 5-hydroxytryptamine （5-HT） and acetylcholine （Ach）] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor （NK-1R）， p38 mitogen-activated protein kinase （MAPK）， and c-fos in the medulla oblongata， as well as the protein expressions of NK-1R， p38 MAPK， and c-fos in the NTS region， were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine， pseudoephedrine， and methylephedrine. Compared with blank group， the contents of NGF， SP， NA， 5-HT and Ach， and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein were significantly increased in the model group （ P ＜0.01）. Compared with model group， Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein （ P ＜0.01）， with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.

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 investigate the mechanism by which Shaoyaotang regulates the miRNA-155-mediated suppressor of cytokine signaling 1 （SOCS1）/Janus kinase 1 （JAK1）/signal transducer and activator of transcription 1 （STAT1） signaling pathway and thereby affects macrophage polarization. MethodsThe cell-counting kit-8 （CCK-8） assay was used to detect the effect of drug-containing serum of Shaoyaotang at different concentrations on the viability of RAW 264.7 cells. A cell model of inflammation was established by stimulating RAW264.7 cells with lipopolysaccharide （LPS） at a concentration of 10 mg·L^-1 The modeled cells were assigned by the random number table method into seven groups： LPS-induced M1 polarization （model）， M1+miRNA-155 mimics， M1+miRNA-155 inhibitor， M1+Shaoyaotang-containing serum， M1+miRNA-155 mimics+Shaoyaotang-containing serum， M1+miRNA-155 inhibitor+Shaoyaotang-containing serum， and M1+blank serum. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］. Immunofluorescence assay was used to detect the expression of macrophage polarization markers ［inducible nitric oxide synthase （iNOS） and macrophage mannose receptor 1 （CD206）］. Real-time PCR was employed to measure the expression of miRNA-155 in cells. Western blot was performed to determine the protein levels of SOCS1， STAT1， and JAK1. ResultsCompared with the LPS-induced M1 polarization （model） group， the M1+miRNA-155 mimics group showed up-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and down-regulated expression of CD206 （P<0.05）. In both the M1+miRNA-155 inhibitor group and the M1+Shaoyaotang-containing serum group， the expression levels of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS were down-regulated （P<0.05）， while those of SOCS1 and CD206 were up-regulated （P<0.05）. Compared with the M1+miRNA-155 mimics group， the M1+miRNA-155 mimics+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and up-regulated expression of SOCS1 and CD206 （P<0.05）. Compared with the M1+miRNA-155 inhibitor group， the M1+miRNA-155 inhibitor+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and up-regulated expression of SOCS1 and CD206 （P<0.05）. ConclusionShaoyaotang regulates macrophage polarization by modulating miRNA-155 expression and interfering with the SOCS1/JAK1/STAT1 signaling pathway. The findings provide new experimental evidence for the treatment of ulcerative colitis with Shaoyaotang.

ObjectiveTo investigate the potential role and underlying mechanisms of Shaoyaotang in intervening macrophage glycolytic reprogramming in ulcerative colitis （UC）. MethodsForty-eight C57BL/6 mice were randomly divided into six groups： Normal control group， model group， mesalazine group （0.39 g·kg^-1）， Shaoyaotang group （15.54 g·kg^-1）， 2-deoxy-D-glucose （2-DG） group （glycolysis inhibitor， 100 mg·kg^-1）， and 2-DG + Shaoyaotang combined group （100 mg·kg^-1+15.54 g·kg^-1）. Except for the normal control group， mice in the other five groups were induced to establish UC models using dextran sulfate sodium （DSS）. The normal control group was administered pure water via intragastric gavage， while the other groups received intragastric gavage of mesalazine solution， intragastric gavage of Shaoyaotang， and the 2-DG group was treated with 2-DG via intraperitoneal injection. After 7 consecutive days of treatment， colonic tissues were extracted. Hematoxylin and eosin （HE） staining was performed to evaluate histopathological changes and tissue injury in the colon. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-10 （IL-10） and tumor necrosis factor-α （TNF-α） in colonic tissues. Western blot analysis was employed to determine the expression levels of hypoxia-inducible factor-1α （HIF-1α）， glucose transporter （GLUT1）， lactate dehydrogenase A （LDHA）， pyruvate kinase M2 （PKM2）， and 6-phosphofructo-2-kinase/fructose-2，6-biphosphatase 3 （PFKFB3） in colonic tissues. Immunofluorescence was conducted to detect the expression of CD206 and inducible nitric oxide synthase （iNOS） in colonic tissues. Liquid chromatography-mass spectrometry （LC-MS） was utilized to measure lactate and citrate levels in colonic tissues. ResultsCompared with the normal control group， mice in the model group exhibited a significant increase in disease activity index （DAI） scores， accompanied by colonic mucosal congestion， edema， and inflammatory cell infiltration， significantly elevated expression of the inflammatory cytokine TNF-α （P<0.05）， significantly decreased IL-10 expression （P<0.05）， significantly increased levels of HIF-1α， GLUT1， LDHA， PKM2， and PFKFB3 in colonic tissues （P<0.05）， markedly elevated iNOS expression （P<0.05）， significantly decreased CD206 expression （P<0.05）， and significantly elevated lactate and citrate levels in colonic tissues （P<0.05）. In contrast to the model group， the Shaoyaotang group， inhibitor group， and Shaoyaotang combined with inhibitor group demonstrated amelioration of mucosal injury in colonic tissues， markely decreased expression levels of the inflammatory cytokine TNF-α （P<0.05）， elevated IL-10 expression levels， significantly decreased expression of HIF-1α， GLUT1， LDHA， PKM2， and PFKFB3 （P<0.05）， markedly reduced iNOS expression levels （P<0.05）， significantly increased CD206 expression （P<0.05） and significantly decreased lactate and citrate levels （P<0.05）. ConclusionShaoyaotang ameliorates symptoms of DSS-induced UC in mice， and its therapeutic mechanism may be associated with regulating macrophage glycolytic reprogramming via modulation of the HIF-1α signaling pathway.

ObjectiveTo investigate the role of microRNA-155-5p （miR-155-5p） in ulcerative colitis （UC） and study the molecular mechanism of Shaoyaotang in the treatment of UC by regulating miR-155-5p. MethodsForty-eight SPF-grade male C57BL/6 mice were selected and assigned via the random number table method into 6 groups （n=8）： A blank control group， a model group， a mesalazine （0.39 g·kg^-1） group， a Shaoyaotang （31.08 g·kg^-1） group， a Janus kinase 1 （JAK1） inhibitor （baricitinib， 10 mg·kg^-1） group， and a Shaoyaotang combined with inhibitor （baricitinib 10 mg·kg^-1 + Shaoyaotang 31.08 g·kg^-1） group. After successful modeling of UC by gavage of 3% dextran sulphate sodium solution， each group received corresponding drug intervention for 7 days. Shaoyaotang and mesalazine were administered by gavage， and baricitinib by intraperitoneal injection. Twenty-four hours after the last administration， mice were anesthetized by intraperitoneal injection of pentobarbital sodium， and blood was collected for determination of white blood cell count and erythrocyte sedimentation rate （ESR）. Mice were then sacrificed for measurement of colon length. Hematoxylin-eosin staining was used to observe colonic pathological changes and perform pathological scoring. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the relative expression of miR-155-5p in the colonic tissue， and Western blot was used to determine the protein levels of JAK1， phosphorylated JAK1 （p-JAK1）， suppressor of cytokine signaling 1 （SOCS1）， signal transducer and activator of transcription 1 （STAT1）， and phosphorylated STAT1 （p-STAT1）. ResultsCompared with the blank control group， the model group showed increased disease activity index （DAI） score and pathological score， shortened colon， upregulated relative expression of miR-155-5p and protein levels of p-JAK1 and p-STAT1， downregulated protein level of SOCS1 in the colonic tissue， prolonged time of erythrocyte sedimentation， and increased white blood cell count （P<0.01）. Compared with the model group， all drug-treated groups exhibited improvements in the above indicators （P<0.01）. Moreover， the Shaoyaotang group showed better therapeutic effects than the mesalazine group in regulating miR-155-5p expression， related protein levels， DAI score， and colonic pathological score （P<0.01）. ConclusionShaoyaotang may downregulate miR-155-5p to relieve its inhibition on SOCS1， thereby suppressing the excessive activation of the JAK1/STAT1 signaling pathway and ultimately alleviating intestinal inflammatory damage.

ObjectiveTo investigate the role of the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway in intestinal mucosal barrier damage in ulcerative colitis， as well as the intervention mechanism of Shaoyaotang. MethodsSixty SD rats were allocated into a blank group， a model group， a mesalazine （0.42 g·kg^-1） group， and low-， medium-， and high-dose （11.1， 22.2， 44.4 g·kg^-1， respectively） Shaoyaotang groups. A model of ulcerative colitis was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）. After successful modeling， rats were administrated with corresponding agents via gavage for 7 days. Changes in colon length and colon weight were observed. Hematoxylin-eosin staining was performed to examine the pathological changes of the colon， and immunohistochemistry was employed to detect the expression of the inflammatory cytokine interleukin-8 （IL-8）， cyclooxygenase-2 （COX-2）， junction adhesion molecule-1 （JAM-1）， and claudin-1 in the colon. Western blot analysis was performed to determine the protein levels of TLR4， MyD88， and NF-κB in the colon. ResultsCompared with the blank group， the model group showed elevated DAI score （P<0.01）， reduced colon length and colon weight （P<0.01）， down-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and up-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. Compared with the model group， each treatment group showed decreased DAI score （P<0.05， P<0.01）， increased colon length and colon weight （P<0.05， P<0.01）， up-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and down-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. ConclusionShaoyaotang alleviates intestinal inflammation and intestinal mucosal damage to protect intestinal barrier integrity by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveMethylthioadenosine phosphorylase (MTAP) is found to be frequently deleted in malignant cancers, but the role of MTAP underlying metastasis and stemness of liver cancer remains far from clear. 5-fluorouracil (5-Fu) is clinically used in treating advanced liver cancer, however, chemoresistance is one of the major barriers impeding its efficacy. Liver cancer stem cells are considered to be the reservoir for tumor progression and chemoresistance. This study aims to explore the role of MTAP in regulating stemness and chemoresistance of 5-Fu in liver cancer. It is designed to elucidate the molecular mechanisms underlying MTAP-manipulated stemness. How MTAP influences metastasis and chemoresistance against 5-Fu in liver cancer is also elaborated. MethodsThe correlation of MTAP expression with stemness marker CD133 was evaluated by flow cytometry. Colony formation assays were conducted to analyze the tumorigenic ability. Western blot assays were applied to delineate the molecular mechanisms underlying MTAP-regulated stemness. Trans-well assays were conducted to analyze the metastatic potential of liver cancer cells.In vivo experiments were performed using subcutaneous xenograft and lung metastasis model on nude mice. Tumor size and weight were analyzed upon 5-Fu treatment. Metastatic nodules on lungs were evaluated. Immunohistochemical and TUNNEL assays were performed on slides obtained from tumor tissues. ResultsMTAP overexpression inhibited expression of CD133 and colony formation, which is further ablated by MTAP inhibitor. MTAP deprivation augmented stemness and colony formation, which is reversed by protein arginine methyltransferase 5 (PRMT5) overexpression but not its catalytically inactive counterparts. Critically, SRY-box transcription factor 2 (SOX2) was found to be a downstream regulator of MTAP/PRMT5, leading to stemness of liver cancer cells. MTAP overexpression suppressed SOX2 expression, while MTAP inhibition augmented expression of SOX2. Critically, MTAP overexpression inhibited migration and invasion of liver cancer cells. In vivo experiments in animal model found that MTAP deprivation promotes tumor growth and metastatic nodules of liver cancer. Additionally, MTAP overexpression inhibits tumor growth. Moreover, MTAP deprivation contributes to chemoresistance shown by increased tumor size and weight treated by 5-Fu. In contrast, MTAP overexpression led to further decline in tumor size and weight elicited by 5-Fu treatment. Accordingly, SOX2 was inhibited in tumor tissues after MTAP overexpression. Marker of proliferation Ki67 (Ki67) expression was dampened while apoptosis was found in MTAP-overexpressed tumor tissues. ConclusionIn this study, plethora of experimental studies collectively demonstrated that MTAP deprivation enhances stemness of liver cancer by regulating SOX2, exerting anti-cancer and chemoresistant role against 5-Fu in liver cancer. It is also worth noting that MTAP inhibition promoted metastasis of liver cancer. MTAP overexpression augmented tumor shrinking elicited by 5-Fu and SOX2 was involved in this process. These results concluded that MTAP/PRMT5/SOX2 signaling axis was involved in regulating stemness and chemoresistance of liver cancer. These findings help to exploit novel therapies by targeting stemness in MTAP-depleted liver cancer. It shed novel light on unveiling MTAP-regulated stemness in antagonizing 5-Fu treatment in liver cancer. It also adds mounting evidence to the theoretical basis for accomplishing personalized chemotherapy of liver cancer patients by targeting MTAP or its downstream PRMT5/SOX2.

Objective To explore the correlation of traditional Chinese medicine(TCM)syndrome elements with language function and activities of daily living(ADL)in patients suffering post-stroke aphasia(PSA).Methods Ninety-eight PSA patients hospitalized at the College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine from April 2023 to April 2024 were selected.The language function,TCM syndrome elements,and their correlations were analyzed.Results(1)Among PSA patients,males outnumbered females.PSA patients exhibited different performances on various aphasia-related scales,with language impairments mainly concentrated in naming and spontaneous speech.(2)The distribution of TCM syndrome elements varied in PSA patients with different age groups.In the age group＜50 years old,qi obstruction(100.00%),phlegm syndrome(100.00%),and dampness syndrome(100.00%)were predominant.In the age group of 50-59 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.30%)were predominant.In the age group of 60-69 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.15%)were also predominant.In the age group of 70-79 years old,qi deficiency syndrome(100.00%)was predominant.In the age group of 80-89 years old,syndromes such as qi insecurity,qi obstruction,qi deficiency,phlegm,yang hyperactivity,blood stasis,wind stirring,and blood cold were concentrated(all 100.00%).However,there were no statistically significant differences in the distribution of TCM syndrome elements among various age groups(P＞0.05).(3)The distribution of deficiency and excess syndrome elements varied in PSA patients with different genders.Among deficiency syndrome elements,yang hyperactivity,qi deficiency,and yin deficiency were predominant in males,while yang hyperactivity,qi deficiency,and blood deficiency were predominant in females.Among excess syndrome elements,phlegm syndrome,qi obstruction,and dampness syndrome were predominant in males,while phlegm syndrome,qi obstruction,and qi stagnation syndrome were predominant in females.However,there were no statistically significant differences in the distribution of deficiency and excess syndrome elements between genders(P＞0.05).(4)After controlling the factors of age group and gender,partial correlation analysis of syndrome elements and language function showed that among the disease-location syndrome elements,spontaneous naming(r=-0.588,P=0.027)and sematic cued naming(r=-0.558,P=0.038)in the Boston Naming Test(BNT)were negatively correlated with the large intestine;among the disease-nature syndrome elements,BNT sematic cued naming(r=0.821,P＜0.001)was positively correlated with qi sinking,while BNT spontaneous naming was negatively correlated with blood heat(r=-0.544,P=0.044)and was positively correlated with fluid depletion(r=0.860,P=0.028);BNT recognitive naming was positively correlated with external wind(r=0.966,P=0.034);errors in BNT sematic cued naming were negatively correlated with qi sinking(r=-0.540,P=0.005);the Modified Barthel Index(MBI)was positively correlated with essence deficiency(r=0.572,P=0.021).Conclusion The TCM syndrome elements of phlegm,qi block,yang hyperactivity,and qi deficiency are commonly seen in PSA patients.There is a certain correlation of language function and ADL with TCM syndrome elements in PSA patients.

Objective To investigate the association between rest-activity rhythm(RAR)and the risks of rheumatoid arthritis(RA),and to evaluate whether genetic susceptibility modifies this relationship.Methods This prospective cohort study utilized data from the UK Biobank,including 88 060 participants who did not have RA at baseline.RAR parameters(e.g.,relative amplitude)were calculated using data obtained through wrist-worn accelerometers.The participants'genetic susceptibility to RA was assessed using a polygenic risk score.Cox proportional hazards models were employed to analyze the association between RAR and RA risk,with interaction terms incorporated to evaluate the effect modification by genetic susceptibility.Results Over a median follow-up period of 7.97 years,660 incident RA cases were identified.After adjusting for age,sex,ethnicity,educational attainment,Townsend deprivation index,drinking status,smoking status,dietary score,body mass index,and polygenic risk score for incident RA,the dose-response analysis revealed a linear relationship between the RAR-related parameters,including the average amplitude during the most active 10 h(M10),interdaily stability(IS),intradaily variability(IV),and the risk of developing RA(P>0.05).In contrast,relative amplitude and the average amplitude during the least active 5 h(L5)showed a nonlinear relationship with the risk of developing RA(P<0.05).Compared to those in the the highest quartile of relative amplitude,participants in the lowest quartile had a 49%increase in the risk of developing RA(hazard ratio[HR]=1.49;95%CI,1.17-1.90).Compared to those in the lowest quartile,participants in the highest quartile of L5 had a 40%increased risk of developing RA(HR=1.40;95%CI,1.12-1.75).Every time M10 increased by one standard deviation,the risk of developing RA decreased by 12%(HR=0.88;95%CI,0.80-0.96).No evidence of effect modification by genetic susceptibility was observed in the RAR-RA association(P>0.05).Conclusion Disrupted rest-activity rhythm is associated with an increased risk of RA,which is independent of genetic susceptibility to RA.Our findings suggest that improving rest-activity rhythm may help reduce RA risks.