BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

BACKGROUND:Forskolin,a diterpenoid natural compound extracted from Coleus forskohlii,has a crucial regulatory role in skeletal muscle repair.However,the regulatory role of forskolin on myogenic differentiation of C2C12 skeletal muscle cells has not been fully explored.OBJECTIVE:To explore the effects of forskolin on the differentiation of C2C12 myoblast cell line and probe into the underlying molecular mechanisms.METHODS:C2C12 cells were treated with 0,0.1,0.25,0.5,1,5,10 and 20 μmol/L forskolin during growth,and cell proliferation was detected by cell counting kit-8 and qRT-PCR.C2C12 cells were treated with 0,0.25,0.5 and 1 μmol/L forskolin during the induction of myogenic differentiation.Immunofluorescence staining and qRT-PCR were used to detect C2C12 cells differentiation.Western blot was used to detect the expression level of myogenic differentiation-related signaling pathway proteins.RESULTS AND CONCLUSION:(1)The viability of C2C12 cells was decreased and cell proliferation was inhibited after treatment with high concentrations(＞1 μmol/L)of forskolin.(2)The qRT-PCR results showed that forskolin up-regulated the expression of Myh2,Myh4,Myomaker,but down-regulated the expression of Myh7 compared with the 0 μmol/L group,when C2C12 cells were differentiated for 4 days.Immunofluorescence staining results showed that the fusion index and myotube diameter of C2C12 cells were increased after forskolin treatment,and the number of myotubes was also increased.(3)Western blot results showed that the phosphorylated extracellular signal-regulated kinase 1/2 expression was inhibited;however,the phosphorylated protein kinase B was promoted after treatment with forskolin.The protein expression level of the myogenic differentiation transcription factor Myogenin was significantly up-regulated after treatment with forskolin.The above results demonstrate that forskolin may promote myogenic differentiation of C2C12 skeletal muscle cells through the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathway.

OBJECTIVE:Some studies have shown that physical exercise can effectively improve knee extensor strength and cardiorespiratory function in burn patients;some studies have also shown that physical exercise is not effective in improving respiratory function in burn patients.Improvement effects of physical exercise on physical functions(muscle function,walking function,cardiopulmonary function,and lean body mass)of burn patients were evaluated by a systematic evaluation and meta-analysis.METHODS:Based on databases including Web of Science,PubMed,Embase,Cochrane Library,CNKI,WanFang,and the Chinese Biomedical Database,literature on the improvement of physical function in burn patients through physical exercise was searched using subject headings and free terms.With muscle function,walking ability,cardiopulmonary function,and lean body mass as the primary outcome measures,a meta-analysis was conducted to compare the efficacy of physical exercise with traditional physical therapy or conventional care methods.RESULTS:A total of 38 papers were included,of which 26 papers were included in the meta-analysis,involving 1 658 patients.Meta-analysis results showed that:(1)Physical exercise significantly enhances the knee extensor strength of the dominant leg in burn patients(mean difference[MD]=8.34,95％confidence interval[CI]:6.95-9.72,P＜0.000 01),increases quadriceps strength,peak oxygen uptake,forced vital capacity and maximum ventilation volume in 1 second,and resting heart rate(standardized mean difference[SMD]=4.41,95％CI:2.52-6.30,P＜0.000 01;MD=4.91,95％CI:3.52-6.29,P＜0.000 01;MD=5.86,95％CI:0.09-11.63,P=0.05;MD=6.90,95％CI:2.93-10.87,P=0.000 7;MD=5.03,95％CI:1.45-8.61,P=0.006),and improves the 6-minute walking distance,gait parameters,and total lean body mass(MD=45.29,95％CI:24.7-65.89,P＜0.0001;SMD=7.84,95％CI:6.05-9.63,P＜0.000 01;MD=2.47,95％CI:2.01-2.93,P＜0.000 01).(2)The subgroup analysis results indicated that the improvement in knee extensor strength of the dominant leg may be better in children than in adults and better in the extra-heavy group than in the heavy group.Improvement in the 6-minute walking distance is better in children than in adults,and higher degree of burn indicates better improvement effects,with no difference from the control group for＜12 weeks.Peak oxygen uptake may be better in adults and severe burn groups than in children and moderate burn groups,resistance combined with aerobic exercise modalities may be better than aerobic exercise alone,and exercise duration＞60 minutes may be better than＜60 minutes.CONCLUSION:Physical activity is effective in improving physical function in burn patients,as evidenced by improvements in muscle strength,walking ability,cardiorespiratory fitness,and lean body mass.The quality of evidence recommended for all indicator results is moderate or below,with imprecision and inconsistency being the main factors for downgrading.Therefore,more high-quality randomized controlled trials are needed in the future to verify the reliability of the results.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

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 explore risk factors of sodium-dependent glucose transporters 2 （SGLT2） inhibitor-associated euglycemic diabetic ketoacidosis （euDKA） and to construct a risk prediction model. Methods A retrospective analysis was performed on the clinical data of type 2 diabetes patients treated with SGLT2 inhibitors in Dongnan Hospital of Xiamen University from January 2020 to December 2023, including age, gender and course of diabetes. The risk factors of SGLT2 inhibitor-associated euDKA were analyzed by univariate analysis and multivariate Logistic regression, and a prediction model was established. According to the receiver's operating characteristic （ROC） curve, the area under the curve （AUC） and the optimal critical value of the prediction model were determined. The prediction model was subjected to both internal and external validation. Results A total of 119 patients with type 2 diabetes treated with SGLT2 inhibitors were included in this study. Among them, there were 98 cases without euDKA （non-euDKA group）and 21 cases with euDKA （euDKA group）. Multivariate Logistic regression analysis showed the DKA history (OR=114.153), appetite or diet decreased three days before admission (OR=21.774), elevated neutrophil count (OR=2.056) and pre-hospital adjustment of hypoglycemic agents (OR=45.745) were independent factors to increase risks of euDKA associated with SGLT2 inhibitors （P<0.05）. Surgical history before admission was an independent factor to reduce this risk （OR=0.007, P<0.05）. By establishing the calculation formula of the prediction model = neutrophil count+6.571 （DKA history）−6.874 （surgical history before admission）+4.273 （appetite or diet decreased three days before admission）+5.302 （pre-hospital adjustment of hypoglycemic drugs）, the ROC curve was drawn. The AUC of the ROC of the prediction model was 0.982 （95%CI: 0.961-1.000, P<0.001）, with accuracy of 94.96%, sensitivity of 0.905, specificity of 0.959 and a critical value of 7.405. The AUC of ROC curve after the model’s ten-fold cross validation was 0.930. And the accuracy of the external validation of the prediction model was 85.29%. Conclusion The DKA history, appetite or diet decreased three days before admission, elevated neutrophil count and pre-hospital adjustment of hypoglycemic agents increased the risk of SGLT2 inhibitor-associated euDKA, while the surgical history before admission reduced this risk. The risk prediction model constructed on this basis could better predict the risk of SGLT2 inhibitor-associated euDKA.