ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis（RA） and traditional Chinese medicine（TCM） syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide， in which general information such as name， gender， age， height， body weight， and course of disease were collected by completing a questionnaire； patients were classified into eight types of syndrome according to the information of their four examinations，i.e. wind-dampness obstruction syndrome， cold-dampness obstruction syndrome， dampness-heat obstruction syndrome， phlegm-stasis obstruction syndrome， stasis-blood obstructing collateral syndrome， qi-blood deficiency syndrome， liver-kidney insufficiency syndrome， and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events， they were divided into the occurrence group and the non-occurrence group， and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events， and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included， including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height， gender， insomnia， appetite， white blood cell（WBC）， hemoglobin（HGB）， platelets（PLT）， rheumatoid factor（RF）， anti-cyclic peptide containing citrulline（CCP）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， γ-glutamyl transpeptidase（GGT）， urea creatinine（CREA）， and glucose（GLU）（P＞0.05）. The TCM syndromes between groups showed significant statistic differences（P＜0.05）. Patients in occurrence group had longer disease duration， heavier body weight， and older age； more severe conditions such as disease activity（DAS-28）， number of painful joints（TJC）， number of swollen joints（SJC）， health questionnaire scores（HAQ）， visual analog scores（VAS）， restlessness， and fatigue； higher blood sedimentation rate（ESR）， low-density lipoprotein（LDL-C）， triglyceride（TG）， total cholesterol（TC）， D-Dimer， and lower high-density lipoprotein（HDL-C）（P＜0.05）. The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome［OR=5.937， 95%CI （4.434， 7.949）， P＜0.001］. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes， and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To evaluate the association between the preoperative aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and postoperative delirium (POD) in patients undergoing total knee/hip arthroplasty.Methods:In this nested case-control study, medical records from patients, aged ≥55 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with Mini-Mental State Examination (MMSE) scale score >24 on preoperative day 1, scheduled for elective total knee/hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between November 2021 and December 2023, were collected. POD was assessed using the Confusion Assessment Method. Patients were categorized into POD and non-POD groups based on the occurrence of POD. Logistic regression was employed to identify protective and risk factors for POD. The predictive performance of preoperative AST/ALT ratio alone and its combination with cerebrospinal fluid (CSF) biomarker concentrations for POD was evaluated using receiver operating characteristic curves, and the clinical utility of the prediction models was assessed using decision curve analysis. Mediation analysis was conducted to examine the mediation role of CSF biomarkers in the relationship between the preoperative AST/ALT ratio and POD. Restricted cubic splines were used to assess the nonlinear relationship between the preoperative AST/ALT ratio and POD.Results:A total of 460 patients were finally included, with 49 in POD group and 411 in non-POD group. After adjustment for multiple confounding factors including age, sex, educational level, MMSE score, history of hypertension, history of diabetes, history of smoking and history of alcohol use, multivariable logistic regression identified that the higher preoperative AST/ALT ratio, CSF total tau protein (t-tau) and phosphorylated tau protein (p-tau) concentrations were independent risk factors for POD, whereas lower CSF β-amyloid 42 (Aβ 42) concentration, Aβ 42/t-tau ratio and Aβ 42/p-tau ratio served as protective factors ( P<0.05). The area under the receiver operating characteristic curve of the preoperative AST/ALT ratio combined with CSF biomarkers in predicting POD was 0.939 ( P<0.001), demonstrating high clinical efficacy. After adjusting for age, educational level, sex, MMSE score, history of hypertension, history of diabetes, history of smoking, history of alcohol use and body mass index, restricted cubic splines revealed a nonlinear relationship between preoperative AST/ALT levels and the probability of POD, and the probability of POD increased with rising ratios when the preoperative AST/ALT ratio ranged from 1.09 to 1.40 ( Poverall < 0.05, Pnonlinear <0.05). After stratification by sex, the preoperative AST/ALT ratio demonstrated a linear relationship with the probability of POD ( Poverall <0.05, Pnonlinear>0.05). Mediation analysis indicated that the relationship between the preoperative AST/ALT ratio and POD was partially mediated by CSF p-tau concentration (proportion mediated 18.1%), CSF t-tau concentration (proportion mediated 12.0%), and the Aβ 42/t-tau ratio (proportion mediated 15.4%). Conclusions:A higher preoperative AST/ALT ratio is an independent risk factor for POD in total knee/hip arthroplasty patients. The concentrations of CSF t-tau and p-tau and Aβ 42/t-tau ratio have a mediating role in the relationship between the preoperative AST/ALT ratio and POD.

Systemic lupus erythematosus （SLE） may lead to secondary gynecological and obstetric disorders such as decreased ovarian reserve function， menstrual abnormalities， and adverse pregnancy outcomes. Based on "bi （痹） of both body and viscera" theory， this paper proposed that the core mechanism of SLE secondary gynecological and obstetric diseases lies in the mutual transformation between "body bi" and "viscera bi"， which together affect the uterus. Physiologically， uterus forms an internal-external network with the body and viscera through the meridians and blood vessels. Pathologically， when the healthy qi is deficient， nourishment of the body and viscera is impaired； when toxins and stasis accumulate， pathogenic factors disturb the uterus through the chong （冲） and ren （任） meri-dians. The resulting obstruction in the uterus can， in turn， manifest externally and aggravate damage to the body and viscera. Therefore， the pathogenesis of SLE secondary gynecological and obstetric diseases follows a dynamic trajectory of "body bi first， body bi affecting viscera， and then bi of both body and viscera". In treatment， the principle of harmonizing and balancing the healthy qi is emphasized. The main approach is to regulate the viscera， stabilize the body， and nourish the uterus， with the coordination of nourishing the viscera through the body， thereby achieving simultaneous treatment of both body and viscera. This highlights the guiding significance of the "bi of both body and viscera" theory in preventing and treating SLE secondary gynecological and obstetric diseases.

ObjectiveTo investigate the syndrome evolution patterns， characteristics of the used herbal medicinals， and efficacy variations across different stages of rheumatoid arthritis （RA） progression. MethodsBased on the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine （CERTAIN）， 2,506 RA patients were retrospectively enrolled and categorized into ＜6 months group （166 cases）， 6 months to ＜5 years group （1063 cases）， 5 to ＜20 years group （1067 cases）， and ≥20 years group （210 cases）. Syndromes were differentiated before and after traditional Chinese medicine （TCM） treatment， including damp-heat obstruction， wind-damp obstruction， cold-damp obstruction， blood stasis obstructed in the collaterals， phlegm-stasis obstruction， liver-kidney insufficiency， qi and blood deficiency， and qi-yin deficiency. The syndrome evolution rate was calculated for high-frequency syndromes before and after treatment. Analysis was conducted on top 20 frequently used Chinese herbs at the first diagnosis. Clinical efficacy of the 28-joint disease activity score based on erythrocyte sedimentation rate （DAS28-ESR） and 28-joint disease activity score based on C-reactive protein （DAS28-CRP） before and after treatment were assessed. A multivariate logistic regression analysis was performed to identify factors affecting the efficacy of TCM treatment. ResultsPatients with course of disease shorter than 6 months predominantly presented with cold-dampness obstruction syndrome （49/166， 29.5%）， wind-dampness obstruction syndrome （46/166， 27.7%）， and dampness-heat obstruction syndrome （43/166， 25.9%）. For patients with course of disease logner than 6 months and shorter than 5 years and those within 5 to 20 years， the dominant syndrome was dampness-heat obstruction syndrome （324/1063， 30.5% and 318/1067， 29.8%， respectively）. In patients with disease duration ≥20 years， liver-kidney insufficiency syndrome and dampness-heat obstruction syndrome both predominated， each accounting for 25.24% （53/210）. The syndromes with more than 100 cases before treatment and a syndrome evolution rate greater than 10% after treatment were dampness-heat obstruction （201/738， 27.2%）， liver-kidney insufficiency （119/367， 32.4%）， and phlegm-stasis obstruction syndromes （73/172， 42.4%）. These were classified as high-frequency syndromes. After treatment， damp-heat obstruction syndrome and liver-kidney insufficiency syndrome primarily evolved into wind-damp obstruction syndrome， while phlegm-stasis obstruction syndrome evolved into damp-heat obstruction and cold-damp obstruction syndrome. The top two commonly used Chinese herbs across all groups were Gancao （Radix et Rhizoma Glycyrrhizae） and Baishao （Radix Paeoniae Alba）. In the ＜6 months group and the 6 months to ＜5 years group， high-frequency herbs also included Fangfeng （Radix Saposhnikoviae）， Duhuo （Radix Angelicae Pubescentis）， Chuanxiong （Rhizoma Chuanxiong）， and Qianghuo （Radix et Rhizoma Notopterygii）. In the 5 to ＜20 years group and the ≥20 years group， the usage of Huangqi （Radix Astragali）， Fuling （Poria）， Niuxi （Radix Achyranthis Bidentatae）， and Danggui （Radix Angelicae Sinensis） increased， while the proportion of Fangfeng and Duhuo decreased. After treatment， the DAS28-ESR and DAS28-CRP scores in all groups significantly decreased （P＜0.05）. There were statistically significant differences in clinical efficacy based on DAS28-ESR and DAS28-CRP across all groups （P＜0.01）. Multivariate logistic regression revealed significantly reduced treatment efficacy in the 6 months-5 years group （OR=0.4）， 5~20 years group （OR=0.5）， and ≥20 years group （OR=0.4） compared to the ＜6 months group. ConclusionRA syndromes follow a progression pattern from excess to deficiency， with corresponding transition in herbal usage from pathogen-eliminating to healthy qi-reinforcing approaches. TCM intervention can significantly reduce disease activity of RA， with superior efficacy in patients with disease duration shorter than 6 months.

Objective To investigate the effects of 3-methyladenine(3-MA)on mouse mesangial cell line MES-13 cultured in high glucose,and on the kidney of streptozotocin(STZ)-induced mouse model of diabetes and the po-tential mechanism.Methods MES-13 cells were divided into low glucose control group(LG),hyper osmotic pres-sure control group(HOP),high glucose group(HG),3-methyladenine+high glucose group(HG+3-MA)and chloroquine+high glucose group(HG+CQ).The groups were respectively incubated with low glucose DMEM,30 mmol/L mannitol hypertonic control medium,30 mmol/L high glucose medium,5 mmol/L 3-MA+30 mmol/L high glucose medium and 10 mmol/L CQ+30 mmol/L high glucose medium for 24 hours.CCK-8 assay and Western blot were performed.In vivo experiment:Male C57BL/6J mice were induced diabetes for model development by in-tra-peritoneal injection of STZ 60 mg/kg for five consecutive days.After two weeks of injection,the blood glucose was measured.Animals with blood glucose level higher than 16.7 mmol/L(250 mg/dL)were randomly divided in-to diabetes control group(DM),3-MA intervention group(DM+3-MA)and CQ intervention group(DM+CQ),then were fed under the same conditions as normal control group(NC)mice.The DM+3-MA group was given 10 mg/kg of 3-MA aqueous solution by gavage every day,the DM+CQ group was given 50 mg/kg of CQ by intrap-eritoneal injection every three days,the NC group and DM group were given the same amount of normal saline and killed after 6 weeks.The kidneys were stripped for kidney/body weight ratio determination,periodic acid-schiff staining(PAS),MASSON staining microscopy and Western blot.Results In vitro experiment:Compared to the LG group,the cell viability,PCNA expression,ratio of phosphorylated Akt to total Akt(p-Akt/Akt)and ratio of phosphorylated rpS6 to total rpS6(p-rpS6/rpS6)were significantly increased in the HG group(P＜0.05).Com-pared with HG group,the cell viability,PCNA and p-Akt/Akt ratio of HG+3-MA group and HG+CQ group were significantly decreased and p-rpS6/rpS6 ratio of HG+3-MA group was significantly decreased(P＜0.01).In vivo experiment:Compared to NC group,the kidney/body weight ratio,glomerular volume,renal tubular injury index,PCNA,fibronectin,COL1A1,p-Akt/Akt,p-rpS6/rpS6 in DM group were all significantly up-regulated(P＜0.05).Compared with DM group,the kidney/body weight ratio,glomerular volume,renal tubular injury in-dex,PCNA,fibronectin,COL1A1,p-Akt/Akt,p-rpS6/rpS6 of DM+3-MA group mice were all significantly de-creased(P＜0.05).Conclusions 3-MA can improve glomerular mesangial cell proliferation and renal ECM deposi-tion in early diabetes nephropathy(DN).The improvement of 3-MA in early DN may be related to the inhibition of Akt/rpS6 signaling pathway.

Objective:To explore the anal function and postoperative complications of 2-stage Turnbull-Cutait pull-through coloanal anastomosis (TCA) for low rectal cancer.Methods:Patients undergoing radical rectal cancer resection from Feb 2023 to Nov 2024 in the First Hospital of Jilin University were divided into the TCA surgery group and the low anterior resection combined with prophylactic stoma (LAR) surgery group.Results:Among the 102 patients, there were 50 cases in the TCA group and 52 cases in the LAR group. In the single-arm analysis of the TCA group, the overall complication rate was 44%. The incidence rates of severe LARS at 1 month, 3 months, and 6 months after surgery were 97%, 77%, and 64% respectively. There was no significant difference in the complication rate within 30 days after surgery between the two groups,(44% vs. 38%, χ2=0.135, P>0.05). There was no significant difference in the incidence rate of severe LARS between the TCA group and the LAR group (77% vs. 69%, χ2=0.202, P>0.05), and there was not significant difference in the incidence rate of severe LARS between the two groups at the 6th month after surgery,(64% vs. 48%, χ2=1.132, P>0.05). Conclusion:In patients who underwent TCA surgery, the LARS symptoms gradually decreased over time. Compared with patients undergoing low anterior resection and stoma reversal, there were no significant differences in complications within 30 days after surgery and LARS symptoms within half a year.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.

Suppressor of cytokine signaling 3(SOCS3),a member of SOCS family,plays a major role in cell signaling trans-duction.SOCS3 is important in regulation of immune homeostasis and also involved in the control of energy metabolism,mainly through regulating JAK/STAT pathway.Recent studies have shown that SOCS3 was closely associated with glycolipid metabolic diseases like diabetes and obesity,and can be used as a new target for treatment of these glycolipid metabolic diseases.This review focuses on the latest research progress of the role and mechanism of SOCS3 in glycolipid metabolic diseases,and discusses the possibility of SOCS3 as a therapeutic target for glycolipid metabolic diseases.