OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

ObjectiveTo evaluate the comprehensive intervention effects of Huangqin Qingre Chubi Capsule （黄芩清热除痹胶囊， HQC） on self-perception of patients （SPP） and immune inflammation in patients with rheumatoid arthritis （RA）， and to explore its potential mechanisms. MethodsClinical data of 452 RA patients were retrospectively collected. Patients were divided into a control group （274 cases）， treated with conventional western medicine， and an observation group （178 cases）， treated with HQC for at least 2 weeks in addition to conventional western medicine. The treatment duration was 2 weeks for both groups. Propensity score matching （PSM） was performed at a ratio of 1∶1 to match patients between groups. SPP including the Chinese version of the short form-36 health survey （SF-36）， self-rating anxiety scale （SAS）， self-rating depression scale （SDS）， visual analog scale （VAS）， and Chinese patient-reported index for rheumatoid arthritis （CPRI-RA）， as well as immune inflammatory indicators， including erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide antibody （anti-CCP）， interleukin-6 （IL-6）， immunoglobulin A （IgA）， immunoglobulin G （IgG）， immunoglobulin M （IgM）， complement C3， and complement C4， were collected before and after treatment. Spearman correlation analysis was used to assess the relationships between SPP and immune inflammatory indicators. Logistic regression， association rule analysis， and mediation analysis were performed to evaluate the effects and potential pathways of HQC on SPP and immune inflammatory indicators. Network pharmacology was applied to identify the active components and core targets of HQC in the treatment of RA， followed by molecular docking verification. In cell experiments， cells were divided into normal group， model group， 20% medicated serum group， and 80 nmol/L control group. Human synovial fibroblasts （FLS） were cultured with complete medium in the normal group， while human rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were cultured in the model group. In the 20% medicated serum group， RA-FLS were cultured with medium containing 20% HQC-medicated serum， and in the 80 nmol/L control group， RA-FLS were cultured with complete medium containing 80 nmol/L methotrexate suspension. After 48 h of culture， cell viability was detected by cell counting kit-8 （CCK-8） assay. Levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and interleukin-10 （IL-10） in the cell supernatant were measured by enzyme-linked immunosorbent assay （ELISA）. Protein levels of matrix metalloproteinase 9 （MMP9）， transcription factor AP-1 subunit （JUN）， vascular endothelial growth factor A （VEGFA）， and C-X-C motif chemokine ligand 8 （CXCL8） were detected by Western Blot， and cell migration ability was evaluated using Transwell assay. ResultsAfter PSM， 178 cases were included in each group. After treatment， SF-36 scores increased， while scores of SAS， SDS， VAS and CPRI-RA， levels of ESR， hs-CRP， IL-6， complement C3， and complement C4 levels decreased in both groups； IgG and IgM levels were also reduced in the observation group （P＜0.05）. Physical functioning （correlation coefficient -0.19， P＜0.05） and social functioning （correlation coefficient -0.18， P＜0.05） of SF-36 were negatively correlated with hs-CRP， while VAS score was positively correlated with hs-CRP （correlation coefficient 0.19， P＜0.05）. HQC showed high associations with improvements in multiple indicators of SPP and immune inflammatory， and acted as a protective factor for the improvement of several SPP； hs-CRP and ESR played partial mediating roles in the improvement of SPP induced by HQC （P＜0.05）. Network pharmacology analysis identified baicalein， quercetin， α1-sitosterol， β-sitosterol， stigmasterol， baicalin， and crocetin as the core active components， and JUN， IL-6， VEGFA， MMP9， IL-1β， and CXCL8 as the core targets. Molecular docking results showed strong binding affinities of quercetin with VEGFA， JUN， MMP9， IL-6， and IL-1β， of baicalin with VEGFA and MMP9， and of wogonin with CXCL8. Cell experiments demonstrated that HQC and methotrexate inhibited RA-FLS viability and migration， reduced levels of IL-1β， IL-6， and IL-8， decreased protein levels of MMP9， JUN， VEGFA， and CXCL8， and increased IL-10 levels （P＜0.05）. ConclusionHQC can improve SPP in RA by regulating immune inflammatory responses. Its mechanism may be related to multi-pathway and multi-target inhibition of synovial cell inflammation and migration.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Objective To investigate status of postoperative kinesiophobia in patients with ankle fracture and to identify the factors influencing kinesiophobia,thereby offering references for developing targeted nursing interventions.Methods A cross-sectional study was conducted between June 2023 and May 2024.With convenience sampling,338 first-time ankle fracture patients who received surgical treatment were recruited from a Tier-IIIA orthopaedic hospital in Xinjiang.Data was collected among the patients at 24 hours after surgery through the general information questionnaire,kinesiophobia scoring scale,pain visual analogue scale,hospital anxiety and depression scale,social support rating scale and general self-efficacy scale.Logistic regression was employed to identify factors influencing kinesiophobia.Results A total of 320 patients completed the study.The prevalence among the patients with kinesiophobia was 38.1%,and scored at(39.6±1.5).Logistic regression analysis identified that the pain,social support and self-efficacy were the independent risk factors of kinesiophobia(all P<0.05).Conclusion Patients with ankle fractures have a high prevalence of postoperative kinesiophobia.Pain,social support and self-efficacy are the key factors that influence kinesiophobia.Intervention strategies should be adopted in response to the influencing factors in order to promote the recovery of patients.

Objective:To investigate the association of skeletal muscle function(including muscle strength and physical performance) and insulin resistance as well as type 2 diabetes mellitus(T2DM).Methods:The retrospective study included 942 patients who visited the Department of Geriatrics at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between October 2020 and July 2024. Low skeletal muscle function was defined as either reduced muscle strength or impaired physical performance. Muscle strength was assessed by grip strength, while physical performance was evaluated using the 5-time chair stand test. The associations between muscle function, insulin resistance, and T2DM were analyzed.Results:A significant association was observed between decreased skeletal muscle function and a higher prevalence of T2DM( P=0.001). Further analysis revealed that decreased physical performance was significantly associated with increased T2DM prevalence( P<0.001), whereas reduced muscle strength showed no significant association with T2DM prevalence( P=0.331). Linear regression analysis indicated that both the homeostasis model assessment of insulin resistance(HOMA2-IR) and fasting blood glucose levels increased significantly with longer chair stand times( P<0.05). Restrictive cubic spline(RCS) analysis demonstrated a nonlinear relationship between chair-rising time and HOMA2-IR. Notably, when the cumulative chair-rising time exceed 8.1 s, HOMA2-IR increased significantly with prolonged chair stand time. Logistic regression analysis showed that compared with patients with normal physical performance, those with decreased physical performance had significantly higher odds of T2DM( OR=2.64, P<0.001) and insulin resistance( OR=2.34, P=0.002). Conclusion:Decline in physical performance is significantly positively associated with insulin resistance and the risk of T2DM. Morever, when the cumulative chair stand time exceed 8.1 s, HOMA2-IR increases progressively with further prolongation of chair stand time.

Objective To investigate the incidence and risk factors of dysphagia in patients after re-cent small subcortical infarction(RSSI).Methods A total of 188 RSSI patients admitted to our department from May 2018 to May 2024 were enrolled,and according to Gugging swallowing screen(GUSS),they were divided into dysphagia group(GUSS score≤19,n=51)and non-dysphagia group(the score=20,n=137).The clinical manifestations and imaging data were com-pared between the two groups.Results When compared with the non-dysphagia group,the dys-phagia group had significantly older age,larger proportion of dysarthria,higher NIHSS and mRS scores,larger lesion diameter,higher incidence of pontine infarction,and higher scores of periven-tricular and deep white matter hyperintensities,but lower scores of mini-mental state examination and Montreal cognitive assessment(P＜0.05,P＜0.01).Binary logistic regression analysis showed that age,dysarthria,NIHSS score,lesion diameter,and pontine infarction were risk factors for dysphagia in RSSI patients(OR=1.203,95％CI:1.070-1.352;OR=34.464,95％CI:5.013-236.942;OR=4.579,95％CI:2.180-9.617;OR=0.623,95％CI:0.463-0.838;OR=0.020,95％CI:0.002-0.191,P＜0.01).Conclusion For RSSI patients,especially those with older age,larger lesion diameter,dysarthria,severe neurological deficits,and pontine infarction,clinicians should be alert to the occurrence of dysphagia in order to avoid serious complications.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Objective To investigate the incidence and risk factors of dysphagia in patients after re-cent small subcortical infarction(RSSI).Methods A total of 188 RSSI patients admitted to our department from May 2018 to May 2024 were enrolled,and according to Gugging swallowing screen(GUSS),they were divided into dysphagia group(GUSS score≤19,n=51)and non-dysphagia group(the score=20,n=137).The clinical manifestations and imaging data were com-pared between the two groups.Results When compared with the non-dysphagia group,the dys-phagia group had significantly older age,larger proportion of dysarthria,higher NIHSS and mRS scores,larger lesion diameter,higher incidence of pontine infarction,and higher scores of periven-tricular and deep white matter hyperintensities,but lower scores of mini-mental state examination and Montreal cognitive assessment(P＜0.05,P＜0.01).Binary logistic regression analysis showed that age,dysarthria,NIHSS score,lesion diameter,and pontine infarction were risk factors for dysphagia in RSSI patients(OR=1.203,95％CI:1.070-1.352;OR=34.464,95％CI:5.013-236.942;OR=4.579,95％CI:2.180-9.617;OR=0.623,95％CI:0.463-0.838;OR=0.020,95％CI:0.002-0.191,P＜0.01).Conclusion For RSSI patients,especially those with older age,larger lesion diameter,dysarthria,severe neurological deficits,and pontine infarction,clinicians should be alert to the occurrence of dysphagia in order to avoid serious complications.

Objective To explore the hearing characteristics and early screening methods of hearing loss in diabetes mellitus(DM)patients.Methods From September 2022 to November 2023,800 DM patients in the Department of Endocrinology in People's Liberation Army General Hospital of Southern Theater Command were enrolled.According to the results of electrical audiometry,they were divided into a normal hearing DM group(n=214)and a hearing loss group(n=586).Binary logistic regression was used to analyze the influencing factors of hearing loss in DM patients.Results Age,homeostasis model assessment of insulin resistance(HOMA-IR),serum creatinine(Scr),urinary albumin/creatinine ratio(UACR)DM duration,hearing loss value,and proportion of DPN,DR,DKD,hypertension,coronary heart disease,perceived hearing loss,DPOAE abnormality and ABR abnormality in hearing loss group was higher than that in normal hearing group(P<0.05).DBP,homeostasis model insulin sensitivity index and estimated glomerular filtration rate(eGFR)were lower than those in normal hearing group(P<0.05).Logistic regression analysis showed that DM duration(OR 0.987,95%CI 0.987～1.002,P=0.001),eGFR(OR 0.974,95%CI 0.964～0.983,P=0.000),and hypertension(OR 0.659,95%CI 0.443～0.980,P=0.040)and coronary heart disease(OR 0.488,95%CI 0.246～0.968,P=0.040)were the influencing factors of hearing loss in DM patients.Conclusions Hearing loss is the complications of DM and is related to factors such as the DM duration.Given the insidious onset of hearing loss,DM patients should undergo a combined hearing screening using multiple methods in the early stage.