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.

Objective To establish the phylogenic relationships among genus Botrychium,and to develop better molecular markers,along with to gain better understanding of cytonuclear coordination patterns of RuBisCO enzyme,the current article sampled two species(e.g.Botrychium ternatum(Thunb.)Sw.and Botrychium virginianum(L.)Sw.),and applied sequencing approaches for the data mining.Methods The assembly results of chloroplast(cp)genomes from B.ternatum and B.virginianum were determined via de novo hybrid assemble approach with the help of short reads(Illumina)and long reads(PacBio and Nanopore).Then the phylogenic relationships of 18 fern species were reconstructed based on the protein coding sequences from the cp genome and the rbcS gene,which were fished out of the RNA-seq data from SRA database,respectively.Then the adaptive selection and co-evolutionary analysis were employed to investigate the evolutionary trajectories of rbcL(cp genome)and rbcS(nuclear genome)genes.Results The full length of cp genome in the two genus Botrychium species were determined as 139 063 bp(NC_060644)and 139 372 bp(OR609363).Then 92 SSR sites and 78 SSR sites were identified in the current two cp genomes,respectively.The collinearity analysis showed high relevant relationship between the current two species,and significant relationship within both species among the inverted repeats regions.The adaptation and coevolution investigations illustrated the following results:①Coevolution network exists between RBCL and RBCS subunits from the fern RuBisCO enzyme.②Positively selected sites were significantly detected among both rbcL and rbcS genes.③Two coevolutionary pair sites from the two genes(e.g.site 11 in RBCL and site 106 in RBCS)were significantly positively selected,which may demonstrate a molecular pattern for the fern species fine-tuning the RuBisCO enzyme during the long earth history via the cytonuclear coordination.Conclusion Our current research shed a new light on the phylogenetic relationship of the genus Botrychium among the fern backbone-tree and provided amount of cpSSR sites with the potential as molecular markers for further population study on B.ternatum and B.virginianum.Moreover,our adaptation and coevolution investigations on rbcL and rbcS genes might indicate that the underlying cytonuclear coordination between the organelle and nuclear in cell of fern species for fine-tuning the key photosynthesis enzyme RuBisCO to gain better fitness according to the changing environment of earth during the geologic time-scale.

Objective In this research,the documents in the field of plant tissue culture in the past decade were compared by the form of charts,and the possible reasons for these results were analyzed.The application of plant tissue culture in the field of medicinal plants was introduced in detail,and the shortcomings of its development were pointed out,in order to provide a reference for the future development of medicinal plant tissue culture.Methods The CNKI and WOS database were used as the data sources,the visual analysis software Bibliometrix,CiteSpace,and VOSviewer were used to analyze the study of plant tissue culture in the past decade.The publication,author,country,institution,citations,and keywords were visualized and discussed.And then,the results were retrieved by using medicinal plants as keywords,and focusing on medicinal plant tissue culture research.Results Within the scope of the study,902 publications in CNKI and 7658 publications in WOS were filtered out.The journals with the largest number of publications in medicinal plant tissue culture accounted for a relatively high proportion.The study reveals that the author of the largest number of Chinese publications,Wei Kunhua specializing in medicinal plants,whereas the most prolific author in English also dabbles in medicinal plants.The institutions with the most amount of publications mainly concerned on the establishment of tissue culture system in the medicinal plant tissue culture.In the issuing country,Chinese output occupies the first place.The hotspots of plant tissue culture research focus on the optimization of culture conditions,metabolomics and genomics in the research.Conclusion The domestic development in the field of plant tissue culture is lagging behind compared with that of foreign countries,and the cooperation and communication among various units should be strengthened;although domestic and foreign countries have paid attention to the medicinal plant tissue culture,most of research still remains in the basic application,and its development can be promoted by combining the research with multi-omics technology.

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 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.

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.

Chimeric antigen receptor-modified T(CAR-T)cell therapy,as a new type of cellular immunotherapy,has shown good clinical efficacy in the treatment of malignant hematological tumors,especially B-cell acute lympho-blastic leukemia.However,there are problems such as antigen loss and immune evasion in single-target selection,so multi-target therapy strategies are gradually gaining attention.Multi-target CAR-T can effectively avoid antigen escape caused by a single target by targeting multiple tumor-associated antigens at the same time,reduce the risk of recurrence,and is expected to improve the therapeutic effect.This paper primarily discusses the structural types of multi-target CAR-T cell therapy and its clinical trial applications in the treatment of B-cell acute lymphoblastic leu-kemia(B-ALL),aiming to provide future references for the treatment of B-ALL.

Objective To investigate the isokinetic muscle strength,balance ability and gait characteristics in patients with ankle fractures,providing references for the formulation of rehabilita-tion plans and the establishment of efficacy evaluation criteria.Methods Thirty-six patients with an-kle fracture were selected as experimental group,while 20 healthy individuals were recruited as con-trol group.The isokinetic muscle strength of the ankle and hip joints,balance ability,and gait char-acteristics of the two groups were measured and compared.Results At angular velocities of 60°/s and 120°/s,the relative peak torque of isokinetic muscle strength for hip abduction and extension in the experimental group was significantly lower than that in the control group(P＜0.05).Similarly,the relative peak torque of isokinetic muscle strength for ankle plantarflexion and dorsiflexion in the experimental group was also significantly lower than those in the control group(P＜0.05).The bal-ance instrument measurement indicators(length of center of gravity sway trajectory,peripheral area of center of gravity sway)in the experimental group were significantly greater than those in the control group(P＜0.05).The Tinetti Performance-Oriented Mobility Assessment(POMA)score in the ex-perimental group was significantly lower than that in the control group(P＜0.05).According to the Tinetti POMA scoring criteria,the proportion of individuals at risk of falling(Tinetti POMA score＜24)in the experimental group was significantly higher than that in the control group(P＜0.05).The range of motion of the affected hip joint,stride length,and walking speed during the gait cycle in the experimental group were significantly smaller than those in the control group,while the gait cycle duration was significantly longer(P＜0.05).Conclusion After a certain period of rehabilitation,there is a certain gap in the isokinetic muscle strength of the ankle and hip joints,balance ability,and gait function between patients with ankle fractures and healthy individuals.Our findings in the study are of great significance for the subsequent formulation of rehabilitation plans and efficacy evaluation.