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.

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

OBJECTIVE: To preliminarily investigate the effects and mechanism of action of Yishen Yangsui Formula (, YSYSF)on the recovery of neurological function in rats with degenerative cervical myelopathy. METHODS: Fifty adult SD female rats were randomly divided into control group, sham group, model group, YSYSF group and positive drug group by using randomized numerical table method. In the model group, YSYSF group and positive drug group, polyvinyl alcohol acrylamide interpenetrating network hydrogel(water-absorbent swelling material) was used to construct a rat spinal cord chronic compression model. The sham group was implanted with the water-absorbent swelling material and then removed without causing spinal cord compression. The control group, the sham group and the model group were given equal amounts of saline by gavage, the group of YSYSF was given Chinese herbal medicine soup by gavage 9.1 g·kg^-1 once a day, and the positive drug group was given tetrahexylsalicylglucoside sodium monosialate ganglioside by intraperitoneal injection 4.2 mg·kg^-1 once a day. The motor function of the rats was assessed by the BBB method after 1, 3, 7, and 14 d of drug administration. The spinal cord tissues were taken from rats executed 14 d after drug administration, and the morphological changes of the spinal cord compression site were observed by HE staining, and the expression levels of Caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 were detected in the area of spinal cord injury by Western blot method. RESULTS: The BBB scores of the control group and the sham group were normal at all time points after modeling, which were higher than the BBB scores of the model group, the YSYSF, and the positive drug group (P<0.05). From the 3rd day after gavage, at all time points, the BBB scores of rats in the YSYSF group and the positive drug group were higher than those of rats in the model group (P<0.05). The staining pattern of HE spinal cord tissue was normal in the control group and the sham group, and the HE spinal cord in the model group was severely damaged with a large number of neuron deaths, whereas the damage to the spinal cord and neuron cells was reduced in the YSYSF group and the positive drug group. The expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β and IL-18 in the spinal cord of the model group were significantly higher than those of the sham group (P<0.0001), and the expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 in the YSYSF group and the drug group were significantly lower than those in the model group (P<0.05). CONCLUSION YSYSF can improve the motor function of rats with degenerative cervical spinal cord disease, alleviate the pathological changes, and promote the recovery of spinal cord neurological function. The specific mechanism may be related to the inhibition of the activation of inflammatory vesicles NLRP3 and PYCARD, the reduction of the release of inflammatory factors IL-1β and IL-18, the reduction of the expression of caspase-1 and GSDMD, the reduction of cellular death, and the inhibition of inflammatory response.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Pyroptosis/drug effects* ; Spinal Cord/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Spinal Cord Diseases/drug therapy* ; Interleukin-1beta/metabolism*

OBJECTIVE To formulate an expert consensus on the prevention and control of respiratory infectious diseases in railway stations and trains in China,and to standardize the prevention and control of respiratory infec-tious diseases in railway stations and trains scientifically.METHODS The government authorities organized multi-ple prevention and control experts from transportation,medical care and prevention fields to conduct in-depth re-search through methods such as meetings and on-site investigations,and combined with their practical experi-ence in this field to formulate this expert consensus.RESULTS In-depth studies were conducted on the prevention and control strategies,measures and emergency response system construction of respiratory infectious diseases in railway stations and trains,and this expert consensus was formed.CONCLUSION This expert consensus supple-ments improves the existing prevention and control system for respiratory infectious diseases in railway stations and trains,and provides an important reference basis for the prevention and control of respiratory infectious disea-ses in railway stations and trains.

BACKGROUND:The incidence of inflammatory bowel disease has been steadily rising,accompanied by a lack of definitive therapeutic strategies.Recent research endeavors have illuminated the promising potential of mesenchymal stem cells in mitigating the symptoms of inflammatory bowel disease,offering a glimmer of hope for afflicted patients.OBJECTIVE:To review the mechanisms of action of mesenchymal stem cells derived from various sources in the management of inflammatory bowel disease,aiming to provide insights for future research endeavors.METHODS:Utilizing the keywords"mesenchymal stem cells,MSCs,exosomes,extracellular vesicles,EVs,inflammatory bowel disease,IBD,ulcerative colitis,UC,Crohn's disease,CD"in English and their Chinese equivalents in CNKI and PubMed databases,a total of 89 eligible articles were selected for this review.RESULTS AND CONCLUSION:Currently,six types of mesenchymal stem cells are being explored for inflammatory bowel disease therapy:bone marrow-derived mesenchymal stem cells,adipose tissue-derived mesenchymal stem cells,perinatal tissue-derived mesenchymal stem cells,induced pluripotent stem cell-derived mesenchymal stem cells,embryonic stem cell-derived mesenchymal stem cells,and gingival mesenchymal stem cells.Five administration routes have been adopted,with intravenous and intraperitoneal injections being the most prevalent,followed by local,mesenteric,and intra rectal injections.Their therapeutic mechanisms encompass differentiation,regeneration,anti-inflammatory effects,immune modulation,neuroprotection,antioxidant stress response,homing,modulation of gut microbiota,autophagy,ferroptosis,and endoplasmic reticulum stress.While sharing functional similarities,mesenchymal stem cells from different sources exhibit unique characteristics that confer them with distinct advantages and therapeutic potentials.Nevertheless,research into the specific properties of these mesenchymal stem cells remains limited,necessitating deeper exploration of their nuanced differences to optimize their therapeutic efficacy in inflammatory bowel disease.Additionally,the clinical safety of mesenchymal stem cells-based therapies warrants further observation and evaluation.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.