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.

Objective:To construct a comprehensive nursing evaluation indicator system for HIV infected patients with hematological malignancies receiving chimeric antigen receptor T cell therapy, and provide theoretical support for clinical nursing practice.Methods:From November 2023 to February 2024, the first draft of indicator system was developed through literature review and panel meeting, experts from 6 provinces and cities were interviewed by Delphi consultations, and the final draft were formed by revision.Results:A total of 18 experts took part in the expert consultation, included 4 males and 14 females, aged (44.00 ± 7.24) years. The effective recovery rates of questionnaire for both rounds were 18/18, and the authority coefficient were 0.894 and 0.900, respectively. The coordination coefficients of the third level items were 0.146 and 0.128 respectively (both P<0.05) regarding the importance, and 0.156 ( P<0.05) regarding the operability. The final comprehensive nursing evaluation indicator system for HIV infected patients with hematological malignancies receiving chimeric antigen receptor T cell therapy consisted of 5 first-level items, 28 second-level items and 89 third-level items. Conclusions:The comprehensive nursing evaluation indicator system of CAR-T therapy for HIV infected patients with hematological malignancies is scientific, reliable and comprehensive, which can provide reference for clinical nurses in nursing practice and training related to CAR-T and AIDS.

OBJECTIVE To study the pharmacokinetics/pharmacodynamics(PK/PD)profiles of meropenem in the plasma,lung,muscle and skin tissues of rabbits,and to explore the effects of sepsis and continuous renal replacement therapy(CRRT)on the probability of target attainment(PTA)of meropenem.METHODS Twenty-four New Zealand rabbits were randomly divided into four equal groups:sepsis-CRRT group,sepsis group,normal-CRRT group and normal control group.Six hours after a rabbit model of sepsis was established via cecal ligation and puncture(CLP)surgery,an auto-matic infusion pump with meropenem[(1 000/60)×3.27=54.5 mg·kg-1,converted from that of humans(1g)to that of rabbits]was used to administer the drug to the animals for 0.5 h,while CRRT was started simultaneously with drug administration in the CRRT group.Microdialysis samples were collected from 4 target sites of each group once every 30 min for 480 min.The concentration of meropenem was deter-mined using liquid chromatography-tandem mass spectrometry(LC-MS/MS)before a concentration-time curve was constructed.Pharmacokinetic parameters such as the peak concentration(Cmax),time to reach peak concentration(Tmax),area under the concentration-time curve(AUC),and elimination half-life(t1/2)were calculated using a non-atrioventricular model.Monte Carlo simulation(MCS)was performed at various minimum inhibitory concentrations(MICs)using pharmacokinetic parameters of meropenem to assess the probability of target attainment(PTA).The predefined PK/PD target was％fT＞4MIC＞40％,where the percentage of time that the free drug concentration[f]exceeded 4 times that of the MIC during a dosing interval was above 40％and Cmax/MIC exceeded 4.RESULTS The results indicated no statistically significant differences between the PK parameters of skin tissue in the normal control group and sepsis group,whereas Cmax of other tissues was significantly lower in the sepsis group than in the normal control group(P＜0.01).AUCplasma and AUCskin were significantly increased(P＜0.01),while AUCIung and AUCmuscle were significantly decreased(P＜0.01)when the sepsis-CRRT group was compared with the sepsis group.With a target value of％fT＞4MIC＞40％,the plasma and skin tissues of the sepsis-CRRT group,the muscle tissues of the normal-CRRT group and the lung,muscle and skin tissues of the normal control group achieved a PTA of over 90％(MIC=1 mg·L-1).The skin tissues of the sepsis-CRRT group and the lung tissues of the normal control group achieved an efficacy target of more than 90％(MIC=2 mg·L-1).However,our results did not indicate that either AUC or Cmax was involved in the changes of PTA in the normal control group.For all tissues except skin tissues(MIC=4 mg·L-1),PTA decreased with Cmax in the sepsis group.The PTA of plasma and skin tissues increased with the AUC,while the PTA of lung(MIC=2,4 mg·L-1)and muscle tissues(MIC=1,2,4 mg·L-1)decreased with the AUC in the sepsis-CRRT group.CONCLUSION Sepsis has little effect on the distri-bution of meropenem in skin tissues.Sepsis may reduce the efficacy of meropenem in various tissues,and CRRT can improve the efficacy of plasma and skin tissues in sepsis.This method of collecting target samples with microdialysis probes is accurate and reliable,which can be used in therapeutic drug monitoring.

Objective To develop an assessment scale of oropharyngeal candidiasis risks in HIV-infected patients,and to test its reliability and validity.Methods The draft of the assessment scale was constructed by the literature analysis method,Delphi consultations and analytic hierarchy process.Totally 231 HIV-infected patients in a tertiary A hospital of Hangzhou were recruited for questionnaire survey in October 2023 to January 2024.Results The scale includes 3 dimensions,including general factors,HIV related factors and oral related factors,12 first-level items and 21 second-level items.The Cronbach's α coefficient of the scale was 0.813;the content validity index was 0.98;the correlation of each dimension was 0.574～0.733(P＜0.05).Confirmatory factor analysis showed that the 3 factor models fitted the data well.The critical value(30.5 points)of the scale was determined by ROC curve;the area under the curve was 0.909;the sensitivity of index system was 0.962,and specificity was 0.697.Conclusion The assessment scale of oropharyngeal candidiasis risks in HIV-infected patients has good reliability and validity,and it can be used as an auxiliary tool for effective identification and prediction of oropharyngeal candidiasis risk.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:To construct a comprehensive nursing evaluation indicator system for HIV infected patients with hematological malignancies receiving chimeric antigen receptor T cell therapy, and provide theoretical support for clinical nursing practice.Methods:From November 2023 to February 2024, the first draft of indicator system was developed through literature review and panel meeting, experts from 6 provinces and cities were interviewed by Delphi consultations, and the final draft were formed by revision.Results:A total of 18 experts took part in the expert consultation, included 4 males and 14 females, aged (44.00 ± 7.24) years. The effective recovery rates of questionnaire for both rounds were 18/18, and the authority coefficient were 0.894 and 0.900, respectively. The coordination coefficients of the third level items were 0.146 and 0.128 respectively (both P<0.05) regarding the importance, and 0.156 ( P<0.05) regarding the operability. The final comprehensive nursing evaluation indicator system for HIV infected patients with hematological malignancies receiving chimeric antigen receptor T cell therapy consisted of 5 first-level items, 28 second-level items and 89 third-level items. Conclusions:The comprehensive nursing evaluation indicator system of CAR-T therapy for HIV infected patients with hematological malignancies is scientific, reliable and comprehensive, which can provide reference for clinical nurses in nursing practice and training related to CAR-T and AIDS.

Objective To analyze the effect of Hsa-circ-0101216 on gemcitabine(GEM)chemotherapy resistance in pancreatic cancer and its mechanism.Methods Differentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database.Pancreatic cancer GEM resistant cell lines(BxPC-3-GEM and Capan-1-GEM)were constructed by intermittent concentration gradient method.qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells.GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group(knockdown of circ-0101216),sh-NC group(transfected with sh-NC),and blank control group(untreated).CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration(IC50)of GEM and proliferation ability of cells in each group.Western blotting was performed to detect the expression of multidrug resistance-related protein 1(MRP1),breast cancer resistance protein(BCRP),and human equilibrative nucleoside transporter-1(hENT-1).A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed,and sh-NC+GEM group and sh-circ-0101216+GEM group(n=6)were set up.The volume and weight of xenograft tumor in nude mice were compared between the two groups.Western blotting and immunohistochemistry were used to detect the expression of MRP1,BCRP,and hENT-1 proteins in xenograft tumor tissues,and EDU proliferation assay was used to detect the proliferation ability of tumor cells.Results The GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines.Pancreatic cancer GEM-resistant cell lines were successfully constructed,and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells(P<0.05).In sh-circ-0101216 group,the IC50 values of GEM,cell viability,EdU positivity rate,and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group,while the expression level of hENT-1 protein was significantly higher(P<0.05 or P<0.001).In sh-circ-0101216+GEM group,the weight and volume of subcutaneous xenograft tumors in nude mice,the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues,and the EdU positive rate were significantly lower than those in sh-NC+GEM group,while the expression level and positive expression rate of hENT-1 protein were significantly higher(P<0.05).Conclusions Hsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines.Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM.The mechanism may be related to the regulation of transmembrane transporter protein expression.

Objective To explore whether creatine therapy regulates neuronal ferroptosis by inhibiting the activation of STAT1 signaling pathway associated with suppressor of cytokine signaling 1(SOCS1)in Alzheimer's disease.Methods Immunohistochemical staining and counting of positive results using paraffin sections of human brain frontal lobes were employed to determine the trend of changes in the target proteins.Further validation was performed by immunofluorescence and Western blotting.STAT1 phosphorylation was inhibited by creatine injection using eleven FAD4T mice and by cerebellar medullary pool puncture,and the expression of target proteins was examined by immunohistochemistry and immunofluorescence after postmortem sampling.Results Compared with the age controls,interferon-γ(IFN-γ),an activating cytokine of the STAT1 signaling pathway,and SOCS1,a negative regulator of STAT1 activation,were both significantly up-regulated,STAT1 phosphorylation was enhanced,and the ferroptosis markers ferritin light chain(FTL)and cystine/glutamate transporter(xCT)increased markedly in the cortex of AD human brains;Creatine treatment of FAD4T mice resulted in a reduction of both IFN-γ and SOCS1,and a significant decrease in the ferroptosis markers FTL and xCT(SLC7A11).Conclusion Creatine ameliorates neuronal ferroptosis in AD model mice by reducing neuronal STAT1-SOCS1 signalling activation.