OBJECTIVE To analyze the influencing factors for achieving target plasma drug concentration （trough） （abbreviated as “PDC”） of vancomycin in patients from high-altitude regions and establish a predictive model for PDC using single- center data， providing references for rational clinical drug use. METHODS Inpatients with vancomycin （1 g， q12 h） administered intravenously in our hospital from January 2021 to June 2024 were retrospectively included. Demographic data， liver and kidney function and hematological indexes were collected. Spearman correlation analysis was used to evaluate the correlation between vancomycin PDC and each detection index. Univariate analysis was used to evaluate the differences of each index in patients with different PDC， and the effects of different gender， body mass index， age and underlying diseases （hypertension/diabetes） on vancomycin PDC. Based on the results of correlation analysis and univariate analysis， multiple linear stepwise regression analysis was used to obtain the independent predictors of vancomycin PDC and construct the prediction model. RESULTS A total of 141 patients were included， with an overall attainment rate of 46.81% for the target PDC of vancomycin. Correlation analysis showed that the vancomycin PDC was positively correlated with age， blood urea nitrogen， uric acid （UA）， serum creatinine （CRE） and β2- microglobulin （β2-MG）， and negatively correlated with height， weight， creatinine clearance rate （CCR）， glomerular filtration rate （GFR）， alanine transaminase （ALT）， hemoglobin （HGB）， white blood cell count and neutrophils （P＜0.05）. There were significant differences in age， CRE and other 14 indexes among different PDC groups （P＜0.05 or P＜0.01）. Age and underlying diseases had significant effects on vancomycin PDC （P＜0.05 or P＜0.01）. CCR， direct bilirubin （DBil）， β2-MG， UA， HGB and height （standardized coefficients were －0.371， 0.367， 0.169， 0.232， －0.140， －0.132； P＜0.05） were independent predictors of vancomycin PDC. The F value of the regression equation was 34.858 （P＜0.05）， the R2 was 0.610， and the adjusted R2 was 0.592. CONCLUSIONS The vancomycin PDC of patients in high-altitude regions is affected by multiple factors such as renal function， liver function and hematological indexes. CCR， HGB and height could be used to predict vancomycin PDC negatively， while DBil， β2-MG and UA could be used to predict vancomycin PDC positively. The variables of the established prediction model could explain 59.2% of the variation of vancomycin PDC.

Objective:To evaluate the application of blood glucose management evidence in hemodialysis patients with diabetic nephropathy within clinical practice, establish review indicators, and analyze both obstacles and enablers.Methods:Based on the feasibility, appropriateness, meaningfulness, and effectiveness (FAME) principle, the best evidence for blood glucose management in hemodialysis patients with diabetic nephropathy was evaluated. Ultimately, 21 pieces of evidence were included, and review indicators were established. A baseline review was conducted at the Hemodialysis Center of the Department of Nephrology, Zhongshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, from August to September 2024. Based on the review findings, obstacles and enablers in the evidence-based practice process were analyzed, and change strategies were developed.Results:A total of 39 review indicators were established. Among these, one indicator achieved a 100.00% implementation rate, four indicators achieved an implementation rate between 80.00% and <100.00%, six indicators achieved an implementation rate between 60.00% and<80.00%, 19 indicators achieved an implementation rate between>0 and<60.00%, and nine indicators achieved a 0 implementation rate. After analyzing each review indicator, the primary obstacles included evidence not being transformed into clear and accessible formats, low awareness among healthcare providers and patients, lack of incentive mechanisms, significant gaps from existing nursing processes, insufficient manpower, need for external support, and requirement for additional training. Additionally, factors that promoted evidence translation included reliable sources of evidence, recognition and support for change from administrators and teams, a culture and experience of change within the team, the potential for change to yield significant benefits, and the availability of resources within the hospital to support the change.Conclusions:There is a significant gap between blood glucose management evidence and clinical practice among hemodialysis patients with diabetic nephropathy. Appropriate change strategies should be developed through clinical review and analysis of obstacles and enablers to promote the translation and application of evidence in clinical practice.

Meropenem （MEM） is one of the important drugs for the treatment of severe infections， but the standard dose is often difficult to achieve an effective therapeutic concentration target. This article reviews the related studies on the population pharmacokinetics of MEM in patients with severe infection. It is found that the apparent volume of distribution （Vd） and clearance rate are the most important factors affecting the dose adjustment， and the factors affecting Vd include serum albumin， age， overall weight， shock status， and chest/abdomen/cerebrospinal fluid drainage. The main factors affecting the clearance rate were renal function， renal replacement therapy treatment mode and combination therapy. For adult patients with severe infections in China， MEM is recommended to be administered in an individualized manner based on glomerular filtration rate， with a dosage range of 500 to 1 500 mg given every 4 to 6 hours， and prolonged infusion is preferred. When the minimum inhibitory concentration （MIC） of the pathogenic bacteria reaches 64 mg/L， therapeutic drug monitoring is required. For therapeutic efficacy， it is essential to ensure that the trough concentration remains above the MIC； to prevent drug resistance， it should be maintained above 4×MIC. Regarding safety， it is recommended that the upper limit of the trough concentration be 32 mg/L， and blood sampling for monitoring can be conducted as early as after 1 to 2 doses of administration.

Objective:To evaluate the application of blood glucose management evidence in hemodialysis patients with diabetic nephropathy within clinical practice, establish review indicators, and analyze both obstacles and enablers.Methods:Based on the feasibility, appropriateness, meaningfulness, and effectiveness (FAME) principle, the best evidence for blood glucose management in hemodialysis patients with diabetic nephropathy was evaluated. Ultimately, 21 pieces of evidence were included, and review indicators were established. A baseline review was conducted at the Hemodialysis Center of the Department of Nephrology, Zhongshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, from August to September 2024. Based on the review findings, obstacles and enablers in the evidence-based practice process were analyzed, and change strategies were developed.Results:A total of 39 review indicators were established. Among these, one indicator achieved a 100.00% implementation rate, four indicators achieved an implementation rate between 80.00% and <100.00%, six indicators achieved an implementation rate between 60.00% and<80.00%, 19 indicators achieved an implementation rate between>0 and<60.00%, and nine indicators achieved a 0 implementation rate. After analyzing each review indicator, the primary obstacles included evidence not being transformed into clear and accessible formats, low awareness among healthcare providers and patients, lack of incentive mechanisms, significant gaps from existing nursing processes, insufficient manpower, need for external support, and requirement for additional training. Additionally, factors that promoted evidence translation included reliable sources of evidence, recognition and support for change from administrators and teams, a culture and experience of change within the team, the potential for change to yield significant benefits, and the availability of resources within the hospital to support the change.Conclusions:There is a significant gap between blood glucose management evidence and clinical practice among hemodialysis patients with diabetic nephropathy. Appropriate change strategies should be developed through clinical review and analysis of obstacles and enablers to promote the translation and application of evidence in clinical practice.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (Dmd^Mu/+) mice were obtained after genotype identification. Male hemizygous Dmd^Mu/+(Dmd^Mu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in Dmd^Mu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (Dmd^Mu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of Dmd^Mu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, Dmd^Mu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old Dmd^Mu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old Dmd^Mu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old Dmd^Mu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old Dmd^Mu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.

Objective To observe the effect of immersion virtual reality (IVR) training combined with occupational therapy (OT) in the treatment of stroke patients with unilateral neglect. Methods Fifty stroke patients with unilateral neglect in Shanghai Fourth Rehabilitation Hospital were randomly divided into IVR plus OT group and OT group, with 25 cases in each group. The OT group received conventional OT for unilateral neglect, and the IVR plus OT group received IVR training and OT. Both groups were treated for 4 weeks. Before and after treatment, the Catherine Bergego Scale (CBS), line cancellation test, star cancellation test, and drawing clock test were used to evaluate unilateral neglect symptoms; the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Barthel index (BI) were used to evaluate motor function of upper extremity and activities of daily living. Results After treatment, the results of CBS, line cancellation test, star cancellation test, drawing clock test, FMA-UE and BI scores were significantly improved when compared with those before treatment in both groups, and the improvement effects in the IVR plus OT group were significantly better than those in the OT group (P < 0.05 or P < 0.01). Conclusion IVR training combined with OT can improve unilateral neglect symptoms, motor function of affected upper extremity, and activities of daily living in stroke patients.

AL3810, a molecular dual inhibitor of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), has earned the permission of phase II clinical trial for tumor treatment by China FDA. As a reversible ATP-competitive inhibitor, AL3810 targets ATP-binding site on intracellular region of VEGFR and FGFR, whereas, AL3810 lacking interplay with extracellular region of receptors rendered deficient blood-brain tumor barrier (BBTB) recognition, poor brain penetration and unsatisfactory anti-glioma efficacy. Integrin

Objective : To investigate the mental health status of the pupils from Grade Four and Five in Jiading District of Shanghai, and to provide evidence for mental health intervention. Methods : All the students from Grade Four and Five in Jiading District, Shanghai were selected as survey objects. The MHT was used to evaluate their mental health status, and the influencing factors of mental health problems were analyzed by multivariate logistic regression model. Results : A total of 3 788 questionnaires were issued, of which 3 100 ones were valid and the effective rate was 81.84%. The detection rate of mental health problems was 17.06%. The detection rates of impulse tendency, terror tendency, physical symptoms, sensitivity tendency, self-blame tendency, loneliness tendency, anxiety towards people and learning anxiety were 11.77%, 15.55%, 12.97%, 16.19%, 10.10%, 4.81%, 13.16% and 14.00%, respectively. The results of multivariate logistic regression analysis showed that female students ( OR=1.617,95%CI: 1.325-1.974 ) , poor self-rated appearance ( OR=3.683, 95%CI: 2.428-5.586 ) ,only one or two friends ( OR=1.806, 95%CI: 1.342-2.428 ) , poor academic performance ( OR=1.626, 95%CI: 1.167-2.267 ) , primary school education or below of mother ( OR=1.539, 95%CI: 1.107-2.139 ) general or poor relationship with mother ( OR=1.785, 95%CI: 1.303-2.444 ) or father ( OR=1.745, 95%CI: 1.336-2.280 ) were risk factors for mental health problems. Conclusion The fourth-to fifth-grade primary school students in Jiading District of Shanghai have high detection rate of psychological problems. Gender, the number of friends, academic performance, education level of mother and the relation with parents are associated.

Objective:To investigate the predictive value of platelet reactivity for early neurological deterioration (END) in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke within 48 h of onset admitted to the Department of Neurology, the Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University from January 2017 to March 2019 were enrolled prospectively. Aspirin was taken on the day of admission, and the platelet aggregation rate was detected using a PL-11 Platelet Function Analyzer 7 d after taking it. END was defined as the National Institutes of Health Stroke Scale (NHISS) score at any time point within 7 d after admission increased by ≥2 or the motor function item score increased by ≥1 from baseline. The demographics, baseline data, imaging examination and laboratory findings of patients in the END and non-END groups were compared. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of platelet aggregation rate for END. Results:A total of 230 patients were included in the study. They aged 63.24±9.75 years, 126 were females (51.4%). The median baseline NIHSS score was 6 (interquartile range, 4-10). The median time from onset to admission was 15 h (interquartile range, 9-28 h). There were 54 patients (23.5%) in the END group and 176 (76.5%) in the non-END group. There were significant differences in arachidonic acid-induced maximum platelet aggregation ratio (MAR-AA), epinephrine-induced maximum platelet aggregation ratio (MAR-EPI) and collagen-induced maximum platelet aggregation ratio (MAR-COL) between the END group and the non-END group (all P<0.05). Multivariate logistic regression analysis showed that MAR-AA (odd ratio [ OR] 1.165, 95% confidence interval [ CI] 1.091-1.243; P<0.001) and MAR-EPI ( OR 1.035, 95% CI 1.006-1.067; P=0.023) were the independent risk factors for END in patients with acute ischemic stroke. ROC curve analysis showed that MAR-AA had good predictive value for END, and the area under the curve was 0.775 (95% CI 0.707-0.843; P<0.001). The optimal cut-off value was 21.80%. The sensitivity and specificity of MAR-AA for predicting END were 72.2% and 77.3%, respectively. Conclusions:The platelet function measured by PL-11 is closely related to the risk of END in patients with acute ischemic stroke. It has a better predictive value for END.