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 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 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 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.

Objective:To evaluate the screening value of serum pepsinogen (PG) Ⅰ, pepsinogen ratio (PGR, PG Ⅰ/PG Ⅱ) and gastrin 17 (G17) levels combined with gastroscopy for early-stage gastric cancer in high incidence areas of gastric cancer in Qinghai Province.Methods:A total of 2 700 cases were identified as the appropriate age (40-69 years) target population through the questionnaire survey from 25 000 local residents in high incidence areas of gastric cancer in Qinghai Province. The serum PGⅠ, PGⅡ and G17 levels of the 2 700 target population were determined by ELISA, and PGR were calculated. And then 949 patients with abnormal levels of PG and G17 were screened out as a high-risk group of gastric cancer to receive gastroscopy and pathologic biopsy. According to the results of gastroscopy and biopsy, the patients were divided into non-atrophic gastritis group, atrophic gastritis group, peptic ulcer group, early-stage gastric cancer group, and advanced gastric cancer group. The optimal threshold and its sensitivity and specificity of serum PG Ⅰ, PGR and G17 levels for diagnosis of early-stage and advanced gastric cancer were determined based on the receiver operator characteristic curve (ROC).Results:Totally 949 cases received gastroscopy and 649 cases received pathological biopsy, including 239 cases of non-atrophic gastritis, 500 cases of atrophic gastritis, 197 cases of peptic ulcer, 5 cases of early-stage gastric cancer, and 8 cases of advanced gastric cancer. The level of serum PG Ⅰ in the early-stage gastric cancer group (70.00±12.35 μg/L) and advanced gastric cancer group (38.39±2.77 μg/L) was significant lower than that in the non-atrophic gastritis group (103.89±37.45 μg/L, both P<0.05), and the value of early-stage gastric cancer group was obviously higher than that of advanced gastric cancer group ( P<0.05). The PGR of the early-stage gastric cancer group (3.74±1.40) and the advanced gastric cancer group (2.05±0.59) was significantly lower than that in the non-atrophic gastritis group (9.18±4.10, both P<0.05), and the value of early-stage gastric cancer group was significantly higher than that of the advanced gastric cancer group ( P<0.05). The level of serum G17 in the early gastric cancer group (18.03±4.52 pmol/L) and the advanced gastric cancer group (25.15±3.76 pmol/L) was significantly higher than that in the non-atrophic gastritis group (14.99±7.12 pmol/L, both P<0.05), and the level of early-stage gastric cancer group was significantly lower than that of advanced gastric cancer group ( P<0.05). According to the analysis of ROC in the diagnosis of early-stage gastric cancer, the best threshold of PG Ⅰ, PGR and G17 was 71.85 μg/L, 5.04, and 15.65 pmol/L, respectively, and the corresponding sensitivity and specificity was 80.0% and 59.0%, 100.0% and 70.4%, and 80.0% and 69.3%, respectively, for PG Ⅰ, PGR and G17. The analysis of ROC in the diagnosis of advanced gastric cancer showd that the best critical value of PG Ⅰ, PGR and G17 was 42.55 μg/L, 2.79 and 20.55 pmol/L, respectively, and the corresponding sensitivity and specificity was 100.0% and 95.3%, 100.0% and 92.1%, and 100.0% and 89.7%, respectively. Conclusion:Using serological detection of PG and G17 to screen high-risk group of gastric cancer, and then making diagnosis by gastroscopy and biopsy is an effective, low-cost and non-invasive approach for the early-stage gastric cancer in high incidence areas of gastric cancer in Qinghai Province.

Objective To explore the imaging characteristics and make the differential diagnosis of intraspinal extramedullary epidural lesions. Methods 23 cases with intraspinal extramedullary epidural lesions confirmed by puncture or surgical pathology were selected for retrospective analysis of the lesion morphology,MRI signs and the relationship between the lesion and surrounding tissues.Results Intraspinal extramedullary epidural lesions were more often located at thoracic spinal canal.The shapes of lesions were always various.The malignant tumors were irregular.It could damage the adjacent bone and grew surrounding the spinal cord.Leaping growth and multiple vertebral involvements could be seen in metastasis.The complex components of lesions were related to heterogeneous signal intensity on MRI,which could be presented with hypoGto hyperGintense on T1 WI and T2 WI.The angiolipoma showed hypoGto hyperGintense on T1 WI,and the hyperGintense signal could be suppressed with fatGsuppressed sequence.Meningioma tended to present with homogeneous signal on both T1 WI and T2 WI, with dural tail on contrast MRI.All of the lesions were moderately or significantly enhanced on contrast MRI.Conclusion Intraspinal extramedullary epidural lesions include a wide range of lesions,and the components of lesions are very complex.Among them,the distinctive MRI characteristics include the lesions containing fat and vascular components,besides malignant lesions invading adjacent tissues.Comprehensive analysis of the shape and signal of lesions,as well as the relationship between lesions,and surrounding structures is very helpful in differential diagnosis of intraspinal extramedullary epidural lesions.

Objective: To explore the effect of rapid rehabilitation concept nursing on prognosis and quality of life of patients after laparoscopic choledocholithotomy. Methods: A total of 140 patients undergoing laparoscopic choledocholithotomy in our hospital were selected as the subjects, and they were divided into control group (n=70) and experimental group (n=70) by random number table method. The patients in the control group received routine nursing intervention during the perioperative period, and the patients in the experimental group were based on the idea of rapid rehabilitation to carry out nursing intervention. The operation condition, postoperative recovery, incidence of postoperative complications, anti-oxidative stress ability, postoperative fatigue (fatigue visual analogue scale) and postoperative quality of life (QLO-C30 quality of life scale) were compared between the two groups. Results: The operation time, hospitalization time, hospitalization cost, incidence of postoperative complications, postoperative fatigue score on the 4th and 5th day after operation in the experimental group were (120.49±16.74) min, (7.05±1.47) d, (17 482.82±849.37) yuan, 31.43% (22/70) , (1.56±0.12) points, (0.92±0.10) points, the control group were (156.13±14.59) min, (13.75±1.45) d, (28 544.58±1 549.05) yuan, 71.43% (50/70), (3.38±0.87) points and (1.89±0.29) points, respectively. The differences between the two groups were significant (t=8.446, 9.325, 7.763, χ²=9.545, t=10.235, 12.402, P< 0.05). The postoperative recovery, quality of life and anti-oxidative stress ability of the patients in the experimental group were significantly better than those of the control group (P<0.05) . Conclusion Rapid rehabilitation nursing can improve the recovery of gastrointestinal function, reduce the incidence of complications, eliminate fatigue and improve the quality of life of patients after laparoscopic choledocholithotomy.