ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

BackgroundWith the rapid development of the networking technologies， internet addiction has increasingly become a serious mental health issue. Previous studies have revealed the link between childhood trauma and internet addiction， while the mediating role of perceived stress in this link is not yet clear. ObjectiveTo investigate the role of medical students' perceived stress in the relationship between childhood trauma and internet addiction， so as to provide references for the intervention of internet addiction. MethodsFrom February to March 2023， a random sampling technique was used to select 1 232 undergraduate students from the School of Clinical Medical Sciences of Southwest Medical University as research subjects. The Childhood Trauma Questionnaire-Short Form （CTQ-SF）， Perceived Stress Scale （PSS）， Internet Gaming Disorder Scale （IGDS）， and Bergen Social Media Addiction Scale （BSMAS） were used for assessment. Pearson's correlation coefficients were calculated. The mediation effect of perceived stress in the relationship between childhood trauma and internet addiction was tested using Model 4 in the SPSS Process 4.1， and Bootstrapping procedure involving 5 000 replicates was employed to confirm the statistical significance. ResultsA total of 1 016 （82.47%） valid completed questionnaires were gathered. The CTQ-SF scores of medical students were positively correlated with PSS scores， IGD scores， and BSMAS scores （r=0.583， 0.474， 0.465， P<0.01）. PSS scores were positively correlated with IGD scores and BSMAS scores （r=0.369， 0.479， P<0.01）. Childhood trauma in medical students was found to positively predict perceived stress （β=0.191， P<0.01）， social media addiction （β=0.160， P<0.01）， and internet gaming disorder （β=0.106， P<0.01）. Perceived stress played a significant mediating role in the relationship between childhood trauma and internet gaming disorder， indirect effect value was 0.018 （95% CI： 0.009~0.027）， accounting for 16.98%. Perceived stress also exhibited a significant mediating role in the relationship between childhood trauma and social media addiction， indirect effect value was 0.063 （95% CI： 0.048~0.079）， accounting for 39.38%. ConclusionChildhood trauma in medical students may affect internet gaming disorder and social media addiction through perceived stress. ［Funded by 2022 Annual Research Project of Sichuan Applied Psychology Research Center，（number，CSXL-22102）］

Objective To investigate the application value of CT perfusion imaging in patient with traumatic brain injury(TBI).Methods Thirty-seven patients with TBI were included retrospectively and divided into mild,moderate,and severe groups according to Glasgow coma scale(GCS)score.Perfusion parameters of the cerebral hemispheres on the injured side and the contralateral side of the level of basal ganglia were compared.After three months,the correlations between perfusion parameters and GCS score at baseline and Glasgow outcome scale-extended(GOSE)score at follow-up were further analyzed,respectively.Results The injured side of TBI patients showed hypo-perfusion compared with that of the contralateral side.The abnormal perfusion volumes of time to maximum of the residual function(Tmax)>10 s was significantly negatively correlated with GOSE score(ρ=-0.55,P=0.01),and could distinguish the good prognosis group from the poor prognosis group with GOSE score[area under the curve(AUC)=0.82,P= 0.01].In the group of patients undergoing decompressive craniectomy,the abnormal perfusion volumes of Tmax>4 s and Tmax>6 s were significantly associated with GCS score(ρ=0.61,P=0.01;ρ=0.53,P=0.03).Conclusion CT perfusion imaging may be useful in assessing the hemodynamics and severity of TBI,and in predicting the clinical prognosis.

Objective To establish a method for the determination of lorlatinib in human plasma by two-dimensional high performance liquid chromatography.Methods In the two-dimensional high performance liquid chromatography method,one-dimensional column SX1E-1A(50 mm × 3.5 mm,5 μm)and two-dimensional column SCB-C18(125 mm × 4.6 mm,5 μm)were used with flow rates of 0.8 mL·min-1 and 1.0 mL·min-1,respectively.The column temperature was 40 ℃,The UV detection wavelength was 317 nm,and the sample size was 500 μL.This study investigated the specificity,standard curve and minimum quantification limit,precision and recovery rate,as well as stability of the method.Results The concentration of lolatinib in human plasma showed a good linear relationship in the range of 11.72-1 018.98 ng·mL-1,and the regression equation was y=944.50x-588.90(R2=0.999 7).The minimum limit of quantification was 11.72 ng·mL-1.The extraction recovery rates of the three quality control samples were 97.61％-99.86％,and the intra-day and inter-day precisions were less than 5.29％,indicating that the detection performance of the method was good.Conclusion The method has the characteristics of good stability,high sensitivity and strong anti-interference ability,and is suitable for the determination of loratinib in human plasma.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

A portable electrochemical sensing system for simultaneous detection of species relevant to carbon cycle(i.e.,Ca2+,CO32-and pH)in seawater was developed,in which a highly sensitive polymeric membrane ion-selective electrode array with NiCo2S4-based transduction layer was used as the core element.Such an electrochemical sensor array was developed via the combination of all-solid-state ion selective electrode technology and electrode integration technology based on screen printing.The proposed sensing system offered the linear response concentration ranges of 1.0×10-5-1.0×10-1 mol/L and 3.2×10-5-1.9×10-3 mol/L for Ca2+,CO32-and 5-9 for pH in 0.5 mol/L NaCl background,respectively,as well as a relative deviation of less than 2.0%for evaluation of detection accuracy(mean deviation compared to the readings of reference techniques).For successive measurements,the relative standard deviations(RSDs)of less than 2.5%were obtained.The proposed electrochemical sensing system was successfully used for seawater analysis,and the whole analysis process could be completed within 15 min.

Objective To investigate the effect of Tongsheng Prescription on trimethylamine N-oxide(TMAO)and related metabolites substrate in patients with acute cerebral infarction after intervention and to evaluate its clinical efficacy.Methods A prospective randomized controlled study was conducted in 48 patients with acute ischemic stroke with large vessel occlusion(AIS-LVO)who had received endovascular treatment(EVT).The patients were divided into an observation group(25 cases)and a control group(23 cases).After emergency EVT,the control group was treated with routine western medicine,and the observation group was treated with nasogastric feeding or oral use of Tongsheng Prescription on the basis of treatment for the control group.The course of treatment lasted for seven days,and then the patients were followed up for three months.Before operation,7 days and 90 days after operation,National Institutes of Health Stroke Scale(NIHSS)scores in the two groups were observed.The functional prognosis evaluated with Modified Rankin Scale(MRS)scores was compared between the two groups,and the effects of Tongsheng Prescription on serum TM AO and related metabolites choline,betaine and L-carnitine were investigated.Results(1)On the postoperative day 7 and 90,the NIHSS scores of the two groups were decreased compared with those before operation(P＜0.01),and the decrease of NIHSS scores on the postoperative day 7 and 90 in the observation group was significantly superior to that in the control group(P＜0.01).(2)On the postoperative day 90,the rate of good functional outcome in the observation group was 96.00％(24/25),which was significantly higher than 69.57％(16/23)in the control group,and the difference was statistically significant(P＜0.05).(3)On the postoperative day 7 and 90,the levels of TMAO,L-carnitine and betaine in the observation group tended to decrease compared with those before operation,but the difference was not statistically significant(P＞0.05).However,the levels of TMAO,L-carnitine and betaine in the control group were significantly increased compared with those before operation(P＜0.01).On the postoperative day 7,the levels of TMAO,L-carnitine and betaine in the observation group were significantly lower than those in the control group,and the differences were statistically significant(P＜0.05).(4)Spearman correlation analysis showed that TMAO was positively correlated with NIHSS score,L-carnitine and choline(P＜0.05 or P＜0.01).Conclusion Tongsheng Prescription has a significant effect on AIS-LVO patients seven days after EVT.The Prescription is beneficial to obtain a good functional outcome,and its mechanism may be related to the decrease of TMAO level through L-carnitine and betaine pathways,so as to improve the neurological deficit symptoms of stroke 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:RS4;11 cell line was used to establish BCL-2 inhibitor-resistant cell lines of B-cell acute lymphoblastic leukemia(B-ALL)and explore the possible mechanisms of drug resistance.Methods:RS4;11 cell line was continuously induced and cultured by low and ascending concentrations of BCL-2 inhibitors navitoclax and venetoclax to construct navitoclax-resistant cell line RS4;11/Nav and venetoclax-resistant cell line RS4;11/Ven.The cell viability was detected by MTT assay,and the cell apoptosis was detected by flow cytometry.Differentially expressed genes(DEGs)between RS4;11 drug-resistant cell lines and parental cell line were detected by transcriptome sequencing technology(RNA-seq),and mRNA expression levels of DEGs between drug-resistant cell lines and parental cell line were detected by real-time PCR(RT-PCR).Western blot was used to detect the expression levels of BCL-2 family anti-apoptotic proteins in drug-resistant cell lines and parental cell line.Results:The drug-resistant cell lines RS4;11/Nav and RS4;11/Ven were successfully established.The resistance index(RI)of RS4;11/Nav to navitoclax and RS4;11/Ven to venetoclax was 328.655±47.377 and 2 894.027±300.311,respectively.The results of cell apoptosis detection showed that compared with the drug-resistant cell lines,RS4;11 parental cell line were significantly inhibited by BCL-2 inhibitors,while the apoptosis rate of drug-resistant cell lines was not affected by the drugs.Western blot assay showed that the expression of anti-apoptotic proteins of BCL-2 family did not increase significantly in drug-resistant cell lines.RNA-seq,RT-PCR and Western blot assays showed that the expression of EP300 in drug-resistant cell lines was significantly higher than that in parental cell line(P＜0.05).Conclusion:Drug-resistant B-ALL cell lines could be successfully established by exposing RS4;11 cell line to the ascending concentration of BCL-2 inhibitors,and the drug resistance mechanism may be related to the overexpression of EP300.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.