BACKGROUND:Agomelatine is a clinically proven treatment for neuropsychiatric symptoms,such as anxiety and depression.Furthermore,our previous study has demonstrated that agomelatine ameliorates cognitive behaviors,hippocampal synaptic plasticity,and brain pathology in a mouse model of Alzheimer's disease.However,it remains unclear whether agomelatine can improve anxiety and depression-like behaviors in Alzheimer's disease model mice. OBJECTIVE:To investigate the improving effects of agomelatine on anxiety-and depression-like behaviors in APP/PS1 transgenic mice and its underlying molecular mechanisms. METHODS:(1)Eighteen APP/PS1 transgenic mice were randomly divided into model control group(n=9)and model intervention group(n=9).Another wild-type mice were randomized into control group(n=9)and intervention group(n=9).Model intervention group and intervention group were intraperitoneally injected with 10 mg/kg agomelatine per day for 31 continuous days.Behavioral experiments,including the elevated cross maze and forced swimming tests,and mRNA sequencing of the hippocampus were then performed.(2)Mouse hippocampal neuronal cell lines(HT22)and brain microvascular endothelial cell lines(bEnd.3)were cultured and divided into four groups:blank group without any drug,drug group with 20 μmol/L agomelatine,model group with 10 μmol/L β-amyloid 1-42,and experimental group with 10 μmol/L β-amyloid 1-42+20 μmol/L agomelatine.After 24 hours of incubation,protein expression of S416p-tau and S9p-GSK3β in HT22 cells was detected by immunoblotting,and protein expression of low-density lipoprotein receptor-related protein 1 and glycosylation end-product receptor in bEnd.3 cells was detected by immunoblotting. RESULTS AND CONCLUSION:In the elevated plus maze test,the time spent in the open arms(P＜0.01)and the entries into open arms(P＜0.05)in the mice of model control group were evidently lower than those in the control group,whereas those were obviously increased in the model intervention group compared with the model control group(P＜0.05).Forced swimming test results showed that the immobile time exhibited a marked increase in the model control group compared with the control group(P＜0.05),but it was significantly decreased in the model intervention group compared with the model control group(P＜0.05).Hippocampal tissue mRNA sequencing showed that agomelatine enhanced the expression of low-density lipoprotein receptor-related protein 1 in the hippocampus of APP/PS1 mice.Western blot analysis revealed that the level of S416p-tau in HT22 cells was higher in the model group than the blank group(P＜0.05),while it was markedly decreased in the experimental group compared with the model group(P＜0.05);the level of S9p-GSK3β in HT22 cells was higher in the drug group than the blank group(P＜0.05)as well as higher in the experimental group than the model group(P＜0.05).Moreover,the expression of low-density lipoprotein receptor-related protein 1 in bEnd.3 cells was higher in the experimental group than the model group(P＜0.05).To conclude,agomelatine can alleviate anxiety-and depression-like behaviors in Alzheimer's disease mice by promoting the clearance of β-amyloid and phosphorylated tau.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

ObjectiveThe U6 promoter is an essential element for driving sgRNA expression in the clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9（CRISPR/Cas9）gene editing system in dicotyledonous plants. Endogenous U6 promoters typically exhibit higher transcriptional activity， which can significantly improve gene editing efficiency. This study aims to identify endogenous U6 promoters in Artemisia annua to optimize its CRISPR/Cas9 gene editing system， which holds significant importance for its molecular breeding. MethodsOn the basis of the highly conserved U6 snRNA sequences in Arabidopsis thaliana， endogenous U6 promoters were screened in the A. annua genome. Expression vectors were constructed with candidate AaU6 promoter driving the firefly luciferase （LUC） reporter gene， and then transiently transformed into Nicotiana benthamiana. Transcriptional activities of the promoters were measured and compared by in vivo imaging and the Dual Luciferase Reporter assay. ResultsEight endogenous U6 promoters were successfully cloned from A. annua. Sequences alignment revealed that all these promoters contained the two conserved cis-acting elements， upstream sequence element （USE） and TATA-box， which affected their transcriptional activity. Dual-luciferase activity assays indicated that the transcriptional activities of AaU6-3， AaU6-1， and AaU6-5 were significantly higher than that of the Arabidopsis AtU6-26 promoter， with AaU6-3 exhibiting the highest activity. ConclusionThis study identified three endogenous AaU6 promoters with high transcriptional activity in A. annua， providing key functional elements for establishing an efficient gene editing system in A. annua. These findings will contribute to advancing precision molecular breeding and high-quality germplasm innovation in A. annua.

Objective: To construct a scientific and perfect evaluation index system of infectious disease prevention and control ability in colleges and universities, so as to provide reference tools for colleges and universities to effectively respond to infectious disease. Methods: The initial framework of the evaluation index system of infectious disease prevention and control ability in colleges and universities was constructed by using literature analysis method. Experts familiar with infectious disease prevention and control or school health work were selected to conduct two rounds( n =16，18) of Delphi expert consultation for determining the evaluation index system. Analytical hierarchy process was used to calculate the index weights and combined weights. About 198 prevention and control personnel were conveniently selected from 3 universities in Inner Mongolia Autonomous Region to comprehensively evaluate the evaluation indicators by using fuzzy comprehensive evaluation method. Results: After two rounds of Delphi consultation questionnaire, the effective recovery rates were 80.0% and 90.0%, the expert authority levels were 0.89 and 0.86, the expert harmony coefficients for Kendall W were 0.166 and 0.310, and the variation coefficient of each index was <0.25. Finally, the evaluation index system of infectious disease prevention and control ability of colleges and universities included 4 first level indicators, 14 second level indicators and 75 third level indicators. The weights of prevention and monitoring and early warning, organizational system guarantee, emergency management, rehabilitation and summary were 0.176, 0.476, 0.268 and 0.080, respectively. The top 3 weights of the secondary indexes were 0.623 for infectious disease surveillance and early warning, 0.595 for loss assessment and 0.370 for emergency response. The score of fuzzy comprehensive evaluation of the index system of infectious disease prevention and control ability in colleges and universities was 79.148, suggesting a high level. Conclusion The established evaluation index system of infectious disease prevention and control ability in colleges and universities is scientific and reasonable, which is conducive to provide tool reference for the evaluation of infectious disease prevention and control ability in colleges and universities.

Objective To investigate the factors affecting the distribution of Pomacea and project the trends in the spread of suitable distribution areas of Pomacea in 2050 and 2070 in Dali Bai Autonomous Prefecture, so as to provide insights into Pomacea control in the prefecture. Methods The longitudes and latitudes of Pomacea sampling sites were captured based on Pomacea field survey data in 12 cities (counties) of Dali Bai Autonomous Prefecture from 2023 to 2024. A total of 19 climatic factors (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest month, mean temperature of the coldest month, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, mean temperature of the warmest quarter, and mean temperature of the coldest quarter) and representative concentration pathways (RCPs) were retrieved from the world climate database (www.worldclim.org). All climatic variables were employed to create a maximum entropy (MaxEnt) model. The predictive accuracy of the model was assessed with the area under the receiver operating characteristic (ROC) curve (AUC), and the contributions of these 19 climatic factors to the distribution of Pomacea were analyzed in Dali Bai Autonomous Prefecture using Jackknife test. In addition, the suitable distribution areas of Pomacea were predicted with the MaxEnt model in Dali Bai Autonomous Prefecture in 2024 and in 2050 and 2070 under RCP4.5. Results Data pertaining to 91 Pomacea sampling sites were captured. ROC analysis revealed the MaxEnt model had an AUC value of 0.885 ± 0.088 for predicting the suitable distribution areas of Pomacea in Dali Bai Autonomous Prefecture. Of the 19 climatic factors, the maximum temperature of the warmest month had the highest contribution to the distribution of Pomacea in Dali Bai Autonomous Prefecture, followed by mean temperature of the driest quarter, mean temperature of the wettest quarter and minimum temperature of the coldest month. The suitable distribution area of Pomacea was predicted to be 14 555.69 km² in Dali Bai Autonomous Prefecture in 2024, and would expand gradually to the southeastern part of the prefecture in the future due to climatic factors. The suitable distribution areas of Pomacea were projected to expand to 21 475.61 km² in 2050 and 25 782.52 km² in 2070 in Dali Bai Autonomous Prefecture, respectively. Conclusions Temperature is an important contributor to the distribution of Pomacea in Dali Bai Autonomous Prefecture, and the suitable distribution area of Pomacea will gradually expand to the southeastern part of the prefecture in 2050 and 2070.

OBJECTIVE To analyze the characteristics of global surgical site infection(SSI)outbreaks and provide references for targeted prevention and control measures.METHODS SSI outbreak events from Jan.1,1990 to Dec.31,2023 were searched from Wanfang Med,CNKI,VIP and PubMed.Data on department distribution dur-ing the outbreak,duration,investigation methods,main causes,transmission modes,pathogen composition and outbreak outcomes were summarized for analysis.RESULTS A total of 111 SSI outbreaks in 20 countries were identi-fied,involving 1 382 patients and 24 deaths.The source of the outbreak was identified in 78 cases,mainly involving med-ical personnel in 27 cases(34.62％),hospital equipment in 19 cases(24.36％),environmental factors in 11 cases(14.10％),workflow factors in 10 cases(12.82％),hospital water factors in 7 cases(8.97％)and disinfectant fac-tors in 4 cases(5.13％).The duration of SSI outbreaks abroad was 5.00(1.50,12.00)months,longer than that in China[1.00(1.00,2.00)month](P＜0.05).In China,the outbreaks mainly occurred in neurosurgery,cardiac surger-y,orthopedics,obstetrics and general surgery,while at abroad,they mainly occurred in cardiac surgery,orthopedics,and involved multiple surgical departments.Environmental hygiene methods were adopted in up to 90.63％of cases in China.Compared with China,analytical epidemiological methods and molecular epidemiological methods were more com-monly used abroad.Targeted measures and strengthened basic measures were implemented for different outbreak sources to terminate the SSI outbreaks.Pulsed-field gel electrophoresis(34 times)was a widely used molecular typing method in outbreak investigations.CONCLUSIONS Based on the analysis of SSI outbreak characteristics and risk factors,it is neces-sary to strengthen medical personnel training and monitoring of special pathogens.At the same time,the epidemiologi-cal investigation capabilities of infection control professionals should be strengthened.