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.

Objective To investigate the relationship between serum glial fibrillary acidic protein(GFAP)level and transcranial Doppler(TCD)parameters in carotid stenosis patients after carotid stent implantation.Methods A total of 123 patients with carotid stenosis who received carotid stent implantation in our hospital from September 2021 to February 2024 were recruited,and di-vided into a normal group(39 cases)and a damaged group(84 cases)according to their cerebro-vascular reserve.The GFAP level and TCD parameters were collected before and after treatment.ROC curve analysis was employed to analyze the value of GFAP level in evaluating cerebrovascu-lar reserve in the patients.Results Significantly larger proportion of diabetes and higher level of total cholesterol were observed in the damaged group than the normal group(P＜0.05).Mean flow velocity(MFV),pulse index(PI),peak systolic velocity(PSV),and levels of GFAP,neuron-specific enolase(NSE)and S-100β were all obviously decreased in both groups after surgery than the levels before(P＜0.05).When compared with the normal group,the damaged group had nota-bly higher serum GFAP level before operation,and lower PI and PSV values and higher GFAP,NSE and S-100β levels after operation(P＜0.05,P＜0.01).Both pre-and post-operative serum GFAP levels were negatively correlated with postoperative MFV,PI and PSV(P＜0.01).The concomitant diabetes,pre-and post-operative serum GFAP levels,and postoperative PSV value and NSE and S-100β levels were independent influencing factors for cerebrovascular reserve in ca-rotid stenosis patients after carotid stent implantation(P＜0.05,P＜0.01).The post-operative se-rum GFAP level showed significantly better value than the pre-operative level in assessing cere-brovascular reserve,with an AUC value of 0.860(95％CI:0.786-0.916)and 0.777(95％CI:0.693-0.847),respectively.Conclusion Serum GFAP level is related to TCD parameters in ca-rotid stenosis patients after carotid stent implantation.Combined GFAP level and TCD parameters together can be used to evaluate the cerebrovascular reserve for the patients.

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.

OBJECTIVE To investigate the analgesic effects and potential mechanisms of the partial agonist of the 5-hydroxytryptamine 1A(5-HT1A)receptor and the selective 5-HT reuptake inhibitor,viladazone(Vil),in various animal models of pain.METHODS ① Mouse acetic acid writhing test:KM mice were divided into the model group,model+morphine 10 mg·kg-1 group,and model+Vil 2,4,8 mg·kg-1 groups.Thirty minutes after ig administration of saline(model group)or corresponding drugs,each group was ip injected with a 2%acetic acid aqueous solution(0.01 mL·g-1),and the writhing frequency of the mice was observed and recorded from 5 to 20 min.② Mouse formalin pain test:KM mice were divided into the model group and model+Vil 2,4 and 8 mg·kg-1 groups.Thirty minutes after ig adminis-tration of saline(model group)or drugs,20 μL of 5%formalin solution was sc injected into the right plantar region of the mice.The licking time(the sum of the duration of licking and biting the paw)of the mice was observed and recorded during two periods:the acute phase(0-5 min after sc formalin injec-tion)and the delayed phase(15-35 min after sc formalin injection).③ Rat chronic constriction injury(CCI)of the sciatic nerve experiment:SD rats successfully examined with a paw withdrawal threshold(PWT)<5 g were randomly divided into a CCI model group and a CCI model+Vil 2,4 and 8 mg·kg-1 group.Solvent(model group)or corresponding drugs were ig administered,and the PWT of the modeled side was measured at 30,60,120 and 240 min after the first administration to evaluate the acute anal-gesic effect of Vil on mechanical pain.Then,Vil was continuously ig administered for 14 d,and the PWT was measured 1 h after Vil administration on the 7th and 14th d to evaluate the long-term analgesic effect of Vil.Immunofluorescence staining was employed to analyze the expression levels of inflamma-tion-related proteins,ionized calcium binding adapter molecule 1(IBA-1),tumor necrosis factor α(TNF-α),and interleukin 1β(IL-1β),in brain tissues.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of IBA-1,TNF-α and IL-1β in the dorsal root ganglion of the spinal cord in the CCI model.RESULTS ① In the mouse model of acetic acid writhing,single ig administration of morphine 10 mg·kg-1 and Vil at varied doses significantly reduced the number of writhings induced by acetic acid compared to the model group.② In the formalin-induced pain model,the average licking time of the model group was 50.5 s during the acute phase of inflammatory pain(0-5 min after intraplantar injec-tion of 5%formalin),and 347.9 s during the delayed phase of inflammatory pain(25-35 min after formalin injection).Compared to the model group,single ig administration of Vil 2-8 mg·kg-1 reduced chronic pain induced by formalin in mice,and each dose of Vil significantly decreased the licking time of mice,but had no notable impact on the licking duration exhibited by mice during acute phase.③ In the CCI model,the PWT values of CCI model rats significantly decreased compared with the control group.Pathological damage to varying extents was observed in brain slices,manifested as enlarged intercellular spaces and the appearance of vacuoles.The expression of IBA-1 in brain tissue significantly increased,while TNF-α and IL-1β hardly changed.The levels of IBA-1,TNF-α and IL-1β in the spinal dorsal root ganglion significantly increased.Compared with the CCI model,after single administration of Vil 2-8 mg·kg-1 for 60,120 and 240 min,Vil significantly reduced the PWT values.After two-week continuous administration,the PWT values in Vil 4 and 8 mg·kg-1 were significantly reduced,and Vil 2-8 mg·kg-1 could alleviate the neuropathic pain to some extent.Vil 8 mg·kg-1 significantly reduced the elevated levels of inflammatory factors compared to CCI rats.CONCLUSION The antidepressant Vil exhibits analgesic effects in mouse models of acetic acid writhing,formalin-induced inflammation,and neuropathic pain induced by CCI in rats,with a more pronounced effect on neuropathic pain.The mechanism of action may be related to the inhibition of inflammatory pathways of IBA-1.

Objective: To investigate the correlation between the levels of calcitonin gene-related peptide α (CGRPα) and the poor responses to the treatment of phenylephrine in pregnant women with hypotension during caesarean section under intraspinal anesthesia. Methods : A total of 87 pregnant women who underwent intraspinal anesthesia cesarean section were recruited . They were grouped according to the presence or absence of hypotension after anesthesia and the response to ephedrine and Phe . As to Anesthesia-0 group , pregnant women had no hypo- tension , 35 cases (40. 2% ) ; Anesthesia-1 group , pregnant women had hypotension and good response to ephed- rine treatment , 12 cases (13 . 8% ) ; Anesthesia-2 group , pregnant women had hypotension and had poor response to ephedrine treatment , 6 cases (6. 9% ) ; Anesthesia-3 group , pregnant women had hypotension and good response to Phe treatment , 8 cases (9. 2% ) ; Anesthesia-4 group , pregnant women had hypotension and no response to Phe treatment , 26 cases (29. 9% ) . The levels of CGRPαin serum and placental tissues of pregnant women were deter- mined by ELISA . The rats pregnant normally. A hypotension rat model was established by intragastric administra- tion of risserpine . 50 rats were randomly divided into control group , model group , pregnancy group , model + preg- nancy group , model + pregnancy + phenylephrine group , with 10 rats in each group . Body weight of the rats was continuously monitored during the 2nd to 6th week of risserpine administration . Systolic blood pressure was meas- ured at the end of the 6th induction week . And the peripheral blood sample and placental tissues were collected and the levels of CGRPαwere determined . Results : The detection of CGRPαlevels in the pregnant women serum and placental tissues showed that compared with Anesthesia-0 group , CGRPαlevels in Anesthesia-1-4 groups serum were higher (P < 0. 05) . Compared with Anesthesia-3 group , serum CGRPαlevels in Anesthesia-4 group were higher (P < 0. 05) . Compared with Anesthesia-2 group , CGRPαlevels in Anesthesia-4 group serum were higher (P < 0. 05) . Compared with Anesthesia-0 group , tissues CGRPαlevels in Anesthesia-4 group were higher (P < 0. 05) . Compared with Anesthesia-3 group , CGRPαlevels in Anesthesia-4 group tissues were higher (P < 0. 05) . Compared with Anesthesia-2 group , CGRPαlevels in Anesthesia-4 group tissues were higher ( P < 0. 05) . From the 2nd to 6th week of hypotension modeling induction , compared with pregnancy group , body weight decreased in the model + pregnancy group and the model + pregnancy + phenylephrine group (P < 0. 05) . There was no signifi- cant difference in baseline systolic blood pressure among all groups (P > 0. 05) . At the end of the 6th week , com- pared with pregnancy group , systolic blood pressure decreased in model + pregnancy group and model + pregnancy + phenylephrine group(P < 0. 05) ; the levels of CGRPαin serum and placental tissues increased ( P < 0. 05) . Compared with model + pregnancy group , systolic blood pressure increased in model + pregnancy + phenylephrine group (P < 0. 05) . Conclusion The poor response of pregnant women with hypotension during caesarean section under intraspinal anesthesia to the treatment of phenylephrine may be related to the increased levels of CGRPαin placenta and peripheral blood .

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 investigate the status of development and application of information system of central sterile supply department(CSSD)in hospitals of China,so as to provide references for the promotion of CSSD information system in hospital.Methods:Hierarchical sampling method was adopted to combine with CSSD Professional Committee of Chinese Nursing Association to design questionnaire for Questionnaire Star Network Survey about basic information,CSSD information system,whether the CSSD information system connected with equipment,tracing links and tracing levels,identification method of apparatuses,automation of equipment in 3,074 hospitals of 22 provinces,4 municipalities directly under the central government,and 5 autonomous regions.Results:In 3,074 hospitals,1,811 hospitals(accounting for 58.91%)adopted the CSSD information system.The utilization rate of tertiary hospitals was 81.90%for the information system,which was higher than that(34.51%)in secondary hospitals,and the difference was statistically significant(x2=636.65,P<0.05).The proportion of hospitals that included the recycling,cleaning,disinfection,inspection and packaging,sterilization,storage,and distribution links of CSSD internal management into information management was all>88%,while the utilization link only accounted for 15.18%.The proportion that surgical apparatuses and the apparatuses of clinical diagnosis and treatment were included in management was higher in 1811 hospitals that used CSSD information system,which were respectively 88.02%and 84.70%,while the proportion of surgical soft endoscope was lower,which only was 49.20%.A total of 84.37%of hospitals conducted informatization management for using extracorporeal apparatuses and implants.The connection rates of the main CSSD equipment,which included the washing and disinfection machine,the pressure steam sterilizer and the low-temperature sterilizer,were connected with information system were respectively 56.60%,63.06%and 43.95%.The full compatibility between the information system and all monitoring methods did not be realized in these hospitals.Barcode was the main identification form(69.91%)of the CSSD information system,and personnel management was the most common management module(53.62%)of the information system.The utilization rate(2.93%-5.14%)of automated equipment was low,and 35.45%of the CSSD information systems had the function of automatic emergency handling.Conclusion:The CSSD informatization management of China has achieved remarkable results,but there are still problems such as insufficient connection of equipment,inclusion of monitoring data,and insufficient automation and intelligence.It is necessary to increase the promotion efforts to promote the high-quality development of hospitals.

Objective To explore the effectiveness of integrating virtual simulation technology with case-based learning(CBL)in the teaching of clinical blood transfusion testing technology.Methods From January to June 2024,99 undergraduate students majoring in medical laboratory science at our university were selected and divided into an observation group(50 students)and a control group(49 students)based on their classes.The control group followed a traditional theoretical teaching model,while the observation group employed virtual simulation technology combined with CBL.Results The study compared as-sessment scores for theory learning,practical skills,case analysis,and comprehensive quality,teaching effects such as coordina-tion and cooperation abilities,self-efficacy measured by the GSES scale,and teaching satisfaction between the two groups.The results indicated that the observation group had significantly higher scores in all assessment categories,teaching effect abilities,and total GSES scores compared to the control group(P＜0.05).The total teaching satisfaction rate in the observation group reached 100%,significantly higher than the 80% in the control group(P＜0.05).Conclusion The integration of virtual simu-lation technology with CBL innovates the teaching model for clinical blood transfusion testing courses,effectively enhancing students'professional skills and comprehensive quality,boosting self-efficacy,and achieving high student satisfaction,demon-strating significant potential for broader application.

Purpose To compare the HRCT findings of lung damage in patients with idiopathic inflammatory myopathies(IIMs)with positive and negative anti-Ro-52 antibody.Materials and Methods Fifty patients with IIMs admitted to Beijing Shijitan Hospital,Capital Medical University from January 2015 to July 2023 were retrospectively analyzed.The patients were divided into anti-Ro-52 antibody negative group(18 cases)and positive group(32 cases),the lung CT findings of the two groups were compared,the distribution of lung lesions and related signs were analyzed.Results The incidence of interstitial lung disease in the anti-Ro-52 antibody-negative group was 11.1%(1 case),which was lower than that in the positive group 75.6%(31 cases)(P=0.001).Among the interstitial lung disease-positive patients,the proportion of lesions in the anti-Ro-52 positive group was more symmetrical(28 cases,87.5%,P=0.022)and peripheral distribution(20 cases,62.5%,P=0.039)than that in the anti-Ro-52 negative group.Non-specific interstitial pneumonia-like lesions were the main lesions in the two groups,including 14 cases(43.8%)in the anti-Ro-52 positive group and 7 cases(38.9%)in the negative group.However,9 cases(28.1%)of the anti-Ro-52 positive group had acute interstitial pneumonia-like lesions and 1 case(5.6%)of the negative group had acute interstitial pneumonia-like lesions.Imaging accompanying signs:anti-Ro-52 positive combination and consolidation(14 cases,43.8%,P=0.009),nodular shadow(17 cases,53.1%,P=0.025),and reverse halo sign(12 cases,37.5%,P=0.021)were more than those in the anti-Ro-52 negative group.Conclusion IIMs patients with positive anti-Ro-52 antibody have a higher incidence of interstitial lung disease.HRCT findings are of great significance for diagnosis and treatment of IIMs.

OBJECTIVE To investigate the analgesic effects and potential mechanisms of the partial agonist of the 5-hydroxytryptamine 1A(5-HT1A)receptor and the selective 5-HT reuptake inhibitor,viladazone(Vil),in various animal models of pain.METHODS ① Mouse acetic acid writhing test:KM mice were divided into the model group,model+morphine 10 mg·kg-1 group,and model+Vil 2,4,8 mg·kg-1 groups.Thirty minutes after ig administration of saline(model group)or corresponding drugs,each group was ip injected with a 2%acetic acid aqueous solution(0.01 mL·g-1),and the writhing frequency of the mice was observed and recorded from 5 to 20 min.② Mouse formalin pain test:KM mice were divided into the model group and model+Vil 2,4 and 8 mg·kg-1 groups.Thirty minutes after ig adminis-tration of saline(model group)or drugs,20 μL of 5%formalin solution was sc injected into the right plantar region of the mice.The licking time(the sum of the duration of licking and biting the paw)of the mice was observed and recorded during two periods:the acute phase(0-5 min after sc formalin injec-tion)and the delayed phase(15-35 min after sc formalin injection).③ Rat chronic constriction injury(CCI)of the sciatic nerve experiment:SD rats successfully examined with a paw withdrawal threshold(PWT)<5 g were randomly divided into a CCI model group and a CCI model+Vil 2,4 and 8 mg·kg-1 group.Solvent(model group)or corresponding drugs were ig administered,and the PWT of the modeled side was measured at 30,60,120 and 240 min after the first administration to evaluate the acute anal-gesic effect of Vil on mechanical pain.Then,Vil was continuously ig administered for 14 d,and the PWT was measured 1 h after Vil administration on the 7th and 14th d to evaluate the long-term analgesic effect of Vil.Immunofluorescence staining was employed to analyze the expression levels of inflamma-tion-related proteins,ionized calcium binding adapter molecule 1(IBA-1),tumor necrosis factor α(TNF-α),and interleukin 1β(IL-1β),in brain tissues.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of IBA-1,TNF-α and IL-1β in the dorsal root ganglion of the spinal cord in the CCI model.RESULTS ① In the mouse model of acetic acid writhing,single ig administration of morphine 10 mg·kg-1 and Vil at varied doses significantly reduced the number of writhings induced by acetic acid compared to the model group.② In the formalin-induced pain model,the average licking time of the model group was 50.5 s during the acute phase of inflammatory pain(0-5 min after intraplantar injec-tion of 5%formalin),and 347.9 s during the delayed phase of inflammatory pain(25-35 min after formalin injection).Compared to the model group,single ig administration of Vil 2-8 mg·kg-1 reduced chronic pain induced by formalin in mice,and each dose of Vil significantly decreased the licking time of mice,but had no notable impact on the licking duration exhibited by mice during acute phase.③ In the CCI model,the PWT values of CCI model rats significantly decreased compared with the control group.Pathological damage to varying extents was observed in brain slices,manifested as enlarged intercellular spaces and the appearance of vacuoles.The expression of IBA-1 in brain tissue significantly increased,while TNF-α and IL-1β hardly changed.The levels of IBA-1,TNF-α and IL-1β in the spinal dorsal root ganglion significantly increased.Compared with the CCI model,after single administration of Vil 2-8 mg·kg-1 for 60,120 and 240 min,Vil significantly reduced the PWT values.After two-week continuous administration,the PWT values in Vil 4 and 8 mg·kg-1 were significantly reduced,and Vil 2-8 mg·kg-1 could alleviate the neuropathic pain to some extent.Vil 8 mg·kg-1 significantly reduced the elevated levels of inflammatory factors compared to CCI rats.CONCLUSION The antidepressant Vil exhibits analgesic effects in mouse models of acetic acid writhing,formalin-induced inflammation,and neuropathic pain induced by CCI in rats,with a more pronounced effect on neuropathic pain.The mechanism of action may be related to the inhibition of inflammatory pathways of IBA-1.