Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To establish an element framework and template of broad informed consent applicable to clinical research,and to standardize the collection,storage,and reuse of medical data and biological samples,making them comply with ethical and legal requirements.Methods:A literature review and group discussion were employed to construct the draft of the element framework and template of broad informed consent form.The Delphi expert consultation method was used to conduct two rounds of correspondence with 13 experts in relevant fields to determine the two-level element framework and template of broad informed consent form.Results:The response rates for the two rounds of expert consultation questionnaires were above 90%,the experts'positive coefficients were good,and the coefficients of authority(Cr)were higher than 0.85.In the second round of consultation,the average importance value was≥4.4,the coefficient of variation(CV)was<0.17,and Kendall's W was 0.184(P<0.001),indicating that the expert opinions tended to be consistent.Ultimately,an element framework and template of broad informed consent form was established,consisting of 4 first-level items and 21 second-level items.Conclusion:The constructed element framework and template of broad informed consent form is highly scientific and applicable,providing references for clinical research.

ObjectiveTo investigate the relationship between mitochondrial DNA copy number (mtDNAcn) and cognitive dysfunction, and its mediating role between type 2 diabetes mellitus (T2DM) and cognitive dysfunction. MethodsA case-control study was conducted from May 2019 to April 2021 at the Shanghai Yangpu District Central Hospital, China. A total of 193 subjects were recruited and divided into two groups based on the Montreal Cognitive Assessment (MoCA): normal control (NC) group (n=95) and cognitive impairment group (n=98). The prevalence of T2DM was determined on the basis of medical history, while mtDNAcn in peripheral blood samples was quantified using realtime fluorescent quantitative polymerase chain reaction. ResultsUnivariate analyses revealed that the mean mtDNAcn in the cognitive impairment group was 0.76±0.37, significantly lower than that in the NC group (1.06±0.45) (P<0.05). Logistic regression analyses showed that higher mtDNAcn was associated with a reduced risk of cognitive impairment (OR=0.315, 95%CI: 0.125‒0.795). Additionaly, a statistically significant positive correlation was observed between mtDNAcn and the total MoCA score (r=0.381, P<0.01). Morever, T2DM history (OR=2.741, 95%CI: 1.002‒7.497) and elevated glycosylated hemoglobin (HbA1c) levels (OR=1.796, 95%CI: 1.190‒2.711) were identified as risk factors for cognitive impairment. Mediation analyses indicated that mtDNAcn served as a mediator between T2DM/HbA1c and the risk of cognitive impairment, with proportions of mediating effect of 9.04% and 9.18%, respectively. ConclusionPatients with mild and moderate cognitive impairment have significantly lower mtDNAcn than those with normal cognitive function. Reduced mtDNAcn is an influencing factor for cognitive dysfunction and may play a mediating role in the association between T2DM and mild to moderate cognitive impairment.

Objective To explore the application effects of an innovative teaching model(blended 5MP)that organically combines blended teaching and the five-minute teaching method in clinical teaching for operating room nursing students.Methods Using convenience sampling,94 nursing students who interned in operating room of Kunming Children's Hospital from July 2023 to March 2024 were randomly assigned to observation and control groups,with 47 students in each group.For the control group,a traditional blended learning approach was utilized,whereas the observation group implemented a blended 5MP teaching model.Results The observation group's post-class assignment scores,theoretical exam scores,and practical skills assessment scores were all significantly higher than those in the control group,with a statistically significant difference(P<0.05).The observation group also had higher scores in the Self-Assessment of Clinical Reasoning and Reflection Scale,with a statistically significant difference(P<0.05).Furthermore,the observation group reported higher satisfaction rates regarding teaching methods,teaching formats,theoretical instruction,practical instruction,and overall satisfaction compared to the control group,with statistically significant differences(P<0.05).Conclusion The blended approach combines online and offline instructional modalities,allowing for a more strategic allocation of educational resources.This methodology enables students to thoroughly acquire essential knowledge and skills while simultaneously fostering advanced clinical reasoning and reflective competencies.By adopting this innovative educational model,institutions can significantly enhance the academic experience and professional development of nursing students.

Objective: To investigate the effect of loss of function of lanosterol synthase( LSS) gene on intestinal function in a mouse model of non-alcoholic fatty liver disease( NAFLD) induced by a high-fat diet． Methods: LSS gene heterozygous knockout C57 mice ( LSS + / －) were established using the CRISRP / Cas9 system．After being fed a high-fat diet with 60% fat content for 6 months，the fat deposition in liver tissues was detected by HE and Oil red O staining，the morphological changes of small intestine tissue were detected by HE staining．The changes in total cholesterol content in intestinal tissue were detected by kits．The gastrointestinal motility function of mice was detected by phenol red paste．The intestinal permeability was detected by Evans blue staining，and the expression of LSS，tight junction protein ( Claudin) -1，Claudin-5，cluster of differentiation 36 ( CD36) ，and Niemann-Pick type C1-like 1 protein ( NPC1L1) proteins in small intestinal tissues were detected by Western blot． Results : The results of HE and Oil red O staining of liver tissues showed that liver fat deposition in LSS gene heterozygous knockout mice was lower than that in wild-type mice in the high-fat diet group．The total cholesterol content in intestinal tis- sue of LSS gene heterozygous knockout mice decreased ( P ＜0. 01) ，but no morphological differences were ob- served between the two groups of mice by HE staining of intestinal tissues．The gastrointestinal motility function of LSS gene heterozygous knockout mice did not show significant changes．The intestinal permeability of LSS gene het- erozygous knockout mice in the high-fat diet group decreased as detected by Evans blue ( P＜0. 05) ．The expres- sion levels of Claudin-5 protein in the intestinal tissue of LSS gene heterozygous knockout mice in the high-fat diet group increased ( P ＜0. 05 ) ，while the expression of LSS protein in the intestinal tissues of LSS heterozygous knockout mice decreased ( P ＜0. 05) ． Conclusion In the NAFLD model induced by a high-fat diet，LSS gene heterozygous knockout reduces liver fat deposition induced by a high-fat diet and improves intestinal barrier function by regulating cholesterol metabolism in intestinal tissues and up-regulating the expression of Claudin-5．

Objective : To explore the changes in behavior and spatial memory of C57BL/6J female mice of different ages (youth , middle-aged , and elderly) . Methods: C57BL/6J female mice were divided into female youth group (YG group) , female middle-aged group ( MG group) and female elderly group ( OG group) according to age. The Morris water maze test measured spatial memory ability , and the open field and elevated cross maze test observed activity level and anxiety level. Western blot was used to determine the protein expressions of CREB , CaMKⅡ(pan) and CaMKⅡ(p) in the hippocampus of the brain tissues of female mice in each group. Results: Compared with the YG group , the weight of the MG group and the OG group significantly increased (P < 0. 01 , P < 0. 001) . Compared with the OG group , the third quadrant escape latency and the number of crossings in the YG group and MG group were shortened , and the difference was not statistically significant. Compared with the OG group , there was a statistically significant difference in the exercise speed in the open field of the YG group (P < 0. 01) , there was no significant difference in the movement speed in the open field of the MG group , the number of entries into the central zone significantly increased in the MG group ( P < 0. 05 ) , and there was no significant difference in the number of entries in the YG group (P > 0. 05) . Compared with the OG group , the YG group had a statistically significant difference in the elevated cross maze (P < 0. 05) , the MG group had no statistically signif- icant difference in the elevated cross maze , and the number of closed arm entries in the YG group and MG group significantly increased (P < 0. 001 , P < 0. 01) . Compared with the YG group , the relative expression level of CaMKⅡ(pan) in the OG group was statistically significant ( P < 0. 05 ) , while the relative expression level of CaMKⅡ(pan) in the MG group was not statistically significant ( P > 0. 05) . Conclusion With the increase of age , the weight of C57BL/6J female mice gradually increased , the activity level and desire to explore gradually de- creased , the spatial memory ability also declined , and the anxiety level and anxiety-like behavior increased. This study helps to reveal the effect of age on the activity level and cognitive function of females , and provides a refer- ence for studying cognitive and memory decline in older females.

Ornithine transcarbamylase(OTC)is a member of the transcarbamylase protein family,commonly found in the mitochondrial matrix of living organisms.It generally functions in a trimeric form and can catalyze the production of L-ornithine to L-citrulline.OTC is mainly expressed in the liver and intestines of mammals,playing an important role in the urea cycle and amino acid homeostasis.This article introduces the research progress of OTC genes,proteins,physiological functions,the impact of OTC deficiency on body health,and the diagnosis and treatment of OTC deficiency.

Objective:To understand the current status of epidemiological investigation task force construction and the performance of infectious disease epidemic response in county (district) Centers for Disease Control and Prevention (CDCs) in China, analyze the influencing factors and provide scientific evidence to improve the construction of grassroot epidemiological investigation task force.Methods:A survey was conducted in epidemiological investigation staff in county (district) CDCs in 31 provinces (autonomous regions/municipalities) and Xinjiang Production and Construction Corps in China. A self-designed questionnaire was used to collect information based on the epidemiological dynamic data collection platform of China CDC. A descriptive epidemiological analysis was conducted, and multiple linear regression models were used to identify the factors associated with the performance of infectious disease epidemic response.Results:A total of 24 934 epidemiological investigation task force members from 2 897 county (district) CDCs were surveyed in the study. In the epidemiological investigation task force, women, those with bachelor's degree and public health workers accounted for 62.46%, 71.36%, and 49.05% respectively. Up to 91.72% of the task force members had participated in field epidemic response. The average score of awareness of epidemic investigation procedures was 60.00, while the average score of key skill proficiency in the investigation was 42.22. The epidemic response performance showed correlations with area, gender, age, education level, major, and field epidemiology training programs, those who had received longer training showed higher competency scores (all P<0.001). Conclusions:Progress has been made in the construction of epidemiological investigation task force in grass-root CDCs in China, but further improvements are needed, especially in the knowledge awareness and investigation skills of the task force. Field epidemiology training demonstrated substantial impact on the improvement of epidemic response performance, indicating that it is necessary to further strengthen the training in grassroot public health workers for the better response to infectious disease epidemics.

Objective To investigate the value of constructing a risk prediction model of brain metastasis in lung cancer based on clinical-CT imaging.Methods The clinical and CT imaging data of 208 patients with lung cancer confirmed by surgical pathology or puncture biopsy were analyzed retrospectively,including 98 patients in the metastasis group and 110 patients in the non-metastasis group.Univariable and binary logistic regression analyses were performed between the two groups,and the clinical,CT imaging,and clinical-CT imaging models were constructed according to the selected independent risk factors.Prediction model performance was eval-uated with receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA).Results Multivariate analysis showed that T stage,pathological type,radiotherapy and chemotherapy,surgery,long diameter(LD),short diameter(SD),minimum CT value(CTmin)were the independent risk factors for predicting brain metastasis in lung cancer(P<0.05).The area under the curve(AUC)of clinical,CT imaging and clinical-CT imaging models were 0.925,0.764,0.941,respectively.DeLong test analysis showed that the AUC of clinical-CT imaging model,clinical model and CT imaging model was statistical difference(Z=2.093,5.777,all P<0.05).The calibration curve suggested a good fit of the clinical-CT imaging model.The DCA suggested that the clinical-CT imaging model demonstrates good clinical benefits.Conclusion The clinical-CT imaging model can effectively predict the occurrence of brain metastasis in lung cancer,which is helpful to guide the development of accurate diagnosis and treatment plan.

Objective To investigate the value of constructing a risk prediction model of brain metastasis in lung cancer based on clinical-CT imaging.Methods The clinical and CT imaging data of 208 patients with lung cancer confirmed by surgical pathology or puncture biopsy were analyzed retrospectively,including 98 patients in the metastasis group and 110 patients in the non-metastasis group.Univariable and binary logistic regression analyses were performed between the two groups,and the clinical,CT imaging,and clinical-CT imaging models were constructed according to the selected independent risk factors.Prediction model performance was eval-uated with receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA).Results Multivariate analysis showed that T stage,pathological type,radiotherapy and chemotherapy,surgery,long diameter(LD),short diameter(SD),minimum CT value(CTmin)were the independent risk factors for predicting brain metastasis in lung cancer(P<0.05).The area under the curve(AUC)of clinical,CT imaging and clinical-CT imaging models were 0.925,0.764,0.941,respectively.DeLong test analysis showed that the AUC of clinical-CT imaging model,clinical model and CT imaging model was statistical difference(Z=2.093,5.777,all P<0.05).The calibration curve suggested a good fit of the clinical-CT imaging model.The DCA suggested that the clinical-CT imaging model demonstrates good clinical benefits.Conclusion The clinical-CT imaging model can effectively predict the occurrence of brain metastasis in lung cancer,which is helpful to guide the development of accurate diagnosis and treatment plan.