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 analyze the acupoint selection law of acupuncture and moxibustion for pediatric cerebral palsy based on data mining techniques.Methods Clinical research literature about acupuncture and moxibustion for the treatment of pediatric cerebral palsy was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from the establishment of the databases to April 1,2024.Excel 2021 was used to establish a database of prescription acupoints.The frequency of use of acupoints,attributed to the meridians,parts and specific acupoints were under statistically analysis,and SPSS Modeler 18.0 and SPSS Statistics 27.0 were used to conduct the association rules analysis,factor analysis and clustering analysis of acupoints.Results A total of 579 articles were included,579 prescriptions were extracted,containing 245 acupoints with the frequency of 6 422 times.The high-frequency acupoints were Zusanli,Baihui,Hegu,Sanyinjiao and Quchi,etc.The commonly used meridians were Governor Vessel,gall bladder meridian,stomach meridian,large intestine meridian and bladder meridian;mostly used acupoints were in the lower limbs,head and neck,upper limbs,waist and back.The association rules analysis showed that the top combinations were"Hegu-Quchi","Zusanli-Quchi","Zusanli-Quchi-Hegu","Hegu-Quchi-Zusanli";clustering analysis showed that 6 valid clusters were extracted;factor analysis extracted 7 valid common factors.Conclusion Acupuncture and moxibustion treatment for pediatric cerebral palsy is based on the principle of strengthening the brain,improving intelligence and tonifying the five zang organs,reflecting the principle of matching acupoints far and near.The core combination of acupoints is"Zusanli-Quchi-Hegu".

Objective To investigate the correlation of vascular senescence indicators,brachial-ankle pulse wave velocity(baPWV),cardio-ankle vascular index(CAVI),ankle-brachial index(ABI)with total burden of MRI in patients with cerebral small vessel disease(CSVD).Methods A total of 200 CSVD patients admitted to our hospital from November 2023 to October 2024 were retrospectively recruited,and based on their total MRI burden,they were divided into a low-burden group(score:0-1,103 cases)and a high-burden group(score:2-4,97 cases).A athero-sclerosis monitoring device(VS-1500A)was used to detect baPWV,CAVI,and ABI values.The relationships of the three indicators with total MRI burden score and their predictive values for the burden score were analyzed.Results The high-burden group had significantly higher BMI,el-evated homocysteine and uric acid levels,and increased baPWV and CAVI,but lower ABI than the low-burden group(P＜0.01).Multivariate logistic analysis showed that baPWV,CAVI and ABI were independent influencing factors for high MRI burden of CSVD patients.Spearman correlation analysis showed that baPWV and CAVI values were positively correlated(r=0.589,P=0.000;r=0.458,P=0.000),and ABI was negatively correlated with the total MRI burden score of CSVD patients(r=-0.352,P=0.000).ROC curve analysis showed that baPWV(AUC=0.816,P=0.000),CAVI(AUC=0.725,P=0.000)and ABI(AUC=0.676,P=0.000)were all predic-tors for high MRI burden score in CSVD patients.Conclusion baPWV and CAVI are positively,and ABI is negatively correlated with the total MRI burden score of CSVD patients.baPWV,CAVI and ABI show higher predictive value for the high burden score,with baPWV most significant.

Objective:To evaluate the efficacy of an etoposide (Vp16) -intensified conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of relapsed/refractory acute myeloid leukemia (AML).Method:A retrospective analysis was conducted on the clinical data of 27 recipients with relapsed/refractory AML who underwent allo-HSCT using a Vp16-intensified conditioning regimen at Aerospace Center Hospital from January 2019 to January 2022. Transplantation-related complications and treatment outcomes were observed. Kaplan-Meier survival analysis was used to assess the overall survival (OS) and disease-free survival (DFS) rates.Result:Among the 27 recipients, there were 14 males and 13 females, with a median age of 41 years (range: 12~55 years). Except for one recipient who experienced primary graft failure, the remaining 26 recipients achieved hematopoietic reconstitution. The median neutrophil and platelet engraftment times were 13 days (range: 9~20 days) and 13.5 days (range: 11~33 days), respectively. Regimen-related toxicity (RRT) was mainly gastrointestinal toxicity and oral mucositis, and no deaths were attributed to RRT. A total of 12 recipients (44.44%) developed acute graft-versus-host disease (aGVHD), of whom 3 cases (11.11%) had grade III~IV aGVHD. Chronic GVHD (cGVHD) occurred in 13 recipients (48.15%), including 8 cases (29.63%) of extensive cGVHD. The median follow-up time after transplantation was 17 months (range: 1~48 months). Fifteen recipients (55.56%) survived without disease, while 12 recipients (44.44%) died— 9 due to relapse and 3 due to transplant-related complications. The 1-year overall survival and DFS rates were 74.07% and 59.26%, respectively; the 2-year overall survival and DFS rates were 59.26% and 55.56%, respectively. The 2-year relapse rate and transplant-related mortality (TRM) were 33.33% and 11.11%, respectively.Conclusion:The Vp16-intensified conditioning regimen in allo-HSCT appears to be a viable treatment option for patients with relapsed/refractory AML, offering favorable efficacy and manageable safety.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective:To construct and validate a prognostic prediction model for patients with ovarian metastases from colorectal cancer after radical resection.Methods:A retrospective case series analysis was conducted on the clinical and pathological data of 81 patients with colorectal cancer and ovarian metastases who underwent radical resection for ovarian metastases at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, between January 2014 and December 2023. The patients were all female, with an age ( M(IQR)) of 49(13) years (range: 22 to 79 years). The primary tumor was located in the colon in 60 cases (74.1%) and in the rectum in 21 cases (25.9%). Univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting prognosis. A risk scoring system was constructed, and patients were assigned to high-risk and low-risk groups based on their risk scores. The predictive performance of the scoring system was assessed, and 5-fold cross-validation was performed to evaluate the model′s stability on the internal dataset. Results:Among the 81 patients with ovarian metastases, a high proportion had T4 stage (58 cases, 71.6%), lymph node positivity (68 cases, 84.0%), and colon cancer (60 cases, 74.1%). Preoperative imaging suggested unilateral ovarian metastasis in 15 patients (23.4%), but pathological examination after bilateral oophorectomy confirmed bilateral ovarian metastases. Among the 17 patients who initially underwent unilateral oophorectomy, 11 developed contralateral ovarian metastases at varying times postoperatively. Univariate Cox proportional hazards regression analysis revealed that positive lymph node ratio ( HR=2.68,95% CI:1.41 to 5.09, P=0.003), N stage ( HR=2.07,95% CI:1.08 to 3.95, P=0.028),maximum diameter of metastatic tumors ( HR=2.27,95% CI:1.04 to 4.96, P=0.040),and peritoneal metastasis or ascites at the time of ovarian metastasis ( HR=2.04,95% CI:1.02 to 4.08, P=0.043) were significantly associated with overall survival in patients with ovarian metastasis from colorectal cancer. Multivariate regression analysis identified that positive lymph node ratio ( HR=3.34,95% CI:1.08 to 10.34, P=0.037) and maximum diameter of metastatic tumors ( HR=2.65,95% CI:1.19 to 5.88, P=0.017) were independent prognostic factors for overall survival following radical oophorectomy in patients with ovarian metastasis from colorectal cancer. Based on the regression coefficients from the multivariate analysis for variables (ovarian metastatic tumor diameter ≥6 cm, positive lymph node ratio ≥0.3,and presence of peritoneal metastasis or ascites), a risk scoring system was developed. Using the optimal cutoff value (154 points) for the risk score,patients were divided into high-risk (19 cases) and low-risk (62 cases) groups. Kaplan-Meier survival curves demonstrated that the high-risk group had significantly lower median overall survival (27 months) and median disease-free survival (22 months) compared to the low-risk group (median overall survival 90 months,median disease-free survival not reached; both P<0.01). Receiver operating characteristic curve analysis showed that the area under the curve(AUC) for predicting 1-,3-,and 5-year overall survival was 0.731(95% CI:0.563 to 0.899), 0.703(95% CI:0.573 to 0.833), and 0.776(95% CI: 0.657 to 0.894), respectively. The AUC for predicting 1-,3-, and 5-year disease-free survival was 0.724(95% CI:0.397 to 0.993),0.710(95% CI:0.514 to 0.906),and 0.688(95% CI:0.478 to 0.898),respectively,indicating good performance of the model.The decision curve analysis showed that the model has good clinical net benefit and the results of the 5-fold cross-validation showed that the model demonstrated stability in the internal dataset. Conclusions:When performing radical resection for ovarian metastasis from colorectal cancer,bilateral oophorectomy should be considered to minimize the risk of postoperative recurrence. Patients with ovarian metastasis from colorectal cancer,characterized by a metastatic tumor diameter ≥6 cm,a positive lymph node ratio ≥0.3,and the presence of peritoneal metastasis or ascites, tend to have a poorer prognosis. Based on these findings,a clinical prognostic scoring system for radical resection of ovarian metastasis from colorectal cancer has been developed to stratify patients into different risk groups and may assist in postoperative risk assessment and management.

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 effects of Duzhi Pills combined with MOTOmed training on limb function and activities of daily living in patients with cerebral infarction of qi deficiency and blood stasis type.Methods A prospective randomized controlled trial enrolled 98 cerebral infarction patients with qi deficiency and blood stasis treated at Qinhuangdao Hospital,Oriental Hospital of Beijing University of Chinese Medicine(Qinhuangdao Hospital of Traditional Chinese Medicine)from June 2022 to December 2024.Participants were randomized into control group(n=49,receiving conventional rehabilitation)and observation group(n=49,receiving additional Duzhi Pills+MOTOmed training)for 8 weeks.All patients received standard medication.Limb motor function and activities of daily living,and quality of life were assessed before and after treatment.Results(1)After treatment,both groups showed significant increases in Carroll Hand Function Test for Upper Extremity(CHFT-UE)scores,Fugl-Meyer Assessment Scale for Upper Extremity(FMA-UE)scores,and Simple Test for Evaluating Hand Function(STEF)scores compared to baseline(P＜0.05),with significantly greater improvements observed in the observation group(P＜0.01).(2)After treatment,both groups exhibited significant increases in Barthel Index scores for daily activity(P＜0.05),with the observation group demonstrating significantly greater improvement(P＜0.01).(3)After treatment,all subscale scores of the 36-Item Short-Form Health Survey(SF-36),including physical function,bodily pain,mental health,vitality,social functioning,emotional role,and general health,were significantly increased in both groups(P＜0.05),with significantly greater improvements in the observation group,the difference being statistically significant(P＜0.01).Conclusion The combined regimen of Duzhi Pills and MOTOmed training significantly enhances limb function,daily activity,and quality of life in cerebral infarction patients with qi deficiency and blood stasis syndrome,demonstrating clinical value for rehabilitation.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.