Objective To investigate the role of circular RNAs(circRNA)in Alzheimer's disease(AD)and its potential mechanism.Methods Six-month-old APP/PS1 mouse model of AD and wild type(WT)mice were subjected and then randomly divided into WT group,WT+circ-Olfm1 knockout group,AD group(transgenic APP/PS1 mice),AD+circ-Olfm1 knockout group,AD+FOXO3a knockout group,with 3 mice in each group.① The total RNA of mouse brain was extracted,and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected,and the obtained circRNAs and mRNAs were analyzed with gene ontology(GO)analysis.② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs,as well as the expression of circ-Olfm1 and miR-330-5p.③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene.Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function,and immunofluorescence assay was employed to observe the deposition of amyloid β(Aβ)plaque in the brain.④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis.⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting.⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus.⑦ The levels of inflammatory factors IL-6,IL-1β and TNF-α were detected by ELISA.Results There were totally 52 differentially expressed circRNAs identified between the AD and WT mice,including 28 up-regulated and 24 down-regulated(fold change>1.5,P<0.05).These differentially expressed genes are mainly involved in signal transduction,learning and memory and other functions.circ-Olfm1 was identified as the most significantly differentially expressed circRNA,which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice.Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice(P<0.01).In starBase database,there are complementary sequences observed between circ-Olfm1 and miR-330-5p.Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells(P<0.01).And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42(P<0.01).ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage(P<0.01).Conclusion circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats,and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

[Objective]To investigate the relationship between the non-fasting triglyceride and glucose(TyG)index and hyperglycemia in pregnancy during the third trimester in high altitudes.[Methods]This study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region,from January 2023 to April 2025.The non-fasting TyG index was calculated from non-fasting triglyceride(TG)and random plasma glucose(PG).Based on the tertiles of the non-fasting TyG index values,the individuals were split into three groups(corresponding to non-fasting TyG index of 8.89 and 9.21,respectively).The baseline clinical characteristics,lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups.Statistical analyses were performed using ANOVA,Kruskal-Wallis H test,Chi-square test,or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting.[Results]A total of 774 Tibetan singleton pregnant women were included,with a average age of 27.3±6.1 years,a pre-delivery body mass index(Pre-BMI)of(25.2±2.3)kg/m2,a proportion of 26.7%(207/774)primigravid women,the mean non-fasting TyG index was 9.1±0.4.Thirty pregnant women were diagnosed with hyperglycemia in pregnancy,with a detection rate of 3.9%(30/774).Statistically significant differences in serum total cholesterol(TC),TG,low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)levels were identified when comparing different non-fasting TyG groups(all P values<0.05).Subsequent trend test analysis indicated that the levels of TC,TG,LDL-C,and PG gradually increased with elevated the non-fasting TyG index(Ftrend TC=95.61,P<0.001;Ftrend TG=1 051.91,P<0.001;Ftrend LDL-C=97.20,P<0.001;Ftrend TG=195.20;P<0.001).After adjustment for maternal age,pre-delivery BMI,altitude,TC,LDL-C,and HDL-C,multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy(Model 1:OR=2.72,95%CI:1.13-6.53,P=0.026;Model 2:OR=2.56,95%CI:1.01-6.50,P=0.048;Model 3:OR=2.72,95%CI:1.06-6.97,P=0.037;Model 4:OR=4.02,95%CI:1.42-11.40,P=0.009)and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index,however,this association did not statistical significance(P trend>0.05).Curve fitting by restricted cubic splines(RCS)were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy,and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy(P for non-linear=0.515).[Conclusion]Non-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.

Objective To investigate the effects of amylin,also known as islet amyloid polypeptide(IAPP),on learning and memory abilities and the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway in APP/PS1 mice.Methods A total of 20 APP/PS1 mice were randomly divided into Alzheimer's disease(AD)group and IAPP group,with 10 mice in each group.The mice in the latter group were given an intraperitoneal injection of 0.5 μmol/L IAPP,and those of the former group received same dose of PBS.Both interventions were given once per day,for 10 weeks.Morris water maze test was used to measure the learning and memory abilities;HE staining was employed to observe the pathological changes in the hippocampus;Transmission electron microscopy was utilized to observe the ultrastructure of hippocampal neurons;Biochemical assay were conducted to detect the contents of glutathione peroxidase(GSH-Px),malondialdehyde(MDA)and superoxide dismutase(SOD)in hippocampal tissues;ELISA was applied to measure the levels of inflammatory factors such as IL-1β,IL-6,and TNF-α as well as content of Aβ42 in hippocampal tissues;And Western blotting was conducted to detect the expression of PI3K/Akt proteins.Results Compared with the AD group,significantly shorter platform latency(P＜0.01),increased number of traversing the platform and longer time to explore the hidden platform(P＜0.01)were observed in the IAPP group,but no such difference was seen in the swimming speed of the mice.HE staining displayed that the IAPP group had more and well-arranged nerve cells in the hippocampal tissue when compared with the AD group(P＜0.05).Lower Aβ protein expression(P＜0.01),reduced oxidative stress and decreased contents of inflammatory factors(P＜0.01)in hippocampal tissue were observed in the IAPP group than the AD group.The IAPP group showed clearer structure of neuronal mitochondria,reduced vacuolization,and better arranged microtubules and microfilaments,and elevated expression of p-PI3K/PI3K and p-Akt/Akt proteins when compared with the AD group(P＜0.01).Conclusion Amylin can reduce oxidative stress and inflammatory responses,improve learning and memory abilities in AD mice,and promote the activity of PI3K/Akt signaling pathway.

BackgroundThe prevalence of depressive disorder in adolescents is on the rise. There have been studies on the pairwise relations between dysfunctional attitude， negative automatic thoughts， positive coping style and depressive symptoms in the past. However， the impact of the intrinsic relations among dysfunctional attitude， negative automatic thoughts and positive coping style on depressive symptoms is still unclear. ObjectiveTo explore the influence of dysfunctional attitude on adolescent depressive symptoms and examine the action path of negative automatic thoughts and positive coping style on it， in order to provide references for intervention for adolescent patients with depressisve disorder. MethodsThis study involved 162 adolescent patients with depressive disorder， who met the diagnostic criteria for depressive episodes in the International Classification of Diseases， 10th edition （ICD-10） and received treatment in Taiyuan Psychiatric Hospital from October 1， 2022 to October 31， 2023. These patients were evaluated using Self-rating Depression Scale （SDS）， Dysfunction Attitude Scale （DAS）， Positive Coping Style Subscale in Simplified Coping Style Questionnaire（SCSQ） and Automatic Thoughts Questionnaire （ATQ）. Pearson correlation analysis was adopted to examine the correlation among scores of scales above. Model 6 in Process 3.4.1 was adopted to test the acting path of negative automatic thoughts and positive coping style between dysfunctional attitude and adolescent depression symptoms. ResultsA total of 148 adolescent patients with depressive disorder completed an effective questionnaire survey， with a response rate of 91.36%. The direct effect value of dysfunctional attitude on depressive symptoms was 0.423 and the effect size was 63.32%. Negative automatic thoughts and positive coping style affected as acting path between dysfunctional attitude and depressive symptoms， with effect values of 0.156 （accounting for 23.35% of the total effect） and 0.045 （accounting for 6.74% of the total effect） respectively. Meanwhile， negative automatic thoughts and positive coping style affected as a chain reaction pathway between dysfunctional attitude and depressive symptoms， with an effect value of 0.044， accounting for 6.59% of the total effect. ConclusionDysfunctional attitude can not only directly affect the depressive symptoms of adolescent patients with depressive disorder， but also affect the depressive symptoms of adolescent patients with depressive disorder through the independent path or chain path of negative automatic thoughts and positive coping style.

Objective:To explore the causal relationship between social activity and depressive symptoms in the elderly, and to provide a reference for preventing and interventing depressive symptoms in the elderly.Methods:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) program, involving 3 164 elderly individuals aged≥60 years with data collected in two measurements, in 2015 (T1) and 2018 (T2). The sample included 1 240 males and 1 924 females aged (71±7) years. Social activities were assessed by constructing a social activity index from the 11 social activities included in the CHARLS questionnaire and the frequency of their activities. The depressive symptoms were assessed using the short version of the Center for Epidemiological Studies Depression Scale (the 10-item Center for Epidemiological Studies Depression Scale, CESD-10). A mixed-design ANOVA was used to explore the trends in social activity and depressive symptoms over time and across genders in the elderly adults. Pearson correlation analysis was used to investigate whether social activity and depressive symptoms in the elderly met the criteria for simultaneous and sequential correlations, followed by a cross-lagged model to analyze the causal temporal or mutual prediction between social activeness and depressive symptoms over a 3-year intervals.Results:The social activity of elderly men at T2 was significantly lower than at T1 ( F=21.00, P<0.001), while no significant difference observed in elderly women ( F=0.31, P<0.001). At both T1 and T2, elderly men scored higher in social activity than elderly women [T1: 2.93±2.98 vs 2.55±2.65,T2: 2.28±2.49 vs 2.24±2.43); F=43.60, 11.24, both P<0.01]. Depressive symptoms at T2 were higher than at T1 for both elderly men and elderly women ((male: 1.90±6.10 vs 21.52±6.08, female: 23.84±6.54 vs 23.07±6.44); F=5.20, 32.77, both P<0.05). Elderly men scored lower than elderly women on depression symptoms at both T1 and T2 (T1: F=45.74, P<0.001; T2: F=69.96, P<0.001). Pearson correlation analysis showed a negative correlation between social activity and depressive symptoms at both measurement points (T1: r=-0.329, P<0.01; T2: r=-0.343, P<0.01), and a positive correlation across T1 and T2 ( r=0.391, 0.573; both P<0.01), meeting the criteria for simultaneous and sequential correlations, and supporting the basic assumptions of cross-lagged design. Cross-lagged analysis revealed that T1 social activity negatively predicted T2 depressive symptoms (β=-0.128, P<0.001), and T1 depressive symptoms negatively predicted T2 social activity (β=-0.202, P<0.001). Conclusion:There is a bidirectional predictive relationship between social activity and depression symptoms in the elderly. Depression symptoms lead to a decrease in social activity, and a decrease in social activity predicts an exacerbation of depression in the elderly.

Objective:To explore the causal relationship between social activity and depressive symptoms in the elderly, and to provide a reference for preventing and interventing depressive symptoms in the elderly.Methods:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) program, involving 3 164 elderly individuals aged≥60 years with data collected in two measurements, in 2015 (T1) and 2018 (T2). The sample included 1 240 males and 1 924 females aged (71±7) years. Social activities were assessed by constructing a social activity index from the 11 social activities included in the CHARLS questionnaire and the frequency of their activities. The depressive symptoms were assessed using the short version of the Center for Epidemiological Studies Depression Scale (the 10-item Center for Epidemiological Studies Depression Scale, CESD-10). A mixed-design ANOVA was used to explore the trends in social activity and depressive symptoms over time and across genders in the elderly adults. Pearson correlation analysis was used to investigate whether social activity and depressive symptoms in the elderly met the criteria for simultaneous and sequential correlations, followed by a cross-lagged model to analyze the causal temporal or mutual prediction between social activeness and depressive symptoms over a 3-year intervals.Results:The social activity of elderly men at T2 was significantly lower than at T1 ( F=21.00, P<0.001), while no significant difference observed in elderly women ( F=0.31, P<0.001). At both T1 and T2, elderly men scored higher in social activity than elderly women [T1: 2.93±2.98 vs 2.55±2.65,T2: 2.28±2.49 vs 2.24±2.43); F=43.60, 11.24, both P<0.01]. Depressive symptoms at T2 were higher than at T1 for both elderly men and elderly women ((male: 1.90±6.10 vs 21.52±6.08, female: 23.84±6.54 vs 23.07±6.44); F=5.20, 32.77, both P<0.05). Elderly men scored lower than elderly women on depression symptoms at both T1 and T2 (T1: F=45.74, P<0.001; T2: F=69.96, P<0.001). Pearson correlation analysis showed a negative correlation between social activity and depressive symptoms at both measurement points (T1: r=-0.329, P<0.01; T2: r=-0.343, P<0.01), and a positive correlation across T1 and T2 ( r=0.391, 0.573; both P<0.01), meeting the criteria for simultaneous and sequential correlations, and supporting the basic assumptions of cross-lagged design. Cross-lagged analysis revealed that T1 social activity negatively predicted T2 depressive symptoms (β=-0.128, P<0.001), and T1 depressive symptoms negatively predicted T2 social activity (β=-0.202, P<0.001). Conclusion:There is a bidirectional predictive relationship between social activity and depression symptoms in the elderly. Depression symptoms lead to a decrease in social activity, and a decrease in social activity predicts an exacerbation of depression in the elderly.

【Objective】   As the main active ingredient of Tibetan medicine Hongjingtian (Rhodiolae Crenulatae Radix et Rhizoma), salidroside (Sal) has a good anti-apoptotic potential. Currently, there are some conflicting results on the anti-apoptotic mechanisms of Sal. Here we conducted a systematic review and meta-analysis to provide the preclinical evidence of its anti-apoptotic properties in preventing and treating hypoxic-ischemic cerebral damage(HICD). 【Methods】   The literature on the anti-apoptotic potential of Sal in the treatment of HICD from January 1, 1980 to November 9, 2021 was searched online using Chinese databases including Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database, and English databases including PubMed and Web of Science. The quality of the included articles was evaluated by the Cochrane Collaboration network bias risk assessment criteria, and meta-analysis was performed using RevMan 5.3 software. 【Results】  A total of 40 articles were finally included. Among the 40 articles, 30 were about in vivo animal experiments and 17 about in vitro cell experiments, and 7 of them included both animal and cell experiments. After analysis, it was found that Sal had significant effects on disease-related indicators of HICD (P < 0.05), such as cerebral infarctsize and brain water content. As to in vivo studies, Sal mainly affects the expressions of apoptotic factors through antiinflammation, anti-oxidation, activation of complement pathway, and regulation of signal transduction and autophagy, thus exerting anti-apoptotic potential in treating HICD. While for in vitro studies, Sal plays the anti-apoptotic role in HICD models mainly through anti-oxidation, anti-inflammation, reduction of Ca2+ overload, regulation of mitochondrial function, signal transduction, and C3 complement. 【Conclusion】  Sal can take anti-apoptotic effects to prevent and treat HICD through mechanisms such as anti-inflammation, anti-oxidation, enhanced autophagy, complement and signal transduction, regulation of mitochondrial membrane potential, and reduction of Ca2 + overload.

Background::Many studies have emphasized that selective resection of epileptic lesions in temoral lobe is associated with better preservation of cognition function; whether this applies to patients with refractory mesial temporal lobe epilepsy (MTLE) remains unknown. The objective of this study was to evaluate changes in cognitive functions, mood status, and quality of life after anterior temporal lobectomy in patients with refractory MTLE.Methods::This single-arm cohort study assessed cognitive function, mood status, and quality of life, as well as electroencephalography findings, in patients with refractory MTLE who underwent anterior temporal lobectomy at Xuanwu Hospital from January 2018 to March 2019. Pre- and post-operative characteristics were compared to evaluate the effects of surgery.Results::Anterior temporal lobectomy significantly reduced the frequencies of epileptiform discharges. The overall success rate of surgery was acceptable. Anterior temporal lobectomy did not result in significant changes in overall cognitive functions (P > 0.05), although changes in certain domains, including visuospatial ability, executive ability, and abstract thinking, were detected. Anterior temporal lobectomy resulted in improvements in anxiety and depression symptoms and quality of life. Conclusions::Anterior temporal lobectomy reduced epileptiform discharges and incidence of post-operative seizures as well as resulted in improved mood status and quality of life without causing significant changes in cognitive function.

OBJECTIVE：To provide evidence for promoting the scientific resea rch ability and talent team construction of hospital pharmacists. METHODS ：From Dec. 2019 to Apr. 2020，“Survey Form for Scientific Research Ability of Hospital Pharmacists”were issued to pharmacists in 62 medical institutions from 20 provinces across the country. The questionnaire was mainly based on five aspects ，i.e. general information of surveyed pharmacists ，the number of internal/external funds and patents approved in recent five years （2015-2019），the number of papers published in domestic/abroad/SCI journals ，the familiarity with scientific research projects ，the difficulties in carrying out scientific research. The collected data were summarized and analyzed with R 4.0.3 software. RESULTS ：A total of 300 questionnaires were sent out ，and 288 valid questionnaires were collected with effective recovery rate of 96％. Among surveyed pharmacists ，94 were male and 194 were female. The majority of them were 31-39 years old （52.78％）；56.25％，28.12％ and 15.63％ of them had bachelor ’s degree ，master’s degree and doctor ’s degree respectively，and 156（54.17％）had intermediate title. Totally 74.66％ of hospital pharmacists thought it was very necessary or necessary to carry out research projects （involving all doctors ，26 masters and 4 bachelors）. There were significant differences among pharmacists with different educational background in respects of the number of applications for internal and external funds and patents ，as well as the number of papers published in domestic/foreign/SCI journals ，and most of them were doctors （P＜ 0.05）. In recent five years ，most of hospital pharmacists had published 1-3 papers in domestic journals ，accounting for 44.80％， while 27.08％ had published papers in SCI journals. Totally 51.39％ of hospital pharmacists were not familiar or not very familiar with scientific research projects funding （most of them had bachelor ’s degree ）；52.43％ expressed that experimental conditions were the biggest difficulty in conducting scientific research. CONCLUSIONS：This survey shows that hospital pharmacists have a relatively positive attitude towards scientific researchprojects. Most of papers are published in domestic journals. 8804919。E-mail：songjc1234@126.com However， there are still many shortcomings in scientific research status. Scientific research capabilities need to be improved. Experimental conditions also limit the scientific research projects to a certain extent. Hospitals need to strengthen funding for pharmacist research projects ，strengthen academic exchanges ， so that pharmacists can understand scientific research projects more comprehensively and systematically.

Objective To construct a human renal epithelial cell line HEK293T by CRISPR-Cas9-based site-directed knock-in of vascular endothelial growth factor 165 (VEGF165) gene, and avoid the off-target effect caused by lentivirus infection. Methods The VEGF165 expression vector with homologous arm (pUCm-T-VEGF165 plasmid) and the sgRNA expression vector [pSpCas9(BB)-2A-Puro-sgRNA plasmid] were designed and constructed based on the DNA sequence of the EZH2 gene, and then co-transfected into HEK293T cells. The expression of VEGF165 mRNA was detected by qPCR and the expressions of VEGF165 proteins were detected by Western Blot. Results The qPCR and Western Blot results showed that, comparing with the control, the pUCm-T-VEGF165 plasmid and pSpCas9(BB)-2A-Puro-sgRNA plasmid, the expression of the co-transfection plasmid were significantly increased, i.e. 3.42±0.30 vs. 1.02±0.21, 1.13±0.16 and 0.98±0.18 for the VEGF165 mRNA level (all P<0.01), and 1.13±0.16 vs. 1.02±0.06, 0.88±0.03 and 0.80±0.05 for the VEGF165 protein level (all P<0.01), respectively. Besides, the expression of EZH2 was significantly down-regulated, i.e. 0.14±0.06 vs. 1.08±0.11, 1.02±0.12 and 1.13±0.16 for the EZH2 mRNA level (all P<0.01), and 0.23±0.03 vs. 1.05±0.13, 0.91±0.04 and 0.81±0.06 for the EZH2 protein level (all P<0.01), respectively. This result showed that the VEGF165 was successfully inserted into the EZH2 genome, interfering the EZH2 expression. Conclusions VEGF165 gene can be successfully knocked into HEK293T cells by CRISPR/Cas9 system.