Objective: To analyze the association between drinking behaviors and anxiety symptoms, with the mediating role of insomnia symptoms among college freshmen, so as to provide a reference basis for reducing the occurrence of anxiety symptoms in college freshmen. Methods: From October to December 2021, 31 856 freshmen were selected by the purposive sampling method in 22 colleges across 11 provinces (Fujian, Jiangsu, Guangdong, Henan, Anhui, Hubei, Shanxi, Jiangxi, Shaanxi, Yunnan, Chongqing) in China. The Semi quantitative Food Frequency Questionnaire was used to investigate college freshmen drinking behaviors. The Depression Anxiety Stress Scale 21 and the Insomnia Severity Index were used to assess anxiety symptoms and insomnia symptoms in college freshmen. The generalized linear model was employed to analyze the association between drinking behaviors and anxiety symptoms in college freshmen, and the structural equation modeling was used to assess the mediating effect of insomnia symptoms on the association. Results: The detection rate of anxiety symptoms among college freshmen was 28.2%, the detection rates of the mild, moderate, severe and extremely severe were 6.6%, 15.9%, 3.2% and 2.6%, respectively. While 23.6% of college freshmen reported drinking in the past month, the rates were 39.8% among boys and 15.9% among girls. After adjusting for demographic variables (ethnicity, education, major, etc.) and confounding variables (self evaluation of learning burden, number of close friends, screen time, etc.), the results of generalized linear model analysis showed that beer consumption was associated with anxiety symptoms in college freshmen( β =0.09, 95% CI =0.04-0.14), girls( β =0.14, 95% CI =0.07-0.21) and those aged 19-20 years ( β =0.12, 95% CI =0.05-0.19)(all P <0.05). Red wine consumption was associated with anxiety symptoms in male students ( β =0.13, 95% CI =0.02-0.24, P <0.05). Alcohol and beer consumption were associated with insomnia in college freshmen[ β (95% CI ) =0.22(0.08-0.36),0.31(0.23-0.39),both P <0.01]. Insomnia symptoms partially mediated the association between drinking behaviors and anxiety symptoms among college freshmen with a mediating effect value of 0.05, accounting for 50.49% of the total effect. Conclusions Insomnia symptoms partially mediates the association between drinking behaviors and anxiety symptoms in college freshmen. Measures should be taken to simultaneously intervene in the drinking behaviors and insomnia symptoms of college freshmen to prevent the occurrence of their anxiety symptoms.

Objective To explore the neuroprotective effect and related mechanism of electroacu-puncture(EA)combined with tanshinone Ⅱ A(Tan ⅡA)for the treatment of rats with cerebral ische-mia-reperfusion(I/R)injury.Methods Model rats with cerebral I/R were established by the modi-fied Longa suture occlusion method and randomly divided into Model group,EA group,Tan Ⅱ A group,and EA+Tan Ⅱ A group,with 16 rats in each group.Rats in the Sham group(n=16)had their carotid arteries exposed and dissected but not occluded.Neurological deficit score and Morris wa-ter maze test were used to assess neurological impairment and cognitive function in rats.2,3,5-triph-enyltetrazolium chloride(TTC)staining was used to evaluate cerebral infarction volume.Hematoxylin-eosin(HE)staining and TUNEL staining were used to assess neuronal damage in the hippocampus.Western blot was used to detect apoptosis-related proteins and proteins related to the Hippo signaling pathway.Results Compared with the Sham group,the Model group showed increased neurological deficit score,percentage of cerebral infarction area,escape latencies during acquisition training,proportion of TUNEL-positive stained cells in brain tissue,Caspase-3 activity,expression of Cleaved Caspase-3 protein and Bax protein,and decreased expression of time spent in the target quadrant during probe training,the number of platform crossings within 60 s,Bcl-2 protein,Yes-associated protein(YAP),and transcriptional co-activator with PDZ-binding motif(TAZ)protein,and all the differences were significant(P＜0.05).Compared with the Model group,the EA group,Tan Ⅱ A group,and EA+Tan Ⅱ A group showed decreased neurological deficit score,percentage of cerebral infarction volume,escape latencies during acquisition training,time spent in the target quadrant during probe training,number of platform crossings within 60 s,proportion of TUNEL-positive stained cells in brain tissue,Caspase-3 activity,expression of Cleaved Caspase-3 protein and Bax protein,with the EA+Tan Ⅱ A group showing lower values than the EA group and Tan Ⅱ A group,and all the differences were significant(P＜0.05).Compared with the Model group,the EA group,Tan Ⅱ A group,and EA+Tan Ⅱ A group showed increased expression of Bcl-2,YAP,and TAZ proteins,with the EA+Tan Ⅱ A group showing higher protein expression levels than the EA group and Tan Ⅱ A group,and all the differences were significant(P＜0.05).Conclusion The combination of EA and Tan Ⅱ A for the treatment of cerebral I/R injury exhibits synergistic effect,and its mechanism may be related to the inhibition of Hippo pathway activity.

Objective:To investigate the prevalence and associated factors of anxiety and depression in outpatients with chronic obstructive pulmonary disease (COPD) visiting the Yuetan Community Health Service Center in Beijing.Methods:This cross-sectional study enrolled COPD patients who visited the center between January 1, 2022, and December 31, 2023, using convenience sampling. After pulmonary function tests, participants completed questionnaires covering demographic characteristics, GOLD classification, number of hospitalizations for acute exacerbations in the past year, modified Medical Research Council (mMRC) dyspnea scale score, COPD Assessment Test (CAT) score, Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). The status and influencing factors of anxiety and depression were analyzed with univariate and multivariate Logistic regression.Results:A total of 243 COPD patients were included, with 74.1% (180/243) being male and a mean age of 67±9 years. The prevalence rates of anxiety and depression were 17.3% (42/243) and 21.0% (51/243), respectively. Multivariate logistic regression analysis identified the following independent factors associated with anxiety (all P<0.05): CAT score 31-40 ( OR=26.621, 95% CI: 4.451-159.209), mMRC score ≥2 ( OR=5.387, 95% CI: 1.589-18.209), GOLD grade ≥3 ( OR=3.227, 95% CI: 1.205-8.645), presence of ≥1 comorbidity ( OR=8.571, 95% CI: 1.132-64.920), being divorced/separated/widowed ( OR=3.125, 95% CI:1.369-7.136), and ≥1 hospitalization for acute exacerbation in the past year ( OR=3.523, 95% CI:1.422-8.726). Independent factors associated with depression (all P<0.05) were: CAT score ≥21 ( OR=3.326, 95% CI:1.038-10.653), mMRC score≥1 ( OR=7.468, 95% CI:1.706-32.697), GOLD grade ≥3 ( OR=3.160, 95% CI:1.225-8.148), presence of ≥1 comorbidity ( OR=5.624, 95% CI:1.295-24.422), smoking history ≥40 pack-years ( OR=2.689, 95% CI: 1.092-6.623), and ≥1 hospitalization for acute exacerbation in the past year ( OR=2.663, 95% CI:1.093-6.486). Conclusions:The prevalence of anxiety and depression among COPD outpatients in this Beijing community health center is considerable. CAT score, mMRC grade, GOLD grade, number of comorbidities, marital status, and history of hospitalization for acute exacerbation are risk factors of anxiety, while CAT score, mMRC grade, GOLD grade, number of comorbidities, smoking pack-years, and hospitalization history are risk factors for depression.

Objective:To investigate the prevalence and associated factors of anxiety and depression in outpatients with chronic obstructive pulmonary disease (COPD) visiting the Yuetan Community Health Service Center in Beijing.Methods:This cross-sectional study enrolled COPD patients who visited the center between January 1, 2022, and December 31, 2023, using convenience sampling. After pulmonary function tests, participants completed questionnaires covering demographic characteristics, GOLD classification, number of hospitalizations for acute exacerbations in the past year, modified Medical Research Council (mMRC) dyspnea scale score, COPD Assessment Test (CAT) score, Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). The status and influencing factors of anxiety and depression were analyzed with univariate and multivariate Logistic regression.Results:A total of 243 COPD patients were included, with 74.1% (180/243) being male and a mean age of 67±9 years. The prevalence rates of anxiety and depression were 17.3% (42/243) and 21.0% (51/243), respectively. Multivariate logistic regression analysis identified the following independent factors associated with anxiety (all P<0.05): CAT score 31-40 ( OR=26.621, 95% CI: 4.451-159.209), mMRC score ≥2 ( OR=5.387, 95% CI: 1.589-18.209), GOLD grade ≥3 ( OR=3.227, 95% CI: 1.205-8.645), presence of ≥1 comorbidity ( OR=8.571, 95% CI: 1.132-64.920), being divorced/separated/widowed ( OR=3.125, 95% CI:1.369-7.136), and ≥1 hospitalization for acute exacerbation in the past year ( OR=3.523, 95% CI:1.422-8.726). Independent factors associated with depression (all P<0.05) were: CAT score ≥21 ( OR=3.326, 95% CI:1.038-10.653), mMRC score≥1 ( OR=7.468, 95% CI:1.706-32.697), GOLD grade ≥3 ( OR=3.160, 95% CI:1.225-8.148), presence of ≥1 comorbidity ( OR=5.624, 95% CI:1.295-24.422), smoking history ≥40 pack-years ( OR=2.689, 95% CI: 1.092-6.623), and ≥1 hospitalization for acute exacerbation in the past year ( OR=2.663, 95% CI:1.093-6.486). Conclusions:The prevalence of anxiety and depression among COPD outpatients in this Beijing community health center is considerable. CAT score, mMRC grade, GOLD grade, number of comorbidities, marital status, and history of hospitalization for acute exacerbation are risk factors of anxiety, while CAT score, mMRC grade, GOLD grade, number of comorbidities, smoking pack-years, and hospitalization history are risk factors for depression.

Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

BACKGROUND:Umbilical cord mesenchymal stem cells(UMSCs)have been proven to have therapeutic effects on cartilage injury,and exosomes are the main carriers for UMSCs to exert therapeutic effects in vivo.Our research group previously found that lncRNA H19 is an important active molecule that mediates the activity of UMSCs-derived exosomes regulating chondrocytes.LncRNA H19 could adsorb miR-29b-3p to promote the proliferation and regeneration of chondrocytes,but its downstream mechanism is still unclear. OBJECTIVE:To reveal the specific mechanism of UMSCs in the treatment of cartilage injury from the perspective of exosomes and lncRNAs,so as to provide a new target for the treatment of cartilage injury. METHODS:UMSCs stably overexpressing lncRNA H19 were constructed.H19-Exos were extracted by ultra-centrifugation.The exosomes were identified by transmission electron microscopy,Nanosight,western blot assay and exosome uptake assay.The effect of miR-29b-3p overexpression and silencing on the TGF-β1/Smad3 pathway was detected by western blot assay,qPCR and dual luciferase reporter gene system.The biological effect of H19-Exos on cartilage regeneration was verified by the specific TGF-β1/Smad3 inhibitor in vitro and in vivo. RESULTS AND CONCLUSION:(1)H19-Exos showed a typical cup shape under an electron microscope,and the particle size was approximately 130 nm.H19-Exos expressed CD63,CD81 and TSG1010.(2)Overexpression of miR-29b-3p could down-regulate the mRNA and protein levels of TGF-β1 and Smad3,while silencing miR-29b-3p could up-regulate the mRNA and protein levels of TGF-β1/Smad3.(3)Dual-luciferase reporter gene system showed that miR-29b-3p had significant differences in the activities of downstream target genes TGF-β1 and Smad3.(4)The osteoarthritis models of rats were successfully established by injection of type II collagenase into the knee joint.H19-Exos significantly promoted cartilage regeneration.The specific TGF-β1/Smad3 inhibitor SB-431542 could block the biological effect of H19-Exos on cartilage regeneration in vitro and in vivo.(5)This study systematically demonstrated the promotion effect of UMSCs-derived exosomes highly expressing lncRNA H19 on cartilage regeneration,and the specific mechanism is that lncRNA H19 promotes cartilage regeneration by targeting miR-29b-3p/TGF-β1/Smad3 pathway.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To investigate the correlation between claudin-5 level and the risk of hemor-rhagic transformation(HT)in elderly stroke patients after thrombolysis.Methods A total of 192 elderly stroke patients hospitalized in our department from February 2021 to October 2022 were recruited,and divided into HT group(32 cases,including 14 of parenchymal hematoma type and 18 of hemorrhagic cerebral infarction type)and non-HT group(160 cases)according to the results of head CT or MRI 48 h after thrombolysis.The clinical data and serum claudin-5 level were com-pared between the two groups.Multivariate logistic regression analysis was used to identify the in-fluencing factors of HT risk after thrombolysis in elderly stroke patients.Restricted cubic splines were drawn to analyze the correlation between claudin-5 level and HT risk after thrombolysis.Re-sults The HT group had higher proportion of atrial fibrillation,longer onset to thrombolysis time,higher baseline NIHSS score,and fasting blood glucose and claudin-5 levels than the non-HT group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that time from onset to thrombolysis(OR=2.589,95％CI:1.202-5.573,P=0.015),baseline NIHSS score(OR=1.415,95％CI:1.213-1.651,P=0.000),and fasting blood glucose(OR=1.552,95％CI:1.014-2.375,P=0.043)and claudin-5 levels(OR=1.174,95％CI:1.076-1.281,P=0.000)were risk factors for HT after thrombolysis in elderly stroke patients.Restricted cubic spline anal-ysis demonstrated that claudin-5 level had a nonlinear relationship with the risk of HT in the pa-tients after thrombolysis(x2=12.380,P=0.006).Conclusion Serum claudin-5 level is associated with HT after thrombolysis in elderly stroke patients,and shows a dose-response relationship with HT.