BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95％Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95％CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95％CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95％CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95％CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95％CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95％CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.

BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95％Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95％CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95％CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95％CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95％CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95％CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95％CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.

ObjectiveTo investigate the contamination status of arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) in commercially available aquatic products in Shanghai and their distribution characteristics among different categories of aquatic products, and to assess the dietary exposure levels and non‑carcinogenic health risks of As, Cd, Pb, and Hg through aquatic product consumption among different age groups, so as to provide a scientific basis for food safety surveillance of aquatic products and dietary risk management for residents in Shanghai. MethodsFrom October to November 2021, a total of 90 aquatic product samples, including marine fish, freshwater fish, freshwater shrimp, marine crab, freshwater crab, and mollusks, were randomly collected from 16 districts of Shanghai. Sample pretreatment was performed according to GB 5009.268‒2016 (National Food Safety Standard—Determination of Multi‑elements in Foods). The concentrations of As, Cd, and Pb in aquatic products were determined by inductively coupled plasma mass spectrometry (ICP‑MS), and Hg was determined by direct mercury analyzer. Inorganic arsenic (iAs) was estimated as 3.5% of total As according to the method recommended by the European Food Safety Authority (EFSA). The contamination levels of As, Cd, Pb, and Hg in aquatic products were evaluated according to GB 2762‒2017 (National Food Safety Standard—Maximum Levels of Contaminants in Foods). A combined approach of point assessment and probabilistic assessment was applied to estimate the estimated daily intake (EDI) and non‑carcinogenic risk indicators—hazard quotient (HQ) and hazard index (HI)—for different age groups. ResultsThe detection rates of As and Hg were both 100.00% in all samples, while those of Cd and Pb were 74.44% and 25.56%, respectively. The arithmetic means (wet weight) of the four elements and estimated iAs were: As (1.432 9±3.736 5) mg·kg^-1, iAs (0.050 2±0.130 8) mg·kg^-1, Cd (0.082 5±0.197 8) mg·kg^-1, Pb (0.006 1±0.005 5) mg·kg^-1, and Hg (0.021 9±0.016 7) mg·kg^-1. According to the relevant maximum residue limits, 2 out of 7 mollusk samples (28.57%) and 3 out of 20 marine fish samples (15.00%) exceeded the limit for iAs, and 2 out of 8 marine crab samples (25.00%) exceeded the limit for Cd. The estimated daily intake (EDI, μg·kg^-1·d^-1, by body weight) of iAs, Cd, Pb, and Hg via aquatic product consumption varied among different age groups, with the highest levels observed in children aged 3‒4 years, decreasing gradually with age to the lowest level at 12 ‒ <15 years, with a slight rebound thereafter. The point assessment results showed that the HQs of iAs, Cd, Pb, and Hg ranged from 0 to 0.25, and the cumulative HI ranged from 0.27 to 0.48, all below 1, indicating a relatively low overall risk. The probabilistic assessment results revealed that under the high‑exposure scenario (P_97.5), the HQs of iAs (1.101‒1.281) and Cd (1.175‒1.366) exceeded 1 in children aged 3‒9 years, suggesting potential health risks, while the HQs of Pb and Hg were all below 1, indicating relatively lower risks. ConclusionHg and As are ubiquitously detected in commercially available aquatic products in Shanghai, while the detection rates of Cd and Pb are relatively low. The overall non-carcinogenic risk is at an acceptable level, but children aged 3‒9 years may have potential health risks from iAs and Cd under high-percentile exposure levels. It is recommended to strengthen the monitoring of toxic elements in key aquatic products such as marine fish, mollusks, and marine crabs, and to implement targeted dietary risk management measures for sensitive populations, including children.

Objective:To analyze the current status, hotspots, and trends of community integration (CI) at home and abroad, providing directions for subsequent research.Methods:The China National Knowledge Infrastructure and the Web of Science Core Collection data were used, and CiteSpace software was employed to analyze the publication, countries, disciplines, and keywords of CI.Results:A total of 932 Chinese and 2 319 English hits were included. The publication of CI had shown an increasing trend both domestically and internationally. Sociology and rehabilitation were the main disciplines in CI domestically and internationally, respectively. Domestically, CI research primarily focused on the community integration of migrant workers, floating populations, and accompanying family members. Internationally, the emphasis was on the integration of individuals with disabilities and other special groups. Future research directions in China were likely to focus on group work, the elderly, and relocated populations. Internationally, CI research would continue to concentrate on CI experiences and intervention methods for individuals with disabilities and special populations.Conclusion:CI is increasingly gaining attention both domestically and internationally. However, domestic research remains insufficient and needs to be expanded through more empirical studies in various vertical subfields. Future domestic scholars should continue to focus on CI of the elderly and engage in interdisciplinary research.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

Objective To clarify the evidence of the frequency and risk factors for falls in knee osteoarthritis(KOA)of adults by meta-analysis.Methods Computerized searches of the CNKI,VIP,Wanfang data,CBM,PubMed,Cochrane Library,Embase,Web of Science were conducted for literature on risk factors for falls in adults with KOA from the inception of the databases to August 2024.After literature screening,data extraction,and quality evaluation,RevMan 5.4 software was used for Meta-analysis.Results A total of 26 articles were involved.Meta-analysis result showed that the rate of falls was 29.0％.Factors associated with increased risk of falls included being female(OR=1.35),decreased lower limb muscle strength(OR=1.72),decreased knee flexion muscle strength(OR=7.05),decreased static posture stability(OR=1.28),opioid use(OR=1.79),antidepressant use(OR=1.69),frequent stair climbing(OR=7.58),combined neurological disease(OR=1.77),history of falls(OR=3.29)and fear of falling(OR=2.54).Conclusion The rate of falls of patients with KOA is high.The adults with KOA who are women,have lower muscle strength of lower limbs and knee flexion muscle strength,poorer static posture stability,use opioids,antidepressant,frequent stair climbing,combined neurological disorders,previous falls in the past year and fear of falls are at higher risk of falls.Healthcare professionals should dynamically assess and detect the risk of falls in the patients with KOA and adopt targeted,individualized interventions to prevent falls.

Objective:To explore and demonstrate the effect of general-specialty hierarchical management mode for chronic heart failure (CHF) in community.Methods:This was a single-blind, randomized, controlled study. A total of 530 CHF inpatients who attended Weifang Community Health Service Center (WCHSC) in Pudong New Area from February 2018 to September 2019 were consecutively enrolled. A random number table method was used to divide the patients into the management group ( n=265) and control group ( n=265). The demographic data and past medical history were collected 1 day before enrolment (baseline), and patients were assessed for New York Heart Association (NYHA) cardiac function classification and tested for blood N-terminal B-type natriuretic peptide proteins (NT-proBNP) levels, while Doppler echocardiography was performed to obtain the relevant indexes. The management group used a comprehensive management mode, co-delivered by both WCHSC (offering primary care) and RHSJUSM (offering specialty care) at Renji-Weifang CHF Studio in WCHSC , using the jointly developed CHF hierarchical CHF diagnosis and treatment criteria and referral procedure under the condition of sharing drugs and laboratory test results for CHF. The control group received routine heart failure care. Intergroup comparisons were made on baseline data obtained before follow-up and on NT-proBNP , left ventricular ejection fraction (LVEF), NYHA functional class , re-hospitalization rate and mortality rate at the end of the 6-month follow-up. Results:A total of 506 cases completed the follow-up. There were 253 patients in the management group, aged (68.26±9.41) years, 117 males (46.2%); 253 were in the control group, aged (66.98±9.63) years, 115 males (45.5%). There were no statistically significant differences in age, sex, marital status, education level, and comorbidities between the two groups (all P>0.05). At baseline, the differences in LVEF and NT-proBNP between the two groups were not statistically significant (all P>0.05), and at 6 months of intervention, LVEF, and NT-proBNP had significantly improved in both groups (all P<0.05) . Moreover, LVEF was higher in the management group than in the control group, and NT-proBNP was lower than in the control group (both P<0.01). At baseline, there were 166 cases (65.6%) in the control group with NYHA class Ⅲ/Ⅳ, and 145 cases (57.3%) in the comprehensive management group. There was no statistically significant difference between the two groups ( P>0.05). At 6 months of intervention, the percentage of NYHA class Ⅲ/Ⅳ patients in the comprehensive management group was lower than at baseline ( P<0.01),while that in the control group was higher than at baseline ( P<0.01), and the comprehensive management group was lower than that in the control group ( P<0.01). During the follow-up period, the rehospitalization rate for CHF in the management group was 13.83%(35/253), which was lower than that in the control group, which was 26.88%(68/253) ( P<0.001). Conclusion:The comprehensive management mode of CHF in the community through collaboration between general and specialized departments can significantly improve the management effect, suggesting that this mode is effective and can be promoted.

Objective:To propose a functional method for locating the shoulder joint center of rotation aimed at rapid estimation of the upper limb reachable domain envelope, thereby informing ergonomic design and task optimization.Methods:In March 2024, shoulder kinematics during gait were recorded from ten adults using a three-dimensional motion-capture system. Assuming the existence of a point near the glenohumeral joint that maintains a fixed spatial relationship to the humerus and the acromion, we estimated both static and dynamic centers of rotation. Localization accuracy was quantified by the standard deviation of distance residuals to upper-arm markers. Upper-limb joint angles and anthropometric parameters were modeled via regression; combined with maximal joint ranges of motion, these were used to infer the reachable domain envelope.Results:The static center of rotation was located approximately twenty-two millimeters medial to the acromial landmark in the coronal plane and thirty-seven millimeters inferior to it. The standard deviation of the residuals for the distances from the dynamic shoulder joint center of rotation to upper-arm markers averaged 1.02 mm, which was 47.42% lower than that of the static center of rotation and 66.56% lower than that of the acromion. Moreover, the trajectory of this dynamic center showed a strong correlation with upper-limb joint angles ( R2>0.7) . Conclusion:The proposed method enables rapid and accurate estimation of the upper limb reachable domain envelope to support ergonomic design and may help reduce the risk of work-related musculoskeletal disorders.

Objective To explore the molecular mechanism of cerebroprotein hydrolysate-1(CH-1)in improving cognitive impairment of VD at animal level,and to determine the regulatory effect of CH-1 on Nrf2/ARE signaling pathway.Methods Thirty-six SD rats were randomly divided into sham operation group,VD group,low-and high-dose groups,with 9 rats in each group.VD model was established by bilateral common carotid artery ligation,and CH-1 was injected intraperitone-ally for 3 weeks.Morris water maze test and new object recognition test were performed to evalu-ate cognitive function.Hippocampal tissues was collected for immunohistochemistry/Western blot analysis.Results Compared with the sham operation group,the VD group exhibited significantly prolonged escape latency at 2-4 d of Morris water maze test,and up-regulated expression of ubiquitinated protein,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 protein in the hippocampus,while down-regulated P62 expression(P＜0.05).Obviously shortened escape latency was observed in the high-dose group at 3-4 d and the low-dose group at 4 d than the VD group(P＜0.05).The resi-dence time in target quadrant,number of platform crossings,total exploration time of novel object recognition in the high-dose group and the total exploration time of novel object recognition in the low-dose group were significantly longer than those in VD group(P＜0.05).The expression levels of ubiquitinated,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 were significantly lower in the low-dose group and high-dose group than the VD group(P＜0.05).The expression level of P62 protein in the VD group,low-and high-dose group were significantly increased in a dose-dependent manner(2.78±0.44,1.80±0.24 vs 3.67±0.34;2.37±0.26,1.53±0.09 vs 2.92±0.19;2.74±0.14,1.81±0.19 vs 3.93±0.50;2.28±0.17,1.72±0.17 vs 3.17±0.31,P＜0.05).Conclusion CH-1 can effectively improve the cognitive ability of VD rats and reduce the autophagy of hippocampal neurons.This therapeutic effect may be closely related to its enhancing activity of Nrf2/ARE signaling pathway.

Objective:To discuss the clinical and genetic characteristics of neurodevelopmental disorder with or without early-onset generalized epilepsy (NEDEGE) caused by NBEA gene variation. Methods:The clinical and genetic records of a patient who was diagnosed with NEDEGE caused by NBEA gene variation at the Department of Neurology, Guangzhou Women and Children′s Medical Center in April 2024 were collected retrospectively. Using " NBEA or neurobeachin" "Autism spectrum disorders or ASD" "Epilepsy" "Neurodevelopmental disorders" as the keywords, relevant articles were searched at CNKI, Wanfang and PubMed databases from establishment of these databases to December 2024. Clinical and genetic features of NEDEGE were summarized in the combination of this case. Results:The proband, a 3 years old boy, was backward in development since childhood. He had autism spectrum disorder-like manifestations such as stereotyped behavior and poor eye contact. At the age of 2, he developed generalized seizures. The whole exome sequencing showed a de novo heterozygous variation of c.244CT(p.Gln82 *) in the NBEA gene (NM-001385012.1), and he was diagnosed with NEDEGE. A total of 10 articles (all in English) were retrieved, reporting 36 cases of NBEA gene related NEDEGE (including this case), 4 of whom coming from China. Twenty-four individuals suffered from mild to severe intellectual disability, and most were moderate.Twenty-eight patients had language delay, including 4 cases of complete loss of language function, and 24 patients had seizures, and 19 patients had autism or autima-like behavior problems. Conclusions:This case enriches the mutation spectrum of the NBEA gene, and the c.244CT is the first reported related variation in the Chinese population. The clinical symptoms of NEDEGE related to NBEA gene mutations are most pronounced in neurodevelopmental disorders, followed by seizures and autistic behavior.