BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

BACKGROUND:The biomechanical analysis of scoliosis cases is limited,with only independent analysis focusing on the spine or lower limbs,thus lacking a comprehensive evaluation of the multidimensional body.As a result,it becomes challenging to reflect the movement relationship between the trunk and lower limbs during daily activities,which hinders comprehensive clinical treatment guidance. OBJECTIVE:To explore the relationship between different segments of the spine and the kinematics/kinetics of the lower limbs during gait activities by measuring spinal kinematics in scoliosis patients,to provide a comprehensive and multi-level assessment of the biomechanical differences between scoliosis patients and the normal population,consequently offering evidence-based guidance for the prevention and treatment of scoliosis. METHODS:A cross-sectional study was conducted from July 2020 to June 2021 at the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine in Fuzhou University City.A total of 28 scoliosis patients and 28 normal individuals in the same age group were included.Three-dimensional motion capture system was used to capture gait kinematic data at a sampling frequency of 100 Hz.Two force plates(AMTI 400600,sampling frequency 1 500 Hz)were embedded in a 10-meter-long 2.4-meter-wide level ground walkway(with an effective data collection length of 4 m)to collect kinetic data.The differences in spatial-temporal parameters,kinematics,and kinetics of gait between the two groups were compared.Immediately after inclusion,all subjects underwent full spinal X-ray measurements to compare the differences between the scoliosis and normal groups. RESULTS AND CONCLUSION:(1)Patients with scoliosis exhibited reduced relative rotational range of motion between the shoulder and trunk,as well as between the thorax and pelvis,compared to the normal group(P<0.05).However,the rotational range of motion in the pelvis was larger in patients with scoliosis compared to the normal group(P<0.05).(2)Patients with scoliosis showed decreased range of motion in the hip and knee joints,as well as reduced peak torque in hip joint flexion and extension,and lower peak values of ground reaction forces in the concave and convex directions,in comparison to the normal group(P<0.05).(3)Patients with scoliosis demonstrated greater asymmetry indices in knee joint range of motion,relative rotational range of motion between the shoulder and trunk,and between the thorax and pelvis,when compared to the normal group(P<0.05).(4)These findings illustrate a rigid movement pattern among the shoulder,thorax,and pelvis in patients with scoliosis during level walking.There is a reduction in range of motion in the hip and knee joints,as well as decreased peak torque values in hip joint flexion and extension,and ground reaction forces in the concave and convex directions.These characteristics can serve as foundational elements for assessing rehabilitation and developing treatment plans.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective: To study the pollution status of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCB), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in cord blood of newborns in an e-waste dismantling area of Guangdong Province. Methods: We recruited 20 eligible mothers and newborns who could meet the inclusion criteria in local hospitals of Guiyu in 2007. The inclusion criteria included directly engaged in dismantling e-waste during pregnancy and within 1 year before pregnancy; living in the e-waste dismantling workshops or the distance between living place and the e-waste dismantling areas was ≤200 m; the father of newborn was directly engaged in electronic waste dismantling for more than 1 year; the frequency of visiting the e-waste dismantling workshop during pregnancy was ≥3 times in a week. Questionnaires and physical examinations were performed on maternal and neonatal, and cord blood was collected from newborns to detect PCDD/Fs, PCB and PBDE. The concentration level of organic pollutants was corrected by the blood lipid content, and the total toxicity equivalent was calculated. The correlation between three compounds was analyzed by Spearman correlation. Results: The mothers of the 20 newborns were (23.45±3.27) years old and lived for more than 5 years. The number of one parent engaged in e-waste dismantling, the mother or father smoking, and parent engaged in e-waste dismantling work were 3, 13, 15 and 19, respectively. The weight of newborns ranged from 2.5 to 3.6 kilogram and the Apgar score was 10 points. No adverse birth outcomes such as preterm birth, malformation or stillbirth were found. The median (maximum, minimum) concentration of PCBs, PCDD/Fs and PBDEs in cord blood were 263.22 (328.29, 244.19), 38.42 (147.49, 12.68), 39.33 (265.11, 14.81) pg/g lipid, respectively. The median (maximum, minimum) of toxic equivalence concentrations of PCDD/Fs and PCB were 3.94 (9.24, 2.69) and 15.95 (26.64, 9.28) pg TEQ/g lipid. PBDE, the proportion of PBDE, PCB and PCDD/Fs in cord blood was 50.41%, 49.25% and 0.34%, respectively. PCBs and PBDEs were positively correlated (r=0.733, P=0.039). Conclusion The high concentrations of PCDD/Fs, PCB, and PBDE were detected in the e-waste dismantling area. It is recommended that the risk of such substances on the health of local people should be assessed in a timely manner.

Increasing e-waste has become a major problem for global environment and public health. In the process of dismantling and recycling of disordered electronic waste, heavy metals such as lead and brominated flame retardants and organic substances are released into environmental media such as air, soil, dust and water, which is harmful to the health of local residents. Taking an e-waste dismantling area in Guangdong Province as an example, this paper reviews exposure levels of heavy metals and organic matters in e-waste recycling areas in China, as well as the health effects of local residents. Previous studies have found that e-waste recycling activities led to serious environmental pollution and high exposure levels of heavy metals and organic matters in local residents, which has a certain impact on the physiological functions of various human systems. The establishment of a centralized dismantling zone can effectively reduce the load level of various pollutants.

Objective To determine whether thyroid hormone (TH) level could also be an independent and incremental predictor of adverse events in patients with hypertrophic cardiomyopathy (HCM).Methods A total of 982 consecutive patients with HCM at the National Center for Cardiovascular Diseases (China) from October 2009 to December 2013 were included in the present study,and followed up till the end of December 2016.The patients were divided into three groups according to the levels of free triiodothyronine (FT3):the group 1 (FT3≤4.28 pmol/L,n=335),the group 2 (FT3＞4.28-＜4.79 pmol/L,n=310),and the group 3 (FT34.79-6.30 pmol/L,n=337).Results After a follow-up period of (53.8 ± 14.1) months,39 patients (4.0％) either suffered death with all causes or received a cardiac transplantation (7.8％,2.9％ and 1.2％ of the patients in the group 1,group 2 and group 3,respectively).A multivariable Cox regression analysis revealed that FT3≤4.28 pmol/L was associated with a significantly higher risk of all-cause mortality or cardiac transplantation (HR 8.83,95％ CI 1.115-69.905,P=0.039) in HCM patients.Conclusions Low levels of FT3 is a risk factor of adverse events for patients with HCM,indicting a role of FT3 as a marker for assessing the risk of long-term adverse events in these patients.

Objective     To analyze the safety and effectiveness of ultrasound-guided thoracoscopic atrial septal defect (ASD) closure. Methods     We prospectively collected the clinical data of 12 patients with ASD treated by ultrasound-guided thoracoscopic ASD closure in Fuwai Hospital from January to September 2017. The characteristics of the patients' ASD and operation, operation safety and effectiveness, postoperative complications and follow-up results were analyzed. Results     Among the 12 patients, 10 were successfully treated with ultrasound-guided thoracoscopic ASD closure. Two patients switched to ASD repair under thoracoscopy-assisted cardiopulmonary bypass. The size of the ASD was 17-40 (27.22±8.97) mm and the size of the occluder was 36 (30-42) mm. The average postoperative length of hospital stay was 6 days. There were no complications such as arrhythmia, bleeding and pericardial effusion after operation. The average follow-up was 6 (3-10) months after the operation. During the follow-up, no Ⅲ-degree conduction block, occluder dislocation, residual shunt or cardiac pericardial effusion was found. Conclusion     Ultrasound-guided thoracoscopic ASD closure is a minimally invasive, safe and effective treatment. This technique provides a new minimally invasive surgical option for patients with large defect diameter and poor edge condition.

Objective: To determine the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the long-term outcome of patients with hypertrophic cardiomyopathy (HCM) . Methods: NT-proBNP was measured in 831 consecutive patients with HCM at Fuwai Hospital from October 2009 to December 2013 and patients were followed up clinically for (53.3±15.4) months. Patients were divided into 3 groups according to NT-proBNP values: NT-proBNP<860 pmol/L (n=276) , 860 pmol/L≤NT-proBNP≤1 905 pmol/L (n=278) , NT-proBNP>1 905 pmol/L (n=277) . The related baseline data, laboratory examination and echocardiographic results were compared among groups. The primary endpoints of this study were all-cause mortality and cardiac transplantation. Cox proportional hazards model was used to estimate hazard ratio (HR) . Kaplan-Meier analysis was used to evaluate the survival status of patients among the 3 groups. Results: During a median follow-up of (53.3±15.4) months, all-cause mortality or cardiac transplantation occurred in 37 patients (4.5%) , event rate was 1.4% (4/276) , 4.0% (11/278) and 7.9% (22/277) in patients with NT-proBNP<860 pmol/L, 860 pmol/L≤NT-proBNP≤1 905 pmol/L and NT-proBNP>1 905 pmol/L, respectively. Multivariable Cox regression analysis identified that age (HR 1.066, 95%CI 1.027-1.107) and NT-proBNP (HR 1.026, 95% CI 1.010-1.042) were independent predictors of all-cause mortality or cardiac transplantation. Among the 3 groups, the survival rate of the NT-proBNP<860 pmol/L group was the highest,and that of the NT-proBNP>1 905 pmol/L group was the lowest (P<0.01) . Conclusions The level of NT-proBNP provides clinically relevant information for long-term adverse events risk stratification in patients with HCM.

Objective: This cross-sectional study aimed to address the relationship between the volume of epicardial adipose tissue (EAT) with cardiovascular risk factors and coronary artery calcification(CAC) in the community residents. Methods: Individuals were recruited from the Jidong Community (Tangshan City, Northern China) which mainly comprised employees of the Jidong Co. Ltd. and their family members. From July 2013 to August 2014, 2 647 participants aged ≥40 years were included in this study. The volume of EAT and coronary artery calcification score (CAC score) were determined by a 64-slice CT. Carotid intima-media thickness (CIMT) was measured by a trained sonographer using a high-resolution B-mode topographic ultrasound system. Venous blood samples were analyzed by automated analyzers in the central laboratory. A validated questionnaire specifically designed for this study was used to collect demographic data from all participants by trained doctors. Characteristics of study cohort were compared according to quartiles of EAT volume (n=660, 663, 662, 662, repectively). Results: (1) The mean age of participants was (55.31±7.76) years and 49.94% (n=1 322) were men. The median EAT volume (interquartile) was 129.42 (95.66, 176.51)cm³. (2) Age, BMI, waist circumference and hip circumference, systolic blood pressure, LDL-C, triglycerides, and fasting blood glucose were significantly higher, while HDL-C level was significantly lower in participants with higher EAT volume than participants with lower EAT volume (all P<0.05). Carotid intima-media thicken (CIMT) and higher CAC score were also significantly higher in participants with higher volume of EAT. Furthermore, percentage of diabetes mellitus, hypertension, hyperlipidemia increased in proportion with increasing EAT volume (P<0.05). (3) In the linear regression, significant positive relations were found for age (β=0.019 3, 95%CI 0.017-0.021, P<0.001), waist circumference (β=0.012 7, 95%CI 0.009-0.016, P<0.001), BMI (β=0.022 4, 95%CI 0.013-0.032, P<0.001), LDL-C (β=0.048 4, 95%CI 0.021-0.076, P<0.001), and HDL-C (β=-0.098 1, 95%CI-0.164--0.032, P<0.001) was inversely related to the EAT volume. (4) Logistic regression analysis indicated that EAT volume was an independent risk factor for CAC score>0 (OR=1.233, 95%CI 1.205-1.262, P<0.001) . Conclusions Our findings indicate that EAT volume is strongly correlated to cardiovascular risk factors and coronary calcification and is an independent risk factor of increased coronary calcification in community residents.