Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective To analyze the clinical characteristics of proximal tubular acidosis induced by deferasirox in children with β-thalassemia major. Methods This study retrospectively analyzed the clinical manifestations, laboratory test results, radiological features, treatment methods and outcomes of proximal tubular acidosis in 5 children with β-thalassemia major. Results Five patients aged 5 to 16 years, included 2 males and 3 females. Two patients were diagnosed with Fanconi syndrome. Four patients received deferasirox doses exceeding the conventional dose, including one with a rapid decline in ferritin levels. Gastrointestinal symptoms were the initial manifestations in 3 patients, while only mild anorexia was observed in 2 patients. There were significant correlations between the severity of clinical manifestations, the degree of acidosis and its duration. All patients had abnormally elevated urine β₂-microglobulin levels, and 4 patients had hepatic iron deposition. After reducing or discontinuing deferasirox and providing symptomatic treatment, the renal tubular function of all 5 patients gradually recovered. Conclusion Proximal tubular acidosis induced by deferasirox in patients with β-thalassemia major can manifest as partial or complete proximal tubular acidosis, which may be associated with high-dose deferasirox administration and rapid decreases in body iron levels. Regular monitoring of relevant indicators is recommended for children receiving long-term deferasirox treatment. Once proximal tubular acidosis is detected, drug dosage adjustment or discontinuation should be promptly implemented, and renal tubular function can recover in most patients.

Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

Objective To explore the predictive value of serum cathepsin S(CTSS),progranulin(PGRN)and chemo-kine ligand 12(CXCL12)for acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods A total of 202 patients with COPD who were admitted to the Tongling Municipal Hospital from January 2020 to February 2023 were selected as the research subjects.The patients were divided into an acute exacerbation group(n=64)and a non-acute exacerbation group(n=138)according to whether acute exacerbation occurred.Clinical data such as serum CTSS,PGRN and CXCL12 levels,age,gender,body mass index(BMI),disease course,smoking history,forced expiratory volume in one second/forced vital capacity ratio(FEV1％),and COPD assessment test(CAT)score in the stable period were collected.Univariate analysis was made to compare the differences in relevant indicators between the two groups,and multivariate logistic regression analysis was made to identify the independent risk factors for acute exacerbation in COPD patients.The Pearson correlation method was used to analyze the correlation between serum CTSS,PGRN,CXCL12 levels and FEV1％,CAT score.Relative risk analysis was used to evaluate the influence of different CTSS,PGRN and CXCL12 levels on acute exacerbation in COPD patients.The predictive efficacy of serum CTSS,PGRN and CXCL12 levels on acute exacerbation in COPD patients was evaluated by receiver operating characteristic(ROC)curve.Results Univariate analysis showed that there was no significant difference in age,sex,BMI and disease course of patients between the two groups(P＞0.05),while there were significant differences in the propor-tion of patients with smoking history,FEV1％,CAT score,and serum CTSS,PGRN and CXCL12 levels between the two groups(P＜0.05).Multivariate logistic regression analysis showed that elevated serum CTSS,PGRN and CXCL12 levels were risk factors for acute exacerbation in COPD patients(P＜0.05).There were significant differences in serum CTSS,PGRN and CXCL12 levels among patients with different FEV1％and CAT scores(P＜0.05).Pearson correlation analysis showed that serum CTSS,PGRN and CXCL12 levels were negatively correlated with FEV1％and positively correlated with CAT score(P＜0.05).Risk analysis showed that the risk of acute exacerbation in COPD patients with high serum CTSS,PGRN and CXCL12 levels was 2.089 times[95％confidence interval(CI):1.341-3.253],2.294 times(95％CI:1.363-3.862)and 2.359 times(95％CI:1.459-3.815)of the COPD patients with low serum CTSS,PGRN and CXCL12 levels.ROC analysis indica-ted that the area under the curve for predicting the risk of acute exacerbation in COPD patients based on serum CTSS,PGRN and CXCL12 levels alone was 0.780,0.811 and 0.755,respectively;the area under the curve for predicting the risk of acute exacerbation in COPD patients based on the combination of serum CTSS,PGRN and CXCL12 levels was 0.923.Conclusion Serum CTSS,PGRN and CXCL12 levels are risk factors for acute exacerbation of COPD.Abnormal elevation of serum CTSS,PGRN and CXCL12 levels can significantly increase the risk of acute exacerbation of COPD.The combination of serum CTSS,PGRN and CXCL12 levels is more effective in predicting the risk of acute exacerbation of COPD.

Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

OBJECTIVE: To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene. METHODS: A patient who had presented at Anhui Provincial Children's Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c.3052C>T (p.Pro1018Ser) missense variant of the CHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3032C>T variant was classified as a likely pathogenic (PS2+PM2_Supporting+PP2+PP3+PP4). CONCLUSION The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T (p.Pro1018Ser) variant of the CHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.
Child ; Humans ; Male ; Amino Acid Sequence ; Computational Biology ; DNA Helicases/genetics* ; DNA-Binding Proteins/genetics* ; Genetic Testing ; Genomics ; Hypogonadism/genetics* ; Mutation

OBJECTIVE: To investigate the clinical characteristics and genetic basis for a child with Keppen-Lubinsky syndrome (KPLBS). METHODS: Trio-whole exome sequencing (Trio-WES) was carried out for the proband and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child has featured peculiar facies including large eyes, alar hypoplasia, microretrognathia, premature aging appearance in addition with growth delay and mental retardation. Trio-WES has identified that she has carried a de novo variant of the KCNJ6 gene, namely c.460G>C (p.Gly154Arg). The variant has not been recorded in the database. Prediction of protein structure indicated that the variant may affect the potassium ion selective filtration structure channel in the transmembrane region of KCNJ6 protein, which may result in up regulation of the function of the channel. CONCLUSION The de novo c.460G>C (p.Gly154Arg) variant of the KCNJ6 gene probably underlay the KPLBS in this child. Above finding has enriched the genotypic and phenotype spectrum of this syndrome.
Cataract ; China ; Female ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics* ; Humans ; Hypogonadism/congenital* ; Intellectual Disability/genetics* ; Mutation ; Whole Exome Sequencing

Objective To assess the effect and underlying molecular events of caffeic acid phenethyl ester (CAPE) on rat hepatic stellate HSC-T6 cells. Methods HSC-T6 cells were grown and treated with different concentrations of CAPE (5, 10, or 15 μmol/L), transfected with or without LC3-GFP plasmid, and then treated with or without an autophagy inducer rapamycin or the autophagy inhibitor 3-methyladenine (3-MA). The changed cell viability and morphology were assessed by using cell viability MTT assay and Transmission electron microscope, respectively. The expression of LC3 protein in HSC-T6 cells was detected by immunofluorescence assay, the autophagy-related genes expression of ATG5, ATG7, ATG12, Beclin1 and LC3 were detected by qRT-PCR, and the expression of ATG7, Beclin1, LC3I/Ⅱ, p-AKT/AKT, p-mTOR protein was detected by Western-blot. Comparison between multiple groups was analyzed by one-way ANOVA with Dunnett t -test. Results Compared with the control, CAPE treatment significantly reduced cell viability but induced formation of lipid droplets and roulette-shaped autophagosomes. Compared with the control (13.34%±2.59), LC3 protein was significantly induced in HSC-T6 cells after CAPE treatment (5 μmol/L, 23.68%±3.76, t =-5.553, P < 0.001; 10 μmol/L, 43.47%±3.83, t =-15.958, P < 0.001; 15 μM, 57.25%±2.78, t =-28.334, P < 0.001), while levels of ATG5, ATG7, ATG12, Beclin 1, and LC3 mRNAs were all significantly increased in 10 μm and 15 μm CAPE treated cells vs the control (all P < 0.05). After LC3 overexpression in HSC-T6 cells, LC3 protein was induced vs the vector control (79.01%±6.69% vs 67.06%±6.74%, t =-3.083, P =0.012), while rapamycin treatment further increased LC3 expression (86.88%±5.42%, t =-2.239, P =0.049); however, 3-MA treatment significantly decreased LC3 expression in cells (71.22%±4.29%, t =-2.404, P =0.037). In addition, levels of ATG7, Beclin1, and LC3 Ⅰ/Ⅱ proteins were increased, whereas levels of AKT/p-AKT and p-mTOR were decreased in the CAPE and rapamycin groups vs controls. However, the 3-MA treatment had an opposite result, indicating that 3-MA reversed CAPE-induced effects in HSC-T6 cells. Conclusion Caffeic acid phenethyl ester may induce autophagy to reduce cell viability in hepatic stellate cells by inhibition of the AKT/mTOR signaling.

Objective:To investigate the role of miR-146a in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA) and its clinical significance.Methods:This article is a prospective clinical cohort study.Twenty-six patients with sJIA (14 cases of initial active group and 12 cases of stable group), 15 patients with multijoint juvenile idiopathic arthritis (JIA) and 15 patients with oligojoint JIA diagnosed in the Department of Rheumatology and Immunology of Anhui Provincial Children′s Hospital from June 2018 to December 2020 were enrolled.Twenty healthy controls from the out-patient clinic were also recruited.The expression level of miR-146a in peripheral blood mononuclear cells (PBMCs) of research objects was detected by real-time fluorescence quantitative polymerase reaction (qPCR), and the serum levels of interleukin (IL) - 6, tumor necrosis factor (TNF) - α and IL-1β in sJIA patients and healthy controls were detected by enzyme-linked immunosorbent assay.The expression levels of miR-146a in PBMCs and cytokines among different groups were compared by analysis of variance. Pearson correlation analysis was used to analyze the correlation of the relative expression level of miR-146a in PBMCs with clinical inflammatory indexes and serum cytokines in sJIA patients. Results:(1) The expression level of miR-146a in PBMCs of early sJIA patients was significantly higher than that in the multijoint JIA group and oligojoint JIA group (8.77±3.15 vs.4.40±1.59, 2.55±1.15, t=6.27, 14.23; all P<0.05). The expression level of miR-146a in PBMCs of sJIA active patients was significantly higher than that in sJIA stable patients (8.77±3.15 vs.3.63±1.37, t=10.27, P<0.05). There was no significant difference in the expression level of miR-146a between the sJIA stable group and healthy control group ( P>0.05). (2) The expression levels of IL-1β, IL-6 and TNF-α were significantly higher in sJIA active patients group than those in sJIA stable group[(58.56±17.47) ng/L vs.(26.32±10.54) ng/L, (73.72±11.16) ng/L vs.(23.20±9.12) ng/L, (70.93±19.97) ng/L vs.(24.25±9.49) ng/L, all P<0.05]. There was no significant difference in the expression levels of IL-1β, IL-6 and TNF-α between the sJIA stable group and healthy control group(all P>0.05). (3)The expression of miR-146a in PBMCs of sJIA patients was positively correlated with serum ferritin levels, platelets, erythrocyte sedimentation rates, C-reactive proteins, IL-1β, IL-6 and TNF-α( r=0.542, 0.433, 0.329, 0.306, 0.333, 0.342, 0.319, all P<0.05). Conclusions:miR-146a may be involved in the inflammatory process of sJIA disease.miR-146a can well distinguish sJIA from multijoint JIA and oligojoint JIA.TNF-α, IL-1β and IL-6 are involved in sJIA inflammatory responses.

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Cox model and Cox model with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95％CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95％CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95％CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95％CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95％CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95％CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95％CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Cox model with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.