BackgroundGraduate students frequently face life events， many of which may adversely affect their mental well-being. However， the interaction between life events and the development of depression， anxiety， and somatic symptoms remains unclear. ObjectiveTo explore the relationship between life events and the development of depressive， anxiety and somatic symptoms in graduate students， thereby informing prevention strategies for these conditions. MethodsA sample of 6 722 newly enrolled graduate students at a comprehensive university in Southwest China from September to November 2018 was selected. The assessment was conducted using the Adolescent Self-rating Life Events Checklist （ASLEC）， the 7-item Generalized Anxiety Disorder scale-7 item （GAD-7）， the Patient Health Questionnaire Depression Scale-9 item （PHQ-9）， and the Patient Health Questionnaire-15 （PHQ-15）. Network analysis was implemented by using the bootnet and qgraph packages in the R software （version 4.2.3）， with centrality indices calculated to identify core and bridge symptoms within the network. ResultsThe study encompassed a total of 6 171 graduate students， representing 91.80% of the target population. The prevalence rates of anxiety， depressive， and somatic symptoms among graduate students were 12.59% （777/6 171）， 16.63% （1 026/6 171）， and 27.66% （1 707/6 171）， respectively. Network analysis revealed that 'academic stress' was the core symptom with the highest strength and expected influence （both values=1.207）， while 'feeling down， depressed， or hopeless' was the bridge symptom with the highest bridge strength and bridge expected influence （both values=0.454）. There was no significant difference in global network strength and edge weight between women and men （P>0.05）. ConclusionAcademic stress， emerging as the core symptom， assumes a dominant position within the symptom network and exhibits strong interactions with other negative affective states. There was no gender difference in the network structure.

Objective To evaluate the methodological and report quality of the randomized controlled trials(RCT)of Traditional Chinese Medicine(TCM)exercise in patients with Parkinson's disease(PD).Know the current quality status and existing problems,and provide reference for future clinical practice.Methods After Chinese and English databases were searched by computer.We referred to Cochrane 5.1.0 Bias Risk Assessment Tool and the CONSORT 2010 Statement,evaluated the methodology and report quality of the in-cluded RCT.Results 54studies were included,57.4％were Tai chi intervention,the concealment of randomization and allocation schemes,blinding of outcome assessors,and other sources of bias were not adequately reported.96.3％(52studies)had a high risk of blinding subjects and intervenors,only 14.8％(8studies)used and described the concealment of randomization,and 38.9％(21 studies)reported the use of blinding of outcome assessors.The evaluation results of CONSORT statement showed that in total 37subitems,5subitems(13.5％)had a report rate of 0.More than half of the subitems(67.6％)had a report rate of less than 50％,in-cluding concealment of allocation(14.8％),implementation of blinding(38.9％),sample-size estimation(16.7％),intention-to-treat analysis(20.4％),and protocol registration(22.2％),etc.Conclusion The methodological and report quality of RCT were low.In the future,researchers should strictly follow the CONSORT statement to standardize the design,implementation and reporting of RCT,improve the higher methodological quality and pay more attention to outcomes in non-motor function and safety outcomes,then provide o-riginal studies with better quality for PD management and promote them to be transformed and utilized.Finally,promote exercise therapy of traditional Chinese medicine in PD management.

Objective To investigate the mechanism of the miR-518a-5p/histone deacetylase 6(HDAC6)axis in DNA oxidative damage in ovarian cancer(OC)SKOV3 cells.Methods Expression levels of miR-518a-5p and HDAC6 mRNA in OC tissues and in various cancer cells(A2780,SKOV3,CAOV3)were detected by qRT-PCR.SKOV3 cells were separated into Control,miR-NC,miR-518a-5p mimics,miR-518a-5p mimics+pcDNA-NC,and miR-518a-5p mimics+pc-HDAC6 groups.Cell proliferation and apoptosis were analyzed by colony-forming assay and Hoechst 33258 staining.Expression of phosphorylated histone H2AX(γ-H2AX)was detected by immunofluorescence assay and reactive oxygen species(ROS)were detected by flow cytometry.HDAC6,Bcl-2-associated X protein(Bax),and B-cell lymphoma-2(Bcl-2)protein expression were analyzed by Western blot.The regulatory relationship between miR-518a-5p and HDAC6 was analyzed by dual luciferase assay.The effect and mechanism of miR-518a-5p on oxidative DNA damage in OC cells were studied in a xenotransplantation tumor model.Results miR-518a-5p expression was decreased and HDAC6 expression was increased in OC tissues and A2780,SKOV3,and CAOV3 cells(P＜0.001).Expression levels of miR-518a-5p were lowest and expression levels of HDAC6 were highest in SKOV3 cells,and SKOV3 cells were therefore selected for subsequent experiments.miR-518a-5p expression,apoptosis rate,number of γ-H2AX-positive cells,relative ROS fluorescence intensity,and expression of Bax were all higher in the miR-518a-5p mimics group compared with the miR-NC group,while HDAC6 mRNA and protein expression,Bcl-2 expression,and colony-formation number were all lower(P＜0.001).HDAC6 mRNA and protein expression,colony-formation number,and expression of Bcl-2 were higher in the miR-518a-5p mimics+pc-HDAC6 group compared with the miR-518a-5p mimics+pcDNA-NC group,and the apoptosis rate,number of γ-H2AX-positive cells,relative ROS fluorescence intensity,and expression of Bax were all lower(P＜0.001).HDAC6 had a targeted regulatory relationship with miR-518a-5p.Overexpression of miR-518a-5p decreased tumor volume,weight,and HDAC6 protein expression in tumor tissues,and increased γ-H2AX expression in vivo(P＜0.001).Upregulation of HDAC6 expression by overexpression of miR-518a-5p increased graft tumor volume,weight,and HDAC6 protein expression and decreased γ-H2AX-positive expression(P＜0.05).Conclusions miR-518a-5p expression is reduced and HDAC6 expression is increased in OC tissues and cells.Overexpression of miR-518a-5p can induce oxidative DNA damage in SKOV3 cells by inhibiting HDAC6 expression,thereby inhibiting cell proliferation and promoting cell apoptosis.

Objective To investigate the mechanism of the miR-518a-5p/histone deacetylase 6(HDAC6)axis in DNA oxidative damage in ovarian cancer(OC)SKOV3 cells.Methods Expression levels of miR-518a-5p and HDAC6 mRNA in OC tissues and in various cancer cells(A2780,SKOV3,CAOV3)were detected by qRT-PCR.SKOV3 cells were separated into Control,miR-NC,miR-518a-5p mimics,miR-518a-5p mimics+pcDNA-NC,and miR-518a-5p mimics+pc-HDAC6 groups.Cell proliferation and apoptosis were analyzed by colony-forming assay and Hoechst 33258 staining.Expression of phosphorylated histone H2AX(γ-H2AX)was detected by immunofluorescence assay and reactive oxygen species(ROS)were detected by flow cytometry.HDAC6,Bcl-2-associated X protein(Bax),and B-cell lymphoma-2(Bcl-2)protein expression were analyzed by Western blot.The regulatory relationship between miR-518a-5p and HDAC6 was analyzed by dual luciferase assay.The effect and mechanism of miR-518a-5p on oxidative DNA damage in OC cells were studied in a xenotransplantation tumor model.Results miR-518a-5p expression was decreased and HDAC6 expression was increased in OC tissues and A2780,SKOV3,and CAOV3 cells(P＜0.001).Expression levels of miR-518a-5p were lowest and expression levels of HDAC6 were highest in SKOV3 cells,and SKOV3 cells were therefore selected for subsequent experiments.miR-518a-5p expression,apoptosis rate,number of γ-H2AX-positive cells,relative ROS fluorescence intensity,and expression of Bax were all higher in the miR-518a-5p mimics group compared with the miR-NC group,while HDAC6 mRNA and protein expression,Bcl-2 expression,and colony-formation number were all lower(P＜0.001).HDAC6 mRNA and protein expression,colony-formation number,and expression of Bcl-2 were higher in the miR-518a-5p mimics+pc-HDAC6 group compared with the miR-518a-5p mimics+pcDNA-NC group,and the apoptosis rate,number of γ-H2AX-positive cells,relative ROS fluorescence intensity,and expression of Bax were all lower(P＜0.001).HDAC6 had a targeted regulatory relationship with miR-518a-5p.Overexpression of miR-518a-5p decreased tumor volume,weight,and HDAC6 protein expression in tumor tissues,and increased γ-H2AX expression in vivo(P＜0.001).Upregulation of HDAC6 expression by overexpression of miR-518a-5p increased graft tumor volume,weight,and HDAC6 protein expression and decreased γ-H2AX-positive expression(P＜0.05).Conclusions miR-518a-5p expression is reduced and HDAC6 expression is increased in OC tissues and cells.Overexpression of miR-518a-5p can induce oxidative DNA damage in SKOV3 cells by inhibiting HDAC6 expression,thereby inhibiting cell proliferation and promoting cell apoptosis.

Objective To evaluate the methodological and report quality of the randomized controlled trials(RCT)of Traditional Chinese Medicine(TCM)exercise in patients with Parkinson's disease(PD).Know the current quality status and existing problems,and provide reference for future clinical practice.Methods After Chinese and English databases were searched by computer.We referred to Cochrane 5.1.0 Bias Risk Assessment Tool and the CONSORT 2010 Statement,evaluated the methodology and report quality of the in-cluded RCT.Results 54studies were included,57.4％were Tai chi intervention,the concealment of randomization and allocation schemes,blinding of outcome assessors,and other sources of bias were not adequately reported.96.3％(52studies)had a high risk of blinding subjects and intervenors,only 14.8％(8studies)used and described the concealment of randomization,and 38.9％(21 studies)reported the use of blinding of outcome assessors.The evaluation results of CONSORT statement showed that in total 37subitems,5subitems(13.5％)had a report rate of 0.More than half of the subitems(67.6％)had a report rate of less than 50％,in-cluding concealment of allocation(14.8％),implementation of blinding(38.9％),sample-size estimation(16.7％),intention-to-treat analysis(20.4％),and protocol registration(22.2％),etc.Conclusion The methodological and report quality of RCT were low.In the future,researchers should strictly follow the CONSORT statement to standardize the design,implementation and reporting of RCT,improve the higher methodological quality and pay more attention to outcomes in non-motor function and safety outcomes,then provide o-riginal studies with better quality for PD management and promote them to be transformed and utilized.Finally,promote exercise therapy of traditional Chinese medicine in PD management.

Objective To screen and verify the genes that play key role in the occurrence and development of esophageal cancer by u-sing bioinformatics and real-time fluorescence quantitative PCR(qRT-PCR)methods to find new markers for diagnosis of esophageal cancer(ESCA).Methods Using the TCGA database and Wayne plot analysis,the cross genes between the differentially expressed genes of ESCA and the genes which have the most significant impacts on disease-free survival(DFS)rate in esophageal cancer patients were preliminarily identified.Following conducting protein-protein interaction(PPI)network analysis on the overlapping genes,GO and KEGG functional analysis was performed to screen the potential key genes as the diagnostic markers of esophageal cancer.qRT-PCR was used to quantitatively analyze the expression of mRNA of the key gene in peripheral blood.Statistical analysis was con-ducted based on the clinico-pathological characteristics of the patients to determine its potential value as a new diagnostic marker for e-sophageal cancer.Results After overlapping of differentially expressed genes of ESCA and disease-free survival genes in the TCGA database,39 upregulated genes and 20 downregulated genes were found to be differentially expressed,all of which affected disease-free survival rate.After conducting PPI network analysis,15 upregulated genes with core interactions were identified,and the downregulat-ed genes did not form any interaction network.Further enrichment analysis of these 15 core interacting genes through GO and KEGG,revealed that fibronectin 1(FN1)may be a potential biomarker for ESCA diagnosis.The qRT-PCR results showed that compared with the healthy control group,the mRNA expression level of FN1 in the peripheral blood of esophageal cancer patients was significantly ele-vated.After analyzing the clinical characteristics of patients,it was found that the patients with poor differentiation and high clinico-pathological staging had significantly increased peripheral blood FN1 mRNA levels.The model with FN1 mRNA expression levels can distinguish esophageal cancer patients from healthy individuals.Conclusion FN1 mRNA may be a potential non-invasive diagnostic biomarker for esophageal cancer.

Background::Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension.Methods::The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60–80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes.Results::The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8–73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7–110.1 cm/s) in the standard treatment group ( P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s –1·year –1vs. 36.7 cm·s –1·year -1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70–80 years or with SBP <140 mmHg. Conclusion::Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension.Clinical trial registration::http://www.clinicaltrials.gov; No. NCT03015311.

Objective::Arterial stiffness is an important predictor of cardiovascular disease. Microbial diversity in the gut has been shown to be associated inversely with arterial stiffness in Caucasian populations. However, due to the different profiles of the gut microbiota among ethnicities, the relationship between gut-microbiota dysbiosis and the progression of arterial stiffness merits further investigation. This study aimed to investigate the association between the composition and functional capacity of the gut microbiota and the progression of arterial stiffness.Methods::"Shotgun" metagenomics sequencing were undertaken in 96 individuals from a hypertension-associated gut-microbiota study in the Kailuan cohort, who measured brachial-ankle pulse wave velocity (baPWV) and provided fecal samples between September 2014 and February 2015 at Kailuan General Hospital and 11 affiliated hospitals. The different composition and functional capacity of the gut microbiota were compared between individuals without arterial stiffness (normal arterial stiffness group, baPWV <1,400 cm/s, n = 27) and participants with arterial stiffness (increased arterial stiffness group, baPWV ≥1,400 cm/s, n = 69) at baseline. These participants were followed up prospectively for a mean duration of 2.6 years, and 50 underwent a repeat baPWV measurement. Associations between the gut microbiota and severity and progression of arterial stiffness were assessed using MaAsLin2 software after adjustment for age, sex, and mean arterial blood pressure and correction for multiple testing. Gene "catalogs" were aligned to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to obtain information for potential functional capacities of the gut microbiota. Results::In this study, 14 genera and 50 species of bacteria were identified to be abundant in participants with normal arterial stiffness compared with those with increased arterial stiffness. Of 14 genera, the prevalence of beneficial bacteria of the genera Leadbetterella and Cytophaga was correlated inversely with baPWV ( P < 0.05). Analyses of functional capacity revealed gut-microbial dysfunctions in the synthetic processes of "threonine dehydratase" "hypothetical protein" "mannosyl transferase" and "type-IV secretion-system proteins" in individuals suffering from arterial stiffness. During follow-up, bacteria of the proinflammatory genera Escherichia, Shigella, and Ruegeria were enriched in individuals with increased baPWV. Functional analyses showed that 26 KEGG orthologs of gut microbes were associated with an increase in baPWV and involved in "carbohydrate metabolism" "amino acid metabolism" and "protein families related to genetic information processing." Conclusions::The composition and functional capacity of the microbial community in the gut of people suffering from arterial stiffness differed from those in individuals not suffering from arterial stiffness. Our data provide a new direction for the causality of the host-gut microbiota in arterial stiffness.

Objective::Arterial stiffness is an important predictor of cardiovascular disease. Microbial diversity in the gut has been shown to be associated inversely with arterial stiffness in Caucasian populations. However, due to the different profiles of the gut microbiota among ethnicities, the relationship between gut-microbiota dysbiosis and the progression of arterial stiffness merits further investigation. This study aimed to investigate the association between the composition and functional capacity of the gut microbiota and the progression of arterial stiffness.Methods::"Shotgun" metagenomics sequencing were undertaken in 96 individuals from a hypertension-associated gut-microbiota study in the Kailuan cohort, who measured brachial-ankle pulse wave velocity (baPWV) and provided fecal samples between September 2014 and February 2015 at Kailuan General Hospital and 11 affiliated hospitals. The different composition and functional capacity of the gut microbiota were compared between individuals without arterial stiffness (normal arterial stiffness group, baPWV <1,400 cm/s, n = 27) and participants with arterial stiffness (increased arterial stiffness group, baPWV ≥1,400 cm/s, n = 69) at baseline. These participants were followed up prospectively for a mean duration of 2.6 years, and 50 underwent a repeat baPWV measurement. Associations between the gut microbiota and severity and progression of arterial stiffness were assessed using MaAsLin2 software after adjustment for age, sex, and mean arterial blood pressure and correction for multiple testing. Gene "catalogs" were aligned to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to obtain information for potential functional capacities of the gut microbiota. Results::In this study, 14 genera and 50 species of bacteria were identified to be abundant in participants with normal arterial stiffness compared with those with increased arterial stiffness. Of 14 genera, the prevalence of beneficial bacteria of the genera Leadbetterella and Cytophaga was correlated inversely with baPWV ( P < 0.05). Analyses of functional capacity revealed gut-microbial dysfunctions in the synthetic processes of "threonine dehydratase" "hypothetical protein" "mannosyl transferase" and "type-IV secretion-system proteins" in individuals suffering from arterial stiffness. During follow-up, bacteria of the proinflammatory genera Escherichia, Shigella, and Ruegeria were enriched in individuals with increased baPWV. Functional analyses showed that 26 KEGG orthologs of gut microbes were associated with an increase in baPWV and involved in "carbohydrate metabolism" "amino acid metabolism" and "protein families related to genetic information processing." Conclusions::The composition and functional capacity of the microbial community in the gut of people suffering from arterial stiffness differed from those in individuals not suffering from arterial stiffness. Our data provide a new direction for the causality of the host-gut microbiota in arterial stiffness.

Objective To analyze the relationship between the level of microRNA-29b in circulation and left ventricular hypertrophy in hypertensive patients.Methods A total of 240 subjects from Henan Province People's Hospital from June 2015 to June 2018 were included in the present study.Among them,160 were hospitalized patients,and were divided into two groups.Patients with simple hypertension and had no left ventricular hypertrophy (80 cases) were in the simple hypertension group (HBP-NLVH),and patients with hypertension combined with left ventricular hypertrophy (80 cases) were in the high blood pressure with left ventricular hypertrophy group (HBP-LVH).Normal control subjects (80 cases) were those with no hypertension and randomly selected from the medical center of Henan Province People's Hospital.Serum microRNA-29b expressions were detected by real time fluorescence quantitative PCR.The thickness of interventricular septum (IVSD) and left ventricular posterior wall thickness (LVPWD) were measured by echocardiography.Results Compared with the normal control group (1.95±0.79),the relative expression of microRNA-29b in the patients both in the HBP-NLVH group (2.67±0.92) and the HBP-LVH group (5.12 ± 1.23) was up-regulated,and the difference between normal control and patients was statistically significant (P＜0.05).In patients,the microRNA-29b level in the HBP-LVH group was significantly higher than that in the HBP-NLVH group (P＜0.05).The expression level of microRNA-29b was positively correlated with IVSD (r=0.71,P＜0.05) and LVPWD (r=0.74,P＜0.05),respectively.The sensitivity and specificity of serum microRNA-29b levels in the diagnosis of left ventricular hypertrophy in hypertension patients were 96.8％ and 91.3％,respectively.Conclusion Serum microRNA-29b level is elevated in hypertensive patients with left ventricular hypertrophy,and is positively correlated with left ventricular hypertrophy.The circulation microRNA-29b might be a useful biomarker with prognostic value in left ventricular hypertrophy in hypertension patients.