ABSTRACT
Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.
Subject(s)
Glaucoma , Retinal Ganglion Cells , Humans , Mice , Animals , Retinal Ganglion Cells/pathology , Vascular Cell Adhesion Molecule-1/metabolism , Th1 Cells/pathology , Glaucoma/metabolism , Retina/pathology , Vision Disorders/pathology , Disease Models, AnimalABSTRACT
This study aimed to assess the diagnostic accuracy of radiomics for predicting osteoporosis and the quality of radiomic studies. The study protocol was prospectively registered on PROSPERO (CRD42023425058). We searched PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to June 1, 2023, for eligible articles that applied radiomic techniques to diagnosing osteoporosis or abnormal bone mass. Quality and risk of bias of the included studies were evaluated with radiomics quality score (RQS), METhodological RadiomICs Score (METRICS), and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tools. The data analysis utilized the R program with mada, metafor, and meta packages. Ten retrospective studies with 5926 participants were included in the systematic review and meta-analysis. The overall risk of bias and applicability concerns for each domain of the studies were rated as low, except for one study which was considered to have a high risk of flow and time bias. The mean METRICS score was 70.1% (range 49.6-83.2%). There was moderate heterogeneity across studies and meta-regression identified sources of heterogeneity in the data, including imaging modality, feature selection method, and classifier. The pooled diagnostic odds ratio (DOR) under the bivariate random effects model across the studies was 57.22 (95% CI 27.62-118.52). The pooled sensitivity and specificity were 87% (95% CI 81-92%) and 87% (95% CI 77-93%), respectively. The area under the summary receiver operating characteristic curve (AUC) of the radiomic models was 0.94 (range 0.8 to 0.98). The results supported that the radiomic techniques had good accuracy in diagnosing osteoporosis or abnormal bone mass. The application of radiomics in osteoporosis diagnosis needs to be further confirmed by more prospective studies with rigorous adherence to existing guidelines and multicenter validation.
ABSTRACT
Cardiovascular disease (CVD) stands as a predominant global cause of morbidity and mortality, necessitating effective and cost-efficient therapies for cardiovascular risk reduction. Mitochondrial coupling factor 6 (CF6), identified as a novel proatherogenic peptide, emerges as a significant risk factor in endothelial dysfunction development, correlating with CVD severity. CF6 expression can be heightened by CVD risk factors like mechanical force, hypoxia, or high glucose stimuli through the NF-κB pathway. Many studies have explored the CF6-CVD relationship, revealing elevated plasma CF6 levels in essential hypertension, atherosclerotic cardiovascular disease (ASCVD), stroke, and preeclampsia patients. CF6 acts as a vasoactive and proatherogenic peptide in CVD, inducing intracellular acidosis in vascular endothelial cells, inhibiting nitric oxide (NO) and prostacyclin generation, increasing blood pressure, and producing proatherogenic molecules, significantly contributing to CVD development. CF6 induces an imbalance in endothelium-dependent factors, including NO, prostacyclin, and asymmetric dimethylarginine (ADMA), promoting vasoconstriction, vascular remodeling, thrombosis, and insulin resistance, possibly via C-src Ca2+ and PRMT-1/DDAH-2-ADMA-NO pathways. This review offers a comprehensive exploration of CF6 in the context of CVD, providing mechanistic insights into its role in processes impacting CVD, with a focus on CF6 functions, intracellular signaling, and regulatory mechanisms in vascular endothelial cells.
ABSTRACT
BACKGROUND: This study aimed to determine the correlation between human-immunodeficiency-virus (HIV) infection and stroke, as well as to estimate the global, regional, and national burden of HIV-associated stroke. METHODS: A registered meta-analysis was performed by searching PubMed, Embase, and Web of Science for relevant literature up to October 31, 2022. The pooled relative risk of stroke in HIV-infected people was calculated using a random-effects model. HIV prevalence and disability-adjusted life years (DALYs) datasets were obtained from the Joint United Nations Program on HIV and AIDS, and the Global Health Data Exchange, respectively. The population attributable fraction was estimated and delivered to calculate the HIV-associated DALYs of stroke from 1990 to 2019, at the global, regional, and national levels. Pearson correlation analysis were conducted to assess the correlation between the age-standardized rate or estimated annual percentage changes and the sociodemographic index. RESULTS: Out of 10â 080 identified studies, 11 were included in this meta-analysis. Compared with individuals without HIV-infection, the pooled relative risk of stroke in HIV-infected individuals was 1.40 (95% CI, 1.18-1.65). From 1990 to 2019, the global population attributable fraction of HIV-associated stroke increased almost 3-fold, while the HIV-associated DALYs increased from 18 595 (95% CI, 7485-31â 196) in 1990 to 60â 684 (95% CI, 24â 281-101â 894) in 2019. Meanwhile, HIV-associated DALYs varied by region, with Eastern and Southern Africa having the highest value of 126â 160 in 2019. Moreover, countries with middle social development index were shouldering the highest increase trend of the HIV-associated DALYs age-standardized rates. CONCLUSIONS: HIV-infected individuals face a significantly higher risk of stroke, and the global burden of HIV-associated stroke has increased over the past 3 decades, showing regional variations. Eastern and Southern Africa bear the highest burden, while Eastern Europe and Central Asia have seen significant growth. Health care providers, researchers, and decision-makers should give increased attention to stroke prevention and management in HIV-endemic areas. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42022367450.
Subject(s)
HIV Infections , Stroke , Humans , Quality-Adjusted Life Years , Stroke/epidemiology , HIV Infections/complications , HIV Infections/epidemiology , Global Health , Research Design , Global Burden of Disease , Risk FactorsABSTRACT
BACKGROUND: The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women. METHODS: Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I2) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed. RESULTS: Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria. CONCLUSIONS: Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk. TRIAL REGISTRATION: PROSPERO registration: CRD42021285206, May 22, 2023.
Subject(s)
Gastrointestinal Microbiome , Microbiota , Polycystic Ovary Syndrome , Humans , Female , Dysbiosis , PhylogenyABSTRACT
Previous studies reported human immunodeficiency virus (HIV) could enhance human papillomavirus (HPV)-induced cervical cancer. Therefore, the burden of cervical cancer associated with HIV across different regions and time periods need to be assessed. We aim to investigate the global burden of cervical cancer associated with HIV infection. Age standardized rates (ASRs) of cervical cancer disability-adjusted life-years (DALYs) in females (≥15 years old) were calculated by standardization, according the age-specific DALYs numbers extracted from GBD data set 2019. Population attributable fractions was calculated by combining the published risk ratio, with the HIV prevalence (≥15 years old) from Joint United Nations Programme on HIV and AIDS (UNAIDS), and transferred to estimate the HIV-associated cervical cancer burden. Expected annual percentage changes (EAPCs) was calculated to describe the temporal trend of ASR from 1990 to 2019. Pearson correlation analysis were conducted to assess the correlation between the ASR or EAPCs and the socio-demographic index. The worldwide DALYs ASR caused by HIV-associated cervical cancer rose from 3.78 (95% confidence interval [CI]: 2.19-5.56) in 1990 to 9.50 (95% CI: 5.66-13.79) in 2019 per 100k population. In 2019, the region with the greatest burden was Eastern and Southern Africa, with the highest DALYs of 273 900 (95% CI: 149 100-476 400) and ASR of 254.44 per 100k population (95% CI: 168.86-329.28). Notably, the Eastern Europe and Central Asia regions had the highest EAPC (14.07%) of HIV-associated DALYs ASR. Women in Eastern and Southern Africa experience the greatest burden of HIV-associated cervical cancer, while the Eastern Europe and Central Asia regions had witnessed the largest increase over the last 30 years. Prioritize the promotion of HPV vaccination and cervical cancer screening for women living with HIV were crucial in these regions.
Subject(s)
HIV Infections , Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Adolescent , HIV Infections/complications , HIV Infections/epidemiology , Uterine Cervical Neoplasms/epidemiology , Global Burden of Disease , Early Detection of Cancer , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Quality-Adjusted Life Years , HIV , Global HealthABSTRACT
Purpose: Acute anterior uveitis (AAU) is the most common extra-articular symptom of ankylosing spondylitis (AS). This study aims to reveal the cytokines and chemokines involved in the immunopathogenesis of human leucocyte antigen (HLA)-B27+ AS-associated AAU. Methods: Twenty-one HLA-B27+ AS-associated AAU patients and 21 healthy controls (HCs) were recruited for this study. Serum cytokine concentrations in all 42 subjects were determined by the Meso Scale Discovery (MSD) electrochemiluminescence method. In each sample, 34 cytokines, 10 chemokines, eight angiogenesis mediators, and four vascular injury mediators were measured. The differences in cytokine and chemokine concentrations were compared between the two groups. Results: Concentrations of serum IL-3, TNF-α, IL-6, IL-17D, IL-22, IP10/CXCL10, MIP-3α/CCL20, sFlt-1/VEGFR-1, CRP, and MCP-4/CCL13 were significantly higher in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). In contrast, concentrations of serum IL-4, IL-8, MIP-1α/CCL3, Eotaxin-3/CCL26, PlGF, VEGF-C, and VEGF-D were significantly lower in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). Conclusions: Significant differences were detected in the levels of several cytokines and chemokines in the serum of HLA-B27+ AS-associated AAU compared with HCs. Some novel differential cytokines and chemokines that have not been reported in other kinds of uveitis were also identified. These results reveal the underlying pathogenesis of HLA-B27+ AS-associated AAU and could potentially aid in clinical diagnosis.
Subject(s)
Spondylitis, Ankylosing , Uveitis, Anterior , Humans , Cytokines , Spondylitis, Ankylosing/complications , HLA-B27 Antigen/genetics , Chemokines , Acute DiseaseABSTRACT
The purpose of this study was to investigate the correlation of thyroid-related hormones changes within the reference range with the changes in anthropometric measures and incidence of obesity. The study included 4850 subjects with normal thyroid-related hormones at baseline and at follow-up. We evaluated the relationship of changes in thyroid-related biomarkers with anthropometric measures changes and incidence of obesity. In euthyroid persons, changes in serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) concentrations and FT3/FT4 ratio were independent predictors of changes in body mass index (BMI) and waist circumference (WC) in men, changes in serum FT3 and FT4 concentrations and FT3/FT4 ratio were independent predictors of changes in BMI and WC in women. Every single unit increment in ΔFT3/FT4 was accompanied by a 7.144 and 7.572 times risk of having obesity in men and women, respectively. Every single unit decrement in ΔFT4 was accompanied by a 21.0% and 26.9% lower risk of having obesity in men and women, respectively. In conclusion, in euthyroid individuals, changes in thyroid-related hormones were associated with anthropometric measures changes and incidence of obesity.
ABSTRACT
BACKGROUND: As the most abundant epigenetic modification of eukaryotic mRNA, N6-methyladenosine (m6A) modification has been shown to play a role in mammalian nervous system development and function by regulating mRNA synthesis and degeneration. However, the role of m6A modification in retinal photoreceptors remains unknown. RESULTS: We generated the first retina-specific Mettl14-knockout mouse models using the Rho-Cre and HRGP-Cre lines and investigated the functions of Mettl14 in retinal rod and cone photoreceptors. Our data showed that loss of Mettl14 in rod cells causes a weakened scotopic photoresponse and rod degeneration. Further study revealed the ectopic accumulation of multiple outer segment (OS) proteins in the inner segment (IS). Deficiency of Mettl14 in cone cells led to the mislocalization of cone opsin proteins and the progressive death of cone cells. Moreover, Mettl14 depletion resulted in drastic decreases in METTL3/WTAP levels and reduced m6A methylation levels. Mechanistically, transcriptomic analyses in combination with MeRIP-seq illustrated that m6A depletion via inactivation of Mettl14 resulted in reduced expression levels of multiple phototransduction- and cilium-associated genes, which subsequently led to compromised ciliogenesis and impaired synthesis and transport of OS-residing proteins in rod cells. CONCLUSIONS: Our data demonstrate that Mettl14 plays an important role in regulating phototransduction and ciliogenesis events and is essential for photoreceptor function and survival, highlighting the importance of m6A modification in visual function.
Subject(s)
Methyltransferases/metabolism , Photoreceptor Cells, Vertebrate , Retina , Animals , Mammals/genetics , Methylation , Methyltransferases/genetics , Mice , Photoreceptor Cells, Vertebrate/metabolism , Proteins/metabolism , RNA, Messenger/metabolism , Retina/metabolism , Retinal Cone Photoreceptor CellsABSTRACT
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is not considered only a liver disease but also associated with an increased risk of extra-hepatic diseases including bone metabolism disorders. In our study, we aim to explore the changes of several bone turnover markers (BTMs) under different fat deposition and stiffness levels of the liver. MATERIALS AND METHODS: We analyzed the physical examination data of 3353 subjects from February 2018 to June 2021 in this study. The steatosis and stiffness of liver were quantitatively detected using the fat attenuation parameter (FAP) and liver stiffness measurements (LSM) of transient elastography (TE). Serum 25-hydroxyvitamin D3 (25(OH)D3), osteocalcin, carboxy-terminal collagen crosslinks (CTX), amino terminal elongation peptide of total type 1 procollagen (P1NP) were tested. Clinical and other biochemical data were also collected. RESULTS: With the increasing of FAP, the levels of 25(OH)D3 and osteocalcin decreased, the difference was statistically significant. No correlation was found between LSM and all the four BTMs. Logistic regression analysis revealed that FAP ≥ 244 dB/m was negatively correlated with 25(OH)D3 (in both males and females) and osteocalcin (only in males). No correlation was found between FAP ≥ 244 dB/m and P1NP or CTX. CONCLUSION: The degree of liver adipose deposition was found to be negatively associated with the serum levels of 25(OH)D3 (in both males and females) and osteocalcin (only in males) in southwest China.
Subject(s)
Bone Diseases, Metabolic , Non-alcoholic Fatty Liver Disease , Biomarkers , Bone Diseases, Metabolic/complications , Bone Remodeling , China , Female , Humans , Male , OsteocalcinABSTRACT
The present study investigated the correlation between dietary patterns (DPs) with skeletal muscle mass (SMM) and cardiovascular risks in Sichuan males aged ≥65-years-old. Three major DPs were extracted by principal component analysis: animal-based and processed food, traditional food, and ovo-lacto vegetarian food, which accounted for 14.83%, 14.36%, and 11.86% of the variance, respectively. Adjusted logistic regression analysis showed that animal-based and processed food DP was positively associated with overweight/obesity(OR: 3.25, 95% CI: 1.94-5.46) and dyslipidemia(OR: 3.53, 95% CI: 2.00-6.22). Traditional DP was negatively associated with overweight/obesity(OR: 0.51, 95% CI: 0.36-0.72), dyslipidemia(OR: 0.50, 95% CI: 0.35-0.75), and high blood pressure(OR: 0.54, 95% CI: 0.38-0.77), but positively associated with decreased SMM (OR: 2.21, 95% CI: 1.36-3.16). Ovo-lacto vegetarian DP was negatively associated with dyslipidemia (OR: 0.56, 95% CI: 0.39-0.81) and hyperuricemia (OR: 0.56, 95% CI: 0.39-0.79), but positively associated with decreased SMM (OR: 1.57, 95% CI: 0.74-2.32). How to choose the best DP to control the cardiovascular risks and fight skeletal muscle loss needs further investigation in the future.
Subject(s)
Cardiovascular Diseases , Diet , Heart Disease Risk Factors , Muscle, Skeletal/anatomy & histology , Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , China/epidemiology , Cross-Sectional Studies , Humans , Male , Risk FactorsABSTRACT
The processing, maturation, and secretion of insulin are under precise regulation, and dysregulation causes profound defects in glucose handling, leading to diabetes. Tmem30a is the ß subunit of the phosphatidylserine (PS) flippase, which maintains the membrane asymmetric distribution of PS. Tmem30a regulates cell survival and the localization of subcellular structures and is thus critical to the normal function of multiple physiological systems. Here, we show that conditional knockout of Tmem30a specifically in pancreatic islet ß cells leads to obesity, hyperglycemia, glucose intolerance, hyperinsulinemia, and insulin resistance in mice, due to insufficient insulin release. Moreover, we reveal that Tmem30a plays an essential role in clathrin-mediated vesicle transport between the trans Golgi network (TGN) and the plasma membrane (PM), which comprises immature secretory granule (ISG) budding at the TGN. We also find that Tmem30a deficiency impairs clathrin-mediated vesicle budding and thus blocks both insulin maturation in ISGs and the transport of glucose-sensing Glut2 to the PM. Collectively, these disruptions compromise both insulin secretion and glucose sensitivity, thus contributing to impairments in glucose-stimulated insulin secretion. Taken together, our data demonstrate an important role of Tmem30a in insulin maturation and glucose metabolic homeostasis and suggest the importance of membrane phospholipid distribution in metabolic disorders.
Subject(s)
Glucose Intolerance/genetics , Glucose Transporter Type 2/metabolism , Hyperglycemia/genetics , Hyperinsulinism/genetics , Insulin Resistance/genetics , Insulin/metabolism , Membrane Proteins/genetics , Obesity/genetics , Animals , Cell Membrane/metabolism , Disease Models, Animal , Gene Knockout Techniques , Glucose/adverse effects , Glucose Intolerance/metabolism , Hyperglycemia/metabolism , Hyperinsulinism/metabolism , Insulin Secretion , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Mice , Obesity/metabolism , Phosphatidylserines/metabolism , trans-Golgi Network/metabolismABSTRACT
OBJECTIVE: To assess the association of 7 single nucleotide polymorphisms (SNPs) including rs13278062 (TNFRSF10A), rs3750846 (ARMS2-HTRA1), rs429358 (APOE), rs5817082 (CEPT), rs2043085 (LIPC), rs1626340 (TGFBR1), and rs8135665 (SLC16A8) identified through genome-wide association study (GWAS) with age-related macular degeneration (AMD) among ethnic Han Chinese from Sichuan, China. METHODS: A cohort of 576 AMD patients and 572 healthy controls were enrolled in a case-control study. The SNPs were genotyped by a Mass array MALDI-TOF System. On the premise that the genotype distribution of each SNP locus in both groups satisfied Hardy-Weinberg equilibrium, the genetic pattern was analyzed and the scores of allele and genotype frequencies ware compared. RESULTS: There was a significant association between TNFRSF10A rs13278062 and AMD under the heterozygous model (P = 0.000, OR = 1.529, 95%CI = 1.196-1.954) and the dominant model (P = 0.002, OR = 1.459, 95%CI = 1.154-1.865), suggesting that subjects carrying rs13278062GT and rs13278062TT + GT are more likely to develop the AMD, whereas no significant difference was observed for rs13278062 under other models. No association was detected with the other six SNPs and AMD under various genetic models. CONCLUSION: This case-control association study has indicated that TNFRSF10A rs13278062 is associated with AMD under the heterozygous and dominant models, suggesting that the TNFRSF10A variant may be involved in the development of AMD among ethnic Han Chinese population.
Subject(s)
Macular Degeneration , Polymorphism, Single Nucleotide , Case-Control Studies , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , High-Temperature Requirement A Serine Peptidase 1/genetics , Humans , Macular Degeneration/geneticsABSTRACT
BACKGROUND: The aim of this study is to investigate the difference of serum pepsinogen (PG) baseline levels in different regions of China and its influencing factors. METHODS: From October 2016 to October 2018, asymptomatic health checkup people who underwent nasal endoscopy in nine health management centers in different regions of China were collected. Lifestyle questionnaires were conducted, and serum PG and gastroscopy were performed. The differences in PG levels in baseline population (OLGA-0 grade) were studied according to geographical subregions of China. SPSS software was used for statistical analysis. RESULTS: 1922 patients were included in the final analysis. Compared with the non-atrophy (OLGA-0) group, PGR levels in atrophy group (OLGA-I to IV) were significantly decreased with the atrophy degree (p < 0.05). A total of 1590 baseline people (OLGA-0) were included in the study, including 254 from South China, 574 from East China, 210 from Southwest China, 332 from Northeast China, and 220 from Central/Northern China. There were significant differences in baseline PGI levels among the five regions (p < 0.05). The PGII levels were also different among the five regions, except for Central/Northern versus Southern China. PGR (PGI/PGII ratio) levels in Southern China were higher than other four regions. Further studies were conducted on the related factors that might affect the baseline PG level, which was affected by nationality, dietary habits, smoking, Helicobacter pylori infection and other related factors. CONCLUSION: Influenced by many factors, the baseline PG levels are different in different regions of China. In the follow-up studies of PG cut-off value, different PG cut-off value based on region may be more effective in the screening of gastric cancer and precancerous lesions in China.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , China/epidemiology , Cross-Sectional Studies , Helicobacter Infections/epidemiology , Humans , Pepsinogen A , Pepsinogen CABSTRACT
OBJECTIVE: To determine the impact of smoking status in the prediction of stroke using CHADS2 and CHA2DS2-VASc schemes. METHODS: Five hundred twenty-eight consecutive patients with arrhythmic symptoms and without any documented arrhythmia from Queen Mary Hospital, Hong Kong, were followed up to determine the incidence of ischemic stroke, new-onset atrial fibrillation (AF), or all-cause mortality. Smoking status was classified into nonsmokers and smokers. The pairwise comparisons of C-statistics for outcomes were performed. RESULTS: During a median follow-up period of 6.2 years, 65 (12.3%) individuals developed ischemic stroke. Smokers experienced higher annual incidence of stroke, a new-onset AF, and all-cause death compare to nonsmokers, with corresponding hazard ratio (HR) of stroke, AF, and all-cause death being 2.51 (95% confidence intervals, CI 1.36als, CIse death bein 1.15a3.24), and 1.95 (95% CI 1.161.95 (95% CIath being 2.51 (95% confidence corr2 and CHA2DS2-VASc for stroke were 0.60 (95% CI 0.51 for stp = 0.09) and 0.59 (95% CI 0.50 (95%, p = 0.15) respectively, whereas the C-statistics of CHADS2 and CHA2DS2-VASc were 0.66 (95% CI 0.61 were 0p = 0.005), 0.75 (95% CI 0.7 CI 0.7p < 0.0001), respectively among nonsmokers. After incorporating smoking, both the CHADS2-smoking and CHA2DS2-VASc-smoking achieved better C-statistics for new-onset ischemic stroke prediction superior to baseline score systems in male groups. CONCLUSION: Cigarette smoking status has impact on stroke stratification using CHADS2 and CHA2DS2-VASc scheme. The discrimination of the CHADS2 and CHA2DS2-VASc scheme for stroke can be significantly improved if smoking status is additionally considered.
Subject(s)
Atrial Fibrillation , Cigarette Smoking , Stroke , Humans , Male , Risk Assessment , Risk Factors , Stroke/epidemiologyABSTRACT
Purpose: This study investigated the impact of sex differences on the relationship of subclinical hypothyroidism (SCH) with the prevalence of metabolic syndrome (MetS) and its components in an older Chinese population.Methods: The study included 1842 older Chinese individuals aged 65 years or older who received annual health checkups. The impact of sex differences on the relationship of SCH with the prevalence of MetS and its components was investigated by multivariate logistic regression analysis. Interaction effect between sex and SCH on the prevalence of MetS and its components were evaluated using a multivariate logistic regression model which includes interaction terms (sex-SCH).Results: The study comprised 1701 (92.3%) individuals with euthyroidism and 141 (7.7%) with SCH. In men, SCH was not associated with MetS or any components of the MetS. In women, the SCH group had higher prevalence of MetS [odds ratio (OR), 1.870; 95% confidence interval (CI), 1.136-3.079], abdominal obesity (OR, 1.693; 95% CI, 1.043-2.748), hypertriglyceridemia (OR, 1.711; 95% CI, 1.054-2.775) and low high-density lipoprotein cholesterol (HDL-C) (OR, 3.039; 95% CI, 1.576-5.861). There was an interaction between sex and SCH in terms of the effect on the prevalence of MetS and its components, including abdominal obesity and hypertriglyceridemia (P < .01 for all), and with a trend for low HDL-C (P = .098).Conclusion: There were sex differences in the correlation of SCH with the prevalence of MetS and its components in the older Chinese population. An interaction effect between sex and SCH on the prevalence of MetS and its components was found.
Subject(s)
Hypothyroidism , Metabolic Syndrome , China/epidemiology , Cross-Sectional Studies , Female , Humans , Hypothyroidism/epidemiology , Male , Metabolic Syndrome/epidemiology , Prevalence , Risk FactorsABSTRACT
BACKGROUND: In China, many people are regarded suitable for participating in regular physical examination for diagnosis and prevention of diseases. Some simplified food frequency questionnaires have been designed and used; however, the accuracy of the questionnaire is absent. This study aimed to examine the reliability and validity of simplified food frequency questionnaire (SFFQ) used among adults undergoing physical examination in southwest region of China. METHODS: This was a cross-sectional study conducted among physical health examination adults in the Southwest region of China. A total of 239 participants aged 20-65 were included from February 2019 to June 2019. The performance of SFFQ was evaluated by means of a three-day 24-h dietary record (3R24). The relative validity and agreement was assessed by Pearson's correlation and intra-class correlation coefficients (ICC), respectively. RESULTS: The median energy-adjusted ICC of food groups between SFFQ2 and SFFQ1 was 0.59 (range: 0.49-0.73) and the ICC of nutrients was 0.47(range: 0.39-0.76). The Pearson correlation showed a valid comparisons between SFFQ1 and 3R24, ranging from -0.086 to 0.93 for food and 0.21 to 0.71 for nutrition, respectively. The energy-adjustment slightly increased the correlation coefficients. CONCLUSIONS: The reliability and validity of SFFQ was acceptable, and it could be an appropriate dietary assessment tool for the future epidemiological studies conducted among physical health examination adults of southwest China. Trial registration CHiCTR, ChiCTR1900020934, Registered 22 January 2019, https://www.chictr.org.cn/edit.aspx?pid=35414&htm=4 .
Subject(s)
Energy Intake , Physical Examination , Adult , Aged , China , Cross-Sectional Studies , Humans , Middle Aged , Reproducibility of Results , Surveys and Questionnaires , Young AdultABSTRACT
Existing evidence has highlighted the effect of ultraviolet light radiation leading to corneal epithelium impairment. During this study, we aim to investigate the effect of microRNA-129-5p (miR-129-5p) on the wound healing process of corneal epithelial cells (CECs) induced by ultraviolet rays in mice by targeting epidermal growth factor receptor (EGFR). First, mouse models of ultraviolet ray-induced CEC injury were established and intrastromally injected with different mimic, inhibitor, and short interfering RNA (siRNA) to detect the effect of miR-129-5p on CEC injury. Subsequently, the corneal tissues were obtained to detect the antioxidant ability and EGFR-positive expression rate. The dual-luciferase reporter gene assay was used to test whether EGFR could directly target miR-129-5p. To further investigate the specific mechanism of miR-129-5p and EGFR in CEC injury, CECs were cultured and transfected with miR-129-5p mimic, miR-129-5p inhibitor, siRNA-EGFR, and miR-129-5p inhibitor + siRNA-EGFR. miR-129-5p has been proven to directly target EGFR. Inhibition of miR-129-5p is able to increase the antioxidant capacity, EGFR-positive rate and the expressions of EGFR, B-cell lymphoma-2, zonula occluden-1, occludin, and keratinocyte growth factor-2, but decrease the expression of vascular endothelial growth factor, BCL2-associated X protein, interleukin (IL)-1ß, and IL-4. Inhibition of miR-129-5p arrests cells at the S and G2 phases and decreases apoptosis. Our study provides evidence stating that inhibiting miR-129-5p and upregulating EGFR could aid in the repair of mice CEC injury induced by ultraviolet radiation. Therefore, inhibition of miR-129-5p might provide a basic theory in the repair of CEC injury caused by ultraviolet rays.
Subject(s)
Epithelial Cells/metabolism , Epithelial Cells/radiation effects , Epithelium, Corneal/injuries , ErbB Receptors/genetics , MicroRNAs/metabolism , Ultraviolet Rays , Up-Regulation/genetics , Animals , Antioxidants/metabolism , Apoptosis/genetics , Apoptosis/radiation effects , Base Sequence , Collagen/metabolism , Epithelial Cells/pathology , Epithelial Cells/ultrastructure , Epithelium, Corneal/pathology , Epithelium, Corneal/radiation effects , Epithelium, Corneal/ultrastructure , ErbB Receptors/metabolism , G1 Phase/genetics , G1 Phase/radiation effects , Luciferases/metabolism , Male , Malondialdehyde/metabolism , Mice, Inbred BALB C , MicroRNAs/genetics , Neovascularization, Pathologic/genetics , Occludin/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Superoxide Dismutase/metabolism , Tight Junctions/metabolism , Tight Junctions/radiation effects , Up-Regulation/radiation effects , Zonula Occludens-1 Protein/metabolismABSTRACT
Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
Subject(s)
Breast Neoplasms/genetics , Genetic Predisposition to Disease/genetics , Adult , Asian People/genetics , Female , Germ-Line Mutation , Humans , Middle AgedABSTRACT
PURPOSE: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease. METHODS: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study. RESULTS: Using exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice. CONCLUSION: This study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.