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Abstract Background Sarcopenia and obesity are two abnormal body composition phenotypes, and sarcopenic obesity (SO) is characterized by both low skeletal muscle mass (sarcopenia) and high adiposity (obesity). SO negatively influences the clinical status of patients with chronic obstructive pulmonary disease (COPD). However, the studies exploring the prevalence and clinical effects of SO in COPD patients are limited. Our study aimed to elucidate the prevalence and impact of SO on COPD patients. Methods In this cross-sectional study, the pulmonary function, St. George’s Respiratory Questionnaire, exercise tolerance, body composition, and serum levels of resistin and TNF-α were assessed in 198 COPD patients. The clinical value of serum resistin and TNF-α for predicting SO in patients with COPD was evaluated. Results In the 198 patients with COPD, the prevalence rates of sarcopenia, obesity, and SO in COPD patients were 27.27%, 29.8%, and 9.6%, respectively. Patients with SO experienced more severe symptoms of dyspnea and worse health related quality of life. The expression of resistin increased in patients with SO compared to other patients. The AUC value of serum resistin level for predicting SO was 0.870 (95% CI: 0.799–0.940). BMI (OR: 1.474, 95% CI: 1.124–1.934) and resistin (OR: 1.001, 95% CI: 1.000-1.002) levels were independent risk factors of SO in patients with COPD in Multivariate analysis. Conclusion The prevalence rates of SO in COPD patients was 9.6%. COPD accompanied by SO is significantly associated with worse pulmonary function and poor physical performance. Serum resistin may be a potential adjunct for predicting SO in COPD patients.

Abstract Background The triglyceride-glucose (TyG) index has been validated as a novel biomarker for cardiovascular disease (CVD) risk. However, the prospective relationship between baseline and long-term trajectories of the TyG index and CVD risk in people living with HIV (PLWH) remains unexplored. Methods This cohort study included 16,122 treatment-naive PLWH who initiated antiretroviral therapy (ART) at the Third People's Hospital of Shenzhen from 2005 to 2022. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Group-based trajectory modeling was used to identify distinct TyG index trajectories over the follow-up period. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using multivariate Cox proportional hazards models to assess the association between TyG index trajectories and CVD risk. Nonlinear relationships were investigated using a restricted cubic spline plot. Results During a median follow-up of 70 months, 214 PLWH developed CVD. Each 1-standard deviation (SD) increase in the baseline TyG index was associated with a 39% higher risk of CVD (HR 1.39, 95% CI 1.22, 1.59) after adjusting for covariates. Participants were categorized into four distinct TyG trajectory groups: low-stable, low-moderate-stable, high-moderate-stable, and high-increasing. After multivariate adjustment, the high-increasing trajectory group had a 2.92-fold (95% CI 1.68, 5.05) increased risk of CVD compared to the low-stable group. The restricted cubic spline plot showed an upward trend between the baseline TyG index and the CVD occurrence (P

Abstract Background Epigenetic age accelerations (EAAs) are a promising new avenue of research, yet their investigation in subacute thyroiditis (SAT) remains scarce. Our study endeavors to fill this void by exploring the potential causal association between EAAs and SAT. Methods Our study utilized publicly available genome-wide association study (GWAS) data of European ancestry to conduct a bidirectional Mendelian randomization (MR) study. Five MR methods were employed to measure causal association between EAAs and SAT multiple analyses were utilized to perform quality control. Results Our study evaluated causal association between SAT and four EAAs, included GrimAge acceleration (GrimAA), Hannum age acceleration (HannumAA), PhenoAge acceleration (PhenoAA), intrinsic epigenetic age acceleration (IEAA). Results showed that there is a significant causal association between PhenoAA and SAT (OR 1.109, 95% CI 1.000–1.228, p = 0.049, by IVW method). On the contrary, SAT was associated with IEAA (OR 0.933, 95% CI 0.884–0.984, p = 0.011, by IVW method; OR 0.938, 95% CI 0.881–0.998, p = 0.043, by weighted median method). Leave-one-out sensitivity analysis, heterogeneity test, pleiotropy test, and MR-PRESSO analysis provide good quality control. Conclusion The bidirectional MR analysis concluded that an increase in PhenoAA was correlated with a higher risk of SAT, indicating a potential causal relationship between PhenoAA and risk of SAT. Conversely, SAT was found to be closely associated with IEAA, suggesting that SAT may accelerate the aging process. Slowing down biological aging has emerged as a new research direction in curbing SAT.

Abstract Background Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. Methods Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. Results A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51–68.29) and lowest of formication (20.5%, 95% CI 13.44–28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p

Abstract Background To assess the long-term association between organised colorectal cancer (CRC) screening strategies and CRC-relate mortality. Methods We systematically reviewed studies on organised CRC screening through PubMed, Ovid Medline, Embase and Cochrane from the inception. We retrieved characteristics of organised CRC screening from included literature and matched mortality (over 50 years) of those areas from the International Agency for Research on Cancer in May 2023. The variations of mortality were reported via the age-standardised mortality ratio. A random-effects model was used to synthesis results. Results We summarised 58 organised CRC screening programmes and recorded > 2.7 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The CRC screening strategy with faecal tests (guaiac faecal occult blood test (gFOBT) or faecal immunochemical tests (FIT)) or colonoscopy as the primary screening offer was associated with a 41.8% reduction in mortality, which was higher than those offered gFOBT (4.4%), FIT (16.7%), gFOBT or FIT (16.2%), and faecal tests (gFOBT or FIT) or flexible sigmoidoscopy (16.7%) as primary screening test. The longer duration of screening was associated with a higher reduction in the pooled age-standardised mortality ratio. In particular, the pooled age-standardised mortality ratio became non-significant when the screening of FIT was implemented for less than 5 years. Conclusions A CRC screening programme running for > 5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised screening providing a choice between faecal tests and colonoscopy as a preferred primary test.

Abstract Background Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) plays an important role in the diagnosis and treatment of breast cancer. However, obtaining complete eight temporal images of DCE-MRI requires a long scanning time, which causes patients’ discomfort in the scanning process. Therefore, to reduce the time, the multi temporal feature fusing neural network with Co-attention (MTFN) is proposed to generate the eighth temporal images of DCE-MRI, which enables the acquisition of DCE-MRI images without scanning. In order to reduce the time, multi-temporal feature fusion cooperative attention mechanism neural network (MTFN) is proposed to generate the eighth temporal images of DCE-MRI, which enables DCE-MRI image acquisition without scanning. Methods In this paper, we propose multi temporal feature fusing neural network with Co-attention (MTFN) for DCE-MRI Synthesis, in which the Co-attention module can fully fuse the features of the first and third temporal image to obtain the hybrid features. The Co-attention explore long-range dependencies, not just relationships between pixels. Therefore, the hybrid features are more helpful to generate the eighth temporal images. Results We conduct experiments on the private breast DCE-MRI dataset from hospitals and the multi modal Brain Tumor Segmentation Challenge2018 dataset (BraTs2018). Compared with existing methods, the experimental results of our method show the improvement and our method can generate more realistic images. In the meanwhile, we also use synthetic images to classify the molecular typing of breast cancer that the accuracy on the original eighth time-series images and the generated images are 89.53% and 92.46%, which have been improved by about 3%, and the classification results verify the practicability of the synthetic images. Conclusions The results of subjective evaluation and objective image quality evaluation indicators show the effectiveness of our method, which can obtain comprehensive and useful information. The improvement of classification accuracy proves that the images generated by our method are practical.

Abstract Background Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. The aim of the present study was to elucidate the role and mechanisms of tissue small extracellular vesicle (sEV) microRNAs (miRNAs) in the pathogenesis of HT. Methods Differentially expressed tissue sEV miRNAs were identified between HT tissue and normal tissue by RNA sequencing in the testing set (n = 20). Subsequently, using quantitative real-time polymerase chain reaction (qRT‒PCR) assays and logistic regression analysis in the validation set (n = 60), the most relevant tissue sEV miRNAs to HT were verified. The parental and recipient cells of that tissue sEV miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of sEV miRNAs that contribute to the development of HT. Results We identified that miR-142-3p encapsulated in T lymphocyte-derived tissue sEVs can induce Treg function defect and thyrocyte destruction through an intact response loop. Inactivation of miR-142-3p can effectively protect non-obese diabetic (NOD).H-2h4 mice from HT development display reduced lymphocyte infiltration, lower antibody titers, and higher Treg cells. Looking at the mechanisms underlying sEV action on thyrocyte destruction, we found that the strong deleterious effect mediated by tissue sEV miR-142-3p is due to its ability to block the activation of the ERK1/2 signaling pathway by downregulating RAC1. Conclusions Our findings highlight the fact that tissue sEV-mediated miR-142-3p transfer can serve as a communication mode between T lymphocytes and thyrocyte cells in HT, favoring the progression of HT.

Abstract Background Heterologous prime-boost with ChAdOx1 nCoV-19 vector vaccine (ChAd) and a messenger RNA vaccine (BNT or mRNA-1273) has been widely facilitating mass coronavirus disease 2019 (COVID-19) immunisation. This review aimed to synthesize immunogenicity and reactogenicity of heterologous immunisations with ChAd and BNT (mRNA-1273) vaccine compared with homologous ChAd or BNT (mRNA-1273) immunisation. Methods PubMed, Web of Science, and Embase databases were searched from inception to March 7, 2022. Immunogenicity involving serum antibodies against different SAS-CoV-2 fragments, neutralizing antibody, or spike-specific T cells response were compared. Any, local and systemic reactions were pooled by meta-analysis for comparison. Results Of 14,571 records identified, 13 studies (3024 participants) were included for analysis. Compared with homologous BNT/BNT vaccination, heterologous ChAd/BNT schedule probably induced noninferior anti-spike protein while higher neutralizing antibody and better T cells response. Heterologous ChAd/BNT (mRNA-1273) immunisation induced superior anti-spike protein and higher neutralizing antibody and better T cells response compared with homologous ChAd/ChAd vaccination. Heterologous ChAd/BNT (mRNA-1273) had similar risk of any reaction (RR = 1.30, 95% CI: 0.86−1.96) while higher risk of local reactions (RR = 1.65, 95% CI: 1.27−2.15) and systemic reactions (RR = 1.49, 95% CI: 1.17−1.90) compared with homologous ChAd/ChAd vaccination. There was a higher risk of local reactions (RR = 1.16, 95% CI: 1.03−1.31) in heterologous ChAd/BNT (mRNA-1273) vaccination compare with homologous BNT/BNT but a similar risk of any reaction (RR = 1.03, 95% CI: 0.79−1.34) and systemic reactions (RR = 0.89, 95% CI: 0.60−1.30). Conclusions Heterologous ChAd/BNT schedule induced at least comparable immunogenicity compared with homologous BNT/BNT and better immunogenicity compared with homologous ChAd/ChAd vaccination. The synthetical evidence supported the general application of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. Graphical Abstract

Abstract Background A growing number of studies have focused on investigating circRNAs as crucial regulators in the progression of multiple cancer types. Nevertheless, the biological effects and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Methods Differentially expressed circRNAs between cancerous tissue and adjacent normal tissues were identified by RNA sequencing in PDAC. Subsequently, in vitro and in vivo functional experiments were performed to investigate the functional roles of circNEIL3 in PDAC tumour growth and metastasis. Furthermore, RNA pull-down, dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, fluorescent in situ hybridization (FISH) and Sanger sequencing assays were performed to examine the circular interaction among circNEIL3, miR-432-5p and adenosine deaminases acting on RNA 1 (ADAR1). Results CircNEIL3 was upregulated in PDAC and promoted the progression of PDAC cells both in vitro and in vivo. Mechanistically, circNEIL3 was shown to regulate the expression of ADAR1 by sponging miR-432-5p to induce RNA editing of glioma-associated oncogene 1 (GLI1), ultimately influencing cell cycle progression and promoting epithelial-to-mesenchymal transition (EMT) in PDAC cells. Moreover, we discovered that the circNEIL3/miR-432-5p/ADAR1 axis was correlated with the PDAC clinical stage and overall survival of PDAC patients, while ADAR1 may reduce the biogenesis of circNEIL3. Conclusions Our findings reveal that circNEIL3 facilitates the proliferation and metastasis of PDAC through the circNEIL3/miR-432-5p/ADAR1/GLI1/cell cycle and EMT axis and that its expression is regulated by ADAR1 through a negative feedback loop. Therefore, circNEIL3 may serve as a prognostic marker and a therapeutic target for PDAC.

Abstract Background Persons with chronic hepatitis B (CHB) infection were reported to suffer severe disease after hepatitis E virus (HEV) superinfection, but the studies regarding HEV seroprevalence in this population were limited. A recent study in Vietnam found higher HEV seroprevalence among CHB patients compared with healthy controls. Methods A community-based case-control study was conducted in two counties of Shandong province, China, where hepatitis E incidence was at the highest (Rushan) and lowest (Zhangqiu) in the province based on data from routine public health surveillance. Four townships were selected randomly from each county and all residents in these townships were tested for hepatitis B surface antigen (HBsAg). Those tested positive for HBsAg (CHB group) and the 1:1 age and sex-matched HBsAg-negative residents (control group) were included. Anti-HEV IgM and IgG were tested and positive rates of IgG and IgM were compared between the CHB group and the control group. Results In total, 2048 CHB participants and 2054 controls were included in the study. In the CHB group, HEV IgG seroprevalence was 9.16% (95% CI: 7.47–11.09) in Zhangqiue and 38.06% (95% CI: 35.07–41.19) in Rushan (P