Gender-specific association between the regular use of statins and the risk of irritable bowel syndrome: A population-based prospective cohort study

Introduction: In addition to lipid-lowering effects, statins might modulate the gut microbiome and alleviate systematic inflammation, which in turn, may have a protective effect against irritable bowel syndrome (IBS). The aim of our study was to evaluate the gender-specific association between statin exposure and the risk of IBS.Method: We undertook a prospective analysis based on the United Kingdom Biobank, a large ongoing cohort including 477,293 participants aged 37–73 years. We included participants based on information on their personal statin use and also those free of IBS and cancer at the baseline. We evaluated the gender-specific hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demographic factors, lifestyle factors, comorbidities, and statin indications.Result: A total of 438,805 participants (206,499 males and 232,306 females) were included in the analysis. Among male participants, the regular use of statins was associated with a decreased risk of IBS (HR: 0.77; 95% CI: 0.61–0.97). This association persists across multiple sensitivity and subgroup analyses and did not show clear evidence of variance among the major types of statins. We did not find sufficient evidence of the association between the statin use and IBS risk in females (HR: 0.98; 95% CI: 0.82–1.16).Conclusion: Our study found that the regular use of statins was associated with a decreased risk of IBS in male participants. Further studies are required to confirm the beneficial effect of statins

PND-Net: Physics based Non-local Dual-domain Network for Metal Artifact Reduction

Metal artifacts caused by the presence of metallic implants tremendously degrade the reconstructed computed tomography (CT) image quality, affecting clinical diagnosis or reducing the accuracy of organ delineation and dose calculation in radiotherapy. Recently, deep learning methods in sinogram and image domains have been rapidly applied on metal artifact reduction (MAR) task. The supervised dual-domain methods perform well on synthesized data, while unsupervised methods with unpaired data are more generalized on clinical data. However, most existing methods intend to restore the corrupted sinogram within metal trace, which essentially remove beam hardening artifacts but ignore other components of metal artifacts, such as scatter, non-linear partial volume effect and noise. In this paper, we mathematically derive a physical property of metal artifacts which is verified via Monte Carlo (MC) simulation and propose a novel physics based non-local dual-domain network (PND-Net) for MAR in CT imaging. Specifically, we design a novel non-local sinogram decomposition network (NSD-Net) to acquire the weighted artifact component, and an image restoration network (IR-Net) is proposed to reduce the residual and secondary artifacts in the image domain. To facilitate the generalization and robustness of our method on clinical CT images, we employ a trainable fusion network (F-Net) in the artifact synthesis path to achieve unpaired learning. Furthermore, we design an internal consistency loss to ensure the integrity of anatomical structures in the image domain, and introduce the linear interpolation sinogram as prior knowledge to guide sinogram decomposition. Extensive experiments on simulation and clinical data demonstrate that our method outperforms the state-of-the-art MAR methods.Comment: 19 pages, 8 figure

PERK-Mediated Cholesterol Excretion from IDH Mutant Glioma Determines Anti-Tumoral Polarization of Microglia

Isocitrate dehydrogenase (IDH) mutation, a known pathologic classifier, initiates metabolic reprogramming in glioma cells and has been linked to the reaction status of glioma-associated microglia/macrophages (GAMs). However, it remains unclear how IDH genotypes contribute to GAM phenotypes. Here, it is demonstrated that gliomas expressing mutant IDH determine M1-like polarization of GAMs, while archetypal IDH induces M2-like polarization. Intriguingly, IDH-mutant gliomas secrete excess cholesterol, resulting in cholesterol-rich, pro-inflammatory GAMs without altering their cholesterol biosynthesis, and simultaneously exhibiting low levels of tumoral cholesterol due to expression remodeling of cholesterol transport molecules, particularly upregulation of ABCA1 and downregulation of LDLR. Mechanistically, a miR-19a/LDLR axis-mediated novel post-transcriptional regulation of cholesterol uptake is identified, modulated by IDH mutation, and influencing tumor cell proliferation and invasion. IDH mutation-induced PERK activation enhances cholesterol export from glioma cells via the miR-19a/LDLR axis and ABCA1/APOE upregulation. Further, a synthetic PERK activator, CCT020312 is introduced, which markedly stimulates cholesterol efflux from IDH wild-type glioma cells, induces M1-like polarization of GAMs, and consequently suppresses glioma cell invasion. The findings reveal an essential role of the PERK/miR-19a/LDLR signaling pathway in orchestrating gliomal cholesterol transport and the subsequent phenotypes of GAMs, thereby highlighting a novel potential target pathway for glioma therapy

Association of modifiable lifestyle with colorectal cancer incidence and mortality according to metabolic status: prospective cohort study

BackgroundMetabolic syndrome has been linked to an increased risk of colorectal cancer (CRC) incidence and mortality, but whether adopting a healthy lifestyle could attenuate the risk of CRC conferred by metabolic syndrome remains unclear. The aim of the study is to investigate the individual and joint effects of modifiable healthy lifestyle and metabolic health status on CRC incidence and mortality in the UK population.MethodsThis prospective study included 328,236 individuals from the UK Biobank. An overall metabolic health status was assessed at baseline and categorized based on the presence or absence of metabolic syndrome. We estimated the association of the healthy lifestyle score (derived from 4 modifiable behaviors: smoking, alcohol consumption, diet, physical activity and categorized into “favorable,” “intermediate”, and “unfavorable”) with CRC incidence and mortality, stratified by metabolic health status.ResultsDuring a median follow-up of 12.5 years, 3,852 CRC incidences and 1,076 deaths from CRC were newly identified. The risk of incident CRC and its mortality increased with the number of abnormal metabolic factors and decreased with healthy lifestyle score (P trend = 0.000). MetS was associated with greater CRC incidence (HR = 1.24, 95% CI: 1.16 – 1.33) and mortality (HR = 1.24, 95% CI: 1.08 – 1.41) when compared with those without MetS. An unfavorable lifestyle was associated with an increased risk (HR = 1.25, 95% CI: 1.15 – 1.36) and mortality (HR = 1.36, 95% CI: 1.16 – 1.59) of CRC across all metabolic health status. Participants adopting an unfavorable lifestyle with MetS had a higher risk (HR = 1.56, 95% CI: 1.38 – 1.76) and mortality (HR = 1.75, 95% CI: 1.40 – 2.20) than those adopting a favorable healthy lifestyle without MetS.ConclusionThis study indicated that adherence to a healthy lifestyle could substantially reduce the burden of CRC regardless of the metabolic status. Behavioral lifestyle changes should be encouraged for CRC prevention even in participants with MetS

The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review

BackgroundGut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear.MethodsThe gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226).ResultsGut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88–97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn’s disease but low to very low quality for other diseases.ConclusionGut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT

A protocol of Chinese expert consensuses for the management of health risk in the general public

IntroductionNon-communicable diseases (NCDs) represent the leading cause of mortality and disability worldwide. Robust evidence has demonstrated that modifiable lifestyle factors such as unhealthy diet, smoking, alcohol consumption and physical inactivity are the primary causes of NCDs. Although a series of guidelines for the management of NCDs have been published in China, these guidelines mainly focus on clinical practice targeting clinicians rather than the general population, and the evidence for NCD prevention based on modifiable lifestyle factors has been disorganized. Therefore, comprehensive and evidence-based guidance for the risk management of major NCDs for the general Chinese population is urgently needed. To achieve this overarching aim, we plan to develop a series of expert consensuses covering 15 major NCDs on health risk management for the general Chinese population. The objectives of these consensuses are (1) to identify and recommend suitable risk assessment methods for the Chinese population; and (2) to make recommendations for the prevention of major NCDs by integrating the current best evidence and experts’ opinions.Methods and analysisFor each expert consensus, we will establish a consensus working group comprising 40–50 members. Consensus questions will be formulated by integrating literature reviews, expert opinions, and an online survey. Systematic reviews will be considered as the primary evidence sources. We will conduct new systematic reviews if there are no eligible systematic reviews, the methodological quality is low, or the existing systematic reviews have been published for more than 3 years. We will evaluate the quality of evidence and make recommendations according to the GRADE approach. The consensuses will be reported according to the Reporting Items for Practice Guidelines in Healthcare (RIGHT)

Research on the invulnerability and optimization of the technical cooperation innovation network based on the patent perspective—A case study of new energy vehicles

This paper takes new energy vehicles as the research object, building the technical cooperation innovation network of new energy vehicles based on the patent perspective by establishing the related technology patent search expression, and analyzing the processes of the invulnerability and optimization in the actual technology cooperation innovation network by using the simulation analysis method. The research results show that the harmfulness of the degree value priority attack in the technical cooperation innovation network of new energy vehicles is stronger than the weighted degree value priority attack and random attack, and the attacks of the State Grid and other hub nodes have an important impact on the network invulnerability. During the network optimization process of three types of connection preferences, the “weak”-“weak” connection is the best connection mode given the situation of an unweighted network without considering the weight of the connected edge. However, the “strong”-“weak” connection is the best mode given the situation of a weighted network considering the weight of the connected edge. In addition, compared with the weighted network situation, the “strong”-“weak” connection has better network optimization results given the situation of an unweighted network. Finally, we propose counter measures and suggestions to promote the innovation network invulnerability capabilities of technical cooperation in new energy vehicles

Embryo location in the uterus during embryo transfer: An in vitro simulation.

ObjectiveTo evaluate the location of transferred embryos under various parameters during embryo transfer in in vitro fertilization (IVF) by applying an in vitro experimental model for embryo transfer (ET).MethodsMock ET simulations were conducted with a laboratory model of the uterine cavity. The transfer catheter was loaded with a sequence of air and liquid volumes, including development-arrested embryos donated by patients. The transfer procedure was recorded using a digital video camera. An orthogonal design, including three independent variables (uterine orientation, distance of the catheter tip to the fundus, and injection speed) and one dependent variable (final embryo position), was applied.ResultsThe uterine cavity was divided into six regions. The distribution of the transferred matter within the uterine cavity varied according to the uterine orientation. Medium speed-injected embryos were mostly found in the static region while fast- and slow-speed injected embryos were mostly found in the fundal region and the cervical-left region, respectively. The possibility of embryo separation from the air bubble increased from 11.1% in slow injection cases to 29.6% and 48.1% in medium and fast injection cases, respectively.ConclusionThe experimental model provides a new method for investigating ET procedures. Fast injection of embryos into a retroverted uterus may be more likely to result in embryo separation from the air bubble

Functions of Small Non-Coding RNAs in Salmonella–Host Interactions

Salmonella species infect hosts by entering phagocytic and non-phagocytic cells, causing diverse disease symptoms, such as fever, gastroenteritis, and even death. Therefore, Salmonella has attracted much attention. Many factors are involved in pathogenesis, for example, the capsule, enterotoxins, Salmonella pathogenicity islands (SPIs), and corresponding regulators. These factors are all traditional proteins associated with virulence and regulation. Recently, small non-coding RNAs (sRNAs) have also been reported to function as critical regulators. Salmonella has become a model organism for studying sRNAs. sRNAs regulate gene expression by imperfect base-pairing with targets at the post-transcriptional level. sRNAs are involved in diverse biological processes, such as virulence, substance metabolism, and adaptation to stress environments. Although some studies have reported the crucial roles of sRNAs in regulating host–pathogen interactions, the function of sRNAs in host–Salmonella interactions has rarely been reviewed. Here, we review the functions of sRNAs during the infection of host cells by Salmonella, aiming to deepen our understanding of sRNA functions and the pathogenic mechanism of Salmonella

Body composition and risk of liver cancer: a population-based prospective cohort study on gender difference

BackgroundObesity is a common and highly convincing risk factor for many cancers, including liver cancer. Sex disparities in the body composition and regulatory mechanisms involved in energy homeostasis may contribute to the difference in the incidence of cancer. However, evidence on the gender-specific association between body composition and liver cancer incidence is limited. We performed this study to investigate the linear and non-linear associations of body composition with liver cancer risk by gender.Materials and methodsThis prospective analysis included 4,75,659 participants free of cancer, based on the UK Biobank. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline was performed to investigate the potential non-linear associations.ResultsDuring a median follow-up, 275 cases (174 male patients and 101 female patients) of liver cancer were identified. Male patients in the highest body fat percentage group are more likely to develop liver cancer (HR = 1.89, 95% CI: 1.17–3.03) compared with those in the lowest group. The one-unit increase of whole-body fat mass, arm fat mass, and trunk fat mass was associated with 1.03-, 1.14-, and 1.05-fold increased risk of liver cancer in male subjects, respectively. U-shaped associations of body composition with liver cancer risk were observed in the female subjects. Both high and low levels of whole-body fat-free mass, particularly in the arm and trunk, were associated with an increased risk of liver cancer.ConclusionThis study found a gender-specific association between body composition and liver cancer risk and provided evidence for individualized weight management for the prevention of liver cancer