Intestinal homeostasis in the gut-lung-kidney axis: a prospective therapeutic target in immune-related chronic kidney diseases

In recent years, the role of intestinal homeostasis in health has received increasing interest, significantly improving our understanding of the complex pathophysiological interactions of the gut with other organs. Microbiota dysbiosis, impaired intestinal barrier, and aberrant intestinal immunity appear to contribute to the pathogenesis of immune-related chronic kidney diseases (CKD). Meanwhile, the relationship between the pathological changes in the respiratory tract (e.g., infection, fibrosis, granuloma) and immune-related CKD cannot be ignored. The present review aimed to elucidate the new underlying mechanism of immune-related CKD. The lungs may affect kidney function through intestinal mediation. Communication is believed to exist between the gut and lung microbiota across long physiological distances. Following the inhalation of various pathogenic factors (e.g., particulate matter 2.5 mum or less in diameter, pathogen) in the air through the mouth and nose, considering the anatomical connection between the nasopharynx and lungs, gut microbiome regulates oxidative stress and inflammatory states in the lungs and kidneys. Meanwhile, the intestine participates in the differentiation of T cells and promotes the migration of various immune cells to specific organs. This better explain the occurrence and progression of CKD caused by upper respiratory tract precursor infection and suggests the relationship between the lungs and kidney complications in some autoimmune diseases (e.g., anti-neutrophil cytoplasm antibodies -associated vasculitis, systemic lupus erythematosus). CKD can also affect the progression of lung diseases (e.g., acute respiratory distress syndrome and chronic obstructive pulmonary disease). We conclude that damage to the gut barrier appears to contribute to the development of immune-related CKD through gut-lung-kidney interplay, leading us to establish the gut-lung-kidney axis hypothesis. Further, we discuss possible therapeutic interventions and targets. For example, using prebiotics, probiotics, and laxatives (e.g., Rhubarb officinale) to regulate the gut ecology to alleviate oxidative stress, as well as improve the local immune system of the intestine and immune communication with the lungs and kidneys

The effect of electrical stimulation in critical patients: a meta-analysis of randomized controlled trials

ObjectivesWhile electrical stimulation has been demonstrated to improve medical research council (MRC) scores in critically ill patients, its effectiveness remains a subject of debate. This meta-analysis aimed to discuss recent insights into the effectiveness of electrical stimulation in improving muscle strength and its effects on different clinical outcomes in critically ill adults.MethodsA comprehensive search of major electronic databases, including PubMed, Cochrane Library, and Embase, was conducted from inception to June 15, 2024, to identify randomized controlled trials (RCTs) that evaluated the effects of electrical stimulation in critically ill patients. The analysis focused on comparing electrical stimulation to standard care, sham interventions, or placebo. Outcomes of interest included MRC scores, duration of mechanical ventilation (MV), mortality rate, and intensive care unit (ICU) and hospital length of stay (LOS).ResultsA total of 23 RCTs, including 1798 patients, met the inclusion criteria. The findings demonstrated a significant benefit of electrical stimulation over usual care in enhancing global muscle strength, as measured by MRC scores (MD =3.62, 95% CI 0.94 to 6.30, p = 0.0008, I2 = 87%). While subgroup analysis of electrical muscle stimulation (EMS) demonstrated no significant effect on ICU LOS, sensitivity analysis indicated a potential reduction in ICU LOS for both EMS (MD = −11.0, 95% CI −21.12 to −0.88, p = 0.03) and electrical stimulation overall (MD = −1.02, 95% CI −1.96 to −0.08, p = 0.03) compared to the control group. In addition, sensitivity analysis suggested that both electrical stimulation (MD = −2.38, 95% CI −3.81 to −0.94, p = 0.001) and neuromuscular electrical stimulation (NMES) specifically (MD = −2.36, 95% CI −3.85 to −0.88, p = 0.002) may contribute to a decrease in hospital LOS. No statistically significant differences were observed in mortality or duration of MV.ConclusionElectrical stimulation appears to be an effective intervention for improving MRC scores in critically ill patients. However, further research is warranted to explain the potential effects of electrical stimulation on hospital LOS and ICU LOS.Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails

Prevalence of Metabolic Syndrome Among the Adult Population in Western China and the Association With Socioeconomic and Individual Factors: Four Cross-Sectional Studies

Objectives: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation. Design: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015. Setting: From 2010 to 2018, 8-15 counties/districts of West China were included. Participants: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors. Results: The overall prevalence of MS ranged from 21.4% to 27.8% over the 8 years, remaining basically stable within the 95% CI. Our study found that the urbanisation rate and hospital beds per 1000 people were positively associated with MS, and the number of doctors in healthcare institutions per 1000 persons was negatively associated with MS. The ORs for females, people with college education and higher and unmarried or single people were 1.49, 0.67 and 0.51, respectively (p\u3c0.05). The ORs of people who smoked at least 20 cigarettes/day, ate more than 100 g of red meat/day, consumed fruit or vegetable juice and drank carbonated soft drinks less than weekly were 1.10, 1.16, 1.19-1.27 and 0.81-0.84, respectively. The ORs rose with increasing sedentary time and decreased with higher physical activity. Conclusion: The high burden of MS, unreasonable proportions of energy and micronutrient intake and low percentage of high levels of physical activity were the major challenges to public health in western China. Improving the human resources component of medical services, such as the number of doctors, increasing the availability of public sports facilities and E-health tools and improving individual dietary quality and education might help prevent MS

MSIsensor-ct: Microsatellite instability detection using cfDNA sequencing data

MOTIVATION: Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach. RESULTS: We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various levels of circulating tumor DNA (ctDNA) and sequencing depth showed 100% accuracy within the limit of detection (LOD) of 0.05% ctDNA content. MSIsensor-ct requires only BAM files as input, rendering it user-friendly and readily integrated into next generation sequencing (NGS) analysis pipelines. AVAILABILITY: MSIsensor-ct is freely available at https://github.com/niu-lab/MSIsensor-ct. SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online

Dietary Diversity and Nutrient Intake of Han and Dongxiang Smallholder Farmers in Poverty Areas of Northwest China

This study aimed to evaluate the status of dietary diversity and nutrient intake among Han and Dongxiang smallholder farmers in poor rural areas of northwest China. In this cross-sectional study, dietary intake was assessed in 499 smallholder farmers aged 18–75 years from two nationally designated impoverished counties in Gansu Province, China, using three consecutive 24 h dietary recalls. The dietary diversity score (DDS) and nutrient adequacy ratio (NAR) were adopted to assess dietary diversity and micronutrient adequacy, respectively. The mean DDS (range from 1 to 9) in participants was relatively low (3.81 ± 1.01). Consumption of grains was excessive, while consumption of vegetables, fruits, meat, beans, eggs, fish, and dairy was inadequate. The NAR values were higher in Han Chinese, with the exceptions of vitamin C, potassium, pyridoxine, and selenium (p \u3c 0.05). For each nutrient, the high DDS group had a higher mean NAR (p \u3c 0.05), except for pyridoxine. High household monthly income, being Han Chinese, high DDS, and being aged over 45 years were positively associated with mean adequacy ratio (MAR) of 14 micronutrients evaluated. Lack of dietary diversity and insufficient intake of essential micronutrients are public health concerns in northwest China. Nutrition education and other proper methods to address these issues are needed

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)

Ability Tracking and Social Capital in China's Rural Secondary School System

The goal of this paper is describe and analyze the relationship between ability tracking and student social capital, in the context of poor students in developing countries. Drawing on the results from a longitudinal study among 1,436 poor students across 132 schools in rural China, we find a significant lack of interpersonal trust and confidence in public institutions among poor rural young adults. We also find that there is a strong correlation between ability tracking during junior high school and levels of social capital. The disparities might serve to further widen the gap between the relatively privileged students who are staying in school and the less privileged students who are dropping out of school. This result suggests that making high school accessible to more students would improve social capital in the general population

Early Life Adversity and Innate Sensitization: Investigating Inflammatory Reactivity to a Two-Hit Immune Paradigm among Breast Cancer Survivors

Breast cancer survivors experience long-term health consequences beyond the initial cancer diagnosis and treatment, including immune dysregulation, chronic inflammation, and increased vulnerability to infections and other health complications (Heins et al., 2022). Emerging studies suggest that prior exposure to early life adversity (ELA) is associated with chronic inflammation, which can predict worse cancer progression and impair immune function, reducing the body’s ability to effectively respond to pathogens (Crosswell et al., 2014; Holman et al., 2016; Marshall et al., 2023). Additionally, different ELA types may have differential effects on the inflammatory processes in later life, with the most consistent effects seen for a chaotic family environment, which can be defined by the amount of arguments, violence, and alcohol or drug use within households (Crosswell et al., 2014). Similarly, household dysfunction, characterized by exposure to substance abuse, mental illness, domestic violence, or criminal behavior, is progressively linked to health-risk behaviors and chronic disease in adulthood (Felitti et al., 1998). However, other adversities such as neglect, abuse and intimate partner violence, are also closely associated with chronic inflammation, immune dysregulation and heightened susceptibility to stress and disease, following a dose-response relationship (Felitti et al., 1998; Graham‐Bermann et al., 2017; Kuhlman et al., 2020; Sheffler et al., 2019; Springer et al., 2003). Furthermore, lab-based immune stimulation can highlight ELA’s deleterious effects, especially among breast cancer survivors, who generally have weakened immune function compared to their non-cancer peers (Kiecolt-Glaser et al., 2022; Kuhlman et al., 2020). The present study uses a vaccine model to safely stimulate the immune system.The typhoid vaccine, in particular, serves as a mild inflammatory stimulus that typically does not induce sickness symptoms, which makes it especially valuable for studying immune function. More specifically, the typhoid capsular polysaccharide vaccine (ViCPS) was specifically engineered to cause little to no activation of the innate immune system. Thus, the large body of research concerning the typhoid ViCPS has focused on the adaptive immune response (Klugman et al., 1996; Sztein et al., 2014); yet recent research suggests that this vaccine does still provoke a mild acute (innate) inflammatory response (Madison et al., 2023). Thus, the next step is to investigate how the vaccine might subsequently impact innate immune responses to a pathogen (modeled with ex vivo LPS stimulation) – providing critical information about infection vulnerability. This study employs a two-hit model, using vaccination with Typhoid ViCPS followed by blood draws in which PBMCs were stimulated with LPS ex vivo, allowing for the controlled assessment of whether the vaccine modulates the innate response to pathogens in the hours after vaccination among breast cancer survivors. Additionally, the current study investigates whether ELA plays a role in these innate responses to the two-hit model. As described by the conserved transcriptional response to adversity (CTRA) theory, ELA reprograms immune cells to be more sensitive to stress, leading to heightened inflammation and reduced antiviral responses (Cole, 2019). In cancer patients, this inflammatory profile correlates with poorer responses to treatments like radiotherapy and chemotherapy (Pierce et al., 2009). Prior studies have linked early life stress to increased susceptibility to infections, including respiratory and viral illnesses (Caserta et al., 2008), as well as decreased innate and adaptive immune functions (Segerstrom & Miller, 2004). Building upon these considerations, the present study aims to investigate whether ELA modulates the vaccine’s impact on innate immune responsivity to a pathogen, perhaps making breast cancer survivors more vulnerable to infection in the hours after vaccination. We will test two possible immune trajectories: The first is the immune suppression model, which suggests that higher ELA is associated with impaired immune activation, reflected in blunted cytokine responses to LPS stimulation following vaccination. Indeed, in the parent study, we found that certain risk factors (e.g., poorer physical fitness) tracked with a dampened acute inflammatory response to the vaccine (Kiecolt-Glaser et al., 2022). Here we extend this investigation of innate immune function by stimulating immune cells ex vivo following the vaccine. The second is the immune overactivation model, which posits that ELA sensitizes immune cells to stress, leading to heightened inflammatory responses to LPS post-vaccination, in line with theories of stress-induced inflammatory priming (e.g. CTRA). This secondary analyses from the parent study aim to explore three main hypotheses: (1) ELA exposure will track with pre-vaccine LPS-stimulated cytokines; (2) Even though it is designed to have less of an impact on the innate immune system, the ViCPS vaccine will alter LPS-stimulated inflammatory responses; (3) ELA exposure will modulate the vaccine's impact on LPS-stimulated cytokines