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Background: Precise regulation of cell-cell communication is vital for cell survival and normal function during embryogenesis. The Wnt protein family, a highly conserved and extensively studied group, plays a crucial role in key cell-cell signaling events essential for development and regeneration. Congenital anomalies of the kidney and urinary tract (CAKUT) represent a leading cause of chronic kidney disease in children and young adults, and include a variety of birth abnormalities resulting from disrupted genitourinary tract development during embryonic development. The incidence and progression of CAKUT may be related to the Wnt signal transduction mechanism. Summary: This review provides a comprehensive overview of the classical Wnt signaling pathway’s role in CAKUT, explores related molecular mechanisms and provides new targets and intervention methods for the future treatment of the disease. Key Messages: The Wnt signal is intricately engaged in a variety of differentiation processes throughout kidney development.

AbstractContext Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown.Objective This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota.Materials and methods 120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (n = 56) or RAAS inhibitor (n = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics.Results Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium, and Sutterella increased significantly, while pathogenic bacteria such as the Eggerthella and Clostridium innocuum group decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as Lachnospiraceae and the Lachnoclostridium genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism.Discussion and conclusion The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored.Trial registration ChiCTR2300076136, retrospectively registered.

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Abstract Impaired ion channels regulating Golgi pH lead to structural alterations in the Golgi apparatus, such as fragmentation, which is found, along with cognitive impairment, in Alzheimer’s disease. However, the causal relationship between altered Golgi structure and cognitive impairment remains elusive due to the lack of understanding of ion channels in the Golgi apparatus of brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed in astrocytes and neurons that contributes to hippocampus-dependent memory. We find that GolpHCat displays unique voltage-dependent currents, which is potently inhibited by gluconate. Additionally, we gain structural insights into the ion conduction through GolpHCat at the molecular level by determining three high-resolution cryogenic-electron microscopy structures of human GolpHCat. GolpHCat-knockout mice show fragmented Golgi morphology and altered protein glycosylation and functions in the hippocampus, leading to impaired spatial memory. These findings suggest a molecular target for Golgi-related diseases and cognitive impairment.

Abstract Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with the proliferation and activation of myofibroblasts being definite effectors and drivers. Here, increased expression of Meis1 (myeloid ecotropic viral integration site 1) is observed, predominantly in the nucleus of the kidney of CKD patients and mice, and negatively correlates with serum creatinine. Fibroblast‐specific knock‐in of Meis1 inhibits myofibroblast activation and attenuates renal fibrosis and kidney dysfunction in CKD models. Overexpression of Meis1 in NRK‐49F cells suppresses the pro‐fibrotic response induced by transforming growth factor‐β1 but accelerates by its knockdown. Mechanistically, Meis1 targets protein tyrosine phosphatase receptor J (Ptprj) to block renal fibrosis by inhibiting the proliferation and activation of fibroblasts. Finally, a new activator of Ptprj is identified through computer‐aided virtual screening, which has the effect of alleviating renal fibrosis. Collectively, these results illustrate that the Meis1/Ptprj axis has therapeutic potential for clinically treating CKD.

Gut microbiota is involved in intricate and active metabolic processes the host's brain function, especially its role in immune responses, secondary metabolism, and symbiotic connections with the host. Gut microbiota can promote the production of essential metabolites, neurotransmitters, and other neuroactive chemicals that affect the development and treatment of central nervous system diseases. This article introduces the relevant pathways and manners of the communication between the brain and gut, summarizes a comprehensive overview of the current research status of key gut microbiota metabolites that affect the functions of the nervous system, revealing those adverse factors that affect typical communication between the brain-gut axis, and outlining the efforts made by researchers to alleviate these neurological diseases through targeted microbial interventions. The relevant pathways and manners of communication between the brain and gut contribute to the experimental design of new treatment plans and drug development. The factors that may cause changes in gut microbiota and affect metabolites, as well as current intervention methods are summarized, which helps improve gut microbiota brain dialogue, prevent adverse triggering factors from interfering with the gut microbiota system, and minimize neuropathological changes.

Environmental heavy metals pollution have seriously threatened the health of human beings. An increasing number of researches have demonstrated that environmental heavy metals can influence the telomere length of Peripheral Blood Mononuclear Cells (PBMCs), which implicate biological aging as well as predicts diseases. Our previous study has shown that methylmercury (MeHg)-induced telomere shortening in rat brain tissue was associated with urinary melatonin metabolite 6-sulfatoxymelatonin (aMT6s) levels. Here, we aimed to further elucidate the impact of 4 typical heavy metals (As, Hg, Cd and Pb) on telomere length of PBMCs and their association with urinary aMT6s in rats. In this study, eighty-eight male Sprague-Dawley rats were randomized grouped into eleven groups. Among them, forty 3-month-old (young) and forty 12-month-old (middle-aged) rats were divided into young or middle-aged control groups as well as typical heavy metals exposed groups, respectively. Eight 24-month-old rats (old) was divided into aging control group. The results showed that MeHg exposure in young rats while sodium arsenite (iAs), MeHg, cadmium chloride (CdCl2), lead acetate (PbAc) exposure in middle-aged rats for 3 months significantly reduced the levels of and urinary aMT6s, as well as telomere length of PBMCs. In addition, they also induced abnormalities in serum oxidative stress (SOD, MDA and GPx) and inflammatory (IL-1β, IL-6 and TNF-α) indicators. Notably, there was a significant positive correlation between declined level of urinary aMT6s and the shortening of telomere length in PBMCs in rats exposed to 4 typical heavy metals. These results suggested that 4 typical heavy metals exposure could accelerate the reduction of telomere length of PBMCs partially by inducing oxidative stress and inflammatory in rats, while ageing may be an important synergistic factor. Urinary aMT6s detection may be a alternative method to reflect telomere toxic effects induced by heavy metal exposure.

Abstract This study aims to examine whether hypovitaminosis D was associated with cognitive impairment among chronic kidney patients with different level of albuminuria. This population-based cross-sectional study was conducted on elderly (over 60 years old) with urine albumin to creatinine ratio (UACR) ≥ 30 mg/g from 2011 to 2014 in the US National Health and Nutrition Examination Survey (NHANES). Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer’s Disease Word List Learning (CERAD). Subjects were divided into 2 groups according to the absence or presence of cognitive impairment and a propensity score matching (PSM) was further conducted. The association was assessed with Spearman correlation and logistic regression analysis. The positive association of 25-hydroxyvitamin D3 (25(OH)D3) and cognitive score was presented. PSM analysis revealed that a higher level of 25(OH)D3 correlated to a better cognitive function in CKD patients with albuminuria, especially in patients with 30 mg/g ≤ UACR

Abstract In this study, we aimed to investigate the association between handgrip strength (HGS) and cognitive performance in stage 3-5 chronic kidney disease (CKD) patients aged ≥ 60 years. This cross-sectional study analyzed data from National Health and Nutrition Examination Survey (NHANES) database 2011–2014. Three tests were used to assess the cognitive performance, including consortium to establish a registry for Alzheimer’s disease (CERAD), animal fluency test (AFT), and digit symbol substitution test (DSST). The multivariate linear regression analyses adjusting for confounding factors were utilized to evaluate the association of HGS with cognitive performance. A total of 678 older stage 3-5 CKD patients were included in this study. After adjusting for multiple factors, a higher HGS was positively associated with a higher CERAD-delayed recall and DSST score. In addition, our analysis indicated that HGS probably correlated with better performance of immediate learning ability in male, while working memory, sustained attention, and processing speed in female. HGS may be an important indicator for cognitive deficits in stage 3-5 CKD patients, especially for learning ability and executive function. Further research to explore the sex-specific and domain-specific and possible mechanisms are required.

Multidrug-resistant bacteria and multi-resistance genes in sludge have become a serious issue for public health. It is imperative to develop feasible and environmentally friendly methods of sludge composting to alleviate multidrug resistance genes. Plant-derived essential oil is an effective natural and eco-friendly antibacterial, which has great utilization in inhibiting pathogens in the agricultural industry. Nevertheless, the application of plant-derived essential oil to control pathogenic bacteria and antibiotic resistance in composting has not been reported. This study conducted a composting system by adding plant-derived essential oil i.e., oregano essential oil (OEO), to sludge composting. The findings indicated that multidrug resistance genes and priority pathogens (critical, high, and medium categories) were reduced by (17.0 ± 2.2)% and (26.5 ± 3.0)% in the addition of OEO (OH treatment) compared to control. Besides, the OH treatment changed the bacterial community and enhanced the gene sequences related to carbohydrate metabolism in compost microorganisms. Mantel test and variation partitioning analysis revealed that the target virulence factors (VFs), target mobile genetic elements (MGEs), and priority pathogens were the most important factors affecting multidrug resistance in composting. The OH treatment could significantly inhibit the target VFs, target MGEs, and priority pathogens, which were helpful for the suppression and elimination of multidrug resistance genes. These findings provide new insights into the regulation of multidrug resistance genes during sludge composting and a novel way to diminish the environmental risk of antibiotic resistance.

Background: Primary hyperoxaluria (PH) is a rare autosomal recessive disorder, mainly due to the increase in endogenous oxalate production, causing a series of clinical features such as kidney stones, nephrocalcinosis, progressive impairment of renal function, and systemic oxalosis. There are three common genetic causes of glycolate metabolism anomalies. Among them, PH type 1 is the most prevalent and severe type, and early end-stage renal failure often occurs. Summary: This review summarizes primary hyperoxaluria through pathophysiology, genotype, clinical manifestation, diagnosis, and treatment options. And explore the characteristics of Chinese PH patients. Key Messages: Diagnosis of this rare disease is based on clinical symptoms, urinary or blood oxalate concentrations, liver biopsy, and genetic testing. Currently, the main treatment is massive hydration, citrate inhibition of crystallization, dialysis, liver and kidney transplantation, and pyridoxine. Recently, RNA interference drugs have also been used. In addition, technologies such as gene editing and autologous liver cell transplantation are also being developed. C.815_816insGA and c.33_34insC mutation in the AGXT gene could be a common variant in Chinese PH1 population. Mutations at the end of exon 6 account for approximately 50% of all Chinese HOGA1 mutations. Currently, the treatment of PH in China still relies mainly on symptomatic and high-throughput dialysis, with poor prognosis (especially for PH1 patients).

Oxybenzone (OBZ; benzophenone-3, CAS# 131–57–7), as a new pollutant and ultraviolet absorbent, shows a significant threat to the survival of phytoplankton. This study aims to explore the acute toxic effects of OBZ on the growth of the microalga Selenastrum capricornutum, as well as the mechanisms for its damage to the primary metabolic pathways of photosynthesis and respiration. The results demonstrated that the concentrations for 50 % of maximal effect (EC50) of OBZ for S. capricornutum were 9.07 mg L−1 and 8.54 mg L−1 at 72 h and 96 h, respectively. A dosage of 4.56 mg L−1 OBZ significantly lowered the photosynthetic oxygen evolution rate of S. capricornutum in both light and dark conditions for a duration of 2 h, while it had no effect on the respiratory oxygen consumption rate under darkness. OBZ caused a significant decline in the efficiency of photosynthetic electron transport due to its damage to photosystem II (PSII), thereby decreasing the photosynthetic oxygen evolution rate. Over-accumulated H2O2 was produced under light due to the damage caused by OBZ to the donor and acceptor sides of PSII, resulting in increased peroxidation of cytomembranes and inhibition of algal respiration. OBZ’s damage to photosynthesis and respiration will hinder the conversion and reuse of energy in algal cells, which is an important reason that OBZ has toxic effects on S. capricornutum. The present study indicated that OBZ has an acute toxic effect on the microalga S. capricornutum. In the two most important primary metabolic pathways in algae, photosynthesis is more sensitive to the toxicity of OBZ than respiration, especially in the dark.

Methylmercury (MeHg) is a neurotoxin associated with foetal neurodevelopmental and adult cognitive deficits. Neurons are highly dependent on the tricarboxylic acid cycle and oxidative phosphorylation to produce ATP and meet their high energy demands. Therefore, mitochondrial quality control (MQC) is critical for neuronal homeostasis. While existing studies have generated a wealth of data on the toxicity of MeHg, the complex cascades and molecular pathways governing the mitochondrial network remain to be elucidated. Here, 0.6, 1.2 and 2.4 mg/kg body weight of MeHg were administered intragastrically to pregnant Sprague Dawley rats to model maternal MeHg exposure. The results of the in vivo study revealed that MeHg-treated rats tended to perform more directionless repetitive strategies in the Morris Water Maze and fewer target-orientation strategies than control offspring. Moreover, pathological injury and synaptic toxicity were observed in the hippocampus. Transmission electron microscopy (TEM) demonstrated that the autophagosomes encapsulated damaged mitochondria, while showing a typical mitochondrial fission phenotype, which was supported by the activation of PINK1-dependent key regulators of mitophagy. Moreover, there was upregulation of DRP1 and FIS1. Additionally, MeHg compensation promoted mitochondrial biogenesis, as evidenced by the activation of the mitochondrial PGC1-α-NRF1-TFAM signalling pathway. Notably, SIRT3/AMPK was activated by MeHg, and the expression and activity of p-AMPK, p-LKB1 and SIRT3 were consistently coordinated. Collectively, these findings provide new insights into the potential molecular mechanisms regulating MeHg-induced cognitive deficits through SIRT3/AMPK MQC network coordination.

Abstract Background This study aimed to evaluate the correlation between serum methylmalonic acid (MMA) levels and cognition function in patients with chronic kidney disease (CKD). Methods In this cross-sectional study, we included 537 CKD individuals aged ≥ 60-year-old with albuminuria from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Four cognitive tests including the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Delayed Recall and Word Learning tests, and the Animal Fluency test (AF) were performed. Associations between MMA and cognition scores were assessed with linear regression models. Results MMA level was negatively associated with residual renal function and nutrition status. After multivariate adjustment, elevated serum MMA levels were independently correlated with decline of cognition in CKD patients with albuminuria. Conclusion Our study showed that higher serum MMA levels were independently associated with the presence of cognition dysfunction in CKD patients. The exact pathogenesis of MMA and cognition needs further research.

Abstract Background Understanding the trends of tuberculosis (TB) burden and its risk factors at the provincial level in the context of global End TB targets is crucial to identify the progress and challenges in TB control. We aimed to estimate the burden of TB and risk factors for death from 2006 to 2020 for the first time in Guizhou Province, China. Methods Data were collected from the national TB surveillance system. Four indicators of TB burden and their corresponding age-standardized rates (ASRs), including incidence (ASIR), prevalence (ASPR), mortality (ASMR) and disability-adjusted life years (DALYs) (ASDR), were estimated and stratified by year, age, gender and prefecture. Temporal trends of ASRs were presented by locally weighted regression, and the annual percentage change was calculated. The correlation between gross domestic product (GDP) per capita and ASRs was evaluated by Pearson correlation analysis. The associated risk factors for death in PTB patients were determined using logistic regression models. Results A total of 557,476 pulmonary TB (PTB) cases and 11,234 deaths were reported, including 2233 (19.9%) TB specific deaths and 9001 (80.1%) deaths from other causes. The 15-year average incidence, prevalence and mortality rates were 94.6, 102.6 and 2.1 per 100,000 population, respectively. The average DALY rate was 0.60 per 1000 population. The ASIR and ASPR have shown downward trends since 2012, with the largest percentage decrease in 2020 (ASIR: -29.8%; ASPR: -30.5%). The number in TB specific deaths consistently decreased during the study period (P

The C. oleifera oil processing industry generates large amounts of solid wastes, including C. oleifera shell (COS) and C. oleifera cake (COC). Distinct from generally acknowledged lignocellulosic biomass (corn stover, bamboo, birch, etc.), Camellia wastes contain diverse bioactive substances in addition to the abundant lignocellulosic components, and thus, the biorefinery utilization of C. oleifera processing byproducts involves complicated processing technologies. This review first summarizes various technologies for extracting and converting the main components in C. oleifera oil processing byproducts into value-added chemicals and biobased materials, as well as their potential applications. Microwave, ultrasound, and Soxhlet extractions are compared for the extraction of functional bioactive components (tannin, flavonoid, saponin, etc.), while solvothermal conversion and pyrolysis are discussed for the conversion of lignocellulosic components into value-added chemicals. The application areas of these chemicals according to their properties are introduced in detail, including utilizing antioxidant and anti-inflammatory properties of the bioactive substances for the specific application, as well as drop-in chemicals for the substitution of unrenewable fossil fuel-derived products. In addition to chemical production, biochar fabricated from COS and its applications in the fields of adsorption, supercapacitor, soil remediation and wood composites are comprehensively reviewed and discussed. Finally, based on the compositions and structural characteristics of C. oleifera byproducts, the development of full-component valorization strategies and the expansion of the application fields are proposed.

BackgroundArsenic exposure can lead to liver dysfunction, liver steatosis, hepatitis, liver fibrosis, and other liver injuries, but its mechanism is still unclear and effective treatment methods are lacking.ObjectiveTo investigate the potential intervention effect and associated mechanism of Rosa roxburghii Tratt juice on arsenic-induced liver injury in rats from the perspective of S-adenosylmethionine (SAM) metabolism.MethodsThirty-six Wistar rats were randomly divided into six groups, six rats in each group, half male and half female. The low, medium, and high dose groups of sodium arsenite (NaAsO2) were given 2.5, 5.0, and 10.0 NaAsO2 mg·kg−1 (body weight, thereafter), respectively; the control group was given 10 mL·kg−1 deionized water; the Rosa roxburghii Tratt juice intervention group was given 10 mg·kg−1 NaAsO2 for 4 h and then 10 mL·kg−1 Rosa roxburghii Tratt juice; the Rosa roxburghii Tratt juice control group was given 10 mL·kg−1 Rosa roxburghii Tratt juice by gavage. All rats were gavaged once a day, 6 d per week for 4 months. Histopathological changes of rat liver were observed by hematoxylin-eosin (HE) staining. Total bile acids (TBA) and γ-glutamyl transpeptidase (γ-GT) were detected by enzyme cycle method and rate method, respectively. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS) was used to evaluate SAM and S-adenosylhomo cysteine (SAH) in rat liver. Real-time fluorescence quantitative reverse transcriptional PCR (RT-qPCR) was used to detect the mRNA expression levels of the genes of glycine-N-methyltransferase (Gnmt), nicotinamide-N-methyltransferase (Nnmt), and phosphatidylethano-lamine N-mathyltransferase (Pemt).ResultsIn the control group, the liver nuclei were stained clearly, the cytoplasm was stained uniformly, and the liver cords were arranged radially without inflammatory infiltration. In the low, medium, and high dose groups of NaAsO2, hepatic sinusoidal dilation, congestion, and inflammatory infiltration were observed to different degrees. Compared with the control group, TBA in the medium and high dose groups of NaAsO2, and γ-GT in the high dose group of NaAsO2 were significantly increased (P

Background: The NLRP3 inflammasome is a cytoplasmic polymeric protein complex composed of the cytoplasmic sensor NLRP3, the apoptosis-related spot-like protein ASC, and the inflammatory protease caspase-1. NLRP3 activates and releases IL-1β through classical pathways, and IL-18 mediates inflammation and activates gasdermin-D protein to induce cellular pyroptosis. Numerous studies have also emphasized the non-classical pathway activated by the NLRP3 inflammasome in chronic kidney disease (CKD) and the inflammasome-independent function of NLRP3. Summary: The NLRP3-targeting inflammasome and its associated pathways have thus been widely studied in models of CKD treatment, but no drug that targets NLRP3 has thus far been approved for the treatment of CKD. Key Messages: We herein reviewed the current interventional methods for targeting the NLRP3 inflammasome in various CKD models, analyzed their underlying mechanisms of action, classified and compared them, and discussed the advantages and follow-up directions of various interventional methods. This review therefore provides novel ideas and a reference for the development of targeted NLRP3-inflammasome therapy in CKD.

Background: Postoperative delirium (POD) often occurs in elderly patients after surgery. We conducted two clinical studies to determine whether COVID-19 vaccination has a protective effect on POD and to explore the role of CSF biomarkers in this process. Methods: We conducted two clinical studies, Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) and Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE), in which patients more than or equal to 65 years old who have had elective non-cardiac surgery were enrolled. The preoperative cognitive status of patients were evaluated by Mini-Mental State Examination (MMSE) one day preoperatively. Confusion Assessment Method (CAM) was used to diagnose POD. We used the mediation model to analyze the relationship between CSF biomarkers, COVID-19 vaccination and POD, as well as Dynamic Nomogram to calculate the incidence of Non-Postoperative Delirium (NPOD). The main outcome of these studies was the incidence of POD during seven days postoperatively or before discharge, which was assessed by CAM. Results: In the final, 705 participants were enrolled in the PNDRFAP study, and 638 patients in the PNDABLE. In both studies, we found that the occurrence of POD was lower in patients who had injected COVID-19 vaccination before surgery compared with those without vaccination (PNDRFAP: 10.20 % [21/205] vs 25.80 % [129/500], P

Arsenic is an environmentally ubiquitous toxic metalloid. Chronic exposure to arsenic may lead to arsenicosis, while no specific therapeutic strategies are available for the arsenism patients. And Ginkgo biloba extract (GBE) exhibited protective effect in our previous study. However, the mechanisms by which GBE protects the arsenism patients remain poorly understood. A liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics analysis was used to study metabolic response in arsenism patients upon GBE intervention. In total, 39 coal-burning type of arsenism patients and 50 healthy residents were enrolled from Guizhou province of China. The intervention group (n = 39) were arsenism patients orally administered with GBE (three times per day) for continuous 90 days. Plasma samples from 50 healthy controls (HC) and 39 arsenism patients before and after GBE intervention were collected and analyzed by established LC-MS method. Statistical analysis was performed by MetaboAnalyst 5.0 to identify differential metabolites. Multivariate analysis revealed a separation in arsenism patients between before (BG) and after GBE intervention (AG) group. It was observed that 35 differential metabolites were identified between BG and AG group, and 30 of them were completely or partially reversed by GBE intervention, with 14 differential metabolites significantly up-regulated and 16 differential metabolites considerably down-regulated. These metabolites were involved in promoting immune response and anti-inflammatory functions, and alleviating oxidative stress. Taken together, these findings indicate that the GBE intervention could probably exert its protective effects by reversing disordered metabolites modulating these functions in arsenism patients, and provide insights into further exploration of mechanistic studies.

Abstract Background The relationship between Insulin resistance (IR) evaluated through homeostasis model assessment insulin resistance (HOMA-IR) and cognitive function is controversial among nondiabetic individuals. No study so far has reported the association between the IR evaluated through triglyceride glucose (TyG) index and cognitive function among nondiabetics. This study aims to assess this association among US nondiabetic older elderly. Methods Data were obtained from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Low cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease Battery for immediate word list learning (CERAD-WL) and delayed recall (CERAD-DR) test, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Logistic regression analyses were conducted to compute the odds ratio (OR) and 95% confidential interval (CI) to examine the association between the TyG index (continuous and quartiles) and low cognitive function. Results A total of 661 nondiabetic older adults were included with a mean age of 68.62 ± 6.49 years. Compared to the 1st quartile of the TyG index, participants in the TyG index 4th quartile were associated with low cognitive function evaluated through the CERAD test (CERAD-WL and CERAD-DR) [OR: 2.62; 95% CI (1.31, 5.23); P

Abstract Population structure and lifestyles may have contributed to the epidemiological status of Chronic Kidney Disease due to Type 2 Diabetes (CKD-T2D). This study is a secondary data analysis. Using data from the Global Burden of Disease Study, we describe the changes in CKD-T2D burden and its influencing factors in the population aged 20–59 years from 1990 to 2019. Globally, the incidence, death, and Disability Adjusted Life Years (DALYs) rate of CKD-T2D showed an upward trend and increased with age, and the burden in males was higher than that in females. Population growth and aging were important driving factors for the increase of CKD-T2D DALY burden, while high systolic blood pressure and high body-mass index were the primary attributable risk factors. High body-mass index exhibited higher contributions to high Socioeconomic Development Index (SDI) countries, whereas low SDI countries were more impacted by high systolic blood pressure. The population attributable fraction of CKD-T2D DALY caused by high body-mass index was positively correlated with SDI, while high temperature and lead exposure were negatively correlated. Therefore, strengthening disease screening for people aged 20–59 years and formulating early intervention measures based on the level of socioeconomic development may effectively alleviate the burden of CKD-T2D.

Abstract The prevalence of chronic kidney disease (CKD) has been increasing over the past decades. However, no effective therapies are available for delaying or curing CKD. Progressive fibrosis is the major pathological feature of CKD, which leads to end-stage renal disease (ESRD). The present study showed that Polo-like kinase 1 (Plk1) was upregulated in the kidneys of CKD patients and mice subjected to unilateral ureteral obstruction (UUO) with location in proximal tubules and tubulointerstitial fibroblasts. Pharmacological inhibition, genetic silencing or knockout of Plk1 attenuated obstructive nephropathy due to suppressed fibroblast activation mediated by reduced autophagic flux. We found Plk1 plays a critical role in maintaining intralysosomal pH by regulating ATP6V1A phosphorylation, and inhibition of Plk1 impaired lysosomal function leading to blockade of autophagic flux. In addition, Plk1 also prevented partial epithelial-mesenchymal transition (pEMT) of tubular epithelial cells via autophagy pathway. In conclusion, this study demonstrated that Plk1 plays a pathogenic role in renal tubulointerstitial fibrosis by regulating autophagy/lysosome axis. Thus, targeting Plk1 could be a promising strategy for CKD treatment.

Abstract Objectives Microcephaly is caused by reduced brain volume and most usually associated with a variety of neurodevelopmental disorders (NDDs). To provide an overview of the diagnostic yield of whole exome sequencing (WES) and promote novel candidates in genetically unsolved families, we studied the clinical and genetic landscape of an unselected Chinese cohort of patients with microcephaly. Methods We performed WES in an unselected cohort of 103 NDDs patients with microcephaly as one of the features. Full evaluation of potential novel candidate genes was applied in genetically undiagnosed families. Functional validations of selected variants were conducted in cultured cells. To augment the discovery of novel candidates, we queried our genomic sequencing data repository for additional likely disease-causing variants in the identified candidate genes. Results In 65 families (63.1%), causative sequence variants (SVs) and clinically relevant copy number variants (CNVs) with a pathogenic or likely pathogenic (P/LP) level were identified. By incorporating coverage analysis to WES, a pathogenic or likely pathogenic CNV was detected in 15 families (16/103, 15.5%). In another eight families (8/103, 7.8%), we identified variants in newly reported gene (CCND2) and potential novel neurodevelopmental disorders /microcephaly candidate genes, which involved in cell cycle and division (PWP2, CCND2), CDC42/RAC signaling related actin cytoskeletal organization (DOCK9, RHOF), neurogenesis (ELAVL3, PPP1R9B, KCNH3) and transcription regulation (IRF2BP1). By looking into our data repository of 5066 families with NDDs, we identified additional two cases with variants in DOCK9 and PPP1R9B, respectively. Conclusion Our results expand the morbid genome of monogenic neurodevelopmental disorders and support the adoption of WES as a first-tier test for individuals with microcephaly.

Abstract Background Germline gain‐of‐function (GOF) variants in the signal transducer and activator of transcription 3 (STAT3) gene lead to a rare inherited disorder characterized by early‐onset multiorgan autoimmunity. Methods We described a Chinese patient with infantile‐onset diabetes and multiorgan autoimmunity. The patient presented with early‐onset type 1 diabetes and autoimmune hypothyroidism at 7 months. During the 7.5‐year follow‐up, she developed pseudo‐celiac enteropathy at 1 year of age and showed severe growth retardation. Whole‐exome sequencing was performed and the novel variant was further assessed by in vitro functional assays. Results Whole‐exome sequencing revealed a novel variant (c.1069G>A, p.Glu357Lys) in the DNA‐binding domain of STAT3. In vitro functional studies revealed that p.Glu357Lys was a GOF variant by increasing STAT3 transcriptional activity and phosphorylation. In addition, the STAT3 Glu357Lys variant caused dysregulation of insulin gene expression by enhancing transcriptional inhibition of the insulin gene enhancer binding protein factor 1 (ISL1). Conclusion In the current study, we describe clinical manifestations and identify a novel STAT3 GOF variant (c.1069G>A) in a Chinese patient. This activating variant impairs insulin expression by increasing transcriptional inhibition of its downstream transcription factor ISL1, which could be involved in the pathogenesis of early‐onset diabetes.

BackgroundCognitive impairment (CI) is common among patients with chronic kidney disease (CKD), and is associated with a poor prognosis. We assessed the prevalence and associated factors of CI in patients with CKD.MethodsA systematic review and meta-analysis were conducted by searching PubMed, Embase, and the Web of Science through December 1, 2023. Random effects models were performed with subgroup analyses to further explore the heterogeneity.Results50 studies involving 25,289 CKD patients were included. The overall prevalence of CI was 40% (95% confidence interval 33-46). The pooled prevalence of CI was relatively higher in CKD patients from Africa (58%), Asia (44%) and America (37%). Attention and executive dysfunction appeared to be the most common manifestations. The prevalence of CI was higher among patients with hemodialysis (53%) and peritoneal dialysis (39%) than those without dialysis (32%) and post-kidney transplanted (26%). In addition, advanced age, the presence of diabetes and hypertension might increase the risk of CI in CKD patients.ConclusionsPeople with CKD have a high prevalence of CI, especially in patients with hemodialysis. An early and comprehensive screening for CI in CKD patients is needed to improve clinical outcomes.Trial registrationRegistration number: PROSPERO (CRD42023412864).

ObjectiveThis study aims to develop and validate the Posttraumatic Cognitive Appraisal Inventory (PTCAI) for accidental trauma survivors.MethodBased on interviews and expert feedback, the initial item pool was generated for the Negative Cognitive Appraisal Inventory of Loss and Feeling Threatened, and the Positive Cognitive Appraisal Inventory of Positively Face, Self-Sense, and Relationships. Then, we recruited two groups of accidental trauma survivors to examine the reliability and validity of the PTCAI. Item analysis and exploratory factor analysis (EFA) were conducted on Sample 1. Confirmatory factor analysis (CFA), Pearson correlation analysis, and internal consistency reliability analysis were applied to Sample 2. After 2 weeks, 20 survivors completed the PTCAI again to test temporal stability.ResultsFollowing item analysis, the PTCAI was reduced to 27 items. The results of the EFA demonstrated that the five-factor, 27-item solution of the PTCAI was appropriate, which accounted for 63.931% of the total variation. The CFA indicated that the five-factor second-order model offered an excellent fit to the data. Loss and Feeling threatened were equally important in the study participants’ negative cognitive appraisal of accidental traumas. Self-sence was the most important positive cognitive appraisal of accidental traumas by the study participants. Positively Face and Relationships were somewhat behind. Additionally, the PTCAI demonstrated high concurrent validity and reliability (test–retest and internal consistency).ConclusionThe PTCAI appears to be a reliable and valid instrument for assessing cognitive appraisals of accidental trauma survivors.

Background To explore the prospective role of serum fatty acid-binding protein 4 (FABP4) in the outcomes of peritoneal dialysis (PD) patients.Methods A prospective observational study was conducted with 159 patients on PD. Demographic and clinical data at baseline were collected from medical records. Biochemical data were recorded based on blood samples measured in a central laboratory. Serum FABP4 concentrations were determined using enzyme-linked immunosorbent assay. Body composition was measured using a Body Composition Monitor. Abdominal lateral plain radiography was used to evaluate vascular calcification. The primary endpoints were all-cause and cardiovascular death.Results The median of serum FABP4 concentration was 154.6 ng/mL (interquartile range, 132.8–269.7 ng/mL). Increased serum FABP4 was associated with increased vascular calcification proportion, time on dialysis, body mass index, high-sensitivity C-reactive protein (hs-CRP), intact parathyroid hormone (iPTH), triglycerides, body fat mass, and body fat percentage (p

AbstractObjectives Acute kidney injury (AKI) is associated with increased mortality among coronavirus disease 2019 (COVID-19) patients. This meta-analysis aimed to identify risk factors for the development of AKI in patients with COVID-19.Methods A systematic literature search was conducted in PubMed and EMBASE from 1 December 2019 to 1 January 2023. Due to significant study heterogeneity, meta-analyses were conducted using random-effects models. Meta-regression and sensitivity analysis were also performed.Results A total of 153,600 COVID-19 patients from 39 studies were included, and 28,003 patients developed AKI. By meta-analysis, we discovered that age, male sex, obesity, black race, invasive ventilation, and the use of diuretics, steroids and vasopressors, in addition to comorbidities such as hypertension, congestive heart failure, chronic kidney disease, acute respiratory distress syndrome, and diabetes, were significant risk factors for COVID-19-associated AKI.Conclusions Early detection of these risk factors is essential to reduce the incidence of AKI and improve the prognosis of COVID-19 patients.

Abstract Background Electron microscopy is important in the diagnosis of renal disease. For immune-mediated renal disease diagnosis, whether the electron-dense granule is present in the electron microscope image is of vital importance. Deep learning methods perform well at feature extraction and assessment of histologic images. However, few studies on deep learning methods for electron microscopy images of renal biopsy have been published. This study aimed to develop a deep learning-based multi-model to automatically detect whether the electron-dense granule is present in the TEM image of renal biopsy, and then help diagnose immune-mediated renal disease. Methods Three deep learning models are trained to classify whether the electron-dense granule is present using 910 electron microscopy images of renal biopsies. We proposed two novel methods to improve the model accuracy. One model uses the pre-trained ResNet convolutional layers for feature extraction with transfer learning which was firstly improved with skip architecture, then uses Support Vector Machine as the classifier. We developed a multi-model to combine the traditional ResNet model with the improved one to further improve the accuracy. Results Deep learning-based multi-model has the highest model accuracy, and the average accuracy is about 88%. The improved ReseNet + SVM model performance is much better than the traditional ResNet model. The average accuracy of the improved ResNet + SVM model is 83%, while the traditional ResNet model accuracy is only 58%. Conclusions This study presents the first models for electron microscopy image classification of Renal Biopsy. Identifying whether the electron-dense granule is present plays an important role in the diagnosis of immune complex nephropathy. This study made it possible for Artificial Intelligence models assist to analyze complex electron microscopy images for disease diagnosis.

Kidney injury leads to fibrosis during the progression of chronic kidney disease. Here the authors report that the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in a study with male mice, potentially via TAF7/RAPTOR/mTORC1 signaling.

Abstract Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject’s phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolic biomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeutic potentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathways changes as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists have established a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutic target exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-molecule candidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening and treatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.

Realizing robust magnetoelectric (ME) coupling effect near room temperature is still a long-standing challenge for the application of multiferroic materials in next-generation low-power spintronic and memory devices. Here we report a systematic study on the magnetic, dielectric, and ME coupling properties of Y-type hexaferrite Ba0.5Sr1.5Co2Fe12–xAlxO22 (x = 0.0, 0.5, 1.0) single crystals. The Al doping can induce the shifting of the alternating longitudinal conical (ALC)-proper screw (PS) magnetic phase transition temperature from 200 K for x = 0–365 K for x = 1.0. The most interesting feature is that the Ba0.5Sr1.5Co2Fe11AlO22 single crystal displays a direct and converse ME coupling coefficient with αH ∼3,100 ps/m and αE ∼3,900 ps/m at 250 K, respectively, due to the Al-doped enhanced stability of ALC phase. Moreover, the exchange bias also verifies the strong coupling of electric and magnetic orders. These results provide a valuable insight on the modulation of ALC structure and the mechanism of ME effect in Y-type hexaferrites.

Introduction: Steroid resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage kidney disease in children, mostly associated with focal segmental glomerulosclerosis (FSGS). Advances in genomic science have enabled the identification of causative variants in 20 – 30% of SRNS patients. Methods: We used whole exome sequencing (WES) to explore the genetic causes of SRNS in children. Totally 101 patients with SRNS, and 13 patients with nephrotic proteinuria and FSGS were retrospectively enrolled in our hospital between 2018 and 2022. For the known monogenic causes analysis, we generated a known SRNS gene list of 71 genes through reviewing the OMIM database and literature. Results: Causative variants were identified in 23.68% of our cohort, and the most frequently mutated genes in our cohort were WT1 (7/27), NPHS1 (3/27), ADCK4(3/27), and ANLN (2/27). Five patients carried variants in phenocopy genes, including MYH9, MAFB, TTC21B, AGRN, and FAT4. The variant detection rate was the highest in the two subtype groups with congenital nephrotic syndrome and syndromic SRNS. In total, 68.75% of variants we identified were novel, and have not been previously reported in literature. Conclusion: Comprehensive genetic analysis is key to realizing the clinical benefits of a genetic diagnosis. We suggest that all children with SRNS undergo genetic testing, especially those with early onset and extrarenal phenotypes.

AimTo explore the effects of brain–computer interface training combined with mindfulness therapy on Hemiplegic Patients with Stroke.BackgroundThe prevention and treatment of stroke still faces great challenges. Maximizing the improvement of patients’ ability to perform activities of daily living, limb motor function, and reducing anxiety, depression, and other social and psychological problems to improve patients’ overall quality of life is the focus and difficulty of clinical rehabilitation work.MethodsPatients were recruited from December 2021 to November 2022, and assigned to either the intervention or control group following a simple randomization procedure (computer-generated random numbers). Both groups received conventional rehabilitation treatment, while patients in the intervention group additionally received brain–computer interface training and mindfulness therapy. The continuous treatment duration was 5 days per week for 8 weeks. Limb motor function, activities of daily living, mindfulness attention awareness level, sleep quality, and quality of life of the patients were measured (in T0, T1, and T2). Generalized estimated equation (GEE) were used to evaluate the effects. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300070382).ResultsA total of 128 participants were randomized and 64 each were assigned to the intervention and control groups (of these, eight patients were lost to follow-up). At 6 months, compared with the control group, intervention group showed statistically significant improvements in limb motor function, mindful attention awareness, activities of daily living, sleep quality, and quality of life.ConclusionBrain–computer interface combined with mindfulness therapy training can improve limb motor function, activities of daily living, mindful attention awareness, sleep quality, and quality of life in hemiplegic patients with stroke.ImpactThis study provides valuable insights into post-stroke care. It may help improve the effect of rehabilitation nursing to improve the comprehensive ability and quality of life of patients after stroke.Clinical review registrationhttps://www.chictr.org.cn/, identifier ChiCTR2300070382.

Abstract Renal fibrosis is a common characteristic of various chronic kidney diseases (CKDs) driving the loss of renal function. During this pathological process, persistent injury to renal tubular epithelial cells and activation of fibroblasts chiefly determine the extent of renal fibrosis. In this study, the role of tumor protein 53 regulating kinase (TP53RK) in the pathogenesis of renal fibrosis and its underlying mechanisms is investigated. TP53RK is upregulated in fibrotic human and animal kidneys with a positive correlation to kidney dysfunction and fibrotic markers. Interestingly, specific deletion of TP53RK either in renal tubule or in fibroblasts in mice can mitigate renal fibrosis in CKD models. Mechanistic investigations reveal that TP53RK phosphorylates baculoviral IAP repeat containing 5 (Birc5) and facilitates its nuclear translocation; enhanced Birc5 displays a profibrotic effect possibly via activating PI3K/Akt and MAPK pathways. Moreover, pharmacologically inhibiting TP53RK and Birc5 using fusidic acid (an FDA‐approved antibiotic) and YM‐155(currently in clinical phase 2 trials) respectively both ameliorate kidney fibrosis. These findings demonstrate that activated TP53RK/Birc5 signaling in renal tubular cells and fibroblasts alters cellular phenotypes and drives CKD progression. A genetic or pharmacological blockade of this axis serves as a potential strategy for treating CKDs.

Abstract Mitochondria comprise the central metabolic hub of cells and their imbalance plays a pathogenic role in chronic kidney disease (CKD). Here, we studied Lon protease 1 (LONP1), a major mitochondrial protease, as its role in CKD pathogenesis is unclear. LONP1 expression was decreased in human patients and mice with CKD, and tubular‐specific Lonp1 overexpression mitigated renal injury and mitochondrial dysfunction in two different models of CKD, but these outcomes were aggravated by Lonp1 deletion. These results were confirmed in renal tubular epithelial cells in vitro. Mechanistically, LONP1 downregulation caused mitochondrial accumulation of the LONP1 substrate, 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (HMGCS2), which disrupted mitochondrial function and further accelerated CKD progression. Finally, computer‐aided virtual screening was performed, which identified a novel LONP1 activator. Pharmacologically, the LONP1 activator attenuated renal fibrosis and mitochondrial dysfunction. Collectively, these results imply that LONP1 is a promising therapeutic target for treating CKD.

BackgroundLong-term exposure to arsenic can cause liver injury of varying degrees. Mitochondrial damage may be an early key event of arsenic-induced liver injury. Silent mating type information regulation 2 homolog 1 (SIRT1)/ recombinant peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important pathway regulating mitochondrial mass and function. However, whether arsenic-induced liver injury is related to mitochondrial dysfunction mediated by SIRT1/PGC-1α pathway remains unclear.ObjectiveTo investigate potential effects of sodium arsenite (NaAsO2) on mitochondrial function and expressions of SIRT1/PGC-1α pathway-related proteins in human normal liver cell.MethodsHuman normal liver cells (MIHA cells) were used as the research object. MIHA cells were treated with different concentrations of NaAsO2 (0, 5, 10 and 20 μmol·L−1) for 24 h, and the cells were collected for study. The ultrastructure of mitochondria was observed by transmission electron microscopy, adenosine triphosphate (ATP) concentration by fluorescence method, mitochondrial membrane potential (MMP) level by flow cytometry, and SIRT1, PGC-1α and their downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) protein expression levels by Western blotting. One-way analysis of variance and trend test were used for data statistical analysis.ResultsThe viability of MIHA cells decreased gradually with the increase of NaAsO2 concentration (F=6495.47, P

Abstract Background Henoch-Schönlein purpura (HSP) with refractory gastrointestinal (GI) symptoms is always difficult to handle because of its resistance to supportive therapies and glucocorticoid. This study aimed to evaluate the efficacy of hemoperfusion (HP) and intravenous immunoglobulins (IVIG) therapies in this population. Methods Sixty-four HSP patients with refractory GI involvement (R-GI group) and 64 cases with mild GI symptoms (control group) were retrospectively analyzed in our center from March 2016 to October 2019. In R-GI group, 42 cases (subgroup A) were treated with IVIG and steroid, 13 cases (subgroup B) used HP and steroid, 9 cases (subgroup C) executed a combination of IVIG, HP and steroid. Demographic characteristics, clinical features, laboratory indexes and treatment outcomes were recorded. t-test, One-way ANOVA, Mann-Whitney U test, and multivariate logistic regression were used in comparing differences among subgroups and predicting independent risk factors. Results Compared with the control group, R-GI cases experienced higher risk of renal involvement (P = 0.000), more steroid exposure (P = 0.000), six times expenses (P = 0.000) and 2.3 times length of hospitalization (P = 0.000). The independent risk factors of R-GI group were elevated neutrophils (OR 1.250 [95% CI 1.130-1.383]) and the percentage of B lymphocytes (OR 1.100 [95% CI 1.026-1.179]) as well as decreased IgG (OR 0.847 [95% CI 0.732-0.98]). In R-GI group, increased age (OR 1.039 [95% CI 1.016-1.062]) and IgM (OR 5.994 [95% CI 1.403-27.611]) were verified to be risk factors of HSP nephritis. All three subgroups could alleviate the symptoms effectively. Compared with those in subgroup A, patients in subgroup B were elder (P = 0.004), had less relapse (P = 0.002), steroid exposure (P = 0.033) and expenses (P = 0.031), more significant decrease of WBC (P = 0.026) after treatment. Conclusion The HSP with refractory GI involvement had much higher risk of medical burden and renal involvement. Both IVIG and HP therapies could ameliorate refractory GI symptoms efficiently. HP therapy tended to reduce the relapse, costs and steroid exposure in its audiences who were cooperated and with stable hemodynamics, while IVIG had better use in younger children.