ETS translocation variant 5 (ETV5) promotes CD4+ T cell-mediated intestinal inflammation and fibrosis in inflammatory bowel diseases.

ETS translocation variant 5 (ETV5) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the exact roles of ETV5 in regulating CD4+ T cell-mediated intestinal inflammation and fibrosis formation remain unclear. Here, we reveal that ETV5 overexpression induced IL-9 and its transcription factor IRF4 expression in naïve IBD CD4+ T cells under Th9-polarizing conditions. Silencing of IRF4 inhibited ETV5-induced IL-9 expression. CD4+ T cell-specific ETV5 deletion (CKO) ameliorated intestinal inflammation and fibrosis in TNBS-induced experimental colitis and CD4+ T cell-transferred Rag1-/- colitis mice, characterized by less CD4+ T cell infiltration, lower fibroblast activation and collagen deposition in the colonic tissues. Furthermore, IL-9 treatment aggressive TNBS-induced intestinal fibrosis in CKO and wild type (WT) control mice. In vitro, human intestinal fibroblasts cocultured with ETV5 overexpressed-Th9 cells expressed higher levels of collagen I and III, whereas an inclusion of anti-IL-9 antibody could reverse this effect. RNA sequencing analysis demonstrated that IL-9 upregulated TAF1 expression in human intestinal fibroblasts. Clinic data showed that number of α-SMA+TAF1+ fibroblasts are higher in inflamed mucosa of IBD patients. Importantly, TAF1 siRNA treatment suppressed IL-9-mediated profibrotic effect in vitro. These findings reveal that CD4+ T cell-derived ETV5 promotes intestinal inflammation and fibrosis through upregulating IL-9-mediated intestinal inflammatory and fibrotic response in IBD. Thus, the ETV5/IL-9 signal pathway in T cells might represent a novel therapeutic target for intestinal inflammation and fibrosis in IBD.

Decreased TMIGD1 aggravates colitis and intestinal barrier dysfunction via the BANF1-NF-κB pathway in Crohn's disease.

BACKGROUND: Disrupted intestinal epithelial barrier is one of the major causes of Crohn's disease (CD). Novel molecular targets for intestinal epithelial barrier are essential to treatment of CD. Transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) is an adhesion molecule that regulates cell adhesion, migration, and enterocyte differentiation. However, the function and mechanism of TMIGD1 in CD and intestinal epithelial barrier has rarely been studied. Furthermore, the association between TMIGD1 and the clinical features of CD remains unclear. METHODS: Transcriptome analysis on colonic mucosa from CD patients and healthy individuals were performed to identify dysregulated genes. Multi-omics integration of the 1000IBD cohort including genomics, transcriptomics of intestinal biopsies, and serum proteomics identified the association between genes and characteristics of CD. Inflammation was assessed by cytokine production in cell lines, organoids and intestinal-specific Tmigd1 knockout (Tmigd1INT-KO) mice. Epithelial barrier integrity was evaluated by trans-epithelium electrical resistance (TEER), paracellular permeability, and apical junction complex (AJC) expression. Co-immunoprecipitation, GST pull-down assays, mass spectrometry, proteomics, and transcriptome analysis were used to explore downstream mechanisms. RESULTS: Multi-omics integration suggested that TMIGD1 was negatively associated with inflammatory characteristics of CD. TMIGD1 was downregulated in inflamed intestinal mucosa of patients with CD and mice colitis models. Tmigd1INT-KO mice were more susceptible to chemically induced colitis. In epithelial cell lines and colonic organoids, TMIGD1 knockdown caused impaired intestinal barrier integrity evidenced by increased paracellular permeability and reduced TEER and AJC expression. TMIGD1 knockdown in intestinal epithelial cells also induced pro-inflammatory cytokine production. Mechanistically, TMIGD1 directly interacted with cytoplasmic BAF nuclear assembly factor 1 (BANF1) to inhibit NF-κB activation. Exogenous expression of TMIGD1 and BANF1 restored intestinal barrier function and inhibited inflammation in vitro and in vivo. TMIGD1 expression predicted response to anti-TNF treatment in patients with CD. CONCLUSIONS: Our study demonstrated that TMIGD1 maintained intestinal barrier integrity and inactivated inflammation, and was therefore a potential therapeutic target for CD.

Angiopoietin-like 4 (ANGPTL4) Suppression Ameliorates Lupus Nephritis in MRL/lpr Mice by Inactivating NLRP3 Inflammasome and Inhibiting Inflammatory Response.

Background: Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN. Objective: To investigate the detailed role and regulatory mechanism of ANGPTL4 in experimental models of LN. Methods: MRL/lpr mice 11-week-old were injected with adeno-associated virus (AAV)-mediated ANGPTL4 short hairpin RNA (shRNA). At 16 and 20 weeks of age, 24-h urine samples were harvested to measure proteinuria levels. After the mice were sacrificed, blood and kidney tissues were harvested to examine serum creatinine (cr) and blood urea nitrogen (BUN) levels, kidney histological changes, and pro-inflammatory cytokine production. Additionally, the levels of NLRP3 inflammasome-associated molecules in mouse renal tissues were detected to clarify the underlying mechanism. Results: The AAV-sh-ANGPTL4 injection significantly reduced the proteinuria, cr, and BUN levels in MRL/lpr mice. ANGPTL4 silencing ameliorated glomerular, tubular, and interstitial damage in mice, mitigating the pathological alternations of LN. In addition, ANGPTL4 knockdown repressed pro-inflammatory cytokine production in the kidneys. Mechanically, ANGPTL4 suppression inhibited NLRP3 inflammasome expression in renal tissues of mice. Conclusion: ANGPTL4 silencing inhibits the NLRP3 inflammasome-mediated inflammatory response, thereby ameliorating LN in MRL/lpr mice.

A vacuolar transporter plays important roles in zinc and cadmium accumulation in rice grain.

Rice grain is a poor dietary source of zinc (Zn) but the primary source of cadmium (Cd) for humans; however, the molecular mechanisms for their accumulation in rice grain remain incompletely understood. This study functionally characterized a tonoplast-localized transporter, OsMTP1. OsMTP1 was preferentially expressed in the roots, aleurone layer, and embryo of seeds. OsMTP1 knockout decreased Zn concentration in the root cell sap, roots, aleurone layer and embryo, and subsequently increased Zn concentration in shoots and polished rice (endosperm) without yield penalty. OsMTP1 haplotype analysis revealed elite alleles associated with increased Zn level in polished rice, mostly because of the decreased OsMTP1 transcripts. OsMTP1 expression in yeast enhanced Zn tolerance but did not affect that of Cd. While OsMTP1 knockout resulted in decreased uptake, translocation and accumulation of Cd in plant and rice grain, which could be attributed to the indirect effects of altered Zn accumulation. Our results suggest that rice OsMTP1 primarily functions as a tonoplast-localized transporter for sequestrating Zn into vacuole. OsMTP1 knockout elevated Zn concentration but prevented Cd deposition in polished rice without yield penalty. Thus, OsMTP1 is a candidate gene for enhancing Zn level and reducing Cd level in rice grains.

A tale of two cities: Chinese mothers' parental burnout and parenting behaviors in Shanghai and Nanning.

PURPOSE: Parental burnout is a psychological syndrome that develops in response to the chronic stressors in one's role as a parent. It can be detrimental to the health and wellbeing of both parents and children and has been empirically proven to result in more negative parenting behaviours. Based on recent research, parental burnout is more prevalent in individualistic cultures. Considering that parenting norms and practices vary greatly across cultures, there could be different effects of parental burnout on parenting practices in different areas. The present study aimed to determine the relationship between parental burnout and parenting behaviours in Shanghai and Nanning, two cities in China that differ in the extent to which they have been exposed to the cultural influence of Western individualism, and to examine the moderating effect of city on these relationship patterns. METHODS: Three hundred and sixty-eight mothers in Shanghai and 180 mothers in Nanning took part in the survey. RESULTS: On average, mothers in Shanghai had more severe parental burnout than their counterparts in Nanning. Furthermore, parental burnout was associated with positive parenting behaviours (i.e., parental warmth) and negative parenting behaviours (i.e., parental hostility and neglect), and the associations between parental burnout and negative parenting behaviours in Nanning were greater than in Shanghai. CONCLUSIONS: These results can be explained by cultural differences in individualism and collectivism between Shanghai and Nanning. This study extends the knowledge on the role of culture in shaping parental roles.

Overexpression of RAB31 in gastric cancer is associated with released exosomes and increased tumor cell invasion and metastasis.

BACKGROUND: Gastric cancer (GC) is one of most common cancers worldwide. Several studies have suggested that Rab31 functions as a membrane vesicle transport regulator; however, the mechanism by which RAB31 regulates exosome secretion and promotes metastasis remains to be clarified. METHODS: We examined the expression of RAB31 protein and mRNA in GC tissue samples via immunohistochemistry and reverse transcription-polymerase chain reaction assays, respectively. We elucidated the function of RAB31 in GC cells by constructing a cell model and a pulmonary metastatic model of GC with overexpression of RAB31. Protein mass spectrometry was used to identify the exosomal protein. RESULTS: RAB31 expression increased at both the protein and mRNA levels with the development of GC. Cells overexpressing RAB31 showed an enhanced ability to migrate in both the in vitro cell model and the pulmonary metastatic model of GC. Exosome nanoparticle tracking analysis and electron microscopy revealed that the both the number and size of the exosomes secreted by GC cells were reduced when RAB31 expression was depleted. Injection of exosomes derived from RAB31 overexpressing cells promoted pulmonary metastasis in vivo. Analysis of the exosomal proteins revealed that PSMA1 was overexpressed in GC tissue in accordance with RAB31 expression. PSMA1 overexpression was highly associated with poor prognosis of GC patients. CONCLUSION: Our findings revealed a key role for RAB31 in GC metastasis through regulation of exosome secretion.

Correlation between decreased plasma miR-29a and vascular endothelial injury induced by hyperlipidemia.

BACKGROUND: Hyperlipidemia is a major risk factor for vascular endothelial injury and atherosclerosis leading to cardiovascular diseases. Early diagnosis of vascular endothelial injury is important for the prevention and prognosis of cardiovascular diseases. This study aimed to investigate sensitive circulating microRNA (miRNA) as a potential diagnostic biomarker of vascular endothelial injury in a hyperlipidemic rat model. METHODS: The miRNA expression profile was detected by miRNA microarray. The hyperlipidemic rat model was established by intraperitoneal injection of vitamin D3 combined with a high-fat diet. Plasma miRNA levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: No significant difference was found in the types of highly expressed miRNAs between human umbilical artery endothelial cells (HUAEC) and human umbilical vein endothelial cells (HUVEC). A total of 10 highly expressed miRNAs in endothelial cells were selected as candidate miRNAs, including miR-21, miR-126, let-7a, miR-23a, miR-221, miR-125b, miR-26a, miR-29a, miR-16, and miR-100. The plasma levels of let-7a, miR-126, miR-21, and miR-26a were significantly elevated in hyperlipidemic rats at 30 and 50 days after modeling, while the plasma level of miR-29a was significantly decreased. No significant change was found in the plasma levels of miR-125b, miR-23a, miR-221, miR-100, and miR-16. Interestingly, a significant reduction in plasma miR-29 level was detected as early as 20 days after modeling, which was earlier than for soluble intercellular adhesion molecule­1 (sICAM-1). CONCLUSION: The plasma levels of endothelial cell-enriched miRNAs were correlated with vascular endothelial injury induced by hyperlipidemia. miR-29a might serve as a potential early diagnostic biomarker of endothelial injury-related diseases.

The early stage of COVID-19 pandemic: Gastrointestinal manifestations and liver injury in COVID-19 patients in Wuhan, China.

There are few and inconsistent data focusing on gastrointestinal (GI) manifestations and liver injury in China's early stage of COVID-19 pandemic. In this study, we research the prevalence and role of GI symptoms and liver injury in COVID-19 patients in Wuhan during the disease's first outbreak. We conducted a cross-sectional observational study in a non-ICU unit in Wuhan, China. COVID-19 patients were consecutively admitted from 23 February 2020 to 5 April 2020. Demographic and clinical data were retrieved and analyzed throughout the disease course. A total of 93 patients were enrolled, including 45.2% moderate, 54.8% severe, and 2.2% critical type patients. 69.9% of patients had at least one GI symptom; if excluding hyporexia/anorexia, 49.5% of patients showed at least one GI symptom. The incidence rate of hyporexia/anorexia, diarrhea, nausea/vomiting, abdominal discomfort/pain, and elevated liver enzymes were 67.7, 29.0, 28.0, 21.5, and 23.7%, respectively. Patients with GI symptoms or elevated liver enzymes have a higher risk of severe type disease than patients without GI symptoms or elevated liver enzymes (67.7 vs. 25.0%, p < 0.001; 77.3 vs. 47.9%, p = 0.016, respectively), and experienced longer disease duration. In multivariate analysis, hyporexia/anorexia was confirmed as an independent predictive factor of severe type disease (odds ratio: 5.912; 95% confidence interval: 2.247-15.559; p < 0.001). In conclusion, in the early stage of the COVID-19 pandemic, GI symptoms and elevated liver enzymes are common throughout the disease course, and associated with severer disease and longer disease duration.

Effects of the nurse-led program on disabilities improvement in patients with ischemic stroke.

To evaluate whether the nurse-led program can improve disabilities in patients with ischemic stroke for more than 6 months. This is a randomized, open-label study. Participants in the usual-care group received the usual care that included verbal stroke-related education and secondary prevention. Participants in the active group received the usual care plus the nurse-led program intervention. The disability was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Mental Health Inventory-5 (MHI-5) was used to assess mental health status (MHS). The median duration since ischemic stroke was 8.4 and 8.6 months, respectively. At baseline, there was no difference in the median NIHSS value and the NIHSS category between these 2 groups. After 6 months' follow-up, the median NIHSS value was lower in the active group (4.1 vs 6.3). The proportion of patients with NIHSS of 1 to 4 was higher (50.0% vs 28.6%) while the proportion of patients with NIHSS of 5 to 12 (24.1% vs 51.8%) was lower in the active group. After multivariate regression analysis, the nurse-led program was negatively associated with increased NIHSS category (odds ratio of 0.70 and 95% confidence interval of 0.62-0.88). In the group with MHI-5 less than median, the nurse-led program was not associated with NIHSS category. While in the group with MHI-5 greater than median, the nurse-led program was associated decreased NIHSS category, with a significant interaction (P value = .03). In ischemic stroke patients for more than 6 months, the nurse-led program improves disabilities, which might be related to MHS improvement.

FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by Lactobacillus Strains.

Cholesterol gallstone (CGS) disease is characterized by an imbalance in bile acid (BA) metabolism and is closely associated with gut microbiota disorders. However, the role and mechanism by which probiotics targeting the gut microbiota attenuate cholesterol gallstones are still unknown. In this study, Limosilactobacillus reuteri strain CGMCC 17942 and Lactiplantibacillus plantarum strain CGMCC 14407 were individually administered to lithogenic-diet (LD)-fed mice for 8 weeks. Both Lactobacillus strains significantly reduced LD-induced gallstones, hepatic steatosis, and hyperlipidemia. These strains modulated BA profiles in the serum and liver, which may be responsible for the activation of farnesoid X receptor (FXR). At the molecular level, L. reuteri and L. plantarum increased ileal fibroblast growth factor 15 (FGF15) and hepatic fibroblast growth factor receptor 4 (FGFR4) and small heterodimer partner (SHP). Subsequently, hepatic cholesterol 7α-hydroxylase (CYP7A1) and oxysterol 7α-hydroxylase (CYP7B1) were inhibited. Moreover, the two strains enhanced BA transport by increasing the levels of hepatic multidrug resistance-associated protein homologs 3 and 4 (Mrp3/4), hepatic multidrug resistance protein 2 (Mdr2), and the bile salt export pump (BSEP). In addition, both L. reuteri and L. plantarum reduced LD-associated gut microbiota dysbiosis. L. reuteri increased the relative abundance of Muribaculaceae, while L. plantarum increased that of Akkermansia. The changed gut microbiota was significantly negatively correlated with the incidence of cholesterol gallstones and the FXR-antagonistic BAs in the liver and serum and with the FXR signaling pathways. Furthermore, the protective effects of the two strains were abolished by both global and intestine-specific FXR antagonists. These findings suggest that Lactobacillus might relieve CGS through the FXR signaling pathways. IMPORTANCE Cholesterol gallstone (CGS) disease is prevalent worldwide. None of the medical options for prevention and treatment of CGS disease are recommended, and surgical management has a high rate of recurrence. It has been reported that the factors involved in metabolic syndrome are highly connected with CGS formation. While remodeling of dysbiosis of the gut microbiome during improvement of metabolic syndrome has been well studied, less is known about prevention of CGS formation after regulating the gut microbiome. We used the lithogenic diet (LD) to induce an experimental CGS model in C57BL/6J mice to investigate protection against CGS formation by Limosilactobacillus reuteri strain CGMCC 17942 and Lactiplantibacillus plantarum strain CGMCC 14407. We found that these L. reuteri and L. plantarum strains altered the bile acid composition in mice and improved the dysbiosis of the gut microbiome. These two Lactobacillus strains prevented CGS formation by fully activating the hepatic and ileal FXR signaling pathways. They could be a promising therapeutic strategy for treating CGS or preventing its recurrence.

Gypenosides Prevent and Dissolve Cholesterol Gallstones by Modulating the Homeostasis of Cholesterol and Bile Acids.

Gypenosides (GPs), obtained from Gynostemma pentaphyllum (Thunb.) Makino, have been traditionally prescribed to treat metabolic disorders in Asians. This study assessed whether GPs could prevent lithogenic diet (LD)-induced cholesterol gallstone (CG) formation and enhance CG dissolution in mice. Gallstone-susceptible C57BL/6J mice were fed an LD or normal chow, with or without GPs. Bile acids (BAs) in gallbladder bile were analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed hepatic genes were identified by RNA sequencing, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. GPs were found to prevent LD-induced CG formation and to dissolve pre-existing LD-induced CGs. GPs reduced total cholesterol levels and increased BA levels in bile, as well as reducing the BA Hydrophobicity Index, ratio of 12α-hydroxylated (12α-OH) to non-12α-OH BAs, and Cholesterol Saturation Index in gallbladder bile. GO and KEGG pathway enrichment analyses indicated that GPs-induced genes were involved in BA biosynthesis and cholesterol metabolism. GPs increased the hepatic expression of genes encoding the cytochrome P450 (Cyp) enzymes Cyp7a1, Cyp7b1, and Cyp8b1, while decreasing the hepatic expression of genes encoding the adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8. GPs may be a promising strategy for preventing and dissolving CGs.

Effect of Early Rehabilitation and Nursing Intervention on the Rehabilitation Prognosis of Elderly Stroke Hemiplegia Patients in the Department of Neurology.

Objective: To explore the influence of rehabilitation outcomes in older patients with stroke hemiplegia from the neurology department by early rehabilitation nursing. Methods: 70 cases of old patients with stroke hemiplegia from 2020/01 to 2021/01 were randomly divided into observation group (35 cases) and control group (35 cases). The control group was nursed by usual care. The observation group was nursed by early rehabilitation nursing. Nursing efficacy was observed. Results: The scores of active demand, resistance, and rehabilitation nursing cooperation degree after the nursing for the observation group were higher than the control group (P < 005). The score of NIHSS after the nursing for the observation group was lower than that for the control group (P < 005). The scores of BI, BBS, and Fugl-Meyer after the nursing for the observation group were higher than those for the control group (P < 005). The total rate of nursing satisfaction for the observation group was higher than the control group (P < 005). Conclusion: Early rehabilitation nursing can improve rehabilitation initiatives, rehabilitation outcomes, and nursing satisfaction in older patients with stroke hemiplegia from the neurology department.

[Discussion on relationship between autophagy and endometriosis based on pathogenesis of "dampness and stasis"].

Endometriosis(EMs) is a stubborn gynecological disease caused by persistent immune-inflammatory effects, and is known as "benign tumor" because of its similar characteristics to malignant tumors. National physician master Professor BAN Xiu-wen believes that the spread of damp-evil is the pathologic foundation for inflammatory response of ectopic endometrium; accumulation of blood stasis is the pathological product of continuous inflammatory attacks, and the combination of dampness and stasis is the main pathogenesis for refractory EMs. Modern researches have shown that immune-inflammatory effect is the key mechanism for development of EMs, and is closely related to cell autophagy, all of which have made it become the hot spots in research of the pathogenesis, diagnosis and treatment of EMs. Therefore, with immune-inflammatory effect as the breakthrough point in this research, and with reference to the related research of autophagy, the correlation between "combination of dampness and stasis" and abnormal autophagy-induced immune inflammatory response in ectopic endometrium was discussed, to provide guidance for the clinical application of traditional Chinese medicine and modern research.

Astragalus Polysaccharides Ameliorate Diet-Induced Gallstone Formation by Modulating Synthesis of Bile Acids and the Gut Microbiota.

Cholesterol gallstone (CG) disease has relationships with several metabolic abnormalities. Astragalus polysaccharides (APS) have been shown to have multiple benefits against metabolic disorders. We attempted to uncover the effect and mechanism of action of APS on diet-induced CG formation in mice. Animals were fed a chow diet or lithogenic diet (LD) with or without APS supplementation. The effect of APS on CG formation was evaluated. The level of individual bile acids (BAs) in gallbladder bile and ileum were measured by liquid chromatography-tandem mass spectrometry. Real-time reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess expression of the genes involved in BA metabolism and the enterohepatic circulation. Cecal contents were collected to characterize microbiota profiles. APS ameliorated LD-induced CG formation in mice. APS reduced the level of total cholesterol, bile acid hydrophobicity index and cholesterol saturation index in gallbladder bile. The protective effect of APS might result from reduced absorption of cholic acid in the intestine and increased hepatic BA synthesis. APS relieved the LD-induced activation of the intestinal farnesoid X receptor and decreased ileal expression of fibroblast growth factor 15. In the liver, expression of cytochrome P450 (Cyp) enzyme Cyp7a1 and Cyp7b1 was increased, whereas expression of adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8 was decreased by APS. APS improved the diversity of the gut microbiota and increased the relative abundance of the Bacteroidetes phylum. APS had demonstratable benefits against CG disease, which might be associated with enhanced BA synthesis and improved gut microbiota. Our results suggest that APS may be a potential strategy for the prevention of CG disease.

Use of Head and Neck Magnetic Resonance Angiography to Explore Neurological Function Recovery and Impact of Rehabilitation Nursing on Patients with Acute Stroke.

OBJECTIVE: To analyze neurological function recovery and the impact of rehabilitation nursing in patients with cerebral stroke after treatment to aid clinical diagnosis and treatment of cerebral stroke. METHODS: The study comprised 140 patients who were hospitalized in the neurology department for magnetic resonance angiography examination. Patients were divided into a treatment group (70 patients) and a control group (70 patients) based on treatment plan. Digital subtraction angiography was regarded as the gold standard diagnostic examination. In patients in both groups, magnetic resonance angiography features of the M1 segment of the middle cerebral artery and diagnostic specificity and sensitivity were recorded. An activities of daily living score was used to assess neurological function of patients before and after rehabilitation. RESULTS: The activities of daily living scores of patients in both groups increased significantly after treatment (P < 0.05); the scores of patients in the treatment group increased more significantly (P < 0.05). The total effective rate was 89% in the treatment group and 60% in the control group. The difference between the 2 groups was statistically significant (P < 0.05). After treatment, the degree of M1 segment stenosis in both groups was better than before treatment, and the number of collateral circulation branches was increased; the improvements in the treatment group were more significant (P < 0.05). CONCLUSIONS: Rehabilitation nursing could greatly improve the stenosis of blood vessels in patients with acute cerebral stroke and promote the establishment of collateral circulation, thereby effectively enhancing the recovery of neurological function and strengthening the ability of patients to perform activities of daily living.

Integrated management to reduce fistula-related long-term complications and improve the quality of life after arteriovenous fistula surgery: A retrospective cohort study.

AIM: Proper arteriovenous fistula (AVF) management is crucial to avoid AVF complications and prolong its useful life for maintenance haemodialysis (MHD). DESIGN: Retrospective cohort study. METHODS: Patients on MHD who underwent AVF surgery at the Wuhan Third Hospital between January 2018 and July 2018. RESULTS: A total of 144 patients were included, with 56 in the integrated group and 88 in the routine group. There were no differences between the two groups in terms of sex (p = .61), age (p = .62) and type of primary kidney disease (p > .99). At 1 year, the integrated group had significantly fewer fistula-related complications than the routine group (3.6% versus. 23.9%, p < .001). AVF functional scores were lower in the integrated group compared with the routine group (0.1 ± 0.5 versus. 0.8 ± 0.8, p < .001). The pain scores were lower in the integrated group than in the routine group (1.2 ± 0.4 versus. 1.8 ± 0.9, p < .001).

Adiponectin Inhibits NLRP3 Inflammasome Activation in Nonalcoholic Steatohepatitis via AMPK-JNK/ErK1/2-NFκB/ROS Signaling Pathways.

Adiponectin, an adipose-derived adipokine, possesses a hepatoprotective role in various liver disorders. It has been reported that hypoadiponectinemia can affect with the progression of non-alcoholic fatty liver diseases (NAFLD). Inflammasome activation has been recognized to play a major role during the progression of NAFLD. This research aimed to explore the effect of adiponectin on palmitate (PA)-mediated NLRP3 inflammasome activation and its potential molecular mechanisms. Male adiponectin-knockout (adiponectin-KO) mice and C57BL/6 (wild-type) mice were fed a high-fat-diet (HFD) for 12 weeks as an in vivo model of non-alcoholic steatohepatitis (NASH). Serum biochemical markers, liver histology and inflammasome-related gene and protein expression were determined. In addition, the hepatocytes isolated from wide type mice were exposed to PA in the absence or presence of adiponectin and/or AMPK inhibitor. The activation of NLRP3 inflammasome was assessed by mRNA and protein expression. Furthermore, ROS production and related signaling pathways were also evaluated. In the in vivo experiments, excessive hepatic steatosis with increased NLRP3 inflammasome and its complex expression were found in adiponectin-KO mice compared to wild-type mice. Moreover, the expression levels of NLRP3 inflammasome pathway molecules (NFκB and ROS) were upregulated, while the phosphorylation levels of AMPK, JNK, and Erk1/2 were downregulated in adiponectin-KO mice compared with wild-type mice. In the in vitro study, PA increased lipid droplet deposition, NF-kB signaling and ROS production. Additionally, PA significantly promoted NLRP3 inflammasome activation and complex gene and protein expression in hepatocytes. Adiponectin could abolish PA-mediated inflammasome activation and decrease ROS production, which was reversed by AMPK inhibitor (compound C). Furthermore, the results showed that the inhibitory effect of adiponectin on PA-mediated inflammasome activation was regulated by AMPK-JNK/ErK1/2-NFκB/ROS signaling pathway. Adiponectin inhibited PA-mediated NLRP3 inflammasome activation in hepatocytes. Adiponectin analogs or AMPK agonists could serve as a potential novel agent for preventing or delaying the progression of NASH and NAFLD.

Evolution of Plant Architecture in Oryza Driven by the PROG1 Locus.

The genetic control of plant architecture in crops is critical for agriculture and understanding morphological evolution. This study showed that an open reading frame (ORF) of the rice domestication gene PROG1 appeared 3.4-3.9 million years ago (Mya). Subsequently, it acquired a novel protein-coding gene function in the genome of O. rufipogon (~0.3-0.4 Mya). This extremely young gene and its paralogous C2H2 genes located nearby define the prostrate architecture of O. rufipogon and, thus, are of adaptive significance for wild rice in swamp and water areas. However, selection for dense planting and high yield during rice domestication silenced the PROG1 gene and caused the loss of the RPAD locus containing functional C2H2 paralogs; hence, domesticated lines exhibit an erect plant architecture. Analysis of the stepwise origination process of PROG1 and its evolutionary genetics revealed that this zinc-finger coding gene may have rapidly evolved under positive selection and promoted the transition from non- or semi-prostrate growth to prostrate growth. A transgenic assay showed that PROG1 from O. rufipogon exerts a stronger function compared with PROG1 sequences from other Oryza species. However, the analysis of the expression levels of PROG1 in different Oryza species suggests that the transcriptional regulation of PROG1 has played an important role in its evolution. This study provides the first strong case showing how a fundamental morphological trait evolved in Oryza species driven by a gene locus.

High serum uric acid is associated with increased arterial stiffness in hypertension.

Serum uric acid level has been found to be associated with cerebrovascular diseases. However, whether serum uric acid level is a risk factor for arterial stiffness in the hypertension population is unclear. This study was designed to determine the relationship between serum uric acid level and arterial stiffness in the hypertension population. A total of 10450 participants were evaluated for the risk of arterial stiffness. Brachial-ankle pulse wave velocity (baPWV) was assessed, and high baPWV was determined as the highest quartile of baPWV values in a sex-specific manner. We evaluated the association between serum uric acid level and baPWV through multivariate-adjusted linear and logistic regression analyses. There was a significant difference on high baPWV between patients with quartiles of serum uric acid level in females and males (p<0.01), respectively. The odds ratios (95% CI) of the highest baPWV quartile across the sex-specific serum uric acid level were 1.0, 1.71 (1.35, 2.17), 1.75 (1.38, 2.23), and 1.95 (1.51, 2.51) in female, and 1.0, 1.33 (1.09, 1.64), 1.36 (1.11, 1.67), and 1.67 (1.36, 2.04) in male after adjusting for potential confounders. In conclusion, serum uric acid level could be considered as an important risk factor for arterial stiffness in Chinese hypertension population.