Automated detection of small bowel lesions based on capsule endoscopy using deep learning algorithm.

BACKGROUND: In order to overcome the challenges of lesion detection in capsule endoscopy (CE), we improved the YOLOv5-based deep learning algorithm and established the CE-YOLOv5 algorithm to identify small bowel lesions captured by CE. METHODS: A total of 124,678 typical abnormal images from 1,452 patients were enrolled to train the CE-YOLOv5 model. Then 298 patients with suspected small bowel lesions detected by CE were prospectively enrolled in the testing phase of the study. Small bowel images and videos from the above 298 patients were interpreted by the experts, non-experts and CE-YOLOv5, respectively. RESULTS: The sensitivity of CE-YOLOv5 in diagnosing vascular lesions, ulcerated/erosive lesions, protruding lesions, parasite, diverticulum, active bleeding and villous lesions based on CE videos was 91.9 %, 92.2 %, 91.4 %, 93.1 %, 93.3 %, 95.1 %, and 100 % respectively. Furthermore, CE-YOLOv5 achieved specificity and accuracy of more than 90 % for all lesions. Compared with experts, the CE-YOLOv5 showed comparable overall sensitivity, specificity and accuracy (all P > 0.05). Compared with non-experts, the CE-YOLOv5 showed significantly higher overall sensitivity (P < 0.0001) and overall accuracy (P < 0.0001), and a moderately higher overall specificity (P = 0.0351). Furthermore, the time for AI-reading (5.62 ± 2.81 min) was significantly shorter than that for the other two groups (both P < 0.0001). CONCLUSIONS: CE-YOLOv5 diagnosed small bowel lesions in CE videos with high sensitivity, specificity and accuracy, providing a reliable approach for automated lesion detection in real-world clinical practice.

Reprogramming Photoresponsive Liquid Crystalline Elastomer via Force-Directed Evaporation.

Incorporating photothermal agents into thermoresponsive liquid crystalline elastomers (LCEs) offers remote and spatio-temporal control in actuation. Typically, both the light responsiveness and actuation behaviors are fixed since the agent doping and mesogen alignment are conducted before network formation. Here, we report an approach that enables programming photoresponsive LCEs after synthesis via force-directed evaporation. Different photothermal agents can be doped or removed by swelling the fully cross-linked LCEs in a specific solution, achieving the introduction and erasing of the photoresponsiveness. Moreover, the network swelling deletes the registered alignment, which allows for redefining the molecular order via re-evaporating the solvent with force imposed. This "one stone, two birds" strategy paves the way to simultaneously program/reprogram the actuation mode and responsiveness of LCEs, even in a spatio-selective manner to achieve complex actuations. Our approach is expandable to three-dimensional (3D) printed LCEs to access geometrically sophisticated shape-changing.

Secondary metabolites from the Actinomadura sp. and their cytotoxic activity.

Actinomadura sp., which is usually found in muddy habitats, produces various secondary metabolites with biological activities. In this study, five new compounds named formosensin A (1), formosensin B (2), oxanthroquinone-3-O-α-d-mannose (8), oxanthromicin A (9), and oxanthromicin B (10) were isolated from the culture of Actinomadura sp. together with five known compounds (3-7). Their structures were elucidated by extensive spectroscopic methods including NMR and MS. In particular, the absolute configurations of compounds 1 and 2 were determined using computational methods. Moreover, compounds 1-2 and 8-10 were screened for cytotoxic activity using a panel of human tumor cell lines. Compound 9 induced significant cytotoxicity in five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480) with IC50 values of 8.7, 17.5, 15.0, 17.8, and 14.6 µM, respectively. These findings suggested that compound 9 could provide therapeutic benefits in the treatment of tumor-related diseases.

Antibiotic resistance of Helicobacter pylori in Chinese children: A multicenter study from 2016 to 2023.

BACKGROUND: To investigate the antibiotic resistance of Helicobacter pylori (H. pylori) strains to clarithromycin, metronidazole, amoxicillin, levofloxacin, furazolidone, and tetracycline in Chinese children. MATERIALS AND METHODS: This multicenter, retrospective study was conducted from January 2016 through May 2023. Gastric mucosa biopsies were obtained from pediatric participants who underwent upper gastrointestinal endoscopy at 96 hospitals in northern, southwestern, and southeastern China. The susceptibility of H. pylori to six commonly used antibiotics was determined by agar dilution method. RESULTS: Among the 3074 H. pylori isolates, 36.7% were resistant to clarithromycin, 77.3% to metronidazole, 16.6% to levofloxacin, and 0.3% to amoxicillin. No strains were detected to be resistant to furazolidone or tetracycline. During the 8-year study period, resistance to clarithromycin and metronidazole showed a significant upward trend, while the resistance pattern of the other antibiotics demonstrated a slight but nonsignificant fluctuation. Significant regional differences were found in the distribution of clarithromycin resistance among the northern (66.0%), southwestern (48.2%), and southeastern (34.6%) regions. The metronidazole resistance rate was significantly lower in the southeastern coastal region (76.3%) than in the other two regions (88.2% in the north and 87.7% in the southwest). Multi-drug resistance for two or more antibiotics was detected in 36.3% of the H. pylori strains, and the predominant multi-resistance pattern was the dual resistance to clarithromycin and metronidazole. CONCLUSIONS: The prevalence of H. pylori resistance to clarithromycin and metronidazole is rather high in Chinese children and has been increasing over time. A relatively high resistance rate to levofloxacin was also noticed in children, while almost all strains were susceptible to amoxicillin, furazolidone, and tetracycline. It will be of great clinical significance to continuously monitor the antibiotic-resistance patterns of H. pylori in the pediatric population.

Inhibiting Hepatocyte Uric Acid Synthesis and Reabsorption Ameliorates Acetaminophen-Induced Acute Liver Injury in Mice.

BACKGROUND & AIMS: Acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury worldwide. Uric acid (UA) is involved in sterile inflammation in many organs, but its role in APAP-induced liver injury remains elusive. METHODS: We quantified the concentration of UA in the serum and liver tissues of APAP-overdosed mice and explored the changes in proteins involved in UA synthesis, absorption, and degeneration on APAP stimulation. We also examined the effects of inhibiting hepatocyte UA synthesis or reabsorption on APAP-induced liver injury in mice. Furthermore, we explored the process of UA clearance by peripheral macrophages. RESULTS: APAP overdose significantly increased intrahepatic UA contents, which occurred earlier than apparent hepatocyte injury in APAP-overdosed mice. APAP overdose induced significant DNA leakage and may thereby increase the substrate of UA synthesis. APAP overdose also significantly increased the enzymatic activity of xanthine oxidase and urate oxidase and decreased the expression of the UA reabsorption transporter GLUT9 in hepatocytes. Inhibiting hepatocyte UA synthesis by febuxostat or reabsorption by hepatic-specific knockout of GLUT9 alleviated APAP-induced liver injury. Further experiments showed that monosodium urate but not soluble UA may be a major form of UA mediating hepatocyte injury. Additionally, monosodium urate further recruited circulating macrophages into the liver and then aggravated inflammation by increasing the levels of inflammatory factors and reactive oxygen species. Deletion of macrophages significantly ameliorated APAP-induced liver injury in mice. CONCLUSIONS: APAP overdose induces excessive UA production and leads to local high concentrations in the liver, which further injures cells and induces liver inflammation. Inhibiting the production of UA may be a potential therapeutic option for treating APAP-induced liver injury.

A simpler definition of MAFLD precisely predicts incident metabolic diseases: a 7-year cohort study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel definition proposed in 2020 with a relatively complex set of criteria. Thus, simplified criteria that are more applicable are required. This study aimed to develop a simplified set of criteria for identifying MAFLD and predicting MAFLD-related metabolic diseases. METHODS: We developed a simplified set of metabolic syndrome-based criteria for MAFLD, and compared the performance of the simplified criteria with that of the original criteria in predicting MAFLD-related metabolic diseases in a 7-year follow-up. RESULTS: In the 7-year cohort, a total of 13,786 participants, including 3372 (24.5%) with fatty liver, were enrolled at baseline. Of the 3372 participants with fatty liver, 3199 (94.7%) met the MAFLD-original criteria, 2733 (81.0%) met the simplified criteria, and 164 (4.9%) were metabolic healthy and met neither of the criteria. During 13,612 person-years of follow-up, 431 (16.0%) fatty liver individuals newly developed T2DM, with an incidence rate of 31.7 per 1000 person-years. Participants who met the simplified criteria had a higher risk of incident T2DM than those who met the original criteria. Similar results were observed for incident hypertension, and incident carotid atherosclerotic plaque. CONCLUSION: The MAFLD-simplified criteria are an optimized risk stratification tool for predicting metabolic diseases in fatty liver individuals.

Olfactomedin-4 deletion exacerbates DSS-induced colitis through a matrix metalloproteinase-9-dependent mechanism.

Background and Aims: Olfactomedin-4 is a glycoprotein that is upregulated in inflamed gastrointestinal tissues. This study aimed to investigate the role and underlying mechanisms of olfactomedin-4 in ulcerative colitis. Methods: C57BL/6 mice and olfactomedin-4 knockout mice were fed dextran sulfate sodium in drinking water to establish a colitis model. An in vitro inflammation model was constructed in HCT116 and NCM460 cells stimulated with lipopolysaccharide. The expression of olfactomedin-4 was detected by Western blotting, immunohistochemistry staining, and qRT‒PCR. The differences in the severity of colitis between olfactomedin-4 knockout mice and wild-type mice were compared, and the underlying mechanisms were explored. Results: Olfactomedin-4 expression was significantly upregulated in colonic tissues of active ulcerative colitis patients and in cellular and mouse models of colitis. Compared with wild-type littermates, olfactomedin-4 knockout mice were more susceptible to dextran sulfate sodium-induced colitis and produced higher levels of proinflammatory cytokines and chemokines. In addition, olfactomedin-4 deficiency significantly promoted intestinal epithelial cell apoptosis and increased intestinal permeability, which was mediated by the p53 pathway. Moreover, olfactomedin-4 directly interacted with and negatively regulated matrix metalloproteinase-9. Inhibiting matrix metalloproteinase-9 significantly decreased colonic p53 expression and ameliorated experimental colitis in olfactomedin-4 knockout mice, while overexpression of matrix metalloproteinase-9 aggravated colitis. Further experiments showed that matrix metalloproteinase-9 regulated p53 through the Notch1 signaling pathway to promote ulcerative colitis progression. Conclusions: Olfactomedin-4 is significantly upregulated in ulcerative colitis and may protect against colitis by directly inhibiting matrix metalloproteinase-9 and further decreasing p53-mediated apoptosis via Notch1 signaling.

Polyethylene glycol combined with lactulose has better efficacy than polyethylene glycol alone in bowel preparation before colonoscopy: A meta-analysis.

BACKGROUND: The accuracy of diagnosis and the safety of treatment in colonoscopy depends largely on the quality of bowel cleansing. This study aimed to compare the efficacy and adverse reactions of Polyethylene Glycol (PEG) combined with lactulose with that of PEG alone in bowel preparation before colonoscopy. METHODS: The authors searched a number of databases including EMBASE, MEDLINE, Cochrane Library, and China Academic Journals Full-text Database. The authors screened according to literature inclusion and exclusion criteria, assessed the quality of the included literature, and extracted the data. The meta-analysis of included literature used RevMan 5.3 and Stata 14.0 software. RESULTS: A total of 18 studies, including 2274 patients, were enrolled. The meta-analysis showed that PEG combined with lactulose had a better efficacy (OR = 3.87, 95% CI 3.07‒4.87, p = 0.000, and I2 = 36.2% in the efficiency group; WMD = 0.86, 95% CI 0.69‒1.03, p = 0.032 and I2 = 0% in the BBPS score group) in bowel preparation for patients with or without constipation. Moreover, PEG combined with lactulose had fewer adverse reactions, including abdominal pain (OR = 1.42, 95% CI 0.94‒2.14, p = 0.094), nausea (OR = 1.60, 95% CI 1.13‒2.28, p = 0.009) and vomiting (OR = 1.77, 95% CI 1.14‒2.74, p = 0.011), than PEG alone. No significant reduction in the incidence of abdominal distention was observed. CONCLUSION: PEG combined with lactulose may be a better choice for bowel preparation before colonoscopy compared with PEG alone.

LECT2 modulates dendritic cell function after Helicobacter pylori infection via the CD209a receptor.

BACKGROUND: Helicobacter pylori, a gram-negative bacterium persisting on the gastric mucosa, is involved in the pathogenesis of a variety of gastric diseases. Leukocyte cell-derived chemotaxin 2 (LECT2) treatment increased the phagocytic capacity of lymphocytes and improved immune function in bacterial infection. Whether the immune cells infected with H. pylori are affected by LECT2 is unclear. METHODS: Bone marrow-derived dendritic cells (BMDCs) from wild-type C57BL/6 mice, CD209a knockout mice, or LECT2 knockout mice were exposed to H. pylori at a multiplicity of infection of 10 for 24 h. The maturity of DCs and the cytokines secreted by DCs were analyzed by flow cytometry, western blot, and real-time PCR. The signaling pathway underlying CD209a activation after LECT2 treatment were also detected. RESULTS: LECT2 treatment promoted H. pylori-induced BMDC maturation and produced a high level of anti-inflammatory cytokine (IL-10) but a low level of pro-inflammatory cytokine (IL-23p40). Moreover, LECT2-pretreated DCs shifted the development of pro-inflammatory Th1/Th17 cells to Treg cells. CD209a mediated LECT2-induced maturation and secretion of DC in H. pylori-primed BMDCs. LECT2 was further confirmed to induce the secretion of certain cytokines via CD209a-JNK/P38 MAPK pathway. CONCLUSION: This study reveals that LECT2 modulated the functions of H. pylori-primed DCs in a CD209a-dependent manner, which might hinder the clearance of H. pylori and contribute to its colonization.

Association between ultra-processed foods consumption and risk of non-alcoholic fatty liver disease: a population-based analysis of NHANES 2011-2018.

An increasing number of studies have evaluated the association between ultra-processed foods (UPF) consumption and metabolic disorders. However, the association between UPF intake and non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, we analysed data from 6545 participants who were recruited in National Health and Nutrition Examination Surveys 2011-2018. UPF were defined in light of the NOVA food classification system and divided into quartiles based on its proportion of total weight intake. Complex logistic regression models were used to assess the association between UPF and NAFLD. Mediation analyses were conducted to reveal underlying mediators. We found that NAFLD patients consumed more UPF than controls (925·92 ± 18·08 v. 812·70 ± 14·32 g/d, P < 0·001). Dietary intake of UPF (% weight) was negatively related to the Healthy Eating Index-2015 score (Spearman r = -0·32, P < 0·001). In the multivariable model, the highest quartile compared with the lowest, the OR (95 % CI) were 1·83 (1·33, 2·53) for NAFLD (OR per 10 % increment: 1·15; 95 % CI: 1·09, 1·22; P for trend < 0·001) and 1·52 (1·12, 2·07) for insulin resistance (OR per 10 % increment: 1·11; 95 % CI: 1·05, 1·18; P for trend = 0·002). Mediation analyses revealed that poor diet quality, high saturated fat and refined grain intake partly mediated the association between UPF and NAFLD. In conclusion, high UPF intake was associated with an increased risk of NAFLD in US adults. Further prospective studies are needed to verify these findings.

Polyethylene glycol combined with lactulose has better efficacy than polyethylene glycol alone in bowel preparation before colonoscopy: A meta-analysis

Abstract Background: The accuracy of diagnosis and the safety of treatment in colonoscopy depends largely on the quality of bowel cleansing. This study aimed to compare the efficacy and adverse reactions of Polyethylene Glycol (PEG) combined with lactulose with that of PEG alone in bowel preparation before colonoscopy. Methods: The authors searched a number of databases including EMBASE, MEDLINE, Cochrane Library, and China Academic Journals Full-text Database. The authors screened according to literature inclusion and exclusion criteria, assessed the quality of the included literature, and extracted the data. The meta-analysis of included literature used RevMan 5.3 and Stata 14.0 software. Results: A total of 18 studies, including 2274 patients, were enrolled. The meta-analysis showed that PEG combined with lactulose had a better efficacy (OR = 3.87, 95% CI 3.07‒4.87, p = 0.000, and I2 = 36.2% in the efficiency group; WMD = 0.86, 95% CI 0.69‒1.03, p = 0.032 and I2 = 0% in the BBPS score group) in bowel preparation for patients with or without constipation. Moreover, PEG combined with lactulose had fewer adverse reactions, including abdominal pain (OR = 1.42, 95% CI 0.94‒2.14, p = 0.094), nausea (OR = 1.60, 95% CI 1.13‒2.28, p = 0.009) and vomiting (OR = 1.77, 95% CI 1.14‒2.74, p = 0.011), than PEG alone. No significant reduction in the incidence of abdominal distention was observed. Conclusion: PEG combined with lactulose may be a better choice for bowel preparation before colonoscopy compared with PEG alone.

Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study.

Background and aim: Previous observational studies have suggested a paradoxical relationship between iron status and the risk of non-alcoholic fatty liver disease (NAFLD). Observed associations in these epidemiological studies fail to show sequential temporality and suffer from problems of confounding. Therefore, we performed a bidirectional two-sample Mendelian randomization (MR) to evaluate the relationship between serum iron status and NAFLD. Methods: The inverse weighted method (IVW) meta-analysis with the fixed-effect model was the main method to estimate the relationship between iron status, including serum ferritin, iron, transferrin saturation (TSAT) and total iron-binding capacity (TIBC), and NAFLD. Weighted median, penalized weighted median, and MR Robust Adjusted Profile Score (MR RAPS) methods were used as additional analyses. Sensitivity analyses were performed with Cochran's Q test, MR-Egger regression, Steiger filtering, and the MR PRESSO test. Results: Iron status, including serum ferritin, iron, and TSAT, was associated with an increased risk of NAFLD (odds ratio (OR) (95% confidence interval (CI)): 1.25 (1.06, 1.48); 1.24 (1.05, 1.46), 1.16 (1.02, 1.31), respectively). In contrast, minimal effects of NAFLD on serum ferritin, iron, TSAT, and TIBC were observed (OR (95% CI): 1.01 (1.00, 1.02), 1.01 (1.00, 1.02), 1.03 (1.01, 1.05), 1.03 (1.01, 1.05), respectively). Conclusions: Our findings corroborated the causal associations between serum ferritin, iron, TSAT, and NAFLD, which might suggest the potential benefits of iron-related therapy. In addition, NAFLD might, in turn, slightly affect iron homeostasis indicated as serum ferritin, iron, TSAT, and TIBC, but this needs to be further confirmed.

Application of a WeChat-based mini-app as a patient reminder in Helicobacter pylori eradication: a prospective multi-center randomized controlled study.

BACKGROUND: To improve the eradication rate of H. pylori, researchers have investigated the role of WeChat-based mini-app as an electronic reminding system in H. pylori treatment. METHODS: Subjects from three medical centers were divided into two groups. Patients in the daily mini-app-based notification system group received daily notifications via the WeChat mini-app. Patients in the control group received one-time verbal education on the first clinical visit. Both groups received a 14-day quadruple therapy to eradicate H. pylori infection. Eradication rate, compliance, adverse events and satisfaction were evaluated. RESULTS: Both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted. The eradication rate in the daily mini-app-based notification system group was slightly higher compared with the control group (ITT analysis: 76.70% vs. 70.73%, p = 0.312; PP analysis: 85.87% vs. 82.86%, p = 0.562). The compliance was significantly higher in the daily mini-app-based notification system group (ITT analysis: 85.52% vs. 70.48%, p = 0.028; PP analysis: 92.39% vs. 81.90%, p = 0.030). The adverse event rates were similar between the two groups (PP analysis: 36.96% vs. 40.95%, p = 0.566). No significant difference in eradication rate was seen in each subgroup analysis by age, place of residence, grade of education, or endoscopic findings. CONCLUSION: The study showed that daily mini-app-based notification improved patient compliance but not H. pylori eradication rate. Trial registration The research was registered in the Chinese Clinical Trial Registry (ChiCTR2000031011, 21/03/2020).

MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT.

BACKGROUND & AIMS: Excessive inflammatory responses and oxidative stress are considered the main characteristics of inflammatory bowel disease (IBD). Endogenous hydrogen sulfide (H2S) has been reported to show anti-inflammatory activity in IBD. The main aim of this study was to explore the role of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous H2S biosynthesis, in IBD. METHODS: Colonic MPST expression was evaluated in mice and patients with IBD. Various approaches were used to explore the concrete mechanism underlying MPST regulation of the progression of colitis through in vivo and in vitro models. RESULTS: MPST expression was markedly decreased in colonic samples from patients with ulcerative colitis (UC) or Crohn's disease (CD) and from mice treated with DSS. MPST deficiency significantly aggravated the symptoms of murine colitis, exacerbated inflammatory responses and apoptosis, and inhibited epithelium stem cell-derived organoid formation in an H2S-independent manner. Consistently, when HT29 cells were treated with TNF-α, inhibition of MPST significantly increased the expression of proinflammatory cytokines, the amount of ROS and the prevalence of apoptosis, whereas overexpression of MPST markedly improved these effects. RNA-seq analysis showed that MPST might play a role in regulating apoptosis through AKT signaling. Mechanistically, MPST directly interacted with AKT and reduced the phosphorylation of AKT. Additionally, MPST expression was positively correlated with AKT expression in human IBD samples. In addition, overexpression of AKT rescued IEC apoptosis caused by MPST deficiency, while inhibition of AKT significantly aggravated it. CONCLUSIONS: MPST protects the intestines from inflammation most likely by regulating the AKT/apoptosis axis in IECs. Our results may provide a novel therapeutic strategy for the treatment of colitis.

Optical Bistability in a Tunable Gourd-Shaped Silicon Ring Resonator.

In this study, a tunable gourd-shaped ring resonator is demonstrated to generate optical bistability. The system consists of two sub-rings for a gourd shape configuration with a U-shaped wave guiding pathway. The transfer matrix method and FDTD simulation are used to acquire the spectral characteristics of the system. For the fabricated device, the spectra profile and extinction ratio can be effectively tuned by the microheater above the U-shaped waveguide, which matches with the theoretical results. Due to the gourd structure of the resonator, the light waves in two rings can be cross-coupled with each other, and the optical bistability could come out effectively with the change in the input optical power around 6 mW. The presented optical bistability devices have great application potential in optical information processing such as optical storage, switch and logic operation.

The efficacy of vitamin D supplementation for irritable bowel syndrome: a systematic review with meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder involving gut-brain interactions with limited effective treatment options. Vitamin D deficiency is commonly observed in patients with IBS, but whether vitamin D supplementation ameliorates IBS is controversial in randomized controlled trials. The present systematic review and meta-analysis explored the efficacy of vitamin D supplementation in patients with IBS. METHODS: We performed a systematic search of potentially relevant publications from PubMed, EMBASE, the Cochrane Central Register of Controlled Studies and the Web of Science up until January 2022. We assessed the weighted mean difference (WMD) and 95% confidence interval (95% CI) of the IBS severity scoring system (IBS-SSS), IBS quality of life (IBS-QoL) and IBS total score (IBS-TS) before and after vitamin D supplementation intervention. RESULTS: We included four randomized, placebo-controlled trials involving 335 participants. The differences in IBS-SSS score between participants in the intervention group and the placebo group increased after intervention (WMD: -55.55, 95% CI: -70.22 to -40.87, I2 = 53.7%, after intervention; WMD: -3.17, 95% CI: -18.15 to 11.81, I2 = 0.0%, before intervention). Participants receiving vitamin D supplementation showed greater improvement in IBS-SSS after intervention than participants receiving placebo treatment (WMD: -84.21, 95% CI: -111.38 to -57.05, I2 = 73.2%; WMD: -28.29, 95% CI: -49.95 to -6.62, I2 = 46.6%, respectively). Vitamin D supplementation was also superior to placebo in IBS-QoL improvement (WMD: 14.98, 95% CI: 12.06 to 17.90, I2 = 0.0%; WMD: 6.55, 95% CI: -2.23 to 15.33, I2 = 82.7%, respectively). Sensitivity analyses revealed an unstable pooled effect on IBS-TS in participants receiving vitamin D supplementation. Therefore, we did not evaluate the efficacy of vitamin D intervention in IBS-TS. CONCLUSIONS: This systematic review and meta-analysis suggested that vitamin D supplementation was superior to placebo for IBS treatment.

Remnant Cholesterol Predicts Long-term Mortality of Patients With Metabolic Dysfunction-associated Fatty Liver Disease.

CONTEXT: Elevated serum remnant cholesterol independently predicts risks of cardiovascular diseases. However, the association between remnant cholesterol and metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. OBJECTIVE: This study aimed to explore the association of remnant cholesterol with MAFLD and its long-term mortality. METHODS: We extracted data from the NHANES III, 1988 to1994 and the linked mortality data until December 31, 2015. The association between remnant cholesterol and MAFLD was analyzed by multivariable logistic regression. Cox proportional hazards regression was performed to assess whether elevated remnant cholesterol increased all-cause and cause-specific mortalities in MAFLD patients. RESULTS: At baseline, 28.6% (1474/5156) of participants had MAFLD. In multivariable logistic regression, the fourth quartile of remnant cholesterol was associated with an increased risk of MAFLD compared with the first quartile (odds ratio [OR]: 1.714; 95% CI, 1.586-1.971; P < .001). In participants with normal levels of triglycerides, low-density lipoprotein and high-density lipoprotein cholesterol, the relationship between remnant cholesterol and MAFLD risk remained significant (OR: 1.346; 95% CI, 1.248-1.761; P < .001). During a median follow-up of 307 months, MAFLD patients with serum remnant cholesterol in the fourth quartile were associated with a higher risk of all-cause mortality (hazard ratio [HR]: 2.183; 95% CI, 1.825-2.407; P < .001), as well as a higher risk of cardiovascular mortality (HR: 2.346; 95% CI, 2.046-2.885; P < .001) and cancer-related mortality (HR: 2.366; 95% CI, 1.864-2.932; P < .001) compared with MAFLD patients in the first quartile. CONCLUSION: Remnant cholesterol was independently associated with the risk of MAFLD and predicted all-cause, cardiovascular, and cancer-related mortalities in MAFLD patients.

The DEAD-box helicase DDX3x ameliorates non-alcoholic fatty liver disease via mTORC1 signalling pathway.

BACKGROUND & AIMS: The DEAD (Asp-Glu-Ala-Asp)-box helicase family member DDX3x has been proven to involve in hepatic lipid disruption during HCV infection. However, the role of DDX3x in non-alcoholic fatty liver disease (NAFLD), in which lipid homeostasis is severely disrupted, remains unclear. Here, we aimed to illustrate the potential role of DDX3x in NAFLD. METHODS: DDX3x protein levels were evaluated in NAFLD patients and NAFLD models via immunohistochemistry or western blotting. In vivo ubiquitin assay was performed to identify the ubiquitination levels of DDX3x in the progression of steatosis. DDX3x protein levels in mice livers were manipulated by adeno-associated virus-containing DDX3x short hairpin RNA or DDX3x overexpression plasmid. Hepatic or serum triglyceride and total cholesterol were evaluated and hepatic steatosis was confirmed by haematoxylin and eosin staining and oil red o staining. Western blotting was performed to identify the underlying mechanisms of DDX3x involving in the progression of NAFLD. RESULTS: DDX3x protein levels were significantly decreased in NAFLD patients and NAFLD models. DDX3x protein might be degraded via ubiquitin-proteasome system in the progression of steatosis. Knockdown of hepatic DDX3x exacerbated HFD-induced hepatic steatosis in mice, while overexpression of hepatic DDX3x alleviated HFD-induced hepatic steatosis in mice. Further explorative experiments revealed that knockdown of DDX3x could lead to the overactivation of mTORC1 signalling pathway which exacerbates NAFLD. CONCLUSIONS: DDX3x involved in the progression of NAFLD via affecting the mTORC1 signalling pathway. DDX3x might be a potential target for NAFLD treatment.

Association between circulating cystatin C and hyperuricemia: a cross-sectional study.

INTRODUCTION/OBJECTIVES: Circulating cystatin C has reportedly been related to cardiovascular disease, diabetes, and metabolic syndrome, apart from its traditional role in estimating the glomerular filtration rate. However, whether circulating cystatin C is related to hyperuricemia remains unclear. METHOD: We included 2406 men and 1273 women who attended their annual health checkups in this study. Anthropometric and biochemical parameters were measured. Hyperuricemia was diagnosed as fasting serum uric acid > 420 µmol/L in men and women. RESULTS: A total of 695 (18.9%) participants were diagnosed with hyperuricemia. Hyperuricemic patients had significantly higher serum cystatin C levels than healthy controls (0.91 (0.83-1.02) versus 0.82 (0.72-0.92) mg/L, P < 0.001). Serum cystatin C levels were positively related to the prevalence of hyperuricemia, which was 5.18%, 14.76%, 22.66%, and 31.24% in participants with serum cystatin C levels in the first, second, third, and fourth quartiles, respectively (P < 0.001 for trend). In stepwise multivariate logistic regression analysis, participants with serum cystatin C in the fourth quartile had a more than twofold increased risk of hyperuricemia (OR 2.262, 95% CI 1.495-3.422; P < 0.001) compared with those with serum cystatin C in the first quartile. In subgroup analyses, the fourth quartile of cystatin C was related to increased risks of hyperuricemia in both non-obese and obese participants (OR 4.405, 95% CI 1.472-13.184, P = 0.008; OR 1.891, 95% CI 1.228-2.911, P = 0.004, respectively), in non-metabolic syndrome participants (OR 3.043, 95% CI 1.692-5.473; P < 0.001) but not in metabolic syndrome participants (OR 1.689, 95% CI 0.937-3.045; P = 0.081), and in non-non-alcoholic fatty liver disease (non-NAFLD) (OR 2.128, 95% CI 1.424-3.180; P < 0.001, respectively) and young and middle-aged participants (OR 2.235, 95% CI 1.492-3.348, P < 0.001) but not in NAFLD and elderly participants. CONCLUSIONS: This study revealed a positive association of circulating cystatin C with hyperuricemia. Key Points • Serum cystatin C is associated with an increased risk of hyperuricemia. • Serum cystatin C is a useful biomarker in distinguishing patients at high risk of having hyperuricemia.

3-Mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma.

BACKGROUND AND: AIMS: The prognosis of hepatocellular carcinoma (HCC) remains dismal, and its molecular pathogenesis has not been completely defined. The enzyme 3-mercaptopyruvate sulfurtransferase (MPST) regulates endogenous hydrogen sulfide (H2 S) biosynthesis. However, the role of MPST in HCC has never been intensively investigated. METHODS: MPST protein expression was analysed in HCC tumour tissues and matched adjacent tissues. The effect of MPST on HCC progression was studied in vitro and in vivo. RESULTS: The mRNA and protein expression of MPST was significantly downregulated in HCC samples compared with their paired nontumour counterparts. A low MPST expression was associated with larger tumour size and a worse overall survival. Overexpression of MPST in HCC cells inhibited cell proliferation and induced apoptosis. MPST overexpression also significantly suppressed the growth of tumour xenografts in nude mice, whereas silencing MPST by intratumour delivery of siRNA substantially promoted tumour growth. Moreover, diethylnitrosamine-induced mouse HCC was aggravated by MPST gene knockout. Mechanistically, MPST suppressed the cell cycle associated with H2 S production and inhibition of the AKT/FOXO3a/Rb signalling pathway in HCC development. In addition, MPST expression negatively correlated with that of pRb in HCC specimens and the combination of these two parameters is a more powerful predictor of poor prognosis. CONCLUSIONS: MPST may function as a tumour suppressor gene that plays an essential role in HCC proliferation and liver tumorigenesis. It is a candidate predictor of clinical outcome in patients with HCC and may be used as a biomarker and intervention target for new therapeutic strategies.