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Abstract Background We aimed to investigate the post-cessation T2DM risk in male NAFLD and NAFLD-free smokers in a 7-year cohort study. Methods The study population was male adults who underwent annual health checkups in a 7-year cohort study. Recent quitters were categorized into four groups based on their weight gain during follow-up:

Chimeric antigen receptor T (CAR T) cells have shown their potential in hematological malignancies and the treatment of solid tumors, especially in metastases. However, CAR T-cell therapy may carry risks of inducing severe adverse effects, which are recognized as immune-related adverse events. Here, we report two cases of severe colitis presented with refractory bloody diarrhea, which were induced by carcinoembryonic antigen (CEA)-directed CAR T therapy in the treatment of metastatic colorectal adenocarcinoma. These patients were treated as part of a clinical trial. The clinical trial was registered at ClinicalTrials.gov (NCT05396300), submitted, and started on May 25, 2022. Glucocorticoids combined with vedolizumab were used to control their gastrointestinal symptoms but the outcomes were unsatisfactory. This report highlights the potentially serious risks of anti-CEA CAR T therapy and provides management options.

Abstract Background The diagnosis of primary small intestinal lymphoma (PSIL) is difficult. This study aimed to evaluate the clinical, radiological and endoscopic characteristics of PSIL and provide clue for diagnosis. Methods A total of 30 patients diagnosed with PSIL who underwent double balloon endoscopy (DBE) in the First Affiliated Hospital of Zhejiang University were retrospectively analyzed. Clinical, radiological and endoscopic data were collected. Univariate analysis was used to determine significant indicators for differentiating three main subtypes of PSIL. Cox regression analysis was performed to assess the risk factors for survival. Results In this study, 10 patients were pathologically diagnosed as diffuse large B-cell lymphoma (DLBCL), 11 were indolent B-cell lymphoma (BCL) and 9 were T-cell lymphoma (TCL). Compared with DLBCL patients, the body mass index (BMI) of TCL patients was significantly lower (p = 0.004). Meanwhile, compared with patients with DLBCL, the patients with indolent BCL had lower levels of C-reactive protein, lactate dehydrogenase (LDH), fibrinogen and D-Dimer (p = 0.004, p = 0.004, p = 0.006, and p = 0.002, respectively), and lower proportion of thicker intestinal wall and aneurysmal dilation in CT scan (p = 0.003 and p = 0.020, respectively). In terms of ulcer morphology, patients with DLBCL had significantly higher proportion of deep ulcers than patients with indolent BCL (p = 0.020, respectively). Cox regression analysis showed that drink (p = 0.034), concomitant colonic ulcers (p = 0.034) and elevated LDH (p = 0.043) are risk factors for mortality in patients with PSIL. Conclusions This study provides clinical characteristics of patients with PSIL. Thicker intestinal wall and aneurismal dilation detected on CT scan and deeper ulcer on DBE examination helps to establish a diagnosis of DLBCL.

Abstract Background Diagnosis of colorectal cancer (CRC) during early stages can greatly improve patient outcome. Although technical advances in the field of genomics and proteomics have identified a number of candidate biomarkers for non-invasive screening and diagnosis, developing more sensitive and specific methods with improved cost-effectiveness and patient compliance has tremendous potential to help combat the disease. Methods We enrolled three cohorts of 479 subjects, including 226 CRC cases, 197 healthy controls, and 56 advanced precancerous lesions (APC). In the discovery cohort, we used quantitative mass spectrometry to measure the expression profile of plasma proteins and applied machine-learning to select candidate proteins. We then developed a targeted mass spectrometry assay to measure plasma concentrations of seven proteins and a logistic regression classifier to distinguish CRC from healthy subjects. The classifier was further validated using two independent cohorts. Results The seven-protein panel consisted of leucine rich alpha-2-glycoprotein 1 (LRG1), complement C9 (C9), insulin-like growth factor binding protein 2 (IGFBP2), carnosine dipeptidase 1 (CNDP1), inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3), serpin family A member 1 (SERPINA1), and alpha-1-acid glycoprotein 1 (ORM1). The panel classified CRC and healthy subjects with high accuracy, since the area under curve (AUC) of the training and testing cohort reached 0.954 and 0.958. The AUC of the two independent validation cohorts was 0.905 and 0.909. In one validation cohort, the panel had an overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89.9%, 81.8%, 89.2%, and 82.9%, respectively. In another blinded validation cohort, the panel classified CRC from healthy subjects with a sensitivity of 81.5%, specificity of 97.9%, and overall accuracy of 92.0%. Finally, the panel was able to detect APC with a sensitivity of 49%. Conclusions This seven-protein classifier is a clear improvement compared to previously published blood-based protein biomarkers for detecting early-stage CRC, and is of translational potential to develop into a clinically useful assay.

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.

Objective: Some studies have found that cholecystectomy may increase the risk of colorectal cancer (CRC), while others have reached inconsistent conclusions. We thus performed a systematic review and meta-analysis to assess the incidence rate of CRC after cholecystectomy for patients with gallstones or gallbladder diseases, and whether the geographical location of the patients affected the results. Methods: We systematically searched PubMed, Embase, and Cochrane for studies reporting changes in the incidence rate of CRC after cholecystectomy published before January 12, 2023. Our main endpoint was the occurrence of CRC. Data were extracted and pooled, and the relative risk (RR) and 95% confidence interval (CI) were calculated. We assessed pooled data using a random-effects model. Results: In total, 477 articles were identified, and 6 articles were eligible, including 7 studies that included 797,917 participants. Overall, the summarized research results showed that the risk of CRC was reduced in patients with gallbladder diseases who underwent cholecystectomy (RR: 0.80, 95% CI: 0.65 to 0.99, p = 0.040; I2 = 85.0%). In the subgroup analysis based on different geographical locations, cholecystectomy was not associated with the risk of CRC in the Western population (RR: 0.90, 95% CI: 0.65 to 1.25, p = 0.522; I2 = 86.5%), but there was a negative correlation between cholecystectomy and the risk of CRC (RR: 0.66, 95% CI: 0.60 to 0.73, p = 0.000) in the Chinese population. Conclusions: Our findings support that for patients with gallstones or gallbladder diseases, the incidence of CRC after cholecystectomy is lower than that of patients who do not undergo cholecystectomy.

Abstract Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor responsible for mounting an anti-oxidation gene expression program to counter oxidative stress. Under unstressed conditions, Kelch-like ECH-associated protein 1 (KEAP1), an adaptor protein for CUL3 E3 ubiquitin ligase, mediates NRF2 ubiquitination and degradation. We show here that the deubiquitinase USP25 directly binds to KEAP1 and prevents KEAP1’s own ubiquitination and degradation. In the absence of Usp25 or if the DUB is inhibited, KEAP1 is downregulated and NRF2 is stabilized, allowing the cells to respond to oxidative stress more readily. In acetaminophen (APAP) overdose-induced oxidative liver damage in male mice, the inactivation of Usp25, either genetically or pharmacologically, greatly attenuates liver injury and reduces the mortality rates resulted from lethal doses of APAP.

Abstract There are significant risks of adverse events following oesophageal endoscopic submucosal dissection (ESD), such as stricture, delayed bleeding and perforation. Therefore, it is necessary to protect artificial ulcers and promote the healing process. The current study was performed to investigate the protective role of a novel gel against oesophageal ESD-associated wounds. This was a multicentre, randomized, single-blind, controlled trial that recruited participants who underwent oesophageal ESD in four hospitals in China. Participants were randomly assigned to the control or experimental group in a 1:1 ratio and the gel was used after ESD in the latter. Masking of the study group allocations was only attempted for participants. The participants were instructed to report any adverse events on post-ESD days 1, 14, and 30. Moreover, repeat endoscopy was performed at the 2-week follow-up to confirm wound healing. Among the 92 recruited patients, 81 completed the study. In the experimental group, the healing rates were significantly higher than those in the control group (83.89 ± 9.51% vs. 73.28 ± 17.81%, P = 0.0013). Participants reported no severe adverse events during the follow-up period. In conclusion, this novel gel could safely, effectively, and conveniently accelerate wound healing following oesophageal ESD. Therefore, we recommend applying this gel in daily clinical practice.

Abstract 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).

Abstract Background Artificial intelligence (AI) assistance has been considered as a promising way to improve colonoscopic polyp detection, but there are limited prospective studies on real‐time use of AI systems. Methods We conducted a prospective, multicenter, randomized controlled trial of patients undergoing colonoscopy at six centers. Eligible patients were randomly assigned to conventional colonoscopy (control group) or AI‐assisted colonoscopy (AI group). AI assistance was our newly developed AI system for real‐time colonoscopic polyp detection. Primary outcome is polyp detection rate (PDR). Secondary outcomes include polyps per positive patient (PPP), polyps per colonoscopy (PPC), and non‐first polyps per colonoscopy (PPC‐Plus). Results A total of 2352 patients were included in the final analysis. Compared with the control, AI group did not show significant increment in PDR (38.8% vs. 36.2%, p = 0.183), but its PPC‐Plus was significantly higher (0.5 vs. 0.4, p

Abstract Background Trisomy 8 positivity myelodysplastic syndrome with Behçet's disease is rare. Isolated trisomy 8 is a frequent cytogenetic abnormality in the MDS, but the characteristic of trisomy 8 and the association between trisomy 8 positivity myelodysplastic syndrome and Behçet's disease is unclear. Case presentation Here, we reported a 63‐year‐old man, who presented with fever, abdominal pain and hematochezia. Imaging studies revealed bowel wall thickening and mural hyperenhancement of terminal ileum and cecum. Colonoscopy found multiple round ulcers in terminal ileum, ileocecal valve and multiple yellow dotted pseudomembranous attachments throughout the colon. Capsule endoscopy also revealed multiple irregular ulcers in lower ileum. Serum C-reactive protein levels and fecal calprotectin were abnormally high. The clostridium difficile toxin A and B was positive. However, the patient's intestinal ulcers did not resolve after two weeks course of vancomycin. Considered that the patient was diagnosed as MDS-RAEB2 with a karyotype of 47 XX, + 8. And detailed inquiry of medical history revealed epifolliculitis and frequently recurrent oral ulcers 2 months before admission. A diagnosis of trisomy 8 positivity MDS with BD was made. Then he received glucocorticoid along with the 5th course of azacytidine. The follow-up endoscopy showed significantly improved intestinal ulcer 2 months after treatment. we report a rare disease and provide the diagnose and treatment ideas. Conclusions We highlight the challenges and the process of thinking about of the diagnosis. This may provide a new idea for the diagnosis of intestinal ulcers.

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.

Abstract Radiation-induced liver injury (RILI) is a major complication of radiotherapy during treatment for liver cancer and other upper abdominal malignant tumors that has poor pharmacological therapeutic options. A series of pathological changes can be induced by radiation. However, the underlying mechanism of RILI remains unclear. Radiation can induce cell damage via direct energy deposition or reactive free radical generation. Cellular senescence can be observed due to the DNA damage response (DDR) caused by radiation. The senescence-associated secretory phenotype (SASP) secreted from senescent cells can cause chronic inflammation and aggravate liver dysfunction for a long time. Oxidative stress further activates the signaling pathway of the inflammatory response and affects cellular metabolism. miRNAs clearly have differential expression after radiation treatment and take part in RILI development. This review aims to systematically profile the overall mechanism of RILI and the effects of radiation on hepatocyte senescence, laying foundations for the development of new therapies.

Crosstalk between xenobiotic metabolism and energy metabolism in the liver has provided a potential opportunity to target xenobiotic receptors to treat metabolic diseases. Activation of constitutive androstane receptor (CAR), a xenobiotic-sensing nuclear receptor, has been shown to inhibit obesity, suppress hepatic gluconeogenesis, and ameliorate hyperglycemia in rodent models of obesity and type 2 diabetes. However, the underlying molecular mechanism remains to be defined. The growth arrest and DNA damage-inducible gene 45b (Gadd45b), a well-known anti-apoptotic factor, has been shown to be an inducible coactivator of CAR in promoting rapid liver growth. It is unknown whether the effect of CAR on energy metabolism depends on GADD45B. In the present study and by using a high fat diet (HFD)-induced obesity model, we show that reduced body weight gain and improved insulin sensitivity by the CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) were markedly blunted in Gadd45b knockout mice. Mechanistically, the TCPOBOP-responsive inhibition of hepatic lipogenesis, gluconeogenesis, and adipose inflammation observed in wild type mice were largely abolished in Gadd45b knockout mice. We conclude that Gadd45b is required in part for the metabolic benefits of CAR activation.

Abstract Background Previous studies reported that Epstein–Barr virus (EBV) may play a causal role in the pathogenesis of gastric remnant carcinoma (GRC). However, there was still some controversy. Methods Articles published until July 15, 2020, in PubMed, MEDLINE, Embase and CNKI databases were selected. According to the inclusion criteria, corresponding data of included articles were abstracted and used for statistical analysis. Results Thirteen papers were finally enrolled, nine of which showed the result that the risk of EBV infection rate in the GRC was higher than conventional gastric carcinoma (OR = 5.22, 95% CI 3.89–7.00). In addition, we found that EBV associated GRC (EBVaGRC) had higher rate of Billroth-II (OR = 3.80, 95% CI 1.90–7.57), carcinoma in anastomotic site (OR = 2.41, 95% CI 1.27–4.56) and diffuse type (Lauren classification) (OR = 1.97, 95% CI 1.04–3.73),while sex, initial diagnosis and lymphocytic infiltration were calculated no statistical difference. By genetic polymorphism analysis, “V-val” subtype of EBNA1 (OR = 21.84, 95% CI 11.92–31.76) and “C” subtype of BamHI-W1/I1 (OR = 7.07, 95% CI 1.47–34.03) were observed to be highly expressed in EBVaGRC. Conclusion EBV infection rate in the GRC was higher. Further analysis showed that Billroth-II, carcinoma in anastomotic site and diffuse type (Lauren classification) were associated to EBVaGRC. Through analysis of EBV genome polymorphisms, we thought that “V-val” subtype of EBNA1 and “C” subtype of BamHI-W1/I1 may become predictor of EBVaGRC.

Abstract Background Newer epidemiological studies suggest that the incidence of ulcerative colitis might be increasing rapidly. Furthermore, osteoporosis in ulcerative colitis patients has gained great attention, but the epidemiologic evidence remains controversial. Therefore, a meta‐analysis was performed to explore the association between bone density and ulcerative colitis. Methods Two investigators used PubMed, EMBASE and the Cochrane Library databases to identify all studies published before August 2019. Depending on the outcomes, investigators divided these studies into four groups (OR, SMD [BMD], SMD [z-score] and SMD [t-score]). To address the use of steroids, which is a major confounding factor in this analysis, another subgroup analysis of studies of steroid-free patients was conducted. Additionally, heterogeneity, sensitivity and stratified analyses were also performed. Results A total of 13 cross-sectional studies that involved 1154 participants were included in the present meta-analysis, and three of them were included in the steroid-free subgroup analysis. The pooled OR was 6.41 (95% CI 2.59–15.87) and the pooled SMD (BMD), SMD (t-score) and SMD (z-score) were − 0.24 (95% CI − 0.44 to − 0.04), − 0.55 (95% CI − 0.72 to − 0.37), and − 0.38 (95% CI − 0.56 and − 0.19), respectively. Since steroids are a significant confounder, the pooled SMD of the steroid-free subgroup was − 0.55 (− 0.85 to − 0.25), which revealed a strong negative relationship between bone density and ulcerative colitis in steroid-free patients. Additionally, other subgroup analyses also revealed a strong relationship. Conclusions This meta-analysis provides evidence for the potential association between ulcerative colitis and decreased bone density. It is essential for clinicians to consider bone mineral density in ulcerative colitis patients regardless of steroid-therapy.

BackgroundIn recent years, evidence that aldosteronism is a risk factor for metabolic disorders has increased. This study was designed to investigate the role of nonalcoholic fatty liver disease (NAFLD) and hypokalemia in primary aldosteronism (PA).MethodsA total of 222 patients diagnosed with PA and 222 non-PA patients were included in our study. Demographic data, medical histories, clinical evaluations, complete blood counts, serum biochemical analyses, aldosterone and potassium levels were obtained. Data are presented as the means ± standard deviation (SD). To compare the parameters between cases and controls, Student’s t-tests or Mann-Whitney U tests were used for continuous variables, and χ2 tests were used for categorical variables. Pearson correlation analysis was used to define relationships between pairs of parameters. A two-sided P < 0.05 was considered statistically significant. Multivariate logistic regression was performed to assess the independent effects of potassium and other metabolic variables on NAFLD in PA patients.ResultsThe diagnosis of NAFLD was more common in PA patients (n=222, 35.1%) than in non-PA subjects (29.7%). PA patients with and without NAFLD had similar metabolic imbalance characteristics. In PA patients with hypokalemia, relatively higher prevalences of NAFLD (44% vs. 27%, P < 0.05) and diabetes mellitus (19.8% vs. 9.9%, P < 0.05) were observed. Hypokalemic PA patients had a worse metabolic status than PA patients without hypokalemia, including higher body mass index (BMI) (25.4 ± 3.4 vs. 24.1 ± 3.9 kg/m2, P < 0.05), more severe dyslipidemia as well as insulin resistance, higher serum uric acid levels (354 ± 95 vs. 319 ± 87 μmol/L, P < 0.01) and aggravated inflammation.ConclusionThe prevalence of NAFLD was higher in PA patients than in non-PA patients, although the patterns of obesity, dyslipidemia and insulin resistance were similar. Hypokalemic PA patients had a worse metabolic status than normokalemic PA patients. This study provides new insights that can inform further mechanistic studies about metabolic imbalance in patients with aldosteronism.

Helicobacter pylori (H. pylori) is proved to be the main pathogenic agent of various diseases, including chronic gastritis, gastric ulcer, duodenal ulcer, and gastric cancer. In addition, chronic cholecystitis and cholelithiasis are common worldwide, which are supposed to increase the total mortality of patients. Epidemiologic evidence on the relationship between H. pylori infection of the gallbladder and chronic cholecystitis/cholelithiasis still remains unclear. We conducted a systematic review and meta-analysis of overall studies to investigate the relationship between H. pylori infection of the gallbladder and chronic cholecystitis/cholelithiasis. Two researchers searched PubMed, Embase, and Cochrane Library databases to obtain all related and eligible studies published before July 2020. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by the random-effects model. Subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also conducted. Twenty studies were included in the meta-analysis, involving 1735 participants and 1197 patients with chronic cholecystitis/cholelithiasis. Helicobacter species infection of the gallbladder was positively correlated with increased risk of chronic cholecystitis and cholelithiasis, especially H. pylori (OR = 3.05; 95% CI, 1.81–5.14; I2 = 23.5%). Besides, country-based subgroup analysis also showed a positive correlation between the gallbladder H. pylori positivity and chronic cholecystitis/cholelithiasis risk. For Asian and non-Asian country studies, the ORs were 4.30 (95% CI, 1.76–10.50; I2 = 37.4%) and 2.13 (95% CI, 1.23–3.70; I2 = 0.0%), respectively. The association was more obvious using the bile sample and urease gene primer. In conclusion, this meta-analysis provided evidence that there is a positive correlation between H. pylori infection in the gallbladder and increased risk of chronic cholecystitis and cholelithiasis.

Rotated object detection in aerial images is still challenging due to arbitrary orientations, large scale and aspect ratio variations, and extreme density of objects. Existing state-of-the-art rotated object detection methods mainly rely on angle-based detectors. However, angle-based detectors can easily suffer from a long-standing boundary problem. To tackle this problem, we propose a purely angle-free framework for rotated object detection, called Point RCNN. Point RCNN is a two-stage detector including both PointRPN and PointReg which are angle-free. Given an input aerial image, first, the backbone-FPN extracts hierarchical features, then, the PointRPN module generates an accurate rotated region of interests (RRoIs) by converting the learned representative points of each rotated object using the MinAreaRect function of OpenCV. Motivated by RepPoints, we designed a coarse-to-fine process to regress and refine the representative points for more accurate RRoIs. Next, based on the learned RRoIs of PointRPN, the PointReg module learns to regress and refine the corner points of each RRoI to perform more accurate rotated object detection. Finally, the final rotated bounding box of each rotated object can be attained based on the learned four corner points. In addition, aerial images are often severely unbalanced in categories, and existing rotated object detection methods almost ignore this problem. To tackle the severely unbalanced dataset problem, we propose a balanced dataset strategy. We experimentally verified that re-sampling the images of the rare categories can stabilize the training procedure and further improve the detection performance. Specifically, the performance was improved from 80.37 mAP to 80.71 mAP in DOTA-v1.0. Without unnecessary elaboration, our Point RCNN method achieved new state-of-the-art detection performance on multiple large-scale aerial image datasets, including DOTA-v1.0, DOTA-v1.5, HRSC2016, and UCAS-AOD. Specifically, in DOTA-v1.0, our Point RCNN achieved better detection performance of 80.71 mAP. In DOTA-v1.5, Point RCNN achieved 79.31 mAP, which significantly improved the performance by 2.86 mAP (from ReDet’s 76.45 to our 79.31). In HRSC2016 and UCAS-AOD, our Point RCNN achieved higher performance of 90.53 mAP and 90.04 mAP, respectively.

Abstract Background Helicobacter pylori (H. pylori) infection is a worldwide threat to human health with high prevalence. In this study, we analyzed the relationship between latitude, average annual temperature, average daily sunshine time and H. pylori infection. Methods The PubMed, ClinicalTrials.gov, EBSCO and Web of Science databases were searched to identify studies reporting H. pylori infection. Latitude 30° was the cut-off level for low and mid-latitude areas. We obtained information for latitude, average annual temperature, average daily sunshine, and Human Development Index (HDI) from reports of studies of the relationships with H. pylori infection. Results Of the 51 studies included, there was significant difference in H. pylori infection between the low- and mid-latitude areas (P = 0.05). There was no significant difference in the prevalence of H. pylori infection in each 15°-latitude zone analyzed (P = 0.061). Subgroup analysis revealed the highest and lowest H. pylori infection rates in the developing regions at > 30° latitude subgroup and the developed regions at

Immunometabolism provides a new perspective on the pathogenesis of rheumatoid arthritis (RA). In recent years, there have been investigations focusing on the role of intracellular glucose metabolism in the pathogenesis of RA. Previous studies have shown that glycolysis of synovial tissue is increased in RA patients, while glycolysis inhibitors can significantly inhibit synovitis. Pyruvate kinase (PK) is a key enzyme in glycolysis, catalyzing the final rate-limiting step in the process. An isoform of PK, PKM2, provides favorable conditions for the survival of tumor cells via its glycolytic or non-glycolytic functions and has become a potential therapeutic target in tumors. RA synovium has the characteristic of tumor-like growth, and, moreover, increased expression of PKM2 was identified in the synovial tissue of RA patients in recent studies, indicating the underlying role of PKM2 in RA. PKM2 has potential value as a new therapeutic target or biomarker for RA, but its exact role in RA remains unclear. In this review, the properties of PKM2 and existing research concerning PKM2 and RA are thoroughly reviewed and summarized, and the possible role and mechanism of PKM2 in RA are discussed.

This genome-wide association study on persistent hepatitis B virus (HBV) infection among Chinese confirms previously associated genetic loci while discovering a novel protective locus at 8p21.3. The study also demonstrates the nearby gene INST10 suppresses HBV replication in vitro.

Objective Intestinal permeability increases during the course of acute pancreatitis (AP). We assessed duodenal permeability alterations in patients with AP by confocal laser endomicroscopy (CLE). Methods Thirty patients with AP underwent CLE evaluation of the antral and duodenal mucosa. Images were graded based on the appearance of capillaries and the degree of fluorescein leakage. Results Patients with AP had increased duodenal mucosal permeability that could be detected by CLE. The mucosal permeability progressively increased in the gastric antrum, duodenal bulb, and descending duodenum. The CLE parameters in the antrum and duodenal bulb were not significantly different between patients with mild and severe AP. The CLE grades in the descending duodenum were higher in patients with severe than mild AP. The C-reactive protein level in AP was positively correlated with the permeability in the duodenal bulb and descending duodenum, while the computed tomography severity index score was positively correlated with the mucosal permeability in the duodenal bulb and descending duodenum. Conclusion CLE revealed increased duodenal permeability in patients with AP. Higher permeability in the descending duodenum was observed in severe than mild AP. Further large-scale studies are needed to confirm the relationship between altered duodenal permeability and the severity of AP.

Background and Aims. Recent studies have indicated that circulating miRNAs could serve as accurate biomarkers for diagnosing nonalcoholic fatty liver disease (NAFLD). We aimed to assess the evidence on the probability of circulating miRNAs as new diagnostic biomarkers in patients with NAFLD. Methods. We comprehensively retrieved relevant English literature from the databases of PubMed, Embase, and the Cochrane Library from 2000 to 1 January 2019. The diagnostic accuracy of circulating miRNAs as markers for NAFLD was analyzed. Moreover, we evaluated the methodological quality of the included article. STATA was applied to perform statistical analyses. Results. In this meta-analysis, 17 studies that enrolled 1408 patients of NAFLD and 926 healthy people from 6 articles were analyzed. We constructed a summary receiver-operating characteristic (SROC) curve of all circulating miRNAs, and the area under the curve (AUC) was 0.83, with the pooled sensitivity (SEN) 0.70 and the pooled specificity (SPE) 0.82 in distinguishing patients with NAFLD from healthy controls. Among them, miR-122 showed high diagnostic accuracy, with the diagnostic index of pooled SEN, SPE, and AUC being 0.88, 0.66, and 0.86, respectively. We then performed subgroup analyses based on the mode of miRNA regulation, countries, miRNA profiling, sample size, and male proportion. We then did a regression analysis and found the cause of heterogeneity might be miRNA profiling. Finally, publication bias was not found, and Fagan’s nomogram showed valuable clinical utility. Conclusion. Circulating miRNAs, especially miR-122, might be promising diagnostic biomarkers for NAFLD with high-accuracy, and more large-sample studies are required to support the above findings in the future.

Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis, which may be misdiagnosed as pancreatic carcinoma. This study aims to verify new biomarkers for AIP and propose a serological pattern to differentiate AIP from pancreatic adenocarcinoma with routinely performed tests. In this study, data of serum samples were collected and compared between 25 patients with AIP and 100 patients with pancreatic carcinoma. Receiver operating characteristic analysis and logistic regression was performed to evaluate the diagnostic effect of serum parameters in differentiating AIP from pancreatic carcinoma alone or in combination. Among several serum markers observed in the two groups, carbohydrate antigen 19-9 (Ca19-9), globulin, eosinophils and hemoglobin were selected as the independent markers. Serum levels of Globulin, Eosinophil percentage in AIP group were significantly higher than in pancreatic cancer group (P

Caveolin1 (CAV1) is involved in lipid homeostasis and endocytosis, but little is known about the significance of CAV1 in the pathogenesis and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the role of CAV1 in NAFLD.Expression of CAV1 in the in vitro and in vivo models of NAFLD was analyzed. The effects of CAV1 knockdown or overexpression on free fatty acid (FFA)-induced lipid accumulation in L02 cells and AML12 cells were determined. CAV1 knockout (CAV1-KO) mice and their wild-type (WT) littermates were subjected to a high fat diet (HFD) for 4 weeks, and the functional consequences of losing the CAV1 gene and its subsequent molecular mechanisms were also examined.Noticeably, CAV1 expression was markedly reduced in NAFLD. CAV1 knockdown led to the aggravation of steatosis that was induced by FFA in both L02 cells and AML12 cells, while CAV1 overexpression markedly attenuated lipid accumulation in the cells. Consistent with CAV1 repression in the livers of HFD-induced mice, the CAV1-KO mice exhibited more severe hepatic steatosis upon HFD intake. In addition, increased cholesterol levels and elevated transaminases were detected in the plasma of CAV1-KO mice. The protein expression of SREBP1, a key gene involved in lipogenesis, was augmented following CAV1 suppression in FFA-treated hepatocytes and in the livers of HFD-fed CAV1-KO mice.CAV1 serves as an important protective factor in the development of NAFLD by modulating lipid metabolism gene expression.

OBJECTIVE: To conduct a meta-analysis of published, full-length, randomized controlled trials evaluating the efficacy of endoscopic band ligation (EBL) versus pharmacological therapy for the primary and secondary prophylaxis of variceal hemorrhage in patients with cirrhosis.

Despite years of effort, exact pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains obscure. To gain an insight into the regulatory roles of microRNAs (miRNAs) in aberrant energy metabolic status and pathogenesis of NAFLD, we analyzed the expression of miRNAs in livers of ob/ob mice, streptozotocin (STZ)-induced type 1 diabetic mice, and normal C57BL/6 mice by miRNA microarray. Compared with normal C57BL/6 mice, ob/ob mice showed upregulation of eight miRNAs and downregulation of four miRNAs in fatty livers. Upregulation of miR-34a and downregulation of miR-122 was found in livers of STZ-induced diabetic mice. These results demonstrate that distinct miRNAs are strongly dysregulated in NAFLD and hyperglycemia. Comparison between miRNA expressions in livers of ob/ob mice and STZ-administered mice further revealed upregulation of four miRNAs and downregulation of two miRNAs in livers of ob/ob mice, indicating that these miRNAs may represent a molecular signature of NAFLD. A distinctive miRNA expression pattern was identified in ob/ob mouse liver, and hierarchical clustering of this pattern could clearly discriminate ob/ob mice from either normal C57BL/6 mice or STZ-administered mice. These findings suggest an important role of miRNAs in hepatic energy metabolism and implicate the participation of miRNAs in the pathophysiological processes of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major public health problem worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD that may progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of disease progression from NAFLD to NASH has not been fully understood. Immunological mechanisms that have been increasingly recognized in the disease progression include defects in innate immunity, adaptive immunity, Toll-like receptor (TLR) signaling, and gut-liver axis. The NLRP3 inflammasome is an intracellular multiprotein complex involved in the production of mature interleukin 1-beta (IL-1β) and induces metabolic inflammation. NLRP3 inflammasome has been recently demonstrated to play a crucial role in the progression of NASH. This review highlights the recent findings linking NLRP3 inflammasome to the progression of NASH.

BackgroundPrior work suggested that patients with inflammatory bowel diseases (IBD) have lower body mass index (BMI) than controls and patients with lower BMI have more serious complications.GoalThe study was aimed to find relationship between BMI in patients with and without IBD, investigate effects of medicine therapy and disease stages on patients' BMI.MethodsPotentially eligible studies were identified through searching PubMed, Cochrane and Embase databases. Outcome measurements of mean BMI and the number of patients from each study were pooled by a random-effect model. Publication bias test, sensitivity analysis and subgroup analysis were conducted.ResultsA total of 24 studies containing 1442 patients and 2059 controls were included. Main results were as follows: (1) BMI in Crohn's disease (CD) patients was lower than that in health controls (-1.88, 95% CI -2.77 to -1.00, P< 0.001); (2) Medical therapy significantly improved BMI of CD patients (with therapy: -1.58, -3.33 to 0.16; without: -2.09, 95% CI -3.21 to -0.98) while on the contrary not significantly improving BMI of UC patients (with therapy: -0.24, 95% CI -3.68 to 3.20; without: -1.34, 95% CI -2.87 to 0.20, P = 0.57); (3) Both CD and UC patients in active phase showed significantly greater BMI difference compared with controls than those in remission (CD patients: remission: -2.25, 95% CI -3.38 to -1.11; active phase: -4.25, 95% CI -5.58 to -2.92, P = 0.03; UC patients: remission: 0.4, 95% CI -2.05 to 2.84; active phase: -5.38, -6.78 to -3.97, P = 0.001).ConclusionsBMI is lower in CD patients; medical therapy couldn't improve BMI of IBD patients; the state of disease affects BMI of CD patients and UC patients.

There is a gap between the association of non-alcoholic fatty liver disease (NAFLD) and renal function in an apparently healthy population. This study aims to assess whether NAFLD is associated with estimated glomerular filtration rate (eGFR) levels and to understand early changes of eGFR in NAFLD. A cross-sectional study was performed among apparently healthy persons who underwent general health screening including laboratory assessments and hepatic ultrasonography from January 2013 to December 2013 at the First Affiliated Hospital of Zhejiang University, College of Medicine, China. This study included 1,193 subjects with a mean age of 48 years. Prevalence of NAFLD was 31.3%. Mean eGFR was significantly lower in NAFLD than in controls (107 ± 19 mL/min/1.73 m(2) vs. 113 ± 23 mL/min/1.73 m(2), P50 years of age (Both P>0.05). The eGFR level is significantly associated with NAFLD and its risk factors in an apparently healthy population. Effects of NAFLD on eGFR could be dependent on age.

There is no consensus on the vitamin D levels and inflammatory bowel disease (IBD).To conduct a systematic review and meta-analysis to analyze the relationship between IBD and 25(OH)D, sun exposure, and latitude, and to determine whether vitamin D deficiency affects the severity of IBD.We searched the PubMed, EBSCO, and ClinicalTrials.gov databases to identify all studies that assessed the association between 25(OH)D, sun exposure, latitude, and IBD through November 1, 2014, without language restrictions. Studies that compared 25(OH)D levels between IBD patients and controls were selected for inclusion in the meta-analysis. We calculated pooled standardized mean differences (SMDs) and odds ratios (ORs).Thirteen case-control studies investigating CD and 25(OH)D levels were included, and eight studies part of above studies also investigated the relationship between UC and 25(OH)D. Both CD patients (SMD: 0.26 nmol/L, 95% confidence interval [CI]: 0.09-0.42 nmol/L) and UC patients (SMD: 0.5 nmol/L, 95% CI: 0.15-0.85 nmol/L) had lower levels of 25(OH)D than controls. In addition, CD patients and UC patients were 1.95 times (OR, 1.95; 95% CI, 1.48-2.57) and 2.02 times (OR, 2.02; 95% CI, 1.13-3.60) more likely to be 25(OH)D deficient than controls. We also included 10 studies investigating the relationship between CD activity and vitamin D. Results showed that patients with active CD (CD Activity Index ≥ 150) were more likely to have low vitamin D levels. In addition, whether low sun exposure and high latitude were related to a high morbidity of CD need to be provided more evidence.Our study shows that IBD patients have lower vitamin D levels. For active CD patients, vitamin D levels were low. These findings suggest that vitamin D may play an important role in the development of IBD, although a direct association could not be determined in our study.

An association between cholecystectomy and metabolic syndrome has not been fully established. Here we analyzed the association between cholecystectomy and metabolic syndrome in a Chinese population of 5672 subjects who undergone annual health checkups at the First Affiliated Hospital, College of Medicine, Zhejiang University between January 2011 and December 2012. The prevalences of gallstones, cholecystectomy and metabolic syndrome were 6.0%, 3.6%, and 32.5%, respectively. The prevalence of metabolic syndrome was significantly higher in subjects with a history of cholecystectomy (63.5%) than in those with gallstones (47.0%) or in those without gallstone disease (30.3%; P

BACKGROUND AND STUDY AIMS: Chronic abdominal pain is one of the most common chief complaints, but the underlying pathophysiology often remains unknown after routine clinical evaluation. Capsule endoscopy (CE) is a new technique for the visualization of the entire small bowel. The aim of this study was to evaluate the diagnostic efficacy of CE in patients with chronic abdominal pain of obscure origin. PATIENTS AND METHODS: Two hundred forty three patients with chronic abdominal pain with no significant lesions were enrolled in this study. CE was performed in all patients. RESULTS: A diagnosis was made in 23.0% of patients screened with CE. Of the 243 patients, 19 (7.8%) were diagnosed with Crohn's disease, 15 (6.2%) with enteritis, 11 (4.5%) with idiopathic intestinal lymphangiectasia, 5 (2.1%) with uncinariasis, and a number of other diagnoses including small bowel tumor, ascariasis, and anaphylactoid purpura. Five patients had abnormal transit time, and capsule retention occurred in two patients. CONCLUSIONS: In contrast to other previous studies, we found that CE is an effective diagnostic tool for patients with abdominal pain.

BACKGROUND: The incidence of esophageal and gastric cancer has been increasing rapidly worldwide in recent years, although the reason for this increase is unclear. Here, a statistical synthesis of studies that evaluated the association between physical activity, a well-known protecting factor against death and other chronic diseases, and the risk of esophageal and gastric cancer was performed. METHODS: Potentially suitable studies were identified using Medline and Embase. The reference lists of all included articles and those of several recent reviews were searched manually. Studies were included if they (1) were published as case-control or cohort studies evaluating the association between physical activity and risk of esophageal or gastric cancer; and (2) reported point estimates (i.e., risk ratios, odds ratios) and measures of variability (i.e., 95% confidence intervals [CIs]) for physical activity and risk of esophageal or gastric cancer. RESULTS: Fifteen studies were identified (7 cohorts, 8 case-controls; 984 esophageal and 7,087 gastric cancers). Collectively, they indicated that the risk of gastric cancer was 13% lower among the most physically active people than among the least active people (RR = 0.87, 95% confidence interval [CI] = 0.78 to 0.97) and that of esophageal cancer was 27% lower (RR = 0.73, 95% CI = 0.56 to 0.97). CONCLUSIONS: Pooled results from observational studies support a protective effect of physical activity against both esophageal and gastric cancer.

Helicobacter pylori infection is associated with extragastric diseases. The thyroid may be one of the targets of chronic inflammation. Here, we sought to investigate whether H. pylori infections were associated with the presence of thyroid nodules. A total of 988 euthyroid subjects from China were included in this cross-sectional study. Four hundred thirty-five (44.0%) subjects were diagnosed as having thyroid nodules, and 486 (49.2%) were diagnosed with H. pylori infections. The thyroid nodules group had a higher proportion of H. pylori infections than the control group (P = 0.002). Free thyroxine (FT4) levels were lower and the prevalence of thyroid nodules was higher in patients with H. pylori infection compared to those without infection, even after adjustment for age, gender, and body mass index (BMI; all P < 0.05). The prevalence of H. pylori infection showed a decreasing trend as serum FT4 level increased (P(trend) = 0.020). Stepwise logistic regression analysis showed that H. pylori infection was significantly associated with the risk of thyroid nodules (odds ratio: 1.390, 95% confidence interval: 1.059-1.824, P = 0.018). Our results suggested that H. pylori infections were positively associated with the presence of thyroid nodules in the euthyroid population, whose thyroid functions were in the reference range.

Growth hormone (GH) is an important regulator of metabolism and body composition. GH deficiency is associated with increased visceral body fat and other features of the metabolic syndrome. Here we performed a cross-sectional study to explore the association of GH levels with nonalcoholic fatty liver disease (NAFLD), which is considered to be the hepatic manifestation of the metabolic syndrome. A total of 1,667 subjects were diagnosed as NAFLD according the diagnostic criteria, and 5,479 subjects were defined as the controls. The subjects with NAFLD had significantly lower levels of serum GH than the controls. Those with low GH levels had a higher prevalence of NAFLD and the metabolic syndrome. A stepwise logistic regression analysis showed that GH levels were significantly associated with the risk factor for NAFLD (OR = 0.651, 95%CI = 0.574-0.738, P

Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease, and serum uric acid is observed to be significantly elevated in NAFLD patients. However, whether this elevation is causal, a bystander, or a consequence of NAFLD remains unclear. We performed a population-based prospective study among the employees of Zhenhai Refining & Chemical Company Ltd., Ningbo, China to investigate whether the elevation of serum uric acid has a casual role for NAFLD. A total of 6890 initially NAFLD-free subjects were followed up for 3 years. Overall, 11.80% (813/6890) subjects developed NAFLD over 3 years of follow-up. The cumulative incidence of NAFLD increased with progressively higher baseline serum uric acid levels (the cumulative incidence was 7.2%, 9.5%, 11.5%, 13.8%, and 17.2% in quintile 1, quintile 2, 3, 4 and 5, respectively; P value for trend