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BackgroundMagnifying endoscopy with narrow band imaging (M-NBI) has been applied to examine early gastric cancer by observing microvascular architecture and microsurface structure of gastric mucosal lesions. However, the diagnostic efficacy of non-experts in differentiating early gastric cancer from non-cancerous lesions by M-NBI remained far from satisfactory. In this study, we developed a new system based on convolutional neural network (CNN) to analyze gastric mucosal lesions observed by M-NBI.MethodsA total of 386 images of non-cancerous lesions and 1702 images of early gastric cancer were collected to train and establish a CNN model (Inception-v3). Then a total of 341 endoscopic images (171 non-cancerous lesions and 170 early gastric cancer) were selected to evaluate the diagnostic capabilities of CNN and endoscopists. Primary outcome measures included diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value.ResultsThe sensitivity, specificity, and accuracy of CNN system in the diagnosis of early gastric cancer were 91.18%, 90.64%, and 90.91%, respectively. No significant difference was spotted in the specificity and accuracy of diagnosis between CNN and experts. However, the diagnostic sensitivity of CNN was significantly higher than that of the experts. Furthermore, the diagnostic sensitivity, specificity and accuracy of CNN were significantly higher than those of the non-experts.ConclusionsOur CNN system showed high accuracy, sensitivity and specificity in the diagnosis of early gastric cancer. It is anticipated that more progress will be made in optimization of the CNN diagnostic system and further development of artificial intelligence in the medical field.

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.

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.

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. The redox status of a cell is regulated through a number of mechanisms, chief among these is the KEAP1-mediated ubiquitination and degradation of NRF2. Here the authors show that KEAP1 itself is ubiquitinated and degraded in a process that is opposed by the ubiquitin-specific protease USP25.

Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD) 1 – 5 , but the underlying mechanism for this association is unclear. Here we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. We identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. Colonization of B. xylanisolvens reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and therefore increasing intestinal ceramide formation, which contributes to NAFLD progression to non-alcoholic steatohepatitis (NASH). Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine with the ability to metabolize nicotine. These findings suggest a possible route to reduce tobacco smoking-exacerbated NAFLD progression. Nicotine accumulates in the intestine during tobacco smoking and accelerates the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis (NASH), but it can be degraded effectively by the human symbiont Bacteroides xylanisolvens.

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.

Non-alcoholic fatty liver disease (NAFLD) is an important health issue worldwide. We aimed to develop a simple model to determine the presence of NAFLD in a Chinese population. A cross-sectional study with 9602 subjects was conducted. Potential predictors were entered into a stepwise logistic regression analysis to obtain the model. We used 148 patients with liver biopsy to validate this model. The model, named the ZJU index, was developed based on body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG) and the serum alanine aminotransferase (ALT) to serum aspartate transaminase (AST) ratio. The area under the receiver operating characteristic curve (AUROC) of the ZJU index to detect NAFLD was 0.822. At a value of <32.0, the ZJU index could rule out NAFLD with a sensitivity of 92.2% and at a value of >38.0, the ZJU index could detect NAFLD with a specificity of 93.4%. In patients with liver biopsy, the ZJU index could detect steatosis with good accuracy, with an AUROC of 0.896. This study revealed that the ZJU index is a helpful model to detect NAFLD for community physicians in China. It was validated not only by a validation cohort but also by pathological data.

ObjectiveAccumulation of free fatty acids (FFAs) in hepatocytes induces lipotoxicity, leading to non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the underlying mechanisms by which FFA contributes to the pathogenesis of NAFLD via the regulation of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous hydrogen sulfide (H2S) biosynthesis.DesignHepatic MPST expression was evaluated in mice and patients with NAFLD. A variety of molecular approaches were used to study the effects of MPST regulation on hepatic steatosis in vivo and in vitro.ResultsIn vitro treatment of hepatocytes with FFAs upregulated MPST expression, which was partially dependent on NF-κB/p65. Hepatic MPST expression was markedly increased in high fat diet (HFD)-fed mice and patients with NAFLD. Partial knockdown of MPST via adenovirus delivery of MPST short hairpin RNA or heterozygous deletion of the Mpst gene significantly ameliorated hepatic steatosis in HFD-fed mice. Consistently, inhibition of MPST also reduced FFA-induced fat accumulation in L02 cells. Intriguingly, inhibition of MPST significantly enhanced rather than decreased H2S production, whereas MPST overexpression markedly inhibited H2S production. Co-immunoprecipitation experiments showed that MPST directly interacted with and negatively regulated cystathionine γ-lyase (CSE), a major source of H2S production in the liver. Mechanistically, MPST promoted steatosis via inhibition of CSE/H2S and subsequent upregulation of the sterol regulatory element-binding protein 1c pathway, C-Jun N-terminal kinase phosphorylation and hepatic oxidative stress.ConclusionsFFAs upregulate hepatic expression of MPST and subsequently inhibit the CSE/H2S pathway, leading to NAFLD. MPST may be a potential therapeutic target for NAFLD.

The precise prevalence and risk factors for the development of nonalcoholic fatty liver disease (NAFLD) in nonobese adults remains unclear. The objective of this study was to investigate the prevalence of NAFLD and risk factors for its development in a nonobese Chinese population. We firstly investigated the prevalence and factors associated with the presence of NAFLD in nonobese (body mass index (BMI) <25 kg/m(2)) Chinese subjects via a cross-sectional study, and then analyzed the risk factors for the development of NAFLD via a subsequent prospective 5-year follow-up of the same population. A total of 6,905 nonobese subjects were enrolled in the cross-sectional study. Baseline evaluation revealed that the prevalence of NAFLD was 7.27%. A total of 5,562 subjects who were free of NAFLD at baseline completed the follow-up study, and 494 (8.88%) had developed NAFLD during the 5-year follow-up. Further analyses revealed that age, gender, BMI, waist circumference, triglyceride, high-density lipoprotein (HDL) cholesterol, serum uric acid, hemoglobin, and platelet count were independently associated with the presence and development of NAFLD. NAFLD is prevalent in the nonobese Chinese population, and a substantial proportion of subjects developed NAFLD over the 5-year follow-up period. Special attention should be paid to the factors associated with the presence and development of NAFLD in nonobese subjects, to improve prevention and management of NAFLD.

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.