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The objective of this review was to summarize the most pertinent CT imaging findings in patients with coronavirus disease 2019 (COVID-19). A literature search retrieved eligible studies in PubMed, EMBASE, Cochrane Library and Web of Science up to June 1, 2020. A comprehensive review of publications of the Chinese Medical Association about COVID-19 was also performed. A total of 84 articles with more than 5340 participants were included and reviewed. Chest CT comprised 92.61% of abnormal CT findings overall. Compared with real-time polymerase chain reaction result, CT findings has a sensitivity of 96.14% but a low specificity of 40.48% in diagnosing COVID-19. Ground glass opacity (GGO), pure (57.31%) or mixed with consolidation (41.51%) were the most common CT features with a majority of bilateral (80.32%) and peripheral (66.21%) lung involvement. The opacity might associate with other imaging features, including air bronchogram (41.07%), vascular enlargement (54.33%), bronchial wall thickening (19.12%), crazy-paving pattern (27.55%), interlobular septal thickening (42.48%), halo sign (25.48%), reverse halo sign (12.29%), bronchiectasis (32.44%), and pulmonary fibrosis (26.22%). Other accompanying signs including pleural effusion, lymphadenopathy and pericardial effusion were rare, but pleural thickening was common. The younger or early stage patients tended to have more GGOs, while extensive/multilobar involvement with consolidation was prevalent in the older or severe population. Children with COVID-19 showed significantly lower incidences of some ancillary findings than those of adults and showed a better performance on CT during follow up. Follow-up CT showed GGO lesions gradually decreased, and the consolidation lesions first increased and then remained relatively stable at 6-13 days, and then absorbed and fibrosis increased after 14 days. Chest CT imaging is an important component in the diagnosis, staging, disease progression and follow-up of patients with COVID-19.

Although major advances in genomics have initiated an exciting new era of research, a lack of information regarding cis-regulatory elements has limited the genetic improvement or manipulation of pigs as a meat source and biomedical model. Here, we systematically characterize cis-regulatory elements and their functions in 12 diverse tissues from four pig breeds by adopting similar strategies as the ENCODE and Roadmap Epigenomics projects, which include RNA-seq, ATAC-seq, and ChIP-seq. In total, we generate 199 datasets and identify more than 220,000 cis-regulatory elements in the pig genome. Surprisingly, we find higher conservation of cis-regulatory elements between human and pig genomes than those between human and mouse genomes. Furthermore, the differences of topologically associating domains between the pig and human genomes are associated with morphological evolution of the head and face. Beyond generating a major new benchmark resource for pig epigenetics, our study provides basic comparative epigenetic data relevant to using pigs as models in human biomedical research., To date, little is known about the regulatory landscape of the pig genome. Here, the authors characterize cis-regulatory elements in the pig genome using RNA-seq, ChIP-Seq and ATAC-seq, finding a higher degree of usage conservation between pig and human than mouse and human.

Background and Aims. Gastroesophageal variceal bleeding is a serious complication of portal hypertension in cirrhotic patients and could be predicted by hepatic venous pressure gradient (HVPG). However, whether the presence of ascites affects the prognostic value of HVPG for patients with acute variceal bleeding is still unknown. This retrospective study is aimed at investigating the influence of ascites on predictive performance of HVPG for early rebleeding in cirrhotic patients with acute variceal bleeding. Methods. In this retrospective study, a total of 148 patients with cirrhosis hospitalized for acute variceal bleeding who underwent HVPG measurement and endoscopic variceal ligation (EVL) for the prevention of rebleeding were included. The receiver operating characteristic curve (ROC) and logistical regression method were employed to analyze the predictive performance of HVPG for early rebleeding. The locally weighted scatterplot smoothing approach was adopted to assess the monotonicity between bleeding risk and HVPG. Results. A significantly higher HVPG level was observed in patients with early rebleeding compared to patients without rebleeding in the nonascites cohort. When using HVPG to predict early rebleeding, there was a lower area under curve in the ascites cohort compared to the nonascites cohort. HVPG was recognized as a risk factor for early rebleeding by a logistic regression model only in the nonascites cohort. An overall monotonicity in the trend of change in HVPG and risk for early rebleeding was observed in the nonascites cohort solely. Conclusion. The predictive value of HVPG for early rebleeding in patients with cirrhosis that developed acute variceal bleeding is hindered by the presence of ascites.

Endometritis is a common disease affecting fertility in cows during the perinatal period, which disturbs the molecular milieu of the uterine environment and impairs embryo development and implantation. Exosomes are important extracellular components that transmit a variety of micro RNAs (miRNAs), which perform key regulatory functions. In this study, we investigated plasma exosomal miRNAs from cows with endometritis and from cultured endometrial epithelial cells (EECs) challenged with lipopolysaccharide (LPS) to explore the role of EEC-derived exosomes and their miRNAs in bovine endometritis. Plasma exosomes were collected from nine healthy dairy cows and nine dairy cows with endometritis, and culture supernatant exosomes were isolated from EECs challenged with or without LPS. Exosomal RNA was extracted using commercial kits and miRNA profiles were generated using RNA-seq. We found that miR-218 was differentially expressed in EECs under conditions of endometrial inflammation. Inhibition studies suggested that reduced levels of miR-218 in EEC-derived exosomes when transferred into placental trophoblast cells impaired embryonic development and decreased placental trophoblast cell migration by targeting secreted frizzled related protein 2. We propose that exosomal miR-218 secreted from EECs acts as a driver of embryonic development and differentiation. In addition, exosomal miR-218 may provide a valuable diagnostic marker for bovine endometritis.

BACKGROUND AND AIM Gastroesophageal varices (GEV) present in compensated advanced chronic liver disease (cACLD) and can develop into high-risk varices (HRV). The gold standard for diagnosing GEV is esophagogastroduodenoscopy (EGD). However, EGD is invasive and less tolerant. This study aimed to develop and validate radiomics signatures based on noncontrast-enhanced computed tomography (CT) images for non-invasive diagnosis of GEV and HRV in patients with cACLD. METHODS The multicenter trial enrolled 161 patients with cACLD from six university hospitals in China between January 2015 and September 2019, who underwent both EGD and noncontrast-enhanced CT examination within 14 days prior to the endoscopy. Two radiomics signatures, termed rGEV and rHRV, respectively, were built based on CT images in a training cohort of 129 patients and validated in a prospective validation cohort of 32 patients (ClinicalTrials. gov identifier: NCT03749954). RESULTS In the training cohort, both rGEV and rHRV exhibited high discriminative abilities on determining the existence of GEV and HRV with the area under receiver operating characteristic curve (AUC) of 0.941 (95% confidence interval [CI] 0.904-0.978) and 0.836 (95% CI 0.766-0.905), respectively. In validation cohort, rGEV and rHRV showed high discriminative abilities with AUCs of 0.871 (95% CI 0.739-1.000) and 0.831 (95% CI 0.685-0.978), respectively. CONCLUSIONS This study demonstrated that rGEV and rHRV could serve as the satisfying auxiliary parameters for detection of GEV and HRV with good diagnostic performance.

Hepatic venous pressure gradient (HVPG) is a hemodynamic index widely used for evaluating the severity of portal hypertension. Theoretically, HVPG can be measured in any of the three major (i.e., right, middle and left) hepatic veins (HVs); however, it remains unclear whether HVPGs measured in different HVs are exchangeable, and if not, what factors cause inter-HV HVPG differences? In consideration of the potential limitations of invasive in vivo measurements, we employed a computational model implemented in conjunction with stochastic parameter sampling to simulate and compare HVPG measurements in multiple HVs under various sinusoidal portal hypertensive conditions. Results demonstrated that HVPGs measured in the right and middle HVs were basically exchangeable, whereas those in the left HV were relatively lower due primarily to the smaller proportion of hepatic venous flow through the left HV compared with that through the right or middle HV. Moreover, it was found that hepatic vein-to-vein shunts (HVVS) led to a marked augmentation of inter-HV HVPG differences and significant underestimation of portal pressure gradient with HVPG. These findings suggest that understanding the distribution of hepatic venous flow and status of HVVS is essential for selecting a proper HV for implementing HVPG measurement in clinical practice.

Background and Aims: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon co morbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. Methods: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. Result: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR=2.1(1.1-3.7), p=0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR=8.1(1.9-38.8), p=0.002) predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5(11.6%)] or acute decompensation [4(9%)]. Liver related complications increased (p In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis. Conclusions: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Background EDP‐305 is a novel and potent farnesoid X receptor (FXR) agonist, with no/minimal cross‐reactivity to TGR5 or other nuclear receptors. Herein we report therapeutic efficacy of EDP‐305, in direct comparison with the first‐in‐class FXR agonist obeticholic acid (OCA), in mouse models of liver disease. Methods EDP‐305 (10 and 30 mg/kg/day) or OCA (30mg/kg/day) was tested in mouse models of pre‐established biliary fibrosis (BALBc.Mdr2‐/‐, n = 9‐12/group) and steatohepatitis induced by methionine/choline‐deficient diet (MCD, n = 7‐12/group). Effects on biliary epithelium were evaluated in vivo and in primary EpCAM + hepatic progenitor cell (HPC) cultures. Results In a BALBc.Mdr2‐/‐ model, EDP‐305 reduced serum transaminases by up to 53% and decreased portal pressure, compared to untreated controls. Periportal bridging fibrosis was suppressed by EDP‐305 at both doses, with up to a 39% decrease in collagen deposition in high‐dose EDP‐305. In MCD‐fed mice, EDP‐305 treatment reduced serum ALT by 62% compared to controls, and profoundly inhibited perisinusoidal ‘chicken wire’ fibrosis, with over 80% reduction in collagen deposition. In both models, treatment with 30mg/kg OCA reduced serum transaminases up to 30%, but did not improve fibrosis. The limited impact on fibrosis was mediated by cholestasis‐independent worsening of ductular reaction by OCA in both disease models; OCA but not EDP‐305 at therapeutic doses promoted ductular proliferation in healthy mice and favoured differentiation of primary HPC towards cholangiocyte lineage in vitro. Conclusions EDP‐305 potently improved pre‐established liver injury and hepatic fibrosis in murine biliary and metabolic models of liver disease, supporting the clinical evaluation of EDP‐305 in fibrotic liver diseases including cholangiopathies and non‐alcoholic steatohepatitis.

Bayesian network (BN), which is an effective probabilistic graphical model with strong characteristics of practicality and applicability, is often used for real-world faults diagnosis. However, most of the existing BN-based studies merely analyze how to diagnose root cause and do not have the capability of identifying fault propagation path. To address this problem, a novel Gaussian Bayesian network-based faults propagation path identification inference algorithm using parent nodes filter is proposed. For a specific fault node, the set of its parent nodes is firstly reduced according to parameter weights and value fluctuations. Then estimates of the maximum conditional probability for possible subsets of reduced parent set are computed based on decomposition of conditional probability and dichotomy. After estimation, the most probable cause can be determined by the closest estimate to actual value. Through such layer-by-layer inference, fault propagation paths in the network can be finally tracked. Experimental results have demonstrated that the novel approach is capable of identifying fault propagation paths effectively, which provides higher adaptability and faster speed.

Accepted as crucial participators in human malignancies, long noncoding RNAs (lncRNAs) have been proven to exert significant function on the complicated processes of cancer progression. Although existing investigations have revealed the oncogenic role of lncRNA SOX2 overlapping transcript (SOX2-OT) in different kinds of cancers, such as osteosarcoma and cholangiocarcinoma, the potential role of it in prostate cancer (PC) is poorly understood. This study was the first attempt to decipher the underlying regulatory mechanism of SOX2-OT in PC. According to the data from this study, SOX2-OT expression was conspicuously elevated in PC tissues and cells. Silenced SOX2-OT could repress PC cell proliferation and migration. Besides, mechanism assays manifested that SOX2-OT bound with miR-369-3p and negatively correlated with miR-369-3p in PC. Additionally, miR-369-3p was confirmed to elicit suppressive impact on PC progression. What's more, cofilin 2 (CFL2) was testified to be a downstream target gene of miR-369-3p. Final rescue tests uncovered that CFL2 upregulation or miR-369-3p inhibition could largely restore SOX2-OT knockdown-mediated function on PC progression. To sum up, SOX2-OT accelerates cell proliferation and migration by targeting miR-369-3p/CFL2 axis in PC.

In vitro fertilization (IVF) for ovine embryos is strongly associated with low pregnancy rates and negative effects on embryonic and postnatal development, but the mechanisms remain unclear. We aimed to identify genes essential for successful implantation of IVF embryos in sheep by species-specific microarray analysis. Differential gene expression analysis between caruncles and intercaruncle sites of the ovine uterus with in vivo (IVV) -produced embryos on day 10 of pregnancy found 43 differentially expressed genes (DEGs) with at least a 2-fold change, such as coiled-coil domain-containing 152 (CCDC152) and pregnancy-associated plasma protein A (PAPPA). Gene ontology analysis revealed these DEGs were related to cell proliferation, the immune system process, localization and response to stimulus. Moreover, we identified 93 DEGs in endometrial caruncles with IVV- versus in vitro (IVT)-produced embryos on days 12, 14 and 16 of pregnancy, including prostaglandin-endoperoxide synthase 2 (PTGS2) and cubilin (CUBN). GO analysis revealed that these DEGs were related to cell adhesion, cell proliferation, embryo implantation, embryonic morphogenesis, the immune system process and localization. Two DEGs (PAPPA and RSAD2) in caruncle versus intercaruncle sites at day 10 were also differentially expressed between the IVV and IVT groups at the three implantation stages. Self-organizing feature map cluster analysis of transcript profiles during embryo implantation revealed different gene expression patterns between the IVV and IVT groups. In conclusion, this study identified many genes that may be associated with mechanisms underlying IVF-induced ovine embryo implantation failure during the peri-implantation period, and such genes provide potential candidates for further study.

OBJECTIVES A liver stiffness × spleen size/platelet count score (LSPS) model which can rule out high-risk varices and identify high likelihood of clinically significant portal hypertension in patients with compensated cirrhosis has been endorsed by American Association for the Study of Liver Diseases in the 2016 practice guidance on portal hypertension bleeding. This study aims to evaluate the accuracy of LSPS model assessed by ultrasound in well characterized patients with compensated advanced chronic liver disease. METHODS Eligible patients with compensated advanced chronic liver disease were retrospectively enrolled between January 2017 and March 2018, who had undergone routine clinical and laboratory tests, liver stiffness measurement, ultrasound examination, and computed tomography scanning. Spleen sizes were evaluated by ultrasound and computed tomography reconstructed model, respectively. The correlation and agreement of spleen size and LSPS derived from ultrasound and computed tomography imaging modality were compared. RESULTS A total of 158 patients were included and analyzed. Spleen size showed a moderate correlation (R = 0.649, P

The contractile protein MYH9 (non-muscle myosin IIA) is an actin-binding protein that plays a fundamental role in cell adhesion, migration, and division. However, its distinct role in colorectal cancer (CRC) still remains unidentified. In this study, we detected significant MYH9 overexpression in CRC samples compared with paired normal tissues using western blotting and tissue microarray immunohistochemistry (IHC). Moreover, analysis of patient clinical information demonstrated that MYH9 overexpression was strongly correlated with lymph node metastasis and poor overall survival. Endogenous overexpression of MYH9 enhanced the ability of cell proliferation and migration in vitro, and accelerated CRC growth in mouse models. Silencing of MYH9 revealed repressive effects on CRC cells in vitro and in vivo. Furthermore, primary biomechanics that involved MAPK/AKT signaling mediated epithelial-mesenchymal transition (EMT) was uncovered underlying MYH9 dependent cell behaviors. Collectively, our data showed that MYH9 significantly promoted tumorigenesis by regulating MAPK/AKT signaling, and was remarkably correlated with poor prognosis in CRC. MYH9 may thus be a novel biomarker and drug target in the diagnosis and treatment of CRC.

While N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6A modification in mammalian glial development remains unknown. Here, we identify a novel m6A reader, Prrc2a (Proline rich coiled-coil 2 A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model. Further analyses reveal that Prrc2a is involved in oligodendrocyte progenitor cells (OPCs) proliferation and oligodendrocyte fate determination. Accordingly, oligodendroglial-lineage specific deletion of Prrc2a causes a similar phenotype of Nestin-Cre-mediated deletion. Combining transcriptome-wide RNA-seq, m6A-RIP-seq and Prrc2a RIP-seq analysis, we find that Olig2 is a critical downstream target gene of Prrc2a in oligodendrocyte development. Furthermore, Prrc2a stabilizes Olig2 mRNA through binding to a consensus GGACU motif in the Olig2 CDS (coding sequence) in an m6A-dependent manner. Interestingly, we also find that the m6A demethylase, Fto, erases the m6A modification of Olig2 mRNA and promotes its degradation. Together, our results indicate that Prrc2a plays an important role in oligodendrocyte specification through functioning as a novel m6A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases.

BACKGROUND: Endoscopic therapy has been widely applied to prevent variceal rebleeding, but data addressing the effect of endoscopic variceal eradication (VE) are lacking. We aimed to clarify the clinical impact of VE and reveal the long-term incidence and mortality of gastrointestinal rebleeding. METHODS: This prospective study included 228 cirrhotic patients who underwent secondary prophylaxis for variceal bleeding and achieved VE through a systematic procedure we proposed as endoscopic sequential therapy (EST). Rebleeding rates before and after VE were compared and cumulative incidence of rebleeding and mortality were calculated using the Kaplan-Meier method. A logistic regression model and P for trend were used to investigate the optimal time limit for VE. RESULTS: During a median (interquartile range) follow-up duration of 33.0 (23.0–48.75) months, rebleeding was identified in 28 patients (12.3%) after VE and in 27 patients (11.8%) during endoscopic sessions. The cumulative incidence of rebleeding before and after VE was 8.4% and 1.8% at 6 months, and 14.9% and 4.0% at 1 year respectively (P12 months (P for trend

The objective of this study was to evaluate the effects of natural astaxanthin (ASTA) from Haematococcus pluvialis on production performance, egg quality, antioxidant enzyme activity, free radical scavenging ability, and gene expression of antioxidant enzymes in laying hens. Nongda No. 3 laying hens (n = 450) were randomly allocated to 1 of 5 dietary treatments. Each treatment had 6 replicates of 15 hens each. All birds were assigned to a corn-soybean meal-based diet containing 0, 20, 40, 80, or 160 mg/kg ASTA for 4 wk. With increasing dietary ASTA, no significant effects were observed on egg weight, feed consumption, feed efficiency, laying rate, Haugh unit, or eggshell strength. Yolk color darkened linearly with increasing dose of ASTA (P

Background & Aims The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8–28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. Conclusions The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Skeletal muscle development is a complex biological process involving multiple key genes, signaling pathways and noncoding RNAs, including microRNAs and circular RNAs (circRNAs). However, the regulatory relationship among them is so complicated that it has not yet been fully elucidated. In this study, we found that miR-7 inhibited C2C12 cell proliferation and differentiation by targeting transcription factor 12 (TCF12). circHIPK3 acted as a competing endogenous RNA, and its overexpression effectively reversed the regulation of miR-7 on C2C12 cell proliferation and differentiation by increasing TCF12 expression. Taken together, our findings provide evidence that circHIPK3 regulates skeletal muscle development through the miR-7/TCF12 pathway. This study provides a scientific basis for further research on skeletal muscle development at the circRNA level.

Aim: Circulating chemerin level has been reported to be higher in patients with various types of cancer. However, the conclusions obtained are not unified. The aim of present study is to draw an evidence-based conclusion on the relationship between circulating chemerin and risk of cancer. Materials & methods: A systematic search was carried out in PubMed and Web of Science up to 30 June 2019. The random-effects model was applied to calculate summary standardized mean differences with 95% CIs. Results: The meta-analysis included a total of 12 separate studies, 876 cases and 739 healthy controls. The results showed that the expression level of circulating chemerin was significantly higher in cancer patients than that in control group (pooled standardized mean difference = 1.47, 95% CI = 1.03–1.90). Conclusion: This meta-analysis concludes that a high level of circulating chemerin is strongly associated with cancer risk.

Summary Background The incidence of elevated liver chemistries and the presence of the pre‐existing chronic liver disease (CLD) have been variably reported in COVID‐19. Aims To assess the prevalence of CLD, the incidence of elevated liver chemistries and the outcomes of patients with and without underlying CLD/elevated liver chemistries in COVID‐19. Methods A comprehensive search of electronic databases from 1 December 2019 to 24 April 2020 was done. We included studies reporting underlying CLD or elevated liver chemistries and patient outcomes in COVID‐19. Results 107 articles (n = 20 874 patients) were included for the systematic review. The pooled prevalence of underlying CLD was 3.6% (95% CI, 2.5‐5.1) among the 15 407 COVID‐19 patients. The pooled incidence of elevated liver chemistries in COVID‐19 was 23.1% (19.3‐27.3) at initial presentation. Additionally, 24.4% (13.5‐40) developed elevated liver chemistries during the illness. The pooled incidence of drug‐induced liver injury was 25.4% (14.2‐41.4). The pooled prevalence of CLD among 1587 severely infected patients was 3.9% (3%‐5.2%). The odds of developing severe COVID‐19 in CLD patients was 0.81 (0.31‐2.09; P = 0.67) compared to non‐CLD patients. COVID‐19 patients with elevated liver chemistries had increased risk of mortality (OR‐3.46 [2.42‐4.95, P

Three-dimensional (3D) visualization involves feature extraction and 3D reconstruction of CT images using a computer processing technology. It is a tool for displaying, describing, and interpreting 3D anatomy and morphological features of organs, thus providing intuitive, stereoscopic, and accurate methods for clinical decision-making. It has played an increasingly significant role in the diagnosis and management of liver diseases. Over the last decade, it has been proven safe and effective to use 3D simulation software for pre-hepatectomy assessment, virtual hepatectomy, and measurement of liver volumes in blood flow areas of the portal vein; meanwhile, the use of 3D models in combination with hydrodynamic analysis has become a novel non-invasive method for diagnosis and detection of portal hypertension. We herein describe the progress of research on 3D visualization, its workflow, current situation, challenges, opportunities, and its capacity to improve clinical decision-making, emphasizing its utility for patients with liver diseases. Current advances in modern imaging technologies have promised a further increase in diagnostic efficacy of liver diseases. For example, complex internal anatomy of the liver and detailed morphological features of liver lesions can be reflected from CT-based 3D models. A meta-analysis reported that the application of 3D visualization technology in the diagnosis and management of primary hepatocellular carcinoma has significant or extremely significant differences over the control group in terms of intraoperative blood loss, postoperative complications, recovery of postoperative liver function, operation time, hospitalization time, and tumor recurrence on short-term follow-up. However, the acquisition of high-quality CT images and the use of these images for 3D visualization processing lack a unified standard, quality control system, and homogeneity, which might hinder the evaluation of application efficacy in different clinical centers, causing enormous inconvenience to clinical practice and scientific research. Therefore, rigorous operating guidelines and quality control systems need to be established for 3D visualization of liver to develop it to become a mature technology. Herein, we provide recommendations for the research on diagnosis and management of 3D visualization in liver diseases to meet this urgent need in this research field.

Objectives COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear. Design This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death). Results Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death. Conclusions Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.

Background Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. In the present study, we aimed to identify additional susceptibility loci of HBV-related HCC using advanced knowledge-based analysis. Methods We performed knowledge-based analysis (including gene- and gene-set-based association tests) on variant-level association p-values from two existing GWASs of HBV-related HCC. Five different types of gene-sets were collected for the association analysis. A number of SNPs within the gene prioritized by the knowledge-based association tests were selected to replicate genetic associations in an independent sample of 965 cases and 923 controls. Results The gene-based association analysis detected four genes significantly or suggestively associated with HBV-related HCC risk: SLC39A8, GOLGA8M, SMIM31, and WHAMMP2. The gene-set-based association analysis prioritized two promising gene sets for HCC, cell cycle G1/S transition and NOTCH1 intracellular domain regulates transcription. Within the gene sets, three promising candidate genes (CDC45, NCOR1 and KAT2A) were further prioritized for HCC. Among genes of liver-specific expression, multiple genes previously implicated in HCC were also highlighted. However, probably due to small sample size, none of the genes prioritized by the knowledge-based association analyses were successfully replicated by variant-level association test in the independent sample. Conclusions This comprehensive knowledge-based association mining study suggested several promising genes and gene-sets associated with HBV-related HCC risks, which would facilitate follow-up functional studies on the pathogenic mechanism of HCC.

Background In December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then. Aim This study aims to understand the research gaps related to COVID-19 and propose recommendations for future research. Methods We undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies. Results We included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R0). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January. Conclusion The number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.

Background The clinical characteristics and disease course in COVID-19 patients with pre-existing decompensated cirrhosis has not been described so far. Methods In this case series, we report three patients with confirmed COVID-19 and pre-existing decompensated cirrhosis from three hospitals in Hubei, the epicenter of the outbreak in China. Result Patient 1 was a 53-year-old man with hepatitis B virus-related cirrhosis, portal hypertension, and ascites. Though receiving intensive support, he died of irreversible multiple organ dysfunction syndrome 48 days after the onset of the illness. Patient 2 was a 75-year-old woman with a history of schistosomiasis-related cirrhosis, portal hypertension, and ascites. Her family members requested that invasive rescue measures not be undertaken, and she died of acute respiratory distress syndrome 40 days after presenting with COVID-19 infection. Patient 3 was an 87-year-old man with alcohol-related cirrhosis, portal hypertension, and esophageal variceal hemorrhage. He was discharged from the hospital 29 days after illness onset. Conclusion The case series raise the possibility that decompensated cirrhosis may be a risk factor for a poor outcome in patients with COVID-19.

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has outbreak in the world. Little is known about the clinical characteristics of patients with SARS-CoV-2 infection in the high-altitude region of China. We reported the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) in Gansu province, China. METHODS: In this retrospective study, patients with laboratory-confirmed SARS-CoV-2 infection were consecutively enrolled from January 21, 2020 to February 11, 2020. The information on the epidemiological, clinical characteristics, laboratory tests, radiological features on admission, treatment and outcome were obtained with the final follow-up of March 13, 2020. On the basis of the median length of hospital stay, patients were further analyzed in two groups (long- vs. short-hospital stay). RESULTS: Of the 86 patients of COVID-19 in 11 cities of Gansu Province, the median hospital stay was 14.0 days (interquartile rang, 11.0-19.0 days). In the overall cohort, the median age was 41.0 years (interquartile rang, 31.0-54.3 years), and 48 (55.8%) patients were female. Forty (46.5%) had a history of exposure to epidemic regions, but none exposed to the Huanan seafood market in Wuhan. Common symptoms included fever (41, 47.7%), and cough (37, 43.0%). On admission, 30 (34.9%) and 58 (67.4%) patients had leukopenia and lymphopenia. According to chest CT scans, 53 (66.3%) of 80 patients showed bilateral pneumonia, and 19 (23.8%) of 80 patients showed unilateral pneumonia. Of the 15 asymptomatic cases, 10 (66.6%) cases were found CT findings of pneumonia. Besides, there were 65 (75.6%) patients with mild and moderate type of COVID-19. All 86 patients received antiviral and traditional Chinese medicine therapy, 53 (61.6%) received antibacterial therapy, and 3 (3.5%) patients received invasive ventilator mechanical ventilation. The proportion of patients received antibiotic treatment in long-hospital stay group was significantly higher than that in the short-hospital stay group (P=0.045). As of March 13, 2020, 84 (97.7%) patients were discharged, and two (2.3%) cases died. CONCLUSIONS: In the Gansu province cohort of 86 patients of COVID-19, most patients were with mild or moderate type, and most asymptomatic cases showed CT imaging findings of SARS-CoV-2 related pneumonia.

BACKGROUND: Baseline hepatic venous pressure gradient (HVPG) has been applied for prediction of variceal rebleeding in patients after acute variceal bleeding. However, for patients receiving secondary prevention, there still lacks evidence about the predictive performance of baseline-HVPG for rebleeding. This study aims to investigate the predictive value of baseline-HVPG for variceal rebleeding in cirrhotic patients receiving secondary prevention. METHODS: This retrospective study included 122 patients with cirrhosis accepting secondary prevention of variceal rebleeding in a university hospital. All the included patients had HVPG measurements before rebleeding and had at least 1-year follow-up after HVPG measurement unless the rebleeding occurred. The rebleeding rate in patients with different HVPG levels and time-dependent predictive performance of baseline-HVPG were analysed. A Cox regression model and P for trend were used to assess the rebleeding risk. RESULTS: Variceal rebleeding occurred in 22 (18.0%) patients during 1-year follow-up. No significant difference was observed in rebleeding rate between patients with HVPG

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Objective This study aims to clarify the mechanisms underlying transcriptional regulation and regulatory roles of lncRNAs in skeletal muscle cell differentiation. Methods We analysed the expression patterns of lncRNAs via time‐course RNA‐seq. Then, we further combined the ATAC‐seq and ChIP‐seq to investigate the governing mechanisms of transcriptional regulation of differentially expressed (DE) lncRNAs. Weighted correlation network analysis and GO analysis were conducted to identify the transcription factor (TF)‐lncRNA pairs related to skeletal muscle cell differentiation. Results We identified 385 DE lncRNAs during C2C12 differentiation, the transcription of which is determined by chromatin states around their transcriptional start sites. The TF‐lncRNA correlation network showed substantially concordant changes in DE lncRNAs between C2C12 differentiation and satellite cell rapid growth stages. Moreover, the up‐regulated lncRNAs showed a significant decrease following the differentiation capacity of satellite cells, which gradually declines during skeletal muscle development. Notably, inhibition of the lncRNA Atcayos and Trp53cor1 led to the delayed differentiation of satellite cells. Those lncRNAs were significantly up‐regulated during the rapid growth stage of satellite cells (4‐6 weeks) and down‐regulated with reduced differentiation capacity (8‐12 weeks). It confirms that these lncRNAs are positively associated with myogenic differentiation of satellite cells during skeletal muscle development. Conclusions This study extends the understanding of mechanisms governing transcriptional regulation of lncRNAs and provides a foundation for exploring their functions in skeletal muscle cell differentiation., Schematic of TF (MyoD, MyoG, Mef2c and Heyl) and lncRNA (Atcayos and Trp53cor1) regulatory interactions in differentiating C2C12 and ageing satellite cells.

Object To assess the risk factors for and surgical treatment of delayed trapped temporal horn (dTTH) in patients who had undergone removal of lateral ventricular trigone meningioma. Method Patients with lateral ventricular trigone meningioma treated at our institution from 2011 to 2015 were identified. Predictors for dTTH were determined using logistic regression. Literature review and pooled analysis were also conducted to evaluate the comparative effectiveness of surgical treatment for dTTH. Results A total of 110 cases were included in the analysis. Thirteen (11.8%) cases developed dTTH following surgery. Multivariable logistic regression demonstrated an association of longer operative duration with higher incidence of dTTH (OR, 1.34; 95% CI, 1.00–1.80; p = 0.049). As surgical duration prolonged from less than 3 hours to 5 hours or more, the incidence of dTTH increased in a consistent, linear fashion from 7.7% to 13.9% (p = 0.03). Six cases (46.2%, 6/13) of dTTH underwent surgical treatment for their life-threatening symptoms. Seven studies including 13 cases of dTTH in the literature were identified. Literature data, including the current series, revealed a total of 24 procedures were performed in 19 cases. Endoscopic fenestration trended toward fewer complications than shunt (7.7% vs 25.0%, p = 0.530). There were no significant differences in failure rates between the two groups (23.1% vs 25.0%, p = 1.000). Conclusion Patients with prolonged operative duration may be at higher risk of dTTH. Endoscopic fenestration is considered in preference to shunt placement, since it possesses equivalent success rates with fewer complications and avoids the need for a permanent implant.

Doubled haploid technology using inducer lines carrying mutations in ZmPLA1/MTL/NLD and ZmDMP1–4 has revolutionized traditional maize breeding. ZmPLA1/MTL/NLD is conserved in monocots and has been used to extend the system from maize to other monocots5–7, but no functional orthologue has been identified in dicots, while ZmDMP-like genes exist in both monocots and dicots4,8,9. Here, we report that loss-of-function mutations in the Arabidopsis thaliana ZmDMP-like genes AtDMP8 and AtDMP9 induce maternal haploids, with an average haploid induction rate of 2.1 ± 1.1%. In addition, to facilitate haploid seed identification in dicots, we established an efficient FAST-Red fluorescent marker-based haploid identification system that enables the identification of haploid seeds with >90% accuracy. These results show that mutations in DMP genes also trigger haploid induction in dicots. The conserved expression patterns and amino acid sequences of ZmDMP-like genes in dicots suggest that DMP mutations could be used to develop in vivo haploid induction systems in dicots. Mutations in the ZmDMP gene induce maternal haploids and facilitate breeding in maize. Now, a study extends this system of maize to dicots, showing that loss-of-function mutations in the Arabidopsis ZmDMP-like genes also induce maternal haploids.

Clinically significant portal hypertension (CSPH) is associated with an incremental risk of esophageal varices and overt clinical decompensations. However, hepatic venous pressure gradient (HVPG) measurement, the gold standard for defining CSPH (HVPG≥10 mm Hg) is invasive and therefore not suitable for routine clinical practice. This study aims to develop and validate a radiomics-based model as a noninvasive method for accurate detection of CSPH in cirrhosis. The prospective multicenter diagnostic trial (CHESS1701, ClinicalTrials.gov identifier: NCT03138915 ) involved 385 patients with cirrhosis from five liver centers in China between August 2016 and September 2017. Patients who had both HVPG measurement and contrast-enhanced CT within 14 days prior to the catheterization were collected. The noninvasive radiomics model, termed rHVPG for CSPH was developed based on CT images in a training cohort consisted of 222 consecutive patients and the diagnostic performance was prospectively assessed in 163 consecutive patients in four external validation cohorts. rHVPG showed a good performance in detection of CSPH with a C-index of 0·849 (95%CI: 0·786–0·911). Application of rHVPG in four external prospective validation cohorts still gave excellent performance with the C-index of 0·889 (95%CI: 0·752–1·000, 0·800 (95%CI: 0·614–0·986), 0·917 (95%CI: 0·772–1·000), and 0·827 (95%CI: 0·618–1·000), respectively. Intraclass correlation coefficients for inter- and intra-observer agreement were 0·92–0·99 and 0·97–0·99, respectively. A radiomics signature was developed and prospectively validated as an accurate method for noninvasive detection of CSPH in cirrhosis. The tool of rHVPG assessment can facilitate the identification of CSPH rapidly when invasive transjugular procedure is not available.

Clinically significant portal hypertension is associated with an increased risk of developing gastro-oesophageal varices and hepatic decompensation. Hepatic venous pressure gradient measurement and oesophagogastroduodenoscopy are the gold-standard methods for assessing clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mm Hg) and gastro-oesophageal varices, respectively. However, invasiveness, cost, and feasibility limit their widespread use, especially if repeated and serial evaluations are required to assess the efficacy of pharmacotherapy. Although new techniques for non-invasive portal pressure measurement have been pursued for many decades, only recently have new tools been assessed and validated for larger clinical application. This Review focuses on the recent advances in non-invasive approaches for the diagnosis and serial monitoring of portal hypertension and varices for clinical practice.

Background: We aimed to compare the efficacy of different drugs facilitating endoscopy in patients with acute variceal bleeding. Methods: Databases were searched to identify randomized controlled trials which compared the efficacy of vasoactive drugs (vasopressin, terlipressin, octreotide, somatostatin) with placebo or each other. The primary outcomes were 6-week and 5-day mortality. Secondary outcomes were 5-day rebleeding, control of initial bleeding and adverse events. Pairwise and network meta-analysis were performed. Results: We identified 14 RCTs involved 2,187 patients. Four drugs had comparable clinical efficacy in all involving outcomes, except for adverse events. However, we do exhibit a superiority when vasopressin (OR, 4.40; 95% CI: 1.04–19.57), terlipressin (OR, 4.58; 95% CI: 1.63–13.63), octreotide (OR, 5.79; 95% CI: 2.41–16.71) and somatostatin (OR, 5.15; 95% CI: 1.40–27.39) were compared to placebo respectively as for initial hemostasis. In addition, only octreotide was more effective than placebo in decreasing 5-day rebleeding (OR, 0.44; 95% CI: 0.22–0.90). Meanwhile, octreotide was shown to have the highest probability ranking the best to improve initial hemostasis (mean rank =1.8) and carries a lowest risk of adverse events (9.1%) and serious adverse events (0.0%) compared to other drugs. Conclusions: Balanced with curative effect and tolerability, octreotide may be the preferred vasoactive drug facilitating endoscopy.

The transcriptional co-activator Yes-associated protein (YAP) has been implicated as an oncogene and is found to promote breast cancer metastasis. However, the pro-metastatic mechanism of YAP remains unclear. Here, we demonstrated that YAP functions as a transcriptional repressor of growth differentiation factor-15 (GDF15), a divergent member of the transforming growth factor superfamily, in several breast cancer cell lines. Functionally, knockdown of YAP decreased, whereas knockdown of GDF15 increased, the metastatic potential of breast cancer cells. More than that, the reduced metastasis in YAP-depleted cells could be reversed by simultaneous knockdown of GDF15. Mechanistically, the repressive effect of YAP on GDF15 requires its transcriptional factor TEAD (TEA domain family). In addition, YAP recruits polycomb repressive complex 2 (PRC2) to tri-methylate histone H3 lysine 27 in the promoter region of GDF15. Co-immunoprecipitation experiments demonstrated that YAP and enhancer of zeste 2 PRC2 subunit (EZH2) physically interact with each other. In conclusion, our data reveal that YAP promotes metastasis of breast cancer cells by repressing GDF15 transcription and present a novel molecular mechanism underlying the pro-metastasis function of YAP oncoprotein, with the implication of a therapeutic avenue for breast cancer treatment.

Trastuzumab is the only target to be approved as the first-line treatment of HER2 positive metastatic gastric cancer, but ubiquitous resistance decreases its therapeutic benefit. In this study, we found HER4, phosphorylation HER4 (p-HER4) and the mesenchymal marker Vimentin increased in trastuzumab-resistant cells (MKN45TR and NCI-N87TR), while epithelial markers expressions in trastuzumab-resistant cell lines and animal models decreased. Additionally, silencing HER4 prevented the epithelial-mesenchymal transition and led to decreased proliferation and migration in vitro and in vivo. The expression of YAP1, a vital downstream interacted target of HER4, decreased when HER4 was knocked down. Interestingly, stimulation of NRG1 could compromise the inhibitory impact and rescue cell survival; whereas, transfection of siYAP1 sensitized trastuzumab-treated cells. Expression analysis of the proteins in patient-derived xenograft model (PDX) mice showed that HER4, p-HER4, YAP1, and Vimentin were clearly upregulated in the trastuzumab-resistant mice compared to mice without trastuzumab resistance. However, HER2 and E-cadherin were downregulated in response to continuous treatment with trastuzumab. These findings elucidated that the central role of the HER4-YAP1 axis in trastuzumab resistance of HER2-positive gastric cancer cells through induction of EMT. Hence, regulating the HER4-YAP1 axis might be a promising strategy for clinical interventions in patients with HER2-positive gastric cancer.

Cancer cells have metabolic features that allow them to preferentially metabolize glucose through aerobic glycolysis, providing them with a progression advantage. However, microRNA (miRNA) regulation of aerobic glycolysis in cancer cells has not been extensively investigated. We addressed this in the present study by examining the regulation of miR-139-5p on aerobic glycolysis of hepatocellular carcinoma (HCC) using clinical specimens, HCC cells, and a mouse xenograft model. We found that overexpressing miR-139-5p restrained aerobic glycolysis, suppressing proliferation, migration, and invasion in HCC cells. miR-139-5p regulated hexokinase 1 (HK1) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression by directly targeting the transcription factor ETS1, which bound to the promoters of the HK1 and PFKFB3 genes. miR-139-5p-induced aerobic glycolysis, proliferation, migration, and invasion were reversed by ETS1 overexpression, while ETS1 silencing induced the expression of miR-139-5p via a post-transcriptional regulation mode involving Drosha. miR-139-5p expression was reduced in HCC compared to para-carcinoma tissue, which was confirmed in The Cancer Genome Atlas and GSE54751 HCC cohorts. Notably, the lower expression of mir-139 was correlated with worse prognosis. These outcomes indicate that reciprocal regulatory interactions between miR-139-5p and ETS1 modulate aerobic glycolysis, proliferation, and metastasis in HCC cells, suggesting new targets for HCC treatment.

Long non-coding RNAs (lncRNAs) have recently been identified as critical regulators in tumor initiation and development. However, the function of lncRNAs in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of lncRNA MIR22HG in HCC. Methods: We evaluated MIR22HG expression in 52-patient, 145-patient, TCGA, and GSE14520 HCC cohorts. The effects of MIR22HG on HCC were analyzed in terms of proliferation, invasion, and metastasis, both in vitro and in vivo. The mechanism of MIR22HG action was explored through bioinformatics, luciferase reporter, and RNA immunoprecipitation analyses. Results: MIR22HG expression was significantly down-regulated in 4 independent HCC cohorts compared to that in controls. Its low expression was associated with tumor progression and poor prognosis of patients with HCC. Forced expression of MIR22HG in HCC cells significantly suppressed proliferation, invasion, and metastasis in vitro and in vivo. Mechanistically, MIR22HG derived miR-22-3p to target high mobility group box 1 (HMGB1), thereby inactivating HMGB1 downstream pathways. Additionally, MIR22HG directly interacted with HuR and regulated its subcellular localization. MIR22HG competitively bound to human antigen R (HuR), resulting in weakened expression of HuR-stabilized oncogenes, such as β-catenin. Furthermore, miR-22-3p suppression, HuR or HMGB1 overexpression rescued the inhibitory effects caused by MIR22HG overexpression. Conclusion: Our findings revealed that MIR22HG plays a key role in tumor progression by suppressing the proliferation, invasion, and metastasis of tumor cells, suggesting its potential role as a tumor suppressor and prognostic biomarker in HCC.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here., Article Highlights Updated on the basis of AARC data of >3300 cases enrolled into AARC registry prospectivelyACLF is distinct form Acute Decompensation of cirrhosisNewer sections on DILI-ACLF, AIH-ACLF, PVT/HVOTO–ACLFReversibility of Chronic Liver Disease in ACLFPortal and systemic hemodynamics and their relevance in ACLFAcute Portal Hypertension and Variceal progression in ACLFAARC score as a guide for treatment strategies in ACLFACLF in Children-first consensus on pediatric ACLF

// Bingbing Qiao 1, * , Wenqin Luo 2, * , Yanna Liu 2, * , Jing Wang 3, # , Chuan Liu 2 , Zhao Liu 2 , Sizhe Chen 2 , Jingjing Gu 2 , Xiaolong Qi 3 and Tongwei Wu 2, 3 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China 3 Department of Hepatobiliary Disease, The Affiliated (T.C.M) Hospital of Southwest Medical University, Luzhou, China * These authors contributed equally to this work # Co-first author Correspondence to: Bingbing Qiao, email: popzxcbb@163.com Tongwei Wu, email: 445759131@qq.com Keywords: CXCR2; cancer; overall survival; recurrence-free survival; prognostic Received: February 07, 2017 Accepted: September 03, 2017 Epub: December 11, 2017 Published: March 13, 2018 ABSTRACT Background & Aims: Quite a few studies had investigated the correlation between CXC chemokine receptor 2 (CXCR2) and cancer. This meta-analysis was aimed to comprehensively summarize the previous studies and to explore the prognostic value of CXCR2 in patients with cancer. Materials and Methods: An adequate literature search in EMBASE and PubMed was conducted. Articles in English which have reported CXCR2 expression in patients and enough data to calculate hazard ratio (HR) were included. Effect estimates were analyzed with Review Manager 5.2. The endpoint was overall survival (OS) and recurrence-free survival (RFS). Result: Twelve studies from 10 publications with a total of 2,461 patients were identified. It was shown that high level of CXCR2 was significantly associated with poorer overall survival (OS) (HR = 1.69, 95% CI = 1.46–1.96, p < 0.0001, I 2 = 45%) and RFS (HR = 1.50, 95% CI = 1.25–1.80, p < 0.0001, I 2 = 6%). The analyses of different analysis models (univariate or multivariate models), sample size (< 300 or ≥ 300) and ethnicity (Asian and Caucasian) have indicated the negative impact of CXCR2 over-expression on survival of patients with cancer. Stratified by cancer type, high-expression of CXCR2 was associated with unfavorable OS in laryngeal squamous cell carcinoma, lung cancer, pancreatic ductal carcinoma, clear-cell renal cell carcinoma and hepatocellular carcinoma; however, there was significant difference between high- and low-expression of CXCR2 in digestive tract cancer (esophageal adenocarcinoma and squamous cell carcinoma procession, resected esophageal carcinoma, esophageal cancer and gastric cancer). Conclusions: CXCR2 is an unfavorable predictor in terms of OS and RFS in patients with cancer except for digestive tract cancer and is related with poorer prognostic.

To determine whether p21-activated Kinase (PAK) 6 is a prognostic and predictive marker in gastric cancer (GC) and to construct a classifier that can identify a subset of patients who are highly sensitive to 5-fluorouracil/oxaliplatin chemotherapy. We retrospectively analyzed the expression levels of PAK6, cyclooxygenase 2, p21WAF1, Ki-67, excision repair cross-complementing gene 1, and thymidylate synthase in 242 paraffin-embedded GC specimens of the training cohort by immunohistochemistry. Then, we used support vector machine (SVM)-based methods to develop a predictive classifier for chemotherapy (chemotherapy score - CS-SVM classifier). Further validation was performed in an independent cohort of 279 patients. High PAK6 expression was associated with poor prognosis and increased chemoresistance to 5-FU/oxaliplatin chemotherapy. The CS-SVM classifier distinguished patients with stage II and III GC into low- and high-CS-SVM groups, with significant differences in the 5-year disease-free survival (DFS) and overall survival (OS) in chemotherapy patients. Moreover, chemotherapy significantly prolonged the DFS and OS of the high CS-SVM patients in the training and validation cohorts. In conclusion, PAK6 was an independent prognostic factor and increased chemoresistance. The CS-SVM classifier distinguished a subgroup of stage II and III patients who would highly benefit from chemotherapy, thus facilitating patient counseling and individualizing the management.

Although CircRNA_100269 is a biomarker used to predict cancer recurrence, its expression and function in gastric cancer (GC) remain unknown. In this study, the expression of circRNA_100269 and its potential downstream miRNA targets were investigated. The molecular function and regulatory mechanism of circRNA_100269 in GC cell lines were also elucidated. The expression levels of circRNA_100269 and its linear isomer LPHN2 mRNA were found to be downregulated (p

BACKGROUND This is a retrospective observational study evaluating the prevalence and clinical characteristics of spontaneous splenorenal shunt in liver cirrhosis. MATERIAL AND METHODS We included a total of 105 cirrhotic patients who were admitted to our hospital between June 2012 and December 2013 and underwent contrast-enhanced CT and/or MRI scans at admissions. Spontaneous splenorenal shunt was identified. Clinical and laboratory data were compared between cirrhotic patients with and without spontaneous splenorenal shunt. RESULTS The prevalence of spontaneous splenorenal shunt was 10.5% (11/105). The prevalence of hepatic encephalopathy was higher in patients with spontaneous splenorenal shunt than in those without spontaneous splenorenal shunt (18.2% vs. 4.3%, p=0.062), but the difference between them was not statistically significant. The prevalence of acute upper-gastrointestinal bleeding was lower in patients with spontaneous splenorenal shunt than in those without spontaneous splenorenal shunt (0% vs. 18.1%, p=0.205), but the difference between them was not statistically significant. Patients with spontaneous splenorenal shunt had significantly higher Child-Pugh scores (9.50±1.65 vs. 7.43±2.02, p=0.002) and MELD scores (11.26±7.29 vs. 5.67±6.83, p=0.017) than those without spontaneous splenorenal shunt. In-hospital mortality was similar between them (0% vs. 4.3%, p=1.000). CONCLUSIONS Spontaneous splenorenal shunt might be associated with worse liver function in liver cirrhosis, but not with in-hospital mortality.

// Wende Li 1, 2,4 , Weining Yang 3 , Yujiao Liu 2 , Siyu Chen 4 , Shanmin Chin 2 , Xiaolong Qi 2 , Yingchao Zhao 5 , Hao Liu 2 , Jiasheng Wang 1 , Xueting Mei 1 , Peigen Huang 2 and Donghui Xu 1 1 Laboratory of Traditional Chinese Medicine and Marine Drugs, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China 2 Edwin L. Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA 3 Sunnybrook Health Sciences Centre and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada 4 Guangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory of Laboratory Animals, Guangzhou 510663, China 5 Cancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Correspondence to: Donghui Xu, email: donghuixu007@163.com Keywords: miR-378, glioblastoma, U87, curcumin Received: December 29, 2016 Accepted: March 30, 2017 Published: May 16, 2017 ABSTRACT Glioblastoma multiforme is the most aggressive and common primary brain tumor, and is virtually incurable due to its therapeutic resistance to radiation and chemotherapy. Curcumin is a well-known phytochemical exhibiting antitumor activity on many human cancers including glioblastoma multiforme. Given the unique miRNA expression profiles in cancer cells compared to non-cancerous cells, we investigated whether these miRNA could be used to cancer therapy. In this report we show that miR-378, a glioblastoma multiforme down regulated miRNA, may enhance the inhibitory effect of curcumin on this cancer growth. Our results indicated that the inhibitory effect of curcumin was enhanced in miR-378-expressing stable U87 cells in vitro and in vivo, compared to control cells. MiR-378 was found to target p-p38 expression, underlying the observed phenotypic changes. Thus, we concluded that miR-378 enhances the response of glioblastoma multiforme to curcumin treatment, by targeting p38.

BACKGROUND: To evaluate the prognostic value of E-cadherin, CD44, and MSH2 expression for colorectal cancer (CRC) and construct nomograms that can predict prognosis. METHODS: We retrospectively analyzed the expression of E-cadherin, CD44, and MSH2 in 223 paraffin-embedded stage II and III CRC specimens using immunohistochemistry in the training cohort. Their prognostic values were assessed using Kaplan–Meier curves and univariate and multivariate COX regression models. Moreover, a number of risk factors were used to form nomograms to evaluate survival, and Harrell's concordance index (C-index) was used to evaluate the predictive accuracy. Further validation of the nomograms was performed in an independent cohort of 115 cases. RESULTS: Low E-cadherin expression and low CD44 expression were significantly associated with diminished overall survival (OS) and disease-free survival (DFS) in stage II and III CRC patients and patients with negative MSH2 expression had better clinical outcomes. Moreover, the multivariate COX analysis identified E-cadherin, CD44 and MSH2 expression as independent prognostic factors for DFS and OS. Using these three markers and three clinicopathological risk variables, two nomograms were constructed and externally validated for predicting OS and DFS (C-index: training cohort, 0.779 (95% CI 0.722–0.835) and 0.771 (0.720–0.822), respectively; validation cohort, 0.773 (0.709–0.837) and 0.670 (0.594–0.747), respectively). CONCLUSION: The expression levels of E-cadherin, CD44 and MSH2 were independent prognostic factors for stage II and III CRC patients. By incorporating clinicopathological features and these biomarkers, we have established two nomograms that could be used to make individualized predictions for OS and DFS.

// Jing Wang 1, * , Yongzhao Zhao 2, * , Ruizhao Qi 3, * , Xiaoning Zhu 1 , Chenshen Huang 2 , Sijin Cheng 2 , Shengzhi Wang 3 and Xiaolong Qi 1 1 Department of Hepatobiliary Disease, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China 2 School of Medicine, Tongji University, Shanghai, China 3 Department of General Surgery, 302 Hospital of PLA, Beijing, China * These authors have contributed equally to this work Correspondence to: Yongzhao Zhao, email: yongzhao_zhao@163.com Shengzhi Wang, email: 994233529@qq.com Keywords: prognostic, podocalyxin-like protein, cancer, overall survival Received: October 19, 2016 Accepted: November 20, 2016 Published: December 25, 2016 ABSTRACT Several studies were conducted to explore the prognostic significance of podocalyxin-like protein (PODXL) expression in various cancers, with contradictory. This study aims to summarize the prognostic significance of PODXL expression in cancers. PubMed, the Cochrane Library and Embase were completely retrieved. The prospective or retrospective studies focusing on the prognostic role of PODXL expression in cancers were eligible. The endpoints were overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS).12 studies involving a total of 5,309 patients were identified. The results indicated that high PODXL expression was significantly associated with worse OS when compared to the low PODXL expression (HR=1.76, 95%CI=1.53-2.04, p

The reproductive efficiency of roosters is an important trait in poultry production; however, the molecular mechanisms underlying this trait are not clearly understood. Here, we compared the mRNA and microRNA (miRNA) transcriptomes of testis from roosters with divergent sperm motility. A total of 302 differentially expressed genes (DEGs), including 182 upregulated genes and 120 downregulated genes, were identified in high sperm motility groups compared with low sperm motility groups. A subset of these DEGs related to steroid hormone biosynthesis and thus could be important for spermatogenesis. Additionally, we detected 13 differentially expressed miRNAs (DEMs) between two groups, and target gene prediction indicated seven of these could be associated with spermatogenesis. Based on a comprehensive analysis of these transcriptomes, miRNA-mRNA interaction networks were constructed. Six DEGs were predicted to be regulated by DEMs. Subsequently, we validated the negative regulation of family with sequence similarity 84, member A (FAM84A) by miR-215 using a dual-luciferase reporter system. These results provide new insights into the molecular profile of the testis and identify genes that may determine sperm motility in chickens.

Background and Aims. Liver fibrosis blood tests, platelet count/spleen diameter ratio (PSR), and contrast-enhanced CT are diagnostic alternatives for gastroesophageal varices, but they have heterogeneous diagnostic performance among different study populations. Our study is aimed at evaluating their diagnostic accuracy for esophageal varices (EVs) and gastric varices (GVs) in cirrhotic patients with and without previous endoscopic variceal therapy. Methods. Patients with liver cirrhosis who underwent blood tests and contrast-enhanced CT scans as well as endoscopic surveillance should be potentially eligible. EVs needing treatment (EVNTs) and GVs needing treatment (GVNTs) were recorded according to the endoscopic results. Area under the curves (AUCs) were calculated. Results. Overall, 279 patients were included. In 175 patients without previous endoscopic variceal therapy, including primary prophylaxis population (n=70), acute bleeding population (n=38), and previous bleeding population (n=67), the diagnostic accuracy of contrast-enhanced CT for EVNTs was higher (AUCs=0.816‐0.876) as compared to blood tests and PSR; by comparison, the diagnostic accuracy of contrast-enhanced CT for GVNTs was statistically significant among primary prophylaxis population (AUC=0.731, P=0.0316), but not acute or previous bleeding population. In 104 patients with previous endoscopic variceal therapy (i.e., secondary prophylaxis population), contrast-enhanced CT was the only statistically significant alternative for diagnosing EVNTs and GVNTs but with modest accuracy (AUCs=0.673 and 0.661, respectively). Conclusions. Contrast-enhanced CT might be a diagnostic alternative for EVNTs in cirrhotic patients, but its diagnostic performance was slightly weakened in secondary prophylaxis population. Additionally, contrast-enhanced CT may be considered for diagnosis of GVNTs in primary prophylaxis population without previous endoscopic variceal therapy and secondary prophylaxis population.

ObjectiveThis meta-analysis was performed to investigate the correlation between von Willebrand factor (vWF) antigen and hepatic venous pressure gradient (HVPG) and to evaluate the diagnostic performance of vWF to detect clinically significant portal hypertension (CSPH) and severe portal hypertension (SPH).DesignSystematic review and meta-analysis.MethodsMEDLINE, EMBASE, Web of Science and the Cochrane Library were screened up to 5 April 2018. Studies related to the diagnostic performance of vWF to detect CSPH and/or SPH with HVPG as the reference standard were included. Study quality was assessed by using the Quality Assessment of Diagnostic Accuracy Studies scale. Two authors independently used a standardised form to extract data.OutcomesThe primary outcome was the correlation coefficient between vWF and HVPG. The secondary outcome was the diagnostic performance of vWF to detect CSPH or SPH.ResultsA total of six articles involving 994 patients were included in this study. Five of the included articles were used to stratify the results for the correlation coefficient, three for the diagnostic performance of CSPH and two for SPH. The pooled correlation coefficient based on the random effects model was 0.54 (95% CI 0.35 to 0.69), thus suggesting a moderate correlation between vWF and HVPG. The pooled sensitivity, specificity and area under the curve of vWF for CSPH detection were 82% (95% CI 78 to 86), 76% (95% CI 68 to 83) and 0.87 (95% CI 0.80 to 0.94), respectively. Regarding the ability of vWF to detect SPH, the pooled sensitivity and specificity were 86% (95% CI 80 to 90) and 75% (95% CI 66 to 83), respectively. These results supported the satisfactory diagnostic performance of vWF for CSPH and SPH detection.ConclusionsvWF, as a novel biomarker, has a moderate correlation with HVPG and shows a satisfactory performance for the diagnosis of CSPH and SPH in patients with cirrhosis.