FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Ootheca mantidis mitigates renal fibrosis in mice by the suppression of apoptosis via increasing the gut microbe Akkermansia muciniphila and modulating glutamine metabolism.

Renal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut-renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.

Premorbid Steatohepatitis Increases the Seriousness of Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice.

Background and Aims: The concurrence of nonalcoholic steatohepatitis (NASH) and ulcerative colitis (UC) is increasingly seen in clinical practice, but the underlying mechanisms remain unclear. This study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet (HFHCD)-induced NASH and dextran sulfate sodium (DSS)-induced UC, that would support mechanistic studies. Methods: Male C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH modeling. The mice were the divided into four subgroups for UC modeling: (1) A control group given a chow diet with normal drinking water; (2) A colitis group given chow diet with 2% DSS in drinking water; (3) A steatohepatitis group given HFHCD with normal drinking water; and (4) A steatohepatitis + colitis group given HFHCD with 2% DSS in drinking water. Results: NASH plus UC had high mortality (58.3%). Neither NASH nor UC alone were fatal. Although DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice, premorbid NASH significantly increased UC-related gut injury compared with UC alone. It was characterized by a significantly shorter colon, more colonic congestion, and a higher histopathological score (p<0.05). Inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, C-C motif chemokine ligand 2, and nuclear factor kappa B) and apoptotic (Bcl2, Bad, Bim, and Bax) signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis + colitis compared with the other experimental groups. Conclusions: Premorbid steatohepatitis significantly aggravated DSS-induced colitis and brought about a lethal phenotype. Potential links between NASH and UC pathogeneses can be investigated using this model.

Association of maternal obesity and gestational diabetes mellitus with overweight/obesity and fatty liver risk in offspring.

BACKGROUND: Childhood obesity and fatty liver are associated with adverse outcomes such as diabetes, metabolic syndrome, and cardiovascular diseases in adulthood. It is very important to identify relevant risk factors and intervene as early as possible. At present, the relationship between maternal and offspring metabolic factors is conflicting. AIM: To estimate the association of maternal obesity and gestational diabetes mellitus (GDM) with overweight/obesity and fatty liver risk in offspring at 8 years of age. METHODS: The prospective study included mothers who all had a 75-g oral glucose tolerance test at 24-28 wk of gestation and whose offspring completed follow-up at 8 years of age. Offspring birth weight, sex, height, weight, and body mass index (BMI) were measured and calculated. FibroScan-502 examination with an M probe (Echosens, Paris, France) was prospectively conducted in offspring aged 8 years from the Shanghai Prenatal Cohort Study. RESULTS: A total of 430 mother-child pairs were included in the analysis. A total of 62 (14.2%) mothers were classified as obese, and 48 (11.1%) were classified as having GDM. The mean age of the offspring at follow-up was 8 years old. Thirty-seven (8.6%) offspring were overweight, 14 (3.3%) had obesity, and 60 (14.0%) had fatty liver. The prevalence of overweight, obesity and fatty liver in offspring increased significantly across maternal BMI quartiles (all P < 0.05). Among offspring of mothers with GDM, 12 (25.0%) were overweight, 4 (8.3%) were obese, and 12 (25.0%) had fatty liver vs. 25 (6.5%), 10 (2.6%) and 48 (12.6%), respectively, for offspring of mothers without GDM (all P < 0.05). In multiple logistic regression, after adjustment for variables, the OR for fatty liver in offspring was 8.26 (95%CI: 2.38-28.75) for maternal obesity and GDM. CONCLUSION: This study showed that maternal obesity can increase the odds of overweight/obesity and fatty liver in offspring, and GDM status also increases the odds of overweight/obesity in offspring. Weight management and glycemic control before and during pregnancy need to be highlighted in primary prevention of pediatric obesity and fatty liver.

The burden and sexual dimorphism with nonalcoholic fatty liver disease in Asian children: A systematic review and meta-analysis.

BACKGROUND: Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. METHODS: We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed. RESULTS: Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P < .0001) were positively correlated with prevalent NAFLD. CONCLUSIONS: In Asia, paediatric NAFLD is becoming prevalent over the recent decades, particularly among obese children and boys after 10 years old. The hormonal and chromosomal origins of paediatric NAFLD dimorphism need further investigation.

Efficacy of Intragastric Balloons in the Markers of Metabolic Dysfunction-associated Fatty Liver Disease: Results from Meta-analyses.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), is common in obese patients. Intragastric balloon (IGB), an obesity management tool with low complication risk, might be used in MAFLD treatment but there is still unexplained heterogeneity in results across studies. METHODS: We conducted a systematic search of 152 citations published up to September 2020. Meta-analyses, stratified analyses, and meta-regression were performed to evaluate the efficacy of IGB on homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), and to identify patients most appropriate for IGB therapy. RESULTS: Thirteen observational studies and one randomized controlled trial met the inclusion criteria (624 participants in total). In the overall estimate, IGB therapy significantly improved the serum markers change from baseline to follow-up [HOMA-IR: 1.56, 95% confidence interval (CI)=1.16-1.95; ALT: 11.53 U/L, 95% CI=7.10-15.96; AST: 6.79 U/L, 95% CI=1.69-11.90; GGT: 10.54 U/L, 95% CI=6.32-14.75]. In the stratified analysis, there were trends among participants with advanced age having less change in HOMA-IR (1.07 vs. 1.82). The improvement of insulin resistance and liver biochemistries with swallowable IGB therapy was no worse than that with endoscopic IGB. Multivariate meta-regression analyses showed that greater HOMA-IR loss was predicted by younger age (p=0.0107). Furthermore, effectiveness on ALT and GGT was predicted by basal ALT (p=0.0004) and GGT (p=0.0026), respectively. CONCLUSIONS: IGB is effective among the serum markers of MAFLD. Younger patients had a greater decrease of HOMA-IR after IGB therapy.

Influence of weight management on the prognosis of steatohepatitis in chronic hepatitis B patients during antiviral treatment.

BACKGROUND: Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment. METHODS: In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72. RESULTS: A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P > 0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P < 0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/m2 (Asian criteria) [odds ratio (OR): 0.414; 95% confidence interval (95% CI): 0.190-0.899; P = 0.012] and weight gain (OR: 0.187; 95% CI: 0.050-0.693; P = 0.026) were less likely to have NASH resolution. Among patients without NASH at baseline, 22 (3.7%) developed NASH. Baseline BMI ≥ 23 kg/m2 (OR: 12.506; 95% CI: 2.813-55.606; P = 0.001) and weight gain (OR: 5.126; 95% CI: 1.674-15.694; P = 0.005) were predictors of incident NASH. CONCLUSIONS: Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation.

The presence of NAFLD in nonobese subjects increased the risk of metabolic abnormalities than obese subjects without NAFLD: a population-based cross-sectional study.

BACKGROUND: With lifestyle modification and over-nutrition, the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing annually. Here we aimed to assess the updated prevalence of NAFLD, and to evaluate the association of NAFLD with metabolic abnormalities according to gender, body mass index and age. METHODS: A population-based cross-sectional study was conducted in Shanghai from December 2016 to July 2017. With a three-stage stratified sampling strategy, 3,717 eligible participants were enrolled for the analysis. RESULTS: In total, 1,217 subjects (32.7%) had NAFLD. Among them, 400 (16.3%) of the nonobese and 817 (65.0%) of the obese subjects had NAFLD. The prevalence of NAFLD was increased according to the quartiles of age and waist circumference (WC) in the nonobese subjects. Females with nonobese NAFLD had 1.6-, 2.6-, 2.0-, 2.3- and 3.3-fold higher risks for metabolic syndrome, diabetes mellitus, hyperglycemia, hypertriglycerdemia (high TG) and low high-density lipoprotein cholesterol than obese subjects without NAFLD, respectively. Males had comparable metabolic profiles in both groups, except for a 2.0-fold higher risk of high TG in nonobese NAFLD subjects compared with obese subjects without NAFLD. More impressively, the homeostasis metabolic assessment insulin resistance index was comparable between the two groups. CONCLUSIONS: The increase of age and WC had significant impact on the risk of NAFLD in nonobese subjects. The presence of NAFLD in nonobese subjects increased the risk of metabolic diseases than obese subjects without NAFLD, especially in female.

Comparative efficacy and safety of antithrombotic therapy for transcatheter aortic valve replacement: a systematic review and network meta-analysis.

OBJECTIVES: We sought to determine the optimal antithrombotic therapy after transcatheter aortic valve replacement. METHODS: Related scientific databases were searched until December 2018. We conducted a pairwise and a network meta-analysis within a frequentist framework, measuring 30-day bleeding, stroke and all-cause mortality. The surface under the cumulative ranking (SUCRA) curve was estimated to rank the therapies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was performed. The protocol was registered with PROSPERO (CRD42018111163). RESULTS: Eight studies comprising 2173 patients were analysed. The risk of 30-day bleeding was higher for dual antiplatelet therapy (DAPT) than single antiplatelet therapy (SAPT) [odds ratio (OR) 1.90 (1.10-3.28); P = 0.02], whereas there was no difference in the risk of 30-day stroke [OR 1.27 (0.38-4.20); P = 0.69] and mortality [OR 1.46 (0.67-3.22); P = 0.34] between DAPT and SAPT. In the network meta-analysis, DAPT + oral anticoagulant (OAC) increased the risk of 30-day bleeding compared with SAPT [OR 6.21 (1.74-22.17); P = 0.005], DAPT [OR 3.27 (1.04-10.32); P = 0.043], SAPT + OAC [OR 4.87 (2.51-9.45); P < 0.001] and OAC [OR 14.4 (1.3-154.7); P = 0.028]. Additionally, patients receiving DAPT + OAC had the highest risks for 30-day bleeding (SUCRA 1.0%). OAC seemed to be superior to SAPT and DAPT in terms of 30-day bleeding (SUCRA OAC: 86.3%, SAPT: 72.3%, DAPT: 32.3%) and stroke (SUCRA 54.2%, 47.4%, 40.5%), but not mortality (SUCRA 69.6%, 74.1%, 43.4%). CONCLUSIONS: There is a trend towards less bleeding with the application of SAPT, but no mortality benefit with the application of DAPT is shown. The comparison of SAPT, DAPT and OAC shows that OAC may improve the balance between stroke and bleeding, which can reduce the risk of mortality. In addition, the application of DAPT + OAC was ranked the worst amongst all treatment modalities and should be avoided due to an increased risk of bleeding. CLINICAL TRIAL REGISTRATION NUMBER: PROSPERO (International Prospective Register of Systematic Reviews, CRD42018111163).

von Willebrand factor as a biomarker of clinically significant portal hypertension and severe portal hypertension: a systematic review and meta-analysis.

OBJECTIVE: This 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). DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE, 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. OUTCOMES: The primary outcome was the correlation coefficient between vWF and HVPG. The secondary outcome was the diagnostic performance of vWF to detect CSPH or SPH. RESULTS: A 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. CONCLUSIONS: vWF, 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.

Emerging Trends and New Developments in Transient Elastography: A Bibliometric and Cocitation Analysis from 1999 to 2017.

Purpose: To identify and characterize the 100 most-cited articles in the field of transient elastography. Methods: The top-cited articles focusing on transient elastography from 1999 to 2017 were retrieved from Science Citation Index Expanded (SCI-E) database. The most prolific article, journal, country and continent, top-cited article in different period, international collaboration, cocitation analysis of journal were retrieved and analyzed in this article. Bibexcel 2016, Microsoft Excel 2010, and VOSviewer 1.6.5 were used to analyze bibliometric records we downloaded. Results: The 100 most-cited articles were published between 2003 and 2015. The total citations ranged from 54 to 1376 (mean, 167.52 ± 208.46; median, 89.5) and the annual citations ranged from 4.91 to 98.24 (mean, 17.21±15.68; median, 12.1). The top-cited article was published in Gastroenterology in 2005 by Castera L. et al. (n=1376). The most-cited articles in 2003-2007 (n=1380), 2008-2012 (n=599) and 2013-2017 (n=159) were located. All of the most-cited articles in three periods were focusing on the topic of noninvasive assessment of liver fibrosis. The most prolific author was de Ledinghen V. (n=21) and France (n=43) was the leading country. The most productive journal was Journal of Hepatology (n=20). The major article type was original research article. Conclusions: We undertook efforts to provide an insight into the features and evolvement of the most-cited articles in the field of transient elastography. For transient elastography, as a noninvasive assessment of liver fibrosis, its use in the evaluation of liver fibrosis is gradually mature and shows great advantages. Moreover, the field of transient elastography is in a stage of rapid development.

Systematic Review With Meta-analysis: Epidemiology of Nonalcoholic Fatty Liver Disease in Patients With Inflammatory Bowel Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is increasingly identified in patients with inflammatory bowel disease (IBD), but there are few systematic reviews and meta-analyses of the studies of NAFLD in IBD patients. METHODS: MEDLINE, Web of Science, Cochrane Library, and Scopus were searched (until August 2018) to identify observational studies that reported the prevalence and risk factors for NAFLD in IBD patients. Pooled prevalence, odds ratios (OR), mean difference (MD), and 95% confidence intervals (95% CI) were calculated. Study quality was assessed using the modified Newcastle-Ottawa scale. RESULTS: Of the 662 citations evaluated, 19 studies (including 5620 subjects) reported the prevalence of NAFLD in IBD population and were included for the analysis. The overall pooled prevalence was 27.5% (95% CI, 20.7%-34.2%). The prevalence was higher in older patients (MD = 8.22; 95% CI, 6.22-10.22), type 2 diabetes (OR = 3.85; 95% CI, 2.49-5.95), hypertension (OR = 3.18; 95% CI, 2.36-4.28), obesity (OR = 2.79; 95% CI, 1.73-4.50), insulin resistance (OR = 6.66; 95% CI, 1.28-34.77), metabolic syndrome (OR = 4.96; 95% CI, 3.05-8.05), chronic kidney disease (OR = 4.83; 95% CI, 1.79-13.04), methotrexate use (OR = 1.76; 95% CI, 1.02-3.06), surgery for IBD (OR = 1.28; 95% CI, 1.02-1.62), and longer duration of IBD (MD = 5.60; 95% CI, 2.24-8.97). CONCLUSIONS: We found that NAFLD was not uncommon in the IBD population. Older age, metabolic risk factors, methotrexate use, prior surgery, and longer duration of IBD are predictors for the presence of NAFLD in IBD. Screening of NAFLD might be recommended among IBD patients with the aforementioned factors.

Fecal microbiota transplantation research output from 2004 to 2017: a bibliometric analysis.

BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapy against Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although the therapy has gained prominence, there has been no bibliometric analysis of FMT. METHODS: Studies published from 2004 to 2017 were extracted from the Science Citation Index Expanded. Bibliometric analysis was used to evaluate the number or cooperation network of publications, countries, citations, references, journals, authors, institutions and keywords. RESULTS: A total of 796 items were included, showing an increasing trend annually. Publications mainly came from 10 countries, led by the US (n = 363). In the top 100 articles ranked by the number of citations (range 47-1,158), American Journal of Gastroenterology (2017 IF = 10.231) took the top spot. The co-citation network had 7 co-citation clusters headed by 'recurrent Clostridium difficile infection'. The top 7 keywords with the strongest citation bursts had three parts, 'microbiota', ' diarrhea ', and 'case series'. All keywords were divided into four domains, 'disease', 'nosogenesis', 'trial', and 'therapy'. CONCLUSIONS: This study shows the research performance of FMT from 2004 to 2017 and helps investigators master the trend of FMT, which is also an ongoing hotspot of research.

Artificial liver research output and citations from 2004 to 2017: a bibliometric analysis.

BACKGROUND: Researches on artificial livers greatly contribute to the clinical treatments for liver failure. This study aimed to evaluate the research output of artificial livers and citations from 2004 to 2017 through a bibliometric analysis. METHODS: A list of included articles on artificial livers were generated after a comprehensive search of the Web of Science Core Collection (from 2004 to 2017) with the following basic information: number of publications, citations, publication year, country of origin, authors and authorship, funding source, journals, institutions, keywords, and research area. RESULTS: A total of 968 included articles ranged from 47 citations to 394 citations with a fluctuation. The publications were distributed in 12 countries, led by China (n = 212) and the US (n = 207). There were strong correlations of the number of citations with authors (r 2 = 0.133, p < 0.001), and countries (r 2 = 0.275, p < 0.001), while no correlations of the number of citations with the years since publication (r 2 = 0.016, p = 0.216), and funding (r 2 < 0.001, p = 0.770) were identified. Keyword analysis demonstrated that with the specific change of "acute liver failure," decrease in "bioartificial livers" and "hepatocyte," and increase in "tissue engineering" were identified. The top 53 cited keyword and keyword plus (including some duplicates counts) were identified, led by bioartificial liver (405 citations) and hepatocyte (248 citations). The top 50 cited keywords bursts were mainly "Blood" (2004-2008), "hepatocyte like cell" (2008-2015), and "tissue engineering" (2014-2017). All keywords could be classified into four categories: bioartificial livers (57.40%), blood purification (25.00%), clinical (14.81%), and other artificial organs (2.78%). DISCUSSION: This study shows the process and tendency of artificial liver research with a comprehensive analysis on artificial livers. However, although it seems that the future of artificial livers seems brighter for hepatocyte transplantation, the systems of artificial livers now are inclined on focusing on blood purification, plasma exchange, etc.

Comparison of drugs facilitating endoscopy for patients with acute variceal bleeding: a systematic review and network meta-analysis.

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 coexpression of multi-immune inhibitory receptors on T lymphocytes in primary non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is a common disease threatening the health of humankind. It has a low survival rate and a poor prognosis. Under normal circumstances, tumor infiltrating lymphocytes (TILs) play the main role in the antitumor process, but studies in recent years have found that NSCLC is capable of releasing various immunosuppressive factors, inducing the TILs to exhibit high expression of immune inhibitory receptors and relevant immunosuppressive factors. They can not only activate their own signal pathways but also block those of TILs, which causes inefficiency of tumor destruction. Researchers have now developed targeted drugs that specifically bind to immunosuppression receptors. By blocking signal transmission of immune inhibitory receptors, restraint on T lymphocytes can be released to recover antitumor role. Further research and understanding of the immunosuppression signal pathways of NSCLC are of significant importance to promote the development of immune-targeted drugs and the formulation of new treatment plans. This paper summarizes the immunosuppressive mechanisms of multiple important and newly discovered immune inhibitory receptors on T lymphocytes and immunosuppressive factors released by NSCLC cells, and their influence on patients' survival rate and prognosis. Further laboratory and clinical studies on immune-targeted drugs for primary NSCLC are needed to provide more evidence.