Extracellular vesicle biomarkers for pancreatic cancer diagnosis: a systematic review and meta-analysis.

BACKGROUND: Extracellular vesicle (EV) biomarkers have promising diagnosis and screening capacity for several cancers, but the diagnostic value for pancreatic cancer (PC) is controversial. The aim of our study was to review the diagnostic performance of EV biomarkers for PC. METHODS: We performed a systematic review of PubMed, Medline, and Web Of Science databases from inception to 18 Feb 2022. We identified studies reporting the diagnostic performance of EV biomarkers for PC and summarized the information of sensitivity, specificity, area under the curve (AUC), or receiver operator characteristic (ROC) curve) in according to a pre-designed data collection form. Pooled sensitivity and specificity was calculated using a random-effect model. RESULTS: We identified 39 studies, including 2037 PC patients and 1632 noncancerous, seven of which were conducted independent validation tests. Seventeen studies emphasized on EV RNAs, sixteen on EV proteins, and sixteen on biomarker panels. MiR-10b, miR-21, and GPC1 were the most frequently reported RNA and protein for PC diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 79% (95% CI: 77-81%) and 87% (95% CI: 85-89%), 72% (95% CI: 69-74%) and 77% (95% CI: 74-80%), respectively. the pooled sensitivity and specificity of EV RNA combined with protein panels were 84% (95% CI: 81-86%) and 89% (95% CI: 86-91%), respectively. Surprisingly, for early stage (stage I and II) PC EV biomarkers showed excellent diagnostic performance with the sensitivity of 90% (95% CI: 87-93%) and the specificity of 94% (95% CI: 92-95%). Both in sensitivity and subgroup analyses, we did not observe notable difference in pooled sensitivity and specificity. Studies might be limited by the isolation and detection techniques of EVs to a certain extent. CONCLUSIONS: EV biomarkers showed appealing diagnostic preference for PC, especially for early stage PC. Solving the deficiency of technologies of isolation and detection EVs has important implications for application these novel noninvasive biomarkers in clinical practice.

Regular arrangement of collecting venules (RAC) as an endoscopic marker for exclusion of Helicobacter pylori (H. pylori) infection: A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (H. pylori) is the most common cause of gastric cancer. Growing evidence suggests that the regular arrangement of collecting venules (RAC) can be used as an endoscopic marker to diagnose H. pylori infection. However, data on the diagnostic accuracy of RAC for H. pylori infection are conflicting. We performed a systematic review and meta-analysis of relevant studies to determine the diagnostic accuracy and clinical utility of RAC for the diagnosis of H. pylori infection. METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library between inception and Oct 29, 2020, for studies that assessed the diagnostic accuracy of RAC for H. pylori infection. RESULTS: The literature search yielded 2921 non-duplicated screened titles, of which 58 underwent full-text review. Fifteen studies, representing a total of 6621 patients, met the inclusion criteria. The area under the summary receiver operating characteristic curve was 0.98 (95% CI 0.96-0.99). The pooled estimates for RAC were 0.98 (95% CI 0.95-0.99) for sensitivity and 0.75 (95% CI 0.54-0.88) for specificity. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.8 (95% CI 1.9-7.7) and 0.03 (95% CI 0.02-0.07), respectively. CONCLUSIONS: RAC can be used as an endoscopic marker for exclusion of H. pylori infection. However, it cannot be recommended as a single indicator for the confirmation of H. pylori infection. The conclusion of this study should be treated with caution because significant heterogeneity exists between the evaluated studies.

Rotating night shift work is associated with an increased risk of gastroesophageal reflux disease (GERD) symptoms among workers in China: A cross-sectional study.

AIMS OF THE STUDY: Increasing studies suggest a significant association between night shift work and an increased risk of type 2 diabetes, obesity and other metabolic disorders. However, the available evidence of the association of rotating night shift work with gastroesophageal reflux disease (GERD) is limited. Herein, we hypothesised a link between the GERD risk and rotating night shift work among workers in China. METHODS USED TO CONDUCT THE STUDY: A total of 2027 workers who completed a comprehensive health checkup were included. Logistic regression was used to investigate the link between rotating night shift work and the risk of GERD symptoms. Receiver operating characteristic (ROC) curve analysis was used to assess the multivariable model's diagnostic value for identifying GERD symptoms among workers. RESULTS OF THE STUDY: In total, 556 (27.4%) individuals had GERD symptoms among 2027 workers. Multivariate analysis showed five independent factors for GERD: rotating night shift work (OR = 3.66, 95% CI: 2.52-5.40), age (OR = 2.53, 95% CI: 1.67-3.78), smoking (OR = 3.70, 95% CI: 2.63-5.21), Helicobacter pylori (H. pylori) infection (OR = 0.68, 95% CI: 0.48-0.96) and obesity (OR = 3.04, 95% CI: 2.43-3.83). A five-variable model based on five independent factors provided an area under a ROC curve (AUROC) of 0.80 (95% CI: 0.78-0.81) for identifying GERD symptoms among workers. CONCLUSIONS DRAWN FROM THE STUDY AND CLINICAL IMPLICATIONS: Rotating night shift work is independently associated with an increased risk of GERD symptoms. Moreover a five-variable model (rotating night shift work, age, smoking, H pyori infection and obesity) can help identify individuals at high risk for GERD symptoms among workers in China.

Nonalcoholic fatty liver disease increases the risk of gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND: Increasing evidence indicates that nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of extra-hepatic conditions. However, it is currently uncertain whether NAFLD is associated with the risk of gastroesophageal reflux disease (GERD). We performed a systematic review and meta-analysis of relevant studies to examine the association between NAFLD and the risk of GERD. METHODS: We searched PubMed, Scopus, Embase and Web of Science from 1 January 1975 to 15 December 2018, using predefined terms to identify cross-sectional, case-control and cohort studies investigating the association between NAFLD and GERD. RESULTS: Nine observational studies involving 185 118 subjects were eligible for inclusion in the meta-analysis. Overall, NAFLD was significantly associated with an increased risk of GERD (random effect OR 1.28; 95% CI: 1.12-1.44, I2  = 82%). Moreover, the significant association between NAFLD and GERD was consistent both for studies with adjusted OR/HR (n = 6, random effect OR = 1.16, 95% CI: 1.03-1.30) and those with unadjusted OR/HR (n = 3, random effect OR = 2.09, 95% CI: 1.62-2.56) as measures of effect. Both funnel plot and Egger's test suggested the existence of publication bias. However, a sensitivity analysis by sequentially omitting each study did not alter the pooled outcome,suggesting the robustness of the association. CONCLUSION: NAFLD is associated with an increased risk of GERD. However, future large and cohort studies are still needed to determine the causal relationship between NAFLD and the risk of GERD.

Liver stiffness assessed by transient elastography as a potential indicator of chronic kidney disease in patients with nonalcoholic fatty liver disease.

BACKGROUND: This study was designed to determine the diagnostic value of liver stiffness measured by transient elastography (TE) in identifying chronic kidney disease (CKD) in individuals with ultrasonography-diagnosed NAFLD. METHODS: A total of 1439 adult patients with ultrasonography-diagnosed NAFLD between October 2015 and August 2017 in China-Japan union hospital of Jilin university were initially eligible. According to the exclusion criteria, 24 patients were excluded, and eventually, a total of 1415 patients were included in the study. The AST/ALT ratio and FIB-4 score were calculated from blood tests, and liver stiffness was measured using TE. RESULTS: The liver stiffness measured by TE, FIB-4 score, ALT/AST ratio were significantly elevated in CKD patients, compared with those without CKD (P < 0.001). The areas under the curve (AUROC) of liver stiffness, FIB-4 score and AST/ALT ratio were 0.694 (0.670-0.718), 0.707 (0.682-0.730), 0.712 (0.688-0.736), showing no statistically significant difference between these three tests. Further, multivariate analysis identified four independent risk factors for CKD: age, diabetes mellitus, serum uric acid, and liver stiffness. Also, the performance of these four independent variables taken together in a logistic regression model for identifying CKD was 0.834 (AUROC; 95%CI: 0.814-0.853), showing a higher diagnostic performance than that of a single application of liver stiffness. CONCLUSIONS: Liver stiffness assessed by TE is a potential indicator for CKD in ultrasonography-diagnosed NAFLD patients. Further, a four-variable model (liver stiffness, age, serum uric acid, and diabetes mellitus) could be a useful tool for identifying subjects at high risk for CKD in NAFLD patients.

Epidemiology of Hepatitis B and Hepatitis C Infections and Benefits of Programs for Hepatitis Prevention in Northeastern China: A Cross-Sectional Study.

BACKGROUND: To investigate the epidemiology of hepatitis B and C infections and the benefits of programs aimed at hepatitis prevention and control in Northeastern China. METHODS: Individuals receiving health examinations were recruited to complete a questionnaire and undergo laboratory tests for hepatitis infection. Data on demographic characteristics, results of hepatitis B virus (HBV) and hepatitis C virus (HCV) serological tests, for HBV and HCV infection were analyzed. RESULTS: Among 227 808 study participants, the hepatitis B surface antigen (HBsAg) and anti-HCV-positive rates were 6.1% and 3.0%, respectively. Among HBsAg-positive participants, 63.8% tested positive for HBV DNA, 20.2% had an abnormal alanine aminotransferase (ALT) level, and 10.7% had cirrhosis. Among anti-HCV-positive participants, 57.2% tested positive for HCV RNA, 29.6% had an abnormal ALT level, and 8.4% had cirrhosis. Among HBsAg- or anti-HCV-positive participants, 47.1% and 32.0%, respectively, were aware of their infection. Among participants infected with HBV or HCV and suitable for antivirus treatment, 23.5% and 16.1%, respectively, had received antivirus treatment. The HBV plus HCV coinfection rate was 0.08%. CONCLUSIONS: The HBsAg-positive rate decreased significantly after implementation of recently introduced HBV control programs in China. However, the anti-HCV-positive rate showed only a slight decrease, indicating that programs for the prevention and control of hepatitis viruses require continued strengthening. CHINESE CLINICAL TRIALS REGISTRATION: ChiCTR-ECS-13004009.

Pegylated interferon α-2a plus ribavirin for decompensated hepatitis C virus-related cirrhosis: relationship between efficacy and cumulative dose.

BACKGROUND & AIMS: A combination of pegylated interferon alpha-2a (Peg-IFNα-2a) and ribavirin (RBV) achieves a sustained virological response (SVR) in 40-50% of patients infected with genotype 1 hepatitis C virus (HCV), but efficacy rates are significantly lower in patients with decompensated HCV-induced cirrhosis. The efficacy and tolerability of Peg-IFNα-2a and RBV, the cumulative dose effect, time to achieve planned cumulative dose and role of HCV phenotype on treatment response were determined in patients with decompensated HCV-induced cirrhosis. METHODS: In this case-controlled study, 257 patients with decompensated HCV-induced cirrhosis were enrolled, including patients treated with partial splenic embolization for leukopaenia. Of patients with sufficient blood cell counts, 130 patients opted for antiviral therapy (treatment group) consisting of 180 µg/kg Peg-IFNα-2a for 48 weeks with 800-1200 mg/day RBV; the remaining 127 were considered the control group. Primary endpoints were SVR and absence of relapse; the secondary end point was assessment of disease progression. RESULTS: Sustained virological response was highest and relapse rates were lowest when cumulative doses of Peg-IFNα-2a and RBV were both ≥80% of the prescribed dose. Patients achieving ≥80% of the planned cumulative doses in 48 weeks had a significantly higher SVR compared with patients achieving this in 72 weeks. Patients with HCV genotype 1 had significantly lower SVR compared with patients with HCV genotype 2 (19.7% vs. 42.9%, respectively; P = 0.008). Treatment group patients had a significantly lower rate of SVR-independent liver disease-related mortality. CONCLUSIONS: Our findings provide additional evidence to support the use of Peg-IFNα-2a and RBV therapy for decompensated HCV-induced cirrhosis.

Extracellular vesicle biomarkers for prostate cancer diagnosis: A systematic review and meta-analysis.

Extracellular vesicle (EV) biomarkers have promising diagnostic and screening capabilities for several cancers, and growing evidence indicates that EV biomarkers can be used as diagnostic markers for prostate cancer (CaP). However, data on the diagnostic accuracy of EV biomarkers for CaP diagnosis are conflicting. We performed a systematic review and meta-analysis, aimed to summarize the diagnostic performance of EV biomarkers for CaP. We systematically searched PubMed, Medline, and Web of Science from inception to 12 September 2022 for studies that assessed the diagnostic accuracy of EV biomarkers for CaP. We summarized the pooled sensitivity and specificity calculated using a random-effects model. We identified 19 studies involving 976 CaP patients and 676 noncancerous controls; one study conducted independent validation tests. Ten studies emphasized EV RNAs, 6 on EV proteins, and 9 on biomarker panels. MiR-141, miR-221, and PSMA were the most frequently reported RNAs and proteins for CaP diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 70% (95% CI: 68%-71%), 79% (95% CI: 77%-80%), 85% (95% CI: 81%-87%), and 83% (95% CI: 80%-86%), respectively. The pooled sensitivity and specificity of the EV panels were 84% (95% CI: 82%-86%) and 86% (95% CI: 84%-88%), respectively. The studies may have been somewhat limited by the EV isolation and detection techniques. EV biomarkers showed promising diagnostic capability for CaP. Addressing deficiencies in EV isolation and detection techniques has important implications for the application of these novel noninvasive biomarkers in clinical practice.

Extracellular vesicle biomarkers in circulation for the diagnosis of gastric cancer: A systematic review and meta­analysis.

The prognosis of a gastric cancer (GC) diagnosis is poor due to the current lack of effective early diagnostic methods. Extracellular vesicle (EV) biomarkers have previously demonstrated strong diagnostic efficiency for certain types of cancer, including pancreatic and lung cancer. The present review aimed to summarize the diagnostic value of circulating EV biomarkers for early stage GC. The PubMed, Medline and Web of Science databases were searched from May 1983 to September 18, 2022. All studies that reported the diagnostic performance of EV biomarkers for GC were included for analysis. Overall, 27 studies were selected containing 2,831 patients with GC and 2,117 controls. A total of 58 EV RNAs were reported in 26 studies, including 39 microRNAs (miRNAs), 10 long non-coding RNAs (lncRNAs), five circular RNAs, three PIWI-interacting RNAs and one mRNA, in addition to one protein in the remaining study. Meta-analysis of the aforementioned studies demonstrated that the pooled sensitivity, specificity and AUC value of the total RNAs were 84, 67% and 0.822, respectively. The diagnostic values of miRNAs were consistent with the total RNA, as the pooled sensitivity, specificity and AUC value were 84, 67% and 0.808, respectively. The pooled sensitivity, specificity and AUC values of lncRNAs were 89, 69% and 0.872, respectively, markedly higher compared with that of miRNAs. A total of five studies reported the diagnostic performance of EV RNA panels for early stage GC and reported powerful diagnostic values with a pooled sensitivity, specificity and AUC value of 80, 77% and 0.879, respectively. Circulating EV RNAs could have the potential to be used in the future as effective, noninvasive biomarkers for early GC diagnosis. Further research in this field is necessary to translate these findings into clinical practice.

Achieving NIR Light-Mediated Tumor-Specific Fenton Reaction-Assisted Oncotherapy by Using Magnetic Nanoclusters.

As an emerging strategy for oncotherapy, Fenton chemistry can efficiently improve the conversion from endogenous H2O2 into highly toxic ·OH in the whole high-performance therapeutic process. Although promising, the efficiency of Fenton reaction in tumor regions is highly limited by the inefficient delivery of Fenton reagents and the restrictive conditions of tumor microenvironment. One promising strategy against the above limitations is to specifically increase the temperature around the tumor regions. In this study, a novel NIR light-mediated tumor-specific nanoplatform based on magnetic iron oxide nanoclusters (MNCs) was rationally designed and well developed for photothermally enhanced Fenton reaction-assisted oncotherapy. MNCs could accumulate into the tumor regions with the help of an external magnet field to enable T2-weighted magnetic resonance (MR) imaging of tumors and MR imaging-guided combined antitumor therapy. Our well-prepared MNCs also revealed excellent photothermal effect upon a NIR light irradiation, promising their further important role as a photothermal therapy (PTT) agent. More importantly, heat induced by the PTT of MNCs could accelerate the release of Fe from MNCs and enhance the efficiency of Fenton reaction under H2O2-enriched acidic tumor microenvironment. Results based on long-term toxicity investigations demonstrated the overall safety of MNCs after intravenous injection. This work therefore introduced a novel nanoplatform based on MNCs that exerted a great antitumor effect via photothermally enhanced tumor-specific Fenton chemistry.

Atypical adult-onset Still's disease with an initial and sole manifestation of liver injury: A case report and review of literature.

BACKGROUND: Adult-onset Still's disease (AOSD) typically presents with a high spiking fever, polyarthritis, transient maculopapular rash, neutrophilic leukocytosis, and hepatosplenomegaly. It has a wide spectrum of clinical symptoms ranging from mild to severe, with extensive involvement of almost every organ. Although liver involvement in the form of increased hepatic enzymes and bilirubin is common, no AOSD case with liver involvement as the initial manifestation of AOSD has been reported. CASE SUMMARY: A 35-year-old woman presented to the hepatology department with progressively worsening jaundice for one week. Liver chemistry tests revealed a significantly increased liver enzymes and bilirubin level. Given that the clinical examination was unremarkable, liver biopsy was considered because the patient had a history of AOSD 6 years ago. Liver histopathology revealed that most hepatic lobules were still recognizable. Fusional necrosis was observed around most central veins. A few bridging necrotic zones were also found. Infiltration of multiple plasma cells were observed in the necrotic zone, and the reticular scaffold was still expanded. Additionally, no obvious fibrosis was observed in the portal area. Mild mixed inflammatory cell infiltration was noted in the interstitium of the portal area. Further examination was unremarkable except for a remarkably high level of ferritin. Collectively, a presumptive diagnosis of liver injury secondary to AOSD was made. The hepatic involvement responded well to glucocorticoid treatment. CONCLUSION: This case highlights that hepatic involvement as an initial and sole manifestation could be a pattern of relapsed AOSD. The diagnosis of AOSD should be considered in the case of nonresolving liver injury after the exclusion of common etiologies for liver diseases. A liver biopsy can be useful for the differential diagnosis of liver injury associated with AOSD.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the management of nonalcoholic fatty liver disease (NAFLD): A systematic review.

There are no licensed drugs for nonalcoholic fatty liver disease (NAFLD), and there is a lack of consensus on the best outcome measures for controlled trials. This systematic review aimed to evaluate the efficacy of GLP-1 RAs in the management of NAFLD, the degree of heterogeneity in trial design and the robustness of conclusions drawn from these clinical trials. We searched publication databases and clinical trial registries through 2 November 2019 for clinical trials with NAFLD. We evaluated improvements in histological findings, noninvasive markers of hepatic steatosis, inflammation, and fibrosis, insulin resistance and anthropometric measures. Our final analysis included 24 clinical trials, comprising 6313 participants with a mean duration of 37 weeks. Four clinical trials, including RCT (n = 1), single-arm studies (n = 2) and case series studies (n = 1), used biopsy-confirmed liver histological change as their end-points. The remaining studies (n = 20) used surrogate end-points. GLP-1 RAs were effective for the improvement in hepatic inflammation, hepatic steatosis and fibrosis. More importantly, GLP-1 RAs showed promise in improving the histological features of NASH. In addition, 8 ongoing trials were identified. In this systematic review of published and ongoing clinical trials of the efficacy of GLP-1RAs for NAFLD, we found that GLP-1 RAs are effective for hepatic steatosis and inflammation, with the potential to reverse fibrosis. Further prospective studies of sufficient duration using histological end-points are needed to fully assess the efficacy of GLP-1 RAs in the management of NAFLD.

The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection: An updated meta-analysis.

Single nucleotide polymorphisms (SNPs) of the interleukin 28B (IL28B) gene has proven to be associated with the clinical outcome of patients with chronic hepatitis virus B or C (HBV or HCV) infections. However, whether IL28B SNPs have an influence on the risk of hepatocellular carcinoma (HCC) among patients with HBV or HCV infection remains controversial. Therefore, this study aims to determine the association between IL28B polymorphisms and the risk of HCC in individuals with HBV or HCV infection.PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were used to identify studies meeting the selection requirements using the terms "interleukin 28B", "IFN-lambda-3", "IFNL3", "single nucleotide polymorphisms", "SNPs", "hepatocellular carcinoma", "HCC", "liver cancer".A total of 24 eligible original studies (1 cohort study and 23 case-control studies) involved 20238 individuals (HCC group = 8725 vs control group = 11,513) were included. Both IL28B rs12979860 CC and rs8099917 TT genotypes were significantly associated with a decreased risk of HCC among patients with HBV or HCV infection (OR = 0.71, 95% CI = 0.57-0.88; OR = 0.82, 95% CI = 0.72-0.94, respectively). Egger test and Begg test revealed no' publication bias (P > .05). Sensitivity analyses suggested the robustness of the results in this meta-analysis.Both IL28B rs12979860 CC and rs8099917 TT genotypes are protective factors for the development of HCC among patients with HBV or HCV infection. Future prospective studies examining the impact of IL28B polymorphisms on the risk of HCC and investigating the underlying mechanism for the protective role of IL28B polymorphisms in HCC development are warranted.

The association between a non-invasive hepatic fibrosis score and urolithiasis among non-alcoholic fatty liver disease (NAFLD) patients in China: a cross-sectional study.

OBJECTIVE: Mounting data now support a strong link between the presence of non-alcoholic fatty liver disease (NAFLD) and an increased risk of urolithiasis. However, little is known on the association between hepatic fibrosis and the risk of urolithiasis among NAFLD patients. Therefore, this study aimed to investigate the prevalence of urolithiasis among NAFLD patients and determine whether the Fibrosis-4 (FIB-4) score, a surrogate marker of hepatic fibrosis, is associated with urolithiasis among NAFLD patients. DESIGN: Cross-sectional studies. SETTING: China. METHODS: A total of 2058 adult patients with NAFLD were included in this study. Logistic regression analysis was used to detect the association between FIB-4 score and urolithiasis. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of FIB-4 score for the detection of urolithiasis among NAFLD patients. RESULTS: 200 (9.7%) individuals had ultrasonography-diagnosed urolithiasis among 2058 NAFLD patients. FIB-4 score (OR=1.58; 95% CI 1.06 to 2.31), age (OR=1.11; 95% CI 1.08 to 1.13), obesity (OR=3.16; 95% CI 2.29 to 4.39) and hyperuricemia (OR=3.79; 95% CI 2.67 to 5.36) were independent factors associated with urolithiasis among NAFLD patients. Moreover, a novel algorithm including multiple variables (FIB-4 score, age, obesity and hyperuricemia) showed an area under a ROC curve of 0.813 (95% CI 0.795 to 0.829) for identifying urolithiasis among NAFLD patients. The optimal cut-off value of > -2.23 for the multivariate model provides a sensitivity of 76% and a specificity of 74% for predicting urolithiasis among NAFLD patients. CONCLUSION: Urolithiasis among NAFLD patients is associated with FIB-4 score. Further, a novel algorithm based on FIB-4 score could serve as a useful tool for identifying individuals with a higher risk of urolithiasis among NAFLD patients, although prospective cohort studies are still needed in the future.

Non-alcoholic fatty liver disease and the risk of urolithiasis: A systematic review and meta-analysis.

There is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with a higher risk of urolithiasis, but it has not yet been determined that this association is reproducible and consistent across different studies. We performed a systematic review and meta-analysis of these studies to examine the association between NAFLD and the risk of urolithiasis.We searched PubMed, EMBASE, and Google scholar using terms "fatty liver" (OR "non-alcoholic fatty liver disease" OR "non-alcoholic steatohepatitis" OR "NAFLD" OR "NASH") AND "urolithiasis" (OR "nephrolithiasis" OR "kidney stone" OR "urinary calculi" OR "renal colic" OR "urologic disease"). Observational studies in which NAFLD and urolithiasis were diagnosed by either ultrasonography or computerized tomography were included.A total of 7 observational studies with 226,541 individuals (24.7% with NAFLD) and 19,184 urolithiasis (8.5%). NAFLD was significantly associated with an increased risk of urolithiasis (random effect odds ratio, OR 1.73, 95% confidence interval, CI 1.24-2.40, I=94.5%). Sensitivity analyses revealed the robustness of the results. Egger test and Begg test suggested no publication bias (P > .05).NAFLD is associated with an increased risk of urolithiasis. Therefore, patients with NAFLD should be carefully monitored for the development of urolithiasis.

The Significant Pathways and Genes Underlying the Colon Cancer Treatment by the Traditional Chinese Medicine PHY906.

BACKGROUND: We attempted to explore the molecular mechanism underlying PHY906 intervention of colon cancer. METHODS: The microarray data of tumors treated by PHY906 and PBS alone were downloaded from the public Gene Expression Omnibus database. The dataset was further analyzed for the differentially expressed genes (DEGs) and their related biological functions were analyzed, followed by function and pathways. Protein-protein interaction (PPI) network was constructed and the significant nodes were screened by network centralities and then the significant modules analysis. Besides, they were clustered and transcriptional factors (TFs) were predicted. RESULTS: The gene expression patterns changed induced by PHY906 treatment, including 414 upregulated and 337 downregulated DEGs. The biological process of response to steroid hormone stimulus and regulation of interferon-gamma production were significantly enriched by DEGs. Ezh2 (enhancer of zeste 2) was found to be the key node in PPI network. There are 12 significant TFs predicted for module 1 genes and 3 TFs for module 2 genes. CONCLUSIONS: PHY906 treatment may function in protecting the epithelial barrier against tumor cell invasion by modulating IFN-γ level and mediating cancer cell death by activating the response to steroid hormone stimulus and activating the response to steroid hormone stimulus. E2f1, Hsfy2, and Nfyb may be therapeutic targets for colon cancer. PHY906 showed treatment efficacy in modulating cell apoptosis by intervening interferon-gamma production and response to steroid hormone stimulus. Ezh2 and its TFs such as E2f1, Hsfy2, and Nfyb may be the potential therapeutic targets for anticancer agents development.

Endocan silencing induces programmed cell death in hepatocarcinoma.

Hepatocarcinoma is a type of high-grade malignant carcinoma identified worldwide. Its rapid development and late diagnosis prevents effective tumor resection in the majority of patients, and therefore recent studies have targeted metabolic signaling pathways and the tumor microenvironment for potential treatments. To investigate whether endocan may be a gene target for hepatocarcinoma treatment, the present study employed the following measures: MTT and Transwell assays, flow cytometry, western blotting and an mRFP-GFP-LC3 double fluorescence system. Following endocan gene silencing, cell proliferation was significantly inhibited and the number of invasive cells in the endocan siRNA-treated group was reduced compared with the control-siRNA treated-group. Furthermore, the apoptosis rate was 15% and autophagy was detected in the endocan short interfering (si)RNA-treated group compared with the control-siRNA treated-group. Using western blotting to detect NF-κB expression in the nucleus, the NF-κB expression was identified to be significantly reduced in the siRNA-treated group compared with the control groups. Endocan gene silencing inhibited hepatocarcinoma cell viability and invasion, whilst inducing apoptosis and autophagy. The results of the present study suggest that the effect of endocan gene silencing on cell survival was mediated via the NF-κB signaling pathway.

Sex hormone affects the severity of non-alcoholic steatohepatitis through the MyD88-dependent IL-6 signaling pathway.

Recent research has shown that the occurrence of gender disparity in liver cancer associated with sex differences in MyD88-dependent IL-6 production, but the role of this signaling pathway in sex differences of non-alcoholic steatohepatitis (NASH) remains unknown. To investigate the effects of sex hormone-specific intervention on pathology and progression of NASH, and on the inflammatory TLR-MyD88-IL-6 signaling pathway NASH was modeled in C57/BL6 mice by feeding a methionine and choline-deficient (MCD) diet for 4 weeks. Male mice were subjected to sex hormone-related interventions such as orchidectomy, and orchidectomy combined with administration of either testosterone propionate or estradiol benzoate. Next, the degree of non-alcoholic fatty liver disease activity score (NAS), serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the expression level of MyD88 and IL-6, were compared between these groups. Males developed more serious inflammatory problems and had a higher NAS than the females. Sex-specific intervention in male mice by orchidectomy reduced NAS, ALT, and AST, and the expression level of MyD88 and IL-6. But administration of exogenous androgen had no influence on either NAS or the expression of ALT, AST, MyD88, and IL-6. On the other hand, exogenous estrogen could alleviate the pathological damage caused by NASH, as well as reduce NAS, ALT and AST, and the expression of MyD88 and IL-6. The result show different sex hormone-related interventions affected the severity of NASH, possibly by modulating the level of sex hormones and regulating the TLR-MyD88-IL-6 signaling pathway.

Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis.

AIM: To evaluate the clinical outcomes of 240-wk treatment with entecavir (0.5 mg) in Chinese nucleoside-naive patients with cirrhosis. METHODS: A total of 204 nucleoside-naive patients with compensated (n = 96) or decompensated (n = 108) hepatitis B virus (HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital (Jilin University, Changchun, China) who were treated with entecavir (0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment (baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level < 500 copies/mL, the association of interleukin-28B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ(2) test. RESULTS: At week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level < 500 copies/mL. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype (CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pugh class A disease was significantly increased at week 240 (68%) from the baseline (47%; P < 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240 (25%) from the baseline (39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points (7.11 ± 1.80 vs 3.53 ± 1.35, P < 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points (5.58 ± 0.50 vs 4.32 ± 0.81, P < 0.01). CONCLUSION: Entecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.