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OBJECTIVES: Chronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications. METHODS: A Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB. Liver histology was evaluated independently by 2 pathologists. The alanine aminotransferase ratio, Hepascore, and aspartate aminotransferase to platelet index values were calculated. Liver stiffness measurement (LSM) and diameter of the spleen were measured. Logistic regression with ℓ1 penalty of regression coefficients was used to select the optimal predictors. The diagnostic accuracy for the stage of liver fibrosis was assessed by the area under the receiver operator characteristic curve with 95% confidence interval (CI). RESULTS: A total of 1,200 patients with CHB were included, of whom 800 and 400 were in training and validation sets, respectively. LSM, platelets, age, hyaluronic acid, and diameter of the spleen were the top 5 predictors associated with any stage of liver fibrosis and integrated into a novel noninvasive program, named as the Chin-CHB score. The area under the receiver operator characteristic curve of the Chin-CHB score was 0.893 (95% CI: 0.77-0.92) for diagnosing significant fibrosis, 0.897 (95% CI: 0.85-0.95) for advanced fibrosis, and 0.909 (95% CI: 0.87-0.95) for cirrhosis. The diagnostic performance of the Chin-CHB score was similar between training and validation sets. The Chin-CHB score had better diagnostic performance than aspartate aminotransferase to platelet index, alanine aminotransferase ratio, LSM alone, and Hepascore for diagnosing any stage of liver fibrosis. CONCLUSIONS: The Chin-CHB score had good diagnostic performance for any stage of liver fibrosis.

Background: Patients with acute-on-chronic liver failure (ACLF) who take entecavir (ETV) and tenofovir disoproxil fumarate (TDF) experience a reduction in hepatic events and mortality. The effectiveness of tenofovir alafenamide (TAF) was not well investigated. This study was aim to compare the antiviral efficacy and mortality between TAF and ETV in patients with ACLF caused by the hepatitis B virus (HBV). Methods: One hundred and six patients with HBV-ACLF who received TAF (25 mg/day) and ETV (0.5 mg/day) for 12 weeks were analyzed. The primary endpoints were overall mortality and liver transplantation (LT) at week 12. Biochemical responses, virologic responses, mortality, drug safety, and side effects were evaluated. Results: At 4 and 12 weeks of TAF treatment, patients showed significantly higher HBV-DNA reduction (P <.001), higher HBV-DNA undetectability rates (P <.001), and lower HBV DNA levels (P <.001) in serum. Lower Child-Turcotte-Pugh (CTP) scores (P =.003) were observed at 4 weeks in the TAF group, although the CTP scores showed no difference between TAF group and ETV group at 12 weeks (P = 1.143). Lower alanine aminotransferase (ALT) levels of patients in the TAF group at week 4 and 12 were observed (P =.023 and P <.0001, separately). The mortality of TAF group was lower after 4 weeks of treatment (P =.038); however, the 2 groups had similar mortality rates at week 8 and 12. Among the causes of death in HBV-ACLF patients, we found the same incidence of liver-related problems in both groups (P >.05). Conclusions: This study showed that ACLF patients with chronic HBV infection treated with TAF had a rapid decline in HBV DNA, a higher rate of ALT reduction and improved CTP scores compared to the ETV group, thereby improving patient survival. [ABSTRACT FROM AUTHOR]

Background: Integrin‐linked kinase (ILK) is crucial in solid tumors by regulating the Hippo‐Yes‐associated protein 1 (YAP) pathway. This study aimed to uncover how Helicobacter pylori influences ILK levels and its role in regulating YAP during H. pylori‐induced gastric cancer. Materials and Methods: GES‐1 cells with stable Ilk knockdown and overexpression and a mouse carcinogenesis model for H. pylori infection were constructed. And ILK, the phosphorylated mammalian STE20‐like protein kinase 1 (MST1), large tumor suppressor 1 (LATS1; S909, T1079), and YAP (S109, S127) were detected in cells, and mice by western blotting, as well as fluorescence intensity of YAP were assayed by immunofluorescence. YAP downstream genes Igfbp4 and Ctgf, the pathological changes and tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), interleukin‐1beta (IL‐1β), and nitric oxide (NO) levels in mice gastric tissues were detected by real‐time PCR, H&E, and ELISA assays. Results: In this study, stable Ilk knockdown cells exhibited significantly higher phosphorylated levels of MST1, LATS1, and YAP, as well as increased YAP in the nuclei of GES‐1 cells. Conversely, cells with Ilk overexpression showed opposite results. H. pylori infection led to decreased ILK levels in gastric epithelial cells but increased ILK levels in gastric cancer cell lines (MGC803, SGC7901) and gastric cancer tissues in mice. Treatment with the ILK inhibitor OST‐T315 elevated the phosphorylated MST, LATS1, and YAP levels, and inhibited the mRNA levels of Igfbp4 and Ctgf at 44, 48 week‐aged mice. OST‐T315 also reduced the release of TNF‐α, IL‐6, IL‐1β, and NO, as well as the progression of gastric cancer caused by H. pylori and N‐Nitroso‐N‐methylurea (NMU) treatment. Conclusion: Upon initiation of gastric tumorigenesis signals, H. pylori increases ILK levels and suppresses Hippo signaling, thereby promoting YAP activation and gastric cancer progression. ILK can serve as a potential prevention target to impede H. pylori‐induced gastric cancer. [ABSTRACT FROM AUTHOR]

Current research does not fully elucidate the key compounds and their mechanisms that define the aroma profile of fresh jujube fruits. Therefore, this study conducted a comprehensive analysis of both free and glycosidically bound aroma compounds in fresh jujube fruits of ten cultivars. Utilizing gas chromatography–mass spectrometry (GC-MS), we identified 76 volatile free aroma compounds and 19 glycosidically bound volatile compounds, with esters, aldehydes, and ketones emerging as the predominant volatile compounds in the jujube fruits. Odor activity value (OAV) analysis revealed that the primary aroma profile of the jujubes is characterized by fruity and fatty odors, with β-damascenone being a key contributor to the fruity aroma, and (E)-2-oct-en-1-al and nonanal significantly influencing the fatty aroma. Moreover, the integration of sensory evaluation and partial least squares regression (PLSR) analysis pinpointed octanal, (E)-2-oct-en-1-al, nonanal, β-damascenone, and pentanal as significant contributors to the jujube's characteristic aroma, while isoamyl acetate was identified as significantly influencing the fatty acid taste. This study not only underscores the complexity of the jujube aroma composition but also highlights the impact of environmental factors on aroma profiles, offering valuable insights into the sensory characteristics of jujube fruits. [ABSTRACT FROM AUTHOR]