Comparing high-dose dual therapy with bismuth-containing quadruple therapy for the initial eradication of Helicobacter pylori infection on Hainan Island: A randomized, multicenter clinical trial.

BACKGROUND: Traditional bismuth-containing quadruple therapy, as a first-line eradication treatment for Helicobacter pylori (H. pylori), has several disadvantages, including drug side effects, low medication adherence, and high costs. Trials of high-dose dual treatment have demonstrated its advantages, which include good safety and adherence profiles. In this study, we investigated the efficacy, safety, and compliance of a high-dose dual therapy when compared with bismuth-based quadruple treatment for the initial eradication of H. pylori infection on Hainan Island, China. METHODS: We randomized 846 H. pylori-infected patients into two groups. A bismuth-containing quadruple therapy group was administered the following: esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily, and colloidal bismuth pectin in suspension 150 mg three times/day for 2 weeks. A high-dose dual therapy group was administered the following: esomeprazole 20 mg four times/day and amoxicillin 1000 mg three times/day for 2 weeks. Patients were given a 13C urea breath test at 4 weeks at treatment end. Adverse effects and compliance were evaluated at follow-up visits. RESULTS: Eradication rates in the high-dose dual therapy group were: 90.3% (381/422, 95% confidence interval [CI]: 87.1%-92.9%) in intention-to-treat (ITT) and 93.6% (381/407, 95% CI: 90.8%-95.8%) in per-protocol (PP) analyses. Eradication rates were 87.3% in ITT (370/424, 95% CI: 83.7%-90.3%) and 91.8% in PP analyses (370/403, 95% CI: 88.7%-94.3%) for quadruple therapy, with no statistical differences (P = 0.164 in ITT and P = 0.324 in PP analyses). Adverse effects were 13.5% (55/407) in the dual group and 17.4% (70/403) in the quadruple group (P = 0.129). Compliance was 92.4% (376/407) in the dual group and 86.6% (349/403) in the quadruple group (P = 0.007). CONCLUSIONS: High-dose dual therapy had high eradication rates comparable with bismuth-based quadruple treatment, with no differences in adverse effects, however higher adherence rates were recorded.

Lipid dysregulation associated with progression of silica-induced pulmonary fibrosis.

Silicosis is an irreversible, progressive, fibrotic lung disease caused by long-term exposure to dust-containing silica particles at the workplace. Despite the precautions enforced, the rising incidence of silicosis continues to occur globally, particularly in developing countries. A better understanding of the disease progression and potential metabolic reprogramming of silicosis is warranted. The low- or high-dose silica-induced pulmonary fibrosis in mice was constructed to mimic chronic or accelerated silicosis. Silica-induced mice lung fibrosis was analyzed by histology, lung function, and computed tomography scans. Non-targeted metabolomics of the lung tissues was conducted by ultra-high-performance liquid chromatography-mass spectrometry to show the temporal metabolic trajectory. The low-dose silica-induced silicosis characterized inflammation for up to 42 days, with the onset of cellular silicon nodules. Conversely, the high-dose silica-induced silicosis characterized inflammation for up to 14 days, after which the disease developed rapidly, with a large volume of collagen deposition, presenting progressive massive fibrosis. Both low- and high silica-induced fibrosis had aberrant lipid metabolism. Combined with the RNA-Seq data, this multiomics study demonstrated alterations in the enzymes involved in sphingolipid metabolism. Time-dependent metabolic reprogramming revealing abnormal glycerophospholipid metabolism was intimately associated with the process of inflammation, whereas sphingolipid metabolism was crucial during lung fibrosis. These findings suggest that lipid dysregulation, especially sphingolipid metabolism, was involved in the process of silicosis.

Research progress in role of Hippo signaling pathway in diagnosis and treatment for hepatocellular carcinoma. / Hippoä¿¡å·é€šè·¯åœ¨è‚ç»†èƒžç™Œè¯Šæ²»ä¸­ä½œç”¨çš„ç ”ç©¶è¿›å±•.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor worldwide, with high incidence and mortality. However, the exact mechanisms leading to HCC development remain unclear. The cores of the Hippo signaling pathway consist of a kinase cascade to transmit signals, which inhibits the transcriptional coactivator translocate into the nucleus and reduces the transcription of downstream proliferation-related genes. Hippo signaling pathway regulates liver development and regeneration after liver resection, and it is also related to the occurrence of HCC. The Hippo pathway regulates proliferation, apoptosis, metastasis, autophagy, metabolic reprogramming of HCC cells, affects the tumor immune microenvironment, and participates multiple-drug resistance. Further study on the role of Hippo signaling pathway in HCC is important to develop new therapeutic targets.

Development of oleanane-type triterpenes as a new class of HCV entry inhibitors.

Development of hepatitis C virus (HCV) entry inhibitors represents an emerging approach that satisfies a tandem mechanism for use with other inhibitors in a multifaceted cocktail. By screening Chinese herbal extracts, oleanolic acid (OA) was found to display weak potency to inhibit HCV entry with an IC50 of 10 µM. Chemical exploration of this triterpene compound revealed its pharmacophore requirement for blocking HCV entry, rings A, B, and E, are conserved while ring D is tolerant of some modifications. Hydroxylation at C-16 significantly enhanced its potency for inhibiting HCV entry with IC50 at 1.4 µM. Further modification by conjugation of this new lead with a disaccharide at 28-COOH removed the undesired hemolytic effect and, more importantly, increased its potency by ~5-fold (54a, IC50 0.3 µM). Formation of a triterpene dimer via a linker bearing triazole (70) dramatically increased its potency with IC50 at ~10 nM. Mechanistically, such functional triterpenes interrupt the interaction between HCV envelope protein E2 and its receptor CD81 via binding to E2, thus blocking virus and host cell recognition. This study establishes the importance of triterpene natural products as new leads for the development of potential HCV entry inhibitors.

[Effects of enteral nutrition supplemented with glutamine and arginine on gut barrier in patients with severe acute pancreatitis: a prospective randomized controlled trial].

OBJECTIVE: To investigate the effects of continuous early enteral nutrition (EEN) supplemented with glutamine and arginine on gut barrier function in patients with severe acute pancreatitis (SAP). METHODS: Thirty two patients with a diagnosis of acute pancreatitis predicted to develop severe disease were randomized into 2 groups: EEN group (n = 18) and EEN + glutamine and arginine group (enteral immunonutrition group, n = 14). EEN was initiated when homeostasis was achieved within 72 hours after attack, and both group received isocaloric isonitrogenous nutrition. Glutamine and arginine were administered into jejunum in the enteral immunonutrition group. Serum amylase, plasma diamine oxidase (DAO), C-reactive protein (CRP), plasma endotoxin, urinary excretion of lactulose (L), and mannitol (M) were measured, and APACHE-II scores were recorded on days 1, 7, and 14. Complications, and length and cost of hospitalization were recorded as well. RESULTS: EEN and enteral immunonutrition were both tolerated well. There was no difference in APACHE-IIscore between the two groups (P > 0.05). The DAO, CRP, plasma endotoxin, and urinary L/M levels decreased with the course of SAP. However, the plasma endotoxin and urinary L/M on day 7 of the enteral immunonutrition group were (10.0 +/- 3.8) EU/ml and 0.29 +/- 0.15 respectively, both significantly higher than those of the EEN group [(7.9 +/- 2.8) EU/ml and 0.16 +/- 0.08 respectively, both P < 0.05]. The length of hospital stay and cost showed no differences between the two groups. CONCLUSION: EEN is safe and feasible in treatment of SAP. Enteral immunonutrition containing glutamine and arginine improves the gut barrier function by reducing the gut permeability and decreasing plasma endotoxin level in the early stage of SAP.