Establishment and validation of a cuproptosis-related lncRNA signature that predicts prognosis and potential targeted therapy in hepatocellular carcinoma.

BACKGROUND: Cuproptosis is a recently identified form of programmed cell death and could be a new direction for tumour therapy, and it has important clinical implications. Long non-coding RNAs (lncRNAs) can intervene in diverse biological processes and have a decisive role in hepatocellular carcinoma (HCC). However, how cuproptosis-related lncRNAs (CRLs) participate in regulating HCC has yet to be recognised. This study aimed to establish and validate a prognostic signature of CRLs and to analyse their clinical value in HCC patients. METHODS: To analyse the function of CRLs in the prognosis of HCC, RNA sequencing data, mutation data, and clinically relevant data were collected from the Cancer Genome Atlas Database (TCGA). Then, TCGA cohort was randomly divided into training and test sets. The training set was utilized to define prognostic signature of CRLs using bioinformatics methods. Subsequently, we verified the accuracy of this prognostic signature in the test set. Finally, we performed immune-related analysis, the half-maximal inhibitory concentration (IC50) prediction, gene set enrichment analysis, and tumour mutational burden (TMB) analysis. RESULTS: We established a prognostic signature for the CRLs (SNHG4, AC026412.3, AL590705.3, and CDKN2A-DT). This signature-based risk group displayed an accurate predictive ability for the survival time of patients with HCC. We observed discrepancies in immune cells, immune function, the expression level of genes related to immune checkpoints, and TMB in high- and low-risk groups. CONCLUSION: This CRLs prognostic signature could predict clinical outcomes in patients with HCC as well as the efficacy of targeted and therapy immunotherapy.

Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study.

BACKGROUND: The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori ) infection status and CYP2C19 polymorphism on anaprazole. METHODS: In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. RESULTS: The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). CONCLUSIONS: The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers. REGISTRATION: ClinicalTrials.gov, NCT04215653.

Transjugular intrahepatic portosystemic shunt for the prevention of rebleeding in patients with cirrhosis and portal vein thrombosis: Systematic review and meta-analysis.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) has been performed on patients with cirrhosis and portal vein thrombosis (PVT) to prevent rebleeding; however, the associated evidence is scarce. Hence, the study aimed to evaluate the feasibility and efficacy of TIPS in patients with cirrhosis and PVT and promote personalized treatment in such patients. Methods: Literature was systematically obtained from PubMed, EMBASE, Cochrane Library, and Web of Science. Data from the included studies were extracted, and meta-analyses by the random effects model were used to pool data across studies. Heterogeneity was assessed using Cochran's Q and I2 statistics. The source of heterogeneity was explored using subgroup analyses and meta-regressions. Results: A total of 11 studies comprising 703 patients with cirrhosis and portal vein thrombosis (PVT: complete, 32.2%; chronic, 90.2%; superior mesenteric vein or splenic vein involvement, 55.2%; cavernous transformation, 26.8%) were included. TIPS showed feasibility in 95% of the cases (95% confidence interval [CI]: 89%-99%) with heterogeneity (I2 = 84%, p < 0.01) due to cavernous transformation. The pooled rebleeding rate was 13% (95% CI: 7%-20%) with heterogeneity (I2 = 75%, p < 0.01) explained by chronic PVT and anticoagulation (AC) therapy. Hepatic encephalopathy occurred in 32% of patients. The survival rate, portal vein recanalization rate, and shunt patency rate were 80%, 82%, and 77%, respectively. Conclusion: TIPS is feasible and effectively prevents rebleeding in patients with cirrhosis and PVT, regardless of cavernous transformation of the portal vein. Due to a potentially high risk of rebleeding and no apparent benefits of AC, post-TIPS AC must be employed cautiously. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=258765], identifier [CRD42021258765].

Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial.

Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole. Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated. Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -2.9% (95% CI, -16.5-10.7%), and -0.5% (95% CI, -13.5-12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -1.8% (95% CI, -19.8-16.3%), and 5.1% (95% CI, -12.2-22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group. Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.

Furazolidone-based triple and quadruple eradication therapy for Helicobacter pylori infection.

AIM: To evaluate the efficacy of furazolidone-based triple and quadruple therapy in eradicating Helicobacter pylori (H. pylori) in a multi-center randomized controlled trial. METHODS: A total of 720 H. pylori positive patients with duodenal ulcer disease were enrolled at 10 different hospitals in Jiangxi province in China. The patients were randomly assigned to four treatment groups as follows: patients in Groups 1 and 3 received rabeprazole (10 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively; patients in Groups 2 and 4 received rabeprazole (10 mg), bismuth (220 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively. The primary outcome measure was H. pylori eradication rate 4 wk after treatment by intention-to-treat and per protocol analysis, while the secondary outcome measures were symptom and sign changes at the end of treatment and 4 wk after the end of treatment, as well as the proportion of patients who developed adverse events. RESULTS: The demographic data of the four groups were not significantly different. Overall, 666 patients completed the scheme and were re-assessed with the (13)C-urea breath test. The intention-to-treat analysis of the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 74.44%, 82.78%, 78.89% and 86.11%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. According to the per protocol analysis, the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 81.21%, 89.22%, 85.54% and 92.26%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. The number of adverse events was 15 (8.3%), 16 (8.9%), 15 (8.3%) and 17 (9.4%) in Groups 1, 2, 3 and 4, respectively, including dizziness, vomiting, diarrhea, nausea, skin rash, itchy skin, and malaise. The symptoms were relieved without special treatment in all of the patients. CONCLUSION: Both 7- and 10-d quadruple furazolidone-based therapies achieve satisfactory H. pylori eradication rates.

[Heavy metal accumulation during last hundred years and its assessment of potential ecological risk in the coastal wetland of Qi'ao Island, Pearl River Estuary of China].

The processes of fine sediment transport and deposition can record some relative anthropogenic information in estuarine environments. Grain size analysis of the sediment core collected from coastal wetland of Qi'ao Island in the Pearl River Estuary of China show that the sediment is mainly composed by clayey silt, and the mean grain size, contents of clay and silt increase upward gradually. Chronology analysis show that the sedimentation rate above 59 cm is about 4.15 cm x a(-1), and 0.97 cm x a(-1) beneath 59 cm. Heavy metal analysis indicate that the contents of the each heavy metal increased slowly with a slight intensity of potential ecological risk; however, from 1966 to 1992, the heavy metal contents increased obviously because of the quick social-economy development around the Pearl River Estuary area, and the order of polluting degree of these heavy metals in core sediment is Cd > Ni > Pb > Cu > Cr > Zn. The potential ecological risk intensity of Cd increased from slight risk before 1966 to strong risk since 1992, and the potential ecological risk intensities other heavy metal are slight risk; the potential ecological risk index is weak level. The variations of core sediment heavy metal contents and its ecological risk assessments along the vertical profile reveal the interaction processes and intent of anthropogenic influences from the areas around the Pearl River Estuary and the catchments.

[Impact of typhoon "Fung-wong" on the distribution patterns of heavy metals in the Quanzhou Bay].

Based on the inductively coupled plasma mass spectroscopy (ICP-MS) data of concentrations of 7 heavy metals (including Cr, Ni, Cu, Zn, Cd, Pb and As) in suspended particles and surface sediments samples collected at 6 and 1 13-hours-mooring stations, respectively, in Quanzhou Bay 4 days after the landing of typhoon "Fung-wong". The average contents of Cr, Ni, Cu, Zn, As, and Cd are 60.4, 50.3, 26.5, 101.7, 3.36, 40.0 and 0.180 microg/g, respectively, in the surface sediments, and are 1.108-7.408, 0.476-3. 394, 0.809-5.046, 3.190-19.337, 0.087-0.595, 2.621-10.073 microg/L and 4.160-50.828 ng/L, respectively, in different stations in the suspended particles. The contents and distribution patterns of 7 heavy metals during a tidal cycle were significantly changed after typhoon "Fung-wong" by contrasting with that in same stations and tidal time at an ordinary situation. The contents of heavy metals, besides Ni, evidently decreased but the distribution patterns were similar with that in an ordinary condition with relatively large grads after typhoon "Fung-wong" in the surface sediments at station Q4. While in the suspended particles, the contents of heavy metals were evidently increased with the distribution patterns varied obviously and differently due to their geographical position after typhoon "Fung-wong". These impacts of typhoon "Fung-wong" to the contents and distribution patterns of heavy metals could be attribute to the "second contamination" and the increased supply of particles materials from continent during the typhoon process. The results of this study provide a reference to accurate assessing and scientific governing the heavy metals' contamination, and provide a directly support to evaluating the integrated impacts of typhoon process on the contamination of heavy metals in the Quanzhou Bay.

[Distribution patterns of heavy metals in suspended particles of the Quanzhou Bay and their influence factors].

Based on the inductively coupled plasma mass spectroscopy (ICP-MS) data of concentrations of 7 heavy metals (including Cr, Ni, Cu, Zn, Cd, Pb and As) in suspended particles and surface sediments samples collected at 6 and 2 13-hours-mooring stations, respectively, in Quanzhou Bay. The average contents of Cr, Ni, Cu, Zn, As, Pb, and Cd are 1.610-0.359, 0.730-0.150, 2.249-0.319, 6.421-1.266, 0.131-0.027, 4.176-1.101 microg/L and 17.526-2.260 ng/L, respectively, in different stations in the suspended particles and are 65.3-82.6, 37.8-39.8, 37.4-51.4, 121.0-172.8, 3.3-3.4, 42.2-76.9 and 0.217-0.493 microg/g, respectively, in the surface sediments of two stations. The concentrations of heavy metals in suspended particles varied significantly and the distribution patterns corresponded to the tidal and estuarine processes at the estuary area in a tidal cycle. While at the outer area, the varieties of concentrations were relatively unobvious and the re-suspension from surface sediments might play a significant role on distribution patterns of heavy metals in suspended particles. In a tidal cycle, the varieties of heavy metals concentrations in surface sediments were corresponding to that in suspended particles', which indicated that exchanges of heavy metals existed between surface sediments and suspended particles. These study results provide a reference to comprehensive understanding on distribution, migration and exchange of heavy metals in the Quanzhou Bay.

[Distribution patterns of heavy metals in surface sediments of the Quanzhou Bay and environmental quality assessment].

The concentrations of 7 heavy metals were determined in 48 surface sediments in the Quanzhou Bay by an inductively coupled plasma mass spectroscopy (ICP-MS). The average contents of Cr, Ni, Cu, Zn, As, Cd and Pb are 47.66, 52.2, 30.86, 111.6, 5.29, 0.399 and 50.3 microg x g(-1), respectively. The Cd, Pb, Zn and As were mainly discharged into the Quanzhou Bay by Jinjiang River, while the materials near the Bay might supply a considerable amount of Cr, Ni and Cu. The result of the multi-analysis ecological risk index analyses revealed that Cr, Ni, Cu, Zn, Pb and As were moderately contaminated and presented low potential ecological risk, while Cd was heavily contaminated and raised high potential ecological risk. In general, moderately contaminated and potential ecological risk were occurred in whole Quanzhou Bay with the dominated polluted metals were Ni and Cd. The heavily contaminated area was corresponded to the high potential ecological risk area, which located at the confluent area of Jinjiang River and Luoyangjiang River. From the results of this study, we conclude that the Quanzhou Bay has been heavily polluted by heavy metals, therefore much environmental control should be continued and strengthen to Quanzhou Bay and its adjacent areas.