BACKGROUND:Management of refractory Helicobacter pylori (H. pylori) infection remains challenging due to increasing antibiotic resistance and limited effective rescue options. Minocycline and furazolidone retain low resistance rates, while potassium-competitive acid blockers (P-CABs) provide potent and sustained acid suppression. This study aimed to evaluate the efficacy and safety of a 14-day P-CAB-based regimen combining minocycline, furazolidone, and bismuth in patients with refractory H. pylori infection. METHODS:From January 2023 to October 2025, clinical data were collected from patients with refractory H. pylori infection who received the above regimen at Tongji Hospital, Wuhan, China. Eradication was assessed by a urea breath test performed at least 4 weeks after treatment. Adverse events during treatment were recorded. RESULTS:A total of 368 patients were included in modified intention-to-treat analysis. Of them, 183 (49.7%) had two previous eradication failures, 165 (44.8%) had three to four failures, and 20 (5.4%) had five or more failures. Among the 143 patients who underwent antibiotic resistance gene testing, the resistance rates to clarithromycin and quinolones were 96.5% and 79.7%, respectively. The H. pylori eradication rate was 92.7% (95% CI 89.5%-94.9%) in modified intention-to-treat analysis and 96.4% (95% CI 93.8%-97.9%) in per-protocol analysis. Adverse events occurred in 25.8% of patients and were predominantly mild to moderate, with dizziness (9.5%), nausea (5.2%), and abdominal distension (5.2%) most common. Poor compliance (OR = 18.14, 95% CI 6.39-51.51) and peptic ulcer (OR = 4.34, 95% CI 1.27-14.82) were independently associated with eradication failure. CONCLUSIONS:The 14-day regimen of P-CAB, minocycline, furazolidone, and bismuth is highly effective and well tolerated in patients with refractory H. pylori infection. This regimen represents a promising empirical rescue therapy, particularly in settings where antimicrobial susceptibility testing is unavailable.

BACKGROUND:High-dose dual therapy (HDDT) has been shown to achieve eradication rates non-inferior to the bismuth quadruple therapy (BQT) in treatment-naïve patients of Helicobacter pylori (H. pylori) infection, with advantages including greater convenience and fewer adverse events. However, the efficacy of different potassium-competitive acid blockers (P-CABs) in HDDT regimens remains incompletely defined due to variations in their pharmacokinetic properties. Therefore, this study aims to evaluate the eradication rates, incidence of adverse events, and compliance of the dual regimens of vonoprazan/tegoprazan combined with amoxicillin in patients with treatment-naïve H. pylori infection. METHOD:This prospective, multicenter, open-label, randomized controlled clinical trial enrolled newly diagnosed patients with H. pylori infection from six centers in China. All subjects were randomly assigned to the VA group (vonoprazan 20 mg bid+amoxicillin 1 g tid, 14 days) or the TA group (tegoprazan 50 mg bid+amoxicillin 1 g tid, 14 days). The basic information and clinical data of the patients were collected via electronic questionnaires, WeChat, or telephone follow-ups. H. pylori eradication was assessed 4 weeks post-treatment using the urea breath test (UBT). The adverse events and compliance were meticulously recorded throughout the treatment period. RESULT:Between June 2024 and May 2025, 710 patients were randomly assigned, and 653 subjects were included. In the intention-to-treat (ITT) analysis, the eradication rates were 89.3% in the VA group and 76.1% in the TA group, respectively (p < 0.001). The modified intention-to-treat (mITT) analysis showed rates of 94.6% and 80.8%, respectively (p < 0.001), and the per-protocol (PP) analysis yielded 95.1% and 81.0%, respectively (p < 0.001). Although the overall incidence of adverse event rates was comparable between groups (17.2% vs. 13.8%, p = 0.254), gastrointestinal adverse events were less frequent with TA therapy (9.3% vs. 14.4%, p = 0.048). Compliance was excellent and comparable in both groups (94.6% vs. 94.1%, respectively, p = 0.871). None of the factors analyzed significantly influenced eradication rates. CONCLUSION:Vonoprazan/amoxicillin dual therapy achieved satisfactory H. pylori eradication rates with a favorable safety profile in treatment-naïve patients. Tegoprazan/amoxicillin dual therapy was associated with fewer gastrointestinal adverse event incidences, while optimizing tegoprazan dosing frequency may be necessary to improve the eradication. TRIAL REGISTRATION:Chictr.org.cn ChiCTR2400082371.

BACKGROUND:Autoimmune gastritis (AIG) is an immune-mediated chronic atrophic gastritis, and anemia is common in AIG. This study aims to investigate the clinical characteristics of AIG patients with and without anemia. METHODS:This was a single-center retrospective study. The diagnosis of AIG was based on endoscopic or pathologic findings combined with antiparietal cell antibody (PCA) and anti-intrinsic factor antibody (IFA) results. Anemia was defined as hemoglobin levels <110 g/L for females or 120 g/L for males. RESULTS:This study included 117 AIG patients. The median age was 53.6±10.5 years old, and 72.6% were female. Anemia was present in 39.3% patients, with 17.9% iron deficiency anemia (IDA) and 21.4% pernicious anemia (PA). AIG patients with anemia had a higher positive rate of IFA (34.8% vs. 18.3%, P =0.044) and a lower level of pepsinogen I (PG-I) [5.0 (3.3 to 10.4) vs. 8.0 (4.1 to 18.9) ng/mL, P =0.033]. However, no significant differences were observed in the age, sex, PCA positivity, gastrin levels, Helicobacter pylori ( H. pylori ) infection status or the concomitant diseases between patients with and without anemia. Compared with PA patients, IDA patients had a higher incidence of H. pylori infection (66.7% vs. 28.0%, P =0.009), as well as the levels of PG-I ( P =0.001), PG-II ( P =0.016) and PG-I/II ratio ( P =0.007). Univariate and multivariate analyses revealed that IFA positivity (odds ratio=2.379, P =0.047) was a significant risk factor for anemia in AIG patients. CONCLUSIONS:AIG patients with IFA positivity are more prone to anemia, and IDA maybe associated with H. pylori infection.

BACKGROUND:High-dose dual therapy (HDDT) is a promising first-line treatment option for Helicobacter pylori infection. In this study, we aimed to compare the efficacy and safety of different HDDT regimens. METHODS:This multicenter retrospective study included data from 10 centers between January 2022 and January 2025. Inverse probability of treatment-weighted (IPTW) adjustment was used to address the imbalance in variables across groups. The outcomes included the eradication rate, adverse events, and adherence. RESULTS:A total of 1665 patients were included, with a full analysis set (FAS) eradication rate of 88.6% and a per-protocol (PP) eradication rate of 89.5% for HDDT. After IPTW adjustment, the eradication rate of vonoprazan-amoxicillin (VA) 14-day based on FAS analysis was 95.1%, which was significantly higher than VA-10 day (88.7%) (P = .001), esomeprazole-amoxicillin (EA) (85.1%) (P < .001), and tegoprazan-amoxicillin (TA) (87.3%) (P < .001). The incidence of adverse events for VA-14 was 8.1%, which was comparable to VA-10 (11.1%) but lower than TA (14.4%) and EA (15.3%) (P = .002). Adherence showed no significant difference across groups. High body surface area (BSA) (≥1.80 m²) (OR 1.594, 95% confidence interval [CI], 1.018-2.495, P = .041), poor adherence (OR 4.975, 95% CI, 2.753-8.992, P < .001), and non-VA-14 treatment regimen were independent risk factors for eradication failure. Factors varied across regimens. CONCLUSIONS:HDDT, particularly VA-14, is a competitive first-line option for H. pylori eradication. High BSA and low adherence were risk factors for eradication failure but varied across regimens, highlighting the necessity of personalized adjustment.

The introduction of vonoprazan has markedly enhanced the effectiveness of the first-line Helicobacter pylori (H. pylori) eradication regimens. This study aimed to compare the effectiveness of vonoprazan-amoxicillin based dual therapy with that of quadruple therapy as second-line treatments, while also investigating potential clinical predictors of therapeutic success. From January 2023 to June 2025, we retrospectively analyzed clinical data from H. pylori-infected patients who received second-line treatment with either: vonoprazan-amoxicillin dual therapy (VA) or VA based quadruple therapy (VAMB; vonoprazan, amoxicillin, minocycline, and colloidal bismuth pectin). The eradication status was evaluated by 13/14C­urease breath test four weeks after treatment completion. Adverse events and medication compliance were systematically documented during follow-up. The study included 241 patients, with 107 receiving VA dual therapy and 134 undergoing VAMB quadruple therapy. Eradication rates were comparable between groups: 90.7

BACKGROUND:High-Dose Dual Therapy With Amoxicillin Has Shown Advantages to Eradicate Helicobacter pylori (H. pylori), but Not for Penicillin-Allergic Patients. It Is Recommended That Cefuroxime Could Be an Alternative, but Whether Cefuroxime Could Be Used in Dual Therapy Has Not Been Reported. This Study Aimed to Compare the Efficacy, Safety, and Compliance of Cefuroxime-Based Dual Therapy (CDT) With Cefuroxime-Based Bismuth Quadruple Therapy (CQT) to Treat H. pylori Infection. MATERIALS AND METHODS:The Prospective, Multicenter, Open-Label, Randomized Controlled Trial Was Conducted to Enroll Patients With Treatment-Naive H. pylori Infection From 9 Institutions. Patients Were Randomly Assigned to CDT Group (Cefuroxime 500 Mg Three Times/Day and Vonoprazan 20 Mg Twice/Day) or CQT Group (Cefuroxime 500 Mg Twice/Day, Levofloxacin 500 Mg Once/Day, Vonoprazan 20 Mg Twice/Day, and Bismuth 220 Mg Twice/Day), both for 14 Days. RESULTS:700 Patients (350 per Group) Were Enrolled. In the Intention-To-Treat Analysis, Eradication Rates Were 76.0% and 86.3% in CDT Group and CQT Group (P = 0.001). In the Modified Intention-To-Treat Analysis, Eradication Rates Were 78.9% and 89.1% (P < 0.001). In the Per-Protocol Analysis, Eradication Rates Were 80.2% and 91.2% (P < 0.001). The Incidence of Adverse Events Was Significantly Lower in CDT Group Than CQT Group (14.4% vs. 29.8%, P < 0.001). Non-inferiority Was Confirmed Between CDT and CQT Group (All P > 0.025). Compliance Was Good in Both Groups (96.0% vs. 92.8%, P = 0.073). Poor Adherence Was a Risk Factor for Reducing the Efficacy in Both Groups. CONCLUSIONS:CQT Was More Effective Than CDT for H. pylori Eradication, Which Might Be Recommended for Penicillin-Allergic Patients. If There Were Contraindications or Intolerance of CQT, CDT Would Be an Alternative. TRAIL REGISTRATION:ChiCTR2300071210.

Phosphodiesterase 4 (PDE4) is an enzyme that specifically hydrolyzes the second messenger cAMP and has a critical role in the regulation of a variety of cellular functions. In recent years, PDE4 has attracted great interest in cancer research, and its role in tumorigenesis and development has been gradually elucidated. Research indicates that abnormal expression or heightened activity of PDE4 is associated with the initiation and progression of multiple cancers, including lung, colorectal, and hematological cancers, by facilitating cell proliferation, migration, invasion, and anti-apoptosis. Moreover, PDE4 also influences the tumor immune microenvironment, significantly immune evasion by suppressing anti-tumor immune responses, reducing T-cell activation, and promoting the polarization of tumor-associated macrophages toward a pro-tumorigenic phenotype. However, the PDE4 family may have both oncogenic and tumor-suppressive effects, which could depend on the specific type and grade of the tumor. PDE4 inhibitors have garnered substantial interest as potential anti-cancer therapeutics, directly inhibiting tumor cell growth and restoring immune surveillance capabilities to enhance the clearance of tumor cells. Several PDE4 inhibitors are currently under investigation with the aim of exploring their potential in cancer therapy, particularly in combination strategies with immune checkpoint inhibitors, to improve therapeutic efficacy and mitigate the side effects of conventional chemotherapy. This review provides an overview of PDE4 in tumorigenesis, drug resistance, immunotherapy, and the anti-tumor actions of its inhibitors, intending to guide the exploration of PDE4 as a new target in tumor therapy.

Lenvatinib, as a multi-kinase inhibitor, has been approved as a first-line drug for patients with advanced hepatocellular carcinoma (HCC). Gasdermin E (GSDME)-mediated pyroptosis, a form of programmed cell death, can be induced by chemotherapy drugs or certain kinase inhibitors. However, the role of Lenvatinib in inducing pyroptosis in HCC warrants further investigation. Phase contrast microscopy, LDH assays, and gain- and loss-of-function strategies were used to evaluate Lenvatinib-induced pyroptosis in HCC cells. GSDME palmitoylation was assessed via the acyl-biotin exchange method. In vivo, a subcutaneous HCC xenograft model in nude mice were established to assess the effects of interfering with GSDME on the sensitivity of HCC to Lenvatinib. Lenvatinib induced pyroptosis in HCC cells in a dose- and time-dependent manner. Additionally, Lenvatinib promoted GSDME cleavage, with upregulation of GSDME enhancing pyroptosis and downregulation reducing this effect. The ABE method revealed that GSDME is palmitoylated, and Lenvatinib increased its palmitoylation, promoting plasma membrane localization and enhancing protein stability. Inhibition of GSDME palmitoylation by 2-BP blocked Lenvatinib-induced pyroptosis. In vivo, upregulation of GSDME increased HCC sensitivity to Lenvatinib and inhibited tumor growth. Lenvatinib induces pyroptosis in HCC by promoting the palmitoylation of GSDME, enhancing its localization to the plasma membrane and increasing its protein stability. Interfering with GSDME, both in vitro and in vivo, affects Lenvatinib-induced pyroptosis, thereby altering the therapeutic sensitivity of HCC to Lenvatinib. Targeting GSDME palmitoylation represents a potential therapeutic strategy for HCC, as it enhances Lenvatinib-induced pyroptosis and improves the therapeutic response.

Helicobacter pylori (H. pylori) eradication regimens may have different effects on the gut microbiota. Few studies have analyzed the safety of high-dose dual therapy (HDDT) from a micro-ecological perspective. This study aimed to compare the impact of H. pylori eradication with HDDT and bismuth quadruple therapy (BQT) on gut microbiota. H. Pylori-infected treatment-naive patients were recruited and screened from September 2023 to April 2024 and randomly assigned to the HDDT group (esomeprazole 20 mg, amoxicillin 750 mg, qid, 14 days) or BQT group (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 600 mg, bid, 14 days). Fresh stool specimens were collected and stored before treatment and at week 2 and week 8 after treatment. The diversity and composition of the gut microbiota were compared and analyzed in both groups using 16 S rRNA gene sequencing. Forty-nine H. pylori positive patients were enrolled and randomly assigned to either the HDDT (n = 24) or the BQT group (n = 25) group. Compared with baseline, alpha and beta diversities significantly changed at week 2 after receiving BQT and did not recover fully at week 8. However, in the HDDT group, the diversities at week 2 changed mildly without statistical significance, compared to baseline. Additionally, a greater number of species had alterations in their abundances in the BQT group compared to the HDDT group at week 2. However, the abundances of these species were restored to their previous levels at week 8 in both the HDDT and BQT groups. Compared to BQT, HDDT exerted less impact on the diversity and composition of the gut microbiota. ChiCTR2100053268.

This study investigates the knowledge of the high-dose dual therapy (HDDT) in the eradication of Helicobacter pylori (H pylori) infection among gastroenterologists in China. A survey was conducted among gastroenterologists in China using the "Questionnaire Star," and the questionnaire link was sent by WeChat. Descriptive methods were used for statistical analysis. A total of 863 valid questionnaires were collected. The awareness rate of HDDT was 96.5%, and the clinical utilization rate was 69.1%.12.4%, 29.9%, and 25.6% gastroenterologists chose HDDT for the first-line, rescue and refractory treatment of H pylori infection. Amoxicillin was the most commonly used antibiotic in HDDT, followed by clarithromycin, furazolidone, levofloxacin, metronidazole, cefuroxime and tetracycline. Potassium-competitive acid blockers (51.8%) were the most commonly acid inhibitors in high-dose double therapy, followed by proton pump inhibitors and H2-receptor blockers. Most gastroenterologists believed that high-dose double therapy would become the main method of first-line and rescue treatment of H pylori infection. HDDT maybe the main treatment of H pylori eradication, but the application of the HDDT among gastroenterologists in China is insufficient. Better education should be carried out in future to improve the ability of gastroenterologists to standardize the treatment of H pylori infection.

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal changes. Among these, protein lipidations which refer to lipid attachment to proteins are prominent, which primarily encompassing five types including S-palmitoylation, N-myristoylation, S-prenylation, glycosylphosphatidylinositol (GPI) anchor and cholesterylation. Lipid attachment to proteins plays an essential role in the regulation of protein trafficking, localisation, stability, conformation, interactions and signal transduction by enhancing hydrophobicity. Accumulating evidence from genetic, structural, and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of diseases. Decades of dedicated research have driven the development of a wide range of drugs targeting protein lipidation, and several agents have been developed and tested in preclinical and clinical studies, some of which, such as asciminib and lonafarnib are FDA-approved for therapeutic use, indicating that targeting protein lipidations represents a promising therapeutic strategy. Here, we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types, outline the impact of protein lipidations on physiology and disease, and highlight potential therapeutic targets and clinical research progress, aiming to provide a comprehensive reference for future protein lipidation research.

BACKGROUND:Short videos have demonstrated huge potential in disseminating health information in recent years. However, to our knowledge, no study has examined information about colorectal polyps on short-video sharing platforms. OBJECTIVE:This study aimed to analyze the content and quality of colorectal polyps-related videos on short-video sharing platforms. METHODS:The terms "" (intestinal polyps) or "" (colonic polyps) or "" (rectal polyps) or "" (colorectal polyps) or "" (polyps of large intestine) were used to search in TikTok (ByteDance), WeChat (Tencent Holdings Limited), and Xiaohongshu (Xingyin Information Technology Limited) between May 26 and June 8, 2024, and then the top 100 videos for each search term on different platforms were included and recorded. The Journal of American Medical Association (JAMA) score, the Global Quality Scale (GQS), the modified DISCERN, and the Patient Education Materials Assessment Tool (PEMAT) were used to evaluate the content and quality of selected videos by 2 independent researchers. SPSS (version 22.0; IBM Corp) and GraphPad Prism (version 9.0; Dotmatics) were used for analyzing the data. Descriptive statistics were generated, and the differences between groups were compared. Spearman correlation analysis was used to evaluate the relationship between quantitative variables. RESULTS:A total of 816 eligible videos were included for further analysis, which mainly conveyed disease-related knowledge (n=635, 77.8%). Most videos were uploaded by physicians (n=709, 86.9%). These videos had an average JAMA score of 2.0 (SD 0.6), GQS score of 2.5 (SD 0.8), modified DISCERN score of 2.5 (SD 0.8), understandability of 80.4% (SD 15.6%), and actionability of 42.2% (SD 36.1%). Videos uploaded by news agencies were of higher quality and received more likes and comments (all P<.05). The number of collections and shares of videos about posttreatment caveats were more than those for other content (P=.03 and P=.006). There was a positive correlation between the number of likes, comments, collections, and shares (all P<.001). The duration and the number of fans were positively correlated with the quality of videos (all P<.05). CONCLUSIONS:There are numerous videos about colorectal polyps on short-video sharing platforms, but the reliability and quality of these videos are not good enough and need to be improved.

Increasing antibiotic resistance is the primary reason for treatment failure of Helicobacter pylori (H. pylori) infection. To enhance the eradication rate, minimize the development of secondary resistance, and alleviate the socioeconomic burden, it is crucial to select H. pylori-sensitive antibiotics carefully. Furazolidone has been used for H. pylori eradication in developing countries for decades due to its affordability and low resistance rate. Numerous studies have demonstrated that furazolidone-containing regimens are more efficacious than those containing other antibiotics, as both first- and second-line therapies, and are also well tolerated. However, utility of furazolidone is restricted or not optimal in certain countries due to its infrequent but potentially severe adverse effects. The decision to discontinue usage of furazolidone because of concerns regarding adverse effects may be misguided. Here we comprehensively reviewed the studies on furazolidone at different dosages and treatment durations for H. pylori eradication. Further research on the mechanisms of action and clinical trials of furazolidone are of great practical importance.

The application of vonoprazan significantly improved the eradication rate of Helicobacter pylori (H. pylori). This study aimed to compare efficacy and safety of the 10-day vonoprazan–amoxicillin (VA) and 14-day rabeprazole–amoxicillin (RA) dual therapy, and to provide a more efficient, safer, and convenient dual regimen for H. pylori infection. This was a prospective, open-label, multi-center, randomized controlled study of treatment-naive patients with H. pylori infection. The participants were randomly assigned to the 10-day VA group with vonoprazan 20 mg Bid plus amoxicillin 1 g Tid or the 14-day RA group with rabeprazole 10 mg Tid plus amoxicillin 1 g Tid. The effectiveness, the adverse events, and the patient compliance of the two groups were compared. A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3

BACKGROUND:High-dose dual therapy (HDDT) is an emerging and promising therapeutic regime for Helicobacter pylori (H. pylori) eradication. However, the pharmacokinetics of the components of HDDT, amoxicillin and proton pump inhibitor, are likely to be affected by body size. In this study, we aimed to find out the impact of body size on the efficacy of HDDT. METHODS:We collected the medical data of 385 treatment-naive patients infected with H. pylori who received HDDT (esomeprazole 20 mg and amoxicillin 750 mg four times daily) for 14 days from July 2020 to December 2021. The associations among the eradication efficacy, adverse events, and variables (sex, age, height, body weight, body mass index (BMI), body surface area (BSA), smoking, drinking, etc.) were analyzed respectively in our study. Among these factors, continuous variables were classified into categorical variables using the cut-off values which were calculated by receiver operating characteristic analysis. RESULTS:The eradication rate of HDDT was 89.9%. There were 55 (14.3%) patients who occurred adverse events during the treatment. Patients with height <170.5 cm, body weight <60.5 kg, BMI <20.55 kg/m2 , BSA <1.69 m2 had a higher eradication rate (92.1% vs. 84.0%, 93.1% vs. 86.8%, 96.0% vs. 87.8%, 93.4% vs. 84.8%, all p < .05). The multivariate analysis showed that BSA ≥1.69 m2 (OR 2.53, 95% CI: 1.28-4.99, p = .007) was the only independent predictor of eradication failure. CONCLUSION:HDDT could achieve better eradication efficacy in patients with small BSA. Clinicians should be aware of the impact of BSA on the H. pylori eradication rate and pay more attention to patients with large BSA.