Comparison of vonoprazan-based with rabeprazole-based dual therapy for treatment-naive patients of Helicobacter pylori infection: a prospective, multi-center, randomized controlled study.

BACKGROUND: 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. METHODS: 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. RESULTS: A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3% and 84.9% in intention-to-treat (ITT) analysis (P = 0.088); 90.6% and 85.9% by modified intention-to-treat (mITT) analysis (P = 0.059); 91.4% and 86.6% by per-protocol (PP) analysis (P = 0.047). Non-inferiority was confirmed between the two groups (all P < 0.001). No discernible differences were observed in adverse effects and compliance between groups. Poor compliance reduced the eradication efficacy (P < 0.05). CONCLUSIONS: The 10-day VA dual therapy was non-inferior to the 14-day RA dual therapy for H. pylori treatment-naive patients, which should be given priority in the first-line treatment. The application of vonoprazan reduced treatment course and antibiotic use. Patients' adherence was crucial for the success of eradication.

Oral and fecal microbiota in patients with diarrheal irritable bowel syndrome.

Background: This study aimed at investigating the characteristics and correlation between oral (tongue coating) and fecal microbiota in patients with diarrheal irritable bowel syndrome (IBS-D). Methods: Fifty-two IBS-D patients were chosen, with ten healthy volunteers serving as the normal control group. Tongue coating samples and fecal samples of subjects were sequenced for the 16S rRNA gene (V4-V5). Bioinformatics analysis was done on the test data to investigate oral and fecal microbiota composition characteristics in IBS-D patients. Results: The microbial richness of tongue coating in IBS-D group was lower than that in the normal control group (P < 0.05). The beta diversity of tongue coating microbiota and fecal microbiota was significantly different in the IBS-D group compared to the normal control group (P < 0.05). Pseudomonadales (Pseudomonadaceae and Pseudomonas), Moraxellaceae, Parvimonas, Peptostreptococcus, and Alloprevotella were considerably high in number the tongue coating samples of the IBS-D group in comparison to the normal control group. Similarly, the fecal samples from the IBS-D group were significantly enriched in Alphaproteobacteria, Pseudomonadales (Pseudomonadaceae and Pseudomonas), Acidaminococcaceae, Phascolarctobacterium, Alloprevotella, and Escherichia compared to the normal control group. Conclusions: The oral and fecal microbiotas of IBS-D patients differ from those of the control group; hence studying IBS-D from the perspective of the oral-gut microbiome axis is an interesting research avenue.

Optimized dual therapy for treatment-naive patients of Helicobacter pylori infection: A large-scale prospective, multicenter, open-label, randomized controlled study.

BACKGROUND: The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS: The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS: Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS: Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.

Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule in treating chronic non-atrophic gastritis: A multicentre, double-blind, randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. AIM OF THE STUDY: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. MATERIALS AND METHODS: This study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). RESULTS: Both groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001)，especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. CONCLUSION: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.

Comparison of high-dose dual therapy with bismuth-containing quadruple therapy in Helicobacter pylori-infected treatment-naive patients: An open-label, multicenter, randomized controlled trial.

OBJECTIVE: Bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) eradication has a relatively high rate of side effects and high cost, thus the option of a high-dose dual therapy with a high eradication rate and fewer adverse events is a consideration. However, studies of dual therapy are still scarce and are mostly single-center studies with limited generalizability. Large-scale, multicenter studies are required. Our study investigated and compared the effectiveness, adverse events, patient compliance, and costs of high-dose dual therapy with those of bismuth-containing quadruple therapy in H. pylori-infected treatment-naive patients in a prospective, multicenter, open-label, randomized controlled trial. METHOD: Treatment-naive patients infected with H. pylori were randomly assigned to receive high-dose dual therapy (esomeprazole 20 mg 4 times daily and amoxicillin 1000 mg 3 times daily, for 14 days) or bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days). The effectiveness, adverse events, patient compliance, and costs of both groups were compared. RESULTS: A total of 700 patients were enrolled. The high-dose dual therapy group (N = 350) achieved eradication rates of 89.4% (intention-to-treat), 90.4% (modified intention-to-treat), and 90.6% (per-protocol), which were similar to rates in the bismuth-containing quadruple therapy group (N = 350), 84.6%, 88.0%, and 88.2%, respectively (p > 0.05). The high-dose dual therapy group had a lower rate of adverse events (12.9% vs. 28.1%, p < 0.001) and lower costs (¥590.2 vs. ¥723.22) compared with the quadruple therapy group, respectively. The compliance of both groups was satisfactory (97.7% high-dose dual vs. 96.8% quadruple, p > 0.05). CONCLUSION: High-dose dual therapy for H. pylori eradication had similar efficacy and compliance, fewer adverse events, and lower costs than bismuth-containing quadruple therapy for treatment-naive patients.

A retrospective study of the antibiotic-resistant phenotypes and genotypes of Helicobacter pylori strains in China.

Helicobacter pylori antibiotic resistance is a serious concern in China, where it severely influences treatment for H. pylori infection. To overcome this, it is essential to apply personalized therapies based on local or individual data on antibiotic-resistant phenotypes or genotypes. We conducted a large-scale multi-center study with a retrospective cross-sectional observational design to investigate the antibiotic-resistant phenotypes and genotypes of H. pylori in China. Strains were isolated from the gastric biopsy samples of H. pylori-infected patients from five different regions in China. The strains were tested for antibiotic-resistant phenotypes and genotypes, and the agreement between the two was assessed. In total, 4242 H. pylori strains were isolated and cultured, with an 84.43% success rate. The primary and secondary antibiotic resistance rates of H. pylori were 37.00% and 76.93% for clarithromycin, 34.21% and 61.58% for levofloxacin, 2.20% and 6.12% for amoxicillin, 1.61% and 3.11% for furazolidone, 1.18% and 3.31% for tetracycline, and 87.87% and 93.48% for metronidazole, respectively. The dual-resistance patterns for metronidazole/clarithromycin, metronidazole/levofloxacin, and clarithromycin/levofloxacin were 43.6%, 38.4%, and 26.1%, respectively. Clarithromycin- and levofloxacin-resistant H. pylori phenotypes and genotypes showed satisfactory agreement. Based on these findings, clarithromycin- and levofloxacin-resistant genotype testing could partially replace traditional antibiotic susceptibility testing in China. Continuous monitoring and personalized treatments based on individual and local H. pylori antibiotic-resistance data remain necessary.

Analgesic Effects of Ultrasound-Guided Iliohypogastric/Ilioinguinal Nerve Block Combined with Lateral Femoral Cutaneous Nerve Block in Total Hip Arthroplasty via Direct Anterior Approach: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to explore the efficacy and safety of the combination of lateral femoral cutaneous nerve blocks (LFCNB) and iliohypogastric/ilioinguinal nerve blocks (IHINB) on postoperative pain and functional outcomes after total hip arthroplasty (THA) via the direct anterior approach (DAA). METHODS: In this retrospective cohort study, patients undergoing THA via the DAA between January 2019 and November 2019 were stratified into two groups based on their date of admission. Sixty-seven patients received LFCNB and IHINB along with periarticular infiltration analgesia (PIA) (nerve block group), and 75 patients received PIA alone (control group). The outcomes included postoperative morphine consumption, postoperative pain assessed using the visual analogue scale (VAS), the QoR-15 score, and functional recovery measured as quadriceps strength, time to first straight leg rise, daily ambulation distance, and duration of hospitalization. The Oxford hip score and the UCLA activity level rating were assessed at 1 and 3 months after surgery. In addition, postoperative complications were recorded. Patients were also compared based on the type of incision used during surgery (traditional longitudinal or "bikini" incision). RESULTS: Patients in the nerve block group showed significantly lower postoperative morphine consumption, lower resting VAS scores within 12 h postoperatively, lower VAS scores during motion within 24 h postoperatively, and better QoR-15 scores on postoperative day 1. These patients also showed significantly better functional recovery during hospitalization. At 1-month and 3-month outpatient follow up, the two groups showed no significant differences in Oxford hip score or UCLA activity level rating. There were no significant differences in the incidence of postoperative complications. Similar results were observed when patients were stratified by type of incision, except that the duration of hospitalization was similar. CONCLUSION: Compared to PIA alone, a combination of LFCNB and IHINB along with PIA can improve early pain relief, reduce morphine consumption, and accelerate functional recovery, without increasing complications after THA via the DAA.

Effects of morphine on peri-articular infiltration analgesia in total knee arthroplasty: a prospective, double-blind, randomized controlled trial.

PURPOSE: Peri-articular infiltration analgesia (PIA) is a widely used method to control post-operative pain in total knee arthroplasty (TKA) patients. However, there are limited data that support the use of morphine in PIA. This study aims to evaluate the efficacy of peri-articular morphine infiltration for pain management in TKA patients. METHODS: Based on a double-blind, randomized approach, patients were allocated to the morphine or control group. Patients in the morphine group received a peri-articular infiltration of an analgesic cocktail consisting of ropivacaine, epinephrine, and morphine. Morphine was omitted from the cocktail in the control group. Primary outcomes were post-operative consumption of morphine hydrochloride used for rescue analgesia and post-operative pain as assessed by visual analog scale (VAS) score. Secondary outcomes were functional recovery as assessed by a range of knee motion, quadriceps strength, and daily ambulation distance. The duration of hospital stay was also recorded. Tertiary outcomes included the occurrence of post-operative adverse effects and the consumption of antiemetics. RESULTS: Patients in the morphine group had significantly lower post-operative morphine consumption in the first 24 h and total morphine consumption. There was no significant difference between the two groups in post-operative VAS pain scores at rest or during motion. There was no significant difference between the two groups in the post-operative knee range of motion, quadriceps strength, daily ambulation distance, or duration of post-operative hospital stay. The two groups were similar in the incidence of adverse effects and the consumption of antiemetics. CONCLUSION: Adding morphine into the analgesic cocktail of PIA could reduce postoperative morphine consumption in TKA patients, but does not improve early pain relief or accelerate functional recovery or provide clinical benefits for TKA patients. In addition, the complications and safety of peri-articular morphine infiltration need to be further investigated in larger sample studies.

Cap-assisted endoscopic sclerotherapy for internal hemorrhoids: technique protocol and study design for a multi-center randomized controlled trial.

BACKGROUND: Cap-assisted endoscopic sclerotherapy is a new interventional therapy for internal hemorrhoids and rectal prolapse under colonoscopy. The proper length of the endoscopic injection needle is the core for performing cap-assisted endoscopic sclerotherapy well with more benefits and less complications. However, no data are currently available to guide endoscopists to consider the length of injection needle before cap-assisted endoscopic sclerotherapy. This study is designed to evaluate the efficacy and safety of cap-assisted endoscopic sclerotherapy with long or short injection needle in the treatment of internal hemorrhoids. METHODS: This is a nationwide multi-center, prospective, single-blind and randomized controlled trial. Patients with grade I-II internal hemorrhoids who have failed to conservative treatments and grade III internal hemorrhoids who are not suitable for surgery or refuse surgery will be included. Participants will be randomized 1:1 into either long or short injection needle group. The primary outcome is the recurrence rate of internal hemorrhoids 24 weeks after cap-assisted endoscopic sclerotherapy. The secondary outcomes are as follows: (1) symptom severity score, (2) three-level EuroQoL five dimensions health scale scores, (3) occurrence of adverse events and severe adverse events, and (4) patients' attitudes toward cap-assisted endoscopic sclerotherapy. Data collection will be conducted before and during operation, the 1st day, 1st week, 2nd week, and 24th week after cap-assisted endoscopic sclerotherapy. DISCUSSION: The outcome of this study is expected to provide a practical clinical protocol of cap-assisted endoscopic sclerotherapy for patients with internal hemorrhoids and promote the use of this new endoscopic technique. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03917056. Registered on 12 April 2019.

Protective effects of curcumin against chronic alcohol-induced liver injury in mice through modulating mitochondrial dysfunction and inhibiting endoplasmic reticulum stress.

BACKGROUND: Curcumin is a major active ingredient extracted from powdered dry rhizome of Curcuma longa. In Ayurveda and traditional Chinese medicine, it has been used as a hepatoprotective agent for centuries. However, the underlying mechanisms are not clear. OBJECTIVE: The present study is to investigate the hepatoprotective effects of curcumin in chronic alcohol-induced liver injury and explore its mechanism. DESIGN: Alcohol-exposed Balb/c mice were treated with curcumin (75 and 150 mg/kg) once per day for 8 weeks. Tissue from individual was fixed with formaldehyde for pathological examination. The activities of mitochondrial antioxidant enzymes, Na+/k+-ATPase, Ca2+-ATPase, and Ca2+Mg2+-ATPase, were determined. The level of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening was also determined. The expression of PGC-1α, NRF1, Mn-SOD, GRP78, PERK, IRE1α, nuclear NF-κB, and phosphorylated IκBα was quantified by western blot. The contents of TNF-α, IL-1ß, and IL-6 in the liver were measured using the ELISA method. RESULTS: Curcumin significantly promoted hepatic mitochondrial function by reducing the opening of MPTP, thus increasing the MMP, promoting the activity of Na+/k+-ATPase, Ca2+-ATPase, and Ca2+/Mg2+-ATPase, and attenuating oxidative stress. Curcumin upregulated the expression of PGC-1α, NRF1, and Mn-SOD, and downregulated the expression of GRP78, PERK, and IRE1α in hepatic tissue. Curcumin also attenuated inflammation by inhibiting the IκBα-NF-κB pathway, which reduced the production of TNF, IL-1ß, and IL-6. CONCLUSION: Curcumin attenuates alcohol-induced liver injury via improving mitochondrial function and attenuating endoplasmic reticulum stress and inflammation. This study provides strong evidence for the beneficial effects of curcumin in the treatment of chronic alcohol-induced liver injury.