International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by Board of Specialty Committee of Digestive System Disease of World Federation of Chinese Medicine Societies (2023).

Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework. Additionally, it incorporated insights from ancient Chinese medical sources, employing the evidence grading method found in traditional TCM literature. The development process involved collaboration with multidisciplinary experts and included input from patients with UC. The guideline, based on a comprehensive review of available evidence, present 40 recommendations. They offer a condensed overview of TCM's role in understanding the pathogenesis, diagnosis, and treatment of UC, along with an assessment of the efficacy of various TCM-based treatments. TCM exhibits promising outcomes in the treatment of UC. However, to establish its efficacy conclusively, further high-quality clinical studies on TCM for UC are essential.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Herbal medicines in functional dyspepsia-Untapped opportunities not without risks.

BACKGROUND: Contemporary treatments for functional dyspepsia have limitations. Herbal medicine has been suggested as adjunctive treatment. With growing scientific recognition and public interests, an in-depth review of this is timely. AIMS/PURPOSE: To evaluate the therapeutic potential and problems that may be associated with the adoption of herbal medicines in functional dyspepsia. METHODS: We reviewed the treatment landscape of functional dyspepsia and assessed the scientific community's interest in herbal medicine. Preclinical pharmacological and clinical trial data were reviewed for several herbal medicines available in the market. Challenges associated with adoption of herbal medicine in mainstream medicine were critically evaluated. RESULTS: We found that herbal medicines frequently comprise a combination of herbs with multiple reported pharmacological effects on gastrointestinal motility and secretory functions, as well as cytoprotective and psychotropic properties. We identified a number of commercially available herbal products that have undergone rigorous clinical trials, involving large numbers of well-defined subjects, reporting both efficacy and safety for functional dyspepsia. Persisting concerns include lack of rigorous assessments for majority of products, toxicity, consistency of ingredients, dose standardizations, and quality control. We provide a quality framework for its evaluation. CONCLUSIONS: We commend herbal medicine as a viable future option in managing functional dyspepsia. An attractive appeal of herbal medicine is the prospect to simultaneously target multiple pathophysiological mechanisms. Wider adoption and acceptance of herbal medicines in treatment algorithms of functional dyspepsia will require the application of the scientific rigor expected of chemical therapies, to all stages of their development and evaluation.

Herbal medicine in the treatment of functional gastrointestinal disorders: A systematic review with meta-analysis.

BACKGROUND AND AIMS: The efficacy of herbal medicines (HMs) for functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS), functional dyspepsia (FD) and functional constipation (FC) is controversial. A systematic review with meta-analysis was conducted to determine their effectiveness for FGIDs. METHODS: We searched the following electronic databases till July 2019 with English language restriction: The Cochrane Library, EMBASE and PUBMED. Randomized double-blind controlled trials of HMs compared with placebo or conventional pharmacological drugs for adult FGIDs patients were included. RESULTS: In total, 49 trials involving 7396 participants with FGIDs were included. The risk of bias was low in 9, unclear in 36, and high in 4 trials. More than 33 different herbal formulae were tested. HMs demonstrated statistically significant benefits for symptom improvement compared with placebo in 46 trials (RR = 1.67, 95% CI 1.48-1.88). When compared with conventional pharmacological therapy in 5 trials, HMs were found to be non-inferior (RR = 1.10, 95% CI 1.03-1.18). The number of trials with regards to FD, IBS and FC were 19, 23 and 7 respectively. Subgroup analysis found that HMs were better than placebo in alleviating symptoms for FD (RR = 1.50, 95% CI 1.32-1.69), IBS (RR = 1.62, 95% CI 1.32-1.97) and FC (RR = 3.83, 95% CI 2.26-6.50). HMs tended to have more patients with adverse events than placebo, but similar to conventional pharmacological drugs. CONCLUSIONS: Our findings provide a positive signal for HMs as a potentially well-tolerated and effective treatment for FGIDs, deserving further examination in high-quality trials.

The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in patients with postprandial distress syndrome.

BACKGROUND AND AIM: The treatment of patients with functional dyspepsia (FD) remains unsatisfactory. We assessed the efficacy of Zhizhu Kuanzhong (ZZKZ) capsule, a traditional Chinese medicine formula, in patients with postprandial distress syndrome (PDS) of FD. METHODS: The study was designed as a multicenter, randomized, double-blinded, controlled clinical trial. Three-hundred ninety-two patients with PDS defined by Rome III criteria from 16 centers in China were randomly assigned to receive either ZZKZ or placebo. The proportion of the responders at 4 weeks after randomization was considered primary endpoint. Secondary endpoint was the symptom score reduction of each dyspeptic symptom relative to the baseline at 4 weeks after randomization in all subjects. RESULTS: In terms of the primary endpoint, the proportion of the responders concerning the composite PDS symptom score was 38.8% and 54.7% in placebo group and ZZKZ group, respectively (P = 0.003), in per protocol analysis at 4 weeks after randomization. Concerning the individual evaluated upper gastrointestinal symptoms, only postprandial fullness and early satiety showed significant difference in symptom score reduction at 4 weeks after randomization between placebo and ZZKZ groups. CONCLUSIONS: Zhizhu Kuanzhong is superior to placebo in the treatment of PDS with FD. The exact mechanisms by which ZZKZ improves symptoms remain to be established (http://www.chictr.org.cn/ChinCTR-TRC-14004714).

A Prospective Study to Monitor for Tuberculosis During Anti-tumour Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease and Immune-mediated Inflammatory Diseases.

BACKGROUND: Biologic therapies have revolutionised the treatment of immune-mediated diseases including inflammatory bowel disease [IBD] and rheumatological disorders. However, biologic treatments are associated with an increased risk of reactivation of latent tuberculosis. Data from regular monitoring for latent tuberculosis infection [LTBI] during biologic treatment are lacking. METHODS: Consecutive patients eligible for biologic therapies were screened for LTBI and prospectively followed up for 3 years. Incidence and risk factors of latent tuberculosis tests conversion (interferon gamma release assays [IGRA], tuberculin skin tests [TST], and chest radiography [CXR]) with clinical outcomes were studied. RESULTS: A total of 108 patients [83 IBD; 25 rheumatological disorders] were included. At baseline, 18/108 [16.7%] patients [five IBD; 13 rheumatological disorders] were tested positive for LTBI. Of these, 14/18 [77.8%] patients received isoniazid monotherapy for 9 months. Of the remainder, 17/90 [18.9%] patients had LTBI test conversion while on biologic therapies and of these 14/17 [82.4%] received isoniazid monotherapy for 9 months. Age, sex, smoking status, alcohol use, travel history, disease type, and immunosuppressive therapy were not associated with LTBI test conversion. In subjects with IGRA conversion, serial IGRA levels normalised after completion of isoniazid except in one patient whose IGRA remained persistently elevated despite isoniazid and who subsequently developed active TB. CONCLUSIONS: Conversion of LTBI is common and occurred early during biologic therapy in an area with intermediate TB burden. Subjects with latent TB tests conversion and persistently high IGRA levels may have an increased risk of TB reactivation or development of active TB, and they require close observation or intensive workup for active TB.

Autocrine vascular endothelial growth factor signaling promotes cell proliferation and modulates sorafenib treatment efficacy in hepatocellular carcinoma.

UNLABELLED: Tumor cells express vascular endothelial growth factor (VEGF) that can activate VEGF receptors (VEGFRs) on or within tumor cells to promote growth in an angiogenesis-independent fashion; however, this autocrine VEGF pathway has not been reported in hepatocellular carcinoma (HCC). Sorafenib, an angiogenic inhibitor, is the only drug approved for use in advanced HCC patients. Yet the treatment efficacy is diverse and the mechanism behind it remains undetermined. Our aims were to study the molecular mechanisms underlying autocrine VEGF signaling in HCC cells and evaluate the critical role of autocrine VEGF signaling on sorafenib treatment efficacy. By immunohistochemistry, we found robust nuclear and cytoplasmic staining for active, phosphorylated VEGF receptor 1 (pVEGFR1) and phosphorylated VEGF receptor 2 (pVEGFR2), and by western blotting we found that membrane VEGFR1 and VEGFR2 increased in HCC tissues. We showed that autocrine VEGF promoted phosphorylation of VEGFR1 and VEGFR2 and internalization of pVEGFR2 in HCC cells, which was both pro-proliferative through a protein lipase C-extracellular kinase pathway and self-sustaining through increasing VEGF, VEGFR1, and VEGFR2 mRNA expressions. In high VEGFR1/2-expressing HepG2 cells, sorafenib treatment inhibited cell proliferation, reduced VEGFR2 mRNA expression in vitro, and delayed xenograft tumor growth in vivo. These results were not found in low VEGFR1/2-expressing Hep3B cells. In an advanced HCC population on sorafenib treatment for postoperative recurrence, we found that the absence of VEGFR1 or VEGFR2 expression in resected tumor tissues before sorafenib treatment was associated with poorer overall survival. CONCLUSION: Autocrine VEGF signaling directly promotes HCC cell proliferation and affects the sorafenib treatment outcome in vitro and in vivo, which may enable better stratification for clinical treatment decisions.

High-dose esomeprazole is required for intraesophageal acid control in gastroesophageal reflux disease patients with hiatus hernia.

BACKGROUND AND AIM: The aim of this study was to assess whether the efficacy of proton pump inhibitors (PPI) therapy at a standard dose in esophageal acid control is affected by the presence of hiatus hernia in Chinese gastroesophageal reflux disease patients, and whether a higher dose of PPI is required for acid control. METHODS: Consecutive gastroesophageal reflux disease patients who had typical reflux symptoms and abnormal baseline 24-h esophageal pH and underwent upper endoscopy were enrolled to receive esomeprazole at 40 mg once daily for 4 weeks. Patients underwent the dual-channel 24-h pH test at the end of 4-week therapy. If the 24-h esophageal pH was still abnormal at the end of 4-week therapy, then esomeprazole at 40 mg twice daily was given for another 4 weeks after a washout interval of 1 week, and a 24-h pH test was repeated at the end of the therapy. RESULTS: Overall, 76 patients were included, 13 with hiatus hernia. Of the 76 patients treated with a 40 mg of esomeprazole daily, esophageal acid exposure was normalized in 64 (84.2%). Normalization of acid exposure was achieved by standard PPI therapy in 53.2% (7/13) of patients with hiatus hernia and 90.5% (57/63) of those without (P = 0.004). A double dose of esomeprazole was successful in normalizing the esophageal pH in all 12 non-responders to the standard dose of esomeprazole, including the six patients with hiatus hernia and six patients without. CONCLUSIONS: The standard-dose of esomeprazole fails to normalize the esophageal pH in almost 50% of patients with hiatus hernia, in whom the "double-dose" esomeprazole therapy is required.