BACKGROUND/AIMS: Antispasmodics including otilonium bromide (OB) are recommended to treat irritable bowel syndrome (IBS). However, reports about OB experience in Asia is sparse. The purpose of present study was to provide the efficacy of OB in treating Asian IBS patients. METHODS: Overall, 117 IBS patients meeting Rome II criteria were enrolled in an 8-week, double-blind, active-controlled and single center trial. Randomized participants received either OB 40 mg or mebeverine 100 mg 3 doses daily. The primary endpoints were to evaluate the net changes of abdominal pain/discomfort frequency score (APDFS) and safety profile, while the secondary endpoints were to assess the changes in abdominal pain/discomfort intensity, flatulence, abdominal bloating, satisfied stool frequency etc. RESULTS: Finally, 49 OB and 52 mebeverine subjects were eligible for efficacy analysis. Compared to baselines in per protocol populations, the reduced APDFSs in OB and mebeverine were 0.55 +/- 1.20 (P = 0.011) and 0.37 +/- 1.11 (P = 0.042), respectively, to show similarly reduced scores. The most reported side effects included dry mouth, nausea and dizziness. Besides, the improved APDFSs at 4th week visit, final alleviations in abdominal pain intensity, flatulence, abdominal bloating and satisfied stool frequency with global assessments filled by both patients and investigators were significantly achieved by both treatments, and OB was not inferior to mebeverine in treating these parameters. CONCLUSIONS: In Orientals, OB is as effective as mebeverine for alleviating IBS symptoms in terms of abdominal pain, flatulence, abdominal bloating etc. However, obvious side effects are also observed. A large-scaled trial and post-marketing surveillance are recommended to confirm its efficacy and safety.
Abdominal Pain ; Asia ; Asian Continental Ancestry Group ; Dizziness ; Flatulence ; Humans ; Irritable Bowel Syndrome ; Mouth ; Nausea ; Parasympatholytics ; Phenethylamines ; Quaternary Ammonium Compounds ; Research Personnel ; Rome

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Apoptosis* ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Protein-Tyrosine Kinases* ; RNA, Small Interfering ; Triple Negative Breast Neoplasms* ; Tyrosine*

During the Coronavirus Disease 2019 (COVID-19) pandemic, practices of gastrointestinal procedures within the digestive tract require special precautions due to the risk of contraction of severe acute respiratoy syndrome coronavirus-2 (SARS-CoV-2) infection. Many procedures in the gastrointestinal motility laboratory may be considered moderate to high-risk for viral transmission. Healthcare staff working in gastrointestinal motility laboratories are frequently exposed to splashes, air droplets, mucus, or saliva during the procedures. Moreover, some are aerosol-generating and thus have a high risk of viral transmission. There are multiple guidelines on the practices of gastrointestinal endoscopy during this pandemic. However, such guidelines are still lacking and urgently needed for the practice of gastrointestinal motility laboratories. Hence, the Asian Neurogastroenterology and Motility Association had organized a group of gastrointestinal motility experts and infectious disease specialists to produce a position statement paper based-on current available evidence and consensus opinion with aims to provide a clear guidance on the practices of gastrointestinal motility laboratories during the COVID-19 pandemic. This guideline covers a wide range of topics on gastrointestinal motility activities from scheduling a motility test, the precautions at different steps of the procedure to disinfection for the safety and well-being of the patients and the healthcare workers. These practices may vary in different countries depending on the stages of the pandemic, local or institutional policy, and the availability of healthcare resources. This guideline is useful when the transmission rate of SARS-CoV-2 is high. It may change rapidly depending on the situation of the epidemic and when new evidence becomes available.