Exosomes Derived from Caerulein-Stimulated Pancreatic Acinar Cells Mediate Peritoneal Macrophage M1 Polarization and Pyroptosis via an miR-24-3p/MARCH3/NLRP3 Axis in Acute Pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on caerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood. METHODS: A caerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of caerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules. RESULTS: We found that exosomes derived from caerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in caerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells. CONCLUSIONS: Exosomes derived from caerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.

Alterations and clinical relevance of gut microbiota in patients with Peutz-Jeghers syndrome: A prospective study.

OBJECTIVE: In this case-control study we aimed to investigate the intestinal microbiota profile of patients with Peutz-Jeghers syndrome (PJS) and its association with polyp growth. METHODS: Thirty-two PJS patients and 35 healthy controls were enrolled. Fecal samples of all participants were collected for gut microbiota analysis via 16S rRNA gene (regions V3-V4) sequencing. SPSS version 22.0 and R software version 3.1.0 were used for the statistical analysis. RESULTS: The richness was comparable, while the overall structure of the gut microbiota differed significantly between the PJS and control groups (weighted UniFrac, P = 0.001; unweighted UniFrac, P = 0.008). Significantly different abundances of two phyla, seven families, and 18 genera as well as twenty-nine differentially enriched functional modules (false discovery rate, P < 0.05) between the two groups were identified. Morganella was positively associated with the median number of polyps (JPN; r = 0.96, P < 0.001) and number of newly discovered polyps in the jejunum between two recent endoscopic resections (JPNG; r = 0.78, P = 0.04). Desulfovibrio was positively associated with JPNG (r = 0.87, P = 0.01). Blautia was negatively associated with the median maximum size of polyps in the jejunum (JPS). Anaerostipes was negatively associated with JPN, JPNG and JPS. Clostridium XVIII and Fusicatenibacter were negatively associated with JPN and JPS, respectively. CONCLUSIONS: We found remarkably different gut microbiota of patients with PJS compared to healthy individuals and associations between specific fecal bacteria and clinical features of PJS. These findings may provide a new perspective for the management of PJS in clinical practice.

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

Effects of probiotics on gastric microbiota and its precombination with quadruple regimen for Helicobacter pylori eradication.

OBJECTIVES: This study aimed to assess the efficacy and safety of probiotics for Helicobacter pylori (H. pylori) eradication therapy as well as their effects on gastric microbiota. METHODS: Patients who had failed H. pylori eradication therapy for at least twice were prospectively enrolled during March 2019 and March 2021. A 2-week administration of compound Lactobacillus acidophilus probiotic (1 g thrice daily) followed by a 10-day quadruple bismuth-containing H. pylori eradication therapy was administrated. Endoscopy was performed, and gastric biopsy samples were obtained for drug sensitivity testing and 16S rRNA gene sequencing before and after probiotic treatment. Eradication was evaluated by the 13 C-urea breath test at least 4 weeks after treatment completion. Adverse events (AEs) were recorded. RESULTS: Thirty-seven patients were included. Probiotic supplementation had no effects on the diversity, community structure, and composition of gastric microbiota and no inhibition on H. pylori activity. However, it increased some of the beneficial bacteria such as Blautia, Dorea, and Roseburia (P < 0.05). The overall eradication rate was 97.3% (95% confidence interval [CI] 91.8%-100%). AEs, mainly dizziness, nausea, diarrhea, and chest distress, were detected in six individuals, all of which were resolved upon cessation of antibiotic administration. Dyspeptic symptoms were improved after probiotic supplementation and at treatment completion (both P < 0.001). CONCLUSIONS: H. pylori-infected individuals might benefit from probiotics followed by a quadruple bismuth-containing eradication therapy. Further studies with large sample sizes are warranted.

Changhai advanced endoscopy courses for ERCP (CHANCE) training program: A short-term training model in China.

BACKGROUND: There is huge shortage of ERCP practitioners (ERCPists) in China, and ERCP training is urgently needed. ChangHai Advanced eNdoscopy Courses for ERCP (CHANCE) is a 4-month program for ERCP training since 2004. This study evaluated the efficiency of this short-term training model, and reported on the ERCP careers of the trainees following completion of the CHANCE program. METHODS: This study was a retrospective investigation included all the CHANCE trainees from Jan 2004 to Dec 2014. Questionnaires were sent to all trainees. The career competence percentage, ERCP careers and predictive factors of career competence were investigated and analyzed. RESULTS: A total of 413 trainees participated in the CHANCE program over 11 years covered by the survey and 258 questionnaires were valid for the study. The mean (SD) age of the trainees was 35.36 (4.17), and the male to female ratio was 4.4:1. The average follow-up time was 7.77 (3.44) years. A total of 173 (67.1%) trainees had achieved career competence. In terms of ERCP careers, the mean annual ERCP volume was 120.60 (96.67), with a complication percentage of 8.2%. Hospital qualification, compliance with follow-up learning guidance, participating academic activity, and practitioner type were identified predictive factors of career competence. CONCLUSIONS: As a short-term training program, the CHANCE achieved an acceptable career competence percentage, providing endoscopists more chances to learn ERCP and giving them appropriate training guidance for career competence. This training mode is worth promoting in developing countries with shortage of ERCPists.

Rectal indometacin to prevent pancreatitis after extracorporeal shock wave lithotripsy (RIPEP): a single-centre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Pancreatitis is the most common complication of pancreatic extracorporeal shock wave lithotripsy (ESWL). There has been little research into effective prevention of post-ESWL pancreatitis. Therefore, we aimed to assess the efficacy of prophylactic rectal indometacin in preventing post-ESWL pancreatitis. METHODS: In this double-blind, randomised, placebo-controlled trial done at Changhai Hospital (Shanghai, China), patients aged 18 years or older with chronic pancreatitis and pancreatic stones (>5 mm in diameter) who were eligible for treatment with ESWL were randomly allocated using a computer-generated randomisation table, in a 1:1 ratio, to receive 100 mg rectal indometacin or identical glycerin (placebo) suppositories 30 min before ESWL. Patients, endoscopists, and outcome assessors were masked to group allocation. The primary outcome was the incidence of post-ESWL pancreatitis within 24 h of ESWL, analysed by the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02797067. FINDINGS: Between May 31, 2016, and June 26, 2019, 1370 patients were enrolled, with 685 patients randomly assigned to the rectal indometacin group and 685 patients to the placebo group. All patients received their allocated intervention and completed final follow-up, and were included in the intention-to-treat analysis. Post-ESWL pancreatitis occurred in 60 (9%) patients in the rectal indometacin group and 84 (12%) patients in the placebo group (relative risk 0·71, 95% CI 0·52-0·98; p=0·042). Transient adverse events occurred in 235 (34%) patients in the rectal indometacin group and 252 (37%) patients in the placebo group, with asymptomatic hyperamylasaemia being the most common (189 [28%] patients vs 197 [29%] patients). No difference was noted between groups in the incidence of other complications and transient adverse events. INTERPRETATION: Pre-procedural administration of rectal indometacin is an efficacious and safe means of reducing the incidence of post-ESWL pancreatitis. FUNDING: Programs of Shanghai Municipal Government and the "Ten Thousand Plan"-National High Level Talents Special Support Plan.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

A simple new scoring system for predicting the mortality of severe acute pancreatitis: A retrospective clinical study.

It is critical to accurately identify patients with severe acute pancreatitis (SAP) in a timely manner. This study aimed to develop a new simplified AP scoring system based on data from Chinese population.We retrospectively analyzed a consecutive series of 585 patients diagnosed with SAP at the Changhai hospital between 2009 and 2017. The new Chinese simple scoring system (CSSS) was derived using logistic regression analysis and was validated in comparison to 4 existing systems using receiver operating characteristic curves.Six variables were selected for incorporation into CSSS, including serum creatinine, blood glucose, lactate dehydrogenase, heart rate, C-reactive protein, and extent of pancreatic necrosis. The new CSSS yields a maximum total score of 9 points. The cut-offs for predicting mortality and severity (discriminating moderately SAP from SAP) were set as 6 points and 4 points respectively. Compared with 4 existing scoring systems, the area under the receiver operating characteristic of CSSS for prediction of mortality was 0.838, similar to acute physiology and chronic health evaluation II (0.844) and higher than Ranson's score (0.702, P < .001), bedside index of severity in acute pancreatitis (0.615), and modified computed tomography severity index (MCTSI) (0.736). For predicting SAP severity, CSSS was the most accurate (0.834), followed by acute physiology and chronic health evaluation II (0.800), Ranson's score (0.702), MCTSI (0.660), and bedside index of severity in acute pancreatitis (0.570). Further, the accuracy of predicting pancreatic infection with CSSS was the highest (0.634), similar to that of MCTSI (0.641).A new prognostic scoring system for SAP was derived and validated in a Chinese sample. This scoring system is a simple and accurate method for prediction of mortality.

Juvenile polyposis syndrome might be misdiagnosed as familial adenomatous polyposis: a case report and literature review.

BACKGROUND: Juvenile polyposis syndrome (JPS) is a rare disorder characterized by the presence of multiple juvenile polyps in the gastrointestinal tract, and germline mutations in SMAD4 or BMPR1A. Due to its rarity and complex clinical manifestation, misdiagnosis often occurs in clinical practice. CASE PRESENTATION: A 42-year-old man with multiple pedunculated colorectal polyps and concomitant rectal adenocarcinoma was admitted to our hospital. His mother had died of colon cancer. He was diagnosed with familial adenomatous polyposis (FAP) and underwent total proctocolectomy and ileal pouch anal anastomosis. Two polyps were selected for pathological examination. One polyp had cystically dilated glands with slight dysplasia. The other polyp displayed severe dysplasia and was diagnosed as adenoma. Three years later, his 21-year-old son underwent a colonoscopy that revealed more than 50 pedunculated colorectal juvenile polyps. Both patients harbored a germline pathogenic mutation in BMPR1A. Endoscopic resection of all polyps was attempted but failed. Finally, the son received endoscopic resection of polyps in the rectum and sigmoid colon, and laparoscopic subtotal colectomy. Ten polyps were selected for pathological examination. All were revealed to be typical juvenile polyps, with cystically dilated glands filled with mucus. Thus, the diagnosis of JPS was confirmed in the son. A review of the literatures revealed that patients with JPS can sometimes have adenomatous change. Most polyps in patients with JPS are benign hamartomatous polyps with no dysplasia. A review of 767 colorectal JPS polyps demonstrated that 8.5% of the polyps contained mild to moderate dysplasia, and only 0.3% had severe dysplasia or cancer. It is difficult to differentiate juvenile polyps with dysplasia from adenoma, which could explain why juvenile polyps have been reported to have adenomatous changes in patients with JPS. Therefore, patients with JPS, especially those with concomitant dysplasia and adenocarcinoma, might be easily diagnosed as FAP in clinical practice. CONCLUSIONS: Juvenile polyp with dysplasia is often diagnosed as adenoma, which might lead to the misdiagnosis of JPS as FAP. The differential diagnosis of JPS versus FAP, should be based on comprehensive evaluation of clinical presentation, endoscopic appearance and genetic investigations; not on the presence or absence of adenoma.

Double-balloon enteroscopy for retrieving retained small-bowel video capsule endoscopes: a systematic review.

Background and aim: Capsule retention is the most common adverse event associated with video capsule endoscopy. The use of double-balloon enteroscopy-assisted capsule endoscope retrieval has been increasingly reported in recent years. However, evidence is limited regarding its success rate, associated factors, and subsequent clinical outcomes.Methods: A systematic review of relevant studies published before January 2019 was performed. Successful retrieval rate and associated factors, rate of endoscopic balloon dilation, and outcomes after double-balloon enteroscopy were summarized and pooled.Results: Within 154 associated original articles, 12 including 150 cases of capsule retrieval by double-balloon enteroscopy were included. The estimated pooled successful retrieval rate was 86.5% (95% confidence interval, 75.6-95.1%). Anterograde approach and capsules retained in the jejunum or trapped by malignant strictures were associated with a higher successful retrieval rate than the retrograde approach (62/83 [74.7%] vs. 10/38 [26.3%], p < .001) and capsules retained in the ileum (41/41 [100.0%] vs. 43/58 [74.1%], p < .001) or trapped by benign strictures (21/21 [100.0%] vs. 65/83 [78.3%], p = .043). Endoscopic balloon dilation was performed in 38.8% (95% confidence interval, 22.3-56.3%) of patients with benign strictures. Two perforations (1.3%) were reported as severe adverse events after double-balloon enteroscopy. A significantly lower surgery rate was found among cases with successful video capsule removal compared with unsuccessful cases (7.2% vs. 38.5%, p = .002).Conclusions: Double-balloon enteroscopy is feasible and safe for removing retained video capsule endoscopes, and its use could decrease the need for surgery in patients with benign strictures and facilitate subsequent surgery in patients with malignant strictures.

The role of double-balloon enteroscopy in reducing the maximum size of polyps in patients with Peutz-Jeghers syndrome: 12-year experience.

OBJECTIVE: This study aimed to evaluate the role of double-balloon enteroscopy (DBE) in treating intestinal polyps in patients with Peutz-Jeghers syndrome (PJS). METHODS: All patients diagnosed with PJS who underwent a polypectomy under DBE from October 2006 to December 2018 were enrolled. Their clinical records, including surgical history, the method of DBE insertion, the number of DBE procedures, and the maximum size and number of the resected polyps, were retrospectively reviewed. RESULTS: Altogether 97 patients were enrolled. For both antegrade and retrograde DBE the maximum size of the resected polyps during the second hospitalization was significantly smaller than that during the first hospitalization (antegrade DBE: [2.13 ± 1.51] cm vs [3.63 ± 0.92] cm, P = 0.012; retrograde DBE: [1.20 ± 1.10] cm vs [2.95 ± 1.95] cm, P = 0.03), but was significantly larger than that during the third hospitalization (antegrade DBE: [2.13 ± 1.51] cm vs [0.88 ± 0.70] cm, P = 0.012; retrograde DBE: [1.20 ± 1.10] cm vs [0.46 ± 0.40] cm, P = 0.048). The interval between the second and third hospitalizations was significantly longer than that between the first and second hospitalizations ([899.00 ± 382.12] days vs [537.27 ± 326.28] days, P = 0.027). The success rate of total enteroscopy was 58.3% (28/48), which was not affected by a history of laparotomy (61.5% vs 52.4%, P = 0.528). The complication rate was 4.4%. CONCLUSION: DBE is clinically safe and effective for the diagnosis and treatment of intestinal polyps in patients with PJS.

Lumen-apposing metal stents (LAMS) versus plastic stents for EUS-guided drainage of walled-off necrosis (WON) (LVPWON): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Endoscopic ultrasonography (EUS)-guided drainage has become the first-line therapy for late peri-pancreatic fluid collection (PFC). Double pigtail plastic stents (DPPS) and lumen-apposing metal stents (LAMS) are commonly used for PFC drainage. Recently, a multi-institutional consensus on PFC drainage has recommended that LAMS should be the standard care for patients with walled-off necrosis (WON). However, given the poor quality of evidence, we aim to perform a large-scale randomized controlled trial to determine whether LAMS is superior to DPPS for WON drainage. METHODS/DESIGN: The study is an open-label, prospective, parallel-group, superiority, multicenter randomized controlled trial. Two hundred and fifty-six patients with WON who will attend 18 tertiary hospitals in China will be randomly allocated to the LAMS or DPPS group before the procedure. The primary endpoint is the clinical success at one month after drainage (reduction in the size of WON to < 2 cm). Secondary endpoints include technical success, operation time, recurrence, adverse events, and secondary interventions. DISCUSSION: The LVPWON trial is designed to determine whether LAMS is effective, safe, and superior to DPPS for WON drainage. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03027895 . Registered on 14 January 2017.

Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection.

BACKGROUND: Since the 'Fourth Chinese National Consensus Report on the management of H. pylori infection' was published in 2012, three important consensuses (Kyoto global consensus report on H. pylori gastritis, The Toronto Consensus for the Treatment of H. pylori Infection in Adults and Management of H. pylori infection-the Maastricht V/Florence Consensus Report) have been published regarding the management of H. pylori infection. MATERIALS AND METHODS: A Delphi method was adopted to develop the consensus of relevant 'statements'. First, the established 'statements' were sent to experts via email. Second, after undergoing two rounds of consultation, the initial statements were discussed face to face and revised in the conference item by item on 16 December 2016. Finally, 21 core members of conferees participated in the final vote of statements. Voting for each statement was performed using an electronic system with levels of agreements shown on the screen in real time. RESULTS: Consensus contents contained a total of 48 "statements" and related 6 parts, including indications for H. pylori eradication, diagnosis, treatment, H. pylori and gastric cancer, H. pylori infection in special populations, H. pylori and gastrointestinal microbiota. CONCLUSIONS: Recommendations are provided on the basis of the best available evidence.

Epidemiology of obscure gastrointestinal bleeding in China: A single-center series and comprehensive analysis of literature.

OBJECTIVE: To determine the etiologies of obscure gastrointestinal bleeding (OGIB) in a Chinese population using a retrospective case series and a systematic analysis of the literatures on OGIB in Chinese patients. METHODS: A large enteroscopy database in a tertiary endoscopic center was searched to identify patients with OGIB from 2010 to 2016. The patients' characteristics and diagnostic findings were collected and analyzed. A comprehensive search of the literature was carried out to harvest all relevant studies published from 2004 to 2016. RESULTS: In total, 708 patients were included in the case series. The most common causes of OGIB were inflammatory diseases (36.3%), non-small bowel lesions (10.2%) and neoplasms (10.0%). A systematic analysis of the literatures included 39 studies providing relevant data for 3145 patients with a pooled detection rate of 84.2%. Inflammatory lesions (27.4%), neoplasms (18.5%), vascular lesions (16.1%) and diverticula or intestinal duplication (11.9%) were the most common causes of OGIB. CONCLUSIONS: Inflammatory lesions, neoplasms, vascular lesions and diverticula or intestinal duplication are the most common in Chinese OGIB patients, while in pediatric patients diverticula or intestinal duplication, vascular lesions and Crohn's disease are prevalent. Furthermore, the etiologies of OGIB distribute differently across different areas in China.

Rectally administered indomethacin to prevent post-ESWL-pancreatitis (RIPEP): study protocol for a randomized controlled trial.

BACKGROUND: Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is the first-line therapy for large pancreatic duct stones. Although it is a highly effective and safe procedure for the fragmentation of pancreatic stones, it is still not complication-free. Just like endoscopic retrograde cholangiopancreatography (ERCP), pancreatitis is the most common complication. To date, nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be the only effective prophylactic medication for post-ERCP pancreatitis and the European, American and Japanese Society for Gastrointestinal Endoscopy guidelines have recommended prophylactic rectally administered indomethacin for all patients undergoing ERCP. Given the little research about effective prevention for post P-ESWL pancreatitis, we aim to determine whether rectally administered indomethacin can reduce post-ESWL-pancreatitis. METHODS/DESIGN: The RIPEP study is a prospective, randomized, double-blinded, placebo-controlled trial. One thousand three hundred and seventy patients with chronic pancreatitis and pancreatic stones (>5 mm in diameter) treated with P-ESWL at Changhai Hospital will be randomly allocated to rectally administered indomethacin or placebo therapy before the procedure. The primary endpoint is the incidence of post-ESWL pancreatitis. Secondary endpoints include the severity of pancreatitis, occurrence rate of asymptomatic hyperamylasemia and other complications. DISCUSSION: The RIPEP trial is designed to show that rectally administered indomethacin reduces the development and severity of post-ESWL pancreatitis and benefits patients treated with P-ESWL. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02797067 . Registered on 17 November 2016.

Comparison of efficacy and safety of hyoscine butylbromide versus anisodamine for acute gastric or intestinal spasm-like pain: A randomized, double-blinded, multicenter Phase III trial.

OBJECTIVE: Acute gastric or intestinal spasm-like pain is common in clinical setting. Hyoscine butylbromide (HBB), an anti-cholinergic agent, relieves pain in stomach and bowel cramps by inhibiting smooth muscle contractility. In this study, we aimed to compare the efficacy and safety of parenteral HBB and anisodamine for treating acute gastric or intestinal pain. METHODS: In this randomized, controlled, double-blind, parallel-group, multicenter non-inferiority trial, 299 Chinese patients were randomly assigned to HBB or anisodamine in a ratio of 1:1. They were administrated a single dose of either HBB 20 mg or anisodamine 10 mg, and a second dose was given when needed. The primary end-point was the difference in pain intensity (PID) from the pre-dose baseline at 20 min after the first injection. RESULTS: Altogether 295 patients completed the protocol (153 in the HBB and 142 in the anisodamine group). For the primary end-point, the PID was -4.09 (95% confidence interval [CI]: -4.41, -3.76) for the HBB group and -3.66 (95% CI: -4.02, -3.31) for the anisodamine group (P < 0.0001 for non-inferiority). The percentage of patients with at least one adverse event was lower in the HBB group than in the anisodamine group (13.1% vs 17.6%), but there was no statistical significance (P = 0.279). The most frequent adverse events were thirst (7.8%) and dry mouth (2.6%) in the HBB group, and thirst (7.0%), dry mouth (3.5%) and nodal arrhythmia (2.1%) in the anisodamine group. CONCLUSIONS: HBB 20 mg was not inferior to anisodamine 10 mg in pain relief of patients with acute gastric or intestinal spasm-like pain. Both drugs were safe and well tolerated.

Captopril pretreatment protects the lung against severe acute pancreatitis induced injury via inhibiting angiotensin II production and suppressing Rho/ROCK pathway.

Acute pancreatitis (AP) usually causes acute lung injury, which is also known as acute pancreatitis associated lung injury (APALI). This study aimed to investigate whether captopril pretreatment was able to protect lung against APALI via inhibiting angiotensin II (Ang II) production and suppressing Rho/ROCK (Rho kinase) pathway in rats. Severe AP (SAP) was introduced to rats by bile-pancreatic duct retrograde injection of 5% sodium taurocholate. Rats were randomly divided into three groups. In the sham group, sham operation was performed; in the SAP group, SAP was introduced; in the pre-cpl + SAP group, rats were intragastrically injected with 5 mg/kg captopril 1 hour prior to SAP induction. Pathological examination of the lung and pancreas, evaluation of pulmonary vascular permeability by wet/dry ratio and Evans Blue staining, detection of serum amylase, Western blot assay for Ang II receptor type 1 (AT1), RhoA, ROCK (Rho kinase), and MLCK (myosin light chain kinase) were performed after the animals were sacrificed at 24 hours. After the surgery, characteristic findings of pancreatitis were observed, accompanied by lung injury. The serum amylase, Ang II, and lung expression of AT1, RhoA, ROCK, and MLCK increased dramatically in SAP rats. However, captopril pretreatment improved the histological changes, reduced the pathological score of the pancreas and lung, inhibited serum amylase and Ang II production, and decreased expression of AT1, RhoA, ROCK, and MLCK in the lung. These findings suggest that captopril pretreatment is able to protect the lung against APALI, which is, at least partially, related to the inhibition of Ang II production and the suppression of the Rho/ROCK pathway.

Clinical Features and Endoscopic Treatment of Chinese Patients With Hereditary Pancreatitis.

OBJECTIVES: Hereditary pancreatitis (HP) has been rarely investigated in China. We aimed to describe clinical features and mutation frequency of Chinese patients with HP and to evaluate outcomes of endoscopic treatments. METHODS: Inpatients diagnosed with HP from January 1995 to March 2013 were included. Demographic and clinical data including first onset age, age at diagnosis, sex, main symptoms, radiological findings, and outcomes of endoscopic treatments were collected. Mutations in serine protease inhibitor Kazal type 1 (SPINK1), PRSS1, and cystic fibrosis transmembrane conductance regulator (CFTR) were analyzed. RESULTS: A total of 22 inpatients with HP (male, 12; female, 10) participated in this study. Mean (SD) age at first onset and at diagnosis were 24.5 (11.9) years and 29.1 (11.2) years, respectively. The predominant radiological feature was pancreatic calcifications. Thirty-nine endoscopic retrograde cholangiopancreatography procedures were successfully performed on 19 cases. In the final long-term follow-up, 21 patients got complete or incomplete remission after endoscopic retrograde cholangiopancreatography and/or surgery. Genetic analyses were available in 20 patients, and mutation rates of R122H, N29I, and A16V in PRSS1 were 60%, 25% and 5%, respectively. CONCLUSIONS: As compared with previous studies, our patient cohort, with a relatively higher frequency of R122H mutation, showed a much lower surgery rate, and endoscopic interventions may be recommended to be the first-line treatment.