People's perceptions and experience of managing life after recurrent pancreatitis: a qualitative study in eastern China.

There is a high rate of recurrent hypertriglyceridemic acute pancreatitis (HTG-RAP) and risk of developing into chronic pancreatitis among recurrent hypertriglyceridemic acute pancreatitis. The key to avoiding recurrence is home-based self-management. However, self-management has proven to be difficult. Exploring experiences and perceptions of home-based self-management among patients with HTG-RAP could inform intervention development and policy making in primary care. To explore experiences and perceptions of home-based self-management among patients with HTG-RAP. This is primarily a qualitative study involving patients from eastern China. The study was designed using semi-structured interviews combined with open interviews among individuals and focus groups. Interviews with patients (n = 25) and relatives (n = 2) were conducted from October to December, 2021. Data were analyzed using the thematic analysis approach. Five themes were identified: (1) pity, (2) sense of uncertainty, (3) contradiction, (4) the way to cope, and (5) benefits. The themes constituted a continuous process where a final coping strategy was confirmed. Patients expressed sorrow, struggle, pity, adaptation, and benefits. The disease still bothered them without attack, both mentally and physically. These key points deserve considerable attention to improve the quality of life of patients and lifestyle modification. Patients with pancreatitis were more likely to manage the disease but under a tough process, and during the struggle, they experienced a continuous and contradictory period. Ultimately, the final condition was reached.

Increased expression of tight junction protein occludin is associated with the protective effect of mosapride against aspirin-induced gastric injury.

Mosapride is known to affect gastric motility, however whether mosapride has anti-ulcergenic effects in gastric mucosal injury is unclear. The aim of the present study was to investigate the effects of mosapride on aspirin-induced gastric injuries. GES-1 cells were cultured and divided into 5 groups: Control group, aspirin injury group (treated with 18.2 mmol/l aspirin) and mosapride pretreatment groups (treated with 0.4, 0.5, or 0.6 µmol/l mosapride). Cell proliferation was evaluated via MTT assay and cell apoptosis was investigated via flow cytometry. The expression of occludin was determined by western blot analysis. A total of 40 male Sprague-Dawley rats were randomized into five groups: Control group, aspirin injury group (150 mg/kg) and mosapride pretreatment groups (0.25, 0.50 or 0.75 mg/kg). Gastric mucosal lesions were induced by administering 200 mg/kg aspirin daily for 4 days. Rats in the mosapride groups were pretreated with mosapride 1 h prior to aspirin administration. Histological changes were evaluated under a light microscope and gastric epithelial TJs were observed via transmission electron microscopy. The results revealed that cell apoptosis was significantly increased in the aspirin injury group compared with the control (P<0.05), whereas apoptosis was significantly decreased in the mosapride pretreatment groups compared with the aspirin group (P<0.05). Cell viability was significantly increased in the mosapride pretreatment groups compared with the aspirin injury group (P<0.05), and that of the aspirin injury group was significantly decreased compared with the control group (P<0.05). Compared with the aspirin injury group, occludin expression was significantly increased in the three mosapride pre-treatment groups (all P<0.05). It was also demonstrated that gastric damage was significantly attenuated in the mosapride pretreatment groups compared with the aspirin injury group (P<0.05). Impaired TJ integrity was observed in aspirin injury group, whereas TJs in the mosapride groups were almost intact. In conclusion, the results of the present study suggest that mosapride exerts a gastroprotective action on aspirin-induced gastric mucosal injury at least in part via attenuating cell apoptosis and increasing occludin expression.

Increased endoplasmic reticulum stress response is involved in clopidogrel-induced apoptosis of gastric epithelial cells.

BACKGROUND: The widespread use of clopidogrel alone or in combination with aspirin may result in gastrointestinal mucosal injury, clinically represented as recurrent ulceration and bleeding complications. Our recent work suggested that clopidogrel significantly induced human gastric epithelial cell (GES-1) apoptosis and disrupted gastric mucosal barrier, and that a p38 MAPK inhibitor could attenuate such injury. However, their exact mechanisms are largely unknown. METHODS: The GES-1 cells were used as a model system, the effects of clopidogrel on the whole gene expression profile were evaluated by human gene expression microarray and gene ontology analysis, changes of the mRNA and protein expression were determined by real-time PCR and Western blot analysis, and cell viability and apoptosis were measured by MTT assay and flow cytometry analysis, respectively. RESULTS: Gene microarray analysis identified 79 genes that were differentially expressed (P<0.05 and fold-change >3) when cells were treated with or without clopidogrel. Gene ontology analysis revealed that response to stress and cell apoptosis dysfunction were ranked in the top 10 cellular events being affected, and that the major components of endoplasmic reticulum stress-mediated apoptosis pathway - CHOP and TRIB3- were up-regulated in a concentration- and time-dependent manner when cells were treated with clopidogrel. Pathway analysis demonstrated that multiple MAPK kinases were phosphorylated in clopidogrel-treated GES-1 cells, but that only SB-203580 (a p38-specific MAPK inhibitor) attenuated cell apoptosis and CHOP over-expression, both of which were induced by clopidogrel. CONCLUSIONS: Increased endoplasmic reticulum stress response is involved in clopidogrel-induced gastric mucosal injury, acting through p38 MAPK activation.

Proton-pump inhibitors can decrease gastrointestinal bleeding after percutaneous coronary intervention.

BACKGROUND: Current medical therapies for patients who have an acute coronary syndrome (ACS) focus on the coagulation cascade and platelet inhibition. These, coupled with early use of cardiac catheterization and revascularization, have decreased morbidity and mortality rates in patients who have acute ischemic heart disease with risk of bleeding. OBJECTIVE: The study aimed to determine the incidence of gastrointestinal bleeding after percutaneous coronary intervention (PCI). The effect of proton-pump inhibitor (PPI) treatment was also analyzed. METHODS: This case-control study evaluated gastrointestinal bleeding within a year of PCI for stable angina and acute coronary syndromes at Nanjing First Hospital between 2008 and 2011. Cases were identified and outcomes assessed using linkage analysis of data from cardiology and gastroenterology department databases. Analysis of the case and control groups for both risk and protective factors was performed using independent two-sample Student's t-test with Fisher's exact P value and logistic regression. RESULTS: The incidence of gastrointestinal bleeding following PCI was 1.3% (35/2680 patients). The risk factors for gastrointestinal bleeding were advanced age, female gender, smoking, drinking, previous peptic ulcer and previous gastrointestinal bleeding. PPI use after PCI (P=0.000) was accompanied by a lower risk of gastrointestinal bleeding, with only a few cases of gastrointestinal bleeding events reported. CONCLUSION: The incidence of gastrointestinal bleeding associated with the combination of aspirin and clopidogrel therapy was estimated to be 1.3%. Advanced age, being female, smokers, drinkers, previous peptic ulcer and previous gastrointestinal bleeding were significant independent risk factors. PPI for the prevention and treatment of gastrointestinal bleeding induced by the combination of aspirin and clopidogrel in patients after PCI was safe and effective.

Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation.

Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined. This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved. After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0.5-2.5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy. Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot. In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested. Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation. Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric epithelial cells is mediated by the p38 MAPK pathway. It is concluded that attenuated expression of the TJ proteins occludin and ZO-1 in human gastric epithelial cells could be involved in clopidogrel-induced gastric mucosal injury through activation of the p38 MAPK pathway.