Saikosaponin d protects pancreatic acinar cells against cerulein-induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS-STING pathway.

Acute pancreatitis represents an inflammatory disease featuring pancreatic necrosis and inflammation. Inflammatory injury of pancreatic acinar cells (PACs) is critically involved in the initiation and progression of acute pancreatitis. Pyroptosis, a new kind of programmed cell death concomitant with a low-grade inflammatory reaction, plays a function in acute pancreatitis pathology. It is unclear whether saikosaponin d (SSd), a pharmacologically active natural product, could protect PACs by regulating pyroptosis. Here, we established a PAC injury model in vitro using cerulein to treat AR42J cells. SSd restored viability and proliferation and lowered the release of pancreatic enzymes and inflammatory interleukins in cerulein-treated AR42J cells. Cerulein-induced pyroptosis was evidenced by typical ultrastructural changes and NLRP3/caspase-1 activation in AR42J cells, but SSd attenuated cerulein-induced pyroptosis and inhibited NLRP3/caspase-1 pathway. Mechanically, SSd reduced mitochondrial damage and mtDNA release, and blocked cGAS-STING signaling in AR42J cells treated with cerulein, contributing to the inhibition of NLRP3-mediated pyroptosis. Furthermore, SSd abolished cerulein-elevated oxidative stress in AR42J cells, leading to the mitigation of mitochondrial damage and inhibition of cGAS-STING signaling and pyroptosis. In conclusion, SSd protected PACs against cerulein-induced pyroptosis by alleviating mitochondrial damage and inhibiting the cGAS-STING pathway, and it could be a therapeutic candidate for acute pancreatitis.

Lactated Ringer Solution Is Superior to Normal Saline Solution in Managing Acute Pancreatitis: An Updated Meta-analysis of Randomized Controlled Trials.

GOAL: The goal of this study was to further determine the role of lactated Ringer (LR) compared with normal saline (NS) in managing acute pancreatitis (AP) as a consideration of fluid resuscitation. BACKGROUND: Fluid resuscitation play a critically important role in managing AP, and NS and LR solutions were common selection in clinical practice. However, it remains debate about which regime may be more better for patients with AP. MATERIALS AND METHODS: The PubMed, Embase, and the Cochrane library were searched to find eligible randomized controlled trials focusing on the comparative efficacy and safety of LR and NS for the management of patients with AP. RESULTS: Four eligible randomized controlled trials involving 248 patients to perform meta-analysis finally. Meta-analysis suggested no statistical difference between LR and NS groups in reducing the incidence of systemic inflammatory response syndrome at 24 hours [risk ratio (RR)=0.66, 95% confidence interval (CI)=0.33-1.31, P=0.24], 48 hours (RR=0.70, 95% CI=0.29-1.68, P=0.42), and 72 hours (RR=0.68, 95% CI=0.37-1.25, P=0.22). Meanwhile, no statistical difference was detected between LR and NS groups in terms of in-hospital mortality, incidence of local complications, pancreatic necrosis, organ failure, and developing moderate-to-severe AP, and the length of hospital stay. However, incidence of intensive care unit admission in LR group was significantly lower than that in NS group (RR=0.39, 95% CI=0.18-0.85; P=0.02). CONCLUSION: The current updated meta-analysis indicates that LR may be superior to NS in managing patients with AP because of LR has a potential advantage in decreasing the incidence of pancreatic necrosis and intensive care unit admission compared with NS.

Efficacy of Jia Wei Yang He formula as an adjunctive therapy for asthma: study protocol for a randomized, double blinded, controlled trial.

BACKGROUND: Over the past two or three decades, the prevalence of asthma has significantly increased worldwide; therefore, effective treatment without side effects is of utmost importance. Traditional Chinese medicine (TCM) plays a vital role in reducing symptoms and improving the quality of life in persistent-asthma patients. The aim of this study is to evaluate the efficacy of the Jia Wei Yang He (JWYH) formula in the treatment of asthma and to explore the relationship between the airway microbiome and TCM treatment in asthma patients. METHODS/DESIGN: This multicenter, parallel-arm, randomized, double-blinded, placebo-controlled trial will assess the efficacy of JWYH in asthma patients with usual care. Persistent-asthma patients without life-threatening disease will be enrolled on a random basis and are equally assigned to a high- or a low-dose JWYH plus usual care group, or a placebo plus usual care group. Patients are followed up for 4 months. Accordingly, 240 patients will yield sufficient statistical power to determine a difference between groups. Based on modified intent-to-treat (mITT) analyses, the three groups will be compared at 4 weeks after the beginning of treatment. The primary efficacy measurement is the mean change in the Asthma Control Test (ACT) score from baseline to 4 weeks post treatment. Secondary outcomes include forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and asthma exacerbations. This trial also includes analyses of the associations between airway microbiome and asthma treatment. DISCUSSION: In this study, a randomized clinical trial design is described. The results are based on several outcomes that estimate the efficacy of the JWYH formula and prospective links between the airway microbiome and asthma treatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03299322 . Registered on 3 October 2017.