Interleukin-37 relieves PM2.5-triggered lung injury by inhibiting autophagy through the AKT/mTOR signaling pathway in vivo and in vitro.

Autophagy mediates PM2.5-related lung injury (LI) and is tightly linked to inflammation and apoptosis processes. IL-37 has been demonstrated to regulate autophagy. This research aimed to examine the involvement of IL-37 in the progression of PM2.5-related LI and assess whether autophagy serves as a mediator for its effects.To create a model of PM2.5-related LI, this research employed a nose-only PM2.5 exposure system and utilized both human IL-37 transgenic mice and wild-type mice. The hIL-37tg mice demonstrated remarkable reductions in pulmonary inflammation and pathological LI compared to the WT mice. Additionally, they exhibited activation of the AKT/mTOR signaling pathway, which served to regulate the levels of autophagy and apoptosis.Furthermore, in vitro experiments revealed a dose-dependent upregulation of autophagy and apoptotic proteins following exposure to PM2.5 DMSO extraction. Simultaneously, p-AKT and p-mTOR expression was found to decrease. However, pretreatment with IL-37 demonstrated a remarkable reduction in the levels of autophagy and apoptotic proteins, along with an elevation of p-AKT and p-mTOR. Interestingly, pretreatment with rapamycin, an autophagy inducer, weakened the therapeutic impact of IL-37. Conversely, the therapeutic impact of IL-37 was enhanced when treated with 3-MA, a potent autophagy inhibitor. Moreover, the inhibitory effect of IL-37 on autophagy was successfully reversed by administering AKT inhibitor MK2206. The findings suggest that IL-37 can inhibit both the inflammatory response and autophagy, leading to the alleviation of PM2.5-related LI. At the molecular level, IL-37 may exert its anti autophagy and anti apoptosis effects by activating the AKT/mTOR signaling pathway.

Role of sodium-hydrogen exchanger isoform 1 in regulating hepatocyte apoptosis induced by hyperammonaemia.

BACKGROUND: The "secondary injury" theory of liver failure indicated that hyperammonaemia due to liver failure causes further deterioration of hepatocytes. Our previous studies have demonstrated that high blood ammonia levels may lead to hepatocyte apoptosis, as NH4Cl loading caused metabolic acidosis and an increase in sodium-hydrogen exchanger isoform 1 (NHE1). In this study, we established a hyperammonia hepatocyte model to determine the role of NHE1 in the regulation of hepatocyte apoptosis induced by NH4Cl. MATERIALS AND METHODS: In current studies, intracellular pH (pHi) and NHE1 activity were analyzed using the pHi-sensitive dye BCECF-AM. The results showed that intracellular pH dropped and NHE1 activity increased in hepatocytes under NH4Cl treatment. As expected, decreased pHi induced by NH4Cl was associated with increased apoptosis, low cell proliferation and ATP depletion, which was exacerbated by exposure to the NHE1 inhibitor cariporide. We also found that NH4Cl treatment stimulated PI3K and Akt phosphorylation and this effect was considerably reduced by NHE1 inhibition. CONCLUSION: This study highlighted the significant role of NHE1 in the regulation of cell apoptosis induced by hyperammonaemia.

Effect of sertraline in the treatment and prevention of poststroke depression: A meta-analysis.

BACKGROUND: Morbidity of poststroke depression (PSD) remains high worldwide. Additionally, PSD causes multiple sequelae. Although sertraline has been reported to be effective in treating PSD, many studies remain inconsistent. METHODS: PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials, Clinical trials. gov, Wan fang Data (Chinese), VIP (Chinese), and CNKI (Chinese) were retrieved from inception to April 2017. Randomized controlled trials (RCTs) and self-controlled trials (SCTs) were recruited, which met the inclusion criteria in our study. The depression rating scores, the incidence of PSD, activities of daily living (ADL), neurological impairment scores, and adverse effects were assessed. RESULTS: Around 11 studies were recruited in our work, including 1258 participants. For trials enrolled, the results were depicted: the reduction of depression rating scores was significant in sertraline groups (WMD -6.38; 95% CI -8.63 to -4.14; P < .00001); the incidence of PSD was significantly lower in sertraline groups (RR 0.48; 95%CI 0.35-0.67; P < .0001); there was obvious improvement of ADL (WMD 11.48; 95% CI 4.18-18.78; P = .002 <0.05) and neurological impairment (WMD -3.44; 95% CI -6.66 to -0.21; P = .04 <0.05); no significant difference between sertraline and control groups in the morbidity of adverse events (RR 0.94; 95% CI 0.83-1.06; P = .33 >0.05). However, in sensitivity analyses, the conclusions of the reduction of depression rating scores and the improvement of ADL were altered. CONCLUSIONS: The study suggests that sertraline has a potentially protective role compared with control groups and demonstrates sertraline is safe. However, the reduction of depression rating scores and the improvement of ADL should be considered carefully.

Estimating minimum program volume needed to train surgeons: when 4 × 15 really equals 90.

INTRODUCTION: Work-hour restrictions have decreased flexibility in scheduling and reduced exposure to certain operative cases. These restrictions may affect a resident's ability to meet certification requirements, particularly for rare, unscheduled cases (e.g., cardiothoracic transplants). We developed a computer-based simulation model using variables such as case volume and program size to demonstrate the influence of these factors on the likelihood of certifying a set of residents on rare cases. METHODS: We built a simulator to predict the probability of attaining certification for surgical residents, using cardiothoracic transplants as a test case. Inputs to the model included operating times, call schedules, and procurement travel times, as well as information on the distribution of times between transplants. RESULTS: We simulated 100 years of schedules using our current system parameters of an average of 33 heart and 31 lung transplants per year, and assuming an Accreditation Council for Graduate Medical Education-compliant daily-rotating call schedule. Despite having enough transplants to certify all residents for lungs if all opportunities were distributed equally among residents, the certification rate achieved when constrained by arrival time (and call schedules) and work restrictions was only 55%. Our calculations show that meeting minimum transplant-certification requirements for all residents would require at least 1.5 times the expected number of annual transplants. CONCLUSIONS: Our model enables analysis of a given program's ability to certify its residents based on program size and volume. These results could be used to design alternative scheduling paradigms to improve certification rates, without requiring reductions in certification requirements or program size.