ABSTRACT
Coronavirus disease 2019 (COVID-19) outbreaks have occurred in many countries around the world. The numbers of confirmed cases and deaths continue to increase. It is increasingly likely that COVID-19 patients will require emergency surgeries in the operating room (OR). As COVID-19 can easily be transmitted to healthcare workers and other patients during surgery, it is important to establish a set of infection prevent and control management strategy to prevent COVID-19 from spreading in the OR. Based on our experience in COVID-19 prevention and control in the OR, we introduce this COVID-19 prevention and control management strategy for preventing COVID-19 from spreading in the OR. This management strategy includes a number of COVID-19 prevention and control procedures including (I) conduct COVID-19 knowledge training at the early stage of outbreak, (II) formulate the surgery arrangement procedures and suspend the elective surgery if the patient confirmed to COVID-19, (III) divide an isolated OR area for COVID-19 surgery, (IV) preoperative preparation procedures, (V) procedures for wearing and removing personal protective equipment, (VI) anesthesia management, intraoperative management, (VII) post-operative disposable waste management and disinfection. This management strategy has worked very effectively since the outbreak of COVID-19 in Wuhan at the end of 2019. We have performed emergency surgeries on several COVID-19 confirmed patient and dozens of COVID-19 suspected patients under this COVID-19 prevention and control management strategy, and have achieved an excellent result of zero COVID-19 infection in the OR.
ABSTRACT
BACKGROUND: Hydrogen-rich saline (HRS) has been proven effective against ischemia/reperfusion (I/R) injury. However, knowledge on the underlying signaling events remain poor. Having recent highlight of microRNAs (miRNAs) in mediating intestinal I/R injury, we hypothesized that HRS may protect intestine against I/R injury by regulating miRNAs. METHOD: Mice were given intraperitoneal injection of saline or HRS once daily for five consecutive days before undergoing intestinal I/R that was induced by 60-min ischemia followed by 180-min reperfusion of superior mesenteric artery. The intestine was collected for histopathological assay, miRNA microarray profiling, Real-Time PCR, and Western blotting. Next, miR-199a-3p mimics or inhibitors were transfected into IEC-6 cells to explore the relationship between HRS treatment and miR-199a-3p. RESULTS: I/R-induced mucosal injury and epithelial cells apoptosis were attenuated by HRS pretreatment. A total of 64 intestinal I/R-responsive miRNAs were altered significantly by HRS pretreatment, in which we validated four novel miRNAs with top significance by Real-Time PCR, namely miR-199a-3p, miR-296-5p, miR-5126, and miR-6538. Particularly, miR-199a-3p was drastically increased by I/R but reduced by HRS. Computational analysis predicts insulin-like growth factor (IGF)-1, mammalian target of rapamycin (mTOR), and phosphoinositide-3-kinase (PI3K) regulatory subunit 1 as targets of miR-199a-3p, suggesting involvement of the pro-survival pathway, IGF- 1/PI3K/Akt/mTOR. In in vitro experiment, HRS treatment reduced miR-199a-3p level, increase IGF-1, PI3K and mTOR mRNA expression, restore IEC-6 cells viability, and this protective effects were reversed under miR-199a-3p mimics treatment. CONCLUSION: Collectively, miR-199a-3p may serve a key role in the anti-apoptotic mechanism of HRS that contributes to its protection of the intestine against I/R injury.
Subject(s)
Apoptosis/drug effects , Intestinal Diseases/prevention & control , Intestinal Mucosa/drug effects , Intestine, Small/drug effects , MicroRNAs/metabolism , Reperfusion Injury/prevention & control , Saline Solution/administration & dosage , Animals , Cell Line , Disease Models, Animal , Gene Expression Regulation , Injections, Intraperitoneal , Intestinal Diseases/genetics , Intestinal Diseases/metabolism , Intestinal Diseases/pathology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestine, Small/metabolism , Intestine, Small/pathology , Male , Mice, Inbred C57BL , MicroRNAs/genetics , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Signal Transduction , TranscriptomeABSTRACT
Sepsis-related acute kidney injury (AKI) is known to be caused by inflammation. We explored the renal protective effects of aerosol inhalation of a hydrogen-rich solution (HRS; hydrogen gas dissolved to saturation in saline) in a mouse model of septic AKI. Septic AKI was induced through 18 hours of cecal ligation and puncture. AKI occurred during the early stage of sepsis, as evidenced by increased blood urea nitrogen and serum creatinine levels, pathological changes, renal fibrosis and renal tubular epithelial cell apoptosis, accompanied by macrophage infiltration and M1 macrophage-associated pro-inflammatory cytokine (Il-6 and Tnf-α) generation in renal tissues. Aerosol inhalation of the HRS increased anti-inflammatory cytokine (Il-4 and Il-13) mRNA levels in renal tissues and promoted macrophage polarization to the M2 type, which generated additional anti-inflammatory cytokines (Il-10 and Tgf-ß). Ultimately, aerosol inhalation of HRS protected the kidneys and increased survival among septic mice. HRS was confirmed to promote M2 macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The TGF-ß1 receptor inhibitor SB-431542 partly reversed the effects of HRS on renal function, fibrosis, tubular epithelial cell apoptosis and senescence in mice. Thus, HRS aerosol inhalation appears highly useful for renal protection and inflammation reduction in septic AKI.