Propofol induces ferroptosis and inhibits malignant phenotypes of gastric cancer cells by regulating miR-125b-5p/STAT3 axis

BACKGROUND Gastric cancer is a common malignancy with poor prognosis,in which ferroptosis plays a crucial function in its development.Propofol is a widely used anesthetic and has antitumor potential in gastric cancer.However,the effect of propofol on ferroptosis during gastric cancer progression remains unreported.AIM To explore the function of propofol in the regulation of ferroptosis and malignant phenotypes of gastric cancer cells.METHODS MTT assays,colony formation assays,Transwell assays,wound healing assay,analysis of apoptosis,ferroptosis measurement,luciferase reporter gene assay,and quantitative reverse transcription polymerase chain reaction were used in this study.RESULTS Our data showed that propofol was able to inhibit proliferation and induce apoptosis of gastric cancer cells.Meanwhile,propofol markedly repressed the invasion and migration of gastric cancer cells.Importantly,propofol enhanced the erastin-induced inhibition of growth of gastric cancer cells.Consistently,propofol increased the levels of reactive oxygen species,iron,and Fe2+in gastric cancer cells.Moreover,propofol suppressed signal transducer and activator of transcription(STAT)3 expression by upregulating miR-125b-5p and propofol induced ferroptosis by targeting STAT3 in gastric cancer cells.The miR-125b-5p inhibitor or STAT3 overexpression reversed propofol-attenuated malignant phenotypes of gastric cancer cells.CONCLUSION Propofol induced ferroptosis and inhibited malignant phenotypes of gastric cancer cells by regulating the miR-125b-5p/STAT3 axis.Propofol may serve as a potential therapeutic candidate for gastric cancer.

Severer nodular lesion in white matter than in gray matter in simian immunodeficiency virus-infected monkey, but not closely correlated with viral infection

Immune cell accumulation and white matter anomaly are common features of HIV(human immunodeficiency virus)-infected patients in combination antiretroviral therapy(cART) era.Neuroimaging tests on cART treated patients displayed prominent diffuse white matter lesions.Notably,immune cell nodular lesion(NL) was a conspicuous type of pathological change in HIV/SIV(simian immunodeficiency virus) infected brain before cART.Therefore,we used SIV infected brain to investigate the distribution of those NLs in gray and white matters.We found a significant higher number of NLs in white matter than that in gray matter.However,virus infection correlated with macrophage NLs but not with microglia NLs,especially in white matter.In addition,NLs interrupted white matter integrity more severely,since even tiny nodules could disconnect nerve fibers in white matter tracts.In the gray matter with dense myelinated axons,NLs obviously encroached those fibers;in the area of few myelinated axons,small nodules well co-localized with extracellular matrix between neurons.

Comparison of Dezocine and Tropisetron for the Control of Maternal Shivering Undergoing Spinal Anesthesia--A Randomized Double-blind Trail

To compare intravenous Dezocine Tropisetron in reatment of shivering after spinal anesthesia in cesarean. A double-blind trail. From January to June 2014 90 cases elective cesarean under spinal anesthesia randomly divided into three groups of 30, the control group A （Sml saline） given to dezocine （10mg / 5ml） B grou, given tropisetron （5mg / 5ml） C group. The incidence of shivering in groups 46.48%, 31.18%, 60.83% （P = 〈0.01）. Bradycardia is a group （A） 3.3%, the group （B） is 0.0%. Significant differences in other variables （myoclonic seizures and rash） no significant （P = 0.353）. Dezocine and Tropisetron alone can cure shivering effectively for cesarean section after spinal anesthesia.

Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell–Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

抗生素时代的消毒术——追随John Snow和Joseph Lister的足迹

如果麻醉学及流行病学的奠基人John Snow活到现在，他一定会像对1854年伦敦霍乱大流行一样，对现今的医疗相关感染（heath care-assodated infections，HCAIs）提出强烈的批评。虽然当时Snow并不知道霍乱的病原菌是霍乱弧菌，但他已明确提出，霍乱是通过饮用伯德大街抽水泵里被污染的水源传播的。与此相反，外科手术相关HCAIs的致病微生物是明确的，但传染源和传播途径常常不得而知。

围术期收缩压变异性是否可预测心脏手术后死亡率：ECLIPSE研究的探索性分析

背景目前，有关围术期血压稳定性-9手术预后关系的研究很少，本研究旨在验证心脏手术患者中收缩压（systolic blood pressure，SBP）变异性与术后30天死亡率具有相关性这一假设。方法本研究从ECLIPSE试验中随机选取1512例围术期高血压患者，分析其SBP变异性。通过超出既定SBP可变范围的偏差×持续时间（曲线下面积）衡量SBP变异性。手术中既定的SBP可变范围为65—135mmHg，手术前和手术后为75—145mmHg，按10mmHg递增提高SBP低限，将既定的SBP可变汜44-围逐步缩窄到手术中105-135mmHg及手术前手术后115—145mmHg。应用多元逻辑回归分析评价收缩压变异性与从ECLIPSE试验结果中得到手术后30天死亡率的关系。结果超过既定范围的SBP变异性（手术中75—135mmHg及手术前手术后85。145mmHg）与手术后30天的死亡率显著相关。每增加60mmHg·min^-1·h^-1的收缩压偏差，手术后30天死亡风险的比值比为1．16（95％可信区间1．04—1．30）。当曲线下的面积从0增加到300mmHg·min^-1·h^-1对于低危组患者，30天死亡率的预测概率从0．2％增加到0．5％，而高危患者从42．4％增加到60．7％。结论心脏手术患者围术期血压变异性与30天死亡率相关，并与超出既定的SBP可变范围（手术中75—135mlnng及手术前手术后85—145mmHg）的偏差程度成正比。与低危组患者相比，高危组患者死亡率的预测值更高。