Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

急性心肌梗死患者糖化血红蛋白浓度变化分析

目的探究急性心肌梗死患者糖化血红蛋白浓度变化的意义.方法以2009年11月~2012年1月收治的急性心肌梗死患者87例为研究对象.根据糖化血红蛋白浓度分为正常组(49例)与异常组(38例),两组患者入院后采用介入治疗.对比两组患者心功能分级、治疗效果和并发症.结果正常组患者心功能更好,临床治疗效果佳,手术后并发症发生率低,与异常组患者比较,差异有统计学意义(P<0.05).结论急性心肌梗死患者糖化血红蛋白浓度与疾病严重程度、治疗效果有关,有助于临床诊治进行预测.     

Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specifc cell-permeable peptide inhibitor

Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identifcation of new molecular targets for therapeutic intervention. CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efcacy in a xenograft mouse model of human CLL. Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL.     

中西医结合治疗急性乳腺炎32例疗效观察

目的:探讨了中西医结合治疗急性乳腺炎的疗效。方法:回顾性分析了我院2009年1月～2011年12月收治急性乳腺炎64例患者的临床资料,随机分为对照组和观察组,对照组采用一般的治疗方法,观察组在对照组的基础上加用中药治疗。结果:治疗组32例中,有效29例,无效3例,有效率90.63%;对照组32例中,有效22例,无效10例,有效率为68.75%。治疗组明显高于对照组,差异有统计学意义(P0.01)。结论:中西医结合治疗能减轻疼痛、缩短病程、快速消除症状,使大多数患者避免手术切开引流,值得推广。     

Endoscopic ultrasound gallbladder drainage: Patient selection,preparation, and performance

Acute cholecystitis is a common cause of hospital admissions and can result in critically ill patients. For those patients not amenable to cholecystectomy, endoscopic drainage via transpapillary cystic duct stenting or transmural drainage offers a temporizing method for urgent gallbladder decompression. Endoscopic ultrasonography (EUS) and the development of novel lumen apposing metal stents can allow for more permanent drainage with comparable outcomes to percutaneous transhepatic catheters. The merits of this approach including the technical and clinical advantages of EUS-guided drainage are discussed further in this review article.     

Acute Myeloid Leukemia After Myelodysplastic Syndrome and Failure of Therapy With Hypomethylating Agents: An Emerging Entity With a Poor Prognosis

We assessed the outcomes of 63 patients with acute myeloid leukemia (AML) arising from myelodysplastic syndrome (MDS) after hypomethylating agent failure. Their median age was 63 years. All 63 patients had received ≥ 1 salvage regimens for AML, and 35 patients (55%) had received ≥ 2. Of the 31 patients (49%) who had received high-dose cytarabine (HDAC) at first relapse, 2 (6%) achieved complete remission (CR) and 4 (13%) CR with incomplete platelet recovery (overall response rate, 19%). Of the 32 patients (51%) who had received other treatments, including investigational agents, 4 (12%) achieved CR and 4 (12%) CR with incomplete platelet recovery (overall response rate, 24%). The median response duration was 20 weeks. With a median follow-up of 42 months from the AML diagnosis, the median survival (21 weeks) was similar between the 2 groups. The 1- and 2-year survival rate was 19% and 8%, respectively. Multivariate analysis identified low albumin, HDAC treatment, and platelet count < 50 × 10⁹/L as independent adverse factors for CR and a platelet count < 50 × 10⁹/L and age > 65 years as independent adverse factors for survival. Thus, the outcome of AML evolving from MDS after hypomethylating agent failure is poor and not improved with HDAC. Novel therapies directed toward this emerging entity are urgently needed.     

Involvement of extrinsic and intrinsic apoptotic pathways together with endoplasmic reticulum stress in cell death induced by naphthylchalcones in a leukemic cell line: Advantages of multi-target action

Chalcones, naturally occurring open-chain flavonoids abundant in plants, have demonstrated anticancer activity in multiple tumor cells. In a previous work, the potential anticancer activity of three naphthylchalcones named R7, R13 and R15 was shown. In this study, the mechanism of actions of these chalcones was originally shown. The chalcones presented concentration and time-dependent cytotoxicity. To determine the type of cell death induced by chalcones, we assessed a series of assays including measurements of the caspase-8, -9 and -12 activities, expression of important apoptosis-related genes and proteins, changes in the cell calcium concentration and cytochrome c release. The activities of caspase-8, -9 and -12 increased after the treatment of L1210 cells with the three compounds. Chalcones R7 and R13 induced an increase of pro-apoptotic proteins Bax, Bid and Bak (only chalcone R13), as well as a decrease in anti-apoptotic Bcl-2 expression. These chalcones also induced an increase in Fas and a decrease in p21 and p53 expression. Chalcone R15 seems to act by a different mechanism to promote cell death, as it did not change the mitochondrion-related proteins, nor did it induce the cytochrome c release. All compounds induced an increase in cell calcium concentration and an increase in CHOP expression, which together with an increase in caspase-12 activity, suggest that chalcones could induce an endoplasmic reticulum (ER) stress. Taken together, these results suggest that chalcones induce apoptosis by different pathways, being an interesting strategy to suggest for cancer therapy.