Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia

Introduction: The Hedgehog (HH) pathway constitutes a collection of signaling molecules which critically influence embryogenesis. In adults, however, the HH pathway remains integral to the proliferation, maintenance, and apoptosis of adult stem cells including hematopoietic stem cells.

Areas covered: We discuss the current understanding of the HH pathway as it relates to normal hematopoiesis, the pathology of acute myeloid leukemia (AML), the rationale for and data from combination therapies including HH pathway inhibitors, and ultimately the prospects that might offer promise in targeting this pathway in AML.

Expert opinion: Efforts to target the HH pathway have been focused on impeding this disposition and restoring chemosensitivity to conventional myeloid neoplasm therapies. The year 2018 saw the first approval of a HH pathway inhibitor (glasdegib) for AML, though for an older population and in combination with an uncommonly-used therapy. Several other clinical trials with agents targeting modulators of HH signaling in AML and MDS are underway. Further study and understanding of the interplay between the numerous aspects of HH signaling and how it relates to the augmented survival of AML will provide a more reliable substrate for therapeutic strategies in patients with this poor-risk disease.     

活血化瘀方联合针灸治疗对脑梗后遗症患者脑血管血液流变动力学及神经功能的影响

目的:探讨血化瘀方联合针灸治疗对脑梗后遗症患者脑血管血液流变动力学及神经功能的影响。方法:选取2016年1月至2017年1月沈阳市第二中医医院收治脑梗后遗症患者120例作为研究对象,对照组61例患者接受针灸治疗;观察组59例患者接受活血化瘀方联合针灸治疗。2组连续治疗30 d。比较2组患者脑血流流变学指标、神经功能评分、中医证候积分、临床疗效。结果:治疗前2组患者脑部平均血流速度、左侧椎动脉血流量、右侧椎动脉血流量、基底动脉血流量比较,差异无统计学意义(P 0. 05)。治疗后观察组患者脑部平均血流速度、左侧椎动脉血流量、右侧椎动脉血流量、基底动脉血流量大于对照组(P 0. 05)。治疗前2组患者NIHSS评分、MMSE评分比较,差异无统计学意义(P 0. 05)。治疗后观察组患者NIHSS评分显著低于对照组,MMSE评分高于对照组(P 0. 05)。治疗前2组患者头晕目眩、语言謇涩、半身不遂、患侧麻木、舌苔白腻证候评分比较,差异无统计学意义(P 0. 05)。治疗后研究患者头晕目眩、语言謇涩、半身不遂、患侧麻木、舌苔白腻证候评分显著低于对照组(P 0. 05)。2组患者临床疗效比较,差异有统计学意义(Z=-5. 626,P=0. 000)。结论:活血化瘀方联合针灸能改善脑梗后遗症患者脑血管血液流变动力学指标,保护神经功能。     

Effects of the Clearing the Lung and Dissipating Phlegm Method in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Objective: The objective of this study is to evaluate the efficacy and safety of the clearing the lung and dissipating phlegm method in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD) and to provide evidence for the treatment of the disease. Materials and Methods: Literature was searched from the United States National Library of Medicine(PubMed), Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database(Wanfang), and the Full?Text Database of Chinese Scientific and Technical Periodicals(VIP).A comprehensive collection was made of randomized controlled trials(RCTs) before June 2018, in which the treatment groups used either the clearing the lung and dissipating phlegm formulas only or combined it with routine Western medicine therapy, and the control group adopted routine Western medicine therapy only for the acute exacerbation of COPD. The Cochrane risk of bias method was used to evaluate the quality of the literature. The data were analyzed and retrieved independently by two reviewers before meta?analysis was carried out with RevMan 5.3 software to evaluate the primary outcome measures, including the total clinical effective rate, and the secondary outcome measures such as the pulmonary function(forced vital capacity [FVC], forced expiratory volume in the 1 s [FEV1], percentage of FEV1 [FEV1%], and FEV1/FVC)and blood gases(PaO_2 and PaCo_2). Results: A total of 13 RCTs involving 990 patients(496 in the treatment group and 494 in the control group)were included in this study. Meta?analysis revealed significant difference in the efficacy of the group that adopted solely the routine Western medicine method and the group that combined the Western medicine with the clearing the lung and dissipating phlegm method. Outcome measures including the pulmonary function(FVC, FEV1, FEV1%, and FEV1/FVC) and the blood gases(PaO_2 and PaCo_2) were significantly improved as compared to the control group(P 0.00001). However, adverse effects in the treatment group using combined traditional Chinese medicine were not reported due to the short observation time of the study. Conclusion: The clearing the lung and dissipating phlegm method can improve the efficacy in the treatment of acute exacerbation of COPD, the outcome measures of the pulmonary function and the blood gases,as well as the life quality of the patients. However, due to the fact that the existing studies are generally of poor quality in which randomization and its implementation were not properly carried out, more high?quality RCTs are necessary to confirm the findings of this study.     

基于数据挖掘的国医大师刘祖贻治疗脑梗死恢复期方药规律研究

目的挖掘分析国医大师刘祖贻治疗脑梗死恢复期的处方用药规律,总结其学术思想。方法收集整理刘祖贻治疗脑梗死恢复期的病案处方,录入中医传承辅助平台软件中构建数据库,再使用该软件相关功能进行数据挖掘,分析处方中的组方用药规律。结果①共得处方147首,涉及药物179味,累计使用频次2 164次。②使用频次在20次及以上的药物,共有22味,其中前10味高频药物为黄芪、丹参、山楂、葛根、枸杞子、地龙、制何首乌、川芎、石菖蒲、淫羊藿。③黄芪用量从15 g至120 g均可见,最常用剂量为30 g,常用剂量范围主要集中于30～60 g。④药物功效分类排名靠前的为补虚药、活血化瘀药、平肝息风药等。⑤高频药组前5位为丹参-黄芪、黄芪-山楂、葛根-黄芪、葛根-丹参、丹参-山楂;关联度较高的药组有地龙-黄芪、葛根-地龙-黄芪、丹参-地龙-黄芪等。⑥通过聚类分析算法提取出核心组合12个,进而演化出潜在新方6首,如"白芍、威灵仙、桂枝、鸡血藤、白芥子""全蝎、菊花、蜈蚣、刺蒺藜"等。结论国医大师刘祖贻治疗脑梗死恢复期的用药以益气温阳、填精益髓、活血通络、息风化痰为主,重用黄芪,方以自拟芪仙通络方加减,体现出"气阳主用""脑髓阳生阴长"等学术思想。     

CT与MRI对脑梗死后出血性转变的诊断价值

目的探讨CT与MRI在脑梗死后出血性转变(HT)中的诊断价值。方法对2011-01—2014-04我院收治的45例HT患者的临床资料进行回顾性分析,对CT与MRI的检查结果进行对比。结果45例患者中,脑内血肿34例(75.6%),脑梗死病灶内片状、斑点状或条状出血11例(24.4%)。其中大面积脑梗死继发出血24例(53.3%),中等面积继发出血15例(33.3%),小面积脑梗死继发出血6例(13.3%);CT检出HT 10例(22.2%),MRI检出45例(100%),差异有统计学意义(P0.05);在对不同部位的HT检查中,CT检出幕上出血9例(20.0%),幕下出血1例(2.2%);MRI检出幕上出血39例(86.7%),幕下出血6例(13.3%)。MRI对幕上及幕下出血的检出率均优于CT(P0.05)。结论在HT的诊断中,MRI比CT更加准确和敏感,在判断出血时间、指导临床治疗以及预后判断中具有重要意义。     

The interaction between pain and movement

Study DesignClinical commentary.Introduction/PurposePain and movement are universally relevant phenomena that influence human experiences in readily observable ways. Improved understanding of pain-movement relationships can guide medical and rehabilitative approaches to recovery and decrease risk of dysfunctional long-term consequences of otherwise normal neuromuscular responses. Therefore, the overall intent of this article is to elucidate the relationships between pain and movement as they relate to clinical decision making.ConclusionsMotor output is highly adaptable, can be influenced by multiple mechanisms at various levels along the nervous system, and may vary between individuals despite similar diagnoses. Therefore, interventions need to be individualized and consider both the types of motor response observed (ie, whether the response is protective or maladaptive), and the patient's acute physical activity tolerance when prescribing exercise/movement.     

Intra-arterial administration of cell-based biological agents for ischemic stroke therapy

Introduction: Ischemic stroke is becoming a primary cause of disability and death worldwide. To date, therapeutic options remain limited focusing on mechanical thrombolysis or administration of thrombolytic agents. However, these therapies do not promote neuroprotection and neuro-restoration of the ischemic area of the brain.

Areas covered: This review highlights the option of minimal invasive, intra-arterial, administration of biological agents for stroke therapy. The authors provide an update of all available studies, discuss issues that influence outcomes and describe future perspectives which aim to improve clinical outcomes. New therapeutic options based on cellular and molecular interactions following an ischemic brain event, will be highlighted.

Expert opinion: Intra-arterial administration of biological agents during trans-catheter thrombolysis or thrombectomy could limit neuronal cell death and facilitate regeneration or neurogenesis following ischemic brain injury. Despite the initial progress, further meticulous studies are needed in order to establish the clinical use of stem cell-induced neuroprotection and neuroregeneration.     

Discordant Electrocardiogram Left Ventricular Wall Thickness and Strain Findings in Influenza Myocarditis

A 42‐year‐old man presented with a viral prodrome and tested positive for influenza A. He rapidly deteriorated developing cardiogenic shock, rhabdomyolysis, and acute kidney injury. Patient improved 1 week later with supportive measures including vasopressors, inotropes, and an intraaortic balloon pump. We report this case as it highlights the discordance between echocardiographic ventricular wall thickening as a result of myocardial edema, and electrocardiographic findings at presentation, with a reversal in findings at time of resolution. Additionally, there was some suggestion of a regional pattern to the reduced longitudinal strain.     

丹红注射液对急性心肌梗死PCI围手术期心功能和TIMI血流影响的Meta分析

目的:系统评价丹红注射液对急性心肌梗死(AMI)经皮冠状动脉介入治疗(PCI)围手术期心功能和心肌梗塞溶栓治疗(TIMI)血流分级的影响。方法:计算机检索CNKI,万方数据库,维普数据库,Pub Med,CBM,Web of Science,The Cochrane Library共7个数据库,全面采集在PCI围手术期应用丹红注射液治疗急性心梗的临床试验,采用Cochrane风险评价表进行文献质量评价,运用Revman 5.3软件进行Meta分析。结果:共纳入12个临床试验,包含1131例患者,其中丹红治疗组569例,对照组562例,结果显示在常规治疗的基础上加入丹红注射液治疗,患者的左室射血分数明显增高[均数差(MD)=6.62,95%可信区间(CI)(4.91,8.34),P<0.00001],TIMI分级3级患者明显增多[相对危险度(RR)=0.22,95%CI(0.12,0.41),P<0.00001],脑利钠肽水平明显降低[MD=-151.86,95%CI(-247.00,-56.72),P=0.002]。结论:丹红注射液可以提高急性心梗PCI围手术期心功能和增加TIMI血流的分级。