阿魏酸哌嗪分散片联合氯吡格雷治疗冠心病的临床研究

目的观察阿魏酸哌嗪分散片联合氯吡格雷治疗冠心病的疗效。方法选择本院2015年至2016年收治的88例冠心病患者作为研究对象,按随机数表法将患者分为对照组和试验组,每组44例。对照组予以氯吡格雷治疗,于术前接受氯吡格雷75mg,qd,持续治疗6个月;在对照组基础上,试验组予以阿魏酸哌嗪分散片治疗,口服阿魏酸哌嗪分散片100 mg,tid,持续治疗1个月。比较2组的临床疗效和血清同型半胱氨酸(HCY)、超敏C反应蛋白(Hs CRP)、髓过氧化物酶(MPO)、缺血修饰清蛋白(IMA)水平,并观察药物不良反应(ADR)发生情况。结果试验组和对照组总有效率分别为90.90%(40例/44例)和72.72%(32例/44例),组间比较差异有统计学意义(P<0.05)。治疗后,试验组和对照组的血清HCY分别为(12.48±1.91),(16.36±2.02)μmol·L^-1;这2组的Hs CRP分别为(1.34±0.17),(3.82±0.56)mg·L^-1;这2组的MPO分别为(17.36±2.88),(23.26±4.26)mmol·L^-1;这2组的IMA分别为(20.10±2.44),(24.91±3.53)μg·L^-1,组间比较差异均有统计学意义(均P<0.05)。试验组和对照组的ADR发生率分别为25.00%(11例/44例),20.45%(9例/44例),组间比较差异无统计学意义(P>0.05)。结论阿魏酸哌嗪分散片联合氯吡格雷治疗冠心病的疗效优于单用氯吡格雷,能够降低血清HCY、Hs CRP、MPO、IMA水平,减缓病情。     

Cardiovascular safety of oncologic agents: A double-edged sword even in the era of targeted therapies – part 1

Introduction: Patients with cancer are subject to the cardiotoxic effects of cancer therapy and as more patients survive cancer due to improved treatment they are exposed to various forms of cardiovascular (CV) disease as they age, and vice-versa. Such an interplay of age with both malignancy and CV disease may contribute to increased morbidity and mortality.

Areas covered: This two-part review considers the effects of cancer drug treatment on the CV system. In Part I, the various types of CV and cardiometabolic toxicity of anti-cancer drugs and the possible mechanisms involved are discussed. Also, among the specific oncologic agents, the CV effects of the classical agents and of the large molecule immunological agents (monoclonal antibodies, including immune checkpoint inhibitors) are detailed.

Expert opinion: Oncologic agents produce a variety of CV adverse effects, including cardiomyopathy and heart failure, peri-myocarditis, coronary artery disease, peripheral vascular disease, hypertension (HTN), cardiac arrhythmias, valvular heart disease, and pulmonary HTN. Both the oncologist and the cardiologist need to be aware of such adverse effects and of the specific agents that produce them. They need to join forces to prevent, anticipate, recognize, and manage such complications.     

Neuroprotective effect of gold nanoparticles composites in Parkinson's disease model

Parkinson’s disease (PD) is second most common neurodegenerative disorder worldwide. Although drugs and surgery can relieve the symptoms of PD, these therapies are incapable of fundamentally treating the disease. For PD patients, over-expression of α-synuclein (SNCA) leads to the death of dopaminergic neurons. This process can be prevented by suppressing SNCA over-expression through RNA interference. Here, we successfully synthesized gold nanoparticles (GNP) composites (CTS@GNP-pDNA-NGF) via the combination of electrostatic adsorption and photochemical immobilization, which could load plasmid DNA (pDNA) and target specific cell types. GNP was transfected into cells via endocytosis to inhibiting the apoptosis of PC12 cells and dopaminergic neurons. Simultaneously, GNP composites are also used in PD models in vivo, and it can successfully cross the blood-brain barrier by contents of GNP in the mice brain. In general, all the works demonstrated that GNP composites have good therapeutic effects for PD models in vitro and in vivo.     

Clinical ultrasound stimulating angiogenesis following drug-release from polymersomes on the ischemic zone for peripheral arterial occlusive disease

Peripheral Arterial Occlusive Disease (PAOD) is an aging disease that affects the quality of life of many people by its intermittent claudication and critical limb ischemia presentations. Traditional treatment and management of PAOD are asking patients to make a life change and medication with antiplatelet, statins and cilostazol, which decrease the possibility of clot formation. Our strategy has employed a magnetic Fe₃O₄-PLGA polymersome to carry the cilostazol into the ischemic area by magnetic attraction following remote-control drug release through low-energy ultrasound exposure. In the animal studies, the cilostazol-loaded Fe₃O₄-PLGA polymersomes were injected and accumulated at ischemic leg through magnetic attraction. Then, using a clinical-use ultrasound machine the leg was irradiated to forward cilostazol release from the accumulated polymersomes. Dramatically, we found an observable result of bloody flux recovery in the leg after 7?days compared to the non-treated leg that showed no evidence of the blood recovery.     

Mutation spectrum of MMACHC in Chinese pediatric patients with cobalamin C disease: A case series and literature review

Cobalamin (cbl) C disease is a rare autosomal recessive inheritance disease, which is the most common cobalamin metabolic disorder. Its clinical phenotype involves multiple systems with varying degrees of severity, where in mild cases can be asymptomatic for many years, whereas severe cases may cause death during the neonatal period. The disease is caused by mutations in the MMACHC gene located on chromosome 1p34.1 that contains 5 exons; among which, exons 1–4 have an 849 bp coding sequence that encodes a protein containing 282 amino acids. Through clinical physical examination and laboratory tests, especially blood and urine screening, we found 28 cblC pediatric patients with clinical manifestations, such as mental retardation, motor development delay, epilepsy, metabolic acidosis, vomiting and diarrhea. By Sanger sequencing, we found homozygous or compound heterozygous mutations of MMACHC in 27 of the patients, and single heterozygous mutation of MMACHC in one of them. The c.609G > A, c.658-660delAAG, c.80A > G and c.482G > A mutations accounted for 43.64% (24/55), 10.91% (6/55), 9.09% (5/55) and 7.27% (4/55) of all the mutations, respectively. This spectrum finding is basically consistent with the previously reported data in Chinese patients. The most common c.609G > A mutation may likely lead to early-onset cblC disease. In previous literature involving a large sample of Caucasian cblC cases, the mutation spectrum of MMACHC gene is almost completely different from that of the Chinese population. The most common mutations in the Caucasian population were c.271dupA, c.394C > T and c.331C > T, which account for 48.05% (542/1128), 13.65% (154/1128) and 7.36% (83/1128) of all the mutant alleles, respectively. The c.271dupA mutation and c.331C > T mutation were mainly associated with early-onset cblC in children less than 1 year old, whilst the c.394C > T mutation was mainly associated with late-onset cblC patients characterised by isolated acute nervous system abnormalities. We also analysed the cause behind the different mutation spectrum of MMACHC gene between the Chinese and Caucasian populations.     

Invasive mold infections in acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation

Background/purposePatients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are exposed to high risk of developing invasive fungal infections, and the invasive mold infections (IMIs) are becoming more and more common after transplantation. Here, we conducted a retrospective study to analyze demographics, microbiology, and risk factors for IMIs development in adult acute leukemia patients undergoing allo-HSCT.MethodsWe reviewed 245 adult acute leukemia patients undergoing allo-HSCT from January 2003 to December 2014. Clinical characteristics including age, sex, conditioning regimens, European Group for Blood and Bone marrow Transplantation (EBMT) risk score, and presence of acute graft-versus-host disease (aGVHD) or chronic GVHD (cGVHD) were collected and analyzed. Cox proportional hazard model was adopted to explore the independent risk factors for IMIs developments.ResultsSeventeen of 245 patients developed IMIs during the study period. The cumulative incidence of IMIs in this cohort was 8.7% and 16.8% at 6 and 12 months, respectively, with Aspergillus species being the most common pathogen. The significant risk factors predicting IMIs were unrelated donor transplantation (hazard ratio [HR] 5.11), smoking (HR 3.55), EBMT risk score > 2 (HR 4.22), and moderate to severe cGVHD (HR 3.76).ConclusionsWe identified four risk factors-unrelated donor transplantation, smoking, EBMT risk score >2 and moderate to severe cGVHD to predict IMIs among acute leukemia patients undergoing allo-HSCT. This cohort study suggests early identification of high-risk patients and to provide better prevention strategies would reduce the incidence and severity of IMIs in these patients.     

microRNA expression profile in Smooth Muscle Cells isolated from thoracic aortic aneurysm samples

PurposeThoracic aortic aneurysm (TAA) is a cardiovascular disease characterized by increased aortic diameter, treated with surgery and endovascular therapy in order to avoid aortic dissection or rupture. The mechanism of TAA formation has not been thoroughly studied and many factors have been proposed to drive its progression; however strong focus is attributed to modification of smooth muscle cells (SMCs). Latest research indicates, that microRNAs (miRNAs) may play a significant role in TAA development – these are multifunctional molecules consisting of 19–24 nucleotides involved in regulation of the gene expression level related to many biological processes, i.e. cardiovascular disease pathophysiology, immunity or inflammation.Materials and methodsPrimary SMCs were isolated from aortic scraps of TAA patients and age- and sex-matched healthy controls. Purity of isolated SMCs was determined by flow cytometry using specific markers: α-SMA, CALP, MHC and VIM. Real-time polymerase chain reaction (RT-PCR) was conducted for miRNA analysis.ResultsWe established an isolation protocol and investigated the miRNA expression level in SMCs isolated from aneurysmal and non-aneurysmal aortic samples. We identified that let-7 g (0.71-fold, p = 0.01), miR-130a (0.40-fold, p = 0.04), and miR-221 (0.49-fold, p = 0.05) significantly differed between TAA patients and healthy controls.ConclusionsFurther studies are required to improve our understanding of the pathophysiology underlying TAA, which may aid the development of novel, targeted therapies. The pivotal role of miRNAs in the cardiovascular system provides a new perspective on the pathophysiology of thoracic aortic aneurysms.