干细胞移植治疗心力衰竭

干细胞移植是一种新的心力衰竭治疗措施,但是关于干细胞移植,目前仍有很多的问题尚待解决。现就其中一些重要问题的研究进展进行综述。     

Automated reticulocyte counting using the Sysmex RAM-1

Reticulocyte counting using the Sysmex RAM-1 was evaluated. The results of 113 samples analysed on the Sysmex RAM-1 were compared with those from both flow cytometry (FCM) and a manual technique. Reticulocyte counting with the Sysmex RAM-1 showed excellent precision, with an overall coefficient of variance (CV) less than 5%, and almost no carry-over. Reticulocyte counts were stable after blood storage for 48 h at 4 degrees C and room temperature (RT). Linearity was demonstrated very well for Sysmex RAM-1 and FCM (rRAM=0.9998, rFCM=0.9974, P < 0.001) when reticulocyte counts were 5 x 109/l-480 x 109/l. Comparisons of methods showed a good relation for reticulocyte counts between Sysmex RAM-1 and manual counting (r=0.9760), FCM and manual counting (r=0.9623), and Sysmex RAM-1 and FCM (r=0.9527). Analysis of receiver operating characteristic curves showed that the true-positive rate (TPR) was 0.95 for Sysmex RAM-1, and 0.83 for FCM; the area under curve was 0.999 and 0.972 for Sysmex RAM-1, 0.990 and 0.900 for FCM. These findings confirm that Sysmex RAM-1 can make counting reticulocytes easier, more accurate and more reproducible.     

巨噬细胞移动抑制因子在乙型肝炎病毒感染相关性肝病中的表达

巨噬细胞移动抑制因子(MIF)存在于多种器官的正常组织中,并参与多种疾病的病理形成过程,近年研究发现其在胃癌、肝癌及食管癌等肿瘤组织中呈高表达。本研究的目的在于检测MIF在CHB、重症肝炎、肝炎肝硬化和HCC中的表达差异,探讨MIF参与HBV感染相关性病变的可能机制。一、资料与方法1.对象:病理肝组织标本取自1996年10月至2005年     

成年烟雾病患者血清血管细胞黏附分子1、基质金属蛋白酶9、转化生长因子β、血管内皮生长因子水平变化及其临床意义研究

背景目前,烟雾病(MMD)的病因及发病机制尚不完全明确,此类患者通常在发生脑血管事件后才被确诊,因此探讨MMD的预测因子及评估其严重程度的指标具有重要的临床意义。目的探讨成年MMD患者血清血管细胞黏附分子1(VCAM-1)、基质金属蛋白酶9(MMP-9)、转化生长因子β(TGF-β)、血管内皮生长因子(VEGF)水平及其临床意义。方法选取2016年3月-2019年1月四川大学华西广安医院收治的成年MMD患者114例作为病例组,其中缺血型68例,出血型46例;另选取同期在本院门诊健康体检中心体检健康者30例作为对照组。比较对照组受试者体检当日与病例组患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平,比较出血型与缺血型患者入院第1、7、14天血清VCAM-1、MMP-9、TGF-β、VEGF水平,并比较不同Suzuki分级成年MMD患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平;成年MMD患者入院第1天血清VCAM-1、MMP-9水平与血清TGF-β、VEGF水平的相关性分析采用Pearson相关分析。结果病例组患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平高于对照组(体检当日)(P<0.05)。时间与方法在血清VCAM-1、MMP-9水平上不存在交互作用(P>0.05),在血清TGF-β、VEGF水平上存在交互作用(P<0.05);时间在血清VCAM-1、MMP-9、TGF-β、VEGF水平上主效应显著(P<0.05);方法在血清VCAM-1、MMP-9水平上主效应不显著(P>0.05),在血清TGF-β、VEGF水平上主效应显著(P<0.05);出血型患者入院第1、7、14天血清TGF-β、VEGF水平高于缺血型患者(P<0.05)。Suzuki分级3级缺血型患者血清入院第1天MMP-9、VEGF水平高于Suzuki分级2级患者,Suzuki分级3级出血型患者入院第1天血清VEGF水平高于Suzuki分级2级患者(P<0.05);Suzuki分级4级缺血型、出血型患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平分别高于Suzuki分级2、3级缺血型、出血型患者(P<0.05);Suzuki分级5、6级缺血型、出血型患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平分别高于Suzuki分级2、3、4级缺血型、出血型患者(P<0.05);Suzuki分级6级缺血型、出血型患者入院第1天血清VEGF水平分别高于Suzuki分级5级缺血型、出血型患者(P<0.05)。Pearson相关分析结果显示,缺血型、出血型MMD患者入院第1天血清VCAM-1、MMP-9水平分别与血清TGF-β、VEGF水平呈正相关(P<0.05)。结论缺血型和出血型成年MMD患者血清VCAM-1、MMP-9、TGF-β、VEGF水平均异常升高,且均与患者病情严重程度相关;血清VCAM-1、MMP-9水平分别与缺血型、出血型MMD患者血清TGF-β、VEGF水平呈正相关,VCAM-1、MMP-9可能参与了成年MMD患者颅内出血过程。     

三拗片联合特布他林治疗咳嗽变异性哮喘的临床研究

目的探讨三拗片联合特布他林治疗咳嗽变异性哮喘的临床研究。方法选取2019年8月—2020年4月在青岛西海岸新区中医医院门诊急诊治疗的咳嗽变异性哮喘患者90例,随机分为对照组(n=45)和治疗组(n=45)。对照组经雾化器吸入硫酸特布他林雾化液,2.5mg/次,3次/d;治疗组在对照组治疗的基础上口服三拗片,2片/次,3次/d。两组均连续治疗14 d。观察两组的临床疗效,比较两组咳嗽症状的缓解和消失时间。比较两组嗜酸性粒细胞和肺功能的变化情况。结果治疗后,治疗组的总有效率95.56%,显著高于对照组的73.33%(P0.05)。治疗后,治疗组咳嗽缓解时间和咳嗽消失时间明显短于对照组(P0.05)。治疗后,两组患者血清中嗜酸性粒细胞水平明显低于治疗前水平(P0.05);治疗组治疗后血清中嗜酸性粒细胞水平显著低于对照组(P0.05)。治疗后,两组患者肺活量(FVC)、第1秒用力呼气量(FEV1)和最大呼气流量(PEF)明显高于治疗前(P0.05);治疗组治疗后FVC、FEV1和PEF显著高于对照组(P0.05)。结论三拗片联合特布他林治疗咳嗽变异性哮喘具有较好的临床疗效,能降低嗜酸性粒细胞水平,有效改善临床症状和肺功能指标,具有一定的临床推广应用价值。     

Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy

Oral tyrosine kinase inhibitors(TKIs) against epidermal growth factor receptor(EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as small molecule targeted drugs, their applications are still restricted due to their low solubility, capricious oral bioavailability, large requirement of daily dose, high binding tendency to plasma albumin and initial/acquired drug resistance. Nanotechnology is a promising tool to improve efficacy of these drugs. Through non-oral routes. Various nanotechnology-based delivery approaches have been developed for providing efficient delivery of EGFR-TKIs with a better pharmacokinetic profile and tissue-targeting ability. This review aims to indicate the advantage of nanocarriers for EGFR-TKIs delivery.     

尼麦角林联合降纤酶治疗短暂性脑缺血发作的临床研究

目的探讨尼麦角林片联合降纤酶注射液治疗短暂性脑缺血发作的临床疗效。方法选取2018年3月—2018年12月在四川大学华西医院治疗的短暂性脑缺血发作患者236例,根据用药的差别分为对照组和治疗组,每组各118例。对照组静脉滴注降纤酶注射液,2 mL/次加入生理盐水250 mL,1次/d;治疗组在对照组基础上口服尼麦角林片,5 mg/次,3次/d。两组患者经2周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者ABCD2、ESRS和SPI-Ⅱ评分,及基质金属蛋白酶9(MMP-9)、血管紧张素Ⅱ(Ang-Ⅱ)、同型半胱氨酸(Hcy)、趋化因子CXCL12、可溶性血管细胞黏附因子1(s VCAM-1)、血浆黏度(SV)、全血高切黏度(HBV)、全血低切黏度(LBV)、纤维蛋白原(FIB)及血小板聚集率(PAR)、血小板膜糖蛋白CD63、血小板膜糖蛋白CD62P和血小板膜糖蛋白纤维蛋白原受体(PAC-1)水平。结果治疗后,对照组临床有效率为84.75%,显著低于治疗组的97.46%,两组比较差异有统计学意义(P0.05)。治疗后,两组ABCD2评分、ESRS评分、SPI-Ⅱ评分均明显下降(P0.05),且治疗组患者这些评分显著低于对照组(P0.05)。治疗后,两组患者MMP-9、Ang-II、Hcy、CXCL12、s VCAM-1、FIB、LBV、HBV、SV、PAR、CD63、CD62P、PAC-1水平均显著降低(P0.05),且治疗组患者这些指标水平显著低于对照组(P0.05)。结论尼麦角林片联合降纤酶注射液治疗短暂性脑缺血发作效果显著,可有效预防脑卒中的发生,具有一定的临床推广应用价值。     

Serotonin receptors 5-HTR2A and 5-HTR2B are involved in cigarette smoke-induced airway inflammation,mucus hypersecretion and airway remodeling in mice

BackgroundCigarette smoke plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Recently, elevated serotonin (5-HT) levels were found in the plasma of COPD patients. The role of 5-HT and its receptors in airway inflammation and remodeling induced by cigarette smoke is unclear.MethodsBALB/c mice received the 5-HTR2A inhibitor ketanserin, the 5-HTR2B inhibitor RS-127445 or the natural 5-HTR2A/2B inhibitor quercetin intraperitoneally, then were exposed to cigarette smoke for 6 or 12 weeks. Control mice received placebo and were exposed to room air or cigarette smoke. Mice were sacrificed and bronchial alveolar lavage fluid (BALF) and lung tissue samples were collected.ResultsImmunohistochemistry and western blot confirmed an increase in both 5-HTR2A and 5-HTR2B expression in mouse lungs after exposure to cigarette smoke for 6 and 12 weeks. Cigarette smoke induced accumulation of macrophages and neutrophils and increased levels of inflammatory cytokines, including IL-1β and TNF-ɑ, in BALF and lung tissue; these effects were inhibited by ketanserin, RS-127445 and quercetin. Pretreatment with 5-HT receptor antagonists suppressed the goblet cell hyperplasia induced by 6- or 12-week exposure to cigarette smoke, based on Alcian blue-periodic acid Schiff staining. After 12 weeks of cigarette smoke exposure, Masson's staining showed fibrosis surrounding the mouse airways, and inhibitor pretreatment significantly attenuated the thickening and collagen deposition around the small airways.ConclusionsOur results suggest that cigarette smoke-induced airway inflammation and small airway remodeling are partially mediated by 5-HTR2A and 5-HTR2B, which could be a new therapeutic target for airway remodeling in COPD.     

ERK is involved in the differentiation and function of dimethyl sulfoxide-induced HL-60 neutrophil-like cells,which mimic inflammatory neutrophils

Reports show that particulate matter (PM) is related to respiratory and cardiovascular diseases. We previously reported the biological effects of PM in vivo and the endocytosis of PM by primary neutrophils from mice. Cell lines can be used to elucidate the mechanism underlying immune responses in detail; however, information is limited regarding the functions of neutrophils after PM exposure. Here, we investigated the immune response of primary neutrophils and dimethyl sulfoxide (DMSO)- and all-trans retinoic acid (ATRA)-differentiated HL-60 (neutrophil-like) cells to PM. We showed that endocytosis by ATRA-HL cells was enhanced compared to that by DMSO-HL cells and that endocytosis in both cells was inhibited by dynamin inhibitors. A MEK inhibitor, but not p38 or JNK inhibitors, inhibited endocytosis. The MEK inhibitor also inhibited the differentiation of ATRA-HL cells to neutrophils. We identified that endocytosis of PM by neutrophils activated the MAPK ERK and p38 pathways. DMSO-HL and ATRA-HL cells both produced TNF-α and IL-8 after lipopolysaccharide (LPS) or PM treatment, whereas non-differentiated HL-60 cells did not. MCP-1 production was enhanced in DMSO-HL cells after LPS or PM treatment, whereas it was high in ATRA-HL cells. Reactive oxygen species (ROS) production was enhanced after PM treatment to DMSO-HL cells. Further, extracellular extracts promoted endocytosis. The MEK inhibitor also reduced the production of TNF-α, IL-8, and MCP-1. Taken together, ERK activation is key for both differentiation and endocytosis, and DMSO-HL cells at day 6 can serve as a model of inflammatory neutrophils, such as bronchus neutrophils, and a good tool to analyze the molecular events involved in immune responses to PM.