进展型脑梗死患者miRNA的表达水平及临床意义

目的探讨进展型脑梗死患者微小RNA(miRNA)的表达水平及临床意义。方法回顾性分析2016年7月至2018年7月期间我院收治的138例脑梗死患者病例资料。根据斯堪的那维亚卒中量表(SSS)将其分为对照组(稳定型脑梗死,82例)和观察组(进展型脑梗死,56例)。观察组患者按照高级中枢损伤严重程度评定标准(MESSS)评分为轻度进展(30例)、中度进展(17例)、重度进展(9例)三个亚组。对观察组出院两个月后进行预后随访,并将其分为预后不良组及预后良好组。分析进展型脑梗死患者miRNA的表达水平及临床意义。结果进展型脑梗死患者的miRNA-21、miRNA-223水平均显著高于稳定型脑梗死患者(P 0. 05); miRNA-21、miRNA-223的高表达均是进展型脑梗死的危险因素(P 0. 05),且进展型脑梗死的严重程度与血清miRNA-21、miRNA-223的表达水平均呈正相关(r=0. 834,P=0. 008;r=0. 896,P=0. 001)。预后不良组患者血清miRNA-21、miRNA-223表达水平显著高于预后良好组(P 0. 05);血清miRNA-21、miRNA-223表达水平预测进展型脑梗死预后的AUC面积分别为0. 805、0. 834,并分别得出截断值4. 45 (敏感度77. 14%,特异性82. 28%)、7. 06(敏感度82. 86%,特异性73. 42%)。结论进展型脑梗死患者miRNA-21、miRNA-223呈高表达,且其表达水平与脑梗死严重程度呈正相关,同时对预测进展型脑梗死预后均具有较高的敏感度和特异度,有可能成为一种早期诊断和预测进展型脑梗死生物标志物。     

Discriminative stimulus properties of the serotonin agonist MK 212

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT₁/5-HT₂ antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT₂ antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT₁/5-HT₂ but not by selective 5-HT₂, antagonists suggests the possibility that 5-HT₁ receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.Portions of this research were presented at the Meeting of the Committee on Problems of Drug Dependence Satellite Session (International Study Group Interested in Drugs as Reinforcers and the Society for the Stimulus Properties of Drugs) in Baltimore, MD (1985)     

If current mediatesβ-adrenergic enhancement of heart rate but not contractility in vivo

Background: The hyperpolarization-activated I_f current in the sinoatrial (SA) node participates in the spontaneous diastolic depolarization responsible for pacemaking function. Both sympathetic and parasympathetic control of heart rate is thought to involve modulation of I_f. This study tested whether -adrenoceptor activation of heart rate, but not contractile state, could be reduced by blockade of I_f channels in the intact, anesthetized pig.Methods: Both isopterenol (ISO, 0.1 g/kg/min i.v. for 5 min) and norepinephrine (NE, 0.3 g/kg/min i.v. for 5 min) were used sequentially to activate -adrenoceptors in five metomidathydrochloride-anesthetized pigs. Left ventricular pressure and dP/dt, aortic blood pressure and cardiac output were measured. I_f channels were then blocked selectively with 0.3 mg/kg i.v. zatebradine (ULFS49) and the test doses of ISO and NE were repeated. Following a further high dose (10 mg/kg, i.v.) of zatebradine, the test doses of ISO and NE were repeated once again.Results: Before I_f blockade, ISO and NE elicited reproducible increases in both heart rate and left ventricular dP/dt. Whereas NE caused an increase in both systolic (56%) and diastolic (53%) aortic pressure and a modest heart rate increase (22%), ISO caused a decrease in diastolic aortic pressure (–22%) and a marked increase in heart rate (81%). Low dose zatebradine reduced basal heart rate from 98±6 to 66±3 bpm, p<0.05; cardiac output fell by 20%, stroke volume increased by 18% and total peripheral resistance was unchanged. ISO after low-dose zatebradine still elicited marked increases in heart rate (66±3 to 105±5 bpm, p<0.05) and left ventricular dP/dt (774±94 to 3364±206 mmHg/s, p<0.05) and reduced aortic diastolic pressure (37 ±2 to 33±1 mmHg, p<0.05). NE after low-dose zatebradine increased heart rate (73±4 to 89±5 bpm, p<0.05), left ventricular dP/dt (810 ±95 to 3372±196 mmHg/s, p<0.05) and both systolic and diastolic aortic pressures. High dose zatebradine caused no further reduction in heart rate (77±4 vs 82±6 bpm, NS) but left ventricular dP/dt decreased (798 ±92 to 418±50 mmHg/s, p<0.05) as did both systolic and diastolic aortic pressures. Subsequent administration of ISO had no effect on heart rate but increased left ventricular dP/dt from 418±50 to 3468±256 mmHg/s (p<0.05) and systolic aortic pressure increased from 58±7 to 90 ±3 mmHg (p<0.05). NE administered after high dose zatebradine also increased left ventricular dP/dt (580±54 to 2608±182 mmHg/s, p<0.05) while heart rate fell (86±4 to 74±6 bpm, p<0.05). Both systolic and diastolic aortic pressures mereased substantially during the NE infusion after high dose zatebradine.Conclusion: Zatebradine dosedependently inhibits -adrenoceptormediated heart rate increases while leaving -adrenoceptor-mediated increases in myocardial contractile state intact. This observation can be explained by a selective blockade of the hyperpolarization-activated current I_f by low concentrations of the drug.     

DermRx. An experiment in computerizing information on dermatologic therapy

The Task Force for Creating a Biomedical Communications System for Dermatology was commissioned by the American Academy of Dermatology to develop an experimental segment of a computerized data bank on dermatologic therapy. The Task Force has completed such a "first generation" system and has named it DermRx. Its data bank carries the following information on each entry: the name of the disease; topical, systemic, physical, and other kinds of treatment; caveats; references to the literature; and the date and reviewer(s). The DermLit and DermRx programs are two components of a projected broader concept of an eventual comprehensive Biomedical Communications System for Dermatology. Such a system is envisaged as a means of making available to dermatologists diverse data relevant to practice, teaching, research, and business aspects of the specialty. At the moment, access to the stored information on dermatologic literature and therapy is by telephone call to, or by correspondence with, the central computer facility at Northwestern University. Eventually it is projected to be accessible by dedicated microcomputers housed in the physician's office. This preliminary report on DermRx is presented to review the progress of the project to date and to elicit comment upon its structure and value.     

Droplet digital PCR and qRT-PCR to detect circulating miR-21 in laryngeal squamous cell carcinoma and pre-malignant laryngeal lesions

Conclusions: The present study indicates that miR-21 is involved in progression from normal to pre-malignant laryngeal lesions (PLLs) and from PLLs to laryngeal squamous cell carcinoma (LSCC). Furthermore, normalized PCR results for miR-21 might be used to discriminate between normal and ordinary hyperplasia before the emergence of dysplasias and pre-malignant lesions with malignant potential. Objective: To investigate a sensitive marker that contributes to progression from normal tissue to PLLs and from PLLs to LSCC. Methods: In 116 PLLs and LSCC patients and 19 without dysplasia matched sets of tissue and plasma samples from Beijing Tongren Hospital, miR-21 was analysed by droplet digital PCR and quantitative real-time polymerase chain reaction based on paraffin-embedded tumour tissue and plasma. Results: Compared with controls, miR-21 levels in tissue and plasma were significantly higher for both PLL and LSCC groups (for both groups vs controls: p p?相似文献   

高危型HPV阳性宫颈癌患者miRNA-34a-5p的表达及临床意义

目的　探讨高危型人乳头状瘤病毒（high risk-human papilloma virus, HR-HPV）阳性宫颈癌患者组织及血清中微小RNA（microRNA, miRNA）-34a-5p的表达及其对宫颈癌的诊断价值。方法　将100例HR-HPV阳性宫颈癌患者（宫颈癌组）、70例宫颈上皮内瘤变（cervical intraepithelial neoplasia, CIN）患者（CIN组）、70例HR-HPV阳性子宫良性病变或者HPV单纯阳性的健康体检者（对照组）作为研究对象。采集上述研究对象的血清标本及70例行手术治疗的宫颈癌组患者癌组织及癌旁组织。使用实时荧光定量PCR技术测定组织及血清中miRNA-34a-5p水平，并分析miRNA-34a-5p与宫颈癌临床、病理指标的关联及血清miRNA-34a-5p对宫颈癌的诊断价值。结果　①对照组血清中miRNA-34a-5p的相对表达量高于CIN组和宫颈癌组：（0.933±0.097）vs.（0.554±0.099）vs.（0.369±0.099），差异有统计学意义（F=741.401，P=0.000）；宫颈癌组患者术前血清中miRNA-34a-5p相对表达量低于术后1周，差异有统计学意义（t=8.305，P=0.000）。有无淋巴结转移和有无远处转移的宫颈癌患者血清中miRNA-34a-5p相对表达量的差异有统计学意义（P均＜0.05）。②宫颈癌组患者癌旁组织中miRNA-34a-5p的相对表达量高于癌组织，差异具有统计学意义（t=40.313，P=0.000）。③宫颈癌组患者癌组织中的miRNA-34a-5p表达水平与血清中的表达水平呈正相关（r=0.908，P=0.000）。④以0.508为miRNA-34a-5p相对表达量的最佳临界值诊断宫颈癌，其灵敏度为83.6%，特异度为79.4%，AUC为0.860，95%置信区间为0.803～0.917。结论　HR-HPV阳性宫颈癌患者癌组织和血清中miRNA-34a-5p表达下调，对宫颈癌诊断及预后监测具有一定的参考价值。     

microRNA-125b及其相关因子Bcl-2、 MMP-2在扁平苔藓中的表达

 目的:检测microRNA-125b（miRNA-125b）及其下游靶蛋白B细胞淋巴瘤-2 (Bcl-2) 蛋白、基质金属蛋白酶-2（MMP-2）在扁平苔藓(LP）中的表达，探讨其在发病中的意义。方法：采用RT-PCR法检测miRNA-125b在LP组织及正常皮肤组织的表达水平，ELISA法检测Bcl-2、MMP-2在LP组织及正常皮肤组织的表达水平，并进行比较。使用Spearman秩相关检验评估miRNA-125b与Bcl-2表达水平之间的相关性。结果：与正常组相比，LP患者组织中Bcl-2表达明显升高(0.52±0.05比0.49±0.04，t=2.84,P=0.018)，MMP-2表达明显升高(7.48±2.88比5.78±3.82，t=2.19,P=0.032)，而miRNA-125b表达明显下调(0.54±0.62比0.93±0.93，t=2.18,P=0.033)。Spearman秩相关分析显示miRNA-125b表达与Bcl-2呈负相关(r=-0.26，P=0.027),但与MMP-2无明显相关（r=-0.22,P=0.056）。结论：miRNA-125b可能是LP治疗的潜在治疗靶点，在LP发病机制中发挥关键作用。