LncRNA AFAP1-AS1 exhibits oncogenic characteristics and promotes gemcitabine-resistance of cervical cancer cells through miR-7-5p/EGFR axis

Background:Drug resistance is the main factor contributing to cancer recurrence and poor prognosis.Exploration of drug resistance-related mechanisms and effective therapeutic targets are the aim of molecular targeted therapy.In our study,the role of long non-coding RNA(lncRNA)AFAP1-AS1 in gemcitabine resistance and related mechanisms were explored in cervical cancer cells.Methods:Gemcitabine-resistant cervical cancer cell lines HT-3-Gem and SW756-Gem were constructed using the gemcitabine concentration gradient method.The overall survival rates and recurrence-free survival rates were evaluated by Kaplan-Meier analysis.The interaction was verified through a Dual-luciferase reporter gene assay and a Biotinylated RNA pull-down assay.Cell proliferation ability was assessed through methyl-thiazolyl-tetrazolium(MTT),soft agar,and colony formation experiments.Cell cycle and apoptosis were detected byflow cytometry.Results:Up-regulation of AFAP1-AS1 in cervical cancer predicted a poor prognosis.Besides,patients in the gemcitabine-resistance group had higher levels of AFAP1-AS1 than the gemcitabine-sensitive group.AFAP1-AS1 promoted tumor growth and induced gemcitabine tolerance of cervical cancer cells.In addition,AFAP1-AS1 mediated epidermal growth factor receptor(EGFR)expression by serving as a molecular sponge for microRNA-7a-5p(miR-7-5p).This present study also proved that the knockdown of EGFR or overexpression of miR-7a-5p abolished the accelerative role of AFAP1-AS1 overexpression in cancer progression and gemcitabine tolerance.Conclusions:In general,the AFAP1-AS1/miR-7-5p/EGFR axis was tightly related to the progression and gemcitabine tolerance of cervical cancer,providing potential targets for the management of cervical cancer.

Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy

Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.

Effect of angiotensin Ⅱ type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats

AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

Potential protective role of ACE-inhibitors and AT1 receptor blockers against levodopa-induced dyskinesias:a retrospective case-control study

Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as cases.For each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian treatment.Binary logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs use.Ninety-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian treatment.The mean UPDRS part III score was 18.87±7.6 and the median HY stage was 2.In the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/ARBs.Conversely,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between groups.After controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.The study was approved by the Ethics Committee of Novara University Hospital“Maggiore della Carità”(CE 65/16)on July 27,2016.

α_1-受体阻滞剂联合消炎痛栓对慢性非细菌性前列腺炎的临床疗效研究

目的探讨口服α1-受体阻滞剂盐酸坦索罗辛缓释胶囊加直肠给药消炎痛栓对慢性非细菌性前列腺炎(CNP)的临床治疗效果。方法自2008年2月至2010年2月选择门诊CNP患者进行随机对照研究,实验组74例,口服盐酸坦索罗辛缓释胶囊联合直肠给药消炎痛栓;对照组72例,只口服盐酸坦索罗辛缓释胶囊,比较两组治疗效果。结果实验组治疗总有效率,症状减轻程度明显高于对照组,复发率明显低于对照组(P<0.05)。结论盐酸坦索罗辛缓释胶囊可缓解膀胱颈口的紧张度,降低后尿道阻力,减轻CNP引起的排尿困难症状;消炎痛栓直肠给药其有效成分可穿透组织到达前列腺炎症区域,缓解慢性炎症反应,减轻CNP所引起的疼痛和下尿路症状(LUTS)。

Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration

Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.

MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia.

α_1-受体阻滞剂在输尿管下段结石输尿管镜钬激光碎石术后患者中的应用效果

目的探讨α1-受体阻滞剂在输尿管下段结石输尿管镜钬激光碎石术后患者中的应用效果。方法选取四川石油管理局总医院2015年4月—2017年6月收治的输尿管下段结石患者100例,随机分为研究组和对照组,各50例。患者均经输尿管镜钬激光碎石术治疗,研究组患者术后给予α1-受体阻滞剂坦索罗辛治疗。比较两组手术时间、结石大小及结石病程、残余结石率、术后哌替啶用量及肾绞痛发生情况。结果两组患者手术时间、结石大小及结石病程比较,差异无统计学意义(P>0.05)。研究组患者残余结石率低于对照组(P<0.05)。研究组患者哌替啶用量少于对照组,肾绞痛发生率低于对照组(P<0.05)。结论α1-受体阻滞剂在输尿管下段结石输尿管镜钬激光碎石术后患者中的应用效果明显,可提高排石成功率,减少术后镇痛剂使用量及肾绞痛。

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats

Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.

Effects of autoantibodies against AT1-receptor and angiotensin Ⅱ on refractory hypertension

Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO-ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls. The mean age was 54. 3±13 years old in RH group, 53. 5±9 years old in HT group and 51. 2±11. 9 years old in normotensives (NT) group. The mean blood pressure was 154. 2±9. 4/98. 4± 8. 2 mmHg in RH group and 130. 1±7. 6/80. 5±6. 7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8±11. 7/76. 4 ± 7. 2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) II were examined by a radioimmunoassay. Results The autoantibodies against AT1 receptor were positive in 18 (46. 15 %) patients with RH, in 4 (10. 5 % ) hypertension and in 3 (7. 5 % ) normotensives, P < 0. 01. Ang Ⅱwas 57. 01±52. 63 pmol/L in patients with RH. Both the autoantibodies positive and the Ang Ⅱ increasing were 4 (10. 3 % ) cases, both normal were 7 (17. 9 % ) cases, the autoantibodies positive or Ang II increasing was all of 14 (35. 9 % ) cases (x2 = 0. 09, P>0. 05) . There was no relationship between the autoantibodies against AT1 receptor and the angiotensin Ⅱ in refractory hypertension. Conclusion The autoantibodies against AT1 receptor and Ang Ⅱ might be two independent factors in developing of refractory hypertension. The findings suggest that AT1 receptor an-tagnist used in the treatment of refractory hypertension might have an important value.

ADRB1基因多态性对比索洛尔疗效影响的Meta分析

目的基于Meta分析评价β_(1)肾上腺素受体(ADRB1)389位点(rs 1801253)基因多态性对比索洛尔疗效的影响。方法通过计算机检索中国知网、维普网、万方数据知识服务平台、Web of Science、PubMed等数据库收集关于ADRB1与比索洛尔研究的文献,检索时间为建库至2023年7月。研究人员对发表的文献进行筛选,并将纳入文献进入质量评价,提取文献数据,对纳入文献结局指标使用Review Manager 5.3软件进行Meta分析。结果最终纳入文献6篇,其中Gly389Gly(GG型)69例,Gly389Arg(GC型)458例,Arg389Arg(CC型)611例。在降收缩压、舒张压及控制心率疗效方面,GG与CC基因型差异无统计学意义(P=0.96,P=0.84,P=0.87),GC与CC基因型差异无统计学意义(P=0.43,P=0.35,P=0.07),GG与GC基因型差异亦无统计学意义(P=0.60,P=0.68,P=0.77)。结论在比索洛尔降压及控制心率方面,ADRB1389位点基因多态性对其疗效影响并不明显。GG、GC及CC 3个基因型之间均未发现明显差异。

(-)-Stepholodine induced enhancement of cardiac muscle contractions mediated by D_1 receptors

Objective To investigate the effect of(-)-Stepholidine(SPD)on enhancing D1 receptor mediated contraction of cardiac muscle in isolated rat heart and to examine whether SPD has a direct effect on the heart dopamine D1 receptors.SPD an active ingredient of the Chinese herb Stephania intermedia,binds to dopamine D1 and D2 like receptors.Biochemical,electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1/5)agonist and a D(2/4)antagonist,which could indicate unique antipsychotic properties.Methods Normal adult rat working hearts were isolated by Langendorff technique.Results SPD significantly increased the cardiac muscle contraction in a dose-dependent manner.The selective D1 dopamine receptor antagonist SCH23390(1 μM)blocked the SPD induced heart contraction,however,neither the β-receptor antagonist propranolol(1 μM)nor the α1-receptor antagonist prazosin(1 μM)had any effect on blocking SPD induced heart contractions.Moreover,the L-type Ca2+ channel inhibitor nimodipine(1 μM)completely blocked the effect of SPD on cardiac muscle contraction.Conclusions SPD show the effect on enhancing contraction of isolated rat heart through activating L-type Ca2+ channel mediated by heart D1 receptors.

α1受体阻滞剂和5-磷酸二酯酶抑制剂联合治疗男性下尿路症状合并勃起功能障碍的临床研究

目的：研究对下尿路症状（lower urinary tract symptom,LUTS）合并勃起功能障碍（erectile dysfunction,ED）的男性患者,α1受体阻滞剂和5-磷酸二酯酶抑制剂（Phosphodiesterase Type 5 inhibitor,PDE-5i）联合治疗相比于单药治疗的优势及安全性。方法：2012年1~5月我院门诊年龄〉50岁、主诉LUTS合并ED的患者共35名。随机分为三组,坦索罗辛单药治疗组（n=12）、西地那非单药治疗组（n=11）、坦索罗辛和西地那非联合治疗组（n=12）,共治疗12周。统计分析治疗前后国际前列腺症状评分（IPSS）和国际勃起功能评分（IIEF）有无改善。结果：坦索罗辛组、西地那非组、联合治疗组的IPSS和IIEF分别改善了50.3%和11.2%、10.1%和49.7%、61.2%和58.9%。三组治疗前后的IPSS和IIEF均有显著改善（P〈0.05）。其中,联合治疗组的IPSS和IIEF改善最明显。结论：对于LUTS合并ED的部分患者,α1受体阻滞剂和PDE-5抑制剂的联合治疗优于单药治疗。

阴茎背神经离断术联合α_1受体阻断药治疗早泄的疗效

目的探讨阴茎背神经离断术联合高选择性α1受体阻断药治疗早泄的疗效。方法对89例早泄患者随机分为3组:单纯药物治疗组、单纯阴茎背神经离断组、联合治疗组,每组给予相应治疗,观察阴道内射精潜伏期的变化。结果联合治疗组阴道内射精潜伏期(160.4±57.7 s)较单纯药物α1受体阻断药治疗组(64.3±23.2 s)和单纯阴茎背神经离断组(106.5±41.4 s)明显延长(P<0.01)。结论阴茎背神经离断术联合高选择性α1受体阻断药治疗早泄效果明显。

前列腺增生症患者更换α1-受体阻滞剂的原因分析

目的分析前列腺增生症(BPH)患者,治疗期间更换α1-受体阻滞剂的原因。方法回顾性分析我院诊治的BPH患者共890例,分别予4种不同的α1-受体阻滞剂(多沙唑嗪、阿呋唑嗪、特拉唑嗪、坦索洛辛)治疗,分析药物更换率、更换药物的原因和治疗效果。结果 132例更换过药物,药物更换率为14.8%(132/890)。患者更换药物的原因中,疗效不佳占38.6%,副作用大占36.4%,体位性低血压占16.7%,药价偏高占3.8%,服药不便占4.6%。在坦索洛辛药物组中,药物更换率(9.5%)和因体位性低血压而更换药物的发生率(4.2%)都明显低于其他组(P<0.05)。结论 BPH患者治疗期间更换α1-受体阻滞剂的主要原因为疗效不佳和副作用大,服用坦索洛辛组的患者,药物更换率和因体位性低血压而更换药物的发生率较其他3种药物的患者低,值得首诊患者推荐使用,以降低药物更换率。

血管紧张素(1-7)在高盐高脂饮食诱导的代谢综合征小鼠肾脏损伤中的作用

目的采用高盐高脂饮食喂养C57BL/6小鼠建立代谢综合征(MS)模型,探讨血管紧张素转换酶2(ACE 2)及血管紧张素(1-7)[Ang(1-7)]在MS导致的肾脏损伤中的作用。方法 56只SPF级C57BL/6小鼠随机分为7组(每组8只),分别给予正常饮食(ND),高盐(HSD)饮食,高脂(HFD)饮食,高盐高脂(HSFD)饮食,以及分别采用依那普利20mg/(kg·d)+高盐高脂饮食(HSFD-E),缬沙坦50mg/(kg·d)+高盐高脂饮食(HSFD-V),缬沙坦50mg/(kg·d)+Ang(1-7)Mas受体抑制剂A-779 150ng/(kg·d)+高盐高脂饮食(HSFD-VA)。16周后检测血压、体重、血糖及尿蛋白排泄率等基础代谢指标,然后颈动脉取血,ELISA法检测血清中AngⅡ及Ang(1-7)水平,Western blotting检测肾脏中ACE 2及Ⅲ型胶原的表达,HE及Masson染色观察肾脏病理学改变。结果高盐高脂饮食喂养16周后,C57BL/6小鼠血压、内脏脂肪重量与体重比、血脂、血糖以及尿蛋白排泄率等各项代谢指标均明显升高(P<0.05);肾脏出现明显纤维化改变;血清AngⅡ水平升高,Ang(1-7)水平降低(P<0.01);肾脏组织中ACE2表达降低(P<0.05)。给予缬沙坦干预可明显缓解高盐高脂引起的代谢异常,肾脏损伤程度减轻,肾脏和血清中ACE2及Ang(1-7)表达增加(P<0.05)。给予依那普利或缬沙坦+A-779干预后上述指标与未干预组比较均无明显变化。结论应用高盐高脂饮食喂养C57BL/6小鼠可成功建立MS模型。AngⅡ受体1阻滞剂缬沙坦能够缓解高盐高脂导致的代谢异常和肾脏损伤,其对肾脏的保护机制可能与Ang(1-7)表达增加有关。

α_1受体阻滞剂治疗男性神经原性逼尿肌尿道外括约肌功能失调的疗效和安全性分析

目的探讨α_1受体阻滞剂治疗男性神经原性逼尿肌尿道外括约肌功能失调(NDSD)的疗效和安全性。方法 100例NDSD患者,随机分为对照组(47例)和观察组(53例),对照组给予安慰剂治疗,观察组给予α_1受体阻滞剂(盐酸坦索罗辛缓释胶囊)治疗。比较两组患者治疗前后间歇导尿(IC)例数、膀胱剩余尿量(PVR)、泌尿生殖系困扰调查的6项短表(UDI-6)、最大尿流率(Qmax)、最大尿流率时膀胱逼尿肌压力(Pdet.Qmax)、最大尿道闭合压力(MUCP)及不良反应发生情况。结果观察组治疗12周后UDI-6、PVR、IC例数、Qmax、Pdet.Qmax、MUCP均优于对照组(P<0.05)。观察组不良反应发生率(1.89%)与对照组(4.26%)对比,差异无统计学意义(P>0.05)。结论 NDSD患者采用α_1受体阻滞剂治疗,能有效改善自身机体排尿障碍,提高患者生活质量,值得临床推广。

ACEI联合ARB对维持性血液透析患者CRP、IL-1和IL-6的影响

目的探讨联合应用血管紧张素转换酶抑制剂(ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)对维持性血液透析(MHD)患者C-反应蛋白(CRP)、白细胞介素-1(IL-1)和白细胞介素-6(IL-60)的影响。方法选取2012年2月至2014年12月期间在解放军第323医院肾病血透中心治疗的无明显感染症状的MHD患者50例,口服盐酸贝那普利10 mg/d和厄贝沙坦150 mg/d,于用药前和用药1、3、6个月测量血压、血红蛋白、血浆白蛋白、Kt/V值、残余尿量,检测炎症指标CRP、IL-1、IL-6水平,统计分析各项指标差异。结果 42例患者入组获得分析数据。服药6个月时血红蛋白、血浆白蛋白均呈现升高趋势,与用药前比较差异均有统计学意义(P<0.05);服药3、6个月时,CRP显著降低,与用药前比较差异均有统计学意义(P<0.05);IL-1和IL-6水平在1、3、6个月均表现出降低趋势,与用药前比较差异均有统计学意义(P<0.05);服药期间Kt/V值、残余尿量无显著变化(P>0.05)。结论联合应用ACEI和ARB类药物可降低血液透析患者的CRP、IL-1和IL-6水平,可能对改善患者微炎症状态带来益处。

利莫那班对肝纤维化C57小鼠肝组织大麻素受体1及α-SMA表达的影响

目的研究大麻素受体1(CB1)拮抗剂利莫那班对肝纤维化模型C57小鼠肝组织中CB1、α-平滑肌肌动蛋白(α-SMA)表达的影响,及其抗肝纤维化的作用机制。方法 30只C57小鼠随机分为3组,分别为正常对照组、模型对照组及利莫那班组,每组10只。采用四氯化碳腹腔注射诱导形成小鼠肝纤维化模型。造模2周后于继续造模同时,正常对照组和模型对照组每天生理盐水灌胃,利莫那班组用利莫那班灌胃。第8周造模结束时处死小鼠,留取肝脏组织标本,分别进行HE和Masson三色染色,应用免疫组织化学方法检测肝组织中CB1和α-SMA的表达,并进行肝组织纤维化评分(S评分)。结果模型对照组和利莫那班组肝组织S评分、CB1和α-SMA阳性表达量均高于正常对照组(均P<0.05),利莫那班组均低于模型对照组(均P<0.05);正常对照组、模型对照组和利莫那班组CB1评分、α-SMA评分与S评分相互之间均呈正相关(均P<0.05)。结论肝组织CB1的激活可促进肝纤维化的形成,CB1拮抗剂利莫那班通过抑制CB1表达,进而抑制肝星状细胞的增殖和激活,从而起到抗肝纤维化的作用。

可溶性髓样细胞触发受体-1对2型糖尿病合并肺部感染早期诊断价值的研究

目的探讨可溶性髓样细胞触发受体-1(sTREM-1)对糖尿病合并肺部感染的早期诊断价值。方法以2008年7月至2013年6月收治的2型糖尿病并发肺部感染患者79例作为肺部感染组,单纯随机选取同期无并发肺部感染的2型糖尿病患者80例作为对照组,检测2组sTREM-1和降钙素原(PCT)水平。结果肺部感染组sTREM-1和PCT水平均明显高于对照组(P<0.01);sTREM-1和PCT在2型糖尿病患者中早期诊断肺部感染的受试者工作特征曲线(ROC曲线)下面积分别为0.932和0.921,sTREM-1的敏感性和特异性分别为92.4%和86.3%,PCT的敏感性和特异性分别为81.0%和85.0%。结论血清sTREM-1和PCT是2型糖尿病合并肺部感染早期诊断的较好指标,具有较高的敏感性和特异性,sTREM-1优于PCT。