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1.
目的探讨抑制miR-27b基因表达对病毒性心肌炎心肌细胞凋亡的影响及机制。方法将40只健康BALB/c小鼠随机分为对照组:小鼠一次性腹腔注射0. 1 ml的柯萨奇病毒B3(CVB3); miR-27b抑制剂组(抑制组):小鼠一次性腹腔注射0. 1 ml的CVB3,次日,通过尾静脉注射miR-27b抑制剂(10μg/10 g); miR-27b NC组(NC组):小鼠一次性腹腔注射0. 1 ml的CVB3,次日,通过尾静脉注射miR-27b NC(10μg/10 g)每组10只。于接种CVB3病毒后第7天,采集血清及心脏组织。肌酸激酶(CK)试剂盒检测血清CK含量; qRT-PCR检测心肌组织miR-27b表达;TUNEL试剂盒、超氧化物歧化酶(SOD)试剂盒、髓过氧化物酶(MPO)试剂盒及细胞内活性氧(ROS)试剂盒分别检测心肌细胞凋亡率、心肌组织SOD活力、MPO活性及ROS含量。Western blotting检测NF-κBp65、Bcl-2和Bax蛋白表达。结果小鼠感染CVB3后第7天体重减轻率及血清CK活性明显高于对照组小鼠(P 0. 05)。与对照组比较,模型组SOD活力、Bcl-2蛋白表达明显降低,miR-27b mRNA表达、细胞凋亡率、MPO活性、ROS含量及NF-κBp65和Bax蛋白表达均明显升高(P 0. 05),与模型组比较,抑制组SOD活力、Bcl-2蛋白表达明显升高,miR-27b mRNA表达、细胞凋亡率、MPO活性、ROS含量及NF-κBp65和Bax蛋白表达均明显降低(P 0. 05)。结论抑制miR-27b基因表达可降低病毒性心肌炎心肌细胞凋亡率及氧化应激反应,其机制可能与抑制NF-κB信号通路有关。  相似文献   

2.
目的 探讨大蒜素对实验性小鼠病毒性心肌炎的自然杀伤(NK)细胞、T淋巴细胞活性以及心肌损伤的影响.方法 采用200只Balb/c小鼠腹腔注射柯萨奇病毒B3 (CVB3 )建立实验性小鼠病毒性心肌炎模型.小鼠随机分为模型对照组、大蒜素小剂量组、大蒜素中剂量组、大蒜素高剂量组,每组50只.注射病毒后即刻给药,连续13 d,于第1个小时、第1天、第3天、第7天、第14天处死存活鼠取材.观察NK细胞、T淋巴细胞活性及心肌病理变化,测定血清肌钙蛋白I(cTnI)含量.结果 小鼠在感染CVB3后第1天,NK细胞活性增高,第3天后开始下降,第7天后达到最低;T淋巴细胞活性在第7天开始下降,随后维持在较低水平.心肌酶学在第7天增高有统计学意义.感染CVB3后的第3天后心肌内仅有少量炎症浸润,未有明显病变,第7天病变严重,心肌坏死和炎症浸润程度均较重,呈片状.小剂量的大蒜素可提高活性下降的NK细胞、T淋巴细胞的活性,减轻心肌细胞的病变,中剂量的大蒜素疗效最明显,大剂量的大蒜素未能随剂量的增加而提高疗效.结论 大蒜素对实验性小鼠病毒性心肌炎具有治疗作用.  相似文献   

3.
目的:观察溶酶体酶B(Cathepsin B)抑制剂CA-074Me对病毒性心肌炎小鼠的干预作用,并探讨其对心肌保护的作用机制。方法:55只4周龄雄性BALB/c小鼠随机分为正常对照组(N组,n=10)、病毒模型组(V组,n=15)、低剂量干预组(L组,n=15)及高剂量干预组(H组,n=15)。后3组经腹腔接种柯萨奇病毒B3(CVB3)成功诱发急性病毒性心肌炎,L组和H组于病毒接种后第2天分别腹腔注射CA074Me0.4mg·kg^-1和4mg·kg^-1,均连续用7d(第2~8天),第15天处死全部存活小鼠,并采血检测血清cTnI以及收集小鼠心脏标本作组织学检测。结果:小鼠感染CVB后,其心肌组织中Cathepsin B蛋白表达水平及血清cTnI明显增加;经CA-074Me干预后,Cathepsin B表达以及cTnI降低,心肌损害减轻,小鼠生存率升高,尤其以H组最明显。结论:CA-074Me通过抑制Cathepsin B的表达,减轻心肌损害、提高感染小鼠的存活率,起到保护性的作用,并且对心肌细胞的保护存在明显的量效关系,可为今后临床治疗病毒性心肌炎的研究提供参考。  相似文献   

4.
目的:探讨病毒性心肌炎(VMC)小鼠心肌能量产生状况,并用卡托普利进行干预治疗。方法:雄性Palb/c小鼠随机分为柯萨奇B3病毒(CVB3)感染组、CVB3感染加卡托普利治疗组和对照组。分别采用电镜和形态计量学方法观察心肌线粒体形态、数量和膜磷脂定位;酶细胞化学法分析线粒体细胞色素氧化酶(CCO)和琥珀酸脱氢酶(SDH)活性,反相高效液相色谱法测定心肌组织ATP、ADP和AMP含量。结果:感染组小鼠心肌线粒体大量破坏,膜磷脂严重缺失、定位改变,CCO和SDH活性降低,ATP、ADP和AMP含量下降。不同时间点治疗组上述各项指标均较感染组显著改善。结论:VMC心肌线粒体结构严重破坏、功能明显下降,卡托普利能有效保护VMC心肌线粒体结构和功能,改善心肌能量代谢。  相似文献   

5.
目的探讨表没食子儿茶素没食子酸酯(EGCG)对病毒性心肌炎小鼠的心肌保护作用。方法将45只雄性BALA/C小鼠随机分为正常组、对照组及EGCG组,每组15只。对照组、EGCG组小鼠腹腔注射0.1 m L CVB3病毒液。接种成功后,EGCG组予以EGCG 100 mg/(kg·d)灌胃处理,对照组予以等量的生理盐水灌胃。正常组小鼠腹腔注射等量的生理盐水。饲养1周后,摘除眼球取血检测肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白T(c TnT)的活性,然后处死动物取出心脏,HE染色观察心肌细胞形态学改变。结果 EGCG组小鼠的生存率显著高于对照组;对照组血清CK-MB、c Tn T的活性及心肌病理评分显著高于EGCG组。结论 EGCG对病毒性心肌炎具有一定的保护作用。  相似文献   

6.
端粒酶在病毒性心肌炎中的作用及黄芪甲甙干预研究   总被引:1,自引:0,他引:1  
目的:观察病毒性心肌炎小鼠端粒酶活性及其催化亚基(TERT)的表达以及黄芪甲甙不同剂量干预后的改变,进一步探计其治疗病毒性心肌炎的可能机制。方法:Balb/c雄性4周龄小鼠54只,随机分为5组:A组(正常空白对照组,腹腔接种0.1ml病毒培养液+0.1ml羟甲基纤维素钠盐溶液灌胃,n=10);B组(正常黄芪对照组,腹腔接种病毒培养液+0.1ml 9%黄芪甲甙灌胃2周,每日1次,n=10);C组(高刺量黄芪治疗组,腹腔接种同剂量CVB3+0.1ml 9%黄芪甲甙灌胃,n=10);D组(低剂量黄芪治疗组,腹腔接种同剂量CVB3+0.1ml 1%黄芪甲甙灌胃,n=10);E组(模型组,腹腔接种同剂量CVB3+羟甲基纤维素溶液灌胃,n=14)。观察14d后,眼球采血后处死动物,摘取心脏组织。计算及分析各组小鼠的死亡率;用TRAP-ELISA法检测外周血单个核细胞端粒酶活性;RT—PCR技术检测心肌细胞TERT表达。结果:各组小鼠死亡率分别为0%、0%、10%、30%和50%,C组死亡率明显低于E组(P〈0.05),D组与E组之间无显著差异。TRAP—ELISA结果显示,A组、B组和C组外周血单个核细胞端粒酶活性均呈阳性,三者之间无显著差异,而D组和E组均为阴性。RT-PCR结果表明,C组TERT表达明显高于D组和E组(P〈0.01),与A组和B组无显著差异(P〉0.05),而D组与E组之间无显著差异(P〉0.05),A组和B组之间也无显著差异。结论:病毒性心肌炎小鼠外周血有核细胞端粒酶活性下降,心肌细胞催化亚基TERT表达水平明显减低;高剂量黄芪甲甙可通过增强端粒酶活性,并上调其催化亚基表达改善病毒性心肌炎的预后。  相似文献   

7.
目的本研究通过体外培养心脏微血管内皮细胞(CMVECs),经柯萨奇B3病毒(CVB3)感染后,利用miRNA寡核苷酸基因芯片技术筛选差异表达的miRNAs,进一步探讨miRNA在CVB3诱导CMVECs凋亡中的潜在作用机制。方法原代分离培养大鼠CMVECs细胞,以100TCID50CVB3病毒感染48 h后检测Caspase-3活性和细胞凋亡;提取CMVECs细胞RNA,用Agilent大鼠miRNA寡核苷酸基因芯片进行检测,并通过TargetScan、miranda、mirbase和mirdb数据库选取出差异表达明显并与心血管疾病相关的miRNA,经qPCR对其进行验证,通过生物信息学分析预测其调控靶基因;合成miRNA21 mimics转染CMVECs细胞,同时合成miRNA21 inhibitor,与CVB3共转染CMVECs细胞,检测各组细胞Caspase-3活性变化和细胞凋亡。结果 CVB3感染CMVECs细胞48 h后与正常对照组比较Caspase-3活性显著上调(P<0.01),细胞凋亡明显增加;通过基因芯片检测及生物信息学分析后发现,与心血管系统疾病密切相关的miRNA为miRNA21,经qPCR验证结果一致,预测其靶基因为PDCD4;miRNA21mimics转染CMVECs细胞后与正常对照组相比Caspase-3活性显著上调,细胞凋亡增加(P<0.05);而miRNA21 inhibitor与CVB3共转染CMVECs细胞后与CVB3感染组相比Caspase-3活性显著下调,细胞凋亡明显减少(P<0.05)。结论 miRNA21在CVB3感染的CMVECs细胞中的表达有显著变化,并与CMVECs细胞凋亡密切相关,提示miRNA21在CVB3诱导的病毒性心肌炎发病过程中可能起着重要作用。  相似文献   

8.
[目的]探讨黄芪甲甙对Balb/C小鼠CVB3病毒性心肌炎心肌细胞凋亡及Bcl-2/Bax基因与蛋白表达的影响.[方法]Balb/C小鼠50只随机分5组(每组10只),A组空白对照组:腹腔无菌注射不含病毒的Eagle's培养基0.1 mL,30 min后,以生理盐水0.1 mL灌胃,共7 d;B组病毒性心肌炎对照组:小鼠每只腹腔注射0.1 mL内含50%组织感染率(TCID50) 为1×10^5的CVB3病毒Eagle's培养基,30 min后,以生理盐水0.1 mL灌胃,共7 d;黄芪甲甙低、中、高剂量干预组(分别为C、D、E组),在腹腔注射0.1 mL内含TCID50 为1×10^5的CVB3病毒Eagle's培养基,30 min后,用黄芪甲甙[具体剂量分别为0.07、0.2、0.6 mg/(kg·d)]0.1 mL灌胃,共7 d.采用缺口末端标记法(TUNEL)检测心肌凋亡细胞,免疫组织化学检测Bcl-2、Bax蛋白的表达,反转录聚合酶链反应(RT-PCR)检测Bcl-2、Bax基因的表达,并利用图像分析系统测量平均光密度值进行半定量分析.[结果]与A组比较,B组心肌细胞凋亡发生率增高(0.57±0.16vs 0.06±0.02,P〈0.01);抑制凋亡因子Bcl-2基因(0.52±0.12 vs 0.76±0.11,P〈0.01)及蛋白(6.08±1.15 vs 12.38±3.05, P 〈0.01)表达下降,而促进凋亡因子Bax基因(0.79±0.12 vs 0.61±0.14, P 〈0.01)及蛋白(6.21±1.52 vs 3.01±0.75, P 〈0.01)表达增强,Bcl-2/Bax mRNA比值降低(0.58±0.14vs0.87±0.12,P〈0.05).与B组比较,E组CVB3病毒性心肌炎心肌细胞的凋亡指数(0.09±0.03vs 0.57±0.16,P〈0.05)降低,Bcl-2基因(0.74±0.12 vs 0.52±0.12,P〈0.05)及蛋白水平(11.82±2.96 vs 6.08±1.15, P 〈0.05)表达增强,Bax基因(0.63±0.13 vs 0.79±0.12,P〈0.05)及蛋白(3.15±0.72 vs 6.21±1.52,P〈0.05)水平表达下降.[结论]黄芪甲甙在Balb/C小鼠CVB3病毒性心肌炎中抗凋亡作用机制可能是促进抑制凋亡基因Bcl-2表达,而抑制促凋亡Bax基因表达.  相似文献   

9.
[目的]观察新型降糖药物利拉鲁肽对缺氧/复氧(H/R)诱导的乳鼠心肌细胞损伤的影响.[方法]将体外培养Wistar大鼠乳鼠心肌细胞进行分组:单纯H/R组(A组)、利拉鲁肽组+H/R组(B组)、正常对照组(C组),将A,B两组细胞同时进行H/R损伤,复氧后分别检测3组的乳酸脱氢酶(LDH)、丙二醛含量(MDA)、超氧化酶歧化酶(SOD)活性及各组心肌细胞凋亡率.[结果]A组与C组比较,其细胞培养液中LDH、MDA含量、细胞凋亡率均增加,SOD活性降低,且差异有显著性(P<0.01).与A组相比,B组LDH、MDA含量、细胞凋亡率则明显降低(P<0.01),但仍高于C组,且差异有显著性(P<0.01);SOD活性较A组增高,差异亦有显著性(P<0.01).[结论]H/R可以造成心肌细胞的损伤,增加细胞的凋亡;利拉鲁肽作为胰高血糖素样肽-1类似物,其直接作用于心肌细胞,可减轻H/R造成的心肌细胞损伤,抑制心肌细胞的凋亡,具有潜在的心脏保护作用.  相似文献   

10.
目的 :探讨病毒性心肌炎小鼠心肌腺苷酸酶活性及钠、钙含量变化 ,并用大剂量维生素 C干预治疗。方法 :雄性 Balb/ c小鼠随机分为柯萨奇 B3病毒 (CVB3)感染组、CVB3感染加大剂量维生素 C治疗组及对照组。在不同时间点分别测定心肌腺苷酸酶活性、钠和钙含量及组织病理变化。结果 :与对照组比较 ,感染组心肌Na K ATP酶、Ca2 ATP酶活性明显下降 ,钠、钙含量显著升高 (P均 <0 .0 1) ,并早于心肌结构变化 ;治疗组上述各项指标均较感染组显著改善 (P<0 .0 5或 P<0 .0 1) ,心肌炎症、坏死也明显减轻 (P<0 .0 5或 P<0 .0 1)。结论 :心肌腺苷酸酶活性下降 ,反常性钠、钙超载可能是造成病毒感染后心肌继发性损伤的重要因素 ;大剂量维生素 C能明显保护病毒性心肌炎时心肌腺苷酸酶活性 ,降低心肌钠、钙含量 ,改善心肌组织结构 ,促进心肌预后。  相似文献   

11.
This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.  相似文献   

12.
Ranganath C  Heller AS  Wilding EL 《NeuroImage》2007,35(4):1663-1673
Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.  相似文献   

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目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高<20%视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P<0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P<0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P<0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.  相似文献   

15.
The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.  相似文献   

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Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.  相似文献   

18.
Delineating the Concept of Hope   总被引:2,自引:0,他引:2  
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目的 探讨手转胎头术失败的原因与分娩结局.方法 选择2008年1月至2010年12月于我院住院分娩的持续性枕横位、枕后位产妇198例,根据行手转胎头术后结果分为成功组126例、失败组72例.比较两组分娩结局,对比分析失败原因.结果 失败组胎儿体质量≥3500 g的发生率[76.4%(55/72)]明显高于成功组[31.7%(40/126)],差异有统计学意义(x2=30.177,P=0.001)、失败组宫缩乏力发生率[58.3%(42/72)]高于成功组[38.1% (48/126)],差异有统计学意义(x2=7.569,P=0.006)、失败组骨盆临界或轻度狭窄发生率[38.9% (28/72)]高于成功组[23.8%(30/126)],差异有统计学意义(x2 =5.030,P=0.002)、失败组手转胎头时机不当(宫口开大<6 cm、胎头位于坐骨棘上及宫口开大8~10 cm、胎头位于坐骨棘下≥2 cm)发生率[61.1%(44/72)]高于成功组[38.9%(49/126)],差异有统计学意义(x2=9.084,P=0.003).失败组母儿并发症(产后出血、产褥病率、胎儿窘迫、新生儿窒息)发生率高于成功组(x2 =9.586,P=0.002、x2=9.334,P=0.002、x2=5.910,P=0.015、x2=5.240,P=0.022)、失败组剖宫产发生率[72.2%(52/72)]明显高于成功组[34.1 %(43/126),x2=26.641,P=0.001)].结论 手转胎头术能使难产变顺产,降低剖宫产率,减少母儿并发症,但须积极预防、处理导致手转胎头术失败的原因,对矫正失败后继续矫正及试产应慎重.  相似文献   

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