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1.
The effect of pyridostigmine (PYR) - an acetylcholinesterase inhibitor - on hemodynamics and cardiac autonomic control, was never studied in conscious myocardial infarcted mice. Telemetry transmitters were implanted into the carotid artery under isoflurane anesthesia. Seven to ten days after recovery from the surgery, basal arterial pressure and heart rate were recorded, while parasympathetic and sympathetic tone (ΔHR) was evaluated by means of methyl atropine and propranolol. After the basal hemodynamic recording the mice were subjected to left coronary artery ligation for producing myocardial infarction (MI), or sham operation, and implantation of minipumps filled with PYR or saline. Separate groups of anesthetized (isoflurane) mice previously (4 weeks) subjected to MI, or sham coronary artery ligation, were submitted to cardiac function examination. The mice exhibited an infarct length of approximately 12%, no change in arterial pressure and increased heart rate only in the 1st week after MI. Vagal tone decreased in the 1st week, while the sympathetic tone was increased in the 1st and 4th week after MI. PYR prevented the increase in heart rate but did not affect the arterial pressure. Moreover, PYR prevented the increase in sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR not only impaired its attenuation in the 1st week, but enhanced it in the 4th week. MI decreased ejection fraction and increased diastolic and systolic volume. Therefore, the pharmacological increase of peripheral acetylcholine availability by means of PYR prevented tachycardia, increased parasympathetic and decreased sympathetic tone after MI in mice.  相似文献   

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3.
目的:探讨同种异体骨髓间质干细胞(BMSCs)移植联合血管内皮生长因子VEGF静脉注射对兔急性心肌梗死心功能的影响.方法:体外分离、纯化、培养兔BMSCs,以BrdU标记细胞.结扎冠状动脉建立急性心肌梗死模型后,随机将其分为4组(n=8),进行心肌内BMSCs移植和/或VEGF静脉注射,组Ⅰ:BMSCs移植+VEGF静脉注射;组Ⅱ:BMSCs移植;组Ⅲ:VEGF静脉注射:组Ⅳ:DMEM注射作为对照组.4周后行免疫组化和超声心动图检查.结果:组Ⅰ和组Ⅱ梗死及缺血心肌处可见大量BrdU标记的移植细胞,EF值组Ⅰ>组Ⅱ>组Ⅲ,组Ⅳ(均为P<0.01).结论:同种异体骨髓间质干细胞移植联合VEGF静脉注射能改善心功能,有利于心肌梗死后的康复.  相似文献   

4.
目的:探讨瑞舒伐他汀强化治疗对急性ST段抬高型心肌梗死(STEMI)患者PCI术预后的影响。方法:选择2013年6月-2015年6月我院收治的STEMI患者90例,随机分为研究组与对照组,每组各45例。研究组患者PCI术前及术后均给予瑞舒伐他汀强化治疗,对照组仅在术后给予瑞舒伐他汀治疗。观察并比较两组患者术中慢血流及无复流的发生率,TNI、CK-MB、NT-pro BNP及hs-CRP水平变化,以及左室舒张末期内径、左心房内径、左室射血分数、室间隔厚度。结果:研究组术中慢血流及无复流的发生率显著低于对照组(P0.05);两组患者治疗后TNI、CK-MB、NT-pro BNP、hs-CRP水平均低于治疗前,且研究组低于对照组,差异具有统计学意义(P0.05);两组治疗后左室舒张末期内径、左心房内径、左室射血分数、室间隔厚度比较,差异无统计学意义(P0.05)。结论:瑞舒伐他汀强化治疗可以有效降低STEMI患者心肌坏死及炎症反应的发生率,改善心室重构,值得临床推广应用。  相似文献   

5.
Bone marrow mononuclear cells (BMNCs) are widely used in regenerative medicine, but recent data suggests that the isolation of BMNCs by commonly used Ficoll-Paque density gradient centrifugation (DGC) causes significant cell loss and influences graft function. The objective of this study was to determine in an animal study whether and how Ficoll-Paque DGC affects the yield and composition of BMNCs compared to alternative isolation methods such as adjusted Percoll DGC or immunomagnetic separation of polymorphonuclear cells (PMNs). Each isolation procedure was confounded by a significant loss of BMNCs that was maximal after Ficoll-Paque DGC, moderate after adjusted Percoll DGC and least after immunomagnetic PMN depletion (25.6±5.8%, 51.5±2.3 and 72.3±6.7% recovery of total BMNCs in lysed bone marrow). Interestingly, proportions of BMNC subpopulations resembled those of lysed bone marrow indicating symmetric BMNC loss independent from the isolation protocol. Hematopoietic stem cell (HSC) content, determined by colony-forming units for granulocytes-macrophages (CFU-GM), was significantly reduced after Ficoll-Paque DGC compared to Percoll DGC and immunomagnetic PMN depletion. Finally, in a proof-of-concept study, we successfully applied the protocol for BMNC isolation by immunodepletion to fresh human bone marrow aspirates. Our findings indicate that the common method to isolate BMNCs in both preclinical and clinical research can be considerably improved by replacing Ficoll-Paque DGC with adapted Percoll DGC, or particularly by immunodepletion of PMNs.  相似文献   

6.
目的:探讨血小板平均体积(MPV)与老年急性ST段抬高型心肌梗死(STEMI)患者住院期间并发心力衰竭(HF)的相关性。方法:收集我院收治的172例老年STEMI患者,按照住院期间是否发生HF分为HF组(n=55例)和非HF组(n=117例),以患者MPV四分位分四组,比较以上各组之间相关指标的差异,用Logistic回归方程分析MVP与患者HF发生的关系。结果:HF组与非HF组在吸烟、发病至入院时间、前壁梗死、血清B型脑钠肽(BNP)、肌钙蛋白I(c Tn I)、左室射血分数(LVEF)、MVP存在统计学差异(P0.05),HF组MVP水平高于非HF组(P0.05);MVP四分位分组之间的心功能指标LVEF和血清BNP、HF发生率存在统计学差异(P0.05),MVP的第四四分位组(Q4组)的HF发生率高于第一分位组及第二四分位组(Q1及Q2组);多因素Logistic回归方程分析显示高水平MPV是老年STEMI患者近期发生心力衰竭的独立危险因素(P0.05);MVP四分位分组中,从Q1组到Q4组发生HF的风险值(OR)依次增高,且Q3及Q4组的OR值具有统计学意义(P0.05)。结论:高水平MPV与老年STEMI患者住院期间HF发生密切相关,可能是其发生的独立危险因素,应当引起临床关注。  相似文献   

7.

Objective

Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD). We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT) improved liver function in decompensated ALD.

Design

58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy) were randomized early after hospital admission to standard medical therapy (SMT) alone (n = 30), including steroids in patients with a Maddrey’s score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28). Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC) compartment.

Results

Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64%) from the BMMCT group and 18 patients (53%) from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49–5.4) in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001), and proliferating HPC tended to decrease in both groups (−35 and −33%, respectively).

Conclusion

Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis.

Trial Registration

Controlled-Trials.com ISRCTN83972743.  相似文献   

8.
骨髓间充质干细胞是目前广受关注的一群成体干细胞,具有取材容易,增殖能力强,生物学特性稳定,可以跨胚层分化,低免疫源性,参与受损组织修复等优点,随着组织工程的兴起和发展以及其自身所特有的生物学特性,人们逐渐认识到将骨髓间充质干细胞作为肾脏病移植治疗的种子细胞具有良好的应用前景。本文就骨髓间充质干细胞的生物学特性及其在肾脏病移植治疗中的进展做一综述。  相似文献   

9.
卫静  袁发焕  黄云剑 《生物磁学》2011,(10):1987-1990
骨髓间充质干细胞是目前广受关注的一群成体干细胞,具有取材容易,增殖能力强,生物学特性稳定,可以跨胚层分化,低免疫源性,参与受损组织修复等优点,随着组织工程的兴起和发展以及其自身所特有的生物学特性,人们逐渐认识到将骨髓间充质干细胞作为肾脏病移植治疗的种子细胞具有良好的应用前景。本文就骨髓间充质干细胞的生物学特性及其在肾脏病移植治疗中的进展做一综述。  相似文献   

10.
目的:探讨应用远端保护装置GuardWire PlusTM治疗老年急性ST段抬高型心肌梗死(STEMI)对外周血肌钙蛋白(cTnI)、肌酸激酶同工酶(CK-MB)的影响。方法:将2004年9月至2009年12月在我院行急诊PCI的60例年龄>60岁老年STEMI患者分为远端保护组(GW)和非远端保护组(NGW)。于术前、术后4h、8h、12h、16h、24h、2d、3d、5d分别测定外周血cTnI、CK-MB水平,并比较两组间变化及其峰值水平。结果:两组全部病例均成功植入支架。GW组全部成功放置GuardWire PlusTM远端保护装置。发病后12h两组CK-MB的值有明显差别(P<0.05),并且GW组出现酶峰提前,发病后6h、12h两组的CTNI的值有明显差别(P<0.05),并且GW组出现峰值提前。结论:老年心肌梗死急诊PCI中应用远端保护装置可以缩小梗死面积,改善预后。  相似文献   

11.
目的:观察骨髓间充质干细胞(BMSC)移植对脑梗死大鼠神经功能恢复的影响,并对其相关机制进行探讨。方法:90只大鼠随机分为3组:假手术组、对照组、BMSC移植组,每组30只。对照组和BMSC移植组建立大鼠大脑中动脉阻塞(MCAO)模型,假手术组只需要分离大鼠颈部组织,而不造MCAO模型。BMSC移植组在MCAO模型术后1天经尾静脉注射1 mL/3×10~6 BMSC,对照组注射同剂量的生理盐水,于MCAO术后1 d、3 d、7 d、14 d、21 d、28 d、35 d、42 d、49 d分别对各组大鼠进行神经功能评分(mNSS),术后2个月对BMSC移植组及对照组大鼠脑组织进行免疫组化染色,检测MAP2、TUJ1、Ⅷ因子、GFAP的表达情况。结果:在治疗后的第7天至第35天,BMSC移植组mNSS均显著低于对照组(P0.05)。术后2个月,BMSC移植组MAP2、TUJ1、Ⅷ因子表达量显著高于对照组,而GFAP表达量显著低于于BMSC对照组(P0.01)。结论:BMSC移植可以促进脑梗死神经功能的恢复。  相似文献   

12.
Acute graft-versus-host disease (aGvHD) is the most common complication of allogeneic hematopoietic stem cell transplantation (HSCT), which is often accompanied by impaired hematopoietic reconstitution. Sinusoidal endothelial cells (SECs) constitute bone marrow (BM) vascular niche that plays an important role in supporting self-renewal capacity and maintaining the stability of HSC pool. Here we provide evidences that vascular niche is a target of aGvHD in a major histocompatibility complex (MHC)–haploidentical matched murine HSCT model. The results demonstrated that hematopoietic cells derived from GvHD mice had the capacity to reconstitute hematopoiesis in healthy recipient mice. However, hematopoietic cells from healthy donor mice failed to reconstitute hematopoiesis in GvHD recipient mice, indicating that the BM niche was impaired by aGvHD in this model. We further demonstrated that SECs were markedly reduced in the BM of aGvHD mice. High level of Fas and caspase-3 expression and high rate of apoptosis were identified in SECs, indicating that SECs were destroyed by aGvHD in this murine HSCT model. Furthermore, high Fas ligand expression on engrafted donor CD4+, but not CD8+ T cells, and high level MHC-II but not MHC-I expression on SECs, suggested that SECs apoptosis was mediated by CD4+ donor T cells through the Fas/FasL pathway.  相似文献   

13.

Objectives

There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI.

Methods

We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight–6:00 A.M., 6:00 A.M.–noon, noon–6:00 P.M. and 6:00 P.M.–midnight. We used peak creatine kinase as a surrogate marker of infarct size.

Results

Midnight–6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight–6:00 A.M. patients and lowest among 6:00 A.M.–noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight–6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.–noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001).

Conclusion

We observed a circadian peak and nadir in infarct size during STEMI onset from midnight–6:00A.M and 6:00A.M.–noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.  相似文献   

14.

Background

Many diseases associated with bone marrow transplantation (BMT) are caused by transplanted hematopoietic cells, and the onset of these diseases occurs after homing of donor cells in the initial phase after BMT. Noninvasive observation of donor cell homing shortly after transplantation is potentially valuable for improving therapeutic outcomes of BMT by diagnosing the early stages of these diseases.

Methodology/Principal Findings

Freshly harvested near-infrared fluorescence-labeled cells were noninvasively observed for 24 h after BMT using a photon counting device to track their homing process. In a congenic BMT model, the homing of Alexa Fluor 750-labeled donor cells in the tibia was detected less than 1 h after BMT. In addition, subsequent cell distribution in an intraBM BMT model was successfully monitored for the first time using this method. In the allogeneic BMT model, T-cell depletion decreased the near-infrared fluorescence (NIRF) signals of the reticuloendothelial system.

Conclusions/Significance

This approach in several murine BMT models revealed that the transplanted cells homed within 24 h after transplantation. NIRF labeling is useful for tracking transplanted cells in the initial phase after BMT, and this approach can contribute to in vivo studies aimed at improving the therapeutic outcomes of BMT.  相似文献   

15.
目的应用二维斑点追踪成像超声心动图(2D-STE),评价犬心梗后自体骨髓CD34+干细胞移植对心肌功能的影响。方法 12只杂种犬行冠脉左前降支结扎术,导致前壁心肌梗死,随机分为两组,A组为对照组,结扎术后两周二次开胸手术,经心肌注射磷酸盐缓冲液(PBS)1 mL;B组为治疗组,结扎术后两周二次开胸手术,经心肌注射含自体骨髓CD34+干细胞的磷酸盐缓冲液1 mL。应用STE对12只犬结扎术前、术后左室短轴基底段及心尖段心室节段径向应变(RS)、圆周方向应变(CS)以及局部心肌旋转(Rot)进行分析,并对对照组和治疗组治疗后的RS、CS及Rot变化进行比较。结果心肌梗死后梗死节段的RS、CS以及Rot均下降,治疗后治疗组梗死段RS及Rot较对照组好转。结论 STE能够评价左室短轴局部心肌的收缩功能,心肌梗死后梗死段短轴各方向应变减低,自体骨髓CD34+干细胞移植能够提高局部心肌的收缩功能。  相似文献   

16.
Transplantation of unfractionated bone marrow mononuclear cells (BMCs) repairs and/or regenerates the damaged myocardium allegedly due to secretion from surviving BMCs (paracrine effect). However, donor cell survival after transplantation is known to be markedly poor. This discrepancy led us to hypothesize that dead donor BMCs might also contribute to the therapeutic benefits from BMC transplantation. High mobility group box 1 (HMGB1) is a nuclear protein that stabilizes nucleosomes, and also acts as a multi-functional cytokine when released from damaged cells. We thus studied the role of extracellular HMGB1 in the effect of BMC transplantation for heart failure. Four weeks after coronary artery ligation in female rats, syngeneic male BMCs (or PBS only as control) were intramyocardially injected with/without anti-HMGB1 antibody or control IgG. One hour after injection, ELISA showed that circulating extracellular HMGB1 levels were elevated after BMC transplantation compared to the PBS injection. Quantitative donor cell survival assessed by PCR for male-specific sry gene at days 3 and 28 was similarly poor. Echocardiography and catheterization showed enhanced cardiac function after BMC transplantation compared to PBS injection at day 28, while this effect was abolished by antibody-neutralization of HMGB1. BMC transplantation reduced post-infarction fibrosis, improved neovascularization, and increased proliferation, while all these effects in repairing the failing myocardium were eliminated by HMGB1-inhibition. Furthermore, BMC transplantation drove the macrophage polarization towards alternatively-activated, anti-inflammatory M2 macrophages in the heart at day 3, while this was abolished by HMGB1-inhibition. Quantitative RT-PCR showed that BMC transplantation upregulated expression of an anti-inflammatory cytokine IL-10 in the heart at day 3 compared to PBS injection. In contrast, neutralizing HMGB1 by antibody-treatment suppressed this anti-inflammatory expression. These data suggest that extracellular HMGB1 contributes to the effect of BMC transplantation to recover the damaged myocardium by favorably modulating innate immunity in heart failure.  相似文献   

17.
目的:通过对比观察不同年龄鼠骨髓干细胞在体外的生长状态和移入受损心肌后对心肌梗死大鼠心功能的影响,说明年龄对骨髓干细胞的增殖能力和对移植效果的影响。方法:分别分离培养3日龄,1月龄,6月龄,12月龄Wister雄鼠骨髓干细胞,观察细胞生长状态,描记生长曲线。将60只大鼠用结扎冠状动脉前降支的方法制成心肌梗死模型后两周,随机分为三组:Ⅰ组:3日龄组(n=20只):给予3日龄的5-溴脱氧尿嘧啶(Brdu)标记的鼠骨髓干细胞;Ⅱ组:6月龄组(n=20只):给予6月龄的Brdu标记的鼠骨髓干细胞;Ⅲ组:对照组(n=20只):给予培养液。各组均于治疗前及治疗后4周进行心脏超声检查评价心功能改善情况。处死动物取出心脏,进行直接测量后取左心室作石蜡切片,行苏木素-伊红(HE)染色及免疫组化检测,鉴定植入的细胞和心肌、毛细血管再生情况。结果:不同年龄鼠骨髓干细胞培养结果示3日龄及1月龄组增殖能力均高于6月龄及12月龄组,但3日龄与1月龄组之间无统计学差异,12月龄组在原代培养后期即死亡。治疗前超声心动图显示Ⅰ、Ⅱ、Ⅲ组心功能无显著差异(P〉0.05),治疗之后四周超声心动图检查结果示:Ⅰ、Ⅱ组LVEF、FS、IVST、LVPW和LVESD较治疗前均有明显提高,且显著高于Ⅲ组;Ⅰ组LVEF、FS、IVST、LVPWs和LVESD又明显高于Ⅱ组;Ⅰ、Ⅱ、Ⅲ组LVEDD与治疗前比较无统计学意义。心脏直测结果显示Ⅰ、Ⅱ组的Wh、Wh、Wb、L、I度均较第Ⅲ组有所增加,其中Ⅰ组又明显高于Ⅱ组。免疫组化结果显示:Ⅰ、Ⅱ组于梗死周边均发现Brdu(+)细胞存在,心肌特异性抗体阳性,且Ⅰ组阳性率明显高于Ⅱ组。毛细血管密度检测结果显示Ⅰ组毛细血管增生情况明显优于Ⅱ组。结论:不同年龄鼠骨髓干细胞的体外增殖能力不同,年龄越小,增殖能力越强。骨髓干细胞移植可以改善心肌梗死后大鼠的心脏功能,增加梗死区毛细血管密度,抑制心室重构,且年龄与移植效果成反比。  相似文献   

18.
目的:探讨替罗非班与比伐卢定联合治疗在高血栓负荷拟行直接经皮冠状动脉介入(PPCI)的急性ST段抬高型心肌梗死(STEMI)患者中的应用价值。方法:选取我院于2018年3月~2020年3月期间收治的127例高血栓负荷拟行PPCI治疗的STEMI患者。将所有患者按照入院顺序,单号分为对照组(替罗非班治疗),双号分为观察组(比伐卢定联合替罗非班治疗),分别为63例和64例。对比两组术后24 h、术后30 d支架内血栓事件、30 d内的出血事件发生率,对比两组心肌梗死溶栓试验(TIMI)血流分级变化、心功能及肌酸激酶同工酶(CKMB)峰值时间及CKMB峰值,记录两组术后不良心血管事件发生率及住院时间。结果:两组术后24 h、术后30 d均未发生支架内血栓事件,观察组30 d内的出血事件发生率较对照组低(P<0.05)。两组住院时间组间对比无明显差异(P>0.05)。两组术后1个月TIMI血流分级为Ⅲ级的占比高于术前同一分级,TIMI血流分级为0~Ⅰ级、Ⅱ级的占比低于术前同一分级(P<0.05)。观察组术后7 d左心室收缩末期内径(LVESD)、CKMB峰值小于对照组,左心室射血分数(LVEF)高于对照组,CKMB峰值时间短于对照组(P<0.05)。两组心血管不良事件总发生率对比无差异(P>0.05)。结论:比伐卢定联合替罗非班治疗高血栓负荷拟行PPCI的STEMI患者,可改善患者心功能,减少心肌损伤,改善TIMI血流分级,同时还可减少30 d内的出血事件发生率。  相似文献   

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目的:应用定量组织速度成像技术(QTVI)检测经皮冠状动脉介入治疗(PCI)后的ST段抬高的急性心肌梗死(STEMI)患者左心室收缩功能的改变;评价QTVI指标对该类患者未来发生心力衰竭的预测价值。方法:选择行急诊PCI术治疗的冠状动脉单支病变的急性心肌梗死患者,术后一周测量患者的左心室射血分数(LVEF),LVEF<50%者排除,LVEF≥50%者入选。共38例。并设正常对照组30例。入选者继续测二尖瓣环室间隔侧和左室侧壁侧QTVI曲线上心室收缩期速度峰值(Sa),并计算左室平均收缩期速度峰值(mean Sa)。术后12个月随访,查LVEF。结果:PCI术12个月后有17位患者LEVF<50%,21位患者LEVF≥50%。入选的STEMI者术后7天的左室平均Sa波峰值低于正常对照组。术后12个月出现LVEF减低(<50%)的患者,其术后7天的左室平均Sa波峰值低于PCI术12个月后LVEF正常的患者(P<0.01)。结论:通过QTVI检测二尖瓣环的运动速度能够早期发现单支病变所致的急性心肌梗死患者在急诊PCI术后的左心室功能受损;PCI术后LVEF正常的STEMI患者,术后7天QTVI测得的左室平均Sa波峰值减低可能预示着将来发展为LVEF减低的左心室收缩功能不全。  相似文献   

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