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1.
汉防己甲素对肾小球硬化大鼠肾单位的影响   总被引:9,自引:3,他引:6  
目的 :探讨中药汉防己甲素 (Tetrandrine)对单侧肾切除加两次注射阿霉素肾小球硬化大鼠肾单位的作用。方法 :将实验动物分为 :正常对照组、汉防己甲素治疗组、氨氯地平治疗对照组和模型组 ,于第 12周留取尿标本。肾组织病理学检查、图像分析肾单位变化 ,用Northernblot杂交检测TGF - βmRNA表达。 结果 :汉防己甲素治疗组和氨氯地平治疗对照组肾小球ECM明显减少 (肾小球ECM /GA为 0 .2 4± 0 .0 2、0 .2 9± 0 .0 1,比模型组 0 .39± 0 .0 2 ,(P <0 0 5 ) ,肾病理损伤减轻 ,肾皮质TGF - βmRNA表达下调 ,汉防己甲组和模型组肾小管上皮细胞高度无明显差异 (P <0 0 5 )。结论 :汉防己甲素治疗机理为通过下调肾皮质TGF - βmRNA表达参与了延缓肾小球硬化的机理。  相似文献   

2.
目的探讨T型钙通道在实验性糖尿病肾病中的作用.方法采用单侧肾切除(UNx)的糖尿病大鼠模型,分别每日灌胃给予T型钙通道阻滞剂米贝地尔(Mib)、L型钙通道阻滞剂氨氯地平(Aml)、血管紧张素转换酶抑制剂西拉普利(Cil)、及Mib与Cil合用(M+C),共4周,并使各药物处理组血压相近(每组n=6~8).结果Mib、Cil和M+C治疗组较未治疗的糖尿病(DM)组尿白蛋白量明显减少(Mib7.69±1.87,Cil5.53±1.45,M+C3.87±0.88比DM17.67±4.90,单位为μg/24h;P<0.05),增高的Ccr下降.病理学检查显示Mib、Cil与M+C组肾小球Ⅳ型胶原、层粘连蛋白显著少于DM.Aml对尿白蛋白量、肾小球基质和Ⅳ型胶原量无明显改善作用,但也可减少尿蛋白、Ccr和肾小球层粘连蛋白含量.M+C治疗组的肾小球基质和Ⅳ型胶原量在各糖尿病大鼠中最低(均P<0.05).结论阻断T型钙通道可减轻糖尿病大鼠的蛋白尿和肾小球基质沉积,与ACE抑制剂合用有额外的保护效应,提示T型钙通道在糖尿病肾病中的作用不同于血管紧张素和L型钙通道,其机制有待进一步研究.  相似文献   

3.
冬虫夏草治疗肾纤维化研究进展   总被引:15,自引:4,他引:11  
肾纤维化是肾脏对慢性损伤的病理修复反应,以细胞外基质(extracelluar matrix, ECM)成分在肾脏过度增生与沉积为特征,是多种慢性肾病的共同病理基础与慢性肾病向终末期肾衰竭进展的重要途径.肾纤维化发生在肾间质和肾小球等部位,分别表现为肾间质纤维化与肾小球硬化.肾纤维化病理机制复杂,但主要在于肾脏ECM生成细胞的活化.肾脏ECM生成细胞包括肾间质成纤维细胞、肾小球系膜细胞与肾小管上皮细胞,这些细胞在氧自由基、细胞因子、内皮素与血管紧张素等多种因子的刺激下,发生活化或转分化,细胞表型改变,均表现为表达α-平滑肌肌动蛋白的肌成纤维细胞(myofibroblast, MFB)[1].  相似文献   

4.
黄芪当归合剂对肾病综合征鼠肾转化生长因子β1的影响   总被引:94,自引:1,他引:93  
目的探讨黄芪当归合剂降脂及减少肾小球细胞外基质沉积的作用是否与肾脏转化生长因子(TGF)β1表达的改变有关。方法用嘌呤霉素致肾病综合征大鼠,随机分肾病对照、中药、西药治疗三组。用免疫组化及原位杂交观察肾脏TGFβ1表达及细胞外基质(ECM)沉积。以计算机图象分析进行半定量比较。结果正常组,可见TGFβ1蛋白及mRNA于肾小管上皮细胞微弱表达,肾小球系膜区TGFβ1mRNA弱表达。其余各组TGFβ1蛋白表达位于肾小管上皮细胞,mRNA表达位于肾小球系膜细胞及肾小管上皮细胞,而后者表达更明显。两治疗组TGFβ1表达较肾病组明显降低(P<0.001),两治疗组间比较,无显著性差异。两治疗组细胞外基质沉积均明显少于肾病对照组。结论黄芪当归合剂及HMGCoA还原酶抑制剂对肾病综合征鼠能明显减少肾小球细胞外基质沉积,同时使TGFβ1表达的下调。提示黄芪当归合剂可能通过这一下调作用减少肾小球细胞外基质的沉积  相似文献   

5.
目的探讨NADPH氧化酶亚基p22phoxmRNA在糖尿病大鼠肾脏表达时间模式及抑制NADPH氧化酶活性对肾小球细胞外基质(ECM)代谢的影响。方法链脲佐菌素诱导的大鼠糖尿病模型随机地分为糖尿病非治疗组(DM),观察12周;NADPH氧化酶抑制剂apocynin治疗组(DM+Apo,0.2g·kg-1·d-1),疗程8周。用RT-PCR检测肾脏NADPH氧化酶亚基p22phoxmRNA的表达。免疫组织化学检测肾脏纤连蛋白(FN)表达。白明胶酶谱法(zymography)检测肾脏基质金属蛋白酶-9(MMP-9)的活性。并测定Scr、尿蛋白量和肾重指数。结果DM组肾脏p22phoxmRNA的表达在4、6和8周时较正常对照组(C)明显升高(P<0.05);12周时降低至正常水平。DM+Apo组肾脏p22phoxmRNA的表达与DM组差异无统计学意义(P>0.05),但可显著逆转由糖尿病导致的肾小球体积、肾小球FN表达、肾小球ECM含量、Scr、尿蛋白量和肾重指数的升高(P<0.05),并显著提高肾脏MMP-9活性(P<0.05)。结论NADPH氧化酶的过度表达在糖尿病肾病(DN)发病的早期阶段起重要作用。抑制NADPH氧化酶活性的治疗措施可减少DN肾小球ECM积聚、延缓DN的发生和发展。  相似文献   

6.
血管紧张素Ⅱ对大鼠残肾模型微血管的影响   总被引:15,自引:0,他引:15  
目的 探讨大鼠残肾模型中血管紧张素Ⅱ与肾脏新生血管形成间的关系。方法 分别用缬沙坦、氨氯地平或生理盐水治疗大鼠残肾模型12周,测定24h尿蛋白排泄量、血压、BUN和Scr;评估病理切片肾小球硬化和肾小管间质损害程度;采用免疫组化染色技术,分析浸润肾组织巨噬细胞数、毛细血管密度和增生内皮细胞数。结果 缬沙坦和氨氯地平可显著减少残肾模型尿蛋白排泄量、降低血压、改善肾功能、抑制巨噬细胞浸润、减轻肾小球硬化和肾间质纤维化(P<0.05),但缬沙坦组尿蛋白显著少于氨氯地平组(P<0.05)。残肾模型肾小球毛细血管指数(GCI)和肾小管周毛细血管指数(PCI)均显著低于假手术组(P<0.01)。缬沙坦或氨氯地平治疗均显著增加肾小球和肾间质毛细血管数目(P<0.05),而缬沙坦组显著高于氨氯地平组(P<0.05)。缬沙坦或氨氯地平组肾小球和肾间质增生内皮细胞数分别高于生理盐水对照组(P<0.01),而缬沙坦组显著高于氨氯地平组(P<0.01)。结论 缬沙坦能改善大鼠残肾模型新生血管形成和增加毛细血管密度,血管紧张素Ⅱ可能通过直接抑制新生血管形成和升高血压间接加速毛细血管毁损而加重肾缺血和肾损害。  相似文献   

7.
氟伐他汀对5/6肾切除大鼠肾脏皮质细胞外基质积聚的影响   总被引:6,自引:0,他引:6  
目的观察降脂药氟伐他汀对5/6肾切除大鼠肾皮质细胞外基质(ECM)积聚的影响和探讨其降脂作用外的肾脏保护机制。方法将5/6肾切除大鼠随机分为模型组和氟伐他汀治疗组(治疗组),另设假手术组作为对照。实验期间测定尿蛋白排泄率;氟伐他汀处理(7mg·kg-1·d-1)13周后免疫组化法检测肾小球Ⅳ型胶原(ColⅣ)及纤连蛋白(FN)蛋白表达;酶谱法检测肾皮质基质金属蛋白酶(MMP)-2活性;免疫印迹检测金属蛋白酶组织抑制物(TIMP)-2蛋白表达。结果与假手术组相比,模型组大鼠尿蛋白排泄、肾小球Ⅳ型胶原和FN表达均明显增加(均为P<0.01)。模型组大鼠肾皮质MMP-2活性较假手术组明显降低(P<0.01),而TIMP-2蛋白表达明显上调(P<0.01)。氟伐他汀治疗后这些改变均明显好转。结论氟伐他汀可能通过增加5/6肾切除大鼠肾脏MMP-2活性和降低TIMP-2表达,从而能增加细胞外基质降解和减轻肾小球细胞外基质积聚。  相似文献   

8.
糖基化终产物对大鼠肾脏结缔组织生长因子的作用   总被引:5,自引:0,他引:5  
目的探讨糖基化终产物(AGEs)对大鼠肾脏结缔组织生长因子(CTGF)表达及细胞外基质(ECM)合成的影响。方法将Wistar大鼠随机分成4组:正常对照组(Con)、单纯大鼠血清蛋白组(RSP)、糖化血清组(AGEs)和氨基胍组(AG)。尾静脉注射AGE-RSP6周后,采用RT-PCR、免疫组织化学和蛋白质印迹杂交等方法检测AGEs对大鼠肾皮质TGF-β1和CTGF的mRNA和蛋白质表达及ECM蛋白成分表达的影响。结果与Con及RSP组比较,AGEs组肾小球系膜细胞增生,ECM红染区增大。AGEs组大鼠肾皮质TGF-β1和CTGF的mRNA和蛋白质表达均明显上调(P<0.01);TGF-β1和CTGF免疫组化阳性表达部位主要位于肾小球;肾小球ECM蛋白成分胶原(Col)Ⅳ和纤连蛋白(FN)合成也增多(P<0.05)。AG组上述所有变化均减轻。结论AGEs能明显诱导大鼠肾皮质CTGFmRNA和蛋白质表达增强,并使ECM蛋白成分合成增多。AGEs可能通过诱导CTGF表达上调引起ECM合成增多。  相似文献   

9.
目的探讨苯那普利对肾小球硬化大鼠TGF-β1和TIMP-1表达的影响.方法建立单侧肾切除术合并阿霉素静脉双次注射的大鼠肾小球硬化模型,设正常组、模型组和西药组,进行尿蛋白、肾功能、血脂检测和肾组织病理学检查,图像分析肾小球细胞外基质、转化生长因子β1(TGF-β1)和金属蛋白酶组织抑制物(TIMP-1)的变化.结果苯那普利组TC、TG和尿蛋白较模型组明显降低,肾脏病理提示系膜细胞和ECM明显减少,TGF-β1、和TIMP-1的表达降低(P<0.05).结论苯那普利可以降低24h尿蛋白排出量、血脂,抑制系膜细胞增生,下调肾内TGF-β1和TIMP-1的表达,抑制ECM的沉积,从而防治肾小球硬化.  相似文献   

10.
目的:探讨益肾方与厄贝沙坦对糖尿病肾病(DN)大鼠肾组织中尾加压素Ⅱ(urotensin Ⅱ,UⅡ)表达和肾脏病理改变的影响及其意义.方法:将SD大鼠以链脲佐菌素(STZ)制作糖尿病肾病大鼠模型后随机分为糖尿病肾病组(D组)、益肾方治疗组(DZ组)、厄贝沙坦治疗组(DI组),并设正常对照组.治疗8周后取肾组织,免疫组化方法检测肾组织中UⅡ表达水平,光镜及电镜观察肾脏组织结构改变.结果:与正常对照组相比,糖尿病肾病组肾组织中UⅡ表达增高,肾小球肥大,基质增多,足突融合,基底膜增厚;肾组织UⅡ表达与肾小球平均体积及基底膜厚度的关系均呈正相关.益肾方和厄贝沙坦治疗组肾组织UⅡ表达均明显减少,肾脏病理显著改善.结论:益肾方和厄贝沙坦均能减少糖尿病大鼠肾组织UⅡ的表达和改善肾脏病理改变,其保护作用可能与减少UⅡ的产生有关.  相似文献   

11.
Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.  相似文献   

12.
Don Dame 《Artificial organs》1996,20(5):613-617
Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.  相似文献   

13.
Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.  相似文献   

14.
Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H2O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg−1 followed by 0.15 mg · kg−1 · h−1, n=8) or verapamil (0.1 mg · kg−1 followed by 0.3 mg · kg−1 · h−1, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.  相似文献   

15.
Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.  相似文献   

16.
Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.  相似文献   

17.
Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg?1 i. v. and 32 μg · kg?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg?1. The mean ED50s, calculated from dose-response curves, were 5.4 mg · kg?1, 3.9 μg · kg?1 and 0.4 mg · kg?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg?1 and 8 μg · kg?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.  相似文献   

18.
Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg?1 · min?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min?1 · m?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I) were also significantly increased in the dopexamine group (DO2I: from 416±91 to 717±110 ml/m2 · m2; VO2I: from 98±25 to 157±22 ml/m2 · m2), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.  相似文献   

19.
A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.  相似文献   

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