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1.
雷公藤多甙对急性坏死性胰腺炎免疫调节作用的实验研究   总被引:24,自引:0,他引:24  
目的 探讨雷公藤多甙对大鼠急性坏死性胰腺炎(ANP)的免疫调节作用。方法 将60只牛磺胆酸钠诱导的ANP大鼠分成不治疗组、雷公藤多甙组和橄榄油对照组共3组,另取6只下沉大鼠作为对照组。每组分别在术后6和12h各处死6只大鼠取血,测淀粉酶、内毒素、TNF-α和IL-1水平,观察胰腺组织的病理变化。结果 雷公藤组有3只动物生存3d以上,不治疗组及橄缆油对照组大鼠3d内全部死亡。不治疗组与雷公藤组12h  相似文献   

2.
目的 探讨移植肠白细胞介素2受体(IL-2R)和细胞间粘附分子1(ICMA-1)的表达在小肠移植排斥反应中的意义及诊断价值.方法 选用近交系大鼠F344/N和Wistar/A进行全小肠异位移植,实验分4组,第1组:Wistar;第2组:Wistar→Wistar;第3组:F344→Wistar;第4组:F344→Wistar+环孢霉素A(6mg·kg^-1·d^-1)。术后第3、5、7天取各组动物  相似文献   

3.
Leflunomide免疫抑制作用的实验研究   总被引:1,自引:0,他引:1  
为了寻找一种抗排斥、疗效好且毒性低的免疫抑制药物,应用Leflunomide(LFM,雷抑素)对大鼠移植模型进行研究,实验分为对照组、LFM组、CsA组和LFM+CsA组。结果显示LFM2.5mg.kg-1.d-1和CsA2.5mg.kg-1.d-1术后灌服7天,大鼠移植器官存活时间分别为18.2±1.5和13.5±1.3天,较对照组7.2±1.2天明显延长,LFM和CsA联合用药,移植物存活时间26.8±5.7天,较单纯用药效果更好。证明LFM具有显著的抗排斥作用,与CsA合用有协同作用;LFM在移植后4天给药,仍可逆转淋巴细胞在移植物内的浸润,能较快地逆转移植物的排斥反应。  相似文献   

4.
雷公藤多甙在大鼠肾移植模型中的实验研究   总被引:9,自引:0,他引:9  
用显微外科技术建立大鼠肾移植模型(W→SD)。将大鼠分为四组:对照组仅给生理盐水,雷公藤多甙(T_Ⅱ)组给T_Ⅱ30mg·kg~(1)·d~(-1),CsA组给CsA15mg·kg~(-1)·d~(-1),CsA+T_Ⅱ组同时给CsA15mg·kg~(-1)·d~(-1)+T_Ⅱ30mg·kg~(-1)·d~(-1)。对照组大鼠肾移植后平均存活时间为7.3±2.2天,T_Ⅱ组平均存活时间为18.1±3.7天,两组存活时间有显著性差异(P<0.05)。T_Ⅱ+CsA组平均存活时间为34.6±5.2天,CsA组为26.1±4.6天。单纯用药的两组分别与联合用药组比较均有显著性差异(P<0.05)。T_Ⅱ30mg·kg~(-1)·d~(-1)对大鼠肝、肾、心脏及白细胞总数无影响,但显著抑制大鼠脾淋巴细胞的转化。T_Ⅱ也显著抑制大鼠外周血白细胞介素-2受体水平,但抑制能力不及CsA。  相似文献   

5.
动态监测60例肾移植患者术后2个月内血清白细胞介素2(IL-2)、可溶性IL-2受体(sIL-2R)和白细胞介素6(IL-6)的变化。结果发现发生急性排斥反应时,上述细胞因子的升高较临床诊断提早数天,并且显著高于环孢素A肾中毒组;对甲泼尼龙敏感的排斥反应,抗排斥治疗数天后上述因子下降到排斥前水平。提示肾移植术后动态监测患者血清IL-2、sIL-2R和IL-6有助于急性排斥反应的早期诊断、鉴别诊断、及时治疗和甲泼尼龙抗排斥的疗效评价。  相似文献   

6.
目的 探讨移植肠白细胞介素2 受体( I L2 R) 和细胞间粘附分子1( I C A M1) 的表达在小肠移植排斥反应中的意义及诊断价值。方法 选用近交系大鼠 F344/ N 和 Wistar/ A 进行全小肠异位移植,实验分4 组,第1 组: Wistar;第2 组: Wistar→ Wistar ;第3 组: F344 → Wistar;第4 组: F344 → Wistar+环孢霉素 A(6 mg·kg - 1·d - 1) 。术后第3 、5 、7 天取各组动物移植肠标本进行病理学检查,应用免疫组化技术( S P 法) 检测移植肠 I L2 R 和 I C A M1 的表达。结果 病理学检查显示第3 组大鼠在术后第3 、5 、7天分别符合轻、中、重度排斥,第2 、4 组无明显排斥征象。第3 组 I L2 R 表达在术后均非常显著高于其他3 个对照组;第3 组 I C A M1 表达在术后第3 、5 天较相似,尤其在上皮细胞表现为强阳性,并显著高于第1 组。但第2 、4 对照组 I C A M1 表达也较高,第3 组仅在术后第3 天 I C A M1 评分显著高于第2 组。结论  I L2 R 和 I C A M1 阳性细胞在小肠移植排斥反应过程中发挥重要作用。应用单克隆抗体阻  相似文献   

7.
目的:研究雷公藤多甙对实验性小鼠小肠移植的抗排斥作用。方法:以Balb/c小鼠作为供体,C57BL/6小鼠为受体,建立同种异位小肠移植模型。将受体分为5组,各组样本数为12只:1组,无处理(对照组);2组,单独使用雷公藤多甙10mg/(kg.d);3组,小剂量CsA10mg/(kg.d);4组,联合应用雷公藤多甙与小剂量CsA;5组,大剂量CsA20mg/(kg.d)。每组抽取6只于术后5d处死,切除移植物进行组织学检查,其余动物分别观察受体及移植物的生存期。结果:单独使用雷公藤多甙不能抑制小鼠小肠移植的排斥反应,联合应用雷公藤多甙及环孢素(CsA)可使移植物生存期明显延长。结论:雷公藤多甙与CsA协同对小鼠小肠移植的移植物有保护作用。  相似文献   

8.
报告一种成功的猪全胰十二指肠移植模型。将静脉引流入体循环,所带小段十二指肠与空肠吻合,引流胰液于肠道,同时切除受体全胰。I组动物未用免疫抑制剂,平均存活10.2±2.6天,均因急性排斥反应死亡或处死。Ⅱ组动物应用环孢素A、雷公藤和甲基泼尼松龙抗排斥治疗,平均移植物存活70.6±30天以上,移植物功能良好。认为,此种动物模型稳定,抗排斥方案合理  相似文献   

9.
胰液肠内引流式胰肾同期联合移植(附一例报告)   总被引:7,自引:1,他引:6  
目的 观察胰肾联合移植治疗胰岛素依赖型糖尿病能功能衰竭的效果。方法 为1例胰岛素依赖型糖尿病合并肾功能衰竭的患者施行胰肾同期联合移植,移植胰的外分泌采用肠内引流。结果 移植胰术后第1d恢复正常功能,移植肾术后第3d恢复正常功能,术后1周停用胰岛素,空腹及餐后血糖正常,未发生急性排斥反应及肠内引流术式的相关并发症。结论 肠内引流式同期胰肾联合移植是治疗糖现合并肾功能衰竭的较好术式。  相似文献   

10.
目的 总结肝移植后再行胰肾联合移植治疗糖尿病合并肾功能衰竭的临床处理经验.方法 2例肝移植受者术前合并有2型糖尿病,分别于肝移植后7年余和4年余发生肾功能衰竭,遂行胰肾联合移植,2例的移植肝功能均正常.采取腹部器官联合快速切取技术整块切取双肾、全胰及十二指肠节段,先行肾移植,再行胰腺移植,供肾移植于左侧髂窝,供胰移植于右侧髂窝,供者的十二指肠与受者的空肠侧侧吻合,供者的十二指肠内置管,通过受者的空肠引流出体外.例1采用抗白细胞介素受体单克隆抗体诱导的四联免疫抑制方案预防排斥反应;例2术中给予抗胸腺细胞球蛋白和甲泼尼龙,术后继续使用2d,采用他克莫司+吗替麦考酚酯+皮质激素预防排斥反应.结果 2例手术过程顺利,术后移植胰腺功能正常,血糖均于术后10d左右恢复正常,无需胰岛素治疗,移植肾功能1周时恢复正常,第2例1周后血清肌酐渐进性升高,经验性抗排斥反应治疗效果不明显,移植肾活组织检查未见明显排斥反应征象,遂将他克莫司替换为西罗莫司,之后受者的肾功能逐渐恢复正常.目前2例受者已分别随访36个月及9个月,移植肝、肾及胰腺功能均正常.结论 肝移植后合并糖尿病、肾功能衰竭时可考虑行胰肾联合移植,但术后免疫反应复杂,需严密监测移植物功能.  相似文献   

11.
BACKGROUND: Multivisceral transplantation (MVtx) involves simultaneous transplantation of the intestine with other organs, often including the pancreas. The pancreas portion of the graft has always been approached with caution because allograft pancreatitis, rejection or technical complications may be devastating in this setting. We reviewed our experience with multivisceral grafts that included the entire pancreas. METHODS: Twenty-five patients received 27 MVtx that included the entire pancreas between July 2003 and November 2006. In five, a modified MVtx with preservation of the native liver was performed. Two patients required retransplantation for severe rejection. Insulin requirements, graft and patient survival were determined at 6-months posttransplant. Serum amylase and lipase levels were analyzed on postoperative days 3, 7, 30, and 180. RESULTS: Twenty of 25 patients with a transplant pancreas graft were alive at 6-months posttransplant. Median serum amylase and lipase levels posttransplant were normal at all time points. One patient exhibited elevation of amylase and lipase at the time of severe acute cellular rejection of the intestinal graft, likely representing simultaneous pancreas allograft rejection, although this was not confirmed by biopsy. There were no episodes of allograft pancreatitis or technical complications. Once weaned from hyperalimentation, all patients remained normoglycemic and insulin-independent 6-months posttransplant. CONCLUSION: In this series, there were no postoperative pancreatic complications, no episode of isolated pancreas allograft rejection, and no loss of pancreatic graft function. None of the five deaths were related to pancreatic graft complications.  相似文献   

12.
Splenocytes sensitized in vitro to the H-2 allotype of a skin allograft have been shown to cause accelerated rejection of the skin allograft after adoptive transfer of the splenocytes. Treatment of the host with splenectomy or sublethal radiation did not alter the accelerated rejection. In the present study, cyclosporine (CsA) given subcutaneously to mice bearing 1 day old skin grafts prevented the rejection of the graft despite the adoptive transfer of sensitized cells. If the CsA was given for 14 days at 50 mg/kg every other day, the grafts were rejected an average of 6 days after the cessation of CsA. If the CsA was given for 20 days 50 mg/kg every other day, the grafts were not rejected even after cessation of CsA. When no sensitized cells were given, the same pattern resulted; that is, when a 14 day course of CsA was given the grafts were rejected after cessation of the CsA but when a 20-d course was given, the grafts were not rejected even after the CsA was stopped. If splenocytes were sensitized in the presence of interleukin-2 (IL-2), they caused rejection of the skin allografts in animals even on treatment with CsA. We concluded that CsA can prevent skin allograft rejections in the murine system. Moreover, the dose of CsA was critical, in that a longer course of CsA was necessary for tolerance. CsA further prevented the accelerated rejection of skin allografts by adoptive transfer of specifically sensitized splenocytes. Donor irradiation did not alter the effect of the CsA or of the adoptively transferred cells. CsA could not prevent the rejection of skin allografts when the adoptively transferred cells were sensitized to antigen in the presence of IL-2.  相似文献   

13.
目的 研究抑制趋化因子受体CCR5减轻小鼠同种异体移植心脏急性排斥反应的作用机制.方法 采用小鼠颈部心脏移植模型,将96只小鼠用随机数字表法分为4组,每组24只,供、受者各12只,A组术后给予anti-CCR5 mAb和CsA,B组术后给予anti-CCR5 mAb,C组术后给予CsA,D组为对照组,术后给予生理盐水.于术后第7d取各组移植心组织6例,检测CCR5及IL-2和IL-10的表达差异,其余6例用于观察移植心脏存活时间.结果 A、B、C组小鼠移植心脏存活时间明显延长,其CCR5及IL-2的表达较D组明显减少,IL-10的表达明显增加.结论 抑制趋化因子受体CCR5对同种异体移植心脏有明显的保护作用,可能与细胞因子的表达有关.  相似文献   

14.
肾移植患者急性排斥反应与sCD30的相关性   总被引:2,自引:1,他引:1  
目的 研究检测肾移植患者手术前后血清溶解性CD30(sCD30)水平的临床意义。方法 采用酶联免疫吸附剂测定法(ELISA)检测69例肾移植患者术前及术后sCD30的水平,并分析sCD30与肾移植受者术后急性排斥发生的关系。结果 术前sCD30阳性患者11例,其中有6例发生急性排斥,sCD30阴性患者58例,发生急性排斥5例。两组相比排斥反应发生率差异有统计学意义(P〈0.01)。术后5dsCD30在发生排斥患者组中的水平与对照组间差异有统计学意义(P〈0.05),而术后1、3d水平两组间差异无统计学意义(P〉0.05)。结论 肾移植手术前后监测sCD30水平,特别是术前及术后第5天左右时的检测水平,对于评估和预测急性排斥反应发生的可能性,具有重要的参考价值。  相似文献   

15.
Whole pancreas isografts or allografts (ACI donors, RT1a) with bladder drainage of exocrine secretions were performed in Lewis rats (RR1(1] with streptozotocin-induced diabetes. Urinary amylase, pH, and volume and serum glucose were measured daily. They were analyzed alone, or in combination, to determine patterns in deviations from normal values, from isograft control values, or from a posttransplant baseline in relation to rejection (defined as reversion of plasma glucose of greater than 200 mg/dl) in nonimmunosuppressed recipients. Also studied were the sensitivity and specificity by which such deviations predicted rejection. Functioning grafts were associated with increased urinary amylase and pH compared with normal or diabetic controls; urinary volume was less than that of diabetic rats, but greater than that of normal rats. In nonimmunosuppressed allograft recipients (n = 9), rejection occurred at a mean (+/- SD) of 7.78 +/- 0.44 days. Serum glucose rose to above normal (greater than 134 mg/dl) 1 day before rejection in 3 animals (sensitivity 33%, false negative rate 66%; false positive rate in 9 isograft recipients, 44%). Urinary volume dropped below 3 ml at a mean of 3.17 +/- 0.98 days (range 2-5 days) before rejection in 6 animals (sensitivity 66%, false negative rate 33%; false positive rate 0%). Urinary pH fell below 7.25 at a mean of 3.13 +/- 1.81 days (range 1-5 days) before rejection in 8 rats (sensitivity of 89%, false negative rate 11%; false positive rate 29%). Urinary amylase dropped from a posttransplant peak at a mean of 3.56 +/- 1.42 days (range 1-6 days) before rejection in 9 animals (sensitivity 100%, false negative rate 0%; false positive rate 43%), and dropped below 1500 units per 24 hr at a mean of 2.00 +/- 1.32 days (range 1-5 days) before rejection in 8 animals (sensitivity 89%, false negative rate 11%; false positive rate 0%). A drop in urinary amylase combined with a drop in urinary volume or pH occurred at a mean of 3.22 +/- 1.48 days (range 1-5 days) before rejection in 9 rats (sensitivity 100%, false negative rate 0%; false positive rate 0%). In a separate group of 10 allograft recipients, immunosuppression with prednisone and cyclosporine was begun concomitant with, or within 2 days of, the drop in urinary amylase from the peak value; rejection did not occur in 3 animals and was delayed to a mean of 12.0 +/- 5.0 days posttransplant in 7 animals (P less than .05 compared with the nonimmunosuppressed group).(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

16.
Pancreas allograft rejection in dogs with pancreaticocystostomy can be predicted in advance of hyperglycemia by monitoring the urinary amylase (UA) concentration (U/L): In initial experiments, UA values declined to less than 1000 1.3 +/- 0.2 days before hyperglycemia in nonimmunosuppressed dogs, 3.3 +/- 1.0 days in dogs treated with cyclosporine (CsA), and 9.3 +/- 0.7 days in dogs treated with CsA, azathioprine (Aza), and prednisone (triple therapy). Autotransplanted control dogs maintained high urine amylase concentrations indefinitely (mean 125,544 +/- 36,931). In a subsequent experiment, in 19 dogs with bladder-drained pancreas allografts on CsA only for prophylactic immunosuppression, a five-day course of antirejection treatment with Aza (5.0 mg/kg) and antilymphocyte globulin ALG (1 mg/kg) was started in group A (n = 10) when a raise in serum glucose was detected, and in group B (n = 9) when a drop of UA below 1000 was observed. The functional allograft survival rate was 9.2 +/- 0.5 days in group A (treatment started after hyperglycemia) and 29.0 +/- 5.7 days in group B (treatment started after drop in UA) (P = .002). The UA dropped in all dogs before hyperglycemia, at a mean of 2.7 days in group A and 20.8 days in group B. Clinically, 8 patients received a whole cadaver pancreas transplant with urinary drainage of the exocrine secretions. All were followed with UA monitoring. Three recipients lost the grafts for technical reasons. Three recipients lost the grafts for technical reasons. One had a primary non-function and UA was below 1000 U/24 hr; two developed abscesses and the grafts were removed while functioning with high UA values. Five grafts are currently functioning; 3 recipients had no rejection episodes and their UA values ranged from 30,000 to 100,000 U/24 hr during their entire postoperative course. The other two had rejection episodes. In both cases UA decreased to baseline levels 1 and 4 days in advance of the hyperglycemia. After antirejection treatment UA rose again to high values and plasma glucose levels declined. Both patients are currently insulin-independent, with UA values ranging from 10,000 to 200,000 U/24 hr. Both experimentally and clinically UA is an early predictor of pancreas allograft rejection. The institution of early treatment of rejection episodes in dogs, based on UA, significantly improved allograft survival. Urine amylase monitoring in pancreas transplant recipients could lead to an early treatment of rejection and improve graft survival.  相似文献   

17.
We evaluated the survival of highly purified freshly isolated pancreatic islets transplanted from single canine donors into 20 outbred mongrel dogs immunosuppressed with cyclosporine or untreated. The grafts (mean weight +/- SE, 0.5 +/- 0.1 g, containing 122 +/- 8 X 10(3) islets; purity 91% by electron microscopy) were transplanted into 3 groups of dogs: group 1, autograft without CsA (5444 +/- 688 islets/kg body weight, n = 6); group 2, allograft without CsA (6669 +/- 1744, n = 4); and group 3, allograft with CsA (8645 +/- 1149, n = 10). The CsA was injected i.m. daily for 4 days before and 30 days after transplantation. Fasting plasma glucose (PG, mg/dl) and serum CsA trough values were determined daily. Intravenous glucose tolerance tests were done before and after transplantation, for calculation of K values (decline in glucose, %/min; preoperatively, mean K = 3.9 +/- 0.2). In group 1 all 6 dogs were normoglycemic (PG = 98 +/- 2 and K = 1.8 +/- 0.2) at 1 month; in group 2 the graft failed in all 4 dogs, at 4 +/- 1.2 days; in group 3 all 10 dogs were normoglycemic initially. Of the group 3 dogs, 4 died (intussusception developed in 2, and the graft failed at 3 and 9 days in 2 the CsA values of which were less than 300 micrograms/L preoperatively), but the other 6 were still normoglycemic when the CsA was stopped at 30 days (mean PG = 132 +/- 16 and K = 0.9 +/- 0.2; P less than 0.05 vs. group 1). Their CsA values were 708 +/- 197 before and 359 +/- 41 micrograms/L during the third week after transplantation; their grafts failed 12.3 +/- 3.4 days after the cessation of CsA. This data is unique in demonstrating prolonged function of purified allogeneic islets transplanted from individual outbred canine donors, but glucose tolerance was impaired. CsA at serum levels greater than 300 micrograms/L induced prolonged survival of purified canine islets and rejection was prompt when it was stopped.  相似文献   

18.
Thirty-one pancreas transplant recipients were monitored by pancreatic juice cytology in the early post-operative period. An increase in the total amount of cells and, in particular, signs of immunoactivation with the appearance of two or more blast-transformed cells per specimen were taken as evidence of acute rejection. According to these criteria a total of 38 rejection episodes were diagnosed. The first positive cytology appeared after 9 days (mean) and lasted for 2 days (mean). Immunocytochemical analysis of the juice showed increased amounts of CD3+ cells during rejection. When rejection occurred during prophylaxis with antithymocyte globulin, neutrophils were preponderant in the pancreatic juice while during OKT-3 prophylaxis a high percentage of monocytes was a characteristic finding. Antirejection treatment was started when the cytology became positive and all rejection episodes except one were reversed. A decrease in the pancreatic juice amylase activity occurred in 66% of the rejection episodes, but in only 5 of the 38 episodes was the decrease highly significant. No correlation was found between graft rejection and volume excretion of pancreatic juice. There were no persistent or characteristic changes in serum amylase or peripheral white blood cell count at the time of rejection. Graft pancreatitis was diagnosed cytologically in 7 patients, in 5 of whom the grafts were eventually lost.  相似文献   

19.
雷公藤多苷对移植肾长期存活率的影响   总被引:1,自引:0,他引:1  
目的:探讨雷公藤多苷(TW)作为免疫抑制剂对肾移植患者长期存活率的疗效及副作用.方法:104例患者在肾移植术后采用TW 泼尼松(Pred) 环孢霉素(GsA) 硫唑嘌呤(AZa)免疫抑制剂治疗,48例患者在肾移植术后采用Pred GsA 骁悉(MMF)免疫抑制剂治疗,就以下方面对两组患者进行观察比较:(1)术后5年内发生排斥反应及临界改变情况;(2)外周血白细胞下降、肝功能异常的发生率;(3)严重感染情况;(4)出现尿蛋白情况;(5)术后5年内肾功能变化情况及移植肾5年存活率.结果:5年内AZa TW组急性排斥反应及临界改变的发生率较MMF组低,分别为11.5%、16.7%和4.8%、6.3%(P>0.05);GPT高于正常的发生率分别为7.7%、16.6%(P>0.05);外周血白细胞低于正常的发生率分别为0.96%、18.8%(P<0.01);严重感染的发生率分别为1.9%、18.8%(P<0.05),5年内出现蛋白尿的患者例数分别为17.3%、29.2%(P>0.05),两组移植肾5年存活率相似,分别为89.6%、85.4%(P>0.05).结论:在肾移植术后应用CsA Pred AZa TW免疫抑制方案是可行的,既可以使肾移植术后急性排斥反应减少,同时还能减少蛋白尿及慢性排斥反应的发生率下降,为国内提高移植肾长期存活率提供了一条新的途径.  相似文献   

20.
The diagnosis of pancreas allograft rejection is usually made on the basis of blood glucose concentration, a late indicator of rejection. We performed segmental pancreas transplants in totally pancreatectomized dogs with the exocrine secretions drained into the bladder (ductocystostomy). We directly measured exocrine pancreatic secretions (urinary amylase), in an attempt to find a sensitive indicator for early rejection. Five groups were studied: (I) autografts; (II) autografts immunosuppressed with cyclosporine (CsA), azathioprine and prednisone; (III) allografts without immunosuppression; (IV) allografts immunosuppressed with CsA alone; (V) allografts immunosuppressed with CsA, azathioprine, and prednisone. The control groups (I, II) maintained high urine amylase concentrations indefinitely (mean +/- SE of 125,544 +/- 36,931 u/liter). Rejection, as diagnosed by rise of serum glucose to greater than 150 mg/dl, occurred at a mean (+/- SE) of 9.0 +/- 0.2 days in nonimmunosuppressed recipients of Group III, at 9.3 +/- 0.7 days in cyclosporine-treated dogs of Group IV, and at 28.0 +/- 8.3 days after transplantation in dogs immunosuppressed with triple therapy of Group V. In all allograft recipients, urine amylase declined precipitously (less than 1000 u/liter) before the onset of hyperglycemia, by 1.3 +/- 0.2 days in Group III, 3.3 +/- 1.0 days in Group IV, and 9.4 +/- 2.8 days in Group V. In a further experiment, nine dogs with pancreas allografts received cyclosporine for prophylactic immunosuppression; further antirejection therapy with azathioprine and antilymphocyte globulin was given for 5 days beginning the first day that rejection was diagnosed. In five dogs (Group A) rejection was diagnosed when serum glucose rose to greater than 150 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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