肾移植术后感染新型冠状病毒1例

The novel coronavirus is a newly discovered pathogen in late December 2019, and its source is currently unknown, which can lead to asymptomatic infection, new coronavirus pneumonia or serious complications, such as acute respiratory failure. Corona virus disease 2019 (COVID-19) is a new type of respiratory disease that is currently spreading all over the world and caused by this coronavirus. Its common symptoms are highly similar to those of other viruses, such as fever, cough and dyspnea. There is currently no vaccine or treatment for COVID-19. Everyone is susceptible to infection with this disease, and owing to the long-term use of immunosuppressants, the immunity of kidney transplant recipients is suppressed, and it is more likely to be infected with the disease. At present, its impact on kidney transplant recipients is unclear. This article reports the clinical features and therapeutic course of novel coronavirus infection in a patient after renal transplantation. A 37-year-old female patient who received a kidney transplant 6 months before was diagnosed with novel coronavirus pneumonia. The patient’s symptoms (such as fever, chills, dry cough, muscle aches), laboratory tests (such as decreased white blood cell count, elevated liver enzymes and D-dimer, positive viral nucleic acid test), and chest CT (multiple left lower lung plaque ground glass shadow) were similar to those of non-transplanted novel coronavirus pneumonia patients. In terms of treatment, because the immunity of kidney transplant recipients has been suppressed for a long time, it is a very common strategy to suspend the use of immunosuppressive agents. Therefore, the patient immediately discontinued the immunosuppressive agent after admission, so that she could restore immunity against infection in a short time. At the same time, the use of glucocorticoids was also very important. Its immunosuppressive and anti-inflammatory effects played a large role in the treatment process.In addition, prophylactic antibiotics was needed, and nephrotoxic drugs should be used with caution. Finally, following discounting the use of immunosuppressant and a low-dose glucocorticoid-based treatment regimen, COVID-19 in this renal transplant recipient was successfully cured. The cure of this case was of great significance, and this adjuvant nonspecific antiviral therapy could provide a template for the treatment of other such patients.     

膜攻击复合物C5b-9对创伤失血性休克大鼠肝损害的影响研究

目的 观察大鼠创伤失血性休克时肝脏是否受膜攻击复合物攻击,以及膜攻击复合物是否对肝脏细胞凋亡产生影响.方法 雄性Wistar大鼠50只,按随机数字表法均分为正常组及模型1、3、6、24 h组5组.采用骨折后经颈动脉放血至血压40 mm Hg(1 mm Hg=0.133 kPa)制备创伤失血性休克模型.取血浆,采用酶联免疫吸附法(ELISA)检测膜攻击复合物C5b-9浓度,采用速率法测定丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)浓度;取肝脏组织,采用免疫组化法检测C5b-9阳性表达,用原位末端缺刻标记法(TUNEL)检测肝细胞凋亡,苏木素-伊红(HE)染色,光镜下观察病理改变.结果 正常组血中能检测到少量的C5b-9;模型1、3、6 h组血中C5b-9浓度(ng/L)较正常组显著升高(272.91±9.56、192.01±9.04、156.78±8.37比25.98±5.87,均P＜0.05).模型3 h组血ALT(U/L)、模型1 h组血AST(U/L)即显著上升(92.90±8.83、264.83±31.14),24 h达高峰(184.30±12.98、647.36±60.02),与正常组(38.75±5.40、66.69±19.95)比较差异均有统计学意义(均P＜0.05).正常组及模型1 h、6 h组肝脏未发现C5b-9阳性表达;模型3 h组门管区大量肝脏实质细胞存在C5b-9(个)沉积(22.60±1.06),模型24 h组C5b-9沉积明显减少(2.20±0.60,P＜0.05).正常组未检测到凋亡细胞;模型1、6、24 h组发现散在凋亡细胞(个:1.20±0.25、5.60±0.37、1.60±0.26),模型3 h组中央静脉周围凋亡细胞明显增加,出现凋亡高峰(20.60±0.47),与其余各组比较差异均有统计学意义(均P＜0.05).模型组可见肝细胞水肿变性、肝细胞膜完整性破坏,细胞溶解,以24 h病理损害最重.结论 创伤失血性休克时大鼠肝脏受到膜攻击复合物C5b-9的攻击,并且肝脏C5b-9的表达高峰与凋亡高峰在同一时间点出现,但并不是同一部位;模型3 h后血中低水平的C5b-9提示预后极差.

Abstract：

Objective To observe whether the membrane attack complex C5b-9 would accumulate in the rats' liver after receiving the assault of traumatic hemorrhagic shock, and whether the membrane attack complex deals an impact on liver apoptosis. Methods Fifty male healthy Wistar rats were randomly divided into five groups: normal group, 1, 3, 6, 24-hour model groups. The model of traumatic hemorrhagic shock was reproduced by withdrawal of blood from carotid artery after a bone fracture till the blood pressure lowered to 40 mm Hg(1 mm Hg= 0. 133 kPa). Plasma membrane attack complex C5b-9 concentration was assayed using enzyme linked immunoadsorbent assay. Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in blood was determined by Rate method. Immunohistochemistry was used to detect C5b-9 deposition in the liver. Apoptosis of liver cells was then detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay. The pathological changes in paraffin sections stained with hematoxylin-eosin(HE)were observed under light microscope. Results A small amount of C5b-9 in plasma was found in normal group, and the values(ng/L)of 1, 3, 6-hour models were significantly higher than those of the normal group(272. 91±9.56, 192. 01±9. 04, 156. 78±8. 37 vs. 25. 98±5.87, all P＜0. 05). ALT(U/L)in 3-hour model group and AST(U/L)in 1-hour model group were increased significantly(92.90 ± 8. 83, 264.83 ± 31.4), peaked at 24 hours(184.30 ± 12. 98, 647.36 ± 60. 02), and there was significant difference compared with normal group(38. 75±5.40, 66. 69± 19.95, all P＜0. 05). In the normal group and the 1-hour and 6-hour model groups, no C5b-9 was found in liver, but in the 3-hour model group a large number of liver parenchymal cells in the portal area were found to contain C5b-9 (22. 60± 1.06), however the number decreased significantly in the 24-hour model(2. 20±0. 60, P＜0. 05).In normal group there was no apoptotic cell, and in 1, 6, 24-hour model groups there were scattered apoptotic cells(1. 20±0. 25, 5. 60±0. 37, 1. 60±0. 26). In the 3-hour model group apoptosis of hepatic cells around the central vein was increased to the peak(20. 60 ± 0. 47), and there was significant difference compared with other groups(all P＜0. 05). In the model groups the liver cells became edematous, and the integrity of the membrane was lost, and some cells were even lysed. The pathological damage is most serious in 24-hour model group. Conclusion The membrane attack complex C5b-9 insulted the rats' liver after a traumatic hemorrhagic shock, and apoptosis of hepatic cells and the content of C5b-9 peaked in 3-hour model, though they do not occur in the same site. A low level of C5b-9 in blood 3 hours after shock predict a poor prognosis.     

银杏苦内酯B的临床和药理学研究进展

银杏苦内酯为“国宝”银杏叶提取物中的萜类化合物,分为银杏苦内酯A、B、C、M、J和白果内酯,编号分别为BN52020、BN52021、BN52022、BN52023、BN5202A,共同约占银杳提取物的6％。银杏提取物中仅含有微量银杏苦内酯B（BN52021）,但近年来国内外的研究显示该化合物可以抑制血小板聚集、抗炎、抗休克、以及保护心脑血管、治疗急性胰腺炎等。笔者对银杏苦内酯B的结构、理化性质、作用机制、临床和药理作用进行了概述。     

重症急性胰腺炎胰腺组织血小板活化因子受体基因表达变化

近年来血小板活化因子（PAF）信号转导通路在重症急性胰腺炎（SAP）发病机制中的意义引起了人们的关注。PAF是一种由多种细胞产生又可作用于多种细胞的内源活性物质，具有广泛的生物学效应。它通过与PAF受体结合，使G蛋白转导激活磷脂酶C、磷脂酶A2、腺苷酸环化酶和酪氨酸蛋白激酶，从而导致SAP的发生和发展。SAP时血中PAF含量显著增加，是否会刺激PAF受体数量增加从而扩大PAF对组织细胞的损害，本实验从胰腺组织PAF受体的mRNA水平进行研究。     

血浆补体C5a预示创伤失血性休克大鼠肝脏损害严重性

目的 探讨血浆补体C5a和C5b-9是否能够预示大鼠创伤失血性休克时肝脏损害的严重程度.方法 50只雄性健康Wistar大鼠被随机(随机数字法)分为正常组、模型1,3,6,24 h组.用酶联免疫吸附方法(ELISA)检测血浆中总补体活性CH50、补体活性片断C5a和膜攻击复合物C5b9,速率法检测血浆中谷草转氨酶.石蜡切片观察肝脏病理损害.结果 在模型1 h时,CH50显著上升并且达到最高值,3 h开始下降,24 h时达到最低点,1 h与3,6,24 h时点相比较,差异具有统计学意义(P<0.05);在正常组血中可以检测到少量的C5b-9,在模型1 h时C5b-9显著上升达到峰值,与正常组、模型3,6,24 h相比较差异均具有统计学意义(P<0.05),3 h时C5b-9开始下降,模型24 h时降至最低;模型组3,6,24 h时点血浆中C5a开始上升,与正常组相比较,差异均具有统计学意义(P<0.05),模型24 h组达到峰值;谷草转氨酶在模型1 h显著上升,在24 h达到峰值,24 h组与其余模型组及正常组相比较差异具有统计学意义(P<0.05).结论 创伤失m性休克时存在补体的大量活化,早期CH50、C5b-9上升;后期C5a上升.可以认为C5b-9是肝脏损害的启动因素.早期低水平的C5a可能是机体的一种自我保护措施,后期高水平的C5a作为自身不能代偿后的一种表现,作为后期疾病严重程度的一项预测指标.

Abstract：

Objective To discuss the feasibility of using serum complement C5a and C5b-9 as predictive indicators of liver injury severity in traumatic rats with hemorrhagic shock.Method Fifry healthy male Wistar rats were randomly(random number)divided into normal group,model 1 hour group,model 3 hours group,model 6 hours group,and model 24 hours group.Plasma CH50,C5a and C5b-9 were detected by using enzyme-linked immunosorbent assay,and rate method was used for determination of plasma aspartate aminotransferase.Paraffin sections of hepatic tissues were used to observe the damage of liver.Results In the model l h group,the CH50 increased significantly and reached the highest value,it began to decline in 3 hours group,and it reached the lowest point in 24 hours group.Compared with the model 3 hours group,6 hours group,and 24 hours group,the level of CH50 in model 1 hour group increased more significantly(respectively P<0.05).A small amount of C5b-9 in the normal group was detected.In the model 1 h group,C5b-9 increased significantly and reach the peak compared with 3hours group,6hours group and 24 hours group,respectively(P<0.05),but in the model 3hours,it began to decline,and in 24 hours group,it reduced to minimum.C5a increased insignificantly in the model 3 hours group,6 hours group and 24 hours group,and peaked in 24 hours group compared with normal group(P<0.05).Aspartate aminotransferase in the model 1 hour group increased significantly and peaked in 24 hours group compared with other groups(P<0.05).Conclusions A large number of complements are activated in the seRing of hemorrhagie shock.C5b-9 and CH50 increase significantly in the early stage,and C5a.increases significantly in the later stage.C5b-9 can be considered as,an initiative factor of liver injury.The low levels of C5a in the early stage may be a mechanism of self-protection of the body.The high levels of CSa in the later stage may be a kind of decompensation,and C5a can be used as a late predictor of disease severity.     

银杏苦内酯B治疗大鼠急性坏死性胰腺炎量效关系的实验研究

目的 探讨银杏苦内酯B(BN52021)治疗大鼠ANP的最佳量效关系.方法 70只雄性Wistar大鼠随机分为假手术组(SO组),ANP组,二甲基亚砜对照组(DMSO组),BN52021 2.5 mg、5mg、10 mg/kg体重治疗组(BN1、BN2、BN3组),善宁20 μg/kg体重治疗组(SS组)共7组.胰胆管逆行注射5%牛磺胆酸钠制备ANP模型.SO组、DMSO组和BN治疗组分别于术后15 min股静脉注射等量生理盐水、0.5%DMSO和不同浓度的BN52021,SS组皮下注射善宁.各组分别于制模后6 h取血检测血清淀粉酶和磷脂酶A2(PLA2)含量,记录腹水量,取胰腺组织行病理学检查和检测血小板活化因子受体(PAF-R)mRNA表达.结果 ANP组和DMSO组血清淀粉酶、PLA2、腹水量、胰腺病理分值较SO组显著升高(P＜0.05),各治疗组较ANP组显著降低(P＜0.05),且BN2组血清淀粉酶、PLA2含量的降低又较BN1、BN3和SS组更显著(P＜0.05).ANP组胰腺组织PAF-R mRNA表达较SO组显著降低(P＜0.05),各治疗组较ANP组显著升高(P＜0.05),而各治疗组间无显著差异.结论 静脉注射BN52021 5 mg/kg体重治疗ANP大鼠具有最佳的量效关系.     

银杏苦内酯B对急性坏死性胰腺炎大鼠肺组织PAF-R表达的影响

目的 观测银杏苦内酯B(BN52021)干预前后ANP大鼠肺组织血小板活化因子受体(PAF-R)mRNA和蛋白质表达的变化,探讨其作用机制.方法 180只大鼠随机分为对照组(NC组)、ANP组和BN52021治疗组(BN组),每组再分为制模后1 h、2 h、3 h、6 h、12 h、24 h 6个亚组.逆行胰胆管内注射牛磺胆酸钠诱导ANP.BN组于制模后15 min股静脉注入BN52021(0.5 mg/100 g体重).各时间点取血检测血清淀粉酶,取胰腺和肺组织行病理学检查,采用RT-PCR和Western blot检测肺组织PAF-R mRNA和蛋白质表达.结果 ANP组和BN组各时点血清淀粉酶均高于NC组(P＜0.05),BN组1 h、2 h、3 h、6 h、24 h时点均低于ANP组(P＜0.05).ANP组和BN组胰腺和肺的病理分值均高于NC组,BN组在3 h、6 h、12 h显著低于ANP组(P＜0.05).ANP组和BN组PAF-R mRNA和蛋白质水平分别在3 h和1 h显著高于NC组,BN组与ANP组相比无显著差异.结论 PAF-R在ANP早期急性肺损伤中起重要作用,BN52021对其表达无显著影响.     

银杏苦内酯B对急性坏死性胰腺炎大鼠肺组织PAF—R表达的影响

目的观测银杏苦内酯B（BN52021）干预前后ANP大鼠肺组织血小板活化因子受体（PAF-R）mRNA和蛋白质表达的变化,探讨其作用机制。方法180只大鼠随机分为对照组（NC组）、ANP组和BN52021治疗组（BN组）,每组再分为制模后1h、2h、3h、6h、12h、24h6个亚组。逆行胰胆管内注射牛磺胆酸钠诱导ANP。BN组于制模后15min股静脉注入BN52021（0.5mg/100g体重）。各时间点取血检测血清淀粉酶,取胰腺和肺组织行病理学检查,采用RT-PCR和Western blot检测肺组织PAF-R mRNA和蛋白质表达。结果ANP组和BN组各时点血清淀粉酶均高于NC组（P〈0.05）,BN组1h、2h、3h、6h、24h时点均低于ANP组（P〈0.05）。ANP组和BN组胰腺和肺的病理分值均高于NC组,BN组在3h、6h、12h显著低于ANP组（P〈0.05）。ANP组和BN组PAF-R mRNA和蛋白质水平分别在3h和1h显著高于NC组,BN组与ANP组相比无显著差异。结论PAF-R在ANP早期急性肺损伤中起重要作用,BN52021对其表达无显著影响。     

肾移植术后感染新型冠状病毒1例

The novel coronavirus is a newly discovered pathogen in late December 2019, and its source is currently unknown, which can lead to asymptomatic infection, new coronavirus pneumonia or serious complications, such as acute respiratory failure. Corona virus disease 2019 (COVID-19) is a new type of respiratory disease that is currently spreading all over the world and caused by this coronavirus. Its common symptoms are highly similar to those of other viruses, such as fever, cough and dyspnea. There is currently no vaccine or treatment for COVID-19. Everyone is susceptible to infection with this disease, and owing to the long-term use of immunosuppressants, the immunity of kidney transplant recipients is suppressed, and it is more likely to be infected with the disease. At present, its impact on kidney transplant recipients is unclear. This article reports the clinical features and therapeutic course of novel coronavirus infection in a patient after renal transplantation. A 37-year-old female patient who received a kidney transplant 6 months before was diagnosed with novel coronavirus pneumonia. The patient’s symptoms (such as fever, chills, dry cough, muscle aches), laboratory tests (such as decreased white blood cell count, elevated liver enzymes and D-dimer, positive viral nucleic acid test), and chest CT (multiple left lower lung plaque ground glass shadow) were similar to those of non-transplanted novel coronavirus pneumonia patients. In terms of treatment, because the immunity of kidney transplant recipients has been suppressed for a long time, it is a very common strategy to suspend the use of immunosuppressive agents. Therefore, the patient immediately discontinued the immunosuppressive agent after admission, so that she could restore immunity against infection in a short time. At the same time, the use of glucocorticoids was also very important. Its immunosuppressive and anti-inflammatory effects played a large role in the treatment process.In addition, prophylactic antibiotics was needed, and nephrotoxic drugs should be used with caution. Finally, following discounting the use of immunosuppressant and a low-dose glucocorticoid-based treatment regimen, COVID-19 in this renal transplant recipient was successfully cured. The cure of this case was of great significance, and this adjuvant nonspecific antiviral therapy could provide a template for the treatment of other such patients.     

低氧状态及炎症反应是新型冠状病毒肺炎患者发生急性心肌损伤的危险因素

目的: 寻找新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)患者发生急性心肌损伤的危险因素。方法: 本研究为单中心COVID-19住院患者的回顾性队列研究,共纳入149例COVID-19确诊患者,依据2018年欧洲心脏病学会年会发布的第四版心肌梗死全球统一定义中关于心肌损伤的诊断标...