Chronic kidney disease(CKD) is common and the cause of significant morbidity and mortality. The replacement of functioning nephrons by fibrosis is characteristic of progressive disease. The pathways that lead to fibro...Chronic kidney disease(CKD) is common and the cause of significant morbidity and mortality. The replacement of functioning nephrons by fibrosis is characteristic of progressive disease. The pathways that lead to fibrosis are not fully understood, although chronic non-resolving inflammation in the kidney is likely to drive the fibrotic response that occurs. In patients with progressive CKD there is histological evidence of inflammation in the interstitium and strategies that reduce inflammation reduce renal injury in pre-clinical models of CKD. The complement system is an integral part of the innate immune system but also augments adaptive immune responses. Complement activation is known to occur in many diverse renal diseases, including glomeruloneph-ritis, thrombotic microangiopathies and transplant rejection. In this review we discuss current evidence that complement activation contributes to progression of CKD, how complement could cause renal inflammation and whether complement inhibition would slow progression of renal disease.展开更多
The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss afterkidney transplantation. This principally concerns some of the original diseases as the atypical hemolyt...The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss afterkidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome(HUS), the membranoproliferative glomerulonephritis(MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital(genetic) or acquired(autoantibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.展开更多
AIM： To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis （SAP）. METHODS： SAP model of r...AIM： To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis （SAP）. METHODS： SAP model of rats was established by retrograde injection of 5% sodium taurocholate （1 mL/kg） into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators： decay accelerating factor （DAF; CD55）, 20 ku homologous restriction factor （HRF20; CD59） and membrane cofactor protein （MCP; CEH6）, in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A （n = 21） received no treatment after the SAP model was established; group B （n = 20） was given IL-4 （8 IJg/animal） intraperitoneally 0.5 h before the SAP model was established; group C （n = 20） was given IL-4 （8 μg/animal） intraperitoneaUy 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS： Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis （r = -0.748, -0.827, -0.723; P〈0.01）. In the second series of experiments, no matter when the treatment of IL-4 was given （before or after the induction of SAP model）, the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model （P〈0.01, P〈0.05）, but the expression of MCP was not influenced （P〉0.05）. The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model （P〈0.05）, but the expression of CD59 and MCP did not change （P〉0.05）. CONCLUSION： Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.展开更多
The complement system is a key component of the body's immune system. When abnormally activated, this system can induce inflammation and damage to normal tissues and participate in the development and progression ...The complement system is a key component of the body's immune system. When abnormally activated, this system can induce inflammation and damage to normal tissues and participate in the development and progression of a variety of diseases. In the past, many scholars believed that alcoholic liver disease(ALD) is induced by the stress of ethanol on liver cells, including oxidative stress and dysfunction of mitochondria and protease bodies, causing hepatocyte injury and apoptosis. Recent studies have shown that complement activation is also involved in the genesis and development of ALD. This review focuses on the roles of complement activation in ALD and of therapeutic intervention in complement-activation pathways. We intend to provide new ideas on the diagnosis and treatment of ALD.展开更多
Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, i...Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21<sup>st</sup> century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.展开更多
当电网出现有功缺额并导致频率跌落时,风电机组可以通过释放自身轴系动能为电网提供短时频率支撑(short-term frequency support,STFS)。如何利用有限的风电机组轴系动能最大限度地支撑电网频率,是当前研究的热点问题。针对风电机组可...当电网出现有功缺额并导致频率跌落时,风电机组可以通过释放自身轴系动能为电网提供短时频率支撑(short-term frequency support,STFS)。如何利用有限的风电机组轴系动能最大限度地支撑电网频率,是当前研究的热点问题。针对风电机组可释放动能和电网频率变化率约束下的电网最大频率偏差最小化问题,该文提出一种基于有功功率互补控制(active-power complementation control,ACC)的风电机组STFS策略,揭示STFS过程中风电机组的最小动能释放机理,并证明采用ACC释放全部轴系动能的STFS策略为上述问题的最优解。最后,基于含风电的电网动模实验平台的实验结果验证该文提出STFS策略的可行性与频率支撑效果。展开更多
目的探讨系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)患者中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值、中性粒细胞与补体C3的比值与疾病活动度的关系,并根据其水平变化评估患者疾病活动度。方法前瞻性方便选取2022年9月—2...目的探讨系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)患者中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值、中性粒细胞与补体C3的比值与疾病活动度的关系,并根据其水平变化评估患者疾病活动度。方法前瞻性方便选取2022年9月—2023年9月高邮市中医医院收治的86例SLE患者为研究对象,根据患者治疗前SLE疾病活动度评分分为轻度活动组、中度活动组、重度活动组,患者均口服泼尼松连续治疗3个月,比较治疗前后疾病活动度及实验室指标。结果重度活动组中性粒细胞与淋巴细胞比值(Neutrophil to Lymphocyte Ratio,NLR)、血小板与淋巴细胞比值(Platelet to Lymphocyte Ratio,PLR)水平高于轻度活动组和中度活动组,中性粒细胞与补体C3的比值(Neutrophil to Complement C3 Ratio,NC3R)水平低于轻度活动组和中度活动组,差异有统计学意义(P均<0.05);NLR、PLR与疾病活动度正相关(r=0.053、0.299,P均<0.05),NC3R与疾病活动度负相关(r=-0.673,P<0.05)。结论SLE患者经泼尼松治疗后NLR、PLR及NC3R水平变化与疾病活动度密切相关。展开更多
文摘Chronic kidney disease(CKD) is common and the cause of significant morbidity and mortality. The replacement of functioning nephrons by fibrosis is characteristic of progressive disease. The pathways that lead to fibrosis are not fully understood, although chronic non-resolving inflammation in the kidney is likely to drive the fibrotic response that occurs. In patients with progressive CKD there is histological evidence of inflammation in the interstitium and strategies that reduce inflammation reduce renal injury in pre-clinical models of CKD. The complement system is an integral part of the innate immune system but also augments adaptive immune responses. Complement activation is known to occur in many diverse renal diseases, including glomeruloneph-ritis, thrombotic microangiopathies and transplant rejection. In this review we discuss current evidence that complement activation contributes to progression of CKD, how complement could cause renal inflammation and whether complement inhibition would slow progression of renal disease.
文摘The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss afterkidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome(HUS), the membranoproliferative glomerulonephritis(MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital(genetic) or acquired(autoantibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.
基金Supported by the Research Program of Science and Technology Technology Commission Foundation of Liaoning Province, No. 2001225001-17
文摘AIM： To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis （SAP）. METHODS： SAP model of rats was established by retrograde injection of 5% sodium taurocholate （1 mL/kg） into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators： decay accelerating factor （DAF; CD55）, 20 ku homologous restriction factor （HRF20; CD59） and membrane cofactor protein （MCP; CEH6）, in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A （n = 21） received no treatment after the SAP model was established; group B （n = 20） was given IL-4 （8 IJg/animal） intraperitoneally 0.5 h before the SAP model was established; group C （n = 20） was given IL-4 （8 μg/animal） intraperitoneaUy 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS： Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis （r = -0.748, -0.827, -0.723; P〈0.01）. In the second series of experiments, no matter when the treatment of IL-4 was given （before or after the induction of SAP model）, the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model （P〈0.01, P〈0.05）, but the expression of MCP was not influenced （P〉0.05）. The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model （P〈0.05）, but the expression of CD59 and MCP did not change （P〉0.05）. CONCLUSION： Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.
基金Supported by State Key Program of National Natural Science Foundation of China,No.8143000311National Natural Science Foundation of China,No.81660103 and No.81771674+2 种基金111 Project,No.D17011Guangxi BaGui Scholarsthe Natural Science Foundation of Guangxi Province,No.2015GXNSFFA139004
文摘The complement system is a key component of the body's immune system. When abnormally activated, this system can induce inflammation and damage to normal tissues and participate in the development and progression of a variety of diseases. In the past, many scholars believed that alcoholic liver disease(ALD) is induced by the stress of ethanol on liver cells, including oxidative stress and dysfunction of mitochondria and protease bodies, causing hepatocyte injury and apoptosis. Recent studies have shown that complement activation is also involved in the genesis and development of ALD. This review focuses on the roles of complement activation in ALD and of therapeutic intervention in complement-activation pathways. We intend to provide new ideas on the diagnosis and treatment of ALD.
文摘Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21<sup>st</sup> century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.
文摘当电网出现有功缺额并导致频率跌落时,风电机组可以通过释放自身轴系动能为电网提供短时频率支撑(short-term frequency support,STFS)。如何利用有限的风电机组轴系动能最大限度地支撑电网频率,是当前研究的热点问题。针对风电机组可释放动能和电网频率变化率约束下的电网最大频率偏差最小化问题,该文提出一种基于有功功率互补控制(active-power complementation control,ACC)的风电机组STFS策略,揭示STFS过程中风电机组的最小动能释放机理,并证明采用ACC释放全部轴系动能的STFS策略为上述问题的最优解。最后,基于含风电的电网动模实验平台的实验结果验证该文提出STFS策略的可行性与频率支撑效果。
文摘目的探讨系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)患者中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值、中性粒细胞与补体C3的比值与疾病活动度的关系,并根据其水平变化评估患者疾病活动度。方法前瞻性方便选取2022年9月—2023年9月高邮市中医医院收治的86例SLE患者为研究对象,根据患者治疗前SLE疾病活动度评分分为轻度活动组、中度活动组、重度活动组,患者均口服泼尼松连续治疗3个月,比较治疗前后疾病活动度及实验室指标。结果重度活动组中性粒细胞与淋巴细胞比值(Neutrophil to Lymphocyte Ratio,NLR)、血小板与淋巴细胞比值(Platelet to Lymphocyte Ratio,PLR)水平高于轻度活动组和中度活动组,中性粒细胞与补体C3的比值(Neutrophil to Complement C3 Ratio,NC3R)水平低于轻度活动组和中度活动组,差异有统计学意义(P均<0.05);NLR、PLR与疾病活动度正相关(r=0.053、0.299,P均<0.05),NC3R与疾病活动度负相关(r=-0.673,P<0.05)。结论SLE患者经泼尼松治疗后NLR、PLR及NC3R水平变化与疾病活动度密切相关。
