目的:探讨因使用免疫检查点抑制剂(immune checkpoint inhibitors,ICPis)导致ICPis相关性糖尿病患者的临床特点。方法:回顾2例确诊为ICPis相关性糖尿病患者的临床资料,并复习相关文献。结果:2例ICPis相关性糖尿病患者均有肿瘤病史并接受...目的:探讨因使用免疫检查点抑制剂(immune checkpoint inhibitors,ICPis)导致ICPis相关性糖尿病患者的临床特点。方法:回顾2例确诊为ICPis相关性糖尿病患者的临床资料,并复习相关文献。结果:2例ICPis相关性糖尿病患者均有肿瘤病史并接受ICPis治疗,且ICPis治疗前无糖尿病病史。文献报道患者多在使用ICPis治疗后12周,也有在几个月到几年后出现血糖升高。ICPis相关性糖尿病病情进展快,特别在联用细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)抗体与程序性死亡受体1(programmed death 1,PD-1)抗体后,病情进展更快。若不及时治疗易发生糖尿病酮症酸中毒。结论:ICPis相关性糖尿病是ICPis罕见但严重的副作用。建议接受ICPis治疗的患者定期监测血糖,尽早筛查可能出现的ICPis相关性糖尿病,及时治疗,改善预后。展开更多
A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylu...A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006,resulting in good glycemic control. He experienced symptoms of abdominal distention,increased flatus,and constipation in October 2007,and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI,treatment was conservative,ceasing voglibose,with fasting and fluid supplementation. The patient progressed well,and was discharged 2 wk later. Recently,several reports of PCI associated with αGI therapy have been published,predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread,we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms,and the gastrointestinal tract should be thoroughly investigated in these patients.展开更多
T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen...T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody （CTLA-4Ig）, is known to induce to T-cell into ＂anergy＂ by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ through a local expression of CTLA-4Ig via adenoviral-mediated transplantation, we targeted on immunosuppression gene transfer into pancreatic allografts.展开更多
Objective: To search for glucosidase inhibitors from Chinese medicines. Methods: Six kinds of widely-used Chinese medicines with the activity of decreasing blood glucose were prepared by the process of boiling, conden...Objective: To search for glucosidase inhibitors from Chinese medicines. Methods: Six kinds of widely-used Chinese medicines with the activity of decreasing blood glucose were prepared by the process of boiling, condensing, precipitating, exchanging with resins and rinsing. In vitro glucosidase inhibitory activities were examined by photometric bioassay derived from rats, yeast and almond of all the Chinese medicine extracts. Diabetic ICR mice models were established by intraperitoneal injection of STZ (200 mg/kg). To investigate the in vivo effect of lowering blood glucose, the mouse blood glucose level was assayed at 30 min after being given 2.5 g/kg starch and acarbose or varied concentrations of different constituents of some Chinese medicines by stomach tube. Results: The constituents of Sangye, Sangzhi, Sangbaipi, Dihuang and Yuzhu showed potent inhibitory activities against glucosidase. Furthermore, the first kind of constituents was proved to be beneficial in reducing blood glucose by in vivo glucose tolerance experiments. Conclusion: The constituents of Chinese medicines with reducing blood glucose effect have been discovered, thus providing a clue to novel drugs.展开更多
Objective：Hyperglycemia stimulates secretion of transforming growth factor-βl （TGF-βl） in cultured glomerular mesangial cells, thereby increases production of extracellular matrix （ECM）. We examined the effect ...Objective：Hyperglycemia stimulates secretion of transforming growth factor-βl （TGF-βl） in cultured glomerular mesangial cells, thereby increases production of extracellular matrix （ECM）. We examined the effect of antisense mRNA for Smad2 on high glucose-induced ECM production in rat mesangial cells. Methods..A mammalian expression vector, pES2a, which expresses antisense Smad2 mRNA and green fluorescent protein （EGFP）, was transfected into mesangial cells. Following incubation in high glucose medium, EGFP expression and Smad2 mRNA level were determined by fluorescence microscopy and PCR, respectively. Secreted fibronectin and type IV collagen were assessed by enzyme-linked immunosorbent assay. Results ：Within 48 h of incubation in high glucose medium, Smad2 mRNA level significantly increased by 1.6 fold in association with increases in prodtaction of both fibronectin （from [45.86±2.73] to [84.19±6.81] ng/ml） and type IV collagen （from [16. 28±0. 90] to [55.27±4.75] ng/ml） in nontransfected cells （P〈0.05）. In pES2a-transfected cells, the high glucose-induced increase in Smad2 mRNA was abrogated completely, in parallel with significant suppression of the high glucose-indtmed increase in fibronectinproduction （[54.44±4.99] ng/ml） and type Ⅳ collagen （[20.96±2.47] ng/ml）. An empty vector was without effects. Coneluslon：These findings demonstrate that Smad2 plays a critical role in mediating high glucose-stimulated ECM production in mesangial cells, indicating that inhibition of Smad2 activity by antisense Smad2 mRNA may be an effective means to attenuate glomerular matrix accumulation in diabetic nephropathy.展开更多
Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinica...Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3. I software. Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h (-100.748 to-54.256), -5.002 mmHg [-9.630 to 0.685],-2.949 mmHg (-4.005 to 1.892). -4.284 mmHg (-5.444 to 3.123) respectively. Using clinical albuminuria as the end-point, the pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure. diastolic blood pressure or mean arterial blood pressure. Conclusion: ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.展开更多
We conducted a systematic review and meta-analysis of randomized controlled trials（RCTs） to determine the effectiveness and safety of incretin-based therapies（IBTs） for the treatment of type 2 diabetes（T2DM） wit...We conducted a systematic review and meta-analysis of randomized controlled trials（RCTs） to determine the effectiveness and safety of incretin-based therapies（IBTs） for the treatment of type 2 diabetes（T2DM） with nonalcoholic fatty liver disease（NAFLD）. Electronic databases such as the Cochrane library, EMbase, Pub Med, and three Chinese databases were searched for RCTs that compared IBTs with other treatments or placebo for T2 DM with NAFLD. Two reviewers independently assessed the risk of bias, extracted, and analyzed the data. A meta-analysis was performed using Revman 5.2. Publication bias was evaluated. Seven RCTs involving 532 patients were ultimately included. The results of meta-analysis（random-effects model） revealed that IBTs had a significant reduction in serum ALT（WMD –12.30, 95% CI –17.53~–7.06） and BMI（WMD –2.64, 95% CI –4.35~–0.94）. However, there was no significant difference in other outcomes including Hb A1 c, AST, TC, TG and HOMA-RA. IBTs were well tolerated by patients but the evidence was limited. The significant decrease in hepatic biochemical markers following treatment with IBTs, as well as improvements in BMI, suggested that IBTs may be an effective option for T2 DM with NAFLD.展开更多
Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism ca...Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages.It is proved by FDA for the management of type 2 diabetes.In the present work,we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases,such as type 1 and 2 diabetes,obesity,or cardiovascular and kidney diseases.This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure,hypoglycemia,and stroke risk in patients with type 2 diabetes.Some in vitro and animal experiments also show that this drug has good effects on cancer treatment.However,some case reports and experiments also show the side effect of CANA,such as amputation,fracture,and pancreatitis,while the mechanism is still unknown.Overall,CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure,cardiovascular diseases,and stroke.However,as a new drug,more clinical trials and experiments of CANA should be carried out in the future.展开更多
文摘目的:探讨因使用免疫检查点抑制剂(immune checkpoint inhibitors,ICPis)导致ICPis相关性糖尿病患者的临床特点。方法:回顾2例确诊为ICPis相关性糖尿病患者的临床资料,并复习相关文献。结果:2例ICPis相关性糖尿病患者均有肿瘤病史并接受ICPis治疗,且ICPis治疗前无糖尿病病史。文献报道患者多在使用ICPis治疗后12周,也有在几个月到几年后出现血糖升高。ICPis相关性糖尿病病情进展快,特别在联用细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)抗体与程序性死亡受体1(programmed death 1,PD-1)抗体后,病情进展更快。若不及时治疗易发生糖尿病酮症酸中毒。结论:ICPis相关性糖尿病是ICPis罕见但严重的副作用。建议接受ICPis治疗的患者定期监测血糖,尽早筛查可能出现的ICPis相关性糖尿病,及时治疗,改善预后。
文摘A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006,resulting in good glycemic control. He experienced symptoms of abdominal distention,increased flatus,and constipation in October 2007,and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI,treatment was conservative,ceasing voglibose,with fasting and fluid supplementation. The patient progressed well,and was discharged 2 wk later. Recently,several reports of PCI associated with αGI therapy have been published,predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread,we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms,and the gastrointestinal tract should be thoroughly investigated in these patients.
文摘T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody （CTLA-4Ig）, is known to induce to T-cell into ＂anergy＂ by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ through a local expression of CTLA-4Ig via adenoviral-mediated transplantation, we targeted on immunosuppression gene transfer into pancreatic allografts.
文摘Objective: To search for glucosidase inhibitors from Chinese medicines. Methods: Six kinds of widely-used Chinese medicines with the activity of decreasing blood glucose were prepared by the process of boiling, condensing, precipitating, exchanging with resins and rinsing. In vitro glucosidase inhibitory activities were examined by photometric bioassay derived from rats, yeast and almond of all the Chinese medicine extracts. Diabetic ICR mice models were established by intraperitoneal injection of STZ (200 mg/kg). To investigate the in vivo effect of lowering blood glucose, the mouse blood glucose level was assayed at 30 min after being given 2.5 g/kg starch and acarbose or varied concentrations of different constituents of some Chinese medicines by stomach tube. Results: The constituents of Sangye, Sangzhi, Sangbaipi, Dihuang and Yuzhu showed potent inhibitory activities against glucosidase. Furthermore, the first kind of constituents was proved to be beneficial in reducing blood glucose by in vivo glucose tolerance experiments. Conclusion: The constituents of Chinese medicines with reducing blood glucose effect have been discovered, thus providing a clue to novel drugs.
文摘Objective：Hyperglycemia stimulates secretion of transforming growth factor-βl （TGF-βl） in cultured glomerular mesangial cells, thereby increases production of extracellular matrix （ECM）. We examined the effect of antisense mRNA for Smad2 on high glucose-induced ECM production in rat mesangial cells. Methods..A mammalian expression vector, pES2a, which expresses antisense Smad2 mRNA and green fluorescent protein （EGFP）, was transfected into mesangial cells. Following incubation in high glucose medium, EGFP expression and Smad2 mRNA level were determined by fluorescence microscopy and PCR, respectively. Secreted fibronectin and type IV collagen were assessed by enzyme-linked immunosorbent assay. Results ：Within 48 h of incubation in high glucose medium, Smad2 mRNA level significantly increased by 1.6 fold in association with increases in prodtaction of both fibronectin （from [45.86±2.73] to [84.19±6.81] ng/ml） and type IV collagen （from [16. 28±0. 90] to [55.27±4.75] ng/ml） in nontransfected cells （P〈0.05）. In pES2a-transfected cells, the high glucose-induced increase in Smad2 mRNA was abrogated completely, in parallel with significant suppression of the high glucose-indtmed increase in fibronectinproduction （[54.44±4.99] ng/ml） and type Ⅳ collagen （[20.96±2.47] ng/ml）. An empty vector was without effects. Coneluslon：These findings demonstrate that Smad2 plays a critical role in mediating high glucose-stimulated ECM production in mesangial cells, indicating that inhibition of Smad2 activity by antisense Smad2 mRNA may be an effective means to attenuate glomerular matrix accumulation in diabetic nephropathy.
文摘Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3. I software. Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h (-100.748 to-54.256), -5.002 mmHg [-9.630 to 0.685],-2.949 mmHg (-4.005 to 1.892). -4.284 mmHg (-5.444 to 3.123) respectively. Using clinical albuminuria as the end-point, the pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure. diastolic blood pressure or mean arterial blood pressure. Conclusion: ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.
文摘We conducted a systematic review and meta-analysis of randomized controlled trials（RCTs） to determine the effectiveness and safety of incretin-based therapies（IBTs） for the treatment of type 2 diabetes（T2DM） with nonalcoholic fatty liver disease（NAFLD）. Electronic databases such as the Cochrane library, EMbase, Pub Med, and three Chinese databases were searched for RCTs that compared IBTs with other treatments or placebo for T2 DM with NAFLD. Two reviewers independently assessed the risk of bias, extracted, and analyzed the data. A meta-analysis was performed using Revman 5.2. Publication bias was evaluated. Seven RCTs involving 532 patients were ultimately included. The results of meta-analysis（random-effects model） revealed that IBTs had a significant reduction in serum ALT（WMD –12.30, 95% CI –17.53~–7.06） and BMI（WMD –2.64, 95% CI –4.35~–0.94）. However, there was no significant difference in other outcomes including Hb A1 c, AST, TC, TG and HOMA-RA. IBTs were well tolerated by patients but the evidence was limited. The significant decrease in hepatic biochemical markers following treatment with IBTs, as well as improvements in BMI, suggested that IBTs may be an effective option for T2 DM with NAFLD.
基金Beijing Excellent Talents Training Assistance(Grant No.2017000082595G244)the Health and Research Bureau of Tongzhou District(Grant No.TWKY-2016-QN-01-58)。
文摘Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages.It is proved by FDA for the management of type 2 diabetes.In the present work,we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases,such as type 1 and 2 diabetes,obesity,or cardiovascular and kidney diseases.This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure,hypoglycemia,and stroke risk in patients with type 2 diabetes.Some in vitro and animal experiments also show that this drug has good effects on cancer treatment.However,some case reports and experiments also show the side effect of CANA,such as amputation,fracture,and pancreatitis,while the mechanism is still unknown.Overall,CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure,cardiovascular diseases,and stroke.However,as a new drug,more clinical trials and experiments of CANA should be carried out in the future.
