Objective Diabetic foot ulcer(DFU)is one of the most serious complications of diabetes.Leukocyte-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich plasma.This study aims to investigate the...Objective Diabetic foot ulcer(DFU)is one of the most serious complications of diabetes.Leukocyte-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich plasma.This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice.Methods Patients with DFU who received L-PRF treatment and standard of care(SOC)from 2018 to 2019 in Tongji Hospital were enrolled.The clinical information including patient characteristics,wound evaluation(area,severity,infection,blood supply),SOC of DFU,and images of ulcers was retrospectively extracted and analyzed.L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction(PVR)greater than 80%.Therapeutic effectiveness,including overall PVR and the overall and weekly healing rates,was evaluated.Results Totally,26 patients with DFU were enrolled,and they had an ulcer duration of 47.0(35.0,72.3)days.The severity and infection of ulcers varied,as indicated by the Site,Ischemia,Neuropathy,Bacterial Infection,and Depth(SINBAD)scores of 2–6,Wagner grades of 1–4,and the Perfusion,Extent,Depth,Infection and Sensation(PEDIS)scores of 2–4.The initial ulcer volume before L-PRF treatment was 4.94(1.50,13.83)cm3,and the final ulcer volume was 0.35(0.03,1.76)cm3.The median number of L-PRF doses was 3(2,5).A total of 11 patients achieved complete epithelialization after the fifth week of treatment,and 19 patients achieved at least an 80%volume reduction after the seventh week.The overall wound-healing rate was 1.47(0.63,3.29)cm3/week,and the healing rate was faster in the first 2 weeks than in the remaining weeks.Concurrent treatment did not change the percentage of complete epithelialization or healing rate.Conclusion Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index,SINBAD score,or Wagner grade,indicating that this method is appropriate for DFU treatment under different clinical conditions.展开更多
Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve she...Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve sheath.Methods This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our hospital.The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection operator.Subsequently,we constructed a prediction model using multivariate logistic regression.The accuracy of the model was verified using receiver operating characteristic curve analysis.Results In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study.Two variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction model.In the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of 0.901.Moreover,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was 0.890.Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.展开更多
The expression of c-met stimulated by high glucose in human renal tubular epithelial ceils and the role of HGF/c-met system in diabetic nephropathy were examined. The proximal tubular epithelial cells were cultured in...The expression of c-met stimulated by high glucose in human renal tubular epithelial ceils and the role of HGF/c-met system in diabetic nephropathy were examined. The proximal tubular epithelial cells were cultured in vitro under different conditions. MTT was used for the detection of cellular proliferation and RT-PCR was employed for measurement of c-met mRNA level. Our results showed that under different conditions, there were no significant differences in the proliferation of proximal tubular epithelial cells 12 h and 24 h after the culuture （P〉0.05）. The proliferation of proximal tubular epithelial cells showed a significant change 96 h after the culture and the cellular proliferation induced by hepatocyte growth factor （HGF） was very active （P〈0.05）. Moreover, no significant difference in the expression of c-met mRNA was found 12 h after the culture under different conditions （P〉0.05）, while 24 and 96 h after the culture, a persistent and significantly higher expression of c-met mRNA was found in HGF-induced proliferation. It is concluded that addition of exogenous HGF could inhibit the apoptosis induced by high-level glucose, promote the proliferation of proximal tubular epithelial cells, and induce the expression of c-met. Our study suggests that local up-regulation of HGF/c-met system plays an important role in the repair of renal damage in diabetic nephropathy.展开更多
AIM： To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS： According to...AIM： To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS： According to the body mass index （BMI）, 60 type 2 diabetes patients were divided into two groups, one group was non-obese diabetes patients with BMI 〈 25Kg/M^2 （30 cases） and the other group was obese diabetes patients with BMI 〉25Kg/M^2 （30 cases）. There were 28 healthy persons in the control group. EUSA technique was employed to determine the plasma adiponectin and resistin concentrations. The fasting blood glucose, insulin and blood lipid were detected respectively by electrocheminescence immunoassay and immunoturbidimetric assay. Insulin resistance index and insulin sensitive index were calculated by the homeostasis model assessment （HOMO）. RESULTS： The levels of plasma adiponectin were decreased significantly in diabetes group compared to that in control group （non-obese： 8.58±0.86, obese： 6.22±1.34 vs 10.53±1.47 P〈0.05）; moreover, adiponectin concentration in obese diabetes group was significantly decreased compared to that in non-obese diabetes group （6.22±1.34 vs 8.58±0.86, P〈 0.05）. The levels of plasma resistin were increased significantly in diabetes group compared to that in control group （obese： 18.64 ± 4.65, non-obese： 24.05±9.07 vs 14.16±5.25, P〈0.05,P〈0.05）; furthermore, the levels of resistin in obese diabetes group were increased significantly compared to that in non-obese diabetes group （P〈 0.05）. Plasma adiponectin was correlated negatively with BMI, blood glucose, insulin resistance index and triglyceride （respectively, r=-0.55, P〈0.01; r=-0.51, P〈0.05; r=-0.52, P〈 0.05： r=-0.39, P〈 0.05）, while it was positively correlated with insulin sensitive index （r=0.45, P〈0.05）. Conversely, plasma resistin correlated positively with BMI, blood glucose, triglyceride and insulin resistance index （respectively, r=0.40, P〈 0.05; r= 0.52, P〈0.05; r= 0.46, P〈 0.01; r= 0.27, P〈 0.05）, and negatively correlated with insulin sensitive index （r=-0.32, P〈 0.05）. CONCLUSION： Plasma adiponectin and resistin are associatecl with the disorder of metabolism of glucose and lipid in diabetes. The relationship between these hormone and insulin sensitivity suggests that they may take part in the development of insulin resistance of type 2 diabetes.展开更多
Objective To investigate the influence of vitamin D receptor （VDR） gene polymorphisms on susceptibility to type 1 diabetes mellitus （T1DM） in the Chinese Han population. Method One hundred and thirty-six Chinese ...Objective To investigate the influence of vitamin D receptor （VDR） gene polymorphisms on susceptibility to type 1 diabetes mellitus （T1DM） in the Chinese Han population. Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamL Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects （ P = 0. 033 ） while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms. Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibihty to T1DM in the Chinese Han population of Beijing.展开更多
Primary thyroid lymphoma(PTL)is an exceptionally rare and highly aggressive potentially curable malignant disease.We report three typical cases of PTL referred to our hospital.All three cases had long history of Hashi...Primary thyroid lymphoma(PTL)is an exceptionally rare and highly aggressive potentially curable malignant disease.We report three typical cases of PTL referred to our hospital.All three cases had long history of Hashimoto’s thyroiditis,and presented with progressively enlarging neck mass.The first two cases were confirmed by surgical biopsy to be diffuse large B cell lymphoma,and received radiotherapy combined with chemotherapy,or received only chemotherapy.The third case was confirmed by core needle biopsy to be mucosa-associated lymphoid tissue lymphoma,and received radiotherapy.In summary,confirmation of PTL diagnosis is essential for further clinical decisions.Core biopsy should be one of the most important methods to make the diagnosis of PTL,while the use of fine needle aspiration cytology alone is still limited in diagnosing PTL.展开更多
The aim of this investigation was to determine whether a PPAR72 Prol2Ala polymorphism was associated with insulin resistance, β-cellfunction and hypertension in Chinese populations. 289 unrelated Chinese subjects fir...The aim of this investigation was to determine whether a PPAR72 Prol2Ala polymorphism was associated with insulin resistance, β-cellfunction and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes （HbAC1〈6.0） were investigated, including 132 hypertensive diabetic （HTD） subjects, 157 normotensive diabetic （NTD） subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test （OGTT）. Biochemical measurements （high-density lipoprotein （HDL） and low-density lipoprotein-cholesterol （LDL）, triglycerides） and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group （3. 03 %） than in the non-hypertension group （5.7 %） （P〈0.05） after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level （P=0. 0127）, and better glucose tolerance 60 min after oral glucose （P=0. 0361）. Moreover, plasma insulin concentrations at 60 min was lower than those without A variant （P = 0. 0275）, and both hypertensive Ala/Pro in HOMA-β （P ： 0. 0455） and AUC for insulin （P=0. 0473） were higher, and HOMA-IR was lower （P=0. 0375） as compared with hypertensive Pro/Pro subjects. No association was observed between Prol2Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPARγ2 on glucose homeostasis and insulin resistance.展开更多
The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabete...The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus （T2DM）, pregnant physiological insulin resistance （IR） and gestational diabetes mellitus （GDM） was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method. Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol （CHOL）, serum triglycerides （TG）, serum HDL cholesterol （HDL-C） and serum LDL cholesterol （LDL-C） were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index （IRI）. Height, weight, systolic blood pressure （SBP） and diastolic blood pressure （DBP） were measured to calculate body mass index （BMI） and body fat percentage （BF%）. Resistin protein expression in pregnant women placental tissue （67 905±8441） （arbitrary A values） was much higher than that in subcutaneous adipose tissue in pregnant women abdomen （40 718 ± 3818, P〈 0. 01 ）, non-pregnant women abdomen （38 288±2084, P〈0.01）, normal human abdomen （39 421±6087, P〈0.01） and thigh （14 942 ±6706, P〈0.001） respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue （P〈0. 001）. Pearson analysis revealed that resistin protein was correlated with BMI （r=0.42）, fasting insulin concentration （r=0.38）, IRI （r=0.34）, BF% （r=0.43） andfasting glucose （r=0.39）, but not with blood pressure, CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher than that in human thigh subcutaneous adipose tissue. Resistin was closely related with central obesity, leading to IR, subsequently obesity and T2DM. Resistin protein expression in placental tissue was much higher than that in subcutaneous adipose tissue in normal human abdomen, pregnant abdomen, non-pregnant women abdomen and thigh. It was indicated that resistin protein could be secreted from human placental tissue. Resistin might be one of the factors that lead to pregnant physiological IR and GDM.展开更多
In order to explore the expression of erythropoietin receptor （EPOR） in pancreatic cell line NIT-1 and its effect on cell apoptosis after binding with erythropoietin （EPO）, NIT-1 cells were cultured and expanded. ...In order to explore the expression of erythropoietin receptor （EPOR） in pancreatic cell line NIT-1 and its effect on cell apoptosis after binding with erythropoietin （EPO）, NIT-1 cells were cultured and expanded. The expression of EPOR was detected using electrophoresis. NIT-1 apoptosis was induced by cytokines and their effects on cell apoptosis and cell insulin secretion were assayed after binding of EPO to EPOR. The results showed that EPOR was expressed in NIT-1 cells. Recombinant human EPO （rHuEPO） had no effect on cell apoptosis but significantly inhibited apoptosis induced by cytokines, rHuEPO had no effect on cell insulin secretion but significantly improved insulin secretion inhibited by cytokines. From these findings, it was concluded that EPOR was expressed in NIT- 1 cells and EPO could protect NIT- 1 cells from apoptosis induced by cytokines.展开更多
Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(...Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.展开更多
The roles of NF-kappaB （NF-κB） expression, Bax activity and cytochrome C （Cyt C） release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were ...The roles of NF-kappaB （NF-κB） expression, Bax activity and cytochrome C （Cyt C） release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups： G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-rd3 expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in GI, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-κB expression was also increased （P〈0.05）, but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-rd3 expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups （P〈0.05）. It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-κB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-κB expression could be an effective strategy for protecting pancreatic islet cells.展开更多
The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus（T2DM） and pre-diabetes（pre-DM） in the middle-aged rural population in China. A cross-sectional stu...The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus（T2DM） and pre-diabetes（pre-DM） in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test（OGTT） was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases（ALT and GGT）, Hb A1 C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose（IFG）, impaired glucose tolerance（IGT）, impaired fasting glucose combined with impaired glucose tolerance（IFG＋IGT） and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio（WHR）, blood pressure, fasting blood glucose（FBG）, high density lipoprotein-cholesterol（HDL-C）, and liver enzymes（ALT and GGT）. Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance（IR） in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.展开更多
Immunohistochemistry was used to detect tumor necrosis factor (TNF α) expression in arterial wall of diabetic rats. It was found that endothelial cells were swollen and markedly proliferative in these vessels and ac...Immunohistochemistry was used to detect tumor necrosis factor (TNF α) expression in arterial wall of diabetic rats. It was found that endothelial cells were swollen and markedly proliferative in these vessels and accordingly TNF α showed strong positive immunohistochemical reaction in endothelial cells or extracellular intimal matrix of such vessels, which might be caused by the expression and release of TNF α from monocytes and arterial wall cells stimulated by AGEs. These findings suggested that increased TNF α expression might be associated with vascular damage and remodeling in diabetes.展开更多
Summary: In order to investigate the effect of tumor necrosis factor-α (TNFα) on resistin expression in 3T3-L1 adipocytes, and further explore its mechanisms, the differentiated 3T3-L1 adipocytes were incubated with...Summary: In order to investigate the effect of tumor necrosis factor-α (TNFα) on resistin expression in 3T3-L1 adipocytes, and further explore its mechanisms, the differentiated 3T3-L1 adipocytes were incubated with 0, 1, 10, 100 ng/mL TNFα respectively for 24 h, and then the expression of resistin was determined. The differentiated 3T3-L1 adipocytes were incubated with 100 ng/mL TNFα for 3, 6, 24 h respectively, and then the expression of resistin mRNA was analyzed. 3T3-L1 adipocytes were induced to differentiate into mature adipocytes. The cells were randomly divided into 4 groups for culture. In the control group, no drugs were added. Cells of TNFα group were treated with 100 ng/mL TNFα. In Ro-31-8220 group, 5 μmol/L protein kinase C inhibitor Ro-31-8220 was added. With TNFα+Ro-31-8220 group, 100 ng/mL TNFα were added 1 h after the addition of 5 μmol/L Ro-31-8220. All adipocytes were cultured for 24 h. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were employed to detect the expression of resistin gene. Our results showed that resistin protein and mRNA in 3T3-L1 adipocytes were inhibited by TNFα at different concentrations (P<0.01), and the inhibitory effect increased with the concentration (P<0.01). At the same concentrations, the inhibitory effect increased with time (P<0.01). Ro-31-8220 could inhibit its expression and the inhibitive effect remained unchanged with addition of TNFα(P>0.05). It was concluded that TNFα could inhibit the expression of resistin in 3T3-L1 adipocytes. The mechanism may be that the expression of resistin is partly controlled by protein kinase C signal conduction pathway.展开更多
The aim of this study was to assess the effects and safety of salicylates on type 2 diabetes mellitus （T2DM）. We searched six databases （Cochrane Central Register of Controlled Trials, MED- LINE, EMBASE, CBM, CNKI ...The aim of this study was to assess the effects and safety of salicylates on type 2 diabetes mellitus （T2DM）. We searched six databases （Cochrane Central Register of Controlled Trials, MED- LINE, EMBASE, CBM, CNKI and VIP） for all randomized controlled trials （RCTs） and self-control studies which investigated the effects of salicylates on T2DM. We included 34 RCTs and 17 self-control studies involving 13 464 patients with T2DM. It was demonstrated that salicylates had obvious effects on several parameters for patients with T2DM. （1） Any dose of salicylates could significantly reduce HbAIc level [mean difference （MD） -0.39%; 95% C1-0.47 to -0.32] in RCTs, but only high doses of salicylates （〉3000 mg/day） could effectively reduce fasting plasma glucose （FPG） level [standardized mean difference （SMD） -1.05; 95% CI -1.47 to -0.62] for patients with T2DM in both RCTs and self-control studies. Furthermore, high doses of salicylates could also increase plasma fasting insulin level （MD 12.20 mU/L; 95% CI 3.33 to 21.07）; （2） In both RCTs and self-control studies, high doses of salicylates could significantly reduce plasma triglycerides concentration. The results for RCTs were MD -0.44 mmol/L, 95% CI -0.71 to 4）.18, and those for self-control studies were 227±29 mg/dL （pre-treatment） and 117±8 mg/dL （post-treatment） （P=-0.009）; （3） All trials which reported cardiovascu- lar events were RCTs using low doses （〈1000 mg/day） of salicylates, and it was revealed that aspirin could significantly reduce the risk of myocardial infarction （OR 0.73; 95% CI 0.57 to 0.92）; （4） Two RCTs and two self-control studies with 〉3000 mg/day salicylates reported adverse effects, and the over- all effects were mild, and tinnitus occurred most frequently. No evidence of gastrointestinal bleeding was found in all these studies. In conclusion, from our systematic review, the anti-diabetic effect of salicylates is in a dose-dependent manner. High doses of salicylates may have beneficial effects on re- ducing FPG, HbAlc level and increasing fasting insulin concentration, and may also have some positive effects on lipidemia and inflammation-associated parameters for patients with T2DM, without serious adverse effects.展开更多
Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor(P2X7R), which is activated by the abnormal accumulation of extracellular ATP, p...Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor(P2X7R), which is activated by the abnormal accumulation of extracellular ATP, plays an important role in the regulation of oxidative stress in the central nervous system, although the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage remain unclear. Mouse models of intracerebral hemorrhage were established through the stereotactic injection of 0.075 U VII collagenase into the right basal ganglia. The results revealed that P2X7R expression peaked 24 hours after intracerebral hemorrhage, and P2X7R expressed primarily in neurons. The inhibition of P2X7R, using A438079(100 mg/kg, intraperitoneal), reduced nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) expression and malondialdehyde generation, increased superoxide dismutase and glutathione/oxidized glutathione levels, and alleviated neurological damage, brain edema, and apoptosis after intracellular hemorrhage. The P2X7R inhibitor A438079(100 mg/kg, intraperitoneal injection) inhibited the activation of extracellular signal-regulated kinase 1/2(ERK1/2) and nuclear factor kappa-B(NF-κB) after intracerebral hemorrhage. Blocking ERK1/2 activation, using the ERK1/2 inhibitor U0126(2 μg, intraventricular injection), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation after intracellular hemorrhage. Similarly, the inhibition of NF-κB, using the NF-κB inhibitor JSH-23(3.5 μg, intraventricular), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation. Finally, GSK2795039(100 mg/kg, intraperitoneal), a NOX2 antagonist, attenuated P2X7R-mediated oxidative stress, neurological damage, and brain edema after intracerebral hemorrhage. The results indicated that P2X7R activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways following intracerebral hemorrhage in mice. The present study was approved by the Ethics Committee of Huazhong University of Science and Technology, China(approval No. TJ-A20160805) on August 26, 2016.展开更多
Diabetic peripheral neuropathy(DPN)is a common chronic complication of diabetes mellitus.One of the most common types is distal symmetric polyneuropathy,which begins as bilateral symmetry pain and hyperesthesia and gr...Diabetic peripheral neuropathy(DPN)is a common chronic complication of diabetes mellitus.One of the most common types is distal symmetric polyneuropathy,which begins as bilateral symmetry pain and hyperesthesia and gradually progresses into hypoesthesia with nerve fibre disorder and is frequently accompanied by depression and anxiety.Notably,more than half of patients with DPN can be asymptomatic,which tends to delay early detection.Furthermore,the study of adverse outcomes showed that DPN is a prominent risk factor for foot ulceration,gangrene and nontraumatic amputation,which decreases quality of life.Thus,it is essential to develop convenient diagnostic biomarkers with high sensitivity for screening and early intervention.It has been reported that there may be common pathways for microvascular and macrovascular complications of diabetes.The pathogenesis of both disorders involves vascular endothelial dysfunction.Emerging evidence indicates that traditional and novel cardiovascularrelated biomarkers have the potential to characterize patients by subclinical disease status and improve risk prediction.Additionally,beyond traditional cardiovascular-related biomarkers,novel cardiovascular-related biomarkers have been linked to diabetes and its complications.In this review,we evaluate the association between major traditional and nontraditional car-diovascular-related biomarkers of DPN,such as cardiac troponin T,B-type natriuretic peptide,Creactive protein,myeloperoxidase,and homocysteine,and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN.展开更多
Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index（GI） and glycemic load（GL） of a particular pomelo named Majia pomelo and its effects on p...Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index（GI） and glycemic load（GL） of a particular pomelo named Majia pomelo and its effects on postprandial glucose（PPG） in patients with type 2 diabetes（T2D）. Twenty healthy subjects and 20 T2D patients（controlled on lifestyle measures and/or metformin） were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients（controlled on insulin therapy） were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 g Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.展开更多
Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rh...Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH （1-34） in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH （1-34） with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH （1-34） 20 μg （200 U） daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine （L1-4） and femoral neck bone mineral density （BMD）, fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded. Results rhPTH （1-34） increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment （4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P 〈0.01）. There was only a small but significant increase of femoral neck BMD after 18 months （2.6%, P 〈0.01） in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH （1-34） group than those in the elcatonin group after 6, 12, and 18 months （serum bone-specific alkaline phosphatase （BSAP） 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P 〈0.01; urinary C-telopeptide/creatinine （CTX/Cr） 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P 〈0.01）. rhPTH （1-34） showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% （6/112） in elcatonin group and 3.2% （11/341）in rhPTH （1-34）group （P=0.303）. Both treatments were well tolerated. Hypercaluria （9.4%） and hypercalcemia （7.0%） in rhPTH （1-34） group were transient and caused no clinical symptoms. Pruritus （8.2% vs. 2.7%, P=0.044） and redness of injection site （4.4% vs. 0,P=0.024） were more frequent in rhPTH （1-34）. Nausea/vomiting （16.1% vs. 6.2%, P=0.001） and hot flushes （7.1% vs. 0.6%, P 〈0.001） were more common in elcatonin group. Conclusions rhPTH （1-34） was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment, rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH （1-34） is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis. （ChiCTR- TRC-10000924）展开更多
Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） given by injection is a new seventh class drug of biological products, which is prepared by adopting gene recombination technique, rhPTH （1...Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） given by injection is a new seventh class drug of biological products, which is prepared by adopting gene recombination technique, rhPTH （1-34） is mainly used to treat osteoporosis, especially for postmenopausal women. This study compared the clinical efficacy and safety of rhPTH （1-34） with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods Two hundred and five women with osteoporosis were enrolled in a 6-month, multicenter, randomized, controlled study. They were randomized to receive either rhPTH （1-34） 20 ug （200 U） daily or elcatonin 20 U weekly. Lumbar spine （L1-4） and femoral neck bone mineral density （BMD）, as well as biochemical markers of bone turnover were measured. Adverse events were recorded. Results rhPTH （1-34） increased lumbar BMD significantly more than did elcatonin at 3 months and 6 months （2.38% vs 0.59%, P 〈0.05; 5.51% vs 1.55%, P 〈0.01）, but there were no significant increases of BMD in these two groups at femoral neck. There were larger mean increases in bone markers in the rhPTH （1-34） group than in the elcatonin group at 3 months and 6 months （serum bone-specific alkaline phosphatase （BSAP） 36.79% vs 0.31%; 92.42% vs -0.17%; urinary N-telopeptide/creatinine （NTX/Cr） 48.91% vs -5.32%; 68.82% vs -10.86%）. Both treatments were well tolerated and there were no significant differences detected between the two groups in the proportion of any adverse events and any serious adverse events （67.0% vs 59.0%; 0 vs 0）. Conclusions rhPTH （1-34） has more positive effects on bone formation, as shown by the larger increments of lumbar BMD and bone formation markers, than elcatonin, with only mild adverse events and no significant change in the liver, kidney or hematological indices.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81100581)the Bethune Merck Diabetes Research Fund(No.2018)+1 种基金the Fund of the Sichuan Provincial Western Psychiatric Association's CSPC LEADING Scientific Research Project(No.WL2021104)the China International Medical Foundation-Senmei China Diabetes Research Fund(No.Z-2017-26-1902-5).
文摘Objective Diabetic foot ulcer(DFU)is one of the most serious complications of diabetes.Leukocyte-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich plasma.This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice.Methods Patients with DFU who received L-PRF treatment and standard of care(SOC)from 2018 to 2019 in Tongji Hospital were enrolled.The clinical information including patient characteristics,wound evaluation(area,severity,infection,blood supply),SOC of DFU,and images of ulcers was retrospectively extracted and analyzed.L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction(PVR)greater than 80%.Therapeutic effectiveness,including overall PVR and the overall and weekly healing rates,was evaluated.Results Totally,26 patients with DFU were enrolled,and they had an ulcer duration of 47.0(35.0,72.3)days.The severity and infection of ulcers varied,as indicated by the Site,Ischemia,Neuropathy,Bacterial Infection,and Depth(SINBAD)scores of 2–6,Wagner grades of 1–4,and the Perfusion,Extent,Depth,Infection and Sensation(PEDIS)scores of 2–4.The initial ulcer volume before L-PRF treatment was 4.94(1.50,13.83)cm3,and the final ulcer volume was 0.35(0.03,1.76)cm3.The median number of L-PRF doses was 3(2,5).A total of 11 patients achieved complete epithelialization after the fifth week of treatment,and 19 patients achieved at least an 80%volume reduction after the seventh week.The overall wound-healing rate was 1.47(0.63,3.29)cm3/week,and the healing rate was faster in the first 2 weeks than in the remaining weeks.Concurrent treatment did not change the percentage of complete epithelialization or healing rate.Conclusion Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index,SINBAD score,or Wagner grade,indicating that this method is appropriate for DFU treatment under different clinical conditions.
基金supported financially by grants from the National Natural Science Foundation of China(No.81771793).
文摘Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve sheath.Methods This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our hospital.The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection operator.Subsequently,we constructed a prediction model using multivariate logistic regression.The accuracy of the model was verified using receiver operating characteristic curve analysis.Results In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study.Two variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction model.In the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of 0.901.Moreover,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was 0.890.Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.
文摘The expression of c-met stimulated by high glucose in human renal tubular epithelial ceils and the role of HGF/c-met system in diabetic nephropathy were examined. The proximal tubular epithelial cells were cultured in vitro under different conditions. MTT was used for the detection of cellular proliferation and RT-PCR was employed for measurement of c-met mRNA level. Our results showed that under different conditions, there were no significant differences in the proliferation of proximal tubular epithelial cells 12 h and 24 h after the culuture （P〉0.05）. The proliferation of proximal tubular epithelial cells showed a significant change 96 h after the culture and the cellular proliferation induced by hepatocyte growth factor （HGF） was very active （P〈0.05）. Moreover, no significant difference in the expression of c-met mRNA was found 12 h after the culture under different conditions （P〉0.05）, while 24 and 96 h after the culture, a persistent and significantly higher expression of c-met mRNA was found in HGF-induced proliferation. It is concluded that addition of exogenous HGF could inhibit the apoptosis induced by high-level glucose, promote the proliferation of proximal tubular epithelial cells, and induce the expression of c-met. Our study suggests that local up-regulation of HGF/c-met system plays an important role in the repair of renal damage in diabetic nephropathy.
基金Supported by the National Natural Science Foundation of China, No. 30170442
文摘AIM： To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS： According to the body mass index （BMI）, 60 type 2 diabetes patients were divided into two groups, one group was non-obese diabetes patients with BMI 〈 25Kg/M^2 （30 cases） and the other group was obese diabetes patients with BMI 〉25Kg/M^2 （30 cases）. There were 28 healthy persons in the control group. EUSA technique was employed to determine the plasma adiponectin and resistin concentrations. The fasting blood glucose, insulin and blood lipid were detected respectively by electrocheminescence immunoassay and immunoturbidimetric assay. Insulin resistance index and insulin sensitive index were calculated by the homeostasis model assessment （HOMO）. RESULTS： The levels of plasma adiponectin were decreased significantly in diabetes group compared to that in control group （non-obese： 8.58±0.86, obese： 6.22±1.34 vs 10.53±1.47 P〈0.05）; moreover, adiponectin concentration in obese diabetes group was significantly decreased compared to that in non-obese diabetes group （6.22±1.34 vs 8.58±0.86, P〈 0.05）. The levels of plasma resistin were increased significantly in diabetes group compared to that in control group （obese： 18.64 ± 4.65, non-obese： 24.05±9.07 vs 14.16±5.25, P〈0.05,P〈0.05）; furthermore, the levels of resistin in obese diabetes group were increased significantly compared to that in non-obese diabetes group （P〈 0.05）. Plasma adiponectin was correlated negatively with BMI, blood glucose, insulin resistance index and triglyceride （respectively, r=-0.55, P〈0.01; r=-0.51, P〈0.05; r=-0.52, P〈 0.05： r=-0.39, P〈 0.05）, while it was positively correlated with insulin sensitive index （r=0.45, P〈0.05）. Conversely, plasma resistin correlated positively with BMI, blood glucose, triglyceride and insulin resistance index （respectively, r=0.40, P〈 0.05; r= 0.52, P〈0.05; r= 0.46, P〈 0.01; r= 0.27, P〈 0.05）, and negatively correlated with insulin sensitive index （r=-0.32, P〈 0.05）. CONCLUSION： Plasma adiponectin and resistin are associatecl with the disorder of metabolism of glucose and lipid in diabetes. The relationship between these hormone and insulin sensitivity suggests that they may take part in the development of insulin resistance of type 2 diabetes.
文摘Objective To investigate the influence of vitamin D receptor （VDR） gene polymorphisms on susceptibility to type 1 diabetes mellitus （T1DM） in the Chinese Han population. Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamL Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects （ P = 0. 033 ） while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms. Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibihty to T1DM in the Chinese Han population of Beijing.
文摘Primary thyroid lymphoma(PTL)is an exceptionally rare and highly aggressive potentially curable malignant disease.We report three typical cases of PTL referred to our hospital.All three cases had long history of Hashimoto’s thyroiditis,and presented with progressively enlarging neck mass.The first two cases were confirmed by surgical biopsy to be diffuse large B cell lymphoma,and received radiotherapy combined with chemotherapy,or received only chemotherapy.The third case was confirmed by core needle biopsy to be mucosa-associated lymphoid tissue lymphoma,and received radiotherapy.In summary,confirmation of PTL diagnosis is essential for further clinical decisions.Core biopsy should be one of the most important methods to make the diagnosis of PTL,while the use of fine needle aspiration cytology alone is still limited in diagnosing PTL.
文摘The aim of this investigation was to determine whether a PPAR72 Prol2Ala polymorphism was associated with insulin resistance, β-cellfunction and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes （HbAC1〈6.0） were investigated, including 132 hypertensive diabetic （HTD） subjects, 157 normotensive diabetic （NTD） subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test （OGTT）. Biochemical measurements （high-density lipoprotein （HDL） and low-density lipoprotein-cholesterol （LDL）, triglycerides） and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group （3. 03 %） than in the non-hypertension group （5.7 %） （P〈0.05） after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level （P=0. 0127）, and better glucose tolerance 60 min after oral glucose （P=0. 0361）. Moreover, plasma insulin concentrations at 60 min was lower than those without A variant （P = 0. 0275）, and both hypertensive Ala/Pro in HOMA-β （P ： 0. 0455） and AUC for insulin （P=0. 0473） were higher, and HOMA-IR was lower （P=0. 0375） as compared with hypertensive Pro/Pro subjects. No association was observed between Prol2Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPARγ2 on glucose homeostasis and insulin resistance.
文摘The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus （T2DM）, pregnant physiological insulin resistance （IR） and gestational diabetes mellitus （GDM） was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method. Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol （CHOL）, serum triglycerides （TG）, serum HDL cholesterol （HDL-C） and serum LDL cholesterol （LDL-C） were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index （IRI）. Height, weight, systolic blood pressure （SBP） and diastolic blood pressure （DBP） were measured to calculate body mass index （BMI） and body fat percentage （BF%）. Resistin protein expression in pregnant women placental tissue （67 905±8441） （arbitrary A values） was much higher than that in subcutaneous adipose tissue in pregnant women abdomen （40 718 ± 3818, P〈 0. 01 ）, non-pregnant women abdomen （38 288±2084, P〈0.01）, normal human abdomen （39 421±6087, P〈0.01） and thigh （14 942 ±6706, P〈0.001） respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue （P〈0. 001）. Pearson analysis revealed that resistin protein was correlated with BMI （r=0.42）, fasting insulin concentration （r=0.38）, IRI （r=0.34）, BF% （r=0.43） andfasting glucose （r=0.39）, but not with blood pressure, CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher than that in human thigh subcutaneous adipose tissue. Resistin was closely related with central obesity, leading to IR, subsequently obesity and T2DM. Resistin protein expression in placental tissue was much higher than that in subcutaneous adipose tissue in normal human abdomen, pregnant abdomen, non-pregnant women abdomen and thigh. It was indicated that resistin protein could be secreted from human placental tissue. Resistin might be one of the factors that lead to pregnant physiological IR and GDM.
文摘In order to explore the expression of erythropoietin receptor （EPOR） in pancreatic cell line NIT-1 and its effect on cell apoptosis after binding with erythropoietin （EPO）, NIT-1 cells were cultured and expanded. The expression of EPOR was detected using electrophoresis. NIT-1 apoptosis was induced by cytokines and their effects on cell apoptosis and cell insulin secretion were assayed after binding of EPO to EPOR. The results showed that EPOR was expressed in NIT-1 cells. Recombinant human EPO （rHuEPO） had no effect on cell apoptosis but significantly inhibited apoptosis induced by cytokines, rHuEPO had no effect on cell insulin secretion but significantly improved insulin secretion inhibited by cytokines. From these findings, it was concluded that EPOR was expressed in NIT- 1 cells and EPO could protect NIT- 1 cells from apoptosis induced by cytokines.
基金supported by the National Natural Science Foundation of China(No.81100581)the Beijing Bethune Charitable Foundation(No.2021).
文摘Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.
基金supported by the grants from GuangxiSciences foundation(No.0542083)Chunhui Program of theNational Education Ministry(2003)National NaturalSciences Foundation(No.30860116)
文摘The roles of NF-kappaB （NF-κB） expression, Bax activity and cytochrome C （Cyt C） release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups： G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-rd3 expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in GI, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-κB expression was also increased （P〈0.05）, but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-rd3 expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups （P〈0.05）. It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-κB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-κB expression could be an effective strategy for protecting pancreatic islet cells.
基金supported by Chinese Society of Endocrinology,the Key Laboratory for Endocrine and Metabolic Disease of Ministry of Healthy(No.1994DP131044)
文摘The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus（T2DM） and pre-diabetes（pre-DM） in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test（OGTT） was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases（ALT and GGT）, Hb A1 C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose（IFG）, impaired glucose tolerance（IGT）, impaired fasting glucose combined with impaired glucose tolerance（IFG＋IGT） and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio（WHR）, blood pressure, fasting blood glucose（FBG）, high density lipoprotein-cholesterol（HDL-C）, and liver enzymes（ALT and GGT）. Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance（IR） in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.
文摘Immunohistochemistry was used to detect tumor necrosis factor (TNF α) expression in arterial wall of diabetic rats. It was found that endothelial cells were swollen and markedly proliferative in these vessels and accordingly TNF α showed strong positive immunohistochemical reaction in endothelial cells or extracellular intimal matrix of such vessels, which might be caused by the expression and release of TNF α from monocytes and arterial wall cells stimulated by AGEs. These findings suggested that increased TNF α expression might be associated with vascular damage and remodeling in diabetes.
文摘Summary: In order to investigate the effect of tumor necrosis factor-α (TNFα) on resistin expression in 3T3-L1 adipocytes, and further explore its mechanisms, the differentiated 3T3-L1 adipocytes were incubated with 0, 1, 10, 100 ng/mL TNFα respectively for 24 h, and then the expression of resistin was determined. The differentiated 3T3-L1 adipocytes were incubated with 100 ng/mL TNFα for 3, 6, 24 h respectively, and then the expression of resistin mRNA was analyzed. 3T3-L1 adipocytes were induced to differentiate into mature adipocytes. The cells were randomly divided into 4 groups for culture. In the control group, no drugs were added. Cells of TNFα group were treated with 100 ng/mL TNFα. In Ro-31-8220 group, 5 μmol/L protein kinase C inhibitor Ro-31-8220 was added. With TNFα+Ro-31-8220 group, 100 ng/mL TNFα were added 1 h after the addition of 5 μmol/L Ro-31-8220. All adipocytes were cultured for 24 h. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were employed to detect the expression of resistin gene. Our results showed that resistin protein and mRNA in 3T3-L1 adipocytes were inhibited by TNFα at different concentrations (P<0.01), and the inhibitory effect increased with the concentration (P<0.01). At the same concentrations, the inhibitory effect increased with time (P<0.01). Ro-31-8220 could inhibit its expression and the inhibitive effect remained unchanged with addition of TNFα(P>0.05). It was concluded that TNFα could inhibit the expression of resistin in 3T3-L1 adipocytes. The mechanism may be that the expression of resistin is partly controlled by protein kinase C signal conduction pathway.
文摘The aim of this study was to assess the effects and safety of salicylates on type 2 diabetes mellitus （T2DM）. We searched six databases （Cochrane Central Register of Controlled Trials, MED- LINE, EMBASE, CBM, CNKI and VIP） for all randomized controlled trials （RCTs） and self-control studies which investigated the effects of salicylates on T2DM. We included 34 RCTs and 17 self-control studies involving 13 464 patients with T2DM. It was demonstrated that salicylates had obvious effects on several parameters for patients with T2DM. （1） Any dose of salicylates could significantly reduce HbAIc level [mean difference （MD） -0.39%; 95% C1-0.47 to -0.32] in RCTs, but only high doses of salicylates （〉3000 mg/day） could effectively reduce fasting plasma glucose （FPG） level [standardized mean difference （SMD） -1.05; 95% CI -1.47 to -0.62] for patients with T2DM in both RCTs and self-control studies. Furthermore, high doses of salicylates could also increase plasma fasting insulin level （MD 12.20 mU/L; 95% CI 3.33 to 21.07）; （2） In both RCTs and self-control studies, high doses of salicylates could significantly reduce plasma triglycerides concentration. The results for RCTs were MD -0.44 mmol/L, 95% CI -0.71 to 4）.18, and those for self-control studies were 227±29 mg/dL （pre-treatment） and 117±8 mg/dL （post-treatment） （P=-0.009）; （3） All trials which reported cardiovascu- lar events were RCTs using low doses （〈1000 mg/day） of salicylates, and it was revealed that aspirin could significantly reduce the risk of myocardial infarction （OR 0.73; 95% CI 0.57 to 0.92）; （4） Two RCTs and two self-control studies with 〉3000 mg/day salicylates reported adverse effects, and the over- all effects were mild, and tinnitus occurred most frequently. No evidence of gastrointestinal bleeding was found in all these studies. In conclusion, from our systematic review, the anti-diabetic effect of salicylates is in a dose-dependent manner. High doses of salicylates may have beneficial effects on re- ducing FPG, HbAlc level and increasing fasting insulin concentration, and may also have some positive effects on lipidemia and inflammation-associated parameters for patients with T2DM, without serious adverse effects.
基金supported by the National Natural Science Foundation of China,Nos,81471201,81873750the Science and Technology Plan Project of Wuhan of China,No.2018060401011316 (all to ZPT)。
文摘Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor(P2X7R), which is activated by the abnormal accumulation of extracellular ATP, plays an important role in the regulation of oxidative stress in the central nervous system, although the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage remain unclear. Mouse models of intracerebral hemorrhage were established through the stereotactic injection of 0.075 U VII collagenase into the right basal ganglia. The results revealed that P2X7R expression peaked 24 hours after intracerebral hemorrhage, and P2X7R expressed primarily in neurons. The inhibition of P2X7R, using A438079(100 mg/kg, intraperitoneal), reduced nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) expression and malondialdehyde generation, increased superoxide dismutase and glutathione/oxidized glutathione levels, and alleviated neurological damage, brain edema, and apoptosis after intracellular hemorrhage. The P2X7R inhibitor A438079(100 mg/kg, intraperitoneal injection) inhibited the activation of extracellular signal-regulated kinase 1/2(ERK1/2) and nuclear factor kappa-B(NF-κB) after intracerebral hemorrhage. Blocking ERK1/2 activation, using the ERK1/2 inhibitor U0126(2 μg, intraventricular injection), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation after intracellular hemorrhage. Similarly, the inhibition of NF-κB, using the NF-κB inhibitor JSH-23(3.5 μg, intraventricular), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation. Finally, GSK2795039(100 mg/kg, intraperitoneal), a NOX2 antagonist, attenuated P2X7R-mediated oxidative stress, neurological damage, and brain edema after intracerebral hemorrhage. The results indicated that P2X7R activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways following intracerebral hemorrhage in mice. The present study was approved by the Ethics Committee of Huazhong University of Science and Technology, China(approval No. TJ-A20160805) on August 26, 2016.
基金National Natural Science Foundation of China,No.82100922.
文摘Diabetic peripheral neuropathy(DPN)is a common chronic complication of diabetes mellitus.One of the most common types is distal symmetric polyneuropathy,which begins as bilateral symmetry pain and hyperesthesia and gradually progresses into hypoesthesia with nerve fibre disorder and is frequently accompanied by depression and anxiety.Notably,more than half of patients with DPN can be asymptomatic,which tends to delay early detection.Furthermore,the study of adverse outcomes showed that DPN is a prominent risk factor for foot ulceration,gangrene and nontraumatic amputation,which decreases quality of life.Thus,it is essential to develop convenient diagnostic biomarkers with high sensitivity for screening and early intervention.It has been reported that there may be common pathways for microvascular and macrovascular complications of diabetes.The pathogenesis of both disorders involves vascular endothelial dysfunction.Emerging evidence indicates that traditional and novel cardiovascularrelated biomarkers have the potential to characterize patients by subclinical disease status and improve risk prediction.Additionally,beyond traditional cardiovascular-related biomarkers,novel cardiovascular-related biomarkers have been linked to diabetes and its complications.In this review,we evaluate the association between major traditional and nontraditional car-diovascular-related biomarkers of DPN,such as cardiac troponin T,B-type natriuretic peptide,Creactive protein,myeloperoxidase,and homocysteine,and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN.
基金supported by grants from National Natural Science Foundation of China(No.81570740 and No.81100581)the Ministry of Science and Technology of China(No.2011CB100600)+3 种基金the Science and Technology Projects of Wuhan(No.201060938360-04 from the Wuhan Science and Technology Bureau)China International Medical Foundation(CIMF)--Novo Nordisk China Diabetes Yingcai Funding(No.2014)CIMF-Novo Nordisk China β Academy Funding(No.20110059)the Fundamental Research Funds for the Central Universities(No.0118540208)
文摘Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index（GI） and glycemic load（GL） of a particular pomelo named Majia pomelo and its effects on postprandial glucose（PPG） in patients with type 2 diabetes（T2D）. Twenty healthy subjects and 20 T2D patients（controlled on lifestyle measures and/or metformin） were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients（controlled on insulin therapy） were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 g Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.
文摘Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH （1-34） in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH （1-34） with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH （1-34） 20 μg （200 U） daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine （L1-4） and femoral neck bone mineral density （BMD）, fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded. Results rhPTH （1-34） increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment （4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P 〈0.01）. There was only a small but significant increase of femoral neck BMD after 18 months （2.6%, P 〈0.01） in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH （1-34） group than those in the elcatonin group after 6, 12, and 18 months （serum bone-specific alkaline phosphatase （BSAP） 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P 〈0.01; urinary C-telopeptide/creatinine （CTX/Cr） 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P 〈0.01）. rhPTH （1-34） showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% （6/112） in elcatonin group and 3.2% （11/341）in rhPTH （1-34）group （P=0.303）. Both treatments were well tolerated. Hypercaluria （9.4%） and hypercalcemia （7.0%） in rhPTH （1-34） group were transient and caused no clinical symptoms. Pruritus （8.2% vs. 2.7%, P=0.044） and redness of injection site （4.4% vs. 0,P=0.024） were more frequent in rhPTH （1-34）. Nausea/vomiting （16.1% vs. 6.2%, P=0.001） and hot flushes （7.1% vs. 0.6%, P 〈0.001） were more common in elcatonin group. Conclusions rhPTH （1-34） was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment, rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH （1-34） is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis. （ChiCTR- TRC-10000924）
文摘Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） given by injection is a new seventh class drug of biological products, which is prepared by adopting gene recombination technique, rhPTH （1-34） is mainly used to treat osteoporosis, especially for postmenopausal women. This study compared the clinical efficacy and safety of rhPTH （1-34） with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods Two hundred and five women with osteoporosis were enrolled in a 6-month, multicenter, randomized, controlled study. They were randomized to receive either rhPTH （1-34） 20 ug （200 U） daily or elcatonin 20 U weekly. Lumbar spine （L1-4） and femoral neck bone mineral density （BMD）, as well as biochemical markers of bone turnover were measured. Adverse events were recorded. Results rhPTH （1-34） increased lumbar BMD significantly more than did elcatonin at 3 months and 6 months （2.38% vs 0.59%, P 〈0.05; 5.51% vs 1.55%, P 〈0.01）, but there were no significant increases of BMD in these two groups at femoral neck. There were larger mean increases in bone markers in the rhPTH （1-34） group than in the elcatonin group at 3 months and 6 months （serum bone-specific alkaline phosphatase （BSAP） 36.79% vs 0.31%; 92.42% vs -0.17%; urinary N-telopeptide/creatinine （NTX/Cr） 48.91% vs -5.32%; 68.82% vs -10.86%）. Both treatments were well tolerated and there were no significant differences detected between the two groups in the proportion of any adverse events and any serious adverse events （67.0% vs 59.0%; 0 vs 0）. Conclusions rhPTH （1-34） has more positive effects on bone formation, as shown by the larger increments of lumbar BMD and bone formation markers, than elcatonin, with only mild adverse events and no significant change in the liver, kidney or hematological indices.
