糖尿病周围神经病变的中医药研究现状

糖尿病周围神经病变（diabeticperi pheral neuropathy，DPN）是糖尿病的并发症之一，其发病率在有症状者可达50％～70％甚至更高。DPN是糖尿病（diabetes mellitus，DM）患者足溃疡和截肢的危险因素。现将中医药对该病的研究综述如下。     

加味黄芪六一汤治疗糖尿病周围神经病变

糖尿病周围神经病变（DPN）是糖尿病（DM）常见慢性并发症。自2003年1月以来，笔者应用“加味黄芪六一汤”治疗DPN23例，疗效满意，结果报道如下。     

中药配合足浴治疗糖尿病周围神经病变的研究

糖尿病周围神经病变（DPN）是糖尿病（DM）最常见的慢性并发症之一,其发病率占DM患者的60％～90％,如果遇到外伤与感染极易发生溃疡,不易愈合,从而导致截肢,使患者致残,给患者带来严重的生活不便。本研究通过中药益气通脉汤口服与桂枝透骨汤外洗,与弥可保治疗DPN对比观察,临床疗效满意。现报道如下。     

神经妥乐平治疗糖尿病周围神经病变的疗效观察

糖尿病周围神经病变（DPN）是糖尿病（DM）常见的慢性并发症之一,其临床发生率可达47%～91%,病因复杂,治疗困难,是DM患者致残的重要原因,神经妥乐平为牛痘病毒疫苗接种家兔炎病皮肤提取物，通过神经修复、植物神经调节作用改善DPN的临床神经损害的自发痛、麻木感、冷感、热感、下肢痛等感觉障碍。本研究采用神经妥乐平治疗DPN并评估疗效及不良反应。     

中医药治疗糖尿病性视网膜病变的研究进展

糖尿病性视网膜病变是糖尿病的重要并发症之一，属于中医学“视瞻昏渺”、“暴盲”等范畴。糖尿病视网膜病变（diabetic retinopathy，DR）是糖尿病（diabetesmellitus，DM）最为常见和严重的微血管并发症之一。可对患者造成严重的视力损害。近年来，随着DM患者人数的快速增长和寿命的延长，DR的发病率逐步增加，已成为人类最主要的致盲疾病之一，严重影响到糖尿病患者的生存质量。     

2型糖尿病周围神经病变靶向基因与蛋白的初步研究

目的：筛选2型糖尿病周围神经病变（DPN）靶向基因与蛋白,探讨DPN发病机制。方法：利用基因芯片分析2例2型糖尿病伴有DPN患者、2例2型糖尿病不伴周围神经病变（DM）患者以及2例正常对照（CON）外周血单个核细胞基因表达谱的差异;利用蛋白芯片技术比较50例DPN患者、50例DM患者以及15例CON者血清蛋白质谱的差异,寻找DPN可能的致病因子。结果：与DM患者和CON者比较,DPN患者外周血单个核细胞中上调基因4条,     

三酰甘油/高密度脂蛋白胆固醇比值对老年糖尿病患者周围神经病变的预测价值研究

背景　糖尿病周围神经病变（DPN）是老年糖尿病患者常见的慢性并发症之一,严重影响患者的健康。目前针对DPN的发生风险尚无有效的预测手段。有研究发现血清三酰甘油/高密度脂蛋白胆固醇（TG/HDL-C）比值对胰岛素抵抗及心脑血管疾病有一定的预测价值,但关于其与DPN关系的研究较少。目的　探讨TG/HDL-C比值对老年2型糖尿病患者并发DPN的预测价值。方法　选取2018年1月-2019年6月六安市第二人民医院内分泌科收治的老年2型糖尿病患者298例为研究对象,未并发DPN患者150例（对照组）,并发DPN患者148例（DPN组）,比较两组研究对象性别、年龄、糖尿病（DM）病程、DPN病程、高血压史、吸烟史、饮酒史、腰围、收缩压（SBP）、舒张压（DBP）、空腹血糖（FPG）、糖化血红蛋白（HbA1c）、C肽（C-P）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、肌酐（Cr）、尿酸（UA）、胱抑素C（Cys-C）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、TG/HDL-C比值等指标,采用多因素Logistic回归分析探讨老年糖尿病患者并发DPN的影响因素,采用受试者工作特征（ROC）曲线分析TG/HDL-C比值对老年糖尿病患者并发DPN的预测价值。结果　对照组与DPN组患者性别、年龄、DM病程、DPN病程、高血压史、饮酒史、DBP、FPG、HbA1c、C-P、TC、HDL-C、LDL-C、Cr、UA、Cys-C、ALT、AST比较,差异无统计学意义（P>0.05）;DPN组患者有吸烟史占比、腰围、SBP、TG、TG/HDL-C比值高于对照组,差异有统计学意义（P<0.05）。多因素Logistic回归分析结果显示：有吸烟史和TG/HDL-C比值高是T2DM患者并发DPN的危险因素（P<0.05）。以TG/HDL-C比值为诊断变量绘制ROC曲线,结果显示AUC为0.627〔95%CI（0.563,0.690）,P<0.001〕,诊断的最佳切点值为3.7,此时的灵敏度为34.5%,特异度为93.3%。结论　TG/HDL-C比值高的老年糖尿病患者可能更易发生DPN,TG/HDL-C比值检测有望用于临床上老年糖尿病患者并发DPN的风险评估和预测。     

甲状腺激素及抗体表达水平与糖尿病周围神经病变的相关性分析

目的 探讨甲状腺激素及抗体表达水平与糖尿病周围神经病变（diabetic peripheral neuropathy,DPN）的相关性。方法 选取2021年1月至2022年2月绍兴市人民医院肌电图室就诊的糖尿病患者186例,按照合并DPN的情况分为DPN组（n=68）和non-DPN组（n=118）。比较两组患者的身高、体质量、体质量指数（body mass index,BMI）、糖化血红蛋白（glycosylated hemoglobin,HbA1c）、游离三碘甲状腺原氨酸（free triiodothyronine,FT3）、游离甲状腺素（free thyroxine,FT4）、促甲状腺激素（thyroid-stimulating hormone,TSH）、甲状腺球蛋白抗体（thyroglobulin antibody,TGAb）、甲状腺过氧化物酶抗体（thyroid peroxidase autoantibody,TPOAb）,以及患者的年龄、糖尿病病程、糖尿病慢性并发症情况。结果 与NDPN组比较,DPN组患者年龄更大、DM病程更长,高血压患病率、糖尿病慢性并发症比例更高,FT3水平更低,差异均有统计学意义(P<0.05)。Spearman相关性分析显示,患者年龄、糖尿病病程、高血压及糖尿病慢性并发症与DPN呈正相关（P<0.05）,FT3与DPN呈负相关（P<0.05）。Logistic回归分析结果显示,糖尿病病程、FT3是DPN的影响因素（P<0.05）。结论 糖尿病患者积极监测FT3的变化或可为DPN的预测提供参考,积极控制甲状腺疾病,使甲状腺功能恢复正常,这或许能够保护周围神经,延缓糖尿病周围神经病变的发生和发展。     

超声引导下设置骨科下肢手术止血带压力值的应用效果探讨

目的 探讨甲状腺激素及抗体表达水平与糖尿病周围神经病变（diabetic peripheral neuropathy,DPN）的相关性。方法 选取2021年1月至2022年2月绍兴市人民医院肌电图室就诊的糖尿病患者186例,按照合并DPN的情况分为DPN组（n=68）和non-DPN组（n=118）。比较两组患者的身高、体质量、体质量指数（body mass index,BMI）、糖化血红蛋白（glycosylated hemoglobin,HbA1c）、游离三碘甲状腺原氨酸（free triiodothyronine,FT3）、游离甲状腺素（free thyroxine,FT4）、促甲状腺激素（thyroid-stimulating hormone,TSH）、甲状腺球蛋白抗体（thyroglobulin antibody,TGAb）、甲状腺过氧化物酶抗体（thyroid peroxidase autoantibody,TPOAb）,以及患者的年龄、糖尿病病程、糖尿病慢性并发症情况。结果 与NDPN组比较,DPN组患者年龄更大、DM病程更长,高血压患病率、糖尿病慢性并发症比例更高,FT3水平更低,差异均有统计学意义(P<0.05)。Spearman相关性分析显示,患者年龄、糖尿病病程、高血压及糖尿病慢性并发症与DPN呈正相关（P<0.05）,FT3与DPN呈负相关（P<0.05）。Logistic回归分析结果显示,糖尿病病程、FT3是DPN的影响因素（P<0.05）。结论 糖尿病患者积极监测FT3的变化或可为DPN的预测提供参考,积极控制甲状腺疾病,使甲状腺功能恢复正常,这或许能够保护周围神经,延缓糖尿病周围神经病变的发生和发展。     

2 型糖尿病患者血清Betatrophin 与周围神经病变的关系

目的 探讨2 型糖尿病（T2DM）患者血清Betatrophin 水平与周围神经病变的关系。方法 选 取2016 年1 月—2016 年11 月在长沙市第一医院就诊的88 例T2DM 患者的临床资料,根据临床症状、体征及 电生理检查,将患者分为58 例糖尿病周围神经病变（DPN）组和30 例未合并DPN（NDPN）组。采用ELISA 法检测血清Betatrophin 水平;分别对两组血压、血糖、糖化血红蛋白、血脂及Betatrophin 等指标进行比较分析, 并对DPN 危险因素行Logistic 回归分析。结果 两组糖尿病病程、血清Betatrophin 水平有差异（P <0.05）。 Logistic 回归分析显示,糖尿病病程、血清Betatrophin 水平是T2DM 患者合并DPN 的独立危险因素（P <0.05）。 结论 T2DM 患者血清Betatrophin 水平与DPN 发生关系密切。     

The role of central nervous system on hypoglycemia and the feasibility of the brain theory in traditional Chinese medicine on treatment of diabetes mellitus

The central nervous system （CNS） plays a key regulatory role in glucose homeostasis. In particular, the brain is important in initiating and coordinating protective counterregulatory responses when blood glucose levels fall. This may due to the metabolic dependency of the CNS on glucose, and protection of food supply to the brain. In healthy subjects, blood glucose is normally maintained within a relatively narrow range. Hypoglycemia in diabetic patients can increase the risk of complications, such as heart disease and diabetic peripheral neuropathy. The clinical research finds that the use of traditional Chinese medicine （TCM） has a positive effect on the treatment of hypoglycemia. Here the authors reviewed the current understanding of sensing and counterregulatory responses to hypoglycemia, and discuss combining traditional Chinese and Western medicine and the theory of iatrogenic hypoglycemia in diabetes treatment. Furthermore, the authors clarify the feasibility of treating hypoglycemia on the basis of TCM theory and CNS and have an insight on its clinical practice.     

Chromium-containing traditional Chinese medicine,Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTPIB and PCK2 in diabetic rats

OBJECTIVE： Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of-13anmai Xiaoke （TMXK） Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action. METHODS： Diabetes was induced in rats by feeding a high-fat diet and subcutaneously injection with a single dose of streptozotocin （50 mg/kg, tail vein）. One week after streptozotocin-injection, model rats were divided into diabetic group, low dose of TMXK group and high dose of TMXK group. Eight normal rats were used as normal control. After 8 weeks of treatment, skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array and quantitative polymerase chain reaction （qPCR）. Fasting blood glucose, oral glucose tolerance test and homeostasis model assessment of insulin resistance （HOMA-IR） index were also measured. RESULTS： The authors found that the administration of TMXK Tablet can reduce the fasting blood glucose and fasting insulin level and HOMA-IR index. The authors also found that 2 223 genes from skeletal muscle of the high-dose TMXK group had significant changes in expression （1 752 increased, 471 decreased）. Based on Kyoto encyclopedia of genes and genomes pathway analysis, the most three significant pathways were ＂insulin signaling pathway＂, ＂glycolysis/ gluconeogenesis＂ and ＂citrate cycle （-ICA）＂. qPCR showed that relative levels of forkhead box 03 （Fox03）, phosphoenolpyruvate carboxykinase 2 （Pck2）, and protein tyrosine phosphatase 1B （Ptplb） were significantly decreased in the high-dose TMXK group, while v-akt murine thymoma viral oncogene homolog 1 （Aktl） and insulin receptor substrate 2 （Its2） were increased. CONCLUSION： Our data show that TMXK Tablet reduces fasting glucose level and improves insulin resistance in diabetic rats. The mechanism may be linked to the inactivation of PTP1B and PCK enzymes, or through intracellular pathways, such as the insulin signaling pathway.     

Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus

Summary： The relationship between tyrosine phosphorylation （TP） and protein expression of insulin receptor （InsR） and insulin resistance （IR） in patients with gestational diabetes mellitus （GDM） was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM （GDM group, n=22）, normal pregnant women （normal pregnancy group, n=22） and normal non-pregnant women （normal non-pregnant group, n=13）. Fasting plasma glucose （FPG） and fasting insulin （FINS） were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG （5.61±0.78 mmol/L）, FINS （15.42±5.13 mU/L） and Ho- meostasis model assessment-IR （HOMA-IR） （1.21±0.52） in GDM group were significantly higher than those in normal pregnancy group （4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively） （P〈0.01）. The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal non-pregnant group （7.56±2.31 mU/L and 0.47±0.26 respectively） （P〈0.01）. There was no significant difference in the InsR expression level among the three groups （P〉0.05）. TP of InsR with insulin stimulation was significantly decreased in GDM group （0.20±0.05） as compared with normal pregnancy group （0.26±0.06） （P〈0.01）. TP of InsR with insulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group （0.31±0.06） （P〈0.01）. TP of InsR with insulin stimu- lation was negatively related with HOMA-IR in GDM group （r=-0.525, P〈0.01）. There was no correlation between the protein expression of InsR and HOMA-IR in GDM group （r=-0.236, P〉0.05）. It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.     

Protective effect of diosmin against diabetic neuropathy in experimental rats

OBJECTIVE： The present study was undertaken to evaluate the effect of diosmin in diabetic neuropathy in type 2 diabetic rats. METHODS： Type 2 diabetes was induced in male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin （35 mg/kg） and high-fat diet. Four weeks after the confirmation of diabetes, diabetic rats were treated with diosmin （50 and 100 mg/kg, p.o.） for next 4 weeks. Rats were evaluated for biochemical, behavioral and oxidative stress parameters. Eddy＇s hot plate and tail immersion test were performed on 6th, 7th, 8th, 9th and 10th weeks of experiment to assess thermal hyperalgesia and cold allodynia respectively. Further, the walking function test was performed for assessing the motor responses at the end of the treatment schedule. RESULTS： Rats were fed with high-fat diet throughout the experiment schedule and administration of low-dose streptozotocin induced significant elevation in blood glucose level and insulin resistance which was confirmed by oral glucose tolerance test. Treatment with diosmin at doses of 50 and 100 mg/kg significantly restored the reduced body weight, elevated blood sugar and lipid profiles. Further the dose-dependent improvement was observed in thermal hyperalgesia, cold allodynia and walking function in diabetic rats treated with diosmin. Elevated levels of malondialdehyde, and nitric oxide and decreased glutathione levels and superoxide dismutase activity in diabetic rats were restored significantly after the 4 weeks of diosmin treatment. CONCLUSION： Diosmin has shown beneficial effect in preventing the progression of early diabetic neuropathy in rats.     

Preparation of PLLA/bpV（pic） Microspheres and Their Effect on Nerve Cells

In this study, we prepared PLLA/bpV（pic） microspheres, a bpV（pic） controlled release system and examined their ability to protect nerve cells and promote axonal growth. PLLA microspheres were prepared by employing the o/w single emulsification-evaporation technique. Neural stem cells and dorsal root ganglia were divided into 3 groups in terms of the treatment they received： a routine medium group（cultured in DMEM）, a PLLA microsphere group（DMEM containing PLLA microspheres alone） and a PLLA/bpV（pic） group [DMEM containing PLLA/bpV（pic） microspheres]. The effects of PLLA/bpV（pic） microspheres were evaluated by the live-dead test and measurement of axonal length. Our results showed that PLLA/bpV（pic） granulation rate was（88.2±5.6）%; particle size was（16.8±3.1）%, drug loading was（4.05±0.3）%; encapsulation efficiency was（48.5±1.8）%. The release time lasted for 30 days. In PLLA/bpV（pic） microsphere group, the cell survival rate was（95.2 ±4.77）%, and the length of dorsal root ganglion（DRG） was 718±95 μm, which were all significantly greater than those in ordinary routine medium group and PLLA microsphere group. This preliminary test results showed the PLLA/bpV（pic） microspheres were successfully prepared and they could promote the survival and growth of neural cells in DRG.     

The percentage of peripheral blood blasts on day 7 of induction chemotherapy predicts response to therapy and survival in patients with acute myeloid leukemia

Background Rapid clearance of peripheral blood blasts （PBBs） predicts complete remission （CR） and survival in patients with acute myeloid leukemia （AML）.We aimed to explore the correlation between induction therapy response,outcome,and the PBB percentage.Methods Forty-six consecutive patients with de novo AML （excluding acute promyelocytic leukemia） were enrolled in this study.Flow cytometry was performed to identify cells with a leukemia-associated aberrant immunophenotype in the initial bone marrow aspirate and in peripheral blood on day 7 of induction therapy.Results The PBB percentage on day 7 （D7PBBP） was significantly lower in patients who achieved CR （0.03% （0.0%,0.45%）） than in those who did not （10.85% （1.13%,19.38%）; u =-3.92,P 〈0.001）.The CR rate was significantly higher among patients with a D7PBBP of 〈0.945% （84.62%,22/26） than among those with a D7PBBP of 〉0.945% （25.0%,5/20;Х^2 =16.571,P 〈0.001）.D7PBBP was significantly correlated with overall survival （OS; r=-0.437,P=0.003） and relapsefree survival （RFS; r=-0.388,P=0.007）.OS and RFS were significantly higher in patients with a D7PBBP of 〈0.43% than in those with a D7PBBP of 〉0.43% （P 〈0.001 and P=0.039,respectively）.D7PBBP was also found to be an independent prognostic indicator in multivariate analysis for both OS （P=-0.036） and RFS （P=0.035）.Conclusion D7PBBP may be an important risk factor for the achievement of complete remission,for overall survival,and for relapse-free survival.     

Detection of cytokine expression patterns in the peripheral blood of patients with acute leukemia by antibody microarray analysis

The cytokines of acute leukemia （AL） patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission （CR） for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia （AML） and acute lymphoblastic leukemia （ALL）. In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.     

Gliquidone versus metformin: differential effects on aorta in streptozotocin induced diabetic rats

Background Diabetic cardiovascular complication is a major cause of mortality in type 2 diabetic patients.Hyperglycemia markedly increases the risk of cardiovascular disease.Endothelial dysfunction is common in type 2 diabetes mellitus （DM） and is an early indicator of diabetic vascular disease.Therefore,it is necessary to identify the effect of different hypoglycemic agents on vascular endothelium.The aim of the study was to examine and compare the effects of metformin and gliquidone on atherosclerotic lesions in streptozotocin-induced diabetic rats.Methods Forty male Sprague-Dawley rats （age,8 weeks; weight,180-200 g） were included in this study and fed with a normal chow diet for 1 week.Rats （n=10） served as the normal control group （NC group） were fed with a normal chow for another 2 weeks and received an injection of saline.The rest 30 rats fed with a high-fat diet for 2 weeks and injected streptozotocin were randomly assigned to three groups （n=10 rats per group） as follow：type 2 DM group （DM group）,DM ＋ gliquidone group （GLI group） and DM ＋ metformin group （MET group）.Five weeks later,all rats were fasted overnight and taken tail blood samples for biochemical determinations.Then rats in the NC and DM groups were administrated with normal saline,while rats in the MET and GLI groups were administrated with metformin （100 mg/kg） or gliquidone （10 mg/kg）,respectively.All medicines were given via intragastric administration for 8 weeks.After 16 weeks,plasma triglyceride （TG）,total cholesterol （TC）,low density lipoprotein cholesterol （LDL-C）,high density lipoprotein cholesterol （HDL-C） were measured.The aortic arch was isolated from diabetic rats and was assessed by pathological sectioning using H＆E staining.Results Metformin treatment prevented weight gain （（315.80±52.16） g vs.（318.70±68.48） g,P=0.773）,improved plasma TG,HDL-C and LDL-C levels （P=0.006,0.003,0.001,respectively,all P ＜0.05）.However,gliquidone showed no significant effects on plasma TG and TC levels （P=0.819,0.053,respectively）.LDL-C and HDL-C in the GLI group changed （（0.46±0.10） mmol/L vs.（0.36±0.14） mmol/L,P=0.007; （0.99±0.27） mmol/L vs.（1.11±0.18） mmol/L,P=0.049）.Both metformin and gliquidone treatment lowered blood glucose levels （P=0.001,0.004,respectively,P ＜0.05）.Under light microscopy,no changes were observed in the aortic wall structure of each layer; the intima was smooth and the membrane elastic fibers were normal in the NC group.In the DM group,the aortic wall structure was unclear,the intima was thickened with irregular intima,and membrane elastic fibers collapsed.The aortic intima in the MET and GLI groups was smoother compared with the DM group,but the endothelial structure of the MET group was closer to that of the NC group.Conclusions Both metformin and gliquidone have anti-atherosclerotic effects.But the endothelial structure of the MET group was closer to that of the NC group.Metformin and gliquidone therapy can reduce serum level of LDL-C and increase level of HDL-C,whereas gliquidone therapy did not lose weight and decrease serum level of TG.These data may have important implications for the treatment of patients with type 2 DM.     

Role of Sclerostin in the Bone Loss of Postmenopausal Chinese Women with Type 2 Diabetes

Objective To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes me｜litus. Methods The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion.