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.     

Metformin ameliorates insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3

Background SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear. Methods The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 pmol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells （NF-KB） p65, c-Jun N-terminal kinase 1 （JNK1）, and superoxide dismutase 2 （SOD2） were evaluated by Western blotting. Results Over expression of SIRT3 increased glucose uptake and decreased ROS production in L6-1R cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6- IR cells, and these effects were reversed by N-acetyI-L-cysteine （NAC）. Metformin increased the expression of SIRT3 （1.5- fold） and SOD2 （2-fold） while down regulating NF-KB p65 （1.5-fold） and JNK1 （1.5-fold）. Knockdown of SIRT3 （P〈0.05） reversed the metformin-induced decreases in NF-KB p65 and JNK1 and the metformin-induced increase in SOD2 （P〈0.05）. Conclusions Upregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.     

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.     

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.     

Biphasic insulin aspart 30 improved glycemic control in Chinese patients with type 2 diabetes poorly controlled on oral glucose-lowering drugs: a subgroup analysis of the A1chieve study

Background The effectiveness and safety of initiating biphasic insulin aspart 30 in patients who were poorly controlled on oral glucose-lowering drugs were studied in randomized controlled trials,while results from clinical practice remain limited.This subgroup analysis was to provide such findings from a large-scale non-interventional study.Methods A1chieve was a multinational,prospective,open-label,non-interventional,24-week study in patients with type 2 diabetes initiating insulin analogues in 28 countries across Asia,Africa,Europe,and Latin America.After physician had taken the decision to use this insulin,any patient with type 2 diabetes who was not treated with or who had started the study insulin within 4 weeks before inclusion was eligible.Patients were treated with study insulin alone or in combination with oral glucose-lowering drugs.Data on adverse drug reactions,hypoglycemia and glycemic control were collected at baseline,week 12 and 24.This is a report of a Chinese subgroup analysis from the A1chieve study.Results Totally,4 100 patients constituted this subgroup.No serious adverse drug reactions were reported.Rates of total,major,nocturnal hypoglycemic events （events/patient per year） were 1.47,0.10,0.31 at baseline and 1.35,0.00,0.22 at week 24,respectively.Glycemic control was improved as measured by hemoglobin A1c （mean 9.3％ to 7.0％,reduction -2.3％）,fasting plasma glucose （mean 10.2 to 6.8 mmol/L,reduction-3.5 mmol/L） and postprandial plasma glucose （mean 14.4 to 8.8 mmol/L,reduction-5.6 mmol/L）,all P ＜0.001.Change in mean body weight was ＋0.3 kg （P ＜0.001）.Conclusion In this subgroup analysis of the A1chieve study,biphasic insulin aspart 30 improved glycemic control with low risk of hypoglycemia.     

强化胰岛素治疗对颅脑术后患者预后影响

目的探讨强化胰岛素治疗对颅脑损伤术后患者炎性因子及预后的影响。方法选取我院2010年．2012年收治颅脑损伤手术治疗患者50例,按照其治疗方式分为观察组和对照组,各25例,对照组患者采用常规治疗,维持血糖水平在6．1～8．3mmol／L,观察组患者应用胰岛素强化治疗,维持血糖水平在4．4-6．1mmol／L,术后1、2、3、7、14d测定患者外周血白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、肿瘤坏死因子（TNF-α）含量变化;术后4周、12个月对患者进行近期、远期疗效评价,近期疗效观察指标：神经功能缺损程度、Fugl-Meyer进行肢体运动能力评价、Baethel指数对日常生活能力进行评价;远期疗效观察指标：GOS评分、格拉斯哥昏迷评分（GCS）、患者生活质量自评。结果对照组患者术后第1d,IL-6、IL-8、TNF-α含量显著升高,第3d降至最低,观察组观察指标与对照组同时相比显著降低,比较差异有统计学意义（P〈0．05）;观察组患者术后4N神经功能缺损评分、Barthel评分、Fugl-Meyer评分均优于对照组,比较差异有统计学意义（P〈0．05）;观察组患者术后12个月GCS评分、GOS评分、自评分均优于对照组,比较差异有统计学意义（P〈0．05）。结论胰岛素强化治疗颅脑损伤术后患者,能减轻患者炎症反应,有利于促进神经功能的恢复,改善预后,疗效满意,值得推广c     

Assessment of the number and function of macrophages in the placenta of gestational diabetes mellitus patients

In order to assess the number and function of macrophages in the placenta of pregnancy complicated with gestational diabetes mellitus （GDM） as well as those of normal pregnancies, placenta samples were collected from 15 GDM patients （GDM group） and 10 normal pregnant women （control group）. The expression levels of macrophage markers （CD68/CD14） and inflammatory cytokines （IL-6/TNF-α） in placenta were detected using immunohistochemistry and PCR. The results showed that the number of CD68＋ or CD14＋ cells in the GMD group was remarkably higher than that in the control group （P〈0.05）, indicating that the number of macrophages in the GDM group was significantly greater than that in the control group. The mRNA expression levels of CD68＋, IL-6 and TNF-α were higher in the GMD group than in the control group. In conclusion, more macrophages accumulate in placenta of pregnancy complicated with GDM, and the expression levels of pro-inflammation factors are also in- creased in GDM pregnancies, suggesting that macrophages and inflammatory mediators （IL-6 and TNF-α） mav olav an imoortant role in GDM.     

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.     

Association between intervertebral disc degeneration and disturbances of blood supply to the vertebrae

Low back pain is a common public health problem in western industrialized societies and the world as well.Studies indicate that the prevalence rate ranges to 35%, with around 10% of patients from 12% becoming chronically disabled. It also places an enormous economic burden on society. Although the exact cause of low back pain has yet to be defined, intervertebral disc degeneration is considered a major source of it. Since patients with degenerative discs are often asymptomatic, the mechanisms of it are still unclear.     

Triglycerides and ratio of triglycerides to high-density lipoprotein cholesterol are better than liver enzymes to identify insulin resistance in urban middle-aged and older non-obese Chinese without diabetes

Background Insulin resistance （IR） plays an important pathophysiological role in the development of diabetes,dyslipidemia,hypertension,and cardiovascular disease.Moreover,IR can occur even in non-obese people without diabetes.However,direct detection of IR is complicated.In order to find a simple surrogate marker of IR early in nonobese people,we investigate the association of commonly-used biochemical markers （liver enzymes and lipid profiles） with IR in urban middle-aged and older non-obese Chinese without diabetes.Methods This cross-sectional study included 1 987 subjects （1 473 women）.Fasting blood samples were collected for measurement of glucose,insulin,liver enzymes,lipid profiles and creatinine.Subjects whose homeostasis model of assessment-IR （HOMA-IR） index values exceeded the 75th percentile （2.67 for women and 2.48 for men） of the population were considered to have IR.The area under the receiver operating characteristic curve （ROC） was used to compare the power of potential markers in identifying IR.Results Triglycerides （TG） and ratio of TG to high-density lipoprotein cholesterol （TG/HDL-C） discriminated IR better than other indexes for both sexes; areas under the receiver operating characteristic （ROC） curves （AUC） values were 0.770 （95％ confidence interval 0.733-0.807） and 0.772 （0.736-0.809）,respectively,for women and 0.754 （0.664-0.844）and 0.756 （0.672-0.840）,respectively,for men.To identify IR,the optimal cut-offs for TG and TG/HDL-C ratio were 1.315 mmol/L （sensitivity 74.3％,specificity 71.0％） and 0.873 （sensitivity 70.1％,specificity 73.4％）,respectively,for women,and 1.275 mmol/L （sensitivity 66.7％,specificity 74.4％） and 0.812 （sensitivity 75.8％,specificity 69.2％）,respectively,for men.Conclusion TG and TG/HDL-C ratio could be used to identify IR in urban middle-aged and older non-obese Chinese without diabetes.     

痘苗病毒天坛株的减毒与其作为疫苗载体研究进展

1痘苗病毒天坛株的历史天花是人类历史上最可怕的传染病之一。天花由天花病毒（variola virus）引起,人是该病毒的惟一宿主。人感染天花病毒后的死亡率达到30%~40%[1]。世界上公认的对天花最早的准确记录来自中国,晋代药学家葛洪于公元430年左右,在《肘后备急方》中对天花有清楚的描述[1]。     

针刺透穴法对糖尿病周围神经病变神经传导速度的影响：随机对照试验

糖尿病周围神经病变（diabetic peripheral neuropathy,DPN）是糖尿病最常见的慢性并发症和主要的致残因素之一。患者常表现为肢体感觉异常,伴麻木、针刺、灼热或如踏棉垫感,有时伴有痛觉过敏,后期出现肌力减弱以至肌肉萎软和瘫痪,严重影响糖尿病（diabetes mellitus,DM）患者的身心健康和生活质量。国内一项流行病学调查显示DPN占DM所有并发症的16．44％。中医将其归属于消渴病合并“痹证”、“痛证”、“痿证”范畴。目前对于DPN尚无特异性治疗方法,针刺是临床采用的手段之一,本研究探讨了针刺透穴法对DPN神经传导速度的影响。     

Saffron （Crocus sativus L.） and major depressive disorder： a meta-analysis of randomized clinical trials

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder （MDD）. Of these, accumulating trials reveal positive effects of the spice saffron （Crocus sativus L.） for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE： The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY： We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA： The criteria for study selection included the following： （1） adults （aged 18 and older） with symptoms of depression, （2） randomized controlled trial, （3） effects of saffron supplementation on depressive symptoms examined, and （4） study had either a placebo control or antidepressant comparison group. DATA EXTRACTION AND ANALYSIS： Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta- analysis 2 was used to analyze the data. RESULTS： Based on our pre-specified criteria, five randomized controlled trials （n = 2 placebo controlled trials, n = 3 antidepressant controlled trials） were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms （M ES = 1.62, P 〈 0.001）, revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups （M ES = -0.15） indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials. CONCLUSION： Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron＇s efficacy and safety for treating depressive symptoms.     

Gene expression profiles of ERCC1, TYMS, RRM1, TUBB3 and EGFR in tumor tissue from non-small cell lung cancer patients

Background Personalized medicine becomes essential in lung cancer treatment, however lung-cancer-related gene expression profiles in Chinese patients remain unknown. In this study, the correlation of gene expression profiles and clinical characteristics in non-small-cell lung cancer （NSCLC） was investigated. Methods Seventy-six Chinese patients with NSCLC were enrolled in the study to investigate mRNA expression profiles of excision repair cross complement group 1 （ERCC1）, thymidylate synthetase （TYMS）, ribonucleotide reductase （RRM1）, class Ill 13-tubulin （TUBB3）, and epidermal growth factor receptor （EGFR） genes and their correlation with patient clinical characteristics. A novel liquidchip technology was used to detect mRNA expression levels in formalin fixed paraffin embedded tumor pathology samples. The relationships between gene expression and clinical characteristics were assessed using the Mann-Whitney test. Results ERCC1 mRNA levels were higher in tumors from patients with metastatic disease than patients with non- metastatic disease （P=-0.021）, and higher in adenocarcinomas than squamous cell carcinomas （P=0.006）. Increased TUBB3 mRNA expression levels were found in patients with performance status （PS） 1 in comparison with PS 0 （P=0.049）, with poorly differentiated tumors in comparison with tumors that were moderately and well differentiated （P 〈0.000 1）, and with advanced stage in comparison with early stage disease （P 〈0.000 1）. Conclusions ERCC1 mRNA levels were higher in metastatic adenocarcinoma NSCLC; TUBB3 mRNA levels were significantly higher in poorly differentiated tumors and in advanced stage NSCLC, which indicates the poor prognosis.     

WHO西太区与世界中医药学会联合会中医名词术语国际标准比较研究：八纲辨证（三）

The Chinese characters 寒 and 热, 虚, and 实 are quite common concepts in Chinese language. However in traditional Chinese medicine （TCM）, they are used as four principles in syndrome differentiation. In terms of translation, 寒 and 热 are very easy to understand and can be simply translated as ＂cold＂ and ＂heat＂. But the transla- tion of 虚 and 实 used to be a problem. For a quite long time in translation practice,     

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.