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.     

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.     

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。     

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.     

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.     

Antiviral therapy for ＂difficult-to-treat＂ hepatitis C virus-infected patients

Objective To review the updated research on direct antiviral agents （DAAs）-including regimens for hepatitis C virus （HCV）,and focus on ＂difficult-to-treat＂ HCV-infected patients.Data sources The literature concerning DAAs and hepatitis C cited in this review was collected from PubMed and Google Scholar databases published in English up to July 2013.Study selection Data from published articles regarding HCV and DAAs in clinical trials and in clinical use were identified and reviewed.Results It was recognized that some ＂difficult-to-treat＂ patients would still exist,even though stronger treatments using such as DAAs,including telaprevir and boceprevir,which lead to higher sustained virological response rates,are available.Such patients include those with advanced fibrosis/cirrhosis,elderly persons,children,HCV-human immunodeficiency virus co-infected patients,HCV-infected recipients,and so on.Conclusions Certain ＂difficult-to-treat＂ patients would still exist,even though stronger treatment is available.Although evidence from clinical trials is still lacking,interferon-sparing regimens could have stronger effects for eradicating HCV in such cases.     

Prevalence of Abnormity of Blood Lipid and Associated Factors in Health Examination Population in Beijing

Objective To investigate the prevalence of abnormity of blood lipid and associated factors in healthy population in Beijing. Methods Totally, 38462 individuals who received health examination were enrolled in our study. We divided them into eight groups according to their ages. The levels of serum total cholesterol, triglyceride, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were tested, and the relationship of blood lipid abnormity with body mass index （BMI） and fasting blood glucose was analyzed. Results The incidences of hypercholesterolemia, hyperglyceridemia, low high-density lipoprotein cholesterolemia, and hyper low-density lipoprotein cholesterolemia presented increasing trend in this population. The incidence rate of abnormity of blood lipid in health examination population increased with BMI increase. The incidence of abnormity of blood lipid in overweight and obesity population was significantly higher than that in low weight and normal weight populations （P〈0.05）. Meanwhile, the trend of abnormal blood lipid incidence coincided with that of abnormal fasting blood glucose. Conclusions The prevalence of overweight, obesity, and abnormity of blood lipid in Beijing presents increasing trend. The incidence of abnormity of blood lipid increases with BMI increase, in coincidence with that of fasting blood glucose.     

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.     

Evaluation of Carotid Plaque Neovascularization in Patients with Diabetes Mellitus by Contrast-enhanced Ultrasonography简

This study investigated the relationship between carotid plaque neovascularization and diabetes mellitus（DM） by using contrast-enhanced ultrasonography. Contrast-enhanced ultrasonography was performed in 104 patients with carotid plaque thicker than 2.0 mm. There were 36 patients with DM and 68 patients without DM. The enhanced intensity in the plaque and the ratio of enhanced intensity in the plaque to that in the lumen of the carotid artery in patients with DM were significantly greater than those in patients without DM. Our study demonstrated that the enhanced intensity in patients with DM is greater than that their counterparts without DM, suggesting that carotid plaque in DM patients may have more neovessels and may be more vulnerable.     

Breast milk macronutrient composition and the associated factors in urban Chinese mothers

Background Infancy is a critical period of growth and physiological development,in which breast milk is the best source of nutrients.Compared to western countries,research on breast milk of Chinese population are limited.Thus,it is necessary to measure breast milk energy and macronutrient concentrations of healthy urban Chinese mothers at different lactation stages,to expand the database of milk composition of Chinese population,and to examine whether dietary or other maternal factors can affect the levels of macronutrients in breast milk.Methods Breast milk of full expression of one side breast from 436 urban Chinese lactating mothers at 5-11 days,12-30 days,31-60 days,61-120 days,and 121-240 days postpartum was obtained at 9：00 a.m.to 11：00 a.m.Total energy,lactose,protein,and fat contents were measured.24-hour dietary recall was surveyed,and maternal nutrient intakes were analyzed.Results Milk composition changed over the course of lactation and large individual variations were documented.The concentrations were 61.3 kcal/dl for total energy,7.1 g/dl for lactose,0.9 g/dl for protein,and 3.4 g/dl for fat in mature milk.Stage of lactation was a strong factor affecting milk composition.Minimal evidence was found for associations between maternal current dietary intake and milk macronutrient concentration,consistently with prior research.Maternal body mass index （BMI） was positively associated with milk fat content,to a greater extent than did dietary intake.All other maternal characteristics were not significant for milk composition.Conclusion These findings suggest that milk composition is generally weakly associated with maternal factors except for stage of lactation,and is likely to be more susceptible to long-term maternal nutritional status than short-term dietary fluctuation.     

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,     

Relevance of muscle biopsy for diagnosing multifocal motor neuropathy

Multifocal motor neuropathy （MMN） is a rare,.focal,inflammatory,demyelinating disease of the peripheral nerves with pure motor involvementJ MMN is clinically characterized by slowly progressive,asymmetric,distal,upper limb predominant weakness,in the absence of sensory disturbances） Weakness is usually multifocal and connected to a distinct motor nerve,such as the musculocutaneous nerve resulting in biceps weakness,the posterior interosseus nerve resulting in finger drop,the median,ulnar,or radial nerve resulting in dexterity problems or grip weakness,or the peroneal nerve resulting in a foot drop.Onset of clinical manifestations is between 20 and 50 years of age.The prevalence of MMN is reported as 1-2 per 100 000.2 MMN is three times more frequent in men as compared to women.     

Large and giant medial sphenoid wing meningiomas involving vascular structures: clinical features and management experience in 53 patients

Background Large and giant medial sphenoid wing meningiomas that are located deeply in the skull base where they are closely bounded by cavernous sinus,optic nerve,and internal carotid artery make the gross resection hard to achieve.Also,this kind of meningiomas is often accompanied by a series of severe complications.Therefore,it was regarded as a formidable challenge to even the most experienced neurosurgeons.This study aimed to investigate the clinical features and management experience of patients with large and giant medial sphenoid wing meningiomas.Methods In this study,53 patients （33 female and 20 male,mean age of 47.5 years） with large and giant medial sphenoid wing meningiomas were treated surgically between April 2004 to March 2012,with their clinical features analyzed,management experience collected,and treatment results investigated retrospectively.Results In this study,gross total resection （Simpson Ⅰ and Ⅱ） was applied in 44 patients （83％）.Fifty-three patients had accepted the routine computed tomography scan and magnetic resonance imaging scan as postoperative neuroradiological evaluation.Their performance showed surgical complications of vascular lesions and helped us evaluate patients＇ conditions,respectively.Meanwhile,the drugs resisting cerebral angiospasm,such as Nimodipine,were infused in every postoperative patient through vein as routine.As a result,11 patients （21％） were found to have secondary injury of cranial nerves Ⅱ,Ⅲ,and Ⅳ,and nine patients got recovered during the long-term observing follow-up period.Temporary surgical complications of vascular lesions occurred after surgery,such as cerebral angiospasm,ischemia,and edema;24 patients （45％） appeared to have infarction and dyskinesia of limbs.Overall,visual ability was improved in 41 patients （77％）.No patient died during the process.Conclusions Microsurgical treatment may be the most effective method for the large and giant medial sphenoid wing meningiomas.The surgical strategy should focus on survival and postoperative living quality.     

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.     

基于SUV的PET对 4周期化疗后的弥漫大B细胞淋巴瘤患者预后的评估

在过去的十来年中,18氟脱氧葡萄糖（fluorodeoxyglucose,FDG）PET已经成为多种淋巴瘤疗效评价的有力工具,它主要通过视觉分析来评估疗效。修订后的判读标准适合评估化疗结束后的疗效。而不适用于化疗期间的疗效评价。