Expression of nerve growth factor and hypoxia inducible factor-1α and its correlation with angiogenesis in non-small cell lung cancer

Summary： In order to investigate the expression of nerve growth factor （NGF） and hypoxia inducible factor-1α （HIF-1α） and its correlation with angiogenesis in non-small cell lung cancer （NSCLC）, paraffin-embedded tissue blocks from 20 patients with NSCLC were examined. Twenty corresponding para-cancerous lung tissue specimens were obtained to serve as a control. The expression of NGF, HIF-1α, and vascular endothelial growth factor （VEGF） in the NSCLC tissues was detected by using immunohistochemistry. The microvascular density （MVD） was determined by CD31 staining. The resuits showed that the expression levels ofNGF, HIF-1α and VEGF in the NSCLC tissues were remarkably higher than those in the para-cancerous lung tissues （P〈0.05）. There was significant difference in the MVD between the NSCLC tissues （9.19±1.43） and para-cancerous lung tissues （2.23±1.19） （P〈0.05）. There were positive correlations between NGF and VEGF, between HIF-1α and VEGF, and between NGF and HIF-1α in NSCLC tissues, with the spearman correlation coefficient being 0.588, 0.519 and 0.588, respectively. In NSCLC tissues, the MVD had a positive correlation with the three factors （P〈0.05）. Theses results suggest that NGF and HIF-1α are synergically involved in the angiogenesis of NSCLC.     

刘大松老中医眼科临床经验撷英

刘大松(1932~2011),男,湖南洞口县人,湖南省眼科名老中医,系祖传中医眼科第五代传人,自幼随祖父刘乐轩及父亲刘益中习医,耳提面命,勤学苦读,成为享誉一方的眼科名医。刘老一生忙于诊务,临床经验丰富,笔者有幸跟师学习,受益良多,特将其治疗外障眼病及视神经萎缩经验报道如下。     

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.     

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.     

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]。     

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis： study protocol of a multicenter randomized controlled trial

BACKGROUND： Rheumatoid arthritis （RA）, as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN： This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1：1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo （imitation leflunomide）. The control group will receive leflunomide and an herbal placebo （imitation Xinfeng Capsule）. The American College of Rheumatology （ACR） Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate （ACR20）, which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION： The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is N CT01774877.     

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,     

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.     

高维列联表资料的统计分析与SAS软件实现（六）

非条件logistic回归分析方法的主要算法是采用最大似然法对参数进行估计。最大似然法在大样本前提下进行参数估计是非常有效的,但当处理样本量小的数据,特别是按多个定性变量进行分层且每一层中样本量很小时,     

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.     

更好地报告针刺临床试验中的干预措施

“针刺临床试验干预措施报告的标准”(STandardsfor Reporting Interventions in Clinical Trials ofAcupuncture,STRICTA)为作者报告针刺临床试验提供指南。STRICTA旨在帮助临床试验的作者明晰地报告针刺临床试验中所提供的治疗的特定组成部分。我们需要从已发表的试验报告中得到有关干预措施的完整、准确而又透明的信息,从而更好地解释并严格评价其研究结果。CONSORT(Consolidated Standards of ReportingTrials,临床试验报告的统一标准)工作组已着手应对发表的临床试验报告质量低下的问题。CONSORT声明于1996年首次发表[1],之后于2001年[2]和2010年[3]作了修订,该声明为提高平行对照随机临床试验的报告质量制定了指南。最近的修订版即CONSORT2010,包括一份含25项条目的对照检查清单和一张流程图,以及对全部条目的解释和良好报告的实例[3,4]。清单中的条目5涉及干预措施的报告质量。在西医领域中,临床试验干预措施的报告存在诸多问题并已引起注意。有一项研究对这类临床试验报告作了仔细审读,发现...     

Modulating Effects of Chlorogenic Acid on Lipids and Glucose Metabolism and Expression of Hepatic Peroxisome Proliferator-activated Receptor-α in Golden Hamsters Fed on High Fat Diet

Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.     

TGF-β1 Precursor and CD8 Are Potential Prognostic and Predictive Markers in Operated Breast Cancer简

The transforming growth factor β1（TGF-β1） and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130（stageⅠ–Ⅲ） invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival（DDFS）（HR=8.416, 95% CI=1.636–43.292, P=0.011） in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival（OS） than their counterparts with CD8-positive cell infiltration into tumor nests（Log-Rank, P=0.003）. But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy（Log-Rank, P=0.013） and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor（t-TGF-β1-pre）-positive patients than in the negative patients in patients without recieiving chemotherapy（P=0.053）, OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy（P=0.035） and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS（HR=0.392 95% CI=0.157–0.978, P=0.045） in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.     

Effects of the aqueous extract of Schizandra chinensis fruit on ethanol withdrawal-induced anxiety in rats

Background We previously demonstrated that the aqueous extract of the Schizandra chinensis fruit （AESC） ameliorated Cd-induced depletion of monoamine neurotransmitters in the brain through antioxidant activity.In the present study,we investigated the effect of AESC on anxiety-like behavior and the levels of norepinephrine and 3-methoxy-4-hydroxyphenylglycol （a metabolite of norepinephrine） in different brain regions during ethanol withdrawal in rats.Methods Male Sprague-Dawley rats were treated with 3 g/kg of ethanol （20％,w/v） or saline by daily intraperitoneal injection for 28 days followed by three days of withdrawal.During withdrawal,rats were given AESC （100 mg.kg 1.d-1 or 300 mg.kg 1·d1,P.O.） once a day for three days.Thirty minutes after the final dose of AESC,the anxiogenic response was evaluated using an elevated plus maze,and the plasma corticosterone levels were examined by radioimmunoassay.Meanwhile,the concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol in the hypothalamic paraventricular nucleus and hippocampus were also measured by high performance liquid chromatography.Results Rats undergoing ethanol withdrawal exhibited substantial anxiety-like behavior,which was characterized by both the decrease in time spent in the open arms of the elevated plus maze and the increased level of corticosterone secretion,which were greatly attenuated by doses of AESC in a dose-dependent manner.The high performance liquid chromatography analysis revealed that ethanol withdrawal significantly increased norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the hypothalamic paraventricular nucleus,while not significantly altering them in the hippocampus.Similar to the results from the elevated plus maze test,the AESC significantly inhibited the elevation of norepinephrine and its metabolite in the hypothalamic paraventricular nucleus in a dose-dependent manner.Conclusions These results suggest that AESC attenuates anxiety-like behavior induced by ethanol withdrawal through modulation of the hypothalamic norepinephrine system in the brain.