Sphingosine Kinase-1/sphingosine 1-phosphate pathway in diabetic nephropathy

Objective Diabetic nephropathy （DN） is the major cause of end-stage renal disease worldwide and its prevalence continues to increase.Currently,therapies for DN provide only partial renoprotection; hence new targets for therapeutic intervention need to be identified.In this review,we summarized the new target,sphingosine kinase-1/sphingosine 1-phosphate （SphK1/S1P） pathway,explored its potential therapeutic role in the prevention and treatment of DN.Data sources Most relevant articles were mainly identified by searching PubMed in English.Study selection Mainly original articles and critical review articles by major pioneer investigators in this field were selected to be reviewed.Results SphK1/S1P pathway can be activated by hyperglycemia,advanced glycation end products,and many proinflammatory cytokines,which leads to fibronectin,transforming growth factor-31 up-regulation and AP-1 activation.And then it could promote glomerular mesangial cells proliferation and extracellular matrix accumulation,mediating the initiation and progression of diabetic renal fibrosis.Conclusions SphK1/S1P pathway is closely correlated with the pathogenesis of DN.The results suggest that SphK1/ S1P pathway as a new target for clinically improving DN in future is of great prospect.     

Decrease in myostatin by ladder-climbing training is associated with insulin resistance in diet-induced obese rats

Background Suppression of myostatin （MSTN） has been associated with skeletal muscle atrophy and insulin resistance （IR）.However,few studies link MSTN suppression by ladder-climbing training （LCT） and IR.Therefore,we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR.Methods The rats were randomly assigned to two types of diet：normal pellet diet （NPD,n=8） and high-fat diet （HFD,n=16）.After 8 weeks,the HFD rats were randomly re-assigned to two groups （n=8 for each group）：HFD sedentary （HFD-S） and high-fat diet ladder-climbing training （HFD-LCT）.HFD-LCT rats were assigned to LCT for 8 weeks.Western blotting,immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN,GLUT4,PI3K,Akt and Akt-activated targets （mTOR,FoxO1 and GSK-3β）.Results The LCT significantly improved IR and whole-body insulin sensitivity in HDF-fed rats.MSTN protein levels decreased in matching serum （42％,P=0.007） and muscle samples （25％,P=0.035） and its receptor mRNA expression also decreased （16％,P=0.041） from obese rats after LCT.But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD-S groups （P=0.074）.The ladder-climbing training significantly enhanced PI3K activity （1.7-fold,P=0.024） and Akt phosphorylation （83.3％,P=0.022） in HFD-fed rats,significantly increased GLUT4 protein expression （84.5％,P=-0.036）,enhanced phosphorylation of mTOR （4.8-fold,P ＜0.001） and inhibited phosphorylation of FoxO1 （57.7％,P=0.020）,but did not affect the phosphorylation of GSK-3β.Conclusions The LCT significantly reduced IR in diet-induced obese rats.MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.     

Norcantharidin inhibits tumor growth and vasculogenic mimicry of human gallbladder carcinomas by suppression of the PI3-K/MMPs/Ln-5T2 signaling pathway

Background：Vasculogenic mimicry （VM） is a novel tumor blood supply in some highly aggressive malignant tumors. Recently,we reported VM existed in gallbladder carcinomas （GBCs） and the formation of the special passage through the activation of the PI3K/ MMPs/Ln-5γ2 signaling pathway. GBC is a highly aggressive malignant tumor with disappointing treatments and a poor prognosis. Norcantharidin （NCTD） has shown to have multiple antitumor activities against GBCs, etc; however the exact mechanism is not thoroughly elucidated. In this study, we firstly investigated the anti-VM activity of NCTD as a VM inhibitor for GBCs and its underlying mechanisms. Methods ： In vitro and in vivo experiments to determine the effects of NCTD on proliferation, invasion, migration, VM formation, hemodynamic and tumor growth of GBC-SD cells and xenografts were respectively done by proliferation, invasion,migration assays,HE staining and CD31-PAS double staining, optic/electron microscopy, tumor assay, and dynamic micro- MRA. Further, immunohistochemistry, immunofluorescence, Western blotting and RT-PCR were respectively used to examine expression of VM signaling-related markers PI3-K,MMP-2 ,MT1-MMP and Ln-5γ2 in GBC-SD cells and xenografts in vitro and in vivo. Results： After treatment with NCTD, proliferation, invasion, migration of GBC-SD cells were inhibited; GBC-SD ceils and xenografts were unable to form VM-like structures; tumor center-VM region of the xenografts exhibited a decreased signal in intensity; then cell or xenograft growth was inhibited. Whereas all of untreated GBC-SD cells and xenografts formed VM-like structures with the same conditions; the xenograft center-VM region exhibited a gradually increased signal; and facilitated cell or xenograft growth （Figure 1-6 ）. Furthermore, expression of MMP-2 and MT1-MMP products from sections/supemates of 3-D matrices and the xenografts, and expression of PI3-K, MMP-2, MM1-MMP and Ln-5γ2 proteins/mRNAs of the xenografts were all decreased in NCTD or TIMP-2 g     

益智健脑颗粒联合针灸对阿尔茨海默病大鼠学习记忆的影响

目的观察益智健脑颗粒联合针灸对阿尔茨海默病（Alzheimers disease,AD）大鼠学习记忆的影响。方法将大鼠随机分为假手术组（A组）、模型组（B组）、针灸组（C组）、益智＋针灸组（D组）各10只,B、C、D 3组分别以海马CA1区注射β淀粉样蛋白25-35（Aβ25-35）造模,A组注射等量的双蒸水,各组分别治疗20 d后行Morris水迷宫试验,观察大鼠学习记忆能力变化。结果B组较A组的平均潜伏期明显延长,差异具有统计学意义（P〈0.05）;与B组比较,C组、D组的平均潜伏期明显缩短,过台次数增多,差异具有统计学意义（P〈0.05,P〈0.01）;与C组比较,D组的潜伏期缩短,过台次数增多,差异具有统计学意义（P〈0.05）。结论益智健脑颗粒联合针灸能够提高Aβ25-35介导的AD模型大鼠的学习记忆能力。     

Liuwei Dihuang,a traditional Chinese herbal formula,suppresses chronic inflammation and oxidative stress in obese rats

OBJECTIVE： To investigate the anti-inflammatory, anti-oxidative stress, and adipokine-ameliorating effects of Liuwei Dihuang （LWDH）, a traditional Chinese herbal formula, in obese rats. METHODS： After 2 weeks of acclimation with free access to regular rodent chow and water, obese-prone-caesarean-derived （OP-CD） rats were fed a modified AIN-93G diet containing 60% energy from fat. Treatment was performed twice daily by gavage feeding with 500, 1 500, or 3 500 mg/kg body weight LWDH suspended in water （n=12 rats per group）. Twelve obese-resistant-CD （OR-CD） rats were fed the atherogenic diet and gavaged with water, and served as the normal control. Blood biomarkers of inflammation, oxidative stress and adiponectin were measured post-sacrifice and used to determine the treatment effect of LWDH and assess the suitability of OR/OP-CD rats for studying these parameters. RESULTS： After 9 weeks of treatment, LWDH lowered serum C-reactive protein （CRP） and tumour necrosis factor-α （TNF-α） levels. Serum interleukin-6 （IL-6） levels showed a tendency towards reduction, but were not significantly different from the OP-CD control. Liver superoxide dismutase （SOD） activity was increased in response to all three doses of LWDH, while the levels of reduced （GSH） and oxidized glutathione （GSSG） and thiobarbituric acid reactive substances （TBARS） were unchanged. Serum adiponectin levels were increased in response to oral administration of LWDH at the dose of either 500 or 1 500 mg/kg body weight. In addition, comparisons between OR-CD and OP-CD rats revealed differential, and for some biomarkers, conflicting characteristics of high-fat diet-fed OP-CD rats in reference to obese human subjects in terms of inflammatory and oxidative stress biomarkers and circulating adiponectin levels. CONCLUSION： The results show, for the first time, the anti-inflammatory, anti-oxidative stress and adiponectin-ameliorating effects of LWDH in obese rats. The suitability of the OP-JOP-CD rat model as     

Efficacy and safety of vitamin D3 in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials

Background Several studies found that vitamin D3 might alter glucose metabolism,protect kidney from injury and even proposed the mechanisms.But results from previous studies have been conflicting.The aim of this study was to evaluate the efficacy and safety of vitamin D3 in patients with diabetic nephropathy.The underlying mechanism of vitamin D3 decreasing proteinuria is also discussed.Methods We conducted a search of English and Chinese articles using database of Pubmed,Embase,Sinomed,CNKI,Wanfang and clinical trial register centers,for randomized controlled trials of vitamin D3 in diabetic nephropathy patients.Two reviewers performed independently.Meta-analysis was used when studies were homogeneous enough.Results Twenty studies,including 1 497 patients with diabetic nephropathy,were involved in this systemic review.Vitamin D3-treated patients with diabetic nephropathy had a statistically significant reduction in 24-hour proteinuria （weighted mean difference-0.44,95% CI-0.54 to-0.34,Z=8.80,P 〈0.000 01） and urine albumin/creatine ratio （standardized mean difference-0.29,95% CI-0.48 to-0.10,Z=2.96,P=0.003）.But vitamin D3 supplementation did not significantly reduce blood pressure and hemoglobin A1c compared with control group.The potential mechanisms about the renal protection of vitamin D3,including the inhibition of rennin-angiotensin system,the protection of kidney from inflammation,fibrosis and the structure change of kidney are discussed.In addition,vitamin D3 did not significantly increase the incidence of adverse effects,including total adverse effects,gastrointestinal adverse effects and fluctuation of blood pressure.Conclusions Vitamin D3 can ameliorate proteinuria and protect kidney from injury in patients with diabetic nephropathy.This renoprotective effect is independent of blood pressure and glucose reduction.And it does not increase any adverse effects than control,even in combination therapy with angiotensin converting enzyme inhibitors/angiotensin receptor blockers.But due to the limite     

补肾活血方对PCOS大鼠模型卵巢中PAI-1mRNA表达的影响

目的探讨补肾活血方对大鼠PCOS模型卵巢局部纤溶酶原激活物抑制因子-1（PAI—1mRNA）表达的影响。方法选用未成年24d龄SD雌性大鼠60只,随机分为模型组、克罗米酚组、补肾活血方高剂量组、补肾活血方低剂量组、正常对照组5组。用Bogovich法建立大鼠多囊卵巢病理模型。以克罗米酚为对照。用原位杂交法观察补肾活血方对多囊卵巢大鼠局部PAI—1mRNA的影响。结果模型组卵巢局部PAI—1mRNA存在卵泡膜间质细胞显著增高,用补肾活血方高、低剂量与克罗米酚药后,卵巢局部PAI-1mRNA的表达明显降低．差异具有统计学意义（P〈0．05、P〈0．01）。补肾活血方高剂量组与克罗米酚组比较,差异具有显著统计学意义（P〈0．01）;低荆量组与克罗米酚组比较差异无统计学意义（P〉0．05）,补肾活血方高、低剂量组比较,低剂量组卵泡膜间质细胞上PAI-1的基因表达增高更明显,但二者差异无统计学意义（P〉0．05）。结论PAI-1mRNA可能与多囊卵巢综合征的发病机制有关。以补肾活血立法的补肾活血方能降低多囊卵巢大鼠局部PAI—1mRNA的显著增高表达．降低PAI—1mRNA卵巢局部的作用。提示补肾活血方可能通过PAI—1mRNA途径促进卵巢排卵的机制。     

中医疗法治疗运动性疲劳的研究进展

随着竞技体育的发展，运动员经常承受着大负荷、超强度的体力训练，因此极易产生运动性疲劳。疲劳的出现使肌内压增高，局部缺血，造成氧化代谢、H^＋排出率与pH值降低，血乳酸增高，从而影响肌纤维神经传导速度和肌内收缩力量，减弱了肌肉保护能力。致使较多的冲击力传到骨骼上，故易导致疲劳骨折的发生,严重影响了运动员的训练和比赛成绩，对运动员身心产生不必要的伤害。运动性疲劳消除手段的研究一直是竞技体育工作和运动医学关注和研究的焦点。     

Iloprost inhibits fracture repair in rats

Background Previous studies have shown that prostaglandins （PGs） dramatically stimulate healing processes in bone.However,the effect of prostaglandin l2 （PGI2） on fracture healing remains unclear.To investigate the effect of PGI2,a study on fracture healing process in closed tibia fractures was designed.Methods Thirty-six Sprague-Dawley male rats were randomized into two groups.On the first day,their right tibias were fractured by three-point bending technique.The study group （n=18） received a single injection of 10 μg/kg iloprost for 5 days,while the control group （n=18） received saline solution in the same way.On the 7th,14th and 28th days following the fracture,six rats were sacrificed and their right legs were harvested in each group.The progression of fracture healing was assessed for each specimen by the scores of radiography （by Lane-Sandhu） and histology （by Huo et al）.Results On the 7th day,the radiographic and histologic scores were equal.On the 14th day radiographic total score was 6 and histologic total score was 23 in the iloprost group,whereas radiographic total score was 11 and histologic total score was 33 in the control group.On the 14th day radiographic and histologic scores were significantly decreased in the iloprost group compared to the control group （P 〈0.05）.On the 28th day radiographic total score was 12 and histologic total score was 37 in the iloprost group,whereas radiographic total score was 15 and histologic total score was 40 in the control group.On the 28th day although there was a decrease in radiographic and histologic scores of the iloprost group acording to control group,it was not statistically significant （P 〉0.05）.Conclusion Iloprost delays fracture healing in early stage in rats.     

New Mechanism of Herb-herb Interaction between Ginseng and Trogopterus Based on CYPs in Rat Livers

The study was designed to investigate the potential mechanism of herb-herb interaction between ginseng and Trogopterus （Trg） based on Cytochrome P450 isozymes （CYPs） in rat livers. We estimated the influence on CYP1A2, CYP2E1, and CYP3A1/2 activity caused by ginseng and Trg used in combination. The CYP1A2 and CYP2E1 enzyme activity were induced by ginseng and Trg used in combination. And this induction effect was caused via inducing CYP1A2 and CYP2E1 protein expression which was supposed caused by inducing the gene expression of CYP1A2 and CYP2E1.     

Meta-analysis of Quantitative Diffusion-weighted MR Imaging in Differentiating Benign and Malignant Pancreatic Masses

There have been numerous studies done to explore the diagnostic performance of quanti- tative diffusion-weighted （DW） MR imaging to differentiate between benign and malignant pancre- atic masses. However, the results have been inconsistent. We performed a meta-analysis to investigate whether DW-MR imaging can differentiate between these two diseases. Databases including MEDLINE, EMBASE and Cochrane Library were utilized to find relevant articles published between January 2001 and January 2014. A Stata version 12.0 and a Meta-Disc version 1.4 were used to de- scribe primary results. Twelve studies with 594 patients, which fulfilled the inclusion criteria, were enrolled for the analysis. The pooled sensitivity and specificity of DW imaging was 0.91 （95% CI： 0.84, 0.95） and 0.86 （95% CI： 0.76, 0.93） respectively. The area under the curve of the summary re- ceiver operating characteristic was 0.95 （95% CI： 0.93, 0.96）. The results indicated that DW imaging might be a valuable tool for differentiating benign and malignant pancreatic masses.     

程丑夫教授论治情志病验案举隅

程丑夫是国家级名老中医,湖南中医药大学第一附属医院主任医师、教授、博士生导师,享受政府特殊津贴专家,出身于中医世家,从医40余年,经验丰富,对于内科系统及疑难杂症的治疗颇有心得,笔者有幸跟师学习,聆听教诲,受益匪浅,现将程师论治情志病的经典验案略陈一二。1思虑伤脾案患者肖某,女,27岁。初诊：2014年5月20日。半年前因婚变后出现忧心忡忡,多思多虑,近1月来反复腹部胀满,刻诊：腹胀,食后为甚,呃逆,无反酸,通气后可减轻,无腹痛,不欲食,夜寐不安,二便调。舌红苔厚白腻,脉弦,BP：110／70mmHg。     

表皮生长因子受体酪氨酸激酶抑制剂在非小细胞肺癌应用的瓶颈——获得性耐药

以表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI）分子靶向治疗研究为肇始,转化性研究使基础实验和临床实践间的鸿沟迅速填平,改变着人们认识治疗肺癌的视角。无可否认,EGFR-TKI上市后极大地延伸了肿瘤学家治疗肺癌的手段,但不管从临床经验、临床研究数据、分子生物学层面还是文献计量学的角度,     

Reproductive Challenges in Young Female Cancer Patients

The last three decades have seen a significant improvement and advancement in both the diagnostic and therapeutic modalities with improved surgical technique, chemoradio and supportive therapy in cancer treatment. This has produced a correspondingly increase in the 5-year relative survival rate for many cancers and for all races. However, the chemo-radiotherapy which is often gonadotoxic, has a substantial impact on quality of life issues especially that of reproduction in young female patients on account of increasing survival rates and delayed childbearing in the western hemisphere. This case based discussion paper using two real life case scenarios from our department focuses on the negative impact of cancer treatments on fertility and various options available for fertility preservation and / or fertility preservation measures. It is concluded that a lot of variables have to be considered when deciding upon fertility preservation treatments including patient＇s age, cancer stage, proposed treatment regime and time before it is initiated, availability of partner sperm and issues of individual patients. The latter include surgical complications, ovarian hyperstimu-lation syndrome, delay in cancer treatment and reintroduction of cancer cells, cost, low success rates and experimental nature of these treatments and the disposition of gametes in the event that the patient does not survive her cancer. It is very important for physician to advise patients of all these factors so that they can make an informed decision regarding the fertility preservation options and each case is unique and requires a different strategy of fertility preservation.     

Effect of Shenfu on the Expression of Bcl-2 and Bax of Intestinal Mucosal Epithelial Cells after Ischemic Reperfusion in Rats

Objective To study the effect of Shenfu on the expression of bax and bcl-2 in small intestinal mucosal epithelial cells after ischemic reperfusion injury and explore the effect of Shenfu on small intestinal mucosal epithelial cells apoptosis. Methods 36 SD rats were randomized into three groups, each consisting of 12 rats： Sham group （S group）, Ischemic reperfusion group （IR group）, Shenfu group （SF group）, Ischemic reperfusion models were made by ligated the superior menseneric artery for 1 hour followed by 2 hrs reperfusion. Histological mucosal damage in each group was graded according to Chiu＇s score. Immunohistochemistry detected the expression of bax and bcl-2, and obtained the optical density （OD） value using a color image pattern analysis system, and then calculated the ratio of bcl-2/bax. TUNEL method measured apoptotic intestinal mucosal epithelial cells, and calculated the apoptotic index. Results There were edema and epithelial impairment in part of villus and the integral was higher in SF group than S group （P〈0.05）, but lower than IR group （P〈0.01）. Compared IR group with S group and SF group, the average OD value of bcl-2 and bax had significant statistic difference （P〈0.01）, and the average OD value of bcl-2 in SF group was higher than in S group （P〈0.05）, meanwhile bcl-2/bax was significantly lower in IR group than in S group and SF group （P〈0.01）, but that was higher in SF group than in S group （P〈0.05）. Apoptotic index in IR group was significantly higher than that in other two groups （P〈0.01）, and that in SF group was higher than in S group （P〈0.05）. Conclusion Shenfu can enhance the expression of bcl-2, decrease the expression of bax, meanwhile increase the ratio of bcl-2/bax, inhibit small intestinal mucosal epithetlial cells apoptosis, and protect small intestine mucosal epithetlial after ischemic reperfusion.     

郭振球教授高血压病辨治特色

郭振球教授是湖南中医药大学教授,从事临床、科研、教学工作六十一年,积累了丰富的临床经验,在学术上治学严谨。学验俱丰。1986年人选我国首批中医学博士研究生导师．1990年被评为我国首批全国继承老中医学术经验指导老师,开创了微观证治学,系世界传统医学诊断学学科奠基人。     

Expression and Influence of Galectin-3 on Missed Abortion

Objective To explore the influence of galectin-3 on missed abortion. Methods Forty cases of normal intrauterine early pregnancy were randomly divided into 2 groups： surgical abortion group （group A, n=20） and medical abortion group （group B, n =20）. The third group was missed abortion group （group C, n =20） with the gestational age less than 13 weeks. Serum was isolated from the blood samples, collected and used for ELISA quantification of galectin-3. Villus and decidua tissues were collected from the abortus for immunohistochemical examination and real-time fluorescence relative quantitative PCR. Results The level of galectin-3 in the serum was the lowest in missed abortion group （P〈0.05）. Immunohistochemistry showed that galectin-3 expression in villus of missed abortion group was significantly lower than that of surgical abortion group （P〈0. 01）. Real-time fluorescence relative quantitative PCR showed that galectin-3 mRNA relative expression in villus of missed abortion group （2^-△△Ct=0. 04± 0. 01） was significantly lower than that of surgical abortion group （2^-△△Ct=1.00 ± 0.00）. Galectin-3 mRNA relative expression in deciduas of medical abortion group （2-zact=o. 08 ± 0.02） was s!gnificantly lower than that of surgical abortion group （2^-△△Ct=1.00 ± 0.00） （P〈0. 01）. Conclusion Galectin-3 is related to the development of villus and decidua during early pregnancy. The decreased expression of galectin-3 may promote the occurrence of missed abortion.     

UniPron is A Fully Effective Non-hormonal Reversible Contraceptive in Baboon Model （Papio Anubis）

Objective To determine the safety and efficacy of UniPron as a reversible contraceptive.
Methods Vaginal swabs were obtained before and after UniPron administration, cultured onto appropriate culture media and bacteria identification was done based on type of media used, Gram stain reactions, colony morphology and biochemical tests. Vaginal biopsy tissues were processed using paraffin wax method, stained with hematoxylin and eosin and examined under light microscopy to determine the effect of the product on vaginal tissues. The effect of UniPron on sperm was examined by mixing the product with electroejaculated spermatozoa in vitro at different concentrations. For efficacy studies, male baboons of proven fertility were mated with UniPron treated or untreated females of proven fertility during the fertile stages.
Results All the five females （100%） that were treated with UniPron did not conceive and they regained total fertility when the treatment was stopped while all the controls conceived. At a concentration of 40%, UniPron completely immobilized spermatozoa in an in-vitro system. UniPron mechanism of action was by lowering the vaginal pH and on application in baboon, the pH was lowered for at least 3 h after which it went back to normal.
Conclusions As we plan for a study to test UniPron as a microbicide to prevent STIs including HIV, our current study has established that this novel product is effective in contraception and harmless to vaginal tissues and vaginal microbial flora in a baboon model （Papio anubis）.     

Bias in multiple-treatments meta-analysis: a case on comparative efficacy and tolerability of 15 antipsychotic drugs for schizophrenia

Multiple-treatments meta-analysis is thought to be a feasible method to compare the efficacy and safety among different treatments, especially when there was no head-to-head research among some treatments. But sometimes some conclusions are inconsistent with the clinical experience. Recently, we read a multiple-treatment meta-analysis finished by Stefen Leucht et al, which was published in Lancet） The authors summarized the results of the RCT studies on 15 antipsychotics commonly used in practice; they also horizontally compared the efficacy and safety profile by the recta-analysis. We believe that the results provide more solid evidence for the rational usage of antipsychotics to the psychiatrists, also for the government to distribute health resources in a more reasonable way.     

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：精、神、气、血、津、液部分

精、神、气、血、津、液是中医理论中6个非常重要的概念，有关术语在《WHO西太区传统医学国际标准名词术语》中一共收录了59条，“世界中医药学会联合会”（以下简称世中联）《中医基本名词术语中英对照国际标准》中收录了58条。血、津、液的内涵较为具体，有一定的物质基础，理解并不困难。翻译上虽有差异，但亦不难统一。精、神、