Differential effect of calcium-activated potassium and chloride channels on rat basilar artery vasomotion

Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery （BA） of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows： （1） The diameters of BA and middle cerebral artery （MCA） were 314.5±15.7 μm （n=15） and 233.3±10.1 μm （n=12） at 10 mmHg working pressure （P〈0.05）, respectively. Pressure-induced vasomotion occurred in BA （22/28, 78.6%）, but not in MCA （4/31, 12.9%） from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; （2） The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic con- tractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7±4.7 （n=13） per 10 min at 60 mmHg working pressure; （3） The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 181]-GA, TEA or in Ca2＋-free medium. Nifedipine, NFA, 18~-GA or Ca2＋-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results sug- gest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca2＋-activated C1- channels （CaCCs） currents and Kca currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells （VSMCs） to activate CaCCs. Depolarization in turn activates voltage-dependent Ca2＋ channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calc     

Inhibitory Effects of Roscovitine on Proliferation and Migration of Vascular Smooth Muscle Cells In Vitro

Abnormal proliferation and migration of vascular smooth muscle cells （VSMCs） are the major cause of in-stent restenosis （ISR）. Intervention proliferation and migration of VSMCs is an im- portant strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase in- hibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of Go/G1 phase cells after 12 h （69.57±3.65 vs. 92.50±1.68, P=0.000）, 24 h （80.87±2.24 vs. 90.25±0.79, P=0.000） and 48 h （88.08±3.86 vs. 88.87±2.43, P=-0.427） as compared with control group. Roscovifine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concen- tration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine （30 μmol/L） led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.     

Association between interferon gamma receptor 1 -56C/T gene polymorphism and tuberculosis susceptibility: a meta-analysis

Background Genetic variations in the interferon-gamma （IFN-γ） receptor 1 gene （IFNGR1） may contribute to tuberculosis （TB） risk in different populations.Many studies have investigated the relationship between IFNGR1 56C/T polymorphism and the susceptibility to TB,but have yielded conflicting results.A comprehensive meta-analysis is needed to provide a more accurate estimation of the relationship between them.Methods A literature search based on a combination of manual and computer-based methods was conducted on four English databases （PubMed,Science Direct,SpringerLink,and EBSCO） and three Chinese databases （Wanfang,CQVIP,and Chinese National Knowledge Infrastructure databases）.Pooled odds ratios （ORs） and 95％ confidence intervals （95％ Cls） were calculated using either the fixed-effects model or the random-effects model for different genetic models based on the heterogeneity examination.Results A total of six studies comprising 1 497 confirmed TB cases and 1 802 controls were included in this meta-analysis.Overall,no significant association was observed between IFNGR1-56C/T polymorphism and TB susceptibility （C vs.T,OR=0.90,95％ Cl 0.69-1.17; CC vs.TT,OR=0.87,95％ Cl 0.65-1.18; TC vs.TT,OR=-1.031,95％ Cl 0.872-1.219; CC＋TC vs.TT,OR=0.89,95％ Cl 0.64-1.26; CC vs.TC＋TT,OR=0.92,95％ Cl 0.66-1.29）.In subgroup analysis,a significant association was found in the dominant model （CC＋TC vs.TT,OR=1.24,95％ Cl 1.02-1.51） in Africans,but not in Asians or Caucasians.Conclusions Our meta-analysis did not provide enough powerful evidence to identify a significant association between IFNGR1-56C/T polymorphism and TB susceptibility in the overall population.In subgroup analysis,it indicates that IFNGR1-56C/T is possibly associated with increased TB risk in Africans,but not in Asians or Caucasians.However,larger sample size and better-designed case-control studies are needed to validate these findings.     

Depressant effect and mechanism of atorvastatin on the chronic rejection of aortic allograft in rats

Objective To investigate the depressant effect and mechanism of atorvastatin on the chronic rejection of aortic allograft in rats. Methods： The models of abdominal aorta transplantation were made with micro-surgery in rats. The recipients were divided into three groups： allograft control group, atorvastatin-treated group and isograft control group. Vascular intimal thickness in all of the groups were observed by histological examination. The expression of PCNA and α-SMA were determined by immunohistochemistry. The content of nitric oxide was determined by nitrate reductase chromatometry. Results： The vascular intimal thickness in rats of atorvastatin-treated group （11.60% ± 2.40% ） were lower than those in allograft control group （34.60 % ± 6.40 % ; P 〈 0.05） and higher than those in isograft control group （1.15 % ± 0.65 %; P〈 0.05 ）. The expression level of PCNA was decreased in atorvastatin-treated group （4.80% ± 0.80% ） than allograft control group （18.40% ± 1.80% ; P〈0.05） and higher than isograft group （1.20% ± 0.40% ; P〈0.05）. Conclusion： The expression of PCNA in the transplant aorta could be suppressed by atorvastatin, which resalted in relief of chronic rejection of aortic allograft.     

Mechanisms responsible for pulmonary hypertension

Pulmonary hypertension is a pathophysiologic process characterized by progressive elevation of pulmonary vascular resistance and right heart failure, which is a common complication of many diseases. Pulmonary hypertension with no apparent causes （unknown etiology） is termed primary pulmonary hypertension or, more recently, idiopathic pulmonary arterial hypertension （IPAH）. Before the availability of disease-specific （targeted） therapy （through the mid-1980s） the median life expectancy from the time of diagnosis in patients with this disease was 2.8 years. Modem treatment has markedly improved physical function and has extended survival, and the 5-year mortality is 50%. Although there is already more than 100 years of research history, the mechanisms of this disease are still not very clear. Recently, with the development of cell biology and molecular genetics, further research into the mechanisms responsible for pulmonary hypertension have been possible, which has helped in its diagnosis and treatment. It is believed that the mechanisms of pulmonary hypertension can not only be described by pathophysiology but involve multiple factors （pathways） like cellular, humoral and molecular genetics, etc.     

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。     

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.     

Total intravenous anesthesia for cesarean section in a pregnant woman with spinal muscular atrophy

Spinal muscular atrophy （SMA） is a genetic neuromuscular disorder characterized by progressive degeneration of the anterior horn cell leading to a lower motor neuron lesion. It is characterized by degeneration of alpha neurons in the anterior horn cells of the spinal cord leading to progressive muscle atrophy and premature death, usually from respiratory failure.1 There are four types according to the symptoms （Table 1）.     

Microvascular protective role of pericytes in melatonin-treated spinal cord injury in the C57BL/6 mice

Background Pericytes,located on microvessels,help to maintain vascular stability and blood-brain barrier integrity.The influence of pericytes on microvessels after spinal cord injury （SCI） is less clear.Therefore,the aim of this study was to investigate whether pericytes took a protective effect on microvessels in melatonin-treated SCI.Methods C57BL/6 mice were randomly divided into three groups：sham group,SCI group,and melatonin group （n=27per group）.Functional recovery was evaluated using the Basso Mouse Scale.Motor neurons were observed using hematoxylin and eosin staining.Pericyte coverage was analyzed using immunofluorescence.Permeability of blood-spinal cord barrier （BSCB） was assessed by administration of Evan＇s Blue.Protein levels of occludin,aquaporin-4 （AQP4）,angiopoietin-1 （Ang1）,intercellular cell adhesion molecule-1 （ICAM-1）,Bcl-2,and Bax were determined using Western blotting.Mimicking the pathological conditions of SCI,melatonin-treated primary pericytes were subjected to oxygenglucose deprivation/reperfusion （OGD/R）.Secretion of Ang1 was analyzed using an enzyme-linked immunosorbent assay,and the expression of ICAM-1 was detected by immunofluorescence.Results Melatonin treatment improved locomotor functional outcome and rescued motor neurons.Pericyte coverage was significantly reduced after SCI; melatonin treatment alleviated the loss of pericyte coverage and rescued perfused microvessels 7 days after injury.The permeability of BSCB and loss of occludin were attenuated,and edema formation and upregulation of AQP4 were inhibited,after melatonin treatment.The expression of Ang1 and Bcl-2 was improved,while the expression of ICAM-1 and Bax was inhibited,in melatonin-treated SCl mice.Furthermore,the secretion of Ang1 was increased and the expression of ICAM-1 was inhibited in melatonin-treated pericytes after OGD/R.Conclusions Melatonin ameliorated the loss of blood vessels and disruption of BSCB to exert a protective effect on SCI,which might be mediated by increased p     

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。     

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。     

Effect of behavior training on learning,memory and the expression of NR2B,GluR1 in hippocampus of rats offspring with fetal growth restriction

Objective： To study effects of behavior training on learning, memory and the expression of NR2B, GluR1 in hippocampus of rat＇ s offspring with fetal growth restriction（FGR）. Methods： The rat model of FGR was established by passive smoking method. The rats offspring were divided into the FGR group and the control group, then randomly divided into the trained and untrained group, respectively. Morris water maze test was proceeded on postnatal month（PM2/4） as a behavior training method, then the learning-memory of rats was detected through dark-avoidance and step-down tests. The expressions of NR2B and GluR1 subunits in hippocampal CA1 and CA3 areas were detected by immunohistochemical method. Results： In the dark-avoidance and step-down tests, the performance record of rats with FGR was worse than that of control rats, and the behavior-trained rats was better than the untrained rats, when the FGR model and training factors were analyzed singly. The model factor and training factor had significant interaction（P 〈 0.05）. The expressions of NR2B and GluR1 subunits in hippocampal CA1 and CA3 areas of rats with FGR reduced. In contrast, the expressions of GluR1 and NR2B subunits in CA1 area of behavior-trained rats increased, when the FGR model and training factors were analyzed singly. Conclusion： These findings suggested that the effect of behavior training on the expressions of NR2B and GluR1 subunits in CA1 area should be the mechanistic basis for the training-induced improvement in learning-memory abilities.     

糖络方联合弥可保治疗2型糖尿病周围神经病变的临床观察

目的观察益气养阴活血通络之糖络方联合弥可保治疗2型糖尿病周围神经病变的疗效。方法将65例患者随机分成治疗组（中西药组）和对照组（西药组）,均在西药降血糖基本达标的同时,对照组单纯口服弥可保,治疗组口服弥可保的基础上加用糖络方内服,治疗8周。结果总有效率及治疗后证候积分比较,治疗组优于对照组,差异有统计学意义（P〈0．05）;治疗后肌电图比较,治疗组优于对照组,差异有统计学意义（P〈0．01）。结论益气养阴活血通络之糖络方联合弥可保治疗2型糖尿病周围神经病变疗效优于单用弥可保,是治疗该病的有效方剂之一。     

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     

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、     

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。     

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,