Over-expression of heme oxygenase-1 in peripheral blood predicts the progression and relapse risk of chronic myeloid leukemia

Background There are limited eligible clinical markers at present to monitor the progress of chronic myeloid leukemia （CML）.Heme oxygenase-1 （HO-1）,as one of the most important oxidation-regulating enzymes in vivo,suggests the onset and progression of cancer when highly expressed.Furthermore,HO-1 level is related with the occurrence and development of hematological diseases.But the relationship between HO-1 expression and progression/relapse of CML has seldom been studied hitherto.This study aimed to investigate the relationship between them to find out a new molecular marker for prediction.Methods A total of 60 peripheral blood and bone marrow （BM） samples from 25 CML patients in different phases were collected respectively to detect the expressions of HO-1 and bcr/abl using real-time PCR.Routine blood test was performed to detect the changes of leukocyte and platelet counts.The proportion of primitive cells in BM was detected by flow cytometry.The relationship between high HO-1 expression and CML progression and relapse was explored by the analysis of variance by Wilcoxon test and linear regression analysis.The diagnostic accuracy and cutoff values were determined by receiver operating characteristic curve.Results Relative expression of HO-1 mRNA in CML patients peripheral blood was significantly higher than that of donors （P 〈0.0001）,which were 0.57±3.78 and （1.417±1.125）×10-6,respectively.HO-1 expression level in CML patients was 0.061 5±0.062 4,which decreased to 0.009 4±0.006 7 upon CMoR,and remained remarkably higher 0.016 3±0.017 5 than that of normal donors （1.417±1.125）× 10-6,P 〈0.001.When relapse occurred,HO-1 expression significantly increased from 0.020 6±0.021 0 to 3.852±10.285 in CMoR stage and undergoing relapse.According to progression of CML,HO-1 expression level in CML patients increased from CP （0.009 5±0.017 6） to AP （0.028 0±0.055 7） and then to BP （0.276 7± 0.447 0）.And there was a linear correlation between HO-1 expression and proportion     

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。     

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,     

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、     

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     

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。     

Effects of tacrolimus and cyclosporine treatment on metabolic syndrome and cardiovascular risk factors after renal transplantation: a meta-analysis

Background The therapeutic success of renal transplantation has been largely attributable to the development of effective and balanced immunosuppressive treatment regimens.This study provides a meta-analysis of a series of randomized controlled trials that compared the effects of tacrolimus and cyclosporine on metabolic syndrome （MetS） and cardiovascular risk factors after renal transplantation.Methods We searched various electronic databases and bibliographies,including MEDLINE,the Cochrane Central Register of Controlled Trials,and EMBASE,for relevant studies published prior to October 2012.Results Our meta-analysis included five randomized controlled trials that examined a total of 923 patients.The tacrolimus group and the cyclosporine group exhibited no significant differences in MetS incidence after renal transplantation; risk ratio （RR）：1.06,95％ confidence interval （C/）：0.73-1.55,P=0.76.Cyclosporine treatment was associated with a higher incidence of hyperlipidemia （RR：0.50,95％ CI：0.39-0.64,P ＜0.01）.Although there were no statistically significant differences,cyclosporine treatment was associated with a higher incidence of hypertension （RR：0.91,95％ CI：0.83-1.00,P=0.06） after renal transplantation compared to tacrolimus treatment,and tacrolimus treatment was associated with a higher incidence of diabetes after renal transplantation （RR：1.79,95％ CI：0.98-3.27,P=0.06） compared to cyclosporine treatment.Conclusions Compared to tacrolimus treatment,cyclosporine treatment was associated with a higher incidence of hyperlipidemia.Future large-scale studies are expected to be conducted to further confirm our findings.     

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。     

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.     

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。     

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）.     

Mechanical tests on the reconstructed anterior cruciate ligament fixed with allogenetic cortical bone cross-pin on the femoral side

Background Anterior cruciate ligament reconstruction （ACLR） has developed dramatically in the last century.Now,ACLR has become a reliable and productive procedure.Patients feel satisfied in 〉90% cases.The aim of this study was to evaluate the feasibility of allogenetic cortical bone cross-pin （ACBCP） used as a clinical fixation method in anterior cruciate ligament reconstruction on the femoral side based on biomechanical tests in vitro.Methods The specimens were provided by the bone banks of the First Affiliated Hospital of People＇s Liberation Army of General Hospital from September 2011 to June 2012.Fresh deep frozen human allogenetic cortical bone was machined into cross-pins which is 4.0 mm in diameter and 75.0 mm in length.Biomechanical parameters compared with Rigidfix were collected while cross-pins were tested in double-shear test.The load-to-failure test and cycling test were carried out in a goat model to reconstruct anterior cruciate ligament with Achilles tendon autograft on the femoral side fixed by human 4.0 mm ACBCP and 3.3 mm Rigidfix served as control.Maximum failure load,yield load,and stiffness of fixation in single load-to-failure test were compared between the two groups.Cycle-specific stiffness and displacement at cycles 1,30,200,400,and 1 000 were also compared in between.Results In double-shear test both maximum failed load and yield load of 4.0 mm humanACBCP were （1 236.998±201.940） N.Maximum failed load and yield load of Rigidfix were （807.929±110.511） N and （592.483±58.821） N.The differences of maximum failed load and yield load were significant between ACBCP and Rigidfix,P 〈0.05.The shear strength of ACBCP and Rigidfix were （49.243±8.039） MPa and （34.637±3.439） MPa,respectively,P 〈0.05.In the load-to-failure test ex vivo,yield load and maximum failed load of ACBCP fixation complexity （（867.104±132.856）N,（1 032.243±196.281） N） were higher than those of Rigidfix （（640.935±42.836） N,（800.568±64.890） N,P 〈0.05）.However,s     

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.     

程丑夫教授运用六君子汤加减治疗疑难杂症验案举隅

程丑夫教授出身中医世家,是全国第五批名老中医学术继承指导老师,主任医师,博士研究生导师,享受国务院特殊津贴。从医40余年来,善于治疗心脑血管疾病、呼吸系统疾病、脾胃病等,在治疗疑难杂症方面尤为突出。笔者有幸跟师门诊,观程师运用六君子汤加减治疗疑难杂症效果显著,现举验案4则来阐述程丑夫教授从脾胃入手治疗疑难杂病的经验。     

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。     

Comparison of result judgment algorithm of test for interfering factors in the bacterial endotoxins test among Chinese, Japanese, European, American, and Indian pharmacopeias

Background The bacterial endotoxins test （BET） is a method used to detect or quantify endotoxins （lipo-polysaccharide,LPS） and is widely used in the quality control of parenteral medicines/vaccines and clinical dialysis fluid.It is also used in the diagnosis of endotoxemia and in detection of environment air quality control.Although BET has been adopted by most pharmacopoeias,result judgment algorithms （RJAs） of the test for interfering factors in the BET still differ between certain pharmacopoeias.We have evaluated RJAs of the test for interfering factors for the revision of BET described in the Chinese Pharmacopoeia 2010 （CHP2010）.Methods Original data from 1 748 samples were judged by RJAs of the Chinese Pharmacopoeia 2010,the Japanese Pharmacopoeia 2011 （JP2011）,the European Pharmacopoeia 7.0 （EP7.0）,the United States Pharmacopoeia 36 （USP36）,and the Indian Pharmacopoeia 2010 （IP2010）,respectively.A SAS software package was used in the statistical analysis.Results The results using CHP2010 and USP36,JP2011,EP7.0,and IP2010 had no significant difference （P=-0.7740）.The results using CHP2010 of 1 748 samples showed that 132 samples （7.6%） required an additional step; nevertheless there was no such requirement when using the other pharmacopeias.The kappa value of two RJAs （CHP2010 and EP7.0） was 0.6900 （0.6297-0.7504） indicating that the CHP2010 and other pharmacopoeias have good consistency.Conclusions The results using CHP2010 and USP36,JP2011,EP7.0,and IP2010 have different characteristics.CHP2010 method shows a good performance in Specificity,mistake diagnostic rate,agreement rate,predictive value for suspicious rate,and predictive value for passed rate.The CHP2010 method only had disadvantages in sensitivity compared with other pharmacopeias.We suggest that the Chinese pharmacopoeia interference test be revised in accordance with the USP36,JP2011,EP7.0,and IP2010 judgment model.     

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     

Preliminary study on the evaluation of Langerhans cell histiocytosis using F-18-fluoro-deoxy-glucose PET/CT

Background Limited number of studies have been reported regarding the utilization of F-18-fluoro-deoxy-glucose （F-18-FDG） positron emission tomography/computed tomography （F-18-FDG PET/CT） in Langerhans cell histiocytosis （LCH）.The aim of this study was to assess the role of F-18-FDG PET/CT in the diagnosis and treatment of LCH.Methods Eight newly diagnosed and seven recurrent patients with LCH received F-18-FDG PET/CT scans.The diagnosis of LCH was established by pathology,multi-modality imaging,and clinical follow-up.Results F-18-FDG PET/CT was positive in 14 patients with 13 true positives and one false positive.All 45 LCH lesions were F-18-FDG avid including six small bone lesions ＜1.0 cm in diameter.The mean maximal standardized uptake value （SUVmax） was 7.13±4.91.F-18-FDG uptake showed no significant difference between newly diagnosed lesions vs recurrent lesions （SUVmax：6.50±2.97 vs.7.93±6.60,t=-0.901,P=0.376）.Among 45 LCH lesions,68.9％ （31/45） were found in bones and 31.1％ （14/45） in soft tissue.The most commonly involved bones were the pelvis and vertebrae.There was no significant difference in F-18-FDG uptake between bone lesions vs.non-bone lesions （SUVmax：6.30±2.87 vs.8.97±7.58,t=1.277,P=0.221）.In two patients,changes in F-18-FDG uptake on serial PET/CT scans reflected response of lesions to treatment.Conclusions The present study suggests that F-18-FDG PET/CT may be useful for diagnosis and assessing the treatment response of LCH.Because of the small sample size,further research is warranted to confirm our findings.     

Low doses of ethanolic extract of Boldo （Peumus boldus） can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro,but not in cancer cells in vivo or in vitro

OBJECTIVE： Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo （Peumus boldus）, known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin＇s cytotoxicity without affecting its anticancer potential. METHODS： The cytotoxicity of Boldo extract （BE） and cisplatin, administered alone and in combination, was determined in three cancer cell lines （A549, HeLa, and HepG2） and in normal liver cells （WRL-68）. Drug-DNA interaction, DNA damage, cell cycle, apoptosis, reactive oxygen species （ROS） and mitochondrial membrane potential （MMP, Aψ） were also studied. Hepatotoxicity and antioxidant activity levels were determined by alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and glutathione assays in mice. The cytotoxicity of related proteins was tested by Western blotting. RESULTS： Co-administration of BE and cisplatin increased viability of normal cells, but had no effect on the viability of cancer cells. Boldo protected liver from damage and normalized different antioxidant enzyme levels in vivo and also reduced ROS and re-polarized MMP in vitro. Bax and cytochrome c translocation was reduced with caspase 3 down-regulation. Further, a drug- DNA interaction study revealed that BE reduced cisplatin＇s DNA-binding capacity, resulting in a reduction in DNA damage. CONCLUSION： Results indicated that a low dose of BE could be used beneficially in combination with cisplatin to reduce its toxicity without hampering cisplatin＇s anticancer effect. These findings siqnify a potential future use of BE in cancer therapy.