Immune regulation of hydrogen sulfide in children with acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia （ALL） and chemotherapy can cause immune imbalance,and gaseous molecule hydrogen sulfide （H2S） can participate in the process of immune response.This study aimed to investigate the immune regulation of H2S in pediatric ALL.Methods Children （n=78） with ALL admitted during 2010-2013 were included in this study.Two blood samples were collected in period of before chemotherapy,bone marrow remission and two days after chemotherapy,respectively.Serum contents of H2S and cytokines,including interleukin-1β （IL-13）,interleukin-2 （IL-2）,interferon-γ （IFN-γ）,tumor necrosis factor （TNF-α）,interleukin-4 （IL-4）,interleukin-6 （IL-6）,interleukin-10 （IL-10） and macrophage inflammatory protein-1α （MIP-1a）,were detected using ELISA method.Stepwise regression was used to analyze the correlation between H2S and cytokines.Furthermore,human Jurkat cells were cultured in vitro,and nucleoprotein of Jurkat cells and peripheral blood mononuclear cells （PBMCs） were collected,contents of cystathionine γ-lyase （CSE） and certain cytokines were measured by Western blotting.Results Serum concentrations of H2S,IL-13,IL-6,IL-10 and MIP-1α in children with ALL were increased significantly （P ＜0.01）,while concentrations of IL-2,TNF-α,IFN-γ and IL-4 decreased obviously （P ＜0.01）.In patients after chemotherapy,concentrations of H2S and IL-10 were decreased significantly （P ＜0.05）,but IL-4 and IFN-γ concentrations increased markedly （P ＜0.05）.At remission stage,H2S,IL-13,IL-4,IL-6,IL-10 and MIP-1α concentrations were further decreased markedly （P ＜0.05）,but concentrations of IL-2,TNF-α and IFN-γ increased again （P ＜0.05）.Protein contents of CSE,IL-10,IL-4 and IL-2 of PBMCs also increased markedly in children with ALL.Moreover,changes of CSE protein contents of PBMCs were consistent with serum H2S contents,and there were significant correlation between H2S and certain cytokines based on stepwise regression analysis.     

Outcome of childhood acute lymphoblastic leukemia: a report of 121 patients treated at Wuhan Union Hospital of China

Prognostic factors are biological or physical characteristics of a patient or the patient＇s cancer that can be used to predict the outcome of the individual. The prognosis of childhood acute lymphoblastic leukemia （ALL） has been improved greatly in the past 40 years, reaching a long-term event free survival （EFS） of about 75% and overall survival of about 80% in developed countries.3-6 The same result has also been achieved in China. The ALL-XH-99 Protocol at Shanghai Children＇s Medical Center adopted early intensification treatment and triple intrathecal chemotherapy with high-dose methotrexate treatment for all patients and intensive chemotherapy in median risk （MR） and high risk （HR） patients. More intensive chemotherapy might cause more complications. In order to reevaluate the outcome of childhood ALL treated with the ALL-XH-99 Protocol and to fully elucidate the prognostic factors and the sequelae, a retrospective analysis was carried out to evaluate patients diagnosed with childhood ALL who were treated with the ALL-XH-99 Protocol in the past decade.     

Changes of sulfur dioxide, nuclear factor-κB, and interleukin-8 levels in pediatric acute lymphoblastic leukemia with bacterial inflammation

Background Bacterial inflammation is a common complication in patients with leukemia,and sulfur dioxide （SO2） is a bioactive molecule in modulating Gram-negative bacilli infection.This study aimed to examine the changes in SO2,nuclear factor-κB （NF-κB）,and interleukin-8 （IL-8） levels in pediatric acute lymphoblastic leukemia （ALL） with Gram-negative bacterial inflammation.Methods Fifty-five ALL children were enrolled in this study,including 30 males and 25 females,aged 3-13 years,and the median age was 7.8 years.All these children who accepted chemotherapy for ALL were divided into the control group （before chemotherapy）,the infection group （after chemotherapy with infection）,and the recovery group （the infection was controlled after 1 week）.The serum level of SO2 was detected using high performance liquid chromatography with fluorescence assay,and NF-κB and IL-8 levels were measured by enzyme-linked immunosorbent assay （ELISA）.Human THP-1 cells were cultured,induced,and differentiated into macrophages,which were divided into five groups and each group was cultured with different stimulators：lipopolysaccharide （LPS） group,LPS＋L-aspartate-β-hydroxamate （HDX） group,LPS＋SO2 group,SO2,and control groups.NF-κB level and IL-8 protein contents by ELISA were examined in each group.Results In comparison with those of the control group,levels of serum SO2,NF-κB,and IL-8 of the infection group were significantly increased （P ＜0.05）,while those of the recovery group were significantly decreased （P ＜0.05）.A positive correlation was found between levels of serum SO2 and intracellular NF-κB/IL-8,and the correlation coefficients were 0.671 and 0.798 （P ＜0.05）,respectively.According to the results found in human THP-1 cells,levels of NF-κB and IL-8 in LPS group were significantly increased compared with those of the control group （P ＜0.05）; when compared with those in LPS group,levels of NF-κB in LPS＋HDX group further increased significantly （P ＜     

首诊于眼科的急性淋巴细胞白血病1例

1临床资料 患者,男,73岁,因“左眼红肿疼痛、眼球突出1个月”于2011年9月2日来淄博市第一医院眼科就诊。眼部检查：右眼视力0．6,左眼指数／50 cm;右眼眼压17 mmHg,左眼无法检查。右眼前节及眼底未见明显异常。左眼球向前下方突出固定,突出度22 mm,各方向运动受限;上下眼睑充血肿胀,眶压高,触痛明显,眶内触及肿物,质硬、固定、弥漫性;泪腺肿大,睑结膜充血水肿,角膜清,前房深度正常,瞳孔圆,直径约3 mm,对光反应迟钝;晶体皮质部分灰白色混浊;眼底模糊,见视乳头色红,边界模糊,视网膜未见出血及渗出。全身检查：皮肤黏膜无出血点、无瘀斑、无皮下结节,全身浅表淋巴结无肿大,胸骨无压痛,双肺呼吸音清,心律齐,心音可,腹部平软,肝脾肋下未触及,双下肢无浮肿。眼眶MRI提示：左眼眶内眼球外后上方异常信号占位影,考虑为炎性假瘤（图1）。眼B超提示：左眼眶内不规则占位病变,内回声较少（图2）。肝胆胰脾彩超、血常规正常。入院诊断：左眼眶内炎性假瘤？左眼眶内占位性病变,双眼老年性白内障始发期。诊疗过程：甲强龙500 mg,每天1次静脉滴注,共3 d,治疗后患者左眼视力0．2,上下睑充血明显减轻,眶压较前降低,触痛消失,眶内仍触及肿物。停用甲强龙,口服强的松片80 mg,每天晨起顿服,后按疗程规律减量。     

Vindesine induces rhabdomyolysis in patients with acute lymphoblastic leukemia

Rhabdomyolysis is a syndrome which involves myoglobin and other intracellular proteins and electrolytes that occurs from breakdown of skeletal muscleand leak into the circulation. The clinical symptoms of rhabdomyolysis include myalgia, tenderness on palpation, weakness, brown urine, fever, myoglobinuria, electrolyte imbalance, and acute renal failure. Rhabdomyolysis can be severe enough to be life threatening. The causes of rhabdomyolysis include alcohol, electrolyte imbalance （potassium, phosphorus, and magnesium depletion）, viral myositis, trauma, connective tissue diseases, drug reaction, toxication, exercise, metabolic diseases, seizures, and hereditary enzyme deficiencies. The exact mechanisms underlying rhabdomyolysis are not fully understood, but it is clear that muscle damage can be caused by direct muscle injury or metabolic inequalities between energy production and energy consumption.     

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，     

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。     

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.     

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.     

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、     

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 of Bioactive Human β Defensin 4 in COS-7 Cell

Objective To establish a cell line for stable expression of bioactive human beta-defensin 4 （HBD4）. Methods The full-length HBD4-cDNA was isolated from previously constructed cloning vector pMD18-T/HBD4 by restriction endonuclease digestion and cloned into eukaryotic expression vector pcDNA3.1＋ to construct pcDNA3.1＋/HBD4. The recombinant vector identified carrying HBD4 with right sequence was introduced into COS-7 cells by Lipofectamine. Cell clones survived in G418-rich medium and with stable expression of HBD4 in both mRNA and protein level were identified by RT-PCR and western blot respectively. The antimicrobial activity of the secreted HBD4 was also evaluated. Results The full-length HBD4-cDNA was successfully cloned into eukaryotic expression vector pcDNA3.1＋. COS-7 cells transfected with pcDNA3.1＋/HBD4 expressed HBD4 stably in mRNA and protein level. The HBD4 protein secreted into the culture medium showed strong antimicrobial activity against P. aeruginosa ATCC 27853 and E. coli ATCC 25922. Conclusion We successfully established a stable bioactive HBD4-expressing cell line.     

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.     

短程、间歇伊马替尼联合传统化疗（NILG09/00方案）在Ph+ ALL治疗中的作用

1文献来源 Renato B, Giuseppe R, Enrico MP, et al. Chemotherapy-phased Imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia： Northern Italy leukemia group protocol 09/00[J]. J Clin Oncol, 2010,28 （22） ： 3644-3652.     

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.     

社区老年人原发性高血压、冠状动脉粥样硬化性心脏病、脑卒中和糖尿病4种慢性病相关因素分析

原发性高血压、冠状动脉粥样硬化性心脏病、脑卒中和糖尿病在老年慢性病中占有重要地位，以上4种疾病有许多共同的危险因素，为了更有效的了解、控制这些危险因素，并实施有效的干预措施，我们对社区老年健康档案资料进行了调查，并对这4种疾病的危险因素进行了分析，现报道如下。     

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.     

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     

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。