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.     

Tracking in vivo migration and distribution of antigen-specific cytotoxic T lymphocytes by 5,6-carboxyfluorescein diacetate succinimidyl ester staining during cancer immunotherapy

Background Killing of targeted tumors during adoptive cell transfer therapy is associated with cytotoxic T lymphocyte （CTL） numbers,immunophenotype,tumor-specificity,and in vivo residence time,migration,and distribution.Therefore,tracing in vivo persistence,migration,and distribution of CTLs is important for cancer immunotherapy.Methods Optimal staining concentration for CTL proliferation was determined by cell counting kit-8 （CCK-8） assay and killing efficiencies of CTLs or carboxyfluorescein diacetate succinimidyl ester （CFSE）-labeled melanoma antigen-specific cytotoxic T lymphocytes （CFSE-CTLs） for malignant melanoma cells in vitro were compared.Additionally,CFSE-CTLs were intravenously transfused to mice receiving B16 melanoma,and their residence time,migration,and distribution in vivo were observed by measuring fluorescence intensities of CFSE-CTLs per gram of tissue （％FI/g） in various tissues and analyzing tumor/non-tumor （T/NT） values.Anti-tumor effects of transferred CTLs and correlation between ％FI/g and D-value of tumor size were analyzed.Results Five-micromolar CFSE was optimal for labeling CTLs with minimal cytotoxicity.No significant difference occurred between CTLs and CFSE-CTLs for tumor cell killing （P=0.849） or interleukin-2 （P=0.318） and interferon-y （P=0.201）levels.Distribution of CTLs in vivo varied with time.A negative correlation between ％FI/g in tumors and D-value of tumor sizes by Spearman correlation analysis was observed.CTLs were recruited to and killed tumors from 6 hours to 3 days after cell infusion.CTLs were observed up to three weeks later in the tumor,liver,kidneys,and spleen; this was related to the abundant blood supply or the nature of immune organs.Conclusions CCK-8 assay is a novel method to select optimal CFSE staining concentrations.Fluorescence intensity of transferred CTLs reflects their killing efficiency of tumors.CFSE fluorescent markers can trace in vivo CTL persistence,migration,and distribution because of its stability,long half-life,and low toxicity.     

克唑替尼和化疗在进展期ALK阳性肺癌患者中的疗效比较

1文献来源 Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK- positive lung cancer[J]. N Engl J Med,     

确定维持治疗获益的非小细胞肺癌患者:来自JMEN试验的后续分析

1文献来源 Obasaju C, Bowman L, Wang P, et al. Identifying the target NSCLC patient for maintenance therapy： An analysis from a placebo-controlled,     

Antiviral therapy for ＂difficult-to-treat＂ hepatitis C virus-infected patients

Objective To review the updated research on direct antiviral agents （DAAs）-including regimens for hepatitis C virus （HCV）,and focus on ＂difficult-to-treat＂ HCV-infected patients.Data sources The literature concerning DAAs and hepatitis C cited in this review was collected from PubMed and Google Scholar databases published in English up to July 2013.Study selection Data from published articles regarding HCV and DAAs in clinical trials and in clinical use were identified and reviewed.Results It was recognized that some ＂difficult-to-treat＂ patients would still exist,even though stronger treatments using such as DAAs,including telaprevir and boceprevir,which lead to higher sustained virological response rates,are available.Such patients include those with advanced fibrosis/cirrhosis,elderly persons,children,HCV-human immunodeficiency virus co-infected patients,HCV-infected recipients,and so on.Conclusions Certain ＂difficult-to-treat＂ patients would still exist,even though stronger treatment is available.Although evidence from clinical trials is still lacking,interferon-sparing regimens could have stronger effects for eradicating HCV in such cases.     

Biocompatibility, biodegradation, and neovascularization of human single-unit platelet-rich fibrin glue: an in vivo analysis

Background The clinical applications of fibrin glue span over several surgical modalities.The aim of this study was to evaluate the biocompatibility and biodegradation of different formulations of platelet-rich fibrin glue in vivo and examine its effects on the neovascularization of wound sites.Methods Human-derived single-unit fibrin glue was prepared.Incisions were made on the backs of rats,and these were coated with homemade glues containing different concentrations of aminomethylbenzoic acid （Groups A-F） or commercial adhesives （Group G）.A sham control group was included （Group H）.The wounds were examined by histological analysis and immunohistochemistry at several time points.Results Successful wound closure was achieved in all groups by day 12.Acute inflammation occurred during the first six days,but gradually disappeared.The longest sealant duration was achieved using the lowest concentration of antifibrinolytic agent in a 1：10 volume ratio with cryoprecipitate.Expression levels of the platelet endothelial cell adhesion molecule-1 were significantly higher in Groups A and C compared to the control groups （Groups G and H） on day 3 （P ＜0.05）.Conclusions Single-unit platelet-rich fibrin glue has excellent biocompatibility and is associated with the upregulation of neovascularization.The addition of aminomethylbenzoic acid could prevent the degradation of fibrin glue.     

Amplification of functional myeloid-derived suppressor cells during stem cell mobilization induced by granulocyte colony-stimulation-factor

The effects of granulocyte colony-stimulation-factor （G-CSF） on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells （MDSCs） of donor mice were ex- amined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injec- tion of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive mole- cules derived from MDSCs in serum and spleen, including hydrogen dioxide （H202） and nitric oxide （NO）, and the activity of nitric oxide synthase （NOS） were determined during the mobilization. Apop- tosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls （P〈0.01）. The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H202 levels were approximately 4-fold greater than the con- trois. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis ofT lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.     

儿童间变性大细胞淋巴瘤的诊断与治疗

1病历摘要 患儿,男,1岁,因“腹部皮下结节2个月余”入院。患儿于2个月前发现腹部散在丘疹样皮下小结节,无发热及疼痛,伴瘙痒,抗过敏及抗菌治疗无效。入院体查：发育营养良好,皮肤黏膜无黄染,腹部触及多个直径约0．5cm皮下结节。颌下、双侧腹股沟淋巴结多枚（0．2～0．5cm）,左侧腹股沟可触及大小约3．0×4．0cm肿物,右腋前可触及大小约5．0×6．0cm肿物,质中。余体查正常。     

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.     

吉非替尼或紫杉醇-卡铂治疗肺腺癌

1文献来源 Mok TS, Wu YL, Thongprasert S, et at.Gefitinib or Carboplatin-Paclitaxel in pulmonaryadenocarcinoma [J]. N Engl J Med, 2009,361（10）：947-957.     

吉非替尼/厄洛替尼联合同期放疗治疗晚期肺癌

1文献来源 Chang CC, Chi KK, Kao SJ, et al. Upfront Gefitinib/Erlotinib treatment followed by concomitant radiotherapy for advanced lung cancer： A mono- institutional experience [J]. Lung Cancer, 2011,73 （2） ： 189-194. 2 证据水平     

Relevance of muscle biopsy for diagnosing multifocal motor neuropathy

Multifocal motor neuropathy （MMN） is a rare,.focal,inflammatory,demyelinating disease of the peripheral nerves with pure motor involvementJ MMN is clinically characterized by slowly progressive,asymmetric,distal,upper limb predominant weakness,in the absence of sensory disturbances） Weakness is usually multifocal and connected to a distinct motor nerve,such as the musculocutaneous nerve resulting in biceps weakness,the posterior interosseus nerve resulting in finger drop,the median,ulnar,or radial nerve resulting in dexterity problems or grip weakness,or the peroneal nerve resulting in a foot drop.Onset of clinical manifestations is between 20 and 50 years of age.The prevalence of MMN is reported as 1-2 per 100 000.2 MMN is three times more frequent in men as compared to women.     

Inhibitory Effects of Mild Hyperthermia plus Docetaxel Therapy on ER（＋/-） Breast Cancer Cells and Action Mechanisms

Summary： The purpose of this study was to verify that a combination of mild hyperthermia and do- cetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach. The effects of docetaxel on the proliferation of cells from the estrogen receptor （ER）-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, and effective experimental concentrations of docetaxel were determined. The effects of mild hy- perthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate （FITC）/propidium iodide （PI） staining. The effects of these combined treatments on cell cycle progres- sion in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cy- tometry. The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase （MAPK） pathways were analyzed by using Western blotting. The effects of these combined treatments on the expression of the heat shock protein 70 （HSP70） and the multi-drug resistance （MDR） gene product P-glycoprotein （Pgp） were examined by using Western blotting. The results showed that the half-maximal inhibitory concentration （IC50） of do- cetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31 gmol/L respectively. Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453 cells. Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from （23.66±3.59）% and （18.51±3.17）% in docetaxel treatment group to （47.12±6.73）% and （55.16±7.42）% in mild hyperthermia plus docetaxel group, indicating that the mild hyperthermia and docetaxel therapeutic approaches exhib- ited significant synergistic antitumor effects. Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells. Western blotting demonstrated that pro- teins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone. As compared with blank control group, cells from the mild hyperthermia plus docetaxel group exhibited significantly decreased B-cell lym- phoma 2 （Bcl-2） protein expression but slightly increased Bcl-2-associated X protein （Bax） expression. Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia. It was concluded that treatments of mild hyperthermia plus docetaxel in- hibited the proliferation of human breast cancer cells, promoted apoptosis of breast cancer cells, and produced synergistic antitumor effects.     

基于SUV的PET对 4周期化疗后的弥漫大B细胞淋巴瘤患者预后的评估

在过去的十来年中,18氟脱氧葡萄糖（fluorodeoxyglucose,FDG）PET已经成为多种淋巴瘤疗效评价的有力工具,它主要通过视觉分析来评估疗效。修订后的判读标准适合评估化疗结束后的疗效。而不适用于化疗期间的疗效评价。     

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,     

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.     

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...