HIV-Specific IL-2^＋ and/or IFN-γ^＋ CD8^＋ T Cell Reponses during Chronic HIV-1 Infection in Former Blood Donors

Objective Conflicting data have been generated from previous studies to determine which kind of relationship exists between HIV-1 specific CD8 Tcell responses and HIV-1 viral load or CD4 count over the course of infection.In this study,153 HIV-1 infected LTNPs were enrolled to investigate the role of HIV-1 specific CD8 T-cell responses in chronic HIV-1 infection among HIV-1 infected former blood donors.Methods The patients were stratified into three groups according to CD4 count：CD4≥500 cells/μL;350 cells/μL≤CD4〈500 cells/μL;CD4〈350 cells/μL.PBMCs were isolated from the patients＇ anticoagulated blood samples.IL-2 and IFN-γ secretions of CD 8 T cells against 17 HIV-1 consensus B full peptide pools were analyzed by using ICS assay.Results An overall inverse correlation were observed between CD4 count and plasma viral load.Although no significant difference was observed during the comparisons of frequency/breadth of HIV-1 specific CD8 T cell responses,CD4 count stratification analysis showed that different correlation pattern existed in three strata：as for patients whose CD4 counts were less than 350 cells/μL,no significant correlations were identified between frequency/breadth of HIV-1 specific CD8 T cell responses and CD4 count/viral load;as for patients whose CD4 counts ranged from 350 cells /μL to 500 cells/μL,significant correlation was only observed between the response breadth of IL-2＋IFN-γ＋ CD8 T cells and CD4 count;however,as for patients whose CD4 counts were more than 500 cells/μL,direct correlations were identified between IL-2＋IFN-γ＋/IL-2＋/IFN-γ＋ CD8 T cells and viral load or CD4 count.Conclusions Universal consistent inverse correlation was only indentified between CD4 count and viral load.The relationship between HIV-1 specific CD8 T cell responses and CD4 count/viral load varied in different CD4 strata,which showed that better preserved CD4 T cells were correlated with better CD8 T cell functions.     

肿瘤缓解分级和ERCC1核蛋白表达可以预测胃食管肿瘤患者新辅助化疗的临床效果

1文献来源 Fareed KR,Al-Attar A,Soomro IN,et al.Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy[J].Br J Cancer,2010,102（11）：1600-1607.     

Antioxidant and Antigenotoxic Activity of Bioactive Extracts from Corn Tassel简

This study is designed to evaluate antioxidant and antigenotoxic activities of corn tassel extracts（CTTs）. The major bioactive components of CTTs include flavonoid, saponin and polysaccharide. The antioxidant properties of the three bioactive components of CTTs were investigated by Ferric Reducing Antioxidant Property（FRAP） and 1, 1-diphenyl-2-picrylhydrazyl（DPPH） assays. The activities of the extracts were determined by assessing the inhibition of mutagenicity of the direct-acting mutagen fenaminosulf, sodium azide, and indirect-acting mutagen 2-aminofluorene using the Ames test（strains TA98 and TA100）. The results showed that the extraction rates of flavonoid, saponin, and polysaccharide from the dried corn tassels were 1.67%, 2.41% and 4.76% respectively. DPPH and FRAP assay strongly demonstrated that CTTs had antioxidant properties. CTTs at doses of 625, 1250 and 2500 μg per plate reduced 2-aminofluorene mutagenicity by 12.52%, 28.76% and 36.49% in Salmonella typhimurium TA98 strain assay respectively and by 10.98%, 25.27% and 37.83%, at the same doses in Salmonella typhimurium TA100 assay system, respectively. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide（MTT） assay showed that the different concentrations of CTTs inhibited the proliferation of MGC80-3 cells in a dose-dependent manner（P0.01）. It is concluded that these integrated approaches to antioxidant and antigenotoxicity assessment may be useful to study corn tassel as a natural herbal material.     

TGF-β1 Precursor and CD8 Are Potential Prognostic and Predictive Markers in Operated Breast Cancer简

The transforming growth factor β1（TGF-β1） and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130（stageⅠ–Ⅲ） invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival（DDFS）（HR=8.416, 95% CI=1.636–43.292, P=0.011） in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival（OS） than their counterparts with CD8-positive cell infiltration into tumor nests（Log-Rank, P=0.003）. But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy（Log-Rank, P=0.013） and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor（t-TGF-β1-pre）-positive patients than in the negative patients in patients without recieiving chemotherapy（P=0.053）, OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy（P=0.035） and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS（HR=0.392 95% CI=0.157–0.978, P=0.045） in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.     

Protective effect of autophagy inhibition on ischemia-reperfusioninduced injury of N2a cells

Autophagy is a conserved and programmed catabolic process that degrades damaged pro- teins and organelles. But the underlying mechanism and functions of autophagy in the ische- mia-reperfusion （IR）-induced injury are unknown. In this study, we employed simulated IR of N2a cells as an in vitro model of IR injury to the neurons and monitored autophagic processes. It was found that the levels of Beclin-1 （a key molecule of autophay complex, Beclin-1/elass III PI3K） and LC-3 II （an autophagy marker） were remarkably increased with time during the process of ischemia and the process of reperfusion after 90 min of ischemia, while the protein kinases pTOS6K and roTOR which are involved in autophagy regulation showed delayed inactivation after reperfusion. Admini- stration of 3-methyladenine （3MA）, an inhibitor of class III PI3K, abolished autophagy during reper- fusion, while employment of rapamycin, an inhibitor of mTORC1 （normally inducing autophagy）, surprisingly weakened the induction of autophagy during reperfusion. Analyses of mitochondria function by relative cell viability demonstrated that autophagy inhibition by 3-MA attenuated the de- cline of mitochondria function during reperfusion. Our data demonstrated that there were two distinct dynamic patterns of autophagy during IR-induced N2a injury, Beclin-1/class III PI3K com- plex-dependent and mTORCl-dependent. Inhibition of over-autophagy improved cell survival. These suggest that targeting autophagy therapy will be a novel strategy to control IR-induced neuronal damage.     

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     

吉非替尼与标准化疗对EGFR突变的晚期非小细胞肺癌患者疗效和安全性的比较

1文献来源 Makoto M, Akira I, Kunihiko K, et al. Gefitinib or chemotherapy for non-small cell lung cancerwith mutated EGFR [J]. N Engl J Med, 2010, 362（25） ： 2380-2388.     

Competition between TRAF2 and TRAF6 Regulates NF-κB Activation in Human B Lymphocytes

Objective To investigate the role of TNF receptor-associated factor 2 （TRAF-2） and TRAF6 in CD40-induced nuclear factor-κB （NF-κB） signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2,TRAF2-shRNA,or TRAF6-shRNA. The activation of NF-κB was detected by Western blot,kinase assay,transfactor enzyme-linked immunosorbent assay （ELISA）,and fluorescence resonance energy transfer （FRET）. Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-κB activity was examined following stimulation with recombinant CD154. Results TRAF2 induced activity of IκB-kinases （IKKα,IKKi/ε）,phosphorylation of IκBα,as well as nuclear translocation and phosphorylation of p65/RelA. In contrast,TRAF6 strongly induced NF-κB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA,but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However,the two TRAFs competed for CD40 binding. Conclusions These results indicate that TRAF2 can signal in human B cells,but it is not essential for CD40-mediated NF-κB activation. Moreover,TRAF2 can compete with TRAF6 for CD40 binding,and thereby limit the capacity of CD40 engagement to induce NF-κB activation.     

吸烟和肺癌的遗传易感性

1951年．英国所有男医生都收到了来自Doll的邀请,共计40710人加入了一项为期5年的吸烟和非吸烟人群肺癌发病率的队列研究,1957年,英国医学研究委员会宣布：世纪初肺癌激增的始作俑者是吸烟,从而使“吸烟有害健康”写上了烟盒：1963年,Tokuhata等首次展示了遗传与肺癌休戚与共的关系,肺癌患者一级亲属增高2．5倍的肺癌发病率和吸烟无关。从此,吸烟、基因与肺癌的三角关系一直扑朔迷离。而近来一系列革命性的研究正在形成一句话“肺癌在本质上是一种基因病”。     

Role of progesterone in TLR4-MyD88-dependent signaling pathway in pre-eclampsia

The role of progesterone in the Toll-like receptor 4 （TLR4）-MyD88-dependent signaling pathway in pre-eclampsia was studied. Peripheral blood mononuclear cells （PBMCs） from pre-eclampsia （PE） patients were subjected to primary culture, and stimulated with different concentra- tions of progesterone （0, 10^-8, 10^-6, and 10^-4 mol/L）. The mRNA expression of TLR4, MyD88 and nu- clear factor-kappaB （NF-κB） was detected by using real-time PCR. The Ikappa-B protein expression was detected by using Western blotting. The expression of tumor necrosis factor-or （TNF-α and inter- leukin-6 （IL-6） in the supernatant was determined by using ELISA. With the concentrations of proges- terone increasing, the mRNA expression levels of TLR4, MyD88 and NF-κB in 2^△△CT value were sig- nificantly decreased, and the IkappaB protein expression levels were significantly increased. The TNF-α and IL-6 expression showed a downward trend when the progesterone concentration increased, and there were significant differences among all of the groups （P〈0.05）. It was suggested that progesterone can inhibit the TLR4-MyD88-dependent signaling pathway in PE significantly and benefit for the preg- nancy.     

透过现象看本质：腺癌国际新分类更有利于肺癌个体化治疗吗?

国际肺癌研究协会（International Association for the Study of Lung Cancer,IASLC）／美国胸科学会（American Thoracic Society,ATS）／欧洲呼吸学会（European Respiratory Society,ERS）于今年2月份颁布了肺腺癌的国际多学科分类新标准（Travis,et al．JTO 2011）。     

Thl immunity is not required for the effect of lipopolysaccharide exposure on modifying asthmatic responses of mice before sensitization

Background Disequilibrium of Th1/Th2 is known as an important cause of allergic asthma with a biased Th2 type response. It has been shown that lipopolysaccharide （LPS） administration during post-sensitization modified the inflammation of asthma via upregulating the Thl response that decrease the Th2 immunity. We would like to know if, during pre-sensitization, the elevated Thl response is necessary for LPS exposure to modify the asthmatic response. Methods During pre- or post-sensitization, 40 IJg LPS were intraperitoneal injected （i.p.） to asthmatic mice sensitized and challenged by Dermatophagoides farinae （D. farinea）. Inflammation was assessed by examining bronchoalveolar lavage fluid （BALF） for the number and identity of cells and by cytokine titers measured by ELISA. Semi-quantified RT-PCR was used to evaluate the level of Toll-like receptor 4 （TLR4） mRNA in dendritic cells （DCs） from bone marrow （BMDCs）. Results These investigations demonstrated that LPS exposure during pre-sensitization inhibited the Th2 cytokine and inflammatory infiltration, the same as with LPS exposure during post-sensitization in allergic asthma mice. Contrary to post-sensitization LPS exposure, the Thl cytokines were not upregulated by pre-sensitization with LPS. Finally, the study failed to show any significant difference between TLR4 mRNA expressed in BMDCs with the two times of LPS exposure. Conclusions Our data suggest that elevated Thl immunity is not required for the modification of the Th2 response induced by LPS exposure during pre-sensitization in asthmatic mice and that pre-sensitization differs from post-sensitization. Immune modulation with treatment is independent of TLR4 expression in BMDCs. This study implicates a potential wav to protect from allergic disease and an inflammatory response.     

学术自述

1978年,我调往中国社会科学院哲学研究所。到了哲学所,我面临着科研方向的重要抉择。我决定选择科学哲学和生命伦理学作为我今后科研的主要方向。由于闭关多年,我们对世界科学哲学的长足发展一无所知,对波普尔、库恩等科学哲学家一无所知。实际上,自然辩证法是中国马克思主义派的科学哲学,但不参加科学哲学的国际对话,是无法进一步发展自己的。对新出现的生命伦理学这一新领域也一无所知。     

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:津液辨证(英文)

Intraditional Chinese medicine (TCM),the so-called津液refers to all the fluid and liquid flowingand maintaining inside the human body.In Chineselanguage,津液is a phrase composed of twoChinese characters which describes two differentkinds of fluid or liquid in the human body .According to the theory of TCM,津refers to thepart of fluid that is thin in texture and flowss moothly inside the body while液refers to thepart of fluid that is thick in texture and mainlymaintains in the joints of the body to nourish andlubr...     

Dioscin-induced Apoptosis of Human LNCaP Prostate Carcinoma Cells through Activation of Caspase-3 and Modulation of Bcl-2 Protein Family简

Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin（1, 2 and 4 μmol/L） could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family.     

Efficacy of Different Iron Controlling Fortificants in Wheat Flour in Iron Deficiency

Objective To observe the different impacts of electrolytic iron, FeSO4, and NaFeEDTA on body iron store of anemic school students. Methods Four hundreds anemic students at the age of 11-18 years were divided into four groups. Of which, three consumed different iron fortificants from wheat flour as food vehicle for six months and one consumed non-fortified flour （control）. The fortification level of electrolytic iron, FeSO4, and NaFeEDTA was 60 mg Fe/kg, 30 mg Fe/kg, and 20 mg Fe/kg, respectively. Blood samples were collected at 0, 2, 4, and 6 months and hemoglobin （Hb）, serum ferritin （SF）, and transferrin receptor （TfR） were measured. Results The hemoglobin levels in three intervention groups increased, the increments of Hb in the NaFeEDTA group were significantly higher than that in the other groups. SF and TfR levels increased in the tested groups and body iron store in the NaFeEDTA group was higher than that in the other groups. These parameters did not show any significant changes in the control group. Conclusion NaFeEDTA and FeSO4 tortified wheat flour has positive impacts on iron status in anemic students and NaFeEDTA is more effective than FeSO4, while electrolytic iron is less effective in improving iron store in anemic students.     

A （H1N1） Influenza Pneumonia with Acute Disseminated Encephalomyelitis： A Case Report

INTRODUCTION
A 56-year-old Chinese female patient with A （H1N1） influenza pneumonia accompanied by acute disseminated encephalomyelitis （ADEM） of the Central Nervous System （CNS） is described in this article. The patient had typical clinical manifestation, and the diagnosis was reached after MRI and other examinations. From this case, we can conclude that the virus of A （H1N1） influenza can infect CNS, and we should pay more attention to patients of A （H1N1） influenza pneumonia with neurological complications.     

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。