重金属Zn、Cu和Hg对基因重组发光菌的综合毒性及其联合效应

分析了3种常见重金属(Zn^(2+)、Cu^(2+)、Hg^(2+))对基因重组发光菌(E.coli HB101 pUCD607)的单一毒性和不同质量浓度比条件下的联合毒性作用,并采用毒性单位法(Toxic Unit)、Marking相加指数法(Additional Index)和混合毒性指数法(Mixture Toxicity Index)来评价混合体系的联合毒性作用类型.Zn^(2+)、Cu^(2+)和Hg^(2+)3种重金属离子对发光细菌的15 min半数效应浓度(EC50)分别为:4.24、5.99、2.27 mg/L.多元重金属离子混合体系主要呈现不同程度的拮抗作用,不同的评价方法对3种重金属离子的联合效应评价结果具有较好的一致性.上述重金属联合毒性作用研究结果可为重金属复合污染控制和生物毒性测试提供参考.

Does gemcitabine-based combination therapy improve the prognosis of unresectable pancreatic cancer?

AIM:To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS:A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy in locally advanced or metastatic pancreatic cancer.Inclusion was limited to highquality randomized clinical trials.RESULTS:Twenty-six studies were included in the present analysis,with a total of 8808 patients recruited.The studies were divided into four subgroups based on the different kinds of cytotoxic agents,including platinum,fluoropyrimidine,camptothecin and targeted agents.Patients treated with gemcitabine monotherapy had significantly lower objective response rate [risk ratio(RR),0.72;95% confidence interval(CI):0.63-0.83;P < 0.001],and lower 1-year overall survival(RR,0.90;95%CI:0.82-0.99;P = 0.04).Gemcitabine monotherapy caused fewer complications,including fewer grade 3-4 toxicities:including vomiting(RR,0.75;95%CI:0.62-0.89;P = 0.001),diarrhea(RR,0.66;95%CI:0.49-0.89;P = 0.006),neutropenia(RR,0.88;95%CI:0.72-1.06;P = 0.18),anemia(RR,0.96;95%CI:0.82-1.12;P = 0.60),and thrombocytopenia(RR,0.76;95%CI:0.60-0.97;P = 0.03) compared with gemcitabine combination therapies.CONCLUSION:Gemcitabine combination therapy provides a modest improvement of survival,but is associated with more toxicity compared with gemcitabine monotherapy.

Antiviral Activity of Recombinant Cyanovirin-N against HSV-1

In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CV-N on HSV-1 in Vero cells.The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR).The results showed that CV-N had a low cytotoxicity on Vero cells with a CC50 of 359.03±0.56 μg/mL,and that it could not directly inactivate HSV-1 infectivity.CV-N not only reduced the CPE of HSV-1 when added before or after viral infection,with a 50% inhibitory concentration (IC50) with 2.26 and 30.16μg/mL respectively,but it also decreased the copies of HSV-1 DNA in infected host cells.The encephalitis model for HSV-1 infection was conducted in Kunming mice,and treated with three dosages of CV-N (0.5,5 & 10 mg/kg) which was administered intraperitoneally at 2h,3d,5d,7d post infection.The duration for the appearance of symptoms of encephalitis and the survival days were recorded and brain tissue samples were obtained for pathological examination (HE staining).Compared with the untreated control group,in the 5mg/kg CV-N and 10mg/kg CV-N treated groups,the mice suffered light symptoms and the number of survival days were more than 9d and 14d respectively.HE staining also showed that in 5mg/kg CV-N and 10mg/kg CV-N treated groups,the brain cells did not show visible changes,except for a slight inflammation.Our results demonstrated that CV-N has pronounced antiviral activity against HSV-1 both in vitro and in vivo,and it would be a promising new candidate for anti-HSV therapeutics.

Properties of Polysaccharides in Several Seaweeds from Atlantic Canada and Their Potential Anti-Influenza Viral Activities

To explore the polysaccharides from selected seaweeds of Atlantic Canada and to evaluate their potential anti-influenza virus activities, polysaccharides were isolated from several Atlantic Canadian seaweeds, including three red algae (Polysiphonia lanosa, Furcellaria lumbricalis, and Palmaria palmata), two brown algae (Ascophyllum nodosum and Fucus vesiculosus), and one green alga (Ulva lactuca) by sequential extraction with cold water, hot water, and alkali solutions. These polysaccharides were ana-lyzed for monosaccharide composition and other general chemical properties, and they were evaluated for anti-influenza virus activities. Total sugar contents in these polysaccharides ranged from 15.4% (in U. lactuca) to 91.4% (in F. lumbricalis); sulfation level was as high as 17.6% in a polysaccharide from U. lactuca, whereas it could not be detected in an alikali-extract from P. palmaria. For polysaccharides from red seaweeds, the main sugar units were sulfated galactans (agar or carrageenan) for P. lanosa, F. lumbricalis, and xylans for P. palmata. In brown seaweeds, the polysaccharides largely contained sulfated fucans, whereas the polysaccharides in green seaweed were mainly composed of heteroglycuronans. Screening for antiviral activity against influenza A/PR/8/34 (H1N1) virus revealed that brown algal polysaccharides were particularly effective. Seaweeds from Atlantic Canada are a good source of marine polysaccharides with potential antiviral properties.

Human Monoclonal Antibodies as Candidate Therapeutics Against Emerging Viruses and HIV-1

More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.

Current Status of Natural Products from Plants as Anti-herpes Simplex Virus 1 Agents

Nucleoside analogues have been the mainstay of clinical treatment of herpes simplex virus 1 (HSV-1) infections since their development. However, the emergence of drug resistant strains has underlined the urgency of the discovery of novel anti-HSV-1 drugs. Natural products, which provided many novel drug leads, are known to be an important source of anti-HSV-1 agents. Herein, we present an overview of natural products with anti-HSV-1 activities isolated from a variety of plants reported in recent years. Several different compounds, mainly belonging to the three groups of polysaccharides, polyphenols and terpenes, showed antiviral effects against HSV-1, indicating their potential to be promising anti-HSV-1 agents.

Toxicity of single-walled carbon nanotubes on green microalga Chromochloris zofingiensis

Nanoparticles,or particles in size of 1-100 nm,are extensively used in the world in different applications.For instance,single-walled carbon nanotubes(SWCNTs) are commonly used in consumer products,such as biosensors,drug and vaccine delivery transporters,and novel biomaterials.Although nanoparticles do not cause safety concerns to consumers who use nanoparticle-containing products,these small particles are potentially harmful for workers who produce them in factories or in cases of discharge to aquatic ecosystems.SWCNTs do not have a natural analogue,so the effects on health of their disposal remain largely unknown.In this study,we evaluated the effects of SWCNTs on a population of the green microalga Chromochloris zofingiensis and the profile and production of pigments and fatty acids.The alga was incubated with SWCNTs for 6 days in 0(control),40,80,160,or 320 mg/L concentrations.SWCNTs showed both positive and negative effects on the growth of C.zofingiensis,with a biomass enhancement at low levels(40-160 mg/L) but inhibition at high levels(320 mg/L).By contrast,a decreased accumulation of fatty acids and pigments of C.zofingiensis was observed over the range of the tested concentrations.These results indicate that the markers on the inhibitive toxicity of SWCNTs are increasingly sensitive in the following order:biomass and fatty acids < primary carotenoids < chlorophylls < secondary carotenoids.C.zofingiensis is a suitable microalga for evaluating the ecotoxicological hazards of SWCNTs,especially in terms of pigmentation response.

Effects of low dose pre-irradiation on the toxicity of cyclophosphamide

Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide(CTX).Methods:Kunming strain male mice were randomly divided into five groups:control group,sham-irradiated group,low dose irradiation group(LDR group),cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group).Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen(control group excluded).On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ-irradiation,30 h later mice of CTX and LDR + CTX groups were injected i.p.3.0 mg cyclophosphamide.All the mice were sacrificed on day 13.DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis(SCGE);ALT activity,total protein(TP) and albumin(ALB) of the plasma were analyzed using automatic biochemistry analyzer;MDA content,SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry;genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow.Results:1.Differences of MDA contents,SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance(P < 0.01);in control group MDA content was the lowest,SOD and GSH-PX activity were the highest,while in CTX group MDA content was the highest,SOD and GSH-PX activity were the lowest;compared with CTX group MDA content decreased significantly(P < 0.01) and SOD and GSH-PX activity increased significantly(P < 0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance(F = 1.262,P > 0.05).Differences of TP and ALB of plasma between 5 groups had statistical significance(F = 12.879 and 6.336 respectively,P < 0.01);TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group,TP and ALB in LDR group elevated significantly(P < 0.05).3.Differences of DNA damage of peripheral lymphocytes had notable statistical significance(F = 6.383,P < 0.01);DNA damage in control group was the lightest,while DNA damage in CTX group was the severest;compared with CTX group,DNA damage in LDR + CTX group was much lighter(P < 0.05).4.MNF of PCE between 5 groups had remarkable significance(F = 179.652,P < 0.01);compared with control group and sham-irradiated group,MNF in CTX group increased significantly(P < 0.01);compared with CTX group,MNF in LDR + CTX group had a tendency of decline,which had no statistical significance(P > 0.05).Conclusion:1.CTX can damage the hepatic tissue through oxidative stress;75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes,promote elimination of free radicals,so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy.2.A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma,but may have protective effect on the protein synthesis function of liver.3.High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes;75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage.4.CTX has potent mutagenic effect,can cause significant increase of MNF of PCE;75 mGy γ-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.

Development and Characterization of Monoclonal Antibody Specific to Nuclear Protein of Avian Influenza Virus Type A

Five monoclonal antibodies（Mabs） to nuclear protein of avain influenza virus（AIV） were developed by syncretizing SP 2/0 and the spleen cells from BALB of mice immuized with H9 subtype AIV. Specificity of these Mabs were identified by immunofluorescent assay（IFA） and enzyme linked immunosorbent assay （ELISA）. These five Mabs which were named as AIV-NP-2C3, AIV-NP-6A5, AIV-NP-3 H9, AIV-NP-7B4, AIV-NP-2H4 could react with all viruses of AIV-H9 strains in tests. The result of Western blotting showed that only the 60 ku protein antigen of AIV-H9 could be recognized by the Mabs but never recognized by New castle disease virus, REV and infectious bursa disease virus. The result of preliminary application showed that avian influenza viruses could be deetected bv Mabs in IFA and ELISA. All these Mabs will probably play important roles in preventing and monitoring avian influenza viruses.

Antiviral Activity of the Effective Monomers from Folium Isatidis Against Influenza Virus in Vivo

In order to evaluate the anti-influenza virus activity of the effective monomer from Folium Isatidis (FI) in vivo,we established mice model with viral pneumonia and divided them into 3 different dose groups,then observed their lung indexes,pulmonary pathological changes,pulmonary virus hemagglitination titers,living time and death rates.The results showed that the monomer could reduce the pulmonary index from 2.64 to 1.93,1.63 and 1.40 (P<0.01) and decrease the hemagglitination titer from 1.15 to 0.84,0.70 and 0.59 (P<0.01).In addition,different groups of FI could significantly lessen the mortality rate from 100% to 30%,25% and 15%,and prolong the living time from 5.1d to 6.5d,8.4d and 8.9d respectively(P<0.01).The high dose (75 mg/kg/d) has the similar effect with 100 mg/kg/d dose of virazole(P>0.05),and more effective than 200 mg/kg/d dose of antiviral liquor (P<0.05).

Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection

AIM:To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism (SNP) and disease progression in chronic hepatitis C.METHODS: Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity (grading) and architectural changes (staging). In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters of liver disease were also investigated. Samples of genomic DNA were genotyped for the respective SNP by 5'-nuclease assays using fluorescent dye-labeled allele-specif ic probes.RESULTS: Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. In the first group, patients homozygous for the variant allele T were found to be younger than C allele carriers (39.6±12.5 vs 45.7±11.5, P=0.008). Among the histological lesions studied, portal lymphoid aggregates were more frequently observed among TT homozygotes than among C carriers (21/37 vs 32/100, P=0.008). The presence of portal lymphoid aggregates was closely correlated with hepatic inflammation (P=0.003) and with bile duct damage (P<0.001). The degree of fibrosis, in contrast, was not found to be related to the CD14 gene C-159T polymorphism.CONCLUSION: The data suggest a possible relationship between CD14 C-159T polymorphism and the formation of portal lymphoid aggregates, but not liver fibrosis progression in chronic hepatitis C.

Cardiac toxicity of trastuzumab in elderly patients with breast cancer

Breast cancer （BC） is diagnosed in 〉 65 year old women in about half of cases. Experts currently recommend that systemic therapy is offered to elderly patients with BC, if, based on their overall conditions and life expectancy, it can be reasonably anticipated that the benefits will outweigh the risks of treatment. Like for young subjects, the monoclonal antibody against human epidermal growth factor receptor-2 （HER-2）, trastuzumab, represents a valid therapeutic option when BC over-expresses this receptor. Unforttmately, administration of trastu- zumab is associated with the occurrence of left ventricular dysfunction and chronic heart failure （CHF）, possibly because of interference with the homeostatic functions of HER-2 in the heart. Registry-based, retrospective analyses have reported an incidence of CHF around 25% in elderly women receiving trastuzumab compared with 10%-15% in those not given any therapy for BC, and the risk of CHF has been estimated to be two-fold higher in 〉 60455 year old trastuzumab users vs. non-users. Extremely advanced age and preexisting cardiac disease have been shown to predispose to trastuzumab cardiotoxicity. Therefore, selection of older patients for treatment with trastuzumab should be primarily based on their general status and the presence of comorbidities; previous chemotherapy, especially with anthracyclines, should be also taken into account. Once therapy has started, efforts should be made to ensure regular cardiac surveillance. The role of selected biomarkers, such as cardiac troponin, or new imaging techniques （three-dimension, tissue Doppler echocardiography, magnetic resonance imaging） is promising, but must be further investigated especially in the elderly. Moreover, additional studies are needed in order to better understand the mechanisms by which trastuzumab affects the old heart.

Pure red cell aplasia due to parvovirus B19 infection after liver transplantation:A case report and review of the literature

Pure red cell aplasia （PRCA） due to parvovirus B19 （PVB19） infectiori after solid organ transplantation has been rarely reported and most of the cases were renal transplant recipients, Few have been described after liver transplantation. Moreover, little information on the management of this easily recurring disease is available at present. We describe the first case of a Chinese liver transplant recipient with PVB19-induced PRCA during immunosuppressive therapy. The patient suffered from progressive anemia with the lowest hemoglobin level of 21 g/L. Bone marrow biopsy showed selectively inhibited erythropoiesis with giant pronormoblasts. Detection of PVB19-DNA in serum with quantitative polymerase chain reaction （PCR） revealed a high level of viral load. After 2 courses of intravenous immunoglobulin （IVIG） therapy, bone marrow erythropoiesis recovered with his hemoglobin level increased to 123 g/L. He had a lowlevel PVB19 load for a 5-too follow-up period without recurrence of PRCA, and finally the virus was cleared. Our case indicates that clearance of PVB19 by IVIG in transplant recipients might be delayed after recovery of anemia.

Studies on acute toxicity of three heavy metal ions to Artemia

Studies on acute toxicity of Cu2+,Mn2+and Zn2^to Artemianauplii(36h)and adults were carried out at15±3°C in the natural seawater where salinity is30using single-factor acute toxicity;on this basis,equi-toxicity test was used to evaluate the effect of joint toxicity of Cu2+,Mn2+and Zn2+to Artemia nauplii(36h)in the same conditions.Results show that Artemia has different tolerances for the three heavy metal ions when it is in different growth period,and the interaction of heavy metal ions varied with growth period,adults are more sensitive of the three heavy metals;The48h LC50of these three heavy metal to the Artemia nauplii is4.0,27.19and115.95mg/L,and to the adults is1.31,6.86and34.23mg/L;the order of toxicity of cuprum,manganese and zinc for Artemia nauplii and adults was Cu2^>Mn2+>Zn2+;the safe concentration of the three heavy metal ions(Cu2+,Mn2+and Zn2+)to Artemia nauplii(36h)and adults were0.4,2.72,11.6,0.13,0.69and3.42mg/L.The results of combined toxicity test showed that Cu-Mn,Cu-Zn and Mn-Zn were all antagonistic to the Artemia naupli.

Selective proliferation of human γδ T cells in vitro

The effect of monoethylphosphate (MEP, commercial available or synthesized) together with IL-2 on the selective proliferation of human γ~δ T cells in Vitro from peripheral blood mononuclear cells (PBMC) of healthy donors and of cancer patients was investigated. The γ~δ T cells were stimulated by MEP to proliferate in a dose-dependent manner. The effect of synthesized MEP was 10 times greater than that of commercial MEP. When the PBMCs of healthy donors were cultured for 25 d in the medium containing different concentrations of MEP, the total cell number increased about 1000-3000 fold; and the ratio of γ~δ T cells reached to 70-80%. The selective expansion of γ~δ T cells depended on the synergic action of MEP and IL-2. The bulk cultured γ~δ T cells exhibited obvious cytotoxic activities against allogenic tumor cell lines (SQ-5,K562 alld Daudi) and autologous tumor cells. The culture system described here not only offers a simple method for obtaining a large number of γ~δ T cells which may become a new effector in the adoptive immunotherapy, but also provides a useful model for the further studies of the structure and function of γ~δ T cells in vitro.

Feasibility of herpes simplex virus type 1 mutants labeled with radionuclides for tumor treatment

For over one hundred years, viruses have been recognized as capable of killing tumor cells. At present, people are still researching and constructing more suitable oncolytic viruses for treating different malignant tumors. Although extensive studies have demonstrated that herpes simplex virus type 1 (HSV-1) is the most potential oncolytic virus, therapies based on herpes simplex virus type 1 vectors still arouse bio-safety and risk management issues. Researchers have therefore introduced the new idea of treating cancer with HSV-1 mutants labeled with radionuclides, combining radionuclide and oncolytic virus therapies. This overview briefly summarizes the status and mechanisms by which oncolytic viruses kill tumor cells, discusses the application of HSV-1 and HSV-1 derived vectors for tumor therapy, and demonstrates the feasibility and prospect of HSV-1 mutants labeled with radionuclides for treating tumors.

Esophagitis and its causes:Who is “guilty” when acid is found “not guilty”?

Esophagitis is mainly a consequence of gastroesophageal reflux disease, one of the most common diseases affecting the upper digestive tract. However the esophageal mucosa can also be targeted by some infectious, systemic or chemical conditions. Eosinophilic esophagitis(Eo E) is an immune-mediated inflammatory disease, characterized by eosinophilic infiltration in the mucosa. Esophageal localization of Crohn's disease is not very common, but it should always be considered in patients with inflammatory bowel disease complaining of upper digestive tract symptoms. There are also forms of infectious esophagitis(e.g., Herpes simplex virus or Candida albicans) occurring in patients with a compromised immune system, either because of specific diseases or immunosuppressive therapies. Another kind of damage to esophageal mucosa is due to drug use(including oncologic chemotherapeutic regimens and radiotherapy) or caustic ingestion, usually of alkaline liquids, with colliquative necrosis and destruction of mucosa within a few seconds. Dysphagia is a predominant symptom in Eo E, while infectious, drug-induced and caustic damages usually cause chest pain and odynophagia. Endoscopy can be useful for diagnosing esophagitis, although no specific pattern can be identified. In conclusion when a patient refers upper gastrointestinal tract symptoms and the diagnosis of gastro-esophageal reflux disease is not convincing we should always carefully investigate the patient's clinical history to consider possibilities other than the gastric refluxate.

Construction of the recombinant vector carrying herpes simplex virus thymidine kinase and cytokine genes expressed in cell line Tca8113

Objective: To construct expression vector containing fusion genes of herpes simplex virus thymidine kinase(Hsv-tk), Interleukin-2(IL-2) with internal ribosome entry sites(IRES), and to assess their expression in cell line Tca8113. Methods: IL-2 cDNA was obtained by reverse transcription. Hsv-tk, IL-2 and IRES genes were amplified by PCR. The purified amplification products were inserted into pGEM-T-Easy, and transformed into E.coli JM109. The purified recombinant plasmids were identified by restriction endonucleases. The recombinant plasmids were digested and pEGFP-N 3 were linearized, DNA fragments of Hsv-tk, IRES and IL-2 were ligated into linearized pEGFP-N 3, and then transferred into E.coli JM109. The recombinant tk-IL-2 genes were cloned separately and introduced into the expression vector pEGFP-N 3 containing GFP. The recombinant vectors were identified by their restriction sites through PCR. The plasmids pEGFP-TI was also transfected into Tca8113 cells by calcium phosphate method for the expression of fusion proteins. Fusion genes expressing vector PL(TI)SN was generated by the fusion of HSV-tk, IRES and IL-2 with the use of DNA recombination technology. The recombinant retroviruses were transferred into Tca8113 cells by lipofectamine. The positive clones were obtained after G418 selection and named Tca/TI respectively. Results: The pEGFP-TI pasmid was identified respectively by restriction endonucleases, and their fragment sizes were 1 120 bp and 450 bp. The pEGFP-TI pasmid as templates were amplified respectively by PCR, and their PCR products were 1 120 bp and 450 bp. The pEGFP-TI vectors were used to transfect Tca8113 cell, and the cells with fluorescence accounted for 60% of the total amount. Conclusion: pFGFP-tk-IRES-IL-2 expressing vector is easy to assess the expression of tk-IRES-IL-2-GFP fusion protein localization in transfected cells. The successful construction of expressing vector containing fusion genes of Hsv-tk, IRES and IL-2 may be beneficial for gene therapy in cell line Tca8113.

The pooled analysis of efficacy and safety profiles of bevacizumab in Chinese cancer patients

Objective: The aim of this study was to investigate the efficacy and safety profiles of bevacizumab, the commonly used monoclonal antibody and its safety profiles were challenging, based on Chinese cancer patients. Methods: All the papers studied on Chinese cancer patients treated by bevacizumab were found in both databases of Chinese journal database for fulltext and PubMed were collected. The commonly used efficacy index such as disease control rate (CR + PR + SD) and response rate (CR + PR) were analyzed, and the bevacizumab related side effects were analyzed too. Results: (1) There were ten original papers contained total 199 patients who were the candidates to analyze the safety profiles, and 115 patients with colorectal cancer in five papers who were candidates to analyze the efficacy. (2) Nine in ten papers set the dose of bevacizumab in 2.5 mg/kg/week - 5 mg/kg/week, and the biweekly was the standard chemotherapy interval. (3) The disease control rate and response rate in Chinese colorectal cancer patients were 85% (95% CI: 79%-92%) and 61% (95% CI: 52%-70%), respectively. (4) The side effects related to bevacizumab were rare and most of them were grades 1-2, and only one case with grade 4 bleeding was recorded and only two cases with discontinuation of bevacizumab since hemoplysis. Also, the grades 3-4 side effects related cytotoxic agents were not common. Conclusion: This study summarized the data of Chinese cancer patients treated by bevacizumab-contained regimens, and it showed that the monoclonal antibody was effective and safe for Chinese patients as the West patients.

Strategies for Antiviral Screening Targeting Early Steps of Virus Infection

Viral infection begins with the entry of the virus into the host target cell and initiates replication. For this reason, the virus entry machinery is an excellent target for antiviral therapeutics. In general, a virus life cycle includes several major steps: cell-surface attachment, entry, replication, assembly, and egress, while some viruses involve another stage called latency. The early steps of the virus life cycle include virus attachment, receptor binding, and entry. These steps involve the initial interactions between a virus and the host cell and thus are major determinants of the tropism of the virus infection, the nature of the virus replication, and the diseases resulting from the infection. Owing to the pathological importance of these early steps in the progress of viral infectious diseases, the development of inhibitors against these steps has been the focus of the pharmaceutical industry. In this review, Herpes Simplex Virus (HSV), Hepatitis C Virus (HCV), and Human Enterovirus 71 (EV71) were used as representatives of enveloped DNA, enveloped RNA, and non-enveloped viruses, respectively. The current mechanistic understanding of their attachment and entry, and the strategies for antagonist screenings are summarized herein.