HIV-1 fusion inhibitors are a new class of anti-HIV compounds, which block the entry of HIV into target cells through preventing the fusion between viral and cell plasma membrane and thus interrupt the initial steps of viral replication. T-20 (enfuvirtide), which has been clinically approved as the first fusion inhibitor of HIV-1 by U.S. FDA in 2003, can suppress replication of HIV variants with multi-drug resistance to reverse transcriptase and protease inhibitors. Peptides and small molecules display potent anti-HIV fusion activities by targeting gp41 thus inhibit its fusogenic function. In recent years, with the development of studies on the molecular mechanism of HIV membrane fusion process and the function of gp41, many new fusion inhibitors are found and some have been in advanced clinical trials. This review discusses recent progress in the development of HIV-1 fusion inhibitors targeting the gp41.

Objectives: To investigate the treatment effect of enteral nutrition rich in diet fiber in diarrhea because of bacteria disorder after severe brain injuries.Methods:20 cases with severe brain injuries were supported with enteral nutrition rich in diet fiber after the occurrance of diarrhea because of bacteria disorder as clinical treatment group.20 cases with the same conditions were treated with traditional methods as control.Results: Diarrhea of all patients in clinical treatment group had been controlled during 7-10 days,and the feeding quantities reached total calories.The nutrition state was improved,and the body internalenvironment was stable during the 20 days. Conclusion: Enteral nutrition rich in fiber can treat diarrhea caused by bacteria disorder after severe brain injuries.

The levels of ?_2-m、IgG and Alb in CSF of 13 patients with cerebral haemorrhage and 20 patients with cerebral thrombosis and the levels of ?_2-m in CSF of control group consisting of 14 eases were measured. It Was showed that the levels of ?_2-m in CSF of the two groups of the patients with cecrebrovascular disease were obviously higher than that of the control group and the levcls of ?_2-m in CSF of the two groups of the patients with cerebrovascular discase also had rclation to the levels of ?_2-m in serum of the groups of the patients themselves, the valucs of ?_2-m did not corre- lated with the valucs of IgG or Alb in CSF of the paticnts with cerebral hacmorrhage, but there existed a strong correlation between IgG and Alb in CSF of these patients. The values of ?_2-m, IgG and Alb in CSF of patients with cerebral thrombosis were exactly inversdy correlated with that of patients with cerebral haemorrhage. Reviewing some other data about ?_2-m the authors suggest that the clevated ?_2-m in CSf may indicate an increased cell-mediated immune phenomenon of central nervous system in teh pathological process of cerebral haemorrhage, but this phenomenon in the pathological process of cerebral thrombosis is not obviuos.

Objective To develop a core competence evaluation index system for preventive medicine undergraduates.Methods Following the scientific,systematic and applicable principles,we proposed evaluation index system of core competence for professional medical prevention and selected 35 experts for three rounds expert consultation on the index system by using Delphi method.The basic situation,the positive and authority degree of experts and all levels of index weight coefficient were analyzed using SPSS 13.0 software.Results The core competence evaluation index system for preventive medicine undergraduates included six dimensionalities,fifteen secondary indicators and forty-nine tertiary indicators.The six dimensionalities included professional value behavior (0.25),professional knowledge and skills (0.28),basic specialized knowledge (0.20),communication (0.13),information management (0.06) and systems thinking (0.08).Conclusion The establishment of the evaluation system can provide a scientific and objective reference for the evaluation of the core competence of medical students.

Objective To compare the impact of propofol and sevoflurane on thermoregulation in children undergoing orheopaedic surgery.Methods Sixty-eight children scheduled to undergo ortho-paedic surgery were randomly allocated to receive propofol (group P)and sevoflurane(group S)anes-thesia,34 cases in each group.Tympanic temperature was recorded 5 minutes before (T0 )and 5 min (T1 ),1 5 min (T2 ),30 min (T3 ),45 min (T4 ),60 min (T5 ),75 min (T6 ),90 min (T7 ),105 min (T8 )and 120 min (T9 )after anesthesia.Total fluid intake,duration of surgery,duration of anesthe-sia,the incidence of hypothermia,and the incidence of shivering were also recorded.Results Com-pared with T0 ,in both groups body temperature declined at T1-T8 .There was no difference between the two groups in total fluid intake,duration of surgery,duration of anesthesia and the incidence of shivering.Compared with group P,children in group S had a higher incidence of hypothermia(8 vs 1). Children in group S had lower temperature,which had statistical significance at T7 and T8 (P <0.05). Conclusion The core temperature of children undergoing orthopaedic surgery showed a trend of in-crease after the first fall in the surgery.Compared with propofol,sevoflurane anesthesia is more likely to lead to the incidence of hypothermia in children undergoing orthopaedic surgery in 90 min after in-duction of anesthesia.

Hepatitis C virus (HCV) infection is the leading cause of chronic liver diseases worldwide.There is no vaccine to prevent HCV infection.Current standard of care (SOC) for hepatitis C is pegylated interferon-α (pegIFN-α) in combination with ribavirin (RBV).However,the efficacy of pegIFN-α and RBV combination therapy is less than 50％ for genotype 1 HCV,which is the dominant virus in human.Additionally,IFN and RBV are highly toxic,causing severe side effects.Therefore,it is urgent to develop safer and more efficacious anti-HCV drugs.Over the last decade,a number of HCV-specific inhibitors have been discovered with many of them reached to late stages of clinical trials.Recently,2 HCV NS3 protease inhibitors,telaprevir and boceprevir,have been approved by the Unite States Food and Drug Administration (FDA).This opens up a new era for anti-HCV therapy.Several new classes of antiviral drugs targeting HCV NS3 protease,NS5A and NSSB RNA-dependence RNA polymerase (RdRp) are currently at various stages of preclinical and clinical studies.Upon approval of more NS3 protease,NS5A and NS5B polymerase inhibitors,future clinical studies will lead to optimal combination therapies which will have desirable parameters such as IFN-free,higher efficacy,safe,one daily dose and short duration.

BACKGROUND:During the process of acute brain injury after stroke, matrix metaloproteinase can undermine the integrity of vascular basement membrane, promote the migration of neutrophils and inflammatory factors, and cause secondary brain injury. OBJECTIVE:To investigate the activation of matrix metaloproteinase 2/9 and the degradation rule of claudin in rat models of middle cerebral artery ischemia at different ischemic durations. METHODS:Thirty-nine male SD rats were randomly divided into three groups according to different ischemic durations (3, 5 and 7 hours) . Middle cerebral artery occlusion (stroke) model was established using modified suture method,i.e., separation of the external carotid artery, inserting the suture into the internal carotid artery through the external carotid artery, and eventualy reaching the middle cerebral artery. The ischemic duration in these three groups was respectively 3 , 5 and 7 hours. After 2 hours of reperfusion, Zea-Longa score and Ludmila Belayev score, brain infarct area, matrix metaloproteinase 2/9 activities and claudin 5 degradation were determined in each group. RESULTS AND CONCLUSION:With the extension of ischemic duration, brain infarct area gradualy increased, central nervous system damage gradualy aggravated, matrix metaloproteinase 2/9 activities gradualy increased, and claudin-5 expression gradualy decreased. There were significant differences between any two ischemic durations in terms of each of above-mentioned indices. The results indicate that after long duration of ischemia, the progressive damage of brain tissue can cause the gradual increase of activation of matrix metaloproteinase 2/9 and the gradual degradation of claudin 5.

AIM:To determine the effects of glutamine ( Gln) pretreatment on occludin protein in the rats with intestinal ischemia-reperfusion ( I/R ) injury.METHODS: Male Wistar rats ( n =30 ) were randomly divided into 3 groups (n=10):sham group, I/R group and Gln pretreatment group.The rats in Gln pretreatment group were pretreated with Gln at dose of 1 g? kg-1? d-1 by orogastric route for 7 d, and those in the other 2 groups were pretreated with the same volume of normal saline .Intestinal I/R was induced by 30-min occlusion of the superior mesenteric artery followed by 24 h of reperfusion.After the operation, the levels of IL-10, IL-2, TNF-α, SOD and MDA were measured.The occludin protein was determined by the methods of immunohistochemistry and Western blotting .RESULTS: The occludin protein level in I/R group was significantly lower than that in sham group and Gln group (P<0.05).The levels of MDA and TNF-αin I/R group were significantly higher than those in sham group and Gln group ( P<0.05 ) .The levels of SOD , IL-10 and IL-2 in I/R group were significantly lower than those in sham group and Gln group ( P<0.05 ) .CONCLUSION:Glutamine has a protective effect on occludin protein in intestinal ischemia-reperfusion injury .The mechanism may be rela-ted to oxidative stress response and inflammatory inhibition .

Objective To evaluate effects of carbon monoxide (CO) on lipopolysaccharide (LPS) induced damage and possible mechanism in rat alveolar macrophages. Methods Rat alveolar macrophages were cultured in DMEM containing 10%fetal bovine serum with 5%CO2 at 37℃in Heraeus sepatech. The cells were divided into four groups using random number table (n=10): control group (group C),CO group, LPS group and LPS+CO group. The CO release molecule-2 (CORM-2) 100 μmol/L was added into CO group,LPS 10 mg/L was added into LPS group, cells were pretreated with CORM-2 100μmol/L for 1 h then LPS 10 mg/L was added into LPS+CO group, the same amount of PBS was added to group C. Proliferation was measured by MTT assay. Apoptosis and mitochondrial membrane potential were detected with flow cytometer. The content of ATP was tested by ATP content kit. Drp1 mRNA was measured by RT-PCR, and Drp1 expression was determined by Western blot assay. Results Compared with group C, the cell vitality, content of ATP and mitochondrial membrane potential were decreased in LPS group and LPS+CO group,and cell apoptosis rate, Drp1 mRNA and protein expression were increased (P<0.05). There were no significant changes were found in CO group. Compared with LPS group, the cell vitality, content of ATP and mitochondrial membrane potential were increased in LPS+CO group,and the cell apoptosis rate, Drp1 mRNA and protein expression were decreased (P<0.05). Conclusion Carbon monoxide can alleviate LPS-induced damage in rat alveolar macrophages, which is related with down-regulation of Drp1 and amelioration of mitochondrial function.

Objective:To explore the protective effect of sodium channels antagonists HOE642 on lung ischemia reperfusion and the role of the p38 mitogen activated protein kinase (p38MAPK) signaling pathway in this process.Methods:A total of 36 mice were randomly divided into a sham operation group (SHAM group),a lung ischemia reperfusion group (I/R group) and a lung ischemia reperfusion+HOE642 group (HOE group).The water content was detected by electronic scales,and the lung tissue pathological changes were observed under optical microscope.The inflammatory cytokines including IL-6 and TNF-α were examined by ELISA.The intracellular calcium fluorescence intensity was examined and observed under fluorescence microscope,and the protein expression of p38MAPK was detected by Western blot.Results:Lung water content in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P＜0.05).Lung interstitial edema,hemorrhage,lung tissue inflammatory cells infiltration were significantly alleviated in the HOE group than those in the I/R group,while the injury in the HOE group was aggravated than those in the SHAM group (both P＜0.05).T he IL-6 and TNF-α in lung tissues in the HOE group were lower than those in the I/R group,but higher than those in the SHAM group (both P＜0.05).Intracellular calcium fluorescence intensity in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P＜0.05).The protein expression of p38MAPK in lung tissues in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P＜0.05).Conclusion:HOE642 may exert protective effect on pulmonary I/R injury through regulation of the p38MAPK signaling pathway,resulting in reduction of intracellular calcium ion concentration and calcium overload,and decrease of inflammatory response.