In the two decades since AZT was first approved for clinical use in 1987, 24 additional antiretroviral agents have been approved. They include 7 nucleoside analogs, a nucleotide analog and 4 non-nucleoside reverse transcriptase inhibitors, 10 protease inhibitors, 2 entry inhibitors and an integrase inhibitor. More than 20 investigational agents are currently being studied in clinical trials. Highly active antiretroviral therapy (HAART), which involves a combination of anti-HIV-1 drugs, is extremely effective in suppressing HIV-1 replication and increasing CD4+ number and results in substantial reductions in HIV-1-related morbidity and mortality. In last 20 years, much has been learned about resistance to antiretroviral drugs, drug interactions and metabolic complications of antiviral drug use. Drugs are now selected on the basis of resistance tests and on the risk of specific drug complications in individual patients. As a result, decisions about the therapy of HIV/AIDS have become personalized and are made on a patient-by-patient basis. With appropriate medical management, a person with HIV-1 now has the possibility of a nearly normal life expectancy.

Besides 36 (28 single-tablets and 8 fixed-dose combinations) used antiretroviral drugs clinically, there are a number of investigational antiretroviral agents currently in phase 2-3 clinical trial. Tenofoviralafenamidefumarate (TAF) is a novel nucleoside analogue reverse transcriptase inhibitor that is potent and less toxicity than tenofovir (TDF). Doravirine is a non-nucleoside analogue reverse transcriptase inhibitor that demonstrates activity against NNRTI-resistant viral strains. GSK744 is an integrase inhibitor with a long acting preparation. In addition, several drugs with new mechanisms are also noted, for example, BMS-663 068 is a small molecule CD4 attachment inhibitors and cenicriviroc is a novel CCR5/CCR2 antagonist with antiretroviral activity and anti-inflammatory effects. Several drug classes that target known pathways in HIV latency have being developed, and leading the list are histone deacetylase inhibitors. Other agents include protein kinase C activators, positive transcription elongation factor activators, DNA methyl-transferase inhibitors and histone methyl-transferase inhibitors and so on. This review is focused on the above-mentioned drug candidates that may be used in clinical in next couple of years and those compounds that can reverse latent HIV infections.

Objective To study the activity of Wuweilingqi capsule alone and the synergy with other anti-HIV-1 inhibitors against various HIV-1 isolates,and investigate its immunological impacts for CD4+ and CD8+ T cells. Method Wuweilingqi capsule was extracted from a traditional Chinese medicine recipe which contains 5 herbs,it showed anti-retroviral activity in vitro in the cultures of human peripheral blood mononuclear cells (PBMC) and T cell lines (H9 and MT2). Results Wuweilingqi capsule inhibited HIV-1018a (an AZT-sensitive clinical isolate) in PBMC and HTLV-ⅢB (a HIV-1 lab isolate) in H9 and MT-2 T cell lines markedly,and the therapeutic indexes (TI) were 96,84 and 181 separately,but weakly inhibitory activity against HIV-1018c (an AZT-resistant clinical isolate) and chronically infective HTLV-ⅢB were demonstrated. Significant synergy against HIV-1018a and HIV-1018c replication between Wuweilingqi capsule and AZT,indinavir or T-20 were observed. In addition,Wuweilingqi capsule significantly increased PBMC proliferation,interferon-gamma secreting cell number with or without a stimulation of PHA or candida. Conclusion Although Wuweilingqi capsule did not show so strong anti-HIV-1 activity as known west drugs in clinical,its good synergy and significant increase of immune activity suggests that it will be an available and characteristic agent against HIV-1 replication.

Objectives:To study the effects of gene therapy with tissue type plasminogen activator(t PA)cDNA on the formation of thrombo embolism in vascular anastomotic sites. Methods:①The cDNA encoding t PA was amplified by RT PCR using the isolated total RNA as the template from the Bowes melanoma cells.②Recombinant plasmid pAdCMV t PA was cotransfected into 293 cells with pJMa 17 ,and the infectious but replication deficient AdCMV t PA was generated.③The rats were randomly divided into the control and treatment groups.11 0 nylone medical suture was applied to perform rat carotid artery end to end anastomoses.In the treatment group,AdCMV t PA solution was injected into the vascular anastomotic site while AdCMV (no containing t PA DNA) solution was injected into the control group. By means of RT PCR and chromogenic plasmin substrates,the following results were obtained. Results:①The t PA cDNA was successfully cloned and its eukaryotic expressing vector was constructed.②When the isolated RNA was performed with RT PCR,1.69 kb band appeared in the treatment group while the band could not be found in the control group.The t PA activity could be detected postoperatively on the 1st,2 nd,3 rd,4 th,5 th,6 th,7 th,10 th and 13 th day of the treatment,but could not be detected in the control group. Conclusions:The t PA gene can produce t PA having biological activity at anastomotic sites, possibly prevent the formation of thrombus embolism effectively and develop the anastomotic patency.

Resveratrol, isorhapontigenin and pinosylvin, isolated from Gnetum parvifolium, and their analogues have been synthesized and tested for their inhibitory activity of HIV-1. Natural product 12a and analogues (12d, 12e, 12g) display significant inhibitory activity of HIV-1 replication. Among them, compound 12d (trans-3, 4, 5, 4'-tetrahydroxystilbene) exhibits the most potent anti-HIV-1 activity with an IC50 value of 1.84 micromol x L(-1).

Objective To investigate the feature of cerebral glucose metabolism of Alzheimer's disease (AD)and dementia with lewy bodies (DLB).Methods 28 patients with AD and 25 patients with DLB underwent positron emission tomography (PET)with 18 F-fluorodeoxyglucose (18F-FDG)showing glucose metabolism.The region of interest (ROI)was selected from frontal cortex,temporal cortex,parietal cortex,occipital cortex,cerebellum cortex and corpora striata.The 18 F-FDG metabolism ratios between various cerebral regions and cerebellum cortex were compared as an indicator of regional cerebral glucose metabolic patterns.Results The FDG metabolism ratio of parietal cortex and temporal cortex decreased similarly in AD.The FDG metabolism ratio of frontal cortex,parietal cortex,temporal cortex,occipital cortex,dorsal caudate putamen and caudate nucleus in AD was [(0.861 ± 0.173),(0.625 ± 0.149),(0.598 ± 0.185 ),(0.914 ± 0.214),( 1.030 ± 0.084)and ( 0.997 ± 0.102 )].The FDG metabolism ratio of frontal cortex,parietal cortex,occipital cortex,temporal cortex and corpus striatum decreased similarly in DLB.The FDG metabolism ratio of frontal cortex,parietal cortex,temporal cortex,occipital cortex,dorsal caudate putamen and candate nucleus in DLB was [ (0.538 ±0.147),(0.615 ±0.138),( 0.587 ±0.142),(0.415 ±0.107 ),(0.685 ± 0.094)and (0.547 ± 0.103 )].The FDG metabolism ratio of frontal cortex,occipital cortex and corpus striatum decreased more significantly in DLB than in AD (P＜0.01 ).Conclusion There are discrepancies in cerebral glucose metabolism between AD and DLB.These features may be useful in differential diagnosis of these two kinds of dementia.

Objective To explore the characteristics and mechanisms of dysphagia in patients with dorsola-teral medullary syndrome ( DMS). Methods Twelve DMS patients were evaluated clinically and submitted to videofluoroscopic study in order to investigate clinical manifestations and the pathophysiological changes in swallowing. Swallowing function was recorded at discharge and during a three-month follow-up period. Results All patients had difficulties in swallowing and drinking, presenting coughing and throat clearing, and needed nasogastric feeding at admission. Insufficient soft palate elevation was observed in seven patients, who had no other oral phase dysfunction. The pharyngeal phase was injured in all patients. Decreased larynx elevation and invalid swallowing were observed in 10 patients. Delayed pharyngeal swallowing was seen in 8 patients. Under videofluoroscopy, 9 patients showed significantly decreased larynx elevation. Ten patients opened the cricopharyngeal muscles insufficiently, while two could not open at all. Larynx penetration was seen in all patients. Eleven patients were able to return to oral feeding, after 36 days on average (range 13 - 50 d). The patients with a disease history of 3 or more years could not return to oral feeding. Conclusion DMS patients are characterized by decreased larynx elevation and reduced compliance of the cricopharyngeal muscles. Early therapy may provide patients with a good prognosis.

The localization of human swallowing cortical area remains unclear,which prevents the understanding of pathophysiologic change of peripheral swallowing apparatus and the development of swallowing rehabilitation.Animal experiments have found that the non-human primates, premotor cortex,sensorimotor area,frontal,parietal and temple operculum,orbitofrontal cortex and cingulate cortex are associated with swallowing function.Recently,by using the advanced techniques such as functional MRI,position emission tomography and magnetoencephalography,it was found that a number of encephalic regions participated in the human swallowing,mostly concentrated in primary sensorimotor cortex,premotor cortex,cingule,insular lobe,and parietal-occipital area.However,the exact functions and roles of various encephalic regions and their correlations between various encephalic regions remain unclear.Further studies are needed to identify them.

ObjectiveTo compare the prognosis of patiens with acute(within 72 hours) subarachnoid hemorrhage (SAH) within or without the clinical standardized pathway(CSP).Methods123 acute SAH cases were collected before CSP established meanwhile another 146 cases after CSP established from 2005 to 2009 in neurological intensive care unit of our hospital. Information such as age, gender, Hunt-Hess and CT-Fisher grade, timing and result of digital subtraction arteriography, treating time of aneurysm, and Modified Rankin Scale(MRS) at different time were recorded. Rehaemorrhagia, complications, mortality, prognosis and average stay were compared between two groups.ResultsThere was a significant difference between two groups in rehaemorrhagia, vasospasm，hydrocephaly, mortality, prognosis and average stay.ConclusionCSP is helpful to improve the prognosis of aneurysm subarachnoid hemorrhage.

Objective To explore the relationship between lesion sites of stroke and swallowing function. Methods Ischemic stroke patients consecutively admitted into the stroke unit were screened in this study. The new and previous lesion sites of stroke, dysphagia and aspiration under videofluoroscopy (VF) were recorded and their relation was analyzed. Results 211 patients were included and 169 patients had completed the MRI and VF examination. 159 patients had dysphagia and 94 had aspiration under VF. 72 patients (9 missing) were found disorder in oral phase and 150 in pharyngeal phase. There was no significantly difference in dysphagia under VF and in aspiration among different lesion sites (P>0.05). Patients with stroke in medulla tended to happen aspiration (P=0.056). Stroke sites above the tentorium of cerebellum (P=0.028) or above medulla (P=0.005) may cause disorder in oral phase. Conclusion The stroke injury in brain cortex, white matter, brainstem and cerebellum or hemisphere could lead to dysphagia and aspiration. The injury of medulla may cause aspiration. Lesion of brain hemisphere or above the medulla could result disorder in oral phase of swallowing.