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.
Adenine ; analogs & derivatives ; therapeutic use ; Anti-HIV Agents ; therapeutic use ; HIV Infections ; drug therapy ; Humans ; Organophosphates ; therapeutic use ; Organophosphonates ; therapeutic use ; Piperazines ; therapeutic use ; Pyridones ; therapeutic use ; Reverse Transcriptase Inhibitors ; therapeutic use ; Tenofovir

Objective:To investigate the relationship between psychological factors and the serum level of estrogen in menopausal women with glossdynia.Methods:87 menopausal women with glossdynia and a randomly selected control group (n=82) were comprehensively investigated with the method of case-control study.The serum level of estradiol(E2) and follicle stimulating hormone(FSH) were measured.All cases with glossdynia and control were evaluated by the Self-Rating Annxiety Scale(SAS) and Self-Rating Depression Scale(SDS). Results: The serum level of E2 was significantly lower in menopausal women with glossdynia than that in control group( P

Hematologic Diseases ; diagnosis ; Hematologic Tests ; Humans

Objective To establish an animal model of PCOS and to detect the DNA methylation states of LHR, INSR and AR genes. Methods 24-days-old female Sprague-Dawley (SD) rats were randomly divided into two groups. The rats in the experimental group were given subcutaneous implanting of levonorgestrel silica gel staff and injected 1.5 IU hCG twice daily for 9 days from the 4th day. The rats in the control group were injected with normal saline at the same time. Ovarian morphologic changes, sex hormone levels, fasting serum insulin and glucose were detected. The LHR, INSR and AR genes' DNA methylation patterns were checked by methylation specific PCR in modeling group and control group. Results The ovarian weight and volume in modeling group were higher than those in control group. The ovaries in modeling group showed multiple follicular cysts, and the number of theca cells and interstitial cells increased. Less developed follicles and corpus lutea were seem. The serum level of progesterone, testosterone, luteinizing hormone, fasting insulin and glucose were significantly higher in experimental group than those in control group, so as the LH/FSH ratio and HOMA index. No methylation of LHR and AR genes were found in both groups. The methylation frequency of INSR gene (76.7%) was significantly higher in modeling group than that in control group (P<0. 001). Conclusion The depression of INSR gene's transcriptional induced by DNA methylation is important in the development of insulin resistance in PCOS.

Objective:To study the expressions of vascular endothelial growth factor(VEGF), and thrombospondin (TSP) in oral submucous fibrosis(OSF), and to determine the relationship between VEGF and TSP, so as to investigate their roles in the pathogenesis of OSF. Methods:30 patients with OSF, including early (10 cases), middle (10 cases), late stage (10 cases) were studied. 5 healthy volunteers were chosen as control group. Buccal mucosa biopsies were taken in all samples. Expressions of VEGF and TSP were detected by immunohistochemistry. Results:The expression of VEGF increased in early stage compared with normal oral mucous, and decreased in middle and late stage. The expression of VEGF in early stage had statistical difference compared with control group, middle stage and late stage respectively(P<0.05).The expression of TSP upregulated in early and middle, and downregulated in late stage. There were no statistical significant differences among groups(P>0.05). The expressions of VEGF and TSP had negative correlation(r=-0.620,P<0.05). Conclusions: The abnormal expressions of VEGF and TSP may be a pathogenesis factor of OSF.

Objective To observe the protection of aprotinin, ulinastatin and aminomethylbenzoic acid, aminomethylbenzoie acid on blood fibrinolytie system during cardiopulmonary bypass(CPB). Methods Thirty-six patients with rheumatic heart disease who were treated by valve replacement were randomly divided into three groups: aprotinin group (group A, 12 cases): aprotinin 2000 kU was added into the priming solution; ulinastatin and aminomethylbenzoic acid group (group UP, 12 cases): ulinastatin 12 000 U/kg and aminomethylbenzoic acid 10 mg/kg was added into the priming solution; aminomethylbenzoie acid group (group P, 12 cases): aminomethylbenzoic acid 10 mg/kg was added into the priming solution. Results There was no significant difference in CPB time and blood transfusion among three groups; the postoperative 24 h chest tube drainage in group UP was (443.3 ± 150.8) ml, in group P was (430.0 ± 178.3) ml and in group A was (290.0 ± 98.0) ml, there were significant differences between group UP, group P and group A (P < 0.05). There was 1 case of severe allergic reaction in group A. Conclusion Aprotinin, ulinastatin and aminomethylbenzoic acid, aminomethylbenzoic acid are effective in stabilizing blood fibrinolytic system and preserving platelet function during CPB, leading to less postoperative blood loss.

AIM:To investigate the influence of F10 on the activities of transcription factor NF-?B and AP1 in A549 cells.METHODS:The luciferase report plasmids of NF-?B-Luc,AP1-Luc and F10 gene were introduced into A549 cells and the luciferase activity was detected.The DNA binding activities of AP1 and NF-?B in the cells were measured by the electrophoretic mobility shift assay(EMSA).RESULTS:The luciferase activity in F10+ transfection group decreased 30% and increased 2-fold respectively 48 h after transfected with the luciferase report plasmid of NF-?B-Luc and AP1-Luc in A549 cells.The DNA binding activity decreased 49% and increased 23%,respectively.CONCLUSION:F10 gene up-regulates the transcription activity of AP1 and down-regulates the NF-?B in A549 cells.

Objective To investigate the mechanisms and clinical characteristics of fatal asthma attack induced by amiodarone in the elderly,and to discuss its serious potent risks.Methods We reported two cases of fatal asthma attack in the elderly with fast atrial fibrillation induced by amiodarone,and discussed the clinical manifestation and emergency treatment,with literatures review.Results The two patients presented with respiratory arrest.After targeted therapies,including artificial ventilation and hormone injection,the patients were capable of spontaneously breathing,while still in severe asthma attack.And further anti-asthma treatment led to a complete remission.Conclusions Amiodarone may cause extremely severe asthma attack in elder patients with tachyarrhythmia complicated with bronchial hyper-responsiveness diseases such as asthma or chronic obstructive pulmonary diseases.Clinicians should pay great attention to this situation and be prepared to cope with serious adverse reactions.

Objective To establish an animal model of PCOS and to detect the DNA methylation states of LHR,INSR and AR genes. Methods 24-days-old female Sprague-Dawley (SD) rats were randomly divided into two groups. The rats in the experimental group were given subcutaneous implanting of levonorgestrel silica gel staff and injected 1.5 IU hCG twice daily for 9 days from the 4th day. The rats in the control group were injected with normal saline at the same time. Ovarian morphologic changes,sex hormone levels,fasting serum insulin and glucose were detected. The LHR,INSR and AR genes' DNA methylation patterns were checked by methylation specific PCR in modeling group and control group.Results The ovarian weight and volume in modeling group were higher than those in control group. The ovaries in modeling group showed multiple follicular cysts,and the number of theca cells and interstitial cells increased. Less developed follicles and corpus lutea were seem. The serum level of progesterone,testosterone,luteinizing hormone,fasting insulin and glucose were significantly higher in experimental group than those in control group,so as the LH/FSH ratio and HOMA index. No methylation of LHR and AR genes were found in both groups. The methylation frequency of INSR gene (76.7%) was significantly higher in modelinggroup than that in control group (P

Adrenergic receptors are members of the G-protein coupled receptor superfamily. Recent studies revealed that these adrenergic receptors are playing an important role in the growth and metastasis of prostate cancer cells. The expression of adrenergic receptors rises significantly in prostate cancer cells and tissues. Agonists of these receptors promote the growth and mobility of prostate cancer cells, while antagonists may suppress their proliferation, trigger their apoptosis, and inhibit their metastasis. Clinically, receptor antagonists can significantly reduce the risk of prostate cancer and improve its prognosis after androgen depravation therapy. This article presents an overview on the roles of adrenergic receptors in prostate cancer.
Adrenergic Agonists ; pharmacology ; Adrenergic Antagonists ; pharmacology ; Apoptosis ; Humans ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, Adrenergic ; drug effects ; physiology