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

Hematologic Diseases ; diagnosis ; Hematologic Tests ; Humans

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

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 investigate the effects of ulinastatin on autophagy and apoptosis of lung cells in rats with acute paraquat poisoning.Methods A total of 150 Wistar rats were randomly (random number) divided into three groups.The rats in control group had stomach lavaged once with 1 mL of normal saline followed by intraperitoneal injection of 1 mL normal saline twice a day.PQ poisoning model was produced by stomach lavaged once with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline once a day.In PQ + ulinastatin (PU) group,UTI in dose of 12 000 U/kg was intraperitoneally injected in rats twice a day.The lung tissue was obtained on the 7th day after modeling,and the histopathological changes were observed under microscope after hematoxylin and eosin (HE) staining.The positive expressions of autophagy-related LC3 protein LC3 and Bcl-2 pretein in lung tissue were observed after immunohistochemistry staining,and the levels of LC3、Bax 、Bcl-2 proteins were determined by Western blot.Results HE staining Results showed:it was observed from the PQ poisoning group that the abnormal cellular structure,enlargement in the pulmonary alveoli,leaking a lot of inflammatory cells,increased thickness of the alveoli wall and bleeding in the local area of lung tissue.Compared with the PQ poisoning group,the above changes in ulinastatin groups were relieved.Western blot Results showed:compared with the control group,the protein expressions of LC3-A/B were significantly increased in PQ poisoning group [LC3-A/B expression (A scale):0.22 ± 0.05 vs.0.14 ± 0.03,F =22.48,P ＜ 0.01].compared with PQ group,the expression of LC3 A/B obviously increased in the group of PU [LC3-A/B expression (A scale):0.36 ± 0.08 vs.0.22 ± 0.05,F =22.78,P ＜ 0.01].compared with Con group,the expression of Bcl-2/Bax obviously decreased in the group of PQ [Bcl-2/Bax expression (A scale),0.11 ±0.04 vs.0.83 ± 0.09,F =154.43,P ＜ 0.01].Compared with PQ poisoning group,the protein expressions of Bcl-2/Bax were obviously increased in PU groups [Bcl-2/Bax expression (A scale):(0.63 ± 018) vs.(0.11 ±0.04),F =154.43,P ＜0.01].Immunohistochemistry result:compared with Con group,the expression of LC3 and Bcl-2 obviously decreased in the group of PQ [LC3expression (A scale):(78.34±10.71) vs.(117.58±15.26),F=31.63,P＜0.01) (Bcl-2 expression (A scale):(62.54±9.74)vs.(130.52 ± 9.86,F =118.44,P ＜ 0.01).Compared with PQ poisoning group,the protein expressions of LC3 and Bcl-2 were obviously increased in PU groups [LC3expression (A scale):(162.58 ± 25.76) vs.(78.34 ± 10.71),F=31.63,P＜0.01]; [Bcl-2 expression (A scale):(145.56±10.26) vs.(62.54±9.74),F=118.44,P ＜ 0.01].Conclusions Theendoplasmic reticulum stress-autophagy is activated in the lung cells of rats with acute PQ poisoning.UTI can adjust endoplasmic reticul um stress,increased the expression of Bcl-2 and enhance the proportion of Bcl-2/Bax to protect the lungs of rats from acute PQ poisoning.

Objective To investigate the effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat (PQ) poisoning,and to explore its mechanism.Methods 200 Wistar rats were randomly divided into four groups by randomized arrangement table formed by computer,with 50 rats in each group.PQ poisoning model was reproduced by one time gastric lavage with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline (NS) once a day.The rats in control group were lavaged once with 1 mL of NS followed by intraperitoneal injection of 1 mL NS twice a day.The rats in Sal 0.5 and Sal 1.0 groups were intraperitoneal injected with 1 mL Salubrinal 0.5 mg/kg or 1.0 mg/kg on the 1st,3rd,and 5th day after PQ poisoning once a day.The lung tissue was harvested on the 7th day after poisoning,and the changes in histomorphology were observed using hematoxylin and eosin (HE) staining.The positive expression of autophagy-related protein LC3-Ⅱ in lung tissue was observed after immunohistochemistry staining,and LC3-Ⅱ and caspase-3 protein expressions were determined by Western Blot.Results HE staining results showed partial abnormal pulmonary structure in the PQ poisoning group:collapse of pulmonary alveoli,enlargement of the cavity,local infiltration of inflammatory cells,increasing thickness in the alveoli wall and obvious bleeding in the local lung tissue.Compared with the PQ poisoning group,the above changes in Sal 0.5 and Sal 1.0 groups were obviously relieved.It was shown by immunohistochemistry staining that compared with control group,the positive expression of LC3-Ⅱ was obviously decreased in the PQ poisoning group,Sal 0.5,and Sal 1.0 groups (A value:78.34 ± 10.71,76.52 ± 8.21,77.48 ± 9.11 vs.117.58 ± 15.26,all P＜0.05).There was no significant difference in positive expression of LC3-Ⅱ between each of the later three groups (all P＞0.05).Western Blot results showed:compared with the control group,the protein expressions of LC3-Ⅱ and caspase-3 were significantly increased in PQ poisoning group [LC3-Ⅱ (A value):0.22 ±0.05 vs.0.14 ±0.03,caspase-3 (A value):0.115 ± 0.013 vs.0.023 ± 0.006,both P＜0.05].Compared with PQ poisoning group,the protein expressions of LC3-Ⅱ and caspase-3 were obviously decreased in the Sal 0.5 and Sal 1.0 groups [LC3-Ⅱ (A value):0.19 ±0.05,0.18 ±0.04 vs.0.22 ±0.05; caspase-3 (A value):0.078 ±0.012,0.076 ±0.010 vs.0.115 ±0.013,all P＜0.05].Conclusions The endoplasmic reticulum stress-autophagy is activated in the pulmonary cell of acute PQ poisoning rats.Salubrinal can decrease the autophagy and apoptosis in the lung of rats with acute PQ poisoning,which play a role in the treatment.

To lay a foundation for the type selection of the ambulance helicopter. The type selection was explored from the aspects of platform selection, rescue environment and service requirements, analyzing the rescue in the helicopter and the tendency of the ambulance helicopter in foreign countries and China. The types of the am-bulance helicopter were determined as the specific and modified ambulances, with the considerations such as operation environment, flight performance, cabin structure, onboard equipment, cabin configuration, fixation device and protection. Specific ambulance helicopter is supposed to be based on small- or mediate-sized platform, while the modi-fied ambulance helicopter is supposed to be based on large or heavy platform.

Adolescent ; Adult ; Aged ; Cavernous Sinus ; injuries ; Female ; Humans ; Hypophysectomy ; adverse effects ; methods ; Intraoperative Complications ; Male ; Middle Aged ; Pituitary Neoplasms ; surgery ; Young Adult

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