HIV-1 integrase (IN) is an essential enzyme for retroviral replication. There is no analogue for this enzyme in human cells so that inhibition of IN will not bring strong effect on human body. Thus, HIV-1 IN has become a rational target for therapy of AIDS. This review provides a comprehensive report of alpha, gamma-diketo IN inhibitors discovered in recent years. Compilation of such data will prove to be beneficial in developing QSAR, pharmacophore hypothesis generation and validation, virtual screening and synthesis of compounds with higher activity.

Objective To investigate the distribution and drug resistance situation of clinical isolated bacteria in our hospital to provide the basis for rational selection of antibacterial drugs in clinic .Methods The pathogenic bacteria isolated from the clinical sepcimens in our hospital from January 2012 to December 2013 were performed the idenitification and drug susceptibility test by a‐dopting the the bioMerieux VITEK‐2 compact automatic bacterial analyzer .The detection results were judged according to the standard of the Clinical and Laboratory Standard Institute (CLSI) .The WHONET5 .6 software was used for conducting the statisti‐cal analysis .Results 2 274 strains were isolated during 2012-2013 ,in which 1986 strains (72 .4% ) were Gram‐negative bacteria , 675 strains(24 .6% )were Gram‐positive bacteria and 94 ccases(3 .0 % ) were fungi .The top 3 of Gram‐negative bacteria were Esch‐erichia coli(694 strains ,25 .3% ) ,Klebsiella pneumoniae (303 strains ,11 .0% ) and Pseudomonas aeruginosa (266 strains ,9 .7 % ) respectivley .The top 3 of Gram‐‐positive bacteria were Staphylococcus aureus (184 strians ,.6 .7% ) ,coagulase negative staphylococ‐cus(146 strains ,5 .3% )and enterococcus faecium (119 strians ,4 .3% ) .The respiratory tract infection ,urinary tract infection and blood infection were predominant .The detection rate of methicillin‐resistant Staphylococcus aureus (MRSA) was 45 .7% ,while which of methicillin‐resistant coagulase negative Staphylococcus (MRCNS) was 84 .6% .MRSA showed the multiple resistance to fluoroquinolones and aminoglycosides antibcatieral drugs ,the resistance rate> 90 .00% ,but resistance rate macrolide antibiotic was<50 .0% ;no vancomycin‐and linezolid‐resistant Staphylococcus was found ;the resistance rate of enterococcus faecium to vancomy‐cin was 1 .7% and no linezolid‐resistant enterococcus faecium was detected .The detection rates of extended‐spectrum β‐lactamase‐producing K .pneumoniae and E .coli were 65 .2% and 39 .9% respectively ,and which of E .coli and K .pneumoniae to imipenem were 0% and 6 .3% respectively .The resistance rate of Acinetobacter baumannii to commonly used antibacterial drugs was more than 50% .The resistant rate of pseudomonas aeruginosa to common antipseudomonal drugs was <40 .0% .Conclusion The drug resistance phenomena of pathogenic bacteria isolated from our hospital is relatively universal ,especially multi‐drug resistant non‐fer‐mentative bacteria ;the enzyme‐producing mechanism leads to increase the detection rate of multi‐antibacterial resistant Enterobacte‐riaceae bacteria ,which causes the enormous difficulty for clinical anti‐infection therapy .Conducting the bacterial drug‐resistance mo‐nitoring has an important significance for guiding clinically rational drug use ,reducing the nosocomial infection rate and controlling the bacterial drug resistance .

Objective To investigate the therapeutic effect of radial surgery in large cerebral metastatic carcinoma. Methods Adopt three dimensional oriented radial surgery to 15 patients with the biggest diameter of more than 35mm. Observe the variation of clinical symptoms and analysis the change of CT image. Follow up the survival time, complications and the cause of death at the same time. Results Most of the patients got prominent improvement in symptoms. But the imaging change of carcinoma focus was a slow course comparatively. The survival rate in 1 year was 26％ . Conclusion Radial surgery is an effective, simple and safe method in the treatment of large cerebral metastatic carcinoma. It has a good control rate with only slight complications.

Objective To observe the short term effects of Rho-kinase inhibitor and Qiliqiangxin capsule on serum tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels in patients with chronic heart failure,and explore the mechanism.Methods 120 chronic heart failure patients received conventional treatment for 4 weeks were divided into blank control group(Group A,n=30),Rho-kinase inhibitor treated group(Group B,n=30), Qiliqiangxin capsules-treated group (Group C,n =30 ),and the other 30 cases were treated with Rho-kinase inhibitor combined with Qiliqiangxin capsules(GroupD,n=30).TNF-α,IL-6 and BNP were measured and cardiac function was evaluated before and after treatment.The difference between 4 groups was analyzed. Results After treatment,the levels of TNF-α,IL-6,BNP in the observation group were lower than that in the control group.The difference was statistically significant(P<0.05 ).The levels of TNF-α,IL-6,BNP in the D group were lower than that in the B and C group.The difference was statistically significant(P<0.05 ).Conclusion Rho-kinase inhibitor combined with Qiliqiangxin capsule can improve cardiac function and reduce levels of serum cytokines associated with chronic heart failure,which is conducive to the treatment of chronic heart failure.

AIM:To observe the effects of adipose differentiation-related protein ( adipophilin) on the expres-sion of inflammatory factors in RAW264.7 macrophage and to clarify the related mechanism.METHODS:The cell models with high expression and low expression of adipophilin were constructed by transfecting PA317 packaging cells with stable high or low expression adipophilin retroviral vectors into the RAW264.7 cells.The concentrations of IL-6, MCP-1 and TNF-αin the cell culture medium were detected by ELISA.The protein levels of AP-1, p-AP-1, ERK1/2 and p-ERK1/2 were measured by Western blot.The protein levels of adipophilin, p-ERK1/2 and p-AP-1 and the releases of the inflamma-tory factors in the RAW264.7 cells treated with or without ERK1/2 inhibitor PD98059 or AP-1 inhibitor curcumin were de-termined.RESULTS:The RAW264.7 cells with high expression of adipophilin had higher levels of IL-6, MCP-1 and TNF-α, and higher protein levels of p-AP-1 and p-ERK1/2 than those in the cells with low expression of adipophilin. ERK1/2 inhibitor had no significant effect on the expression of adipophilin, but the protein expression of ERK1/2 and AP-1 was significantly inhibited (P<0.05).The administration of AP-1 inhibitor curcumin had no significant effect on the protein expression of adipophilin and ERK1/2, but the protein expression of AP-1 was significantly inhibited (P<0.05). At the same time, the releases of inflammatory factors IL-6, MCP-1 and TNF-αwere significantly decreased.CONCLU-SION:Adipophilin may regulate the expression of inflammatory factors through ERK1/2-AP-1 pathway in RAW264.7 mac-rophages.

OBJECTIVE: To examine the value of self-treatment for Posterior canal benign paroxysmal positional vertigo (PC-BPPV). The treatment effect was compared between patients treated with modified Epley in outpatient clinic combined with self treatment at home and patients treated by modified Epley alone. METHOD: A randomized controlled trial were carried out in the Department of Otolaryngology Head and Neck Surgery, the Affiliated Sixth People's Hospital of Shanghai Jiao Tong University from December 2012 to May 2013. 147 out of 150 patients with unilateral idiopathic BPPV-PSC were enrolled in follow-up. Among which, 73 patients were allocated in modified Epley-alone group and 74 were allocated in slef-treatment group. RESULT: The success rate was 53.4% in modified Epley-alone group vs 83.8% in self-treatment group (P < 0.01) after 1 week treatment. In the modified Epley-alone group,the success rate of hand repositioning group and chair-assisted repositioning group was 45.9% vs 61.1% (P > 0.05), the risk rate was 0.752, 95% CI (0.486 - 1.163). In the self-treatment group, the success rate of hand repositioning group and chair-assisted repositioning group was 87.5% vs 81.0% (P > 0.05), the risk rate was 1.081, 95% CI (0.888-1.316). Incidence rate of serious complications was 0% in the modified Epley-alone group and 1.3% in the self-treatment group (P > 0.05). CONCLUSION Complementary self-treatment with modified Epley maneuver treated PC-BPPV sooner and more effectively, Compared with modified Epley maneuver alone. And its incidence rate of serious complications didn't increase. Chair-assisted repositioning showed better result than hand repositioning alone, and self-treatment at home can reduce the effect of the gap. We found that complementary self-treatment with modified Epley maneuver had more benefits for patients with PC-BPPV.
Aged ; Benign Paroxysmal Positional Vertigo ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Patient Positioning ; methods ; Self Care ; Treatment Outcome

Objective:To investigate the influence of sulforaphane(SFN)on ventricular remodeling in myocardial infarction(MI)rat model by regulating extracellular regulated protein kinase(ERK)/nuclear respiratory factor 1(NRF1)signaling pathway.Methods:Among 48 SD male rats,12 were randomly selected as Sham group.The remaining rats were treated with ligation of left ante-rior descending coronary artery to establish myocardial infarction model.After modeling,36 rats were randomly divided into MI model group,SFN treatment group(10 mg/kg),SFN+SCH772984(ERK inhibitor)group(10 mg/kg+15 mg/kg),with 12 rats in each group.Animal ultrasound was performed to detect cardiac structure and function.Histological analysis was performed to evaluate myo-cardial fibrosis and cell apoptosis.ELISA was used to measure pro-inflammatory factor levels in serum,and Western blot assay was used to observe the expression of ERK/NRF1 pathway related proteins in myocardium of rats in each group.Results:Compared with rats in Sham group,rats in MI model group showed a loss of myocardial compliance and disarray of ventricular myocardial fibers,along with increased myocardial fibrosis and myocardial cell apoptosis.Moreover,rats in MI model group also exhibited overactive inflammatory response and inhibition of the ERK/NRF1 signaling pathway in cardiac tissues(P<0.05).Notably,SFN treatment signifi-cantly not only improved cardiac function,but also ameliorated myocardial fibrosis and cell apoptosis(P<0.05).SFN treatment inhib-ited inflammatory cytokine expression and activated the ERK/NRF1 pathway as well(P<0.05).However,SCH772984 significantly abrogated the protective effect of SFN against myocardial fibrosis and apoptosis in MI rats.Conclusion:SFN may protect against ventricular remodeling in MI rat by activating ERK/NRF1 pathway.

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Deinagkistrodon acutus(also known as the five-paced viper and the traditional Chinese medicine ingredient is called Agkistrodon) venom is a viscous liquid from the venom glands of the Deinagkistrodon acutus. It contains a variety of protein and peptide components such as phospholipase A2, serine protease, metalloproteinase, C-type lectin, L-amino acid oxidase, and has a variety of biological activities, playing an important role in anti-tumour, anti-thrombotic, anti-inflammatory and anti-bacterial activities. In recent years, snake venom research has become increasingly widespread, but there is still a lack of comprehensive and systematic studies on snake venom from Deinagkistrodon acutus. In this paper, the source, identification, active ingredients, toxicity studies and quality researches of Deinagkistrodon acutus venom are summarized and analysed by searching the related research progress, in order to provide reference for further development and utilization of Deinagkistrodon acutus venom.

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.