Objective To observe the distribution and drug resistance of pathogens cultured from the sputum of hospitalized patients with lower respiratory infection in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) .Methods To i‐dentify the germiculture and test the drug susceptibility of the sputum or respiratory secretion isolated from the bronchial brush of 262 hospitalized AECOPD patients in People′s Hospital of Jiangxi Province from Janurary 2013 to December 2014 and analyze the results .Results Among all the AECOPD patients ,215 cases with positive sputum culture ,281 sputum pathogens were isolated . Gram‐negative bacilli were found in 190(67 .6% ) .Gram‐positive aureus were detected in 76(27 .1% ) .Fungus pathogens occurred in 15(5 .3% ) .The top six pathogenic bacteria were acinetobacter baumannii ,escherichia coli ,klebsiella pneumonia ,pseudomonas aeruginosa ,staphylococcus aureus ,streptococcus pneumonia .Drug susceptibility results showed that the drug resistance of acineto‐bacter baumannii was the strongest .Except that the drug resistance rate of cefoperazone/sulbactam and levofloxacin were less than 50 .0% ,the others were no less than 75 .0% .The drug resistance rate of escherichia coli and klebsiella pneumoniae to ampicillin , ampicillin sulbactam ,cefazolin ,ceftriaxone ,cefotetan ,gentamycin ,ofloxacin ,ciprofloxacin ,and compound sulfamethoxazole trime‐thoprim were no less than 70 .0% .The drug resistance rate of staphylococcus aureus to penicillin G ,oxacillin ,erythromycin ,clinda‐mycin were 100% .The drug resistance rate of streptococcus pneumoniae to erythromycin ,clindamycin ,tetracycline ,sulfamethox‐azole trimethoprim were greater than 75 .0% .Conclusion Gram‐negative bacilli are the main pathogenic bacterium in the AECOPD patients with lower respiratory infection .The key of treatment is to pay more attention to the bacterial culture and drug sensitive test ,use antibiotics reasonably according to the results of drug sensitive experiment .

This study is to investigate the mechanism and action characteristics of 6-chloro-3-methyl-4-(2-methyoxycarbonylthiophene-3-sulfonyl)-3, 4-dihydroquinoxa-lin-2-(1 H)-one (XU07011) against HIV-1 replication. XU07011 anti-HIV activity was tested by using VSVG/HIV pseudotype viral system and confirmed by HIV-1 live viruses' infectious assay. Time of addition was used to test HIV-1 reverse transcription process. RNA-dependent DNA polymerase activity and RNase H activity were tested by using enzyme linked immunoabsorbent assay and fluorescence method. Wild type and nine NNRTIs-resistant reverse transcriptase enzymatic models and cell-based pharmacological models were used to evaluate XU07011 bio-characteristics. The results showed that XU07011 inhibited HIV-1 replication with IC50 of (0.057 +/- 0.01) micromol x L(-1) which was comparable to nevirapine [IC50: (0.046 +/- 0.01) micromol x L(-1)]. Mechanism study data indicated that XU07011 blocked HIV-1 reverse transcription process through acting on reverse transcriptase RNA-dependent DNA polymerase with IC 50 of (1.1 +/- 0.3) micromol x L(-1). The compound showed no effect on RNase H activity. XU07011 exhibited better activities comparing with nevirapine on K103N mutated NNRTIs-resistant HIV-1 strains. This study could provide a theoretical basis for novel anti-HIV reagents development.

Fructose-1, 6-bisphosphatase (FBPase), a rate-limiting enzyme involved in the pathway of gluconeogenesis, can catalyze the hydrolysis of fructose-1, 6-bisphosphate to fructose-6-phosphate. Upon inhibiting the activity of FBPase, the production of endogenous glucose can be decreased and the level of blood glucose lowered. Therefore, inhibitors of FBPase are expected to be novel potential therapeutics for the treatment of type II diabetes. Recent research efforts were reviewed in the field of developing allosteric inhibitors interacting with the AMP binding site of FBPase.

【Objective】To study the effect of light weight-bearing activity on postmenopausal osteoporosis.【Methods】36 female rats were randomly divided into 3 groups:① Sham,② Ovx (ovarietomized),③ Ovx+Im (ovarietomized and immobilized).All the group's maintained daily activity.And because of being immobilized,the right hind limbs of the third group lacked weight-bearing activity.12 weeks after ovarietomy,the BMD (bone mineral density),histomorphometry and biomechanics of the right femurs of rats were measured and analyzed.【Results】Comparing with the Sham group,the Ovx group's right femurs were manifested with the decrease of BMD,TBV (trabecular bone volume),MTT(mean trabecular thickness) and MCT(mean cortex thickness),while the increase of RS(resorption surface) and OS(osteotoid surface).Meanwhile their biomechanic nature declined.But statistically the BMD,MCT and the criteria of mechanical strength were not significant decrease.Otherwise,the Ovx+Im group's right femurs showed more apparent decrease of BMD,TBV,MTT and MCT.And the biomechanic nature was worse.Comparing with the Sham group,the BMD,MCT and the criteria of mechanical strength of the Ovx+Im group were statistically significant decreased.【Conclusion】If maintaining light weight-bearing activity,the ovarietomized rats were able to maintain relatively better bone quality.A lack of light weight-bearing activity wouldcause thedecline of bone quality.Thusthestudy suggested light weight-bearing activity was significantly effective on the prevention and treatment of postmenopausal osteoporosis.

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.

PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.

Objective The aim of this study was to assess the value of △Np63α in predicting tumor recurrence after curative resection in esophageal squamous cell carcinoma (ESCC) patients.Methods We analyzed △Np63α protein cxpression in 304 clinicopathologically characterized ESCC cases by immunohistochemistry.Results We found △Np63α expression was positive in 122 (40％) of 304 cases.△Np63α expression was higher in the cancer tissue than in non-tumorous control tissue at protein level(P =0.034).There was a significant difference of △Np63α expression in patients categorized according to invasive depth (P =0.001),tumor position (P =0.001) and lymph nodes metastasis condition (P =0.001).Multivariate analyses showed that △Np63α was an independent prognostic marker for ESCC recurrence.Conclusion △Np63α is associated with outcome of ESCC and can be a novel predictor for poor prognosis of ESCC patients after curative resection.

ObjectiveTo establish a new biomechanical test for evaluating biomechanical properties of femoral metaphysis in ovariectomized rats.MethodsTwenty-five-month-old female Sprague-Dawley rats were randomly divided into ovariectomized (OVX) group and the sham-operated (Sham) group (n=10).Twelve weeks after operation,femur BMD and histomorphometry of distal femur were detected.Furthermore,femur biomechanical parameters were determined by diaphysis three-point bending test and a new designed metaphysis bending test.The relationships between the biomechanical parameters and BMD or bone histomorphometry were assessed with Pearson correlations.ResultsThe femur BMD,bone histomorphometrical indexes(％Th.Ar,Tb.N,Tb.Th),and biomechanical parameters(maximum load,yield load and stiffness) of OVX group significantly decreased compared with Sham group.In metaphysis bending test,the mean difference of the maximum load(Fmax),yield load(Fy) between group OVX and Sham were significant higher than that in diaphysis three-point bending test.Positive correlations between biomechanical parameters and femur BMD or bone histomorphometry indexes were observed in both the diaphysis bending and metaphysis bending test.The biomechanical parameters in the metaphysis bending test showed stronger correlations with BMD and bone.ConclusionFemur metaphysis bending test could be used to evaluate the biomechanical properties of osteoporosis.When compared with diaphysis bending test,femur metaphysis bending test is more sensitive in evaluating the change of biomechanical properties of femur in osteoporotic rats.

Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) belongs to peptidyl-prolyl cis-trans isomerase (PPIase) and is a novel promising anticancer target. Based on the lead structure of benzophenone, a series of novel diarylether derivatives containing a pyrimidine ring were designed and synthesized. The inhibitory activities on Pin1 of compounds 5a-5d and 6a-6i were evaluated by a protease-coupled enzyme assay. Of all the evaluated compounds, 6 compounds displayed inhibitory activities. Molecular docking was performed using FlexX algorithm to explore the binding mode of the active molecules.