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 .

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.

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 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.

【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.

Objective To develop a novel method for treating complete heart block by autotransplantation of simus node node cells to right ventricular anterior wall.Methods Twenty healthy mongrel dogs were involved in the present study.The dogs were randomly assigned to transplant group or control group(n=10).The sinus node (SN)was harvested and isolated in vitro after an electronic pacemaker was implanted and complete heart bolck was introduced.The SN cells from dogs of transplant group were injected to autogenic right ventricular wall.Commensurable culture medium was implanted to ghe same position of dogs in control group.Two weeks later,detailed electropohysiological study was performed.For investigating the variation of the rhythm,epinephrine was administrated through femoral vein to dogs of transplant group.Results Most of isolated SN cells from dogs were thin-spindle shape,and cell activity was fine.The SNs by VG stained displayed typical structural feature.2 weeks after cell autotransplantation,higher heart rates were achieved from transplant group than that in control group(P＜0.05).This rhythm was stable in 4 weeks and became faster remarkably after administration of eninephrine(P＜0.05).Conclusion SN cell of dogs tutorgrfted into right ventricular anterior wall can form new pacemaker site in ventrcle and improve ventricular rate of complete heart bolck.This pacemaker site can also be regulated by epinephrine.

OBJECTIVE: To observe the effects of Xuefu Zhuyu Capsule (XFZYC), a compound traditional Chinese herbal medicine, on endothelin-1 (ET-1) release in myocardium and vascular endothelium and nitric oxide (NO)/nitric oxide synthase (NOS) system of swines after acute myocardial infarction (AMI) and reperfusion, and to explore the action mechanisms of XFZYC in improving the endothelium function. METHODS: Forty-five Yorkshire swines were randomized into 3 groups: sham-operated group, untreated group and XFZYC-treated group. A Yorkshire swine model of reperfusion in AMI was established by ligation of left anterior descending coronary artery for 90 min followed by 2 h relaxation. The content of serum ET-1 and NO was measured by radioimmunoassay before and after AMI and after reperfusion, respectively. Twenty-four hours after operation, all Yorkshire swines underwent diagnostic coronary angiography to delineate coronary arteries. The expressions of ET-1 and endothelial nitric oxide synthase (eNOS) in myocardial tissue of ischemic area were quantified with Western blotting. Microvessel density of the implanting sites was assessed by using HE staining. RESULTS: Compared with the untreated group, the levels of serum ET-1 after AMI and reperfusion were significantly decreased in XFZYC-treated group (P<0.01), while the NO levels after AMI and reperfusion in XFZYC-treated group were significantly increased (P<0.01). There was no significant difference in diagnostic coronary angiography between XFZYC-treated group and untreated group (P=0.253). Western blotting showed that the level of ET-1 in ischemic area in XFZYC-treated group was lower than that in the untreated group (P<0.01), while the eNOS protein expression in XFZYC-treated group was higher than that in the untreated group (P<0.01). The results of HE staining and microvessel density analysis of the implanting sites all showed that the degree of telangiectasis was reduced, the cardiac muscle damage was improved, and the density of capillaries was increased obviously in XFZYC-treated group as compared with the untreated group. CONCLUSION: The endothelium injury may be one of the important mechanisms for no-reflow phenomenon. XFZYC may reduce the no-reflow by protecting endothelium cells.