The plasma ammo acid levels in 21 centenarians(age 100-106), 21 elders (age 65-78) and 37 young human subjects (age 18-21) were determined. 17 of 24 amino acids studied showed lower values in centenarian and elder groups than those in young group (p

OBJECTIVE To analyze the reason of cause of nosocomial infection of AIDS and the events of medical staff exposed to the virus of HIV,to explore the role of activity in the education program and put in practice the education.METHODS To analyze the activity of education about prevention of nosocomial infection of AIDS and postexposure prophylaxis.RESULTS Having practiced the education,all of medical staffs increased the consciousness to prevent the AIDS,there was not a case of exposed to virus of HIV in the first half of year of 2007.CONCLUSIONS Leaders pay attention to and practice the education activity about NI and prevent the staff from exposure to virus of HIV,especially,to realize a series of rules and counter measures,it is key links to prevent AIDS among medical staffs in hospital.

OBJECTIVETo establish a UPLC-MS/MS analysical method for simultaneous determination of concentrations of isoorientin, scutellarin and cynaroside in rat plasma and to study their pharmacokinetic characteristics after intravenous injection of 3 doses of Fufang Hongcao in rats.

METHODAcidified plasma samples were precipitated for protein with methanol. Waters Acquity BEH C18 column was adopted for spectrum, with mobile phase as 0. 1% formic acid acetonitrile-0. 1% formic acid-water gradient elution. Detection was carried out by the multiple reaction monitoring (MRM) positive ion mode with ESI ionization source.

RESULTThree flavonoids show a good linear relationship, with the extraction recovery ranging between 78.56% and 101.91% and a high intra-and inter-day precisions and accuracy. The MRT of the three flavonoids were all lower than 22 min in rats.

CONCLUSIONThe above men tioned method is so specific, rapid, sensitive that it is suitable for pharmacokinetic studies of Fufang Hongcao injection in rats.

Animals ; Apigenin ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; pharmacokinetics ; Female ; Glucosides ; blood ; pharmacokinetics ; Glucuronates ; blood ; pharmacokinetics ; Luteolin ; blood ; pharmacokinetics ; Male ; Rats ; Tandem Mass Spectrometry ; methods ; Time Factors

Objective To screen the active tuberculosis patients among HIV infected patients,and investigate the diagnostic methods for active tuberculosis among TB/HIV co-infected patients.Methods From August 2006 to March 2007,660 HIV/AIDS patients were enrolled.The study was conducted at 4 authorized hospitals for AIDS in Nanning and Liuzhou.Chest X-ray(CXR),acid-fast stain test of sputum smear and fast culture were applied if CD+4 T cell counts were below 350 cells/mm3 or the patients at least have one suspected symptom.Result The CD<;+>4 T cell count in 76.1% (502/660) of the patients was less than 200 cells/mm3.TB/HIV coinfection was found in 22.9% (151/660) of the HIV patients.Among them,74.8% (113/151) of them were pulmonary TB patients.One third of them were extra-pulmonary TB patients,and 68.1% of them involved lymph node.In 264 patients with negative sputum smear test and CXR,20.1% (53/264) of them showed positive results in fast culture tests.In addition,the non-tuberculosis mycobacterium (NTM) infection accounted for 38.5% culture positive cases.Conclusions The TB/HIV coinfection rate is 22.8%.Liquid rapid culture of sputum plays an import role in diagnosing of active tuberculosis among HIV patients.There are considerable proportions of NTM or extra-pulmonary TB coinfection in HIV patients.

A simple and selective ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) assay was developed for the determination of the human plasma protein binding of four bioactive flavonoids (such as orientin and vitexin) in Polygonum orientale. Protein precipitation was used for sample preparation. Equilibrium dialysis technique was applied to determine the plasma protein binding under physiological conditions. The separation was achieved through a Waters C18 column with a mobile phase composed of 0.1%formic acid in acetonitrile and 0.1%aqueous formic acid using step gradient elution at a flow rate of 0.35 mL/min. A Waters ACQUITY?TQD system was operated under the multiple reaction monitoring (MRM) mode of positive electrospray ionization. All of the recovery, precision, accuracy and stability of the method met the requirements. Good correlations (r40.99) of the four compounds were found, which suggested that these compounds can be simultaneously determined with acceptable accuracy. Results showed that the plasma protein bindings of the four bioactive flavonoids were in the range of 74-89% over the six concentrations studied. The binding parameters containing protein binding affinity, protein binding dissociation constant, and protein binding site were studied. The maximum ability to bind with protein was also determined in the assay in order to understand the drug-protein binding of each compound better.

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.