The purpose of this study is to find out anti-HIV-1 reverse transcriptase (RT)/protease (PR) activity and inhibition of virus replication in cell cultures of novel coumarin analogs and determine their structure-activity relationship. Coumarin derivatives have been demonstrated to inhibit the activity of HIV-1 RT/PR in cell free system. It also shows inhibition effects to HIV-1 replication in cell culture. Based on the Chinese traditional pharmacological characteristics and protein three dimension computer aided design, analogs of tetracyclic dipyranocoumarin were synthesized from natural leading compounds. We studied the relationship of antiviral effects and chemical structures via HIV-1 PR/RT enzyme models and cell culture model system. Seven compounds were designed and tested. Several compounds showed anti-HIV-1 activity in varying degrees, especially V0201 showed much higher anti-HIV-1 activity with 3.56 and 0.78 micromol x L(-1) of IC50 against HIV-1 PR/RT and 0.036 micromol x L(-1) against HIV-1 replication in PBMC cultures. V0201 with a novel structure may be a new leading compound. These new compounds are valuable for development of new anti-HIV drugs in the future.

AIM:To investigate the expression of poly(ADP-ribose) polymerase-2 (PARP-2) during rat car-diac hypertrophy in vitro and in vivo, and to explore the effects of PARP-2 on the cardiac hypertrophy.METHODS:Ab-dominal aortic coarctation ( AAC) was performed to establish a model of pressure overload-induced cardiac hypertrophy in SD rats.The expression of PARP-2 at mRNA and protein levels in the myocardium was determined by real-time PCR and Western blot.The hypertrophy model of the cardiomyocytes was induced by treating the cells with angiotensinⅡ( AngⅡ) . PARP-2 was knocked down by siRNAs in neonatal rat cardiomyocytes and the cardiomyocyte hypertrophy was evaluated by measuring the mRNA levels of ANF, BNP, and β-MHC and the cellular surface area.RESULTS: The expression of PARP-2 at mRNA and protein levels was both increased in the AAC rats as compared with those in the sham animals.The expression of PARP-2 at mRNA and protein levels was also increased in a time-and concentration-dependent manner in AngⅡ-induced hypertrophy model of the cardiomyocytes.In the neonatal rat cardiomyocytes, knockdown of PARP-2 ex-pression by siRNA attenuated AngⅡ-induced cardiac hypertrophy of the cardiomyocytes, indicating that endogenous PARP-2 played a positive regulatory role in cardiac hypertrophy.CONCLUSION:The mRNA and protein levels of PARP-2 in-crease in the in vitro and in vivo models of cardiac hypertrophy.Knockdown of PARP-2 protects cardiomyocytes from hyper-trophy.

Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) plus needling the distal acupoints along the pathway of meridians for shoulder periarthritis (SP). Methods: A total of 70 patients with SP were divided into an observation group and a control group using the random number table method, with 35 cases in each group. The patients in the observation group were treated by Tuina combined with needling distal acupoints along the pathway of meridians, while those in the control group only received the same Tuina treatment as in the observation group. The visual analog scale (VAS) and shoulder joint function were scored before and after treatment, and the efficacy after treatment was evaluated. Results: After three courses of treatment, the total effective rate of the observation group was 94.3％, while the total effective rate of the control group was 80.0％, showing a statistical difference (P<0.05). After treatment, the VAS scores of the two groups were significantly lower than the baseline scores (P<0.01), and the VAS score of the observation group was lower than that of the control group (P<0.01). After treatment, the total scores of internal rotation, external rotation, back touching, ear touching and motion function in the two groups were significantly higher than those before treatment (P<0.01), and the above five scores in the observation group were significantly higher than those in the control group (P<0.01). Conclusion: Tuina combined with needling the distal acupoints along the pathway of meridians is more effective than Tuina alone in treating SP. The combined therapy can relieve the pain and improve joint function more effectively.

Objective To study whether the green fluorescent protein ( GFP) gene can be successfully expressed in green fluorescent nude mice and the tissue distribution characteristics.Methods Small animal imaging system and RT-PCR assay were used to detect the GFP tissue distribution and fluorescence expression level.Results The GFP can be expressed in multiple tissues in green fluorescent nude mice.A higher expression was observed in the pancreas, heart, brain, and skin.Conclusion Exogenous GFP can be stably expressed and inherited in green fluorescent nude mice, with the highest expression in the pancreas.

Background:X-linked inhibitor of apoptosis (XIAP) is a vital factor in the anti-apoptosis mechanism of tumors and is highly expressed in renal cell carcinoma (RCC).However,the mechanism through which XIAP regulates DNA damage repair is unknown.This study investigated the regulatory mechanism of XIAP in etoposide-induced apoptosis in two Caki-1 cell lines with high or low XIAP expression.Methods:The two cell lines were established using RNA interference technology.The differentially expressed proteins in the two cell lines were globally analyzed through an isobaric tags for relative and absolute quantitation-based quantitative proteomics approach.Proteomic analysis revealed 255,375,362,and 5 differentially expressed proteins after 0,0.5,3,and 12 h of drug stimulation,respectively,between the two cell lines.The identified differentially expressed proteins were involved in numerous biological processes.In addition,the expression of histone proteins (H1.4,H2AX,H3.1,H3.2,and H3.3) was drastically altered,and the effects of XIAP silencing were accompanied by the marked downregulation of H2AX.Protein-protein interactions were assessed and confirmed through immunofluorescence and Western blot analyses.Results:The results suggested that XIAP may act as a vital cell signal regulator that regulates the expression of DNA repair-related proteins,such as H2AX,and influences the DNA repair process.Conclusions:Given these functions,XIAP may be the decisive factor in determining the sensitivity of RCC cell apoptosis induction in response to chemotherapeutic agents.

Objective To study the extracranial scalp electroencephalography ( EEG ) and intracranial electrocorticography (ECoG) of closed colony New Zealand white rabbits .Methods To record the extracranial scalp EEG and intracranial ECoG of closed colony New Zealand white rabbits , and to compare and analyze the results of those two scanning methods .Results EEG was characteristic of 9-12 c/sαwave and 16-20 c/sβwave with an amplitude of 30-100μV as the basic rhythm .ECoG showed 10-12 c/s αwave and 16-20 c/s βwave with an amplitude of 200-300 μV as the basic rhythm.Anesthesia could attenuate the electrocerebral activity , cause brain tissue hypoxia , and induce δ wave and slow θ wave in ECoG .Conclusions EEG method is a simple , non-invasive and convenient operation , and can be made in rabbits without anesthesia .The recorded EEG waveform is highly consistent with that of ECoG , and may be used as an alternative to the traditional ECoG in neurofunctional studies .

[Objective]This study was designed to investigate the genetic evolution of the neuraminidase(NA)gene of seasonal A/H1N1 and 2009 novel A/H1N1 inflilenza virus,and discuss the genetic variation of influenza A virus.[Methods]The virus strains were separately isolated from the clinical samples collected in 2006 and 2009,and then identified as seasonal A/H1N1 and novel A/H1N1.The full length of the NA gene of these strains was amplified by RT-PCR.Then the genetic evolution and mutations of important functional sites were analyzed.[Results]The homology of NA gene between the 2009 novel A/H1N1 isolates and 2006 seasonal A/H1N1 isolates was low(77.9%～78.8%),so was the homology of NA gene between the 2009 novel A/H1N1 isolates and representative strains of different periods and 1979-2001 WHO recommended vaccine strains(78.1%～79.3%).But compared with the WHO recommended vaccine strains of 2009 novel A/H1N1,the homology reached more than 99%.The genetic evolution analysis revealed that NA gene of 2009 novel A/H1N1 had the closest genetic relationship with the swine influenza A virus(A/swine/Belgium/1/1983)from Eurasian Iineage,and some of the antigenic sites and neuraminidase active sites of NA gene of seasonal A/H1N1 were mutated after 2005.[Conclusion]The NA gene of 2009 novel A/H1N1 may originate from Eurasian Iineage of swine influenza virus.The variation of NA gene of seasonal A/H1N1 has occurred in a certain degree.Hence,it is very necessary to continuously monitor the variant of influenza A virus.

BACKGROUNDRetroperitoneal fibrosis (RPF) is an uncommon disease that is characterized by development of fibrosclerotic tissues involving retroperitoneal structures. This study aimed to investigate the clinical features of 30 patients with RPF in a single center in Beijing in a 10-year period.

METHODSWe retrospectively analyzed clinical data on demographic characteristics, clinical manifestations, laboratory findings, radiological findings, modalities of treatments, outcomes and prognosis of 30 patients with RPF. Patients were treated in Beijing Chao-Yang Hospital between January 2003 and December 2013.

RESULTSThe mean age of patients with RPF was 56.7 ± 14.4 years. Twenty-three patients were men and seven patients were women. Acute phase reactants were elevated in most patients. Rheumatic factor was positive in 4/25 (16.0%) patients, and antinuclear antibody was positive in 6/22 (27.3%) patients. Elevation of IgG4 was observed in 9/22 (40.9%) patients. The most common type was I + III (n = 13), followed by I + II + III (n = 12). Five patients undertook an 18 F-fluoro-deoxy-D-glucose positron emission tomography examination and increased uptake was detected in four patients. Eight patients received combination therapy with glucocorticoids and tamoxifen. Surgical intervention treatments included intraureteral double-J stent implantation (n = 26), percutaneous nephrostomy (n = 2), open ureterolysis and intraperitonealization of the ureters (n = 5) and laparoscopic ureterolysis and intraperitonealization of the ureters (n = 5). Three patients underwent hemodialysis because of renal failure.

CONCLUSIONSClinical characteristics of RPF patients in our study are similar to those previously reported. Steroids and immunosuppressive therapy combined with ureterolysis could be a viable choice of treatment for RPF. More prospective, multi-center studies with a longer follow-up are warranted.

Adult ; Aged ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Immunoglobulin G ; blood ; Male ; Middle Aged ; Retroperitoneal Fibrosis ; blood ; diagnosis ; drug therapy ; surgery ; Retrospective Studies ; Tamoxifen ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the effect of tumor necrosis factor alpha (TNFalpha) on radiosensitivity of nasopharyngeal carcinoma (NPC) in relation to TNFalpha-induced cell cycle synchronization.

METHODSThe radio-resistance of a NPC cell line subclone CNE-2Z-S1 was verified by in vivo experiments and flow cytometry was performed to evaluate cell cycle synchronization in TNFalpha-treated CNE-2Z-S1 cells. The radiosensitivity of the cell synchronized CNE-2Z-S1 cells was determined by clone formation in vitro and in vivo experiment in nude mice.

RESULTSTNFalpha was capable of inducing cell cycle arrest and synchronization of CNE-2Z-S1 cells. Pretreatment with TNFalpha remarkably enhanced the radiosensitivity of CNE-2Z-S1 in vitro, and in vivo experiments with nude mice also suggested the role of TNFalpha in enhancing the radiosensitivity of NPC.

CONCLUSIONTNFalpha can enhance the radiosensitivity of NPC cells by inducing cell cycle synchronization.

Animals ; Cell Cycle ; drug effects ; radiation effects ; Cell Line, Tumor ; Humans ; Mice ; Mice, Nude ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Radiation-Sensitizing Agents ; pharmacology ; Tumor Necrosis Factor-alpha ; pharmacology ; Xenograft Model Antitumor Assays

Objective To investigate the immunization coverage of oral live attenuated rotavirus vaccines and its influencing factors among children under 5 years old in Jinshan District of Shanghai in order to provide references for optimizing vaccination management in this area. Methods A cross-sectional study was conducted in 6 community vaccination clinics randomly selected from 12 vaccination clinics in Jinshan District. In each selected clinic,145 children under 5 years old were continuously recruited. Information on immunization status,demographics of children,family socioeconomic status and parents′knowledge of vacci-nation were collected through questionnaire interview. Logistic regression was used to analyze factors influen-cing immunization status by using SPSS22.0. Results Among the 863 participating children, the immuni-zation coverage rate of oral live attenuated rotavirus vaccines was 61.07%. Multivariate analysis revealed that children having an urban registration status (OR=2.21),better family income (OR=1.47) and par-ents with high recognition of rotavirus diarrhea (OR=8.56) and stronger intention to following "doctor′s suggestions" (OR=1.96) were more likely to accept oral live attenuated rotavirus vaccines, while those from families with a medical professional were less likely to be vaccinated (OR=0.57). Conclusion The immunization coverage rate of oral live attenuated rotavirus vaccines among children in Jinshan District were influenced by various factors such as children′s household registration status, household income, parents′knowledge regarding vaccination and doctors′suggestions. Health education on immunization should be strengthened and tailor-made to improve the coverage of oral rotavirus vaccination.