AIM:To examine and compare the effects of several ARBs that are widely used in clinics , on the ACE-Ang II-AT1 receptor and the ACE2-Ang(1-7)-Mas axis during the development of cardiac remodeling after pressure overload .METHODS: All of the mice used in the study underwent transverse aortic constriction (TAC) or sham operation for 2 or 4 weeks.A solution of either ARBs or sa-line was administered through a stomach tube 3 days before the operation .Meanwhile , to eliminate the influence of Ang II , a recombi-nant adenovirus expressing small interfering RNAs targeting angiotensinogen ( Ad-ATG siRNA) was injected via the tail vein .The sur-gery was then performed and the drug was administered as mentioned above .Cardiac function and remodeling were evaluated by echo-cardiography , hemodynamic measurements and cardiac histology .Western blotting was used to determine the protein expression levels . Meanwhile , we performed similar experiments using ARBs with or without ATG siRNA in cardiomyocytes induced by mechanical stretch.RESULTS:Although all of the six ARBs , none of which repressed the elevation of left ventricular pressure after TAC , attenu-ated the development of cardiac hypertrophy and heart failure in the wild-type mice, the degree of attenuation by Olmesartan , Candesar-tan and Losartan tended to be larger than that of the other three drugs tested .Additionally , the degree of downregulation of the ACE-Ang II-AT1 axis and upregulation of the ACE2-Ang(1-7)-Mas axis was higher in response to Olmesartan, Candesartan and Losartan administration in vivo and in vitro.Additionally, Olmesartan had a larger influence when administered long term .However, the expres-sion of ACE was not influenced by the administration of ARBs in vivo and in vitro.Moreover, in angiotensinogen-knockdown mice, TAC-induced cardiac hypertrophy and heart failure were inhibited by Olmesartan , Candesartan and Losartan but not by Telmisartan , Valsartan and Irbesartan administration .Furthermore , only Olmesartan and Candesartan could downregulate the ACE-Ang II-AT1 axis and upregulate the ACE2-Ang(1-7)-Mas axis in vitro.CONCLUSION: Olmesartan, Candesartan and Losartan could effectively in-hibit pressure overload-induced cardiac remodeling even when with knockdown of Ang II , possibly through upregulation of the expres-sion of the ACE2-Ang(1-7)-Mas axis and downregulation of the expression of the ACE-Ang II-AT1 axis.In contrast, Telmisartan, Valsartan and Irbesartan only played a role in the presence of Ang II , and Losartan had no effect in the presence of Ang II in vitro.

OBJECTIVE:To study improvement effect of modified mahuang chanyi decoction on allergic rhinitis(AR)model guinea pigs and its mechanism. METHODS:32 guinea pigs were randomly divided into normal group (0.9% Sodium chloride in-jection),model group (0.9% Sodium chloride injection),experimental [Modified mahuang chanyi decoction,5.18 g (medicinal materials)/kg] group and control [Fluticasone propionate nasal spray,50 μg/(guinea pig·d)] group. Except for normal group,other groups received ovalbumin 30 mg and calmogastrin 30 mg intraperitoneally to induce AR model. Except for control group,other groups were given relevant medicine intragastrically,twice a day for consecutive 15 d. Nasal symptoms of guinea pigs were ob-served and recorded,and then analyzed and scored. The protein expression of nasal mucosa SHP-1 was detected by immunohisto-chemistry,the serum contents of IL-4 and IFN-γ were determined by enzyme-linked immunosorbent assay. RESULTS:Compared with normal group,model group suffered from AR symptom,and nasal symptoms score was increased;and the protein expression of nasal mucosa SHP-1 and the serum content of IL-4 increased,while the content of IFN-γ decreased(P<0.05). Compared with model group,AR symptom of experimental group and control group were improved;nasal symptoms score,the protein expression of nasal mucosa SHP-1 and the serum content of IL-4 decreased while the content of IFN-γ increased(P<0.05). CONCLUSIONS:Modified mahuang chanyi decoction shows certain improvement effect on AR,and its mechanism is associated the decrease of IL-4 content and the increase of IFN-γcontent in serum.

Questionnaire survey and semi-structured interview were done in December 2005 and April 2006 to explore the reasons why foreign and minority medical students failed in course examinations last year.It is found that many factors affect their studying such as proficiency in Chinese,original foundation,studying and living habits,familiarity to the regulations of educational affairs,time and effort spent for self-studying and the attitude in which the teachers treat them.And also the correspondent countermeasures are given according to the survey and interview.

Objective To study the morphology of normal liver and tumors by breathing motion of hepatocellular carcinoma patients,through comparing the modified demons algorithm and FFD algorithm based on B-spline,and combing four-dimensional computed tomography (4DCT).Methods The 4DCT images of 8 HCC patients were segmented into 10-series which were named CT0,CT10 … CT80,CT90 according to the respiratory phases,CT0 and CT50 are defined to be end-inhale and end-exhale respectively.CT50 was chosen as the reference image.We used the modified demons algorithm and FFD algorithm based on B-spline to deform the images.Linear interpolation was used in both mode 1 and mode 2.The normalized mutual information (NMI),Hausdorff distance (dH) and registration speed were used to verify the registration performance.Results The average NMI for the end-inhale and end-exhale images of 8 HCC patients after demons registration in mode 1 improved 4.75％ with FFD algorithm based on B-spline(P =0.002).And the difference of dH after demons reduced 15.2％ comparing with FFD model algorithm (P =0.02).In addition,demons algorithm has the absolute advantage in registration speed(P =0.036).Conclusions The breathing movement for deformation of normal liver and tumor targets is significant.These two algorithms can achieve the registration of 4DCT images and the modified demons registration can deform 4DCT images effectively.

Objective To investigate the clinical features,the radiological characteristics,and the pathological changes of cerebral sparganosis.Methods We retrospectively collectted and summarized the clinical data of 42 patients with cerebral sparganosis from the Iinstitute of Anti-parasitic Diseases of Jiangxi Province and the First Affiliated Hospital of Nanchang University during January 2000 to January 2014.The follow-up period of the 42 patients ranged from 4 to 96 months.Results Forty-two cases (30 males and 12 females) with cerebral sparganosis were enrolled in the study.Among the 42 patients,34 cases suffered from seizures,16 cases experienced headaches,and 14 cases had limb weakness.The brain CT scan showed the small and punctuate calcifications scattering around the lesions in 18 cases.The features of enhanced MRI included aggregating ring-like enhancement in 38 cases,tunnel lesions in 14 cases,and lesion migration in 13 cases.Twenty-four of the 42 patients were performed surgery.The brain tissues revealed multiple inflammatory tunnels,in which live or degenerated larvae were identified in 20 cases,but only eosinophilia tunnels were observed in the other 4 cases.The serum and cerebro-spiral fluid specimens from 18 patients without surgery were positive to spirometra mansoni antigen.Their cerebral lesions disappeared and got a favorable prognosis after administration of praziquantel in long term follow-ups.Conclusions There is a high incidence of cerebral sparganosis in Poyang lake basin.The clinical features of cerebral sparganosis mainly include seizure,headache and hemiparesis.The enhanced lesions show knot or tunnel signs on multi-planar MRI which are associated with the multiple inflammatory tunnels of larvae migration.A longterm administration of high dose opraziquantel can also get a good treatment prognosis without the classical surgical therapy for cerebral sparganosis.

Objective: To observe the clinical efficacy of tuina manipulations in treating different types of tic disorders (TD). Methods: Eligible TD patients were classified into three types, transient tic disorders (TTD), chronic multiple tic disorders (CMTD) and Tourette syndrome (TS), according to their disease duration and severity. The three types of children were treated with the same tuina manipulations. Changes in the Yale global tic severity scale (YGTSS) score, effective rate for tic, and cervical spine imaging examination results (including asymmetry of the lateral atlanto-dental interval, broadened anterior atlanto-dental interval, C2 spinous process deviation, occipito-atlanto-axial flexion/ extension instability) were observed after 1-month and 3-month treatments respectively. Results: The YGTSS score changed significantly after 1-month and 3-month treatments compared with that before treatment (both P<0.01); the effective rate for TD was 46.6％ and 86.7％ respectively after 1-month and 3-month treatments; there were significant differences comparing the effective rate for tic between different types of TD after 1-month and 3-month treatments (all P<0.05); comparing the effective rate for tic after 1-month treatment with that after 3-month treatment for the same type, the intra-group differences were statistically significant [TTD group (P<0.01), CMTD group (P<0.01), TS group (P<0.05)]; the abnormal parameter rates in neck imaging examination after 3-month treatment were significantly different from those before treatment (all P<0.01). Conclusion: Tuina manipulation is effective for TTD, CMTD and TS. It can correct the abnormal alterations of patients' cervical vertebrae, and its efficacy for TTD is most significant.

Objective To study the effect of antiapoptosis factors PED/PEA-15 and XIAP on prostate cancer cells(PC-3)apoptosis.Methods The expressions of XIAP and PED/PEA-15 in prostate cancer cells(PC-3)were respectively assayed using the RT-PCR technique.XIAP and PED/ PEA-15 specific siRNA vectors were designed and constructed and then were transiently cotransfected into PC-3 cells under induction of liposome.The effects of siRNA vectors on PED/PEA-15 and XIAP transcription were assayed by RT-PCR technique,and the effect of XIAP and PED/PEA-15 on cancer cell apoptosis were determined by flow cytometry and microscope observation.Results PED/PEA- 15 and XIAP were both highly expressed in PC-3 cells.Enzyme digestion analysis and DNA sequencing confirmed that the PED/PEA-15 and XIAP-specific siRNA expression vectors were constructed successfully.The designed siRNA sequences of PED/PEA-15 and XIAP could specifically inhibit their transcription.The PC-3 cells which were cotransfected with PED/PEA-15 and XIAP- specific siRNA vectors were more sensitive to doxorubicin.The apoptosis rate of cotransfected cells was significantly increased.Conclusions PED/PEA-15 and XIAP might be involved in the development of prostate cancer.

Thienorphine is a chemically-new opioid developed in Beijing Institute of Pharmacology and Toxicology. To elucidate the chemical basis for the unique pharmacological effects of thienorphine, 15 derivatives were synthesized according to combinatorial chemistry and the structure-activity relationships of these compounds were studied. It is demonstrated that thienorphine is a potent long-acting partial agonist. N-Cyclopropylmethyl is responsible for the antagonist effect of thienorphine. More importantly, thiophene at the end of side chain is most likely the pharmacophore accounts for the long-lasting effect of thienorphine. Change of the connection of thiophene and the side chain does not result in changes in the antinociceptive activity.
Animals ; Buprenorphine ; analogs & derivatives ; pharmacokinetics ; pharmacology ; Combinatorial Chemistry Techniques ; Dose-Response Relationship, Drug ; Female ; Male ; Mice ; Mice, Inbred Strains ; Morphine ; pharmacology ; Rats ; Rats, Wistar ; Receptors, Opioid ; agonists ; Structure-Activity Relationship

Peptide nucleic acid(PNA) is a kind of artificial DNA mimic. PNA hybridizes with DNA or RNA by means of Watson-Crick's base-pairs complementary with high stability, affinity and selectivity. PNA not only regulates. DNA replication, but also adjusts DNA transcription (or reverse transcription) and translation. Many applications have been explored as a new kind of molecular biological tool and a gene-targeting strategy.
Gene Expression Regulation ; drug effects ; Peptide Nucleic Acids ; pharmacology ; Protein Biosynthesis ; drug effects ; Transcription, Genetic ; drug effects

Objective To observe the effect of raloxifene, a selective estrogen receptor modulator, on osteoporosis in the osteoprotegerin (OPG) gene knock-out female and male mice. Methods Two groups of OPG gene deficient (OPG-/-) female and male mice, 20 mice in each group, were assigned to raloxifene-treated (3 mg The effect of raloxifene was evaluated by comparing the values of bone mineral density (BMD) , bone strength,histomorphometric measurement and osteoclast number between the raloxifene treated group and placebo group.Results As compared with placebo group osteoporotic manifestations were improved in OPG-/- female mice treated with raloxifene orally. BMD was increased both in lumbar vertebrae (P<0.05) and femurs (P<0.01).Bone strength was measured in femurs by three-point bending test and vertebrae by stress test. Results showed that ultimate load, ultimate stress and Young's modulus were increased both at lumbar and femur bone, suggesting decreased risk of fracture. Tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts, was detected, and the number of osteoclasts declined significantly after the treatment of raloxifene. At the same time, results of histomorphometric measurements indicated that bone trabecular volume was increased and bone formation rate decreased from(8.05±4.02)mm3·mm-2·year-1 to (5.48±1.89)mm3·mm-2· year-1(P＜0.05).These findings were found in the group of OPG-/- female mice treated with reloxifene but not in male mice. Conclusions Raloxifene is effective in treating osteoporosis in female OPG-/- mice, indicating that its action is at least in part independent of OPG gene. But it is ineffective in male OPG-/- mice.