AIM: To investigate the changes in nuclear calcium content and permeability of nuclear pore complex in rat myocardium during ischemia reperfusion injury.METHODS: The rat model of myocardial ischemia reperfusion injury was established.Myocardial nuclei were purified using sucrose density gradient centrifugation.The nuclear calcium content was measured by atomic absorption spectrophotometer.The permeability of nuclear pore complex was assessed through measuring the amount of calmodulin conjugated Alexa Fluo~(TM) 488 as fluorescent probes transported across nuclear membrane with spectrofluorometer.RESULTS: The nuclear calcium content at 15,30,60,120 and 180 min reperfusion following 30 min sustained ischemia increased 1.31-,1.55-,1.73-,1.94-and 2.14-fold,respectively,as compared with sham-operation group.The permeability of nuclear pore complex at 15 min reperfusion following 30 min sustained ischemia showed no difference from sham-operation group,but it only increased 1.31-,1.38-,1.40-,and 1.48-fold at 30,60,120 and 180 min reperfusion following 30 min sustained ischemia compared with sham-operation group.CONCLUSION: The nuclear calcium content during myocardial ischemia reperfusion injury increases earlier than the permeability of nuclear pore complex does.The increase in the permeability of nuclear pore complex may result in adaptive regulatory effects on nuclear calcium overload to a certain extent during myocardial ischemia reperfusion injury.

Sonic hedgehog (Shh) signaling has recently been shown to be involved in the pathological angiogenesis in response to tissue hypoxia and ischemic injury. Hypoxia/ischemia is considered to play an important role in the development of choroidal neovascularization (CNV). This study was aimed to examine the effect of blockade of the Shh signaling pathway on CNV and the underlying mechanism. A total of 64 male Brown-Norway (BN) rats were used in this study. One eye of each rat underwent laser photocoagulation. The other eye served as normal control. After the laser treatment, the 64 rats were divided into four groups (n=16 in each group): Blank control group, in which no intravitreal administration was given; cyclopamine group, recombinant Shh N-terminals protein (rShh) group and phosphate-buffered saline (PBS) group, in which cyclopamine (a Shh inhibitor), rShh (a Shh activator) and PBS were intravitreally injected into the laser-treated eyes respectively every other day for a total of four intravitreal injections immediately after the laser treatment. Fourteen days after the intravitreal administration, the changes of CNV-related variables, including positive CNV lesion percentage, CNV membrane area and CNV membrane thickness, were evaluated by fluorescein angiography, indocyanine green angiography and pathological examinations. The mRNA and protein expression of PTCH1, Gli1, HIF-1(α), VEGF and DLL4 in each group on 14 days of CNV model was detected by real-time quantitative PCR and western blot analysis, and the relationship between the Shh cascade and the HIF-1(α)-VEGF-DLL4 cascade in CNV was analyzed. The results showed that the CNV membrane area and the CNV membrane thickness were decreased by 62.5% and 41.9% in the cyclopamine group and increased by 85.7% and 64.3% in the rShh group in comparison to those in the blank control group (P<0.01 for each). There was no significant difference in the CNV membrane area and thickness between the blank control group and PBS group (P=0.102 and P=0.063, respectively). Real-time quantitative PCR revealed a 5.23-, 4.14-, 2.97-, 2.78- and 2.39-fold up-regulation of the mRNA expression of PTCH1, Gli1, HIF-1(α), VEGF and DLL4 genes in the laser-treated eyes compared with the normal control eyes in the control group. In the cyclopamine group, the mRNA and protein expression of Gli1, HIF-1(α), VEGF and DLL4 was significantly down-regulated (P<0.05 for each) while the expression of PTCH1 showed no significant changes at the mRNA (P=0.293) and protein level (P=0.304). The mRNA expression and protein expression (P=0.001 and P=0.021, respectively) of PTCH1, Gli1, HIF-1(α), VEGF and DLL4 was significantly increased in the rShh group when compared with the control group. The expression level of these genes was related to the severity of the CNV. It was concluded that intravitreal administration of cyclopamine can effectively inhibit the formation of laser-induced experimental CNV by down-regulating the expression of the HIF-1(α)-VEGF-DLL4 cascade in CNV. The Shh signaling pathway as an upstream signaling pathway of HIF-1(α)-VEGF-DLL4 cascade is implicated in the development of experimental CNV.

Objective To analyze the impact and its mechanism of down-regulation of AnnexinA2 expression on prostate cancer(PCa) invasion and metastasis.Methods The expression of AnnexinA2 in three prostate cancer cell lines with different metastasis ability,including LNCaP (lower metastasis ability),PC3 (lower metastasis ability),C4-2B (higher metastasis ability) were detected by Western blot.The correlations between the expression of AnnexinA2 and the metastasis ability of prostate cancer cells were also evaluated.The siRNA was used in PC3 cells to down-regulate the expression of AnnexinA2,the cell proliferation assay was performed by MTT method,the cell apoptosis level was detected by flow cytometry,the expression of MMP-2 and MMP-9 were detected by Westrn blot,the in vitro invasiveness of PC3 was detected by transwell cabinet test,and the migration ability of PC3 cells was detected by scratch test,respectively.Results The grayscale value of AnnexinA2 expression in C4-2B cells is 0.22,in contrast with the internal reference,which was obviously lower than those of LNCaP and PC3 cells with lower metastasis potency(relative grey value is 0.93 and 0.95,respectively.P＜0.01).After RNAi was used in PC3 cells to down-regulate the expression of AnnexinA2,the growth became faster for PC3-ANXA2-siRNA cells than PC3,PC3-Lip and PC3-empty vector cells (P＜0.05).After RNAi was used in PC3 cells to down-regulate the expression of AnnexinA2,the ratio of apoptosis was detected by flowcytometry in PC3,PC3-Lip,PC3-empty vector and PC3-ANXA2-siRNA cells,and the apoptosis ratio in PC3-ANXA2-siRNA cells was the highest.However,the difference was not significant compare to others (P＞0.05).After RNAi was used in PC3 cells to downregulate the expression of AnnexinA2,the expression of AnnexinA2 in PC3-ANXA2-siRNA cells was decreased while the expression of MMP-2 and MMP-9 were increased.After RNAi was used in PC3 cells to down-regulate the expression of AnnexinA2,invasiveness of PC3-ANXA2-siRNA cells detected by transwell cabinet test was increased in vitro,and migration of PC3-ANXA2-siRNA cells detected by scratch test was increased in vitro.Conclusions The down-regulation of expression of AnnexinA2 could increase the invasive and metastatic ability of prostate cancer,and this may attribute to the up-regulation of MMP-2 and MMP-9 expression in prostate cancer.

OBJECTIVETo explore the therapeutic effects of amiodarone and metoprolol, either alone or in combination, on chronic heart failure (CHF) complicated by ventricular arrhythmia.

METHODSA total of 110 NYHA class II-III patients with CHF complicated by ventricular arrhythmia were randomly divided into amiodarone group, metoprolol group and amiodarone + metoprolol group. The therapeutic effects was evaluated at the end of the 1-year follow-up.

RESULTSAmiodarone, metoprolol and their combination produced statistically different therapeutic effects (P<0.05). Compared with amiodarone and metoprolol used alone, amiodarone combined with metoprolol resulted in significant cardiac function improvement (P<0.05) and ventricular arrhythmia control (P<0.01). During the 1-year follow-up, the readmission rate and cardiac event rate in the amiodarone + metoprolol group were significantly lower than those in amiodarone group (P<0.01) and metoprolol group (P<0.05). The adverse reaction rates in the 3 groups were similar (P>0.05).

CONCLUSIONThe combination of amiodarone and metoprolol produces better effect than amiodarone or metoprolol alone in the treatment of CHF complicated by ventricular arrhythmia.

Adrenergic beta-Antagonists ; therapeutic use ; Adult ; Amiodarone ; therapeutic use ; Anti-Arrhythmia Agents ; therapeutic use ; Chronic Disease ; Drug Therapy, Combination ; Female ; Heart Failure ; complications ; drug therapy ; physiopathology ; Humans ; Male ; Metoprolol ; therapeutic use ; Tachycardia, Ventricular ; drug therapy ; etiology ; physiopathology ; Treatment Outcome ; Ventricular Premature Complexes ; drug therapy ; etiology

Air ; analysis ; Chromatography, Gas ; Propane ; analogs & derivatives ; analysis ; Reproducibility of Results ; Workplace

Adult ; Fever ; etiology ; Gastrointestinal Hemorrhage ; etiology ; Humans ; Male ; Polyps ; complications ; Stomach Diseases ; complications

Objective To demonstrate the diffusion tensor imaging(DTI)characteristics of multiple sclerosis(MS)plaques,periplaque white matter regions and normal appearing white matter (NAWM)regions in patients with MS,and to evaluate the clinical values of DTI and three-dimensional brain fiber tracking for the diagnosis of MS.Methods Conventional MRI and DTI were performed in 32 patients with MS and 32 age-matched control subjects.Fractional anisotropy(FA)and apparent diffusion coefficient(ADC)maps were generated and coregistered with T_2-weighted MR images,FA and ADC values were calculated in regions of interest in plaques,periplaque white matter regions,NAWM regions and white matter regions in control subjects.And three-dimensional brain fiber tracking maps were generated by using the DTI.Results TheADCwas(1.233?0.119)?10~(-3)mm~2/s in MS plaques,(0.973?0.098)?10~(-3) mm~2/s in periplaque white matter regions,(0.748?0.089)?10~(-3)mm~2/s in NAWM,and(0.620? 0.094)?10~(-3)mm~2/s in control subjects.The FA was 0.225?0.052 in MS plaques,0.311?0.050 in perip]aque white matter regions,0.421?0.070 in NAWM,and 0.476?0.069 in control subjects. Significant differences in FA and ADC values were observed among all white matter regions(P

[Abstract ] Objective The purpose of this study was to observe the effects of dl-3n-butylphthalide (NBP) sodium chloride injection post-processing on the expressions of X-inhibitor of apoptosis (XIAP) and Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in the hippocampus CA1 neurons of focal cerebral ischemia reperfusion (IR) rats, and to investigate the brain-protection mechanisms of NBP. Methods A total of65 adult male Sprague-Dawley rats were divided into five groups of equal number, sham op-eration, IR, and low-,medium -and high-dose NBP, according to the random number table. The IR models were established by modified ligation of the middle cerebral artery.The animals in the NBP groups received intra-abdominal injection of NBP at 2, 4, and 6 mg/kg, re-spectively.All the rats were sacrificed at 24 hours after modeling,neurological scores obtained by Zea Longa, the volume of infarction measured by TTC staining, the number of apoptotic cells counted by TUNEL, and the expressions of XIAP and BNIP3 detected by immunohistochemistry and real-time PCR. Results The neural function defect scores were markedly lower in low-, medium-and high-dose NBP groups than in IR model rats (P<0.05), with statis-tically significant differences among the three dose groups (P<0.05).The volume of infarction was remarkably higher in the low-dose than in the medium-and high-dose NBP groups (P<0.05).The number of apoptotic cells in the hippocampus CA1 neurons was de-creased in the NBP groups as compared with the IR models (P<0.05).The XIAP-and BNIP3-positive cells were significantly in-creased in the IR model rats as compared with the sham operation group ([22.31 ±0.94] and [60.13 ±2.59]/HP vs [3.07 ±1.43] and [5.78 ±0.44]/HP, P<0.05).In comparison with the IR models, the NBP-treated rats showed a progressively increased number of XIAP-positive cells in low-, medium-, and high-dose groups ([28.70 ±1.18], [32.79 ±0.88], and [37.01 ±1.24]/HP) (P<0.05) but a decreased number of BNIP3-positive cells in the three dose groups ([52.07 ±1.02], [40.30 ±2.00], and [31.04 ± 0.43]/HP) (P<0.05).Similarly, the expression of XIAP mRNA was up-regulated while that of BNIP3 mRNA down-regulated in the NBP treatment groups as compared with the IR model rats, both in a dose-dependent manner (P<0.05). Conclusion NBP post-processing has a neuroprotective effect on IR rats, which is associated with its impact on the expressions of XIAP and BNIP3.

· AIM: To report a rare case of mesenchymalchondrosarcoma in the orbit and to explore its clinicmanifestations, pathologic characters, management andprognosis. · METHODS: We report a case of mesenchymalchondrosarcoma of the orbit. The clinical materials,including ophthalmological examination, computed tomo-graphy scan of the orbit, histopathology and immunohis-tochemistry of the biopsy specimen was reported, and itspertinent literatures were reviewed.· RESULTS: A 36-year-old female was seen with proptosisand decreased vision. Histopathology demonstrated anadmixture of undifferentiated mesenchymal cells andislands of mature hyaline cartilage. Immunohistochemicalstudies revealed positivity for vimentin and S-100, whichwas consistent with the diagnosis of mesenchymalchondrosarcoma.· CONCLUSION: Mesenchymal chondrosarcoma in theorbit is extremely rare malignant tumor. Multi-modalitytreatments (surgery, chemotherapy and radiotherapy)may lead to long-term survival.

Objective: Our purpose was to explore the change regularity of β-glucuronidase (β-G) in body of patients with Non-Hodgkin malignant lymphoma. Methods: β-G was examined synchronously both in the serum and in the tumor tissue of 13 cases patient with Non-Hodgkin malignant lymphoma by using the method of enzymlinked immunsorbent assay (ELISA) and immunohistochemistry separately. Among them, 3 cases were studied by using the immuno electron microscopic technique. Results: β-G was highly expressed both in the serum and tumorous tissue in patients with non-Hodgkin malignant lymphoma and there was obviously difference as compared with the control group (P<0.01). Conclusion: The combined detection with functional and morphological methods to β-G, it may be assistant target to early discovery and early diagnosis of Non-Hodskin malignant lymphoma.