[Clustering of vestibular direction-selective neurons in macaque parieto-insular vestibular cortex].

Neurons with direction-selectivity for vestibular stimuli are found in a number of cortical areas, and neurons in the ventral intraparietal area (VIP) and the dorsal subdivision of the medial superior temporal area (MSTd) of the macaque brain are clustered according to their direction preferences for vestibular signals. This raises the question where the clustering inherits from? Previous work has shown that VIP and MSTd most probably receive vestibular input from the parieto-insular vestibular cortex (PIVC), which processes vestibular signals at the earlier stage. Thus, PIVC is also supposed to show a clustered organization similar to that seen in VIP and MSTd. The present study was aimed to examine clustering properties of vestibular response in PIVC area. To address this issue, we compared the tuning of isolated single unit (SU) with the undifferentiated multiunit (MU) activity of several neighboring neurons recorded from the same microelectrode. When directional tuning was observed in MU activity, the direction preference generally agreed closely with that of a simultaneously recorded SU. These results suggest that PIVC neurons are indeed clustered according to preferred direction for both translational and rotational vestibular stimuli.

MiR-34a and miR-206 act as novel prognostic and therapy biomarkers in cervical cancer.

BACKGROUND: Recent evidence indicated that the aberrant expression of microRNA plays a crucial role in the development of cervical cancer. The overall shorter survival was strongly related to the abnormal expression of microRNA-34a (miR-34a) and microRNA-206 (miR-206), which target B cell lymphoma-2(Bcl2) and c-Met. Hepatocyte growth factor (HGF)/c-Met pathway is related to the occurrence, development and prognosis of cervical cancer, and c-Met is significantly overexpressed in cervical squamous cell carcinoma. Bcl2 is also considered to be a promising target for developing novel anticancer treatments. METHODS: In this study, we detect the expression of miR-34a and miR-206 in the cervical cancer tissue through quantificational real-time polymerase chain reaction (qRT-PCR) assay, and the expression of Bcl2 and c-Met from cervical cancer tissue were detected by immunohistochemistry. RESULTS: The expression of miR-34a and miR-206 were down-regulated in the cervical cancer tissue through qRT-PCR assay. As target genes of miR-34a and miR-206, Bcl2 and c-Met were up-regulated in cervical cancer tissues through qRT-PCR assay and immunohistochemistry. Kaplan-Meier and log-rank analysis revealed that down-regulated expression of miR-34a and miR-206 were strongly related to shorter overall survival. Multivariate Cox proportional hazards model for all variables that were statistically significant in the univariate analysis demonstrated that miR-34a (P = 0.038) and miR-206 (P = 0.008) might be independent prognostic factors for overall survival of patients suffering from cervical cancer. CONCLUSIONS: The up-regulation of Bcl2 and c-Met promotes the cervical cancer's progress, and the expression of miR-34a and miR-206 significantly correlated with the progression and prognosis in cervical cancer. All of these suggested that miR-34a and miR-206 might be the novel prognostic and therapy tools in cervical cancer.

Hydrogen sulfide inhibits MPP+-induced aldehyde stress and endoplasmic reticulum stress in PC12 cells: involving upregulation of BDNF.

We have previously demonstrated the protective action of hydrogen sulfide (H2S) in 1-Methy-4-Phenylpyridinium Ion (MPP+)-induced neurotoxicity. However, the exact mechanisms of this protection remain largely unknown. Aldehyde stress and endoplasmic reticulum (ER) stress play significant roles in the neurotoxicity of MPP+. Brain derived neurotrophic factor (BDNF) is an important endogenous neuroprotectant. Therefore, we speculated that the protection of H2S against MPP+ neurotoxicity results from inhibiting MPP+-induced aldehyde stress and ER stress via upregulation of BDNF. In the present study, we found that NaHS, a donor of H2S, inhibited MPP+-induced aldehyde stress (the accumulations of the intracellular 4-HNE and MDA) and ER stress (the increases in the expressions of GRP78 and Cleaved-caspase-12) in PC12 cells and upregulated the BDNF expression in MPP+-exposed PC12 cells. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, not only markedly reversed the inhibitiory role of NaHS in MPP+-induced aldehyde stress and ER stress, but also ablated the protection of NaHS against MPP+-induced neurotoxicity. These data demonstrated that the protective role of H2S against MPP+-induced neurotoxicity by inhibiting aldehyde stress and ER stress, which is involved in upregulation of BDNF.

[Progress in multisensory integration during self motion processing].

In the daily life, we perceive the world around us by integrating multiple sensory cues (visual, auditory, olfactory, gustatory, tactile, vestibular and proprioceptive) to create a coherent, reliable representation that allows us to interact meaningfully with the environment. The integration of different sensory information is necessary for our perception, motor transformation, decision making, learning and memory. In the past decades, many interdisciplinary researchers have been attracted to the field of multisensory research, and tremendous advances have been made in this field. We review the researches on multisensory integration during self-motion perception in the past decades from the candidate areas, the integration principles and the neural correlation of the behaviors, with the intention to provide a comprehensive source for those interested in understanding the neural substrates for multisensory integration. Meanwhile, we also provide a prospect for the future research in this field.

Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress.

AIM: Sulforaphane (SFN), a natural dietary isothiocyanate, is found to exert beneficial effects for cardiovascular diseases. This study aimed to investigate the mechanisms underlying the protective effects of SFN in a model of myocardial hypoxia/reoxygenation (H/R) injury in vitro. METHODS: Cultured neonatal rat cardiomyocytes pretreated with SFN were subjected to 3-h hypoxia followed by 3-h reoxygenation. Cell viability and apoptosis were detected. Caspase-3 activity and mitochondrial membrane potential (ΔΨm) was measured. The expression of ER stress-related apoptotic proteins were analyzed with Western blot analyses. Silent information regulator 1 (SIRT1) activity was determined with SIRT1 deacetylase fluorometric assay kit. RESULTS: SFN (0.1-5 µmol/L) dose-dependently improved the viability of cardiomyocytes, diminished apoptotic cells and suppressed caspase-3 activity. Meanwhile, SFN significantly alleviated the damage of ΔΨm and decreased the expression of ER stress-related apoptosis proteins (GRP78, CHOP and caspase-12), elevating the expression of SIRT1 and Bcl-2/Bax ratio in the cardiomyocytes. Co-treatment of the cardiomyocytes with the SIRT1-specific inhibitor Ex-527 (1 µmol/L) blocked the SFN-induced cardioprotective effects. CONCLUSION: SFN prevents cardiomyocytes from H/R injury in vitro most likely via activating SIRT1 pathway and subsequently inhibiting the ER stress-dependent apoptosis.

Role of aldehyde dehydrogenase 2 in 1-methy-4-phenylpyridinium ion-induced aldehyde stress and cytotoxicity in PC12 cells.

Aldehyde stress contributes to molecular mechanisms of cell death and the pathogenesis of Parkinson's disease (PD). The neurotoxin 1-Methy-4-Phenylpyridinium Ion (MPP(+)) is commonly used to model PD. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme detoxifying aldehydes. The aim of this study is to evaluate whether MPP(+)-induced neurotoxicity is involved in aldehyde stress by modulation of ALDH2. Our results demonstrated that treatment of PC12 cells with MPP(+) leads to aldehyde stress by increasing in loads of malondialdehyde and 4-hydroxynonenal, which indicated that MPP(+)-induced aldehyde stress contributes to its cytotoxicity in PC12 cells. We also showed that MPP(+) up-regulates the expression and activity of ALDH2 in PC12 cells and that inhibition of ALDH2 by its specific inhibitor daidzin prevents MPP(+)-induced decrease in cell viability and increases in apoptosis, oxidative stress and aldehyde stress in PC12 cells. These findings suggest that aldehyde stress contributes to MPP(+)-induced toxicity in PC12 cells by upregulation of ALDH2. This study provides a novel insight into the role of ALDH2 in the neurotoxicity of MPP(+).

Suppression of rat Frizzled-2 attenuates hypoxia/reoxygenation-induced Ca2+ accumulation in rat H9c2 cells.

Growing evidence suggests that Ca(2+) overload is one of the major contributors of myocardial ischemia/reperfusion-induced injury. Since Frizzled-2 receptor, a seven transmembrane protein, transduces downstream signaling by specialized binding of Wnt5a to increase intracellular Ca(2+) release, this work aimed to investigate the effect of Frizzled-2 on Ca(2+) accumulation in H9c2 cells, which were subjected to hypoxia/reoxygenation to mimic myocardial ischemia/reperfusion. After exposing H9c2 cells to hypoxia/reoxygenation, we observed higher expression of Frizzled-2 and Wnt5a as compared to control group cells. Hypoxia/reoxygenation-induced intracellular Ca(2+) accumulation approached that of cells transfected with frizzled-2 plasmid. In cells treated with RNAi specifically designed against frizzled-2, intracellular Ca(2+) in both hypoxia/reoxygenation-treated cells and plasmid-treated cells were decreased. Rats that underwent ischemia/reperfusion injury exhibited increased intracellular Ca(2+) with high expression levels of Frizzled-2 and Wnt5a as compared to the sham group. Our data indicates that upon binding to Wnt5a, increased Frizzled-2 expression after hypoxia/reoxygenation treatment activated intracellular calcium release in H9c2 cells. Our findings provide a new perspective in understanding calcium overload in myocardial ischemia/reperfusion.

Dexpramipexole attenuates myocardial ischemia/reperfusion injury through upregulation of mitophagy.

Reperfusion causes undesirable damage to the ischemic myocardium while restoring the blood flow. In this study, we evaluated the effects of dexpramipexole (DPX) on myocardial injury induced by ischemia/reperfusion (I/R) in-vivo and the hypoxia/reoxygenation (HR) in-vitro and examined the functional mechanisms of DPX. DPX protected cells against H/R-induced mitochondrial dysfunction and prevented H/R damage. Both myocardial infarct size and tissue damage due to I/R was reduced upon DPX treatment. We discovered that DPX enhanced mitophagy in-vivo and in-vitro, which was accompanied by enhanced expression of PINK1 and Parkin. Knock-down of PINK1 and Parkin by specific siRNAs reversed DPX-induced inhibition of myocardial I/R injury. These findings suggest that DPX might protect against myocardial injury via PINK1 and Parkin.

Ultrasound-Mediated Co-Delivery of miR-34a and sPD-1 Complexed with Microbubbles for Synergistic Cancer Therapy.

BACKGROUND: miR-34a was downregulated and PD-L1 was upregulated in cervical cancer; however, the treatment of cervical cancer lacks precision and targeting. This study explored the ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles for synergistic cancer therapy. METHODS: Cationic lipid microbubbles (CLMBs) were prepared by membrane hydration and mechanical oscillation. U14 subcutaneous xenograft mice were injected with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and tumor volume and tumor weight of mice were measured. TUNEL apoptosis test and the mRNA expression of apoptosis-related gene Bcl-2 and Bax were analyzed by qRT-PCR. Antitumor immune-related cytokines IFN-γ were investigated by qRT-PCR, LDH Cytotoxicity Assay Kit were performed to test cytotoxic T lymphocytes (CTL). RESULTS: CLMBs were successfully prepared and the plasmid bound to its surface. The tumor volume and weight were specifically decreased by ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles, apoptosis was induced and the apoptosis suppressor gene Bcl-2 was downregulated and proapoptotic gene Bax were upregulated. qRT-PCR analysis revealed that antitumor immunity-related IFN-γ was strongly upregulated in mice, which were treated with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and the percentage of CTL was increased. CONCLUSION: These findings from the study demonstrated that CLMBs could deliver miR-34a and sPD-1, combined with ultrasound targeted destruction, could suppress the tumor tissue growing, induce apoptosis and enhance antitumor immunity in U14 subcutaneous xenograft mice.

Orientobilharzia turkestanicum is a member of Schistosoma genus based on phylogenetic analysis using ribosomal DNA sequences.

In the present study, samples representing Orientobilharzia turkestanicum from cattle, sheep, cashmere goat and goat in Heilongjiang Province, China, were characterized and grouped genetically by sequences of internal transcribed spacer (ITS, including ITS-1 and ITS2) and 28S ribosomal DNA (28S rDNA). The ITS and 28S rDNA were amplified by polymerase chain reaction (PCR) and then sequenced and compared with that of other members of the Schistosomatidae available in GenBank, and phylogenetic relationships between them were re-constructed using the neighbor-joining and maximum parsimony methods. The lengths of ITS-1, ITS-2 and 28S rDNA sequences for all O. turkestanicum samples from different hosts were 384bp, 331bp and 1304bp, respectively. While the ITS-1 sequences of O. turkestanicum from each of the four different hosts, and ITS-2 of O. turkestanicum from cattle, sheep and cashmere goat were identical, respectively, the ITS-2 of O. turkestanicum from goat differed from that of O. turkestanicum from cattle, sheep and cashmere goat by one nucleotide. The 28S rDNA sequences of O. turkestanicum from sheep and cashmere goat were identical, but differed from that of O. turkestanicum from cattle and goat by two nucleotides, with the latter two also having identical 28S rDNA sequence. Phylogenetic analyses based on the combined sequences of the ITS-1 and ITS-2, or the 28S rDNA sequences placed O. turkestanicum within the genus Schistosoma, and it was phylogenetically closer to the African schistosome group than to the Asian schistosome group. These results should have implications for studying the origin and evolution of O. turkestanicum and other members of the Schistosomatidae.

[Preliminary application of PCR-based assay for the detection of Neospora caninum in bovine aborted fetus].

OBJECTIVE: To establish a PCR diagnostic method based on Nc-5 gene of Neospora caninum, for being used to detect Neospora in brain tissues of bovine aborted fetus. METHODS: Specific primers were designed and synthesized based on the reported Nc-5 gene of N. caninum (GenBank Accession No. AY459289). Using genomic DNA from N.caninum as templates, Nc-5 gene was amplified by PCR. The PCR product was cloned into pMD18-T vector, transformed into Escherichia coli JM109 and then sequenced. To evaluate the specificity of the PCR, genomic DNA of Theileria annulata, Babesia bovis, Toxoplasma gondii, Leishmania donovani and standard strain of N. caninum were used as a template in the PCR. For determining the detection limit of amplification procedure, PCR was run on a dilution series of genomic DNA from N. caninum (1.562 5-200 ng/ml). Brain tissue samples of 32 aborted fetuses were detected by PCR-based assay, and 23 blood samples from mothers were tested by ELISA. RESULTS: The amplified DNA fragment (350 bp) had a high identity of 98% with the Nc-5 gene sequence of N. caninum (GenBank Accession No. AY459289). The PCR was specific for N. caninum and allowed the detection of 3.125 pg DNA of the parasite, while no amplification occurred with the other four species of protozoa. PCR-based assay and ELISA showed a positive rate of 18.8% (6/32) and 17.4% (4/23) of the samples tested, respectively. Moreover, all the 4 antibody positive samples showed PCR positive. There is no significant difference between the two assays (P > 0.05). CONCLUSION: PCR diagnostic method is promising in detecting Neospora infection in brain tissues of aborted bovine.

Spermidine-enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway.

BACKGROUND AND PURPOSE: Spermidine, a natural polyamine, is abundant in mammalian cells and is involved in cell growth, proliferation, and regeneration. Recently, oral spermidine supplements were cardioprotective in age-related cardiac dysfunction, through enhancing autophagic flux. However, the effect of spermidine on myocardial injury and cardiac dysfunction following myocardial infarction (MI) remains unknown. EXPERIMENTAL APPROACH: We determined the effects of spermidine in a model of MI, Sprague-Dawley rats with permanent ligation of the left anterior descending artery, and in cultured neonatal rat cardiomyocytes (NRCs) exposed to angiotensin II (Ang II). Cardiac function in vivo was assessed with echocardiography. In vivo and in vitro studies used histological and immunohistochemical techniques, along with western blots. KEY RESULTS: Spermidine improved cardiomyocyte viability and decreased cell necrosis in NRCs treated with angiotensin II. In rats post-MI, spermidine reduced infarct size, improved cardiac function, and attenuated myocardial hypertrophy. Spermidine also suppressed the oxidative damage and inflammatory cytokines induced by MI. Moreover, spermidine enhanced autophagic flux and decreased apoptosis both in vitro and in vivo. The protective effects of spermidine on cardiomyocyte apoptosis and cardiac dysfunction were abolished by the autophagy inhibitor chloroquine, indicating that spermidine exerted cardioprotective effects at least partly through promoting autophagic flux, by activating the AMPK/mTOR signalling pathway. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that spermidine improved MI-induced cardiac dysfunction by promoting AMPK/mTOR-mediated autophagic flux.

Interleukin-1ß inhibits collagen synthesis and promotes its decomposition in cultured cardiac fibroblasts.

The present study aimed to investigate the effects of interleukin-1ß (IL-1ß) at different doses on collagen synthesis and decomposition in cultured cardiac fibroblasts from neonatal Sprague-Dawley rat. Cardiac fibroblasts were treated with IL-1ß (0.01, 0.1, 1, 10, 100 ng/mL) for 24 h. Cell DNA synthesis was measured by (3)H-thymidine ((3)H-TdR) incorporation and collagen synthesis was measured by (3)H-proline ((3)H-Pro) incorporation. Matrix metalloproteinase (MMP) activity was measured by gelatinase zymography. MMP-2, MMP-9 protein expressions were measured by Western blot. mRNA expressions of MMP-2 and MMP-9 were detected by reverse transcription-polymerase chain reaction (RT-PCR). Compared with that in the control group, the incorporation of (3)H-TdR and (3)H-Pro decreased in high-dose IL-1ß groups (≥0.1 ng/mL) but not in low-dose IL-1ß group (0.01 ng/mL). IL-1ß significantly increased MMP-2 and MMP-9 activities. IL-1ß (0.01-100 ng/mL) also dose-dependently increased the protein and mRNA expressions of MMP-2 and MMP-9 (P<0.05, P<0.01), respectively. These results suggest that IL-1ß decreases collagen synthesis and MMP activities through transcriptional and posttranslational processes via degrading collagen in a dose-dependent way. Elevation of IL-1ß is possibly involved in the process of ventricular remodeling after myocardial infarction, and the concentration of IL-1ß is possibly a major factor which affects the extent of ventricular remodeling.

[ITS and 28S rDNA-LSU sequence analysis of Orientobilharzia turkestanicum from bovine and caprine hosts].

OBJECTIVE: To explore sequence differentiation of ITS and 28S rDNA-LSU of Orientobilharzia turkestanicum from bovine and caprine hosts. METHODS: Adult worms of O. turkestanicum from the naturally infected cattle, sheep, cashmere goat and goat were collected and identified morphologically as O. turkestanicum according to existing keys and descriptions. The genomic DNA was extracted from parasites of different hosts. The internal transcribed spacer (ITS, contains ITS-1, 5.8S nuclear ribosomal DNA, ITS-2) and 28S nuclear ribosomal DNA-LSU were amplified by PCR, sequenced and analyzed by Chromans and DNASTAR softwares, and the RNA secondary structure of 28S rDNA-LSU was analyzed by DNAMAN software. RESULTS: ITS-1, 5.8S rDNA, ITS-2 and 28S rDNA-LSU of O. turkestanicum from bovine and caprine hosts were 384, 159, 331 and 1 304 bp, respectively. ITS-1 and 5.8S rDNA of O. turkestanicum from different definitive hosts were identical; ITS-2 of O. turkestanicum from cattle, sheep and cashmere goat were identical, with one nucleotide variation compared with that of goat; 28S rDNA-LSU of O. turkestanicum from sheep and cashmere goat were identical, with two nucleotides variation compared with that of cattle and goat. The RNA secondary structure of 28S rDNA LSU of O. turkestanicum from caprine hosts were identical or similar, but with large variation compared with that of cattle. CONCLUSION: The rDNA sequence from different definitive hosts shows nucleotide variations to some extent and the RNA secondary structure of 28S rDNA-LSU from caprine hosts shows large variation in comparison to that of bovine.

Diffusion Tensor Imaging Detects Microstructural Differences of Visual Pathway in Patients With Primary Open-Angle Glaucoma and Ocular Hypertension.

Ocular hypertension (OHT), the common situation in adult patients in the outpatients, occurs ∼5% worldwide. However, there are still some practical problems in differentiation of OHT with early primary open-angle glaucoma (POAG) using current standard methods. Application of high resolution diffusion tensor imaging (DTI) enables us to the differentiate axonal architecture of visual pathway between POAG and OHT subjects. Among 32 POAG patients recruited (15 OHT and 14 control subjects), 62.5% of glaucoma were in early stage for the current study. All subjects underwent ophthalmological assessments with standard automated perimetry and optical coherence tomography (OCT). DTI was applied to measure fraction anisotropy (FA) and mean diffusivity (MD) of optic tract (OT), lateral geniculate body (LGN) and optic radiation (OR) using voxel-based analysis. Our data demonstrated that FA values of bilateral OR in POAG were significantly lower in the right or left than that of OHT patients (left OR: 0.51 ± 0.04 vs. 0.54 ± 0.03, p < 0.05; right OR: 0.51 ± 0.05 vs. 0.54 ± 0.03, p < 0.05). In right LGN, MD values were higher in POAG patients compared with OHT subjects (9.81 ± 1.45 vs. 8.23 ± 0.62, p < 0.05). However, no significant difference of all of the DTI parameters was observed between OHT and control subjects. DTI parameters in POAG patients were positively correlated with morphological and functional measurements (p < 0.05). Vertical cup to disc ratio (VCDR) was correlated with ipsilateral FA of OT (p < 0.05), ipsilateral MD of OT (p < 0.05), ipsilateral MD of LGN (p < 0.05), and contralateral MD of OT (p < 0.05). Mean deviation of visual field (MDVF) was correlated with ipsilateral FA of OT (p < 0.05), ipsilateral MD of OT (p < 0.05), and ipsilateral FA of LGN (p < 0.05). Our study demonstrated that DTI can differentiate POAG from OHT subjects in optic pathway, particularly in early POAG, and DTI parameters can quantify the progression of POAG.

Patient-Reported Treatment Satisfaction with Dabigatran versus Warfarin in Patients with Non-Valvular Atrial Fibrillation in China.

BACKGROUND: Anti-coagulant therapy satisfaction for patients with atrial fibrillation is a critical issue, which impacts on their treatment adherence and clinical outcomes. The disadvantages of long-term warfarin treatment are well-described, and novel oral anti-coagulants have become an alternative option. MATERIALS AND METHODS: We compared patient-reported treatment satisfaction with dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients in China. Treatment satisfaction was assessed using the Anti-Clot Treatment Scale (ACTS) questionnaire, which included a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. RESULTS: Among 834 patients, 246 patients (29.5%) were taking dabigatran and the others were on warfarin. Propensity score matching was employed to identify 182 patient pairs with balanced baseline characteristics. The global ACTS Burdens score and the global ACTS Benefits score were comparable between the dabigatran and warfarin groups (44.86 ± 3.95 vs. 44.28 ± 3.51, p = 0.423; 11.49 ± 2.92 vs. 11.42 ± 3.03, p = 0.194, respectively). The monthly cost of dabigatran was significantly higher compared with that of warfarin due to a lack of insurance coverage (USD 176.78 ± 9.15 vs. USD 2.49 ± 0.76, p = 0.000). The discontinuation rate of dabigatran was significantly higher than warfarin at the 6-month follow-up (33.5% vs. 19.2%, p = 0.003). Adjusted logistic regression showed that dabigatran was associated with a significant greater odds of non-persistence (odds ratio: 2.13, 95% confidence interval: 1.27-3.59, p = 0.004). CONCLUSION: Dabigatran therapy in patients with NVAF in China associated with no improvement in satisfaction and a higher discontinuation rate compared with warfarin therapy largely due to increased economic burden.

Female Sex as a Risk Factor for Ischemic Stroke and Systemic Embolism in Chinese Patients With Atrial Fibrillation: A Report From the China-AF Study.

Background Previous studies have provided conflicting results as to whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ). We investigated whether women with AF were at higher risk of ischemic stroke in the China-AF (China Atrial Fibrillation Registry) Study. Methods and Results A total of 19 515 patients were prospectively enrolled between August 2011 and December 2016 in the China- AF Study. After exclusion of patients receiving anticoagulation or ablation therapy, 6239 patients (2574 women) with results from at least 6 months of follow-up were used for the analysis. Cox proportional hazards models were performed to evaluate whether female sex was an independent risk factor for thromboembolism after multivariate adjustment. The primary outcome was the time to the first occurrence of ischemic stroke or systemic embolism. After a mean follow-up of 2.81±1.46 years, 152 female patients reached the primary outcome, as compared with 172 male patients. Crude incidence rates of thromboembolism between women and men were of borderline statistical significance (2.08 versus 1.68 per 100 patient-years, P=0.058). After multivariable analysis, female sex was not independently associated with an increased thromboembolism risk (hazard ratio 1.09, 95% confidence interval 0.86-1.39). There was no significant difference in thromboembolism risk by sex stratified by age and presence or absence of risk factors ( P for interaction all >0.1). Conclusions Although crude incidence rates of thromboembolism were higher in Chinese female patients with AF compared with male patients, female sex did not emerge as an independent risk factor for thromboembolism on multivariate analysis. Clinical Trial Registration URL : http://www.chictr.org.cn/ . Unique identifier: Chi CTR - OCH -13003729.

[Screening for cellular signal transduction pathway involved in C-reactive protein induced endothelial cell inflammation].

OBJECTIVE: To investigate the cellular signal transduction pathway involved in participation of C-reactive protein (CRP) in inflammation process in endothelial cell. METHODS: Human umbilical vascular endothelial cells were cultured and characterized by anti-Factor VIII-related antigen. The cells were divided into CRP group and control group, and they were respectively treated with CRP (20 mg/L) or serum-free medium for 24 hours. RNAs of two groups were extracted and analyzed by human signal transduction pathway gene array. RESULTS: Expressions of 13 genes were increased, whereas expressions of 25 genes were decreased in CRP group compared with control group. Especially, WNT1 inducible signaling pathway protein 2 (WISP2) was increased by 37.63 folds, which was believed to involve in inflammation process as a growth factor, p53 was increased by 30.50 folds, which was a key factor to modulate apoptosis, whereas, Bcl-x and Bcl-2 were decreased by 9.61% and 49.95% which were characterized as an important factor to prevent apoptosis. Vascular cell adhesion molecule-1 (VCAM-1) was increased by 2.75 folds after treated with CRP, while intercellular adhesion molecular (ICAM) between two groups didn't show statistically significant difference. CONCLUSION: CRP may be involved in inflammatory process of endothelial cell, and the mechanism may be to induce apoptosis and activate cellular signal transduction pathway of cell adhesion proteins.

[Isolation and identification of pronuciferine monomer].

OBJECTIVE: To isolate and identify pronuciferine monomer. METHODS: The primary compositions in the seed of Nelumbo nucifera were extracted by supercritical CO2 way, then isolated and purified by column chroatography fractionation and identified by HPLC, TLC, GC-MS. RESULTS: A monomer was further isolated and purifed by column chromatography fractionation from the primary compositions in the seed of Nelumbo nucifera which were extracted by supercritical CO2 way. The compositions of the monomer was pronuciferine which wrer identified by HPLC, TLC, GC-MS. CONCLUSION: The pronucierine monomer could be isolated from the seed of Nelumbo nucifera by combining supercitical CO2 way with column chromatography fractionation, which will be available for further functional study.

Hemoglobin A1c and risk of left atrial thrombus and spontaneous echo contrast in non-valvular atrial fibrillation patients.

OBJECTIVES: To evaluate the relationship between hemoglobin A1c (HbA1c) and risk of left atrial thrombus/spontaneous echo contrast (LAT/SEC) in non-valvular atrial fibrillation (AF) patients. METHODS: In this retrospective study, 1158 consecutive non-valvular AF patients undergoing transesophageal echocardiography prior to radiofrequency catheter ablation or electric cardioversion were enrolled. Baseline characteristics were collected and analyzed. RESULTS: There were 87 (7.5%) patients with LAT/SEC. The HbA1c levels in the patients with LAT/SEC were significantly higher than that in patients without LAT/SEC (6.13 ± 0.41 vs. 5.89 ± 0.45 µmol/L, P < 0.001). The optimal cut-off point for HbA1c predicting LAT/SEC was 6.1% determined by receiver-operating characteristic curve. The area under the curve is 0.788 (95% confidence interval: 0.764-0.812). HbA1c ≥6.1% was an independent risk factor for LAT/SEC (odds ratio, 1.74; 95% confidence interval, 1.01-2.98; P = 0.045). CONCLUSIONS: Elevated HbA1c indicated a significantly increased risk for LAT/SEC in non-valvular AF patients. HbA1c might have significance in predicting the risk for prothrombotic state in non-valvular AF patients.