[Genetic characteristic of hemagglutinin of avian influenza A (H7N9) virus in Guizhou Province in 2017].

The number of H7N9 bird flu cases was high and the situation was grim in guizhou province in 2017. To understand the molecular characteristics of the hemagglutinin gene (HA) and the risk of human infection with avian influenza virus A(H7N9) in Guizhou Province, 2017. Homology, genetic evolution and pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of 14 avian influenza viruses A(H7N9) were analyzed by a series of bioinformation softwares. It was cleared that there was 95.9%-100% similarity among 14 strains in nucleotide of the HA gene, and there were 96.8%-97.8% and 96.8%-97.9% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Phylogenetic analysis showed that 14 HA genes were directly evolved in the Yangtze River Delta evolution branch, but they could be derived from five diffenrent strains. Then 13 of 14 strains cleavage site sequences of HA protein revealed they were low pathogenic avian influenza viruses, while A/Guizhou-Weining/CSY01/2017 was high pathogenic avian influenza virus. Mutation G186V at the receptor binding sites in the HA was found in all 14 strains, and mutation Q226L in 13 strains besides A/Guizhou-Weining/CSY01/2017. All five potential glycosylation motifs in the HA were conservative.

Implication of interleukin 18 in production of matrix metalloproteinases in articular chondrocytes in arthritis: direct effect on chondrocytes may not be pivotal.

OBJECTIVE: To clarify the effect of interleukin (IL) 18 on cartilage degeneration by studying the profile of IL18 receptor (IL18R) on chondrocytes and the direct effect of IL18 on production of matrix metalloproteinases (MMPs), aggrecanases, and tissue inhibitors of metalloproteinases (TIMPs) in articular chondrocytes. METHODS: Monolayer cultured human articular chondrocytes were isolated from non-arthritic subjects and patients with rheumatoid arthritis or osteoarthritis. Gene expression of IL18, IL18Ralpha, IL18Rbeta, MMPs, and aggrecanases was detected by RT-PCR. Protein levels of IL18Ralpha were analysed by flow cytometry. Protein levels of IL18, MMPs, and TIMPs were measured by ELISA. Aggrecanase-2 mRNA expression was quantitatively analysed by real time RT-PCR. Protein levels of signalling molecules were assayed by western blotting. RESULTS: IL18 mRNA was constitutively expressed in chondrocytes, and was enhanced by IL1beta stimulation. Flow cytometric analysis showed that IL1beta, tumour necrosis factor alpha, and IL18 up regulated IL18Ralpha expression levels. The level of IL18Rbeta mRNA was much lower than that of IL18Ralpha, and was slightly up regulated by IL1beta. In chondrocytes responding to IL18, IL18 (1-100 ng/ml) slightly increased the production of MMP-1, MMP-3, and MMP-13, which was blocked by NF-kappaB inhibitor and p38 mitogen activated protein kinase inhibitor. IL18 up regulated mRNA expression of aggrecanase-2, but not aggrecanase-1. IL18 also slightly stimulated TIMP-1 production?through extracellular signal regulated kinase activation. CONCLUSION: IL18 induces production of MMPs from chondrocytes in inflammatory arthritis. Although the direct effect of IL18 on chondrocytes may not be pivotal for the induction of cartilage degeneration, IL18 seems to play some part in the degradation of articular cartilage in arthritis.

Arterial baroreflex deficit induced organ damage in sinoaortic denervated rats.

To verify the independent role of the arterial baroreceptor dysfunction involved in target-organ damage in hypertension, sinoaortic denervated (SAD) rats were used as a model of arterial baroreflex (ABR) deficit. SAD, isolated aortic-denervated (AD), and isolated sinus-denervated (SD) rats were instrumented to record blood pressure (BP), heart rate (HR), BP variability (BPV), HR variability (HRV), ABR function control of heart period (ABR-HP), and BP (ABR-BP). Vascular maximum contractile/relaxant function was determined and organ damage was estimated by observation of morphologic changes. Short-term (postoperative 1 week) SAD caused hypertension and tachycardia in rats. Eighteen weeks after operation, BP and HR values in SAD and SD rats were not different from those in sham-operated rats, but AD rats were hypertensive compared with control group. Although 24-h mean BP values of long-term SAD rats were not different from those of sham-operated rats, 24-h BPV of SAD rats was significantly higher than that of sham-operated rats. Arterial baroreflex function in short-term SAD rats was significantly less than in sham-operated rats, whereas in long-term SAD rats, ABR-HP and ABR-BP were higher than those in short-term SAD rats, but were still significantly lower than those in control groups. At postoperative 18 weeks, baroreflex function in SAD and AD rats was significantly less than function in SD and control groups. SBPmax after phenylephrine and DBPmin after nitroprusside were significantly higher in SAD, AD, and SD rats than in control rats. Baroreflex function was negatively correlated to DBPmin and SBPmax in all denervated rats (n = 44). Some morphologic changes were found 18 weeks after denervation in heart, kidney, and small artery in SAD, AD, and SD rats. Baroreflex function in all denervated rats was negatively related to 24-h BPV values. In contrast, 24-h BPV values in SAD, AD, and SD rats were positively related to organ-damage score. A negative correlation between ABR function and end-organ damage score was found. Arterial baroreflex deficit played an independent and important role in organ-damage in SAD rats with significantly elevated 24-h BPV.

Relationship between baroreceptor reflex function and end-organ damage in spontaneously hypertensive rats.

The purpose of this study was to further illustrate the relationship between baroreceptor reflex sensitivity (BRS) and hypertensive end-organ damage (EOD) and to test the hypothesis that impairment of BRS aggravates EOD in hypertension. We studied baroreflex-mediated changes in heart rate [expressed as baroreceptor sensitivity to heart rate control (BRS(HR))] and blood pressure [expressed as baroreceptor sensitivity to blood pressure control (BRS(BP))] in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) that were used as controls, both at the age of 50-52 wk. Rats were also instrumented to record BP, HR, and BP variability (BPV) in the conscious, unrestrained state. In SHR compared with WKY, BP and BPV were significantly increased, whereas BRS(HR) and BRS(BP) were significantly decreased. SHR had remarkable EOD when compared with WKY (EOD score: 6.3 +/- 2.5 vs. 2.9 +/- 0.8, P < 0.01). Univariate regressive analysis demonstrated that EOD score was increased with BP and BPV and decreased with BRS. In multivariate analysis, EOD score was predicted by greater systolic BP and lower BRS and HR variability. These results indicate that BRS is negatively related to BPV and EOD score, and impaired BRS might be one of the major causes for hypertensive EOD.

Hemodynamic responses to endothelin-1 and endothelin antagonists microinjected into the nucleus tractus solitarius in rats.

The role of endothelin-1 (ET-1) within the nucleus tractus solitarius (NTS) in central cardiovascular control was investigated by local microinjections of ET-1 and ET-receptor antagonists. In urethane-anesthetized Sprague-Dawley rats, a unilateral microinjection of ET-1 (1.0, 3.3, and 10.0 pmol) into the NTS significantly increased arterial pressure, left ventricular systolic pressure, and dP/dt(max) in a dose-dependent manner, and slightly decreased heart rate in a dose-independent manner. The pressor effect lasted >90 min. In normotensive rats, neither PD147953, a selective ETA-receptor antagonist, nor PD142893, a mixed ETA- and ETB-receptor antagonist, microinjected into the NTS elicited any changes in arterial pressure or heart rate. The pressor and bradycardic effects evoked by microinjection of ET-1 into the NTS could be blocked by local pretreatment with PD147953 and completely eliminated by intravenous pretreatment with the ganglionic blocker hexamethonium. The arterial baroreflex sensitivity was almost totally suppressed by microinjection of ET-1 (3.3 pmol) in alpha-chloralose-anesthetized Sprague-Dawley rats. A similar pattern of changes in the hemodynamic variables was elicited by microinjection of ET-1 (3.3 pmol) into the NTS in spontaneously hypertensive rats (SHRs) compared with Wistar-Kyoto (WKY) rats. In SHRs, microinjection of PD142893 did not elicit any changes in arterial pressure or heart rate. These results suggest that ET-1 modulates reflex control of hemodynamics by activation of autonomic nerve via ETA receptors in the NTS, and that the responsiveness of SHRs to ET-1 or PD142893 is similar to that of WKY rats.

The utero-placental circulation, eugenics and the prevention and treatment of high risk pregnancies.

Through systematic experimental and clinical studies, the physiological regulation of utero-placental circulation and the relation of the disturbance in this acirculation to pathogenic mechanisms of high risk pregnancies-Intrauterine Growth Retardation (IUGR) and Pregnancy-induced hypertension (PIH) were explored. The pharmacological effects and mechanism of a Chinese herbal medicine-Qingxintong in improving, the utero-placental circulation and the therapeutic efficacy in treatment of IUGR and PIH, both accompanied by disturbance of utero-placental circulation, were investigated as well.