Antihypertensive Agents ; therapeutic use ; Blood Pressure ; Humans ; Hypertension ; therapy

Despite of great strides already made, China is still lagging behind Western countries in terms of scientific innovation, which is not parallel with China's economic achievement. Here I would like to summarize my experience in 30-year science research from the following two aspects: one is the motivation and source of innovation and the other is the value and implication of innovation. I will mainly focus on the relation of innovation with accidental discovery, reversed thought, long term accumulation, and challenge of the authorities. I will also discuss the great role of innovation in developing new theories, guiding medical practice,and dealing with emergencies.

Animals ; Cardiovascular Diseases ; Cardiovascular System ; Humans ; MicroRNAs

It is well known that the arterial baroreflex(ABR)plays a key role in the regulation of heart rate and stabilization of blood pressure.Currently,it appears that ABR dysfunction is involved in the pathophysiology of cardiovascular disease states.Since the mid-1990s,a number of studies have been carried out in our laboratory to explore the pathological significance of ABR function in cardiovascular damage.This minireview summarizes our research work on the topic of ABR and left ventricular hypertrophy(LVH).On the basis of discussion concerning the importance of ABR dysfunction in hypertensive LVH and sinoaortic denervation-induced LVH,we advance a new strategy for reversal of LVH,that is,restoration of impaired ABR function.We tested this hypothesis in animal models with ABR deficiency.It was found that improvement of impaird ABR function with long-term treatment of ketanserin or candesartan was accompanied by reversal of LVH.The preliminary results indicate that it is feasible to target ABR for treatment of LVH.

It is well known that the arterial baroreflex(ABR)plays a key role in the regulation of heart rate and stabilization of blood pressure.Currently,it appears that ABR dysfunction is involved in the pathophysiology of cardiovascular disease states.Since the mid-1990s,a number of studies have been carried out in our laboratory to explore the pathological significance of ABR function in cardiovascular damage.This minireview summarizes our research work on the topic of ABR and left ventricular hypertrophy(LVH).On the basis of discussion concerning the importance of ABR dysfunction in hypertensive LVH and sinoaortic denervation-induced LVH,we advance a new strategy for reversal of LVH,that is,restoration of impaired ABR function.We tested this hypothesis in animal models with ABR deficiency.It was found that improvement of impaird ABR function with long-term treatment of ketanserin or candesartan was accompanied by reversal of LVH.The preliminary results indicate that it is feasible to target ABR for treatment of LVH.

Objective To evaluate the efficacy and safety of a new drug,human urinary kallidinogenase,against acute brain infarction.Method A 15-center,randomized,double-blinded and 3:1 placebo-controlled study was carried out.Acute brain infarction within 48 hours of onset in the territory of the middle cerebral artery were indicated as subjects;kallidinogenase or placebo which was dissolved in 50 ml saline,was slowly injected intraveousely within 30 minutes daily for 3 weeks.The European Stroke Scale and Barthel Index were used to evaluate the neurological deficit and the activities of daily living(ADL),followed by a follow-up at the end of the third month.Results 446 patients were enrolled,who completed ITT analysis,including 330 in kallidinogenase group and 116 in placebo group,meanwhile 421 proceeded with PP analysis(311 and 110 respectively).There were no significant differences of the baseline data between the 2 groups.At the end of treatment,the ESS scores increased by 55.1%?33.0% and 44.7%?32.8% respectively in kallidinogenase group(KG)and placebo group(PG,P=0.0022),the difference being significant.PP analysis had similar results.As for ADL,follow-up 90 days after the treatment showed 374 cases followed,280 in KG and 94 in PG;1 died in PG,while none in KG.In KG,the cases whose BI≥50 were significantly more than those in PG(P=0.0228).Adverse events possibly or definitely attributable to the drug were observed in 27 cases(7.74%),mostly were mild,such as palpitation,flush,dizziness, nausea etc,without special management needed.Only 2 died which was confirmed not correlated to kallidinogenase,and another 2 cases of sudden blood pressure drop were observed.The blood pressure drop, quickly restoring soon after the withdrawal of kallidinogenase and use of hemopiesic drugs,was considered to be caused by the combination use of anti-hypertensive drug ACEI and quick infusion speed.Conclusion Kallidinogenase is efficacious for acute brain infarction in improving the neurological deficits,which is safe in clinical use.

OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis, the underlying mechanisms remain not well- understood. Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC. METHODS MiR-124 expression in colon tissues and cells was determined by q-PCR and in situ hybridization. The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells. Expression of p-STAT3/STAT3 was detected by immuno?histochemistry and Western blot analysis. RESULTS miR- 124 expression is upregulated in colon tissues from patients and DSS- induced colitis. Nicotine treatment further elevated miR- 124 level in colon tissues of the mice, in infiltrated lymphocytes and epithelial cells, and augmented miR- 124 expression in lymphocytes isolated from human ulcerative colon tissues. Administration of nicotine also reduced weight loss, improved DAI and decreased HE score in DSS-induced colitis. Moreover, knock?down of miR-124 in vivo significantly diminished the beneficial effect of nicotine, and in vitro on IL-6-treated Caco-2 colon epithelial cells. Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes, in which miR-124 knockdown led to increased activation of STAT3. CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3, suggesting that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.

In recent years, miR-124 has emerged as a critical modulator of immunity and inflammation. Here, we summarize studies on the function and mechanism of miR-124 in the immune system and immunity-related diseases. They indicated that miR-124 exerts a crucial role in the development of immune system, regulation of immune responses, and inflammatory disorders. It is evident that miR-124 may serve as an informative diagnostic biomarker and therapeutic target in the future.

Objective To investigate the effect of acupuncture plus Chinese herbal medication on plasma endothelin (ET-1) and calcitonin gene-related peptide (CGRP) in child patients with mesenteric lymphadenitis.Methods One hundred and eighty child patients with mesenteric lymphadenitis were randomly allocated to groups A, B and C, 60 cases each. Group A received acupuncture at Zusanli and pricking Sifeng points plus oral administration of Wudang Babao Zijinding; group B, oral administration of amoxicillin and clavulanate potassium granules; group C, oral administration of Wudang Babao Zijinding alone. ET-1 and CGRP contents were measured in the three groups before and after treatment.Results There were statistically significant pre-/post-treatment differences in ET-1 and CGRP contents in group A (P<0.01). There were statistically significant post-treatment differences in ET-1 and CGRP contents between group A and group B or C (P<0.01).Conclusions Acupuncture plus Chinese herbal medication is an effective way to treat mesenteric lymphadenitis in children. It can regulate ET-1 and CGRP in the patients.

[ ABSTRACT] AIM:To explore the effects of eplerenone on the expression and activity of aortic endothelial nitric oxide synthase ( eNOS) in high salt-induced hypertensive rats .METHODS: Male Wistar rats (4 week old, weighting 50~60 g) were randomly divided into control group , high-salt diet group and eplerenone group .The rats in control group were fed with ordinary rodent animal diet , the rats in high-salt group and eplerenone group were exposed to 5%salt diet for 16 weeks and administrated with the same dosage of saline or eplerenone (40 mg? kg-1? d-1 ) by gavage for 4 weeks, re-spectively.Systolic blood pressure (SBP) was measured by tail-cuff every 2 weeks.The rats were sacrificed after 16 weeks and the thoracic aorta was collected .The aldosterone content in the aorta was measured by ELISA .The protein levels of mineralocorticoid receptor (MR) and eNOS were determined by Western blot.The activitie of constitutive NOS (cNOS) was measured by chemocolorimetry .The protein localization of eNOS , neuronal nitric oxide synthase ( nNOS) and MR was observed by immunohistochemistry .RESULTS: A process of 8-week high-salt diet increased SBP gradually .SBP in the rats exposure to high salt for 16 weeks was significantly higher than that in control group ( P<0.05 ) .After 4 weeks of eplerenone treatment, SBP in the rats was significantly lower than that before treatment (P<0.05).Compared with control group, the aldosterone content in the aorta were significantly increased in high-salt diet group and eplerenone group ( P<0.05), the expression level of MR also increased significantly (P<0.05).Compared with control group, both eNOS pro-tein expression (P<0.05) and cNOS activity in high-salt diet group were significantly decreased (P<0.05).The protein expression of eNOS as well as cNOS activity in aorta increased significantly in eplerenone group compared with high -salt diet group (P<0.05).CONCLUSION:Aldosterone content in aorta of high-salt-induced hypertensive rats increases signifi-cantly .Aldosterone attenuates the protein expression of eNOS and reduces the enzyme activity through the activation of min -eralocorticoid receptor .The selective mineralocorticoid receptor antagonist eplerenone enhances the protein expression of eNOS and its activity , thereby improves eNOS function .