Retinoblastoma(RB)is the most common intraocular malignancy of children with extremely poor prognosis. MicroRNAs are small non-coding single-stranded RNAs in eukaryotic cells, which regulate the expression of gene by mRNA degradation or translation inhibition. MicroRNAs, acting as oncogenes or tumor suppressor genes, are associated with the occurrence and development of RB directly, which is vital for the early diagnosis and clinical targeted therapy of RB. This review summarized the expression of microRNAs in RB and the related mechanism.

OBJECTIVE: To investigate the effects of atorvastatin, rosuvastatin, and pravastatin on antiplatelet activity of clopidogrel in patients with acute coronary syndrome(ACS) and different CYP2C19 genotypes. METHODS: Between November 2017 and November 2018, a total of 300 patients admitted for ACS were enrolled in this study and randomly assigned to three groups. All patients received standard dual antiplatelet therapy. A, B, and C groups received atorvastatin calcium 20 mg•d-1, rosuvastatin calcium 20 mg•d-1, and pravastatin sodium 20 mg•d-1, respectively. The CYP2C19 genotype was detected by pyrosequencing. Thromboelastogram(TEG) was applied to detect the ADP-induced platelet inhibition rate 7 days after treatment. RESULTS: No significant difference was observed in baseline clinical characteristics between three groups. It was also no statistically significant difference in ADP inhibition rate and proportion of clopidogrel resistance between three groups(P>0.05). However, compared with rosuvastatin group and pravastatin group, the ADP inhibition rate was significantly reduced in atorvastatin group in poor metabolizers of CYP2C19. CONCLUSION: In intermediate metabolizers and extensive metabolizers of CYP2C19, there is no significant difference in the effects of atorvastatin, rosuvastatin, and pravastatin on antiplatelet activity of clopidogrel. Compared with rosuvastatin and pravastatin, atorvastatin significantly attenuates the antiplatelet function of clopidogrel in poor metabolizers of CYP2C19.

To observe the effect of intracarotid administration of endothelin (ET-1) on electrical activity of neurons within rostral ventrolateral medulla (RVLM) region, 87 spontaneous active units were extracellularly recorded in 35 Sprague-Dawley rats with sino-aortic denervation. The results obtained are as follows. (1) Intracarotid administration of ET-1 (0.3nmol/kg) increased the discharge firing rate from 17.8±1.5 to 20.9±1.4 spikes/s (P<0.01) in 30 out of 36 RVLM neurons, while blood pressure and heart rate had no significant change. (2) BQ-123 (0.67nmol/kg), a selective ETA blocker, completely blocked the facilitatory effects of ET-1 in 11 out of 14 units. (3) In 10 out of 11 units, glibenclamide (3.3 nmol/kg), a blocker of ATP-sensitive potassium channel, had no effect on the action of ET-1. (4) After ablation of area postrema (AP), the facilitatory action of intracarotid administration of ET-1 on 19 units of RVLM was abolished, while in 7 units of sham ablation animals the response of neurons to ET-1 remained unchanged. Taken together, intracarotid-administered ET-1 may act on the ETA receptors in neurons of AP, thereby resulting in the facilitating effect on RVLM neurons through the efferent projection of AP.

To observe the effect of intracarotid administration of adenosine on the electrical activity of area postrema (AP) neurons, 76 spontaneous active units were recorded from 45 sino-aortic denervated Sprague-Dawley rats using extracellular recording technique. The results obtained are as follows. (1) Following intracarotid administration of adenosine (Ado, 25 μg/kg), the discharge rate of 29 out of 42 units decreased markedly from 6.26±0.75 to 4.74±0.76 spikes/s (P<0.01), whereas that of 6 units increased from 4.13±0.77 to 4.72±0.83 spikes/s (P<0.05), and the other 7 showed no response. Blood pressure (BP) and heart rate (HR) were unaltered throughout the experiment. (2) 8-phenyltheophylline (8-PT, 15 μg/kg), a nonselective adenosine receptor antagonist, completely blocked the inhibitory effect of Ado in 10 units. (3) Selective A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 50 μg/kg), blocked the effect of Ado in 12 units to a remarkable extent. (4) Glibenclamide (500 μg/kg), a blocker of ATP-sensitive potassium channel, abolished the effect of Ado in 12 units. The above results indicate that Ado can inhibit spontaneous electrical activity of AP neurons, which is mediated by adenosine A1-receptor with the involvement of ATP-sensitive potassium channels.

The effect of agmatine (Agm) on vascular tension and the underlying receptor mechanism were investigated in the isolated aortic artery of rats. The results are as follows. (1) Agm (10－7～10－2mol/L) relaxed aortic rings in a concentration-dependent manner under the condition of precontraction induced by phenylephrine (PE) at a concentration of 10－6 mol/L. (2) Either in the intact or the endothelium-denuded rings, pretreatment with NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 0.5 mmol/L) did not affect the vascular relaxant action of Agm, implying that the concentration-dependent vasorelaxation caused by Agm is not endothelium-dependent and NO is not involved. (3) Agm also relaxed aortic rings in a concentration-dependent manner under the condition of precontraction induced by CaCl2 at a concentration of 3 mmol/L. (4) Idazoxan (10－4 mol/L), an α2-adrenergic receptor (α2-AR) and imidazoline receptor (IR) antagonist, abolished the Agm-induced vasorelaxation completely under the condition of CaCl2-induced precontraction. (5) Yohimbine (10－4 mol/L), a selective α2-AR antagonist, could partially block the vascular relaxant action of Agm. It is suggested that the vascular relaxant effect of Agm on the rat aortic artery may be mediated by α2-AR and IR.

To observe the effect of intracarotid administration of adrenomedullin (AM) on the spontaneous electrical activity of area postrema (AP) neurons, 78 spontaneous active units were recorded from 63 sino-aortic denervated Sprague-Dawley rats using extracellular recording technique. The results obtained are as follows. (1) Following intracarotid administration of AM (0.3 nmol/kg), the discharge rate of 47 out of 78 units increased markedly from 2.99+/-0.24 to 4.79+/-0.29 spikes/s (P<0.001), 20 units decreased from 3.24+/-0.46 to 1.97+/-0.37 spikes/s (P<0.001), and the remaining 11 showed no response. Blood pressure (BP) and heart rate (HR) did not change throughout the experimentation. (2) Pretreatment with intracarotid administration of calcitonin gene-related peptide receptor antagonist CGRP8-37 (3 nmol/kg) did not change the effects of AM. (3) Following intracarotid injection of NO precursor L-arginine (30 mg/kg), the excitatory effect of AM was attenuated. The above results indicate that AM can excite spontaneous electrical activity of AP neurons, this effect is not mediated by calcitonin gene-related peptide receptor but may be attenuated by NO precursor L-arginine.
Action Potentials ; physiology ; Adrenomedullin ; pharmacology ; Animals ; Aorta ; innervation ; physiology ; surgery ; Area Postrema ; physiology ; Carotid Sinus ; innervation ; physiology ; surgery ; Denervation ; Injections, Intra-Arterial ; Male ; Neurons ; physiology ; Rats ; Rats, Sprague-Dawley

The purpose of this study was to determine the effects of 17beta-estradiol (E(2)) on electrical activity of the rostral ventrolateral medulla (RVLM) neurons in rats. Male Sprague-Dawley rats were anesthetized with urethane (1.0 g/kg) and subjected to sino-aortic denervation. Blood pressure, heart rate and spontaneous discharge of RVLM neurons were recorded simultaneously. Intracarotid injection of E(2) (10 ng/kg) decreased the discharge rate from 14.46+/-0.47 to 9.73+/-0.33 spikes/s (P<0.001) in 25 out of 30 RVLM neurons, while blood pressure and heart rate showed no significant change. The inhibitory effect of E(2) on RVLM neuronal activity was rapid at the onset (within 1 min) and long-lasting (>5 min). Prior administration of antiestrogen tamoxifen (TAM) did not affect the effect of E(2). However, pretreatment with N( )-nitro-L-arginine-methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, significantly attenuated the inhibitory effect of E(2). In addition, NO donor 3-morpholinosydnonimine (SIN-1) potentiated the effect of E(2). These results suggest that E(2) may inhibit spontaneous electrical activity of RVLM neurons, an effect which is mediated by the activation of NOS with the resultant of NO release via nongenomic actions.
Animals ; Carotid Arteries ; Electrophysiology ; Estradiol ; pharmacology ; Injections, Intra-Arterial ; Male ; Medulla Oblongata ; cytology ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective To observe the clinical efficacy of acupuncture plus oral administration of self-made Chinese herbal decoction in treating cough variant asthma (CVA).Method Sixty-two CVA patients were randomized into a treatment group of 32 cases and a control group of 30 cases.The treatment group was intervened by acupuncture plus oral administration of self-made Chinese herbal decoction,and the control group was intervened by Montelukast sodium tablets.Before and after 3 courses of treatment,the score of cough,eosinophil (EOS) count,pulmonary function tests [peak expiratory flow (PEF),forced vital capacity (FVC),and forced expiratory volume in 1 second (FEV1)] were observed.The clinical efficacies were compared between the two groups.Result After the treatment,the score of cough,EOS count,and pulmonary function tests (PEF,FVC,and FEV1) were changed significantly in both groups (P＜0.05).The score of cough,EOS level and pulmonary function tests in the treatment group were significantly different from those in the control group after the treatment (P＜0.05,P＜0.01).The total effective rate was 93.8％ in the treatment group versus 80.0％ in the control group,and the difference was statistically significant (P＜0.05).Conclusion Acupuncture plus oral administration of self-made Chinese herbal decoction is an effective method in treating CVA.

The present study was undertaken to examine the effects of microinjection of adrenomedullin (AM) into rostral ventrolateral medulla (RVLM) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in 34 anesthetized Sprague-Dawley rats. The results obtained are as follows. (1) Following microinjection of AM (10 micromol/L, 200 nl) into the RVLM, MAP, HR and RSNA were significantly increased from 99.09+/-3.32 mmHg, 370.78+/-7.84 bpm and 100+/-0% to 113.57+/-3.64 mmHg (P>0.001), 383.28+/-7.38 bpm (P>0.001) and 123.72+/-2.74% (P>0.001), respectively. (2) Pretreatment with microinjection of calcitonin gene-related peptide receptor antagonist CGRP8-37 (100 micromol/L, 200 nl) did not change the effects of AM. (3) L-arginine (100 mg/kg, 0.2 ml, i.v.), an NO precursor, abolished the effects of AM. This study demonstrates that AM acting at the rostral ventrolateral medulla may produce significant cardiovascular responses, the effects are not mediated by CGRP receptor but may be abolished by NO.
Adrenomedullin ; administration & dosage ; pharmacology ; Animals ; Blood Pressure ; drug effects ; Heart Rate ; drug effects ; Kidney ; innervation ; Lateral Thalamic Nuclei ; drug effects ; Medulla Oblongata ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sympathetic Nervous System ; drug effects ; physiology

To observe the effect of intracarotid administration of adenosine on neurons in the rostral ventrolateral medulla (RVLM) region, 72 spontaneous active units were extracellularly recorded from 28 Sprague-Dawley rats with sino-aortic denervation. The results obtained are as follows: (1) intracarotid administration of Ado (25 μg/kg) reduced the discharge rate from (23.5 + 3.0) to (16.5 ± 2.6) spikes/s (P ＜ 0.001) in 31 out of 36 RVLM neurons, while the blood pressure and heart rate had no significant change ( P ＞ 0.05); (2) 8-phenyltheophylline (8-PT, 15 μg/kg), a nonselective adenosine receptor antagonist, and 8-cyclopentyl-l,3-dipropylxanthine (DPCPX, 50 μg/kg), a selective A1 adenosine receptor antagonist,completely blocked the inhibitory effects of Ado in 24 units; and (3) in 12 units, glibenclamide (500 μg/kg), a blocker of ATP-sensitive potassium channel, abolished the effect of Ado. These results indicate that Ado can induce an inhibition of spontaneous electrical activity of RVLM neurons, an effect which is mediated by adenosine A1-receptor with the involvement of ATP-sensitive potassium channels.