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.

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

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

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.

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 effect of phytoestrogen genistein (GST) on carotid sinus baroreflex in 30 anesthetized male rats by perfusing the isolated carotid sinus in vivo. The results obtained are as follows. (1) By perfusion with GST (50 micromol/L), the functional curve of baroreflex was shifted to the right and upward, with a peak slope (PS) decrease from 0.36+/-0.01 to 0.23+/-0.01 (P<0.001) and a reflex decrease (RD) in mean arterial pressure from 39.75+/-1.58 to 27.00+/-0.60 mmHg (P<0.001), while the threshold pressure (TP) and saturation pressure (SP) were significantly increased from 65.63+/-2.1 to 82.05+/-1.95 mmHg (P<0.001) and from 192.23+/-3.90 to 215.76+/-3.75 mmHg (P<0.001), respectively. Among the functional parameters of carotid baroreflex, the changes in RD, PS and TP were dose-dependent. (2) Pretreatment with Bay K 8644 (500 nmol/L), an agonist of calcium channels, could completely abolish the inhibitory effect of GST on carotid baroreflex. (3) Preperfusion with an inhibitor of NO synthase, L-NAME (100 micromol/L), did not affect the inhibitory effect of GST. It is proposed that the inhibitory action of GST on carotid baroreflex may be mediated by the inhibition of Ca(2+) channel of vascular smooth muscle, but not by NO release from endothelium.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Animals ; Baroreflex ; drug effects ; Carotid Sinus ; drug effects ; physiology ; Genistein ; pharmacology ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide Synthase ; antagonists & inhibitors ; Phytoestrogens ; pharmacology ; Rats

The cardiac electrophysiological effects of genistein (GST) were examined in guinea pig papillary muscle using intracellular microelectrode technique. The results obtained are as follows. (1) Duration of action potential (APD) in normal papillary muscles was decreased by GST (10 100 micromol/L) in a concentration-dependent manner. (2) In partially depolarized papillary muscles, 50 micromol/L GST not only reduced APD, but also decreased the amplitude of action potential, overshoot and maximal velocity of phase 0 depolarization. (3) Pretreatment with N( )-nitro-L-arginine (L-NNA, 5 mmol/L) failed to affect the above effects of GST (50 micromol/L)on papillary muscles. (4) 17beta-estradiol (E(2), 5 micromol/L) or GST (10 micromol/L) alone did not affect action potential, while GST combined with E(2) at the same doses shortened APD significantly. All these results indicate that the effects of GST on papillary muscles are likely due to a decrease of calcium inflow which is not mediated by NO and that GST has a facilitative or synergetic action with E(2).
Action Potentials ; drug effects ; Agmatine ; pharmacology ; Animals ; Dose-Response Relationship, Drug ; Drug Synergism ; Electrophysiology ; Estradiol ; pharmacology ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Genistein ; pharmacology ; Guinea Pigs ; Isoflavones ; Male ; Papillary Muscles ; drug effects ; physiology ; Phytoestrogens ; Plant Preparations

To define the action sites of adrenomedullin (ADM) in the rat brain, and to examine whether neuronal NO may participate in the actions of ADM, the present study was undertaken to examine the effects of i.c.v. administration of ADM on the induction of Fos protein and on nitric oxide-producing neurons in rat brain nuclei involved in cardiovascular regulation, using double immunohistochemical method for Fos and neuronal nitric oxide synthase (nNOS). Following i.c.v. administration of ADM (1 nmol/kg, 3 nmol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the nucleus of the solitary tract (NTS), the area postrema, the locus coeruleus, the parabrachial nucleus and the nucleus paragigantocelluaris laterialis (PGL) in the brainstem, the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the ventromedial hypothalamic nucleus in the hypothalamus, as well as the central amygdaloid nucleus and the lateral habenular nucleus in the forebrain. Following i.c.v. injection of ADM (1 nmol/kg, 3 nmol/kg), the number of double-labeled neurons for Fos and nNOS was increased in the PVN and SON. Small numbers of double-labeled neurons were also found in the NTS and PGL following i.c.v. injection of ADM (3 nmol/kg), while i.c.v. injection of ADM (1 nmol/kg) did not change the number of double-labeled neurons in the NTS and PGL. Pretreatment with calcitonin gene-related peptide receptor antagonist CGRP(8-37) (30 nmol/kg) significantly reduced the action of ADM (3 nmol/kg) in the brain. These results suggest that centrally administered ADM may increase the expression of c-fos in the forebrain, the hypothalamus and the brainstem and activate nitric oxide-producing neurons in the PVN, SON, NTS and PGL. These effects may be partly mediated by CGRP receptors.
Adrenomedullin ; Animals ; Brain Stem ; metabolism ; Injections, Intraventricular ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type I ; metabolism ; Paraventricular Hypothalamic Nucleus ; metabolism ; Peptides ; pharmacology ; Proto-Oncogene Proteins c-fos ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitonin Gene-Related Peptide ; antagonists & inhibitors ; physiology ; Solitary Nucleus ; physiology

To study the electrophysiological effects of capsaicin on spontaneous activity of rabbit atrioventricular (AV) node cells, parameters of action potential in AV node were recorded using intracellular microelectrode technique. Capsaicin (1-30 micromol/L) not only decreased the amplitude of action potential, maximal rate of depolarization (V(max)), velocity of diastolic (phase 4) depolarization, and rate of pacemaker firing, but also prolonged the duration of 90% repolarization of action potential (APD(90)) in a concentration-dependent manner. Both application of L-type Ca(2+) channel agonist Bay K8644 (0.5 micromol/L) and elevation of calcium concentration (5 mmol/L) in superfusate antagonized the effects of capsaicin on pacemaker cells. Pretreatment with ruthenium red (10 micromol/L), a capsaicin receptor blocker, did not affect the effects of capsaicin on AV node cells. Capsaicin exerted an inhibitory action on spontaneous activity of AV node cells in rabbits. These effects were likely due to reduction in calcium influx, but were not mediated by VR1.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Action Potentials ; drug effects ; Animals ; Atrioventricular Node ; cytology ; physiology ; Calcium ; metabolism ; Calcium Channel Agonists ; pharmacology ; Calcium Channels, L-Type ; drug effects ; Capsaicin ; pharmacology ; Male ; Microelectrodes ; Rabbits ; Receptors, Drug ; antagonists & inhibitors ; Ruthenium Red ; pharmacology