Objective To explore the relationship among genetic polymorphism of angiotension Ⅱ type 1 re-ceptor(AT1 R) A1166-C, angiotensin converting enzyme (ACE) insertion/deletion (I/D), aldosterone synthase (CYP11B2)-344T/C and hypertensive disorder complicating pregnancy.Methods Polymerase chain reaction-re-striction fragment length polymorphism (PCR-RFLP) assay was used to detect the genotypes of AT1 R A1166-C ,ACE (I/O) ,CYP11B2 -344T/C in 86 cases of hypertensive disorder complicating pregnancy and 175 cases of normal control.Results There was 18 combined types in hypertensive disorder complicating pregnancy cases and normal control cases.Compared to AT1R-AA + ACE-Ⅱ + CYP11B2-TT, Odds ratios (OR) of AT1R-AA + ACE-DO +CYP11B2-TC,AT1 R-AC + ACE-ID+CYP11B2-TC and AT1R-AC+ACE-DD+CYP11B2-TC are 7.289,5.315 and 5.694 respectively.There was no statistical significance among the others.Conclusion In all 18 kinds of combined types, AT1 R-AA + ACE-DO + CYP11B2-TC,AT1R-AC+ACE-ID+CYP11B2-TC and AT1 R-AC + ACE-DD +CYP11B2-TC might increase the susceptibility of hypertensive disorder complicating pregnancy.It is possible that multigenes are interacted in the etiology of hypertensive disorder complicating pregnancy.

Objective To observe the cardiosomatic motor reflex (CMR)of rats, and to clarify the descending modulation of nucleus raphes magnus (NRM)in cardiac nociception and its pathway.Methods 34 male healthy SD rats were randomly divided into NRM electrical stimulation group (n=8 ), NRM stimulation combined with dorsolateral funiculus (DLF ) transection group (n= 8 ), NRM stimulation combined with antagonist of 5-hydroxytryptamine (5-HT)methysergide intrathecal administration group (n=18).The rat model of CMR was established through inj ecting capsaicin into the pericardial sac of the rats in various groups. The electromyogram (EMG) response of dorsal spinotrapezius muscle was used as detection index, and by placing the stimulation electrode in NRM and (or)intrathecal catheterization, the descending inhibitory modulation of NRM in CMR and the influence of DLF tansection or methysergide intrathecal administration in descending inhibitory modulation of NRM were observed.Results Compared with before stimulation,the EMG response was decreased after NRM electrical stimulation (75 μA) (P<0.05 );after bilateral DLF transection, the EMG response after NRM stimulation was significantly increased compared with before DLF transection (P<0.05 ), and there was no significant difference compared with its control (P> 0.05 ). In addition, after intrathecal administration of methysergide,the EMG response after NRM stimulation was significantly increased compared with before intrathecal treatment of methysergide (P<0.05),but it was still significantly smaller than that of its control (P<0.05). Conclusion Cardiac nociception evoked by capsaicin stimulation is subject to descending inhibitory modulation from NRM,and the descending inhibition from NRM is conveyed via the DLF and partially mediated by endogenous 5-HT system.

OBJECTIVETo investigate the role of ventrolateral periaqueductal gray (VL-PAG) metabotropic glutamate receptors subtype 7 and 8 (mGluR 7/8) in descending modulation of cardiosomatic motor reflex (CMR) in rats.

METHODSAMN082 (agonist of mGluR 7) and DCPG (agonist of mGluR 8) were injected into the VL-PAG of a rat model of CMR to observe their effects in modulating CMR. The raphe magnus nucleus (NRM) or the gigantocellular reticular nucleus (Gi) was then damaged, and the changes in VL-PAG descending modulation were observed.

RESULTSSelective activation of mGluR 7 of the VL-PAG by AMN082 obviously facilitated capsaicin (CAP)-induced CMR (P<0.05), which was suppressed by DCPG-induced mGluR 8 activation (P<0.05). These facilitatory or inhibitory effects were completely reversed by group III mGluR antagonist MSOP. Damaging the NRM of VL-PAG main relay nucleus did not significantly affect the facilitatory effect produced by AMN082 microinjection (P>0.05), but partially attenuated the inhibitory effect of DCPG microinjection (P<0.05). Both the facilitatory effect of AMN082 and the inhibitory effect of DCPG were reduced obviously after bilateral Gi damage (P<0.05).

CONCLUSIONVL-PAG mGluR 7 and mGluR 8 mediate biphasic regulation of CMR in rats probably through activation of different sub-nuclei and different neurons in the rostroventral medulla.

Animals ; Benzhydryl Compounds ; pharmacology ; Benzoates ; pharmacology ; Glycine ; analogs & derivatives ; pharmacology ; Male ; Medulla Oblongata ; metabolism ; Periaqueductal Gray ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate ; agonists ; metabolism ; Reflex ; physiology

OBJECTIVETo observe the descending modulation of cardiac nociception by the rostral ventromedial medulla (RVM) in rats.

METHODSA rat model of cardiosomatic motor reflex (CMR) was established by injecting capsaicin into the pericardial sac to induce cardiac nociception, and the electromyogram (EMG) response of the dorsal spinotrapezius muscle was studied. The RVM was electrically stimulated (25, 75 and 100 µA) or destroyed to examine whether RVM exerted descending modulation on cardiac nociception.

RESULTSElectrical stimulation of the RVM at 8 sites produced intensity-dependent inhibition of EMG responses to noxious cardiac stimulus (F[2,21]=43.188, P=0.001). Electrical stimulation at 3 sites caused facilitated EMG responses, but the increased magnitude of the EMG was not dependent on stimulation intensity (F[2,6]=0.884, P=0.461). Stimulation at 11 sites produced biphasic effects: at a low intensity (25 µA), the elicited EMG magnitude was significantly larger than baseline (P<0.05), and at greater intensities (75/100 µA), the stimulation caused suppression of the EMG magnitude to a level significantly lower than the baseline (P<0.05). Electrolytic lesion of the RVM resulted in significantly increased EMG responses compared with the baseline and sham lesion group.

CONCLUSIONCardiac nociception evoked by capsaicin stimulation is subjected to descending biphasic modulation by the RVM, which produces predominantly descending inhibition on heart pain.

Animals ; Capsaicin ; pharmacology ; Electric Stimulation ; Electromyography ; drug effects ; Male ; Medulla Oblongata ; physiology ; Nociception ; Nociceptors ; drug effects ; physiology ; Pain ; physiopathology ; Pericardium ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Sensory System Agents ; pharmacology

Objective To observe the descending modulation of cardiac nociception by the rostral ventromedial medulla (RVM) in rats. Methods A rat model of cardiosomatic motor reflex (CMR) was established by injecting capsaicin into the pericardial sac to induce cardiac nociception, and the electromyogram (EMG) response of the dorsal spinotrapezius muscle was studied. The RVM was electricaly stimulated (25, 75 and 100 μA) or destroyed to examine whether RVM exerted descending modulation on cardiac nociception. Results Electrical stimulation of the RVM at 8 sites produced intensity-dependent inhibition of EMG responses to noxious cardiac stimulus (F[2,21]=43.188, P=0.001). Electrical stimulation at 3 sites caused facilitated EMG responses, but the increased magnitude of the EMG was not dependent on stimulation intensity (F[2,6]=0.884, P=0.461). Stimulation at 11 sites produced biphasic effects: at a low intensity (25 μA), the elicited EMG magnitude was significantly larger than baseline (P<0.05), and at greater intensities (75/100 μA), the stimulation caused suppression of the EMG magnitude to a level significantly lower than the baseline (P<0.05). Electrolytic lesion of the RVM resulted in significantly increased EMG responses compared with the baseline and sham lesion group. Conclusion Cardiac nociception evoked by capsaicin stimulation is subjected to descending biphasic modulation by the RVM, which produces predominantly descending inhibition on heart pain.

Objective To investigate the role of ventrolateral periaqueductal gray (VL-PAG) metabotropic glutamate receptors subtype 7 and 8 (mGluR 7/8) in descending modulation of cardiosomatic motor reflex (CMR) in rats. Methods AMN082 (agonist of mGluR 7) and DCPG (agonist of mGluR 8) were injected into the VL-PAG of a rat model of CMR to observe their effects in modulating CMR. The raphe magnus nucleus (NRM) or the gigantocellular reticular nucleus (Gi) was then damaged, and the changes in VL-PAG descending modulation were observed. Results Selective activation of mGluR 7 of the VL-PAG by AMN082 obviously facilitated capsaicin (CAP)-induced CMR (P<0.05), which was suppressed by DCPG-induced mGluR 8 activation (P<0.05). These facilitatory or inhibitory effects were completely reversed by group III mGluR antagonist MSOP. Damaging the NRM of VL-PAG main relay nucleus did not significantly affect the facilitatory effect produced by AMN082 microinjection (P>0.05), but partially attenuated the inhibitory effect of DCPG microinjection (P<0.05). Both the facilitatory effect of AMN082 and the inhibitory effect of DCPG were reduced obviously after bilateral Gi damage (P<0.05). Conclusion VL-PAG mGluR 7 and mGluR 8 mediate biphasic regulation of CMR in rats probably through activation of different sub-nuclei and different neurons in the rostroventral medulla.

Objective To observe the descending modulation of cardiac nociception by the rostral ventromedial medulla (RVM) in rats. Methods A rat model of cardiosomatic motor reflex (CMR) was established by injecting capsaicin into the pericardial sac to induce cardiac nociception, and the electromyogram (EMG) response of the dorsal spinotrapezius muscle was studied. The RVM was electricaly stimulated (25, 75 and 100 μA) or destroyed to examine whether RVM exerted descending modulation on cardiac nociception. Results Electrical stimulation of the RVM at 8 sites produced intensity-dependent inhibition of EMG responses to noxious cardiac stimulus (F[2,21]=43.188, P=0.001). Electrical stimulation at 3 sites caused facilitated EMG responses, but the increased magnitude of the EMG was not dependent on stimulation intensity (F[2,6]=0.884, P=0.461). Stimulation at 11 sites produced biphasic effects: at a low intensity (25 μA), the elicited EMG magnitude was significantly larger than baseline (P<0.05), and at greater intensities (75/100 μA), the stimulation caused suppression of the EMG magnitude to a level significantly lower than the baseline (P<0.05). Electrolytic lesion of the RVM resulted in significantly increased EMG responses compared with the baseline and sham lesion group. Conclusion Cardiac nociception evoked by capsaicin stimulation is subjected to descending biphasic modulation by the RVM, which produces predominantly descending inhibition on heart pain.

Objective To investigate the role of ventrolateral periaqueductal gray (VL-PAG) metabotropic glutamate receptors subtype 7 and 8 (mGluR 7/8) in descending modulation of cardiosomatic motor reflex (CMR) in rats. Methods AMN082 (agonist of mGluR 7) and DCPG (agonist of mGluR 8) were injected into the VL-PAG of a rat model of CMR to observe their effects in modulating CMR. The raphe magnus nucleus (NRM) or the gigantocellular reticular nucleus (Gi) was then damaged, and the changes in VL-PAG descending modulation were observed. Results Selective activation of mGluR 7 of the VL-PAG by AMN082 obviously facilitated capsaicin (CAP)-induced CMR (P<0.05), which was suppressed by DCPG-induced mGluR 8 activation (P<0.05). These facilitatory or inhibitory effects were completely reversed by group III mGluR antagonist MSOP. Damaging the NRM of VL-PAG main relay nucleus did not significantly affect the facilitatory effect produced by AMN082 microinjection (P>0.05), but partially attenuated the inhibitory effect of DCPG microinjection (P<0.05). Both the facilitatory effect of AMN082 and the inhibitory effect of DCPG were reduced obviously after bilateral Gi damage (P<0.05). Conclusion VL-PAG mGluR 7 and mGluR 8 mediate biphasic regulation of CMR in rats probably through activation of different sub-nuclei and different neurons in the rostroventral medulla.

OBJECTIVETo summarize the clinicopathologic features of neuroblastic tumors (NT), and to explore the prognostic significance of MYCN amplification in NT.

METHODSThe clinicopathologic data of 267 NT were reviewed. MYCN gene amplification was detected by fluorescence in situ hybridization (FISH) in 119 cases and the relationship with pathological characteristics and prognostic significance were analyzed.

RESULTSThe study included 267 cases of children NT from patients aged from 1 day to 13 years (median 27 months). The male to female ratio was 1.43. There were 38 cases (14.2%), 43 cases (16.1%), 71 cases (26.6%), and 115 cases (43.1%) of INSS stages I, II, III and IV respectively.Favorable histology group had 157 cases (59.9%); unfavorable histology group had 110 cases (40.1%).Of the 119 NT cases with MYCN FISH performed, 18 cases (15.1%) showed amplification and the signal ratio of MYCN to CEP2 was 4.08-43.29. One hundred and one cases of non-amplified MYCN included MYCN gain in 79 cases (66.3%) and MYCN negative in 22 cases (18.5%). MYCN expression showed significant difference (P = 0.000) between ages, gender, NT type and MKI, but not INPC and clinical stage (P > 0.05).Of the 18 cases with MYCN amplification, 3 were undifferentiated, and 15 poorly differentiated; 17 had high MKI and one moderate MKI. All 18 cases were in unfavorable histology group; the overall survival rate was 3/18, with an average survival time of (17.9 ± 2.4) months.Of the 101 MYCN non-amplification cases, the overall survival rate was 68.3% (69/101), with an average survival time of (29.8 ± 1.3) months. Survival analysis showed the cases with MYCN amplification had worse prognosis (P < 0.05).

CONCLUSIONSNT were commonly diagnosed in early ages and easily to metastasize. Most of cases with favorable histology. The cases of MYCN amplification showed unfavorable histology, and the majority cases with high MKI; The patients with MYCN gene amplification had poor prognosis.

Adolescent ; Cell Differentiation ; Child ; Child, Preschool ; Female ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Male ; N-Myc Proto-Oncogene Protein ; Neuroblastoma ; genetics ; mortality ; pathology ; Nuclear Proteins ; genetics ; Oncogene Proteins ; genetics ; Prognosis ; Survival Analysis ; Survival Rate

Objective: To investigate the pathologic features of gonadal tissues of disorders of sexual development (DSD) in children. Methods: Fifty-three cases of gonadal developmental disorders were collected from July 2015 to August 2017 at Guangzhou Women and Children′s Medical Center. Clinical manifestations, karyotypes, sex hormone levels, ultrasound imaging, histology and immunophenotype of gonadal tissues were analyzed. Results: The age of patients ranged from 7 months to 17 years with an average of (50.7 ± 47.1) months. Social genders of the patients included 32 males and 21 females. Forty-eight patients had abnormal sex hormone levels. Clinical presentations included: toward female genitalia in 25 cases, male genitalia tendency in 17 cases and ambiguous external genitalia in 11 cases. Hypospadias was seen in 31 cases and short stature was seen in 8 cases. Chromosomal karyotyping of peripheral blood revealed 23 cases of sex chromosome disorders, 22 cases of 46 XY disorders, of which 3 cases were 5α-reductase deficiency and 8 cases of 46 XX disorders. Ultrasound examination showed cryptorchidism in 30 cases, including 16 cases of unilateral, 14 cases of bilateral and 1 case presenting a huge pelvic tumor. A total of 97 gonadal tissues from 53 cases of DSD were examined, including 9 cases of unilateral and 44 cases of bilateral gonads. Microscopically, 55 gonads (56.7%) showed dysplastic testes including 17 unilateral and 19 bilateral gonads. Fourteen were streak gonads (14.4%) including 8 unilateral and 3 bilateral gonadal tissues. Nine streak gonad with epithelial cord-like structures (9.3%) were found, of which 5 were unilateral and 2 were bilateral lesions. Seven gonads were ovotestis (7.2%), unilateral in 5 cases (the other side of the gonads of ovary in 4 cases, 1 case of dysplastic testes) and bilateral in 1 case. Seven gonads showed follicular-rich ovarian tissue (7.2%). One case showed bilateral dysplastic testes with gonadoblastoma and ectopic adrenal cortex. One case of streak gonad showed epithelial cord-like structures and undifferentiated glandular tissue embedded in malignant mixed germ cell tumors (mixed gonadoblastoma, dysgerminoma, mature teratoma and yolk sac tumor). One case had testicular microlithiasis. Uterus and fallopian tube structures were found in 11 cases. Immunohistochemical stains were performed in 15 cases. D2-40, PLAP and CKIT were expressed in germ cells and Calretinin, WT1 and inhibin were positive in Setoli cells. SALL4 and OCT3/4 were positive in 3 cases. Inhibin highlighted interstitial Leydig cells in 2 cases. GPC3 was positive in yolk sac tumor component. Conclusions Gonadal dysgenesis presents a broad spectrum of gonadal phenotypes with variable degrees of differentiation. The development of bilateral gonadal tissues has certain variability. Chromosomal karyotypes have no correlation with gonadal phenotypes. Accurate histopathologic diagnosis of gonadal dysgenesis plays an important role in the treatment and prognosis of the patient.