[Multi-center randomized double-blind controlled study on children's anorexia (spleen-stomach disharmony) treated with Child Compound Endothelium Corneum].

Child Compound Endothelium Corneum(CCEC)has the effects in invigorating the spleen and appetizing the appetite, and dissolving the accumulation of food. The recent studies have proved that it could improve gastrointestinal motility, restore physiological gastrointestinal peristalsis, increase gastrointestinal digestive motility, and enhance appetite. This trial aimed to evaluate its clinical efficacy and safety in the treatment of children's anorexia(spleen-stomach disharmony). A total of 240 children with anorexia in line with the inclusion and exclusion criteria were selected and randomly divided into experimental group and control group, with 120 in each group. Patients in the experimental group took CCEC and Erpixing Granules simulant. Patients in the control group took Erpi-xing Granules and CCEC simulant. After 21 days of treatment, there was no statistical difference in the recovery rate of anorexia, reduced food intake, eating time, weight change, traditional Chinese medicine syndrome effect, single symptom effect, and trace element Zn recovery rate between the two groups. Based on the non-inferiority test, the experimental group was not inferior to the control group in efficacy. How-ever, the effect of CCEC in reducing appetite in children with anorexia was better than that of control drugs(P<0.05). There was no statistical difference in the incidence of adverse events and adverse reactions between the two groups during the trial. This experiment confirmed the efficacy and safety of CCEC in the treatment of children's anorexia(spleen-stomach disharmony), with a safety and re-liability in clinical application. In addition, it was a better choice for children with anorexia who were mainly manifested by reduced appetite. Meanwhile, compared with granule, chewable tablets were more convenient to take in clinic. Therefore, the efficacy and safety of CCEC for the treatment of children's anorexia(spleen-stomach disharmony) were not inferior to those of Erpixing Granules, with a safety and reliability in clnic. However, due to the small sample size of this trial, the efficacy results only show a trend. It is suggested to further carry out a large-sample-size clinical study to define the clinical advantages of CCEC.

A cocktail of MCM2 and TOP2A, p16INK4a and Ki-67 as biomarkers for the improved diagnosis of cervical intraepithelial lesion.

The purpose of this paper was to explore the immunohistochemistry (IHC) results for a cocktail of minichromosome maintenance protein 2 (MCM2) and topoisomerase II (TOP2A), p16INK4a and Ki-67 as biomarkers for the diagnosis of cervical intraepithelial neoplasia (CIN), improving the routine interpretation of cervical histopathology. 133 cases of CIN were collected from the archival data. All routine hematoxylin and eosin (HE)-stained slides of the subjects were re-examined independently by three senior pathologists, to provide a "consensus diagnosis". Immunohistochemistry for the three biomarkers was performed, and the results were reviewed independently of the corresponding archival diagnosis to make a "diagnosis assisted by IHC" by the original pathological practitioners. The diagnosis accordance rate of the archival original diagnosis with the "consensus diagnosis" and the "diagnosis assisted by IHC" with the "consensus diagnosis" were verified by Fisher's exact test. The results showed that raw agreement between the original HE diagnosis and the "consensus diagnosis" was 88.55%, and raw agreement between the "diagnosis assisted by IHC" and the "consensus diagnosis" was 95.78%. The latter was significantly higher than the former (Fisher's exact test, p = 0.023). In conclusion, the three biomarkers had a high degree of sensitivity and specificity, and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis, and reduce inter-observer variability in cervical biopsy specimens.

Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

Methylphenidate (MPH), commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD). Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC). To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+) increase, but does not require PKA and extracellular Ca(2+) influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

Stimulation of alpha2-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex of rat.

Stimulation of alpha2-, especially alpha2A-adrenoceptor (AR), in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. Alpha2-adrenergic agonists like clonidine and guanfacine have been used experimentally and clinically for treatment of psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. However, the neurophysiological actions of alpha2-ARs in the PFC are poorly understood. In the present study, we recorded field excitatory post-synaptic potential (fEPSP) and evoked excitatory post-synaptic current (eEPSC) in the medial prefrontal cortex (mPFC) of rats, using in vivo field-potential recording and in vitro whole-cell patch-clamp recording techniques, and examined the effects of the alpha2-AR agonist clonidine and the selective alpha2A-AR agonist guanfacine on fEPSP and eEPSC. Systemic or intra-mPFC application of clonidine or guanfacine significantly reduced fEPSP in the mPFC, either in anesthetized or freely moving rats. Consistently, bath-application of guanfacine suppressed eEPSC in layer V/VI pyramidal neurons, and this effect was blocked by the alpha2-AR antagonist yohimbine or the Gi inhibitor NF023. Moreover, treatment with guanfacine had no effect on paired-pulse facilitation (PPF) of fEPSP and eEPSC. The present study provides the first electrophysiological evidence that stimulation of alpha2A-AR inhibits excitatory synaptic transmission in the mPFC through a post-synaptic mechanism.

Pre- and postsynaptic beta-adrenergic activation enhances excitatory synaptic transmission in layer V/VI pyramidal neurons of the medial prefrontal cortex of rats.

Norepinephrine exerts an important influence on prefrontal cortical functions. The physiological effects of beta-adrenoceptors (beta-ARs) have been examined in other brain regions. However, little is known about beta-AR regulation of synaptic transmission in the prefrontal cortex (PFC). The present study investigated beta-AR modulation of glutamate synaptic transmission in layer V/VI pyramidal cells of the medial PFC (mPFC) of rats. Our results show that 1) isoproterenol (ISO), a selective beta-AR agonist, increased the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSC's); 2) ISO enhancement of miniature EPSC's (mEPSC's) frequency no longer appeared in the presence of the voltage-gated Ca(2+) channel blocker cadmium; 3) ISO enhanced the evoked excitatory postsynaptic currents (eEPSC's) mediated by non-N-methyl-D-aspartic acid receptors (non-NMDA-Rs) and NMDA-Rs. The ISO facilitation of non-NMDA-R eEPSC was blocked by the membrane-permeable cyclic adenosine monophosphate (cAMP) inhibitor Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS); 4) ISO enhanced NMDA-induced current, with no effect on glutamate-induced non-NMDA-R current; 5) ISO enhancement of NMDA-R eEPSC and NMDA-induced current was blocked by intracellular application of Rp-cAMPS or the cAMP-dependent protein kinase (PKA) inhibitor PKI(5-24); and 6) ISO suppressed the paired-pulse facilitation of non-NMDA-R and NMDA-R eEPSC's. Taken together, these results provide the first electrophysiological demonstration that beta-AR activation facilitates excitatory synaptic transmission in mPFC pyramidal cells through pre- and postsynaptic mechanisms, probably via cAMP or cAMP/PKA signaling.

[Gastrointestinal stromal tumor: a clinicopathological study of 74 cases].

OBJECTIVE: To explore a simplified and reproducible approach for the diagnosis and morphologic prognostication of gastrointestinal stromal tumor (GIST). METHODS: Eighty-five cases of gastrointestinal mesenchymal tumors including 74 cases of GIST, 8 esophageal smooth muscle tumor, 1 rectal leiomyosarcoma, 1 Schwannoma, and 1 malignant fibrous histiocytoma were studied by histological evaluation along with an immunohistochemistry panel including vimentin, CD117 (c-kit), CD34, SMA, desmin and S-100. Clinicopathological correlation was performed in 31 cases of GIST that had accompanied with the available follow-up data. RESULTS: Among 74 GISTs, 34 arose principally from the stomach, 30 from the small intestine, and 10 other cases found in the esophagus, retroperitoneum, mesenterium and omentum. The patients' age ranged from 23 to 80 years (mean 52.5 years), with 45 males and 29 females. Histologically, the tumors composed of either spindle or oval to round cells arranged in interlacing fascicles forming whorls or cellular clusters, cytoplasm generally abundant and eosinophilic. There were 48 cases of spindle cell type, 10 cases of epithelioid cell type and 16 cases of mixed cell type. All 74 cases of GIST were positive for CD117 in a cell membranous pattern, however, some variable staining patterns of CD117 had been noticed in a few cases. In addition, 54 GISTs were also positive for CD34 (72.9%), 25 cases positive for SMA, 5 cases positive for S-100 and 5 cases positive for desmin. According to the Fletcher's scheme, GISTs in this study were divided into 4 subcategories including groups of very low risk of aggressive behavior (3 cases), of low risk (15 cases), of intermediate risk (36 cases) and of high risk (20 cases) respectively. Kaplan-Meier survival analysis of 31 GIST cases whom had been followed up for 16 to 72 months showed a statistically significant difference present among the subcategories (P < 0.01). CONCLUSIONS: GISTs predominantly occur in the middle and old age patients, more common in male, and positive CD117 staining is considered to be the defining marker to differentiate GIST from other mesenchymal tumors of the GI tract. Positive CD34 immun-staining, plus a CD117 positivity, strengthens further a diagnosis of GIST. Subclassification of GISTs using Fletcher's scheme appears to be simple, reproducible, and correlates well with the clinical behavior of the tumor.