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Objective:To detect itching,anxiety,depression behaviors in chronic itch models of mice and observe the activation of γ-aminobutiric acid(GABA)neurons in the ventral sector of the zona incerta(ZIv),and provide mor-phological evidence for their involvement in the modulation of itch information.Methods:Diphenylcyclopropenone(DCP)was used in glutamic acid decarboxylase 67-green fluorescent protein(GAD67-GFP)knock-in mice to establish chronic itch model.Itch behaviors were detected by video tracking system to verify whether the models were successfully established.The anxiety,depression behaviors of chronic itch model mice were detected by using elevated plus maze test(EPM)and tail suspention test(TST).By using GAD67-GFP mice,the distribution of GABAergic neurons in va-rious sectors of the zona incerta(ZI)was observed.And combined with immunofluorescence staining method,double labeling of GABAergic neurons with FOS in ZIv were observed respectively in control and DCP group mice.Results:In brain slices of GAD67-GFP mice,GABAergic neurons can be observed within all sectors of ZI and are more concentrat-ed in ZIv.Compared with control group mice,DCP group mice showed a significant increase in the bouts of scratching(P＜0.001).The time of immobility in TST was significantly higher in DCP group mice than in control group mice,which displayed depression-like behavior.The EPM test showed that the numbers of entries and proportion of time in the cross region in DCP group mice were less than in control group mice.EPM test revealed that DCP group mice exhibited anxiety-like behavior.The results of immunofluorescence staining showed that the number of FOS-positive cells in ZIv was significantly higher in DCP group mice than in control group mice,and abundant co-labeled neurons of FOS and GABAergic neurons were observed in ZIv.Conclusion:GABAergic neurons were predominantly distributed in ZI,and were more concentrated in ZIv.The activation of GABAergic neurons in ZIv of DCP group mice provides morphological evidence on the involvement of GABAergic neurons in chronic itch and associated negative emotions.

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Objective:To analyze the differences in neuronal activation during fear memory extinction in various sub-regions of the hippocampus in post-traumatic stress disorder(PTSD)mice.Methods:Two immediate early gene-pro-tein labeling strategies were employed to label neurons associated with fear extinction in PTSD mice.In the first group,Arc protein in hippocampal neurons was labeled and observed through immunofluorescence staining in wild-type mice.In the second group,Fos-CreERT2;Ai9 transgenic mice were injected with tamoxifen 23 hours prior to inducing fear memory extinction,and the relevant neurons were labeled with fluorescent proteins for observation.The number of labeled hippocampal neurons and the dendritic branch structure were analyzed to compare the activation levels of hipp-ocampal neurons and the plasticity of neuronal dendrites.Results:The two groups of Arc and Fos positive neurons were mainly distributed in the dorsal hippocampus,in which Arc protein chromogenic was enriched in CA3 and DG subre-gions,while CA1 and CA2 subregions were scattered,while Fos-positive neurons were enriched in the DG subregion of hippocampus and scattered in CA1,CA2 and CA3 subregions.Compared to the control group,there was no significant difference in the number of neurons expressing Arc protein in each subregion of the hippocampus in the PTSD group.The number of Fos-positive neurons in CA1,CA3 and DG subregions in the hippocampus of the PTSD group was signifi-cantly increased(P＜0.01).The dendritic branches of neurons in the hippocampal region were observed and analyzed in Fos-CreERT2;Ai9 mice from both groups,but no significant changes were found.Conclusion:Abnormal activation of neurons occurs in different subregions of the hippocampus during fear extinction in PTSD mice,although there are no significant plasticity changes in the dendritic branches of the activated neurons.

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Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.

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Objective To compare of clinical effect between radiotherapy and chemoradiotherapy and investigate the prognostic factors in elderly patients with esophageal squamous cell cancer.Methods 229 elderly patients with esophageal squamous cell cancer who received radiotherapy and chemoradiotherapy from January 2009 to December 2013 were retrospective analyzed.The Local control rate and survival rate were calculated by Kaplan-Meier method,and the short effect and long term effect between radiotherapy and chemoradiotherapy were compared.Cox regression model was used for invariant analysis and multivariate analysis.Results The follow up time was 15.3months.The short effect of radiotherapy group was not better than that of chemoradiotherapy group,with CR 35.6％ vs 45.8％,RR 61.0％ vs 53.0％,SD 2.7％ vs 0 and PD 0.7％ vs 1.2％ (P=0.211).The 1-,2-,3-year local control rates of radiotherapy group were significantly poorer than that of chemoradiotherapy group,with 82.8 ％,60.5 ％ and 52.7％ vs 89.5％,85.4％ vs 80.9％,respectively (P=0.009).However,there were no significance difference between the 1-,2-,3-year survival rates of radiotherapy group and chemoradiotherapy group,with 66.4％,29.5％,17.1％ vs.65.9％,40.3 ％,30.8 ％,respectively (P =0.071).In invariant analysis,T stage,N stage,clinical stage and radiotherapy dose (＜ 60 Gy,60 ～66 Gy,＞66 Gy) were related with the prognosis of esophageal carcinoma.The COX regression model showed that T stage,N stage and radiotherapy dose were independent prognostic factors that effected survival rate.Conclusion In elderly patients with esophageal squamous cell cancer,chemoradiotherapy can improve the local control rates,but not benefit the survival rate.T stage,N stage and radiotherapy dose were independent prognostic factors that effected survival rate,which could provided evidence for prognosis judgement and clinical practice.

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Objective To improve the non?surgical N staging system for esophageal carcinoma ( EC) . Methods A retrospective analysis was performed in 501 patients newly diagnosed with esophageal squamous cell carcinoma who received radiotherapy in our hospital from 2009 to 2013. The impacts of the supraclavicular lymph nodes and mediastinal lymph nodes on the overall survival ( OS) rate were analyzed. The original non?surgical N staging system was improved and the proposed N staging system was evaluated. The OS rates were calculated using the Kaplan?Meier method and analyzed using the log?rank test. The univariate and multivariate analyses were performed using the log?rank test and Cox regression model, respectively. Results The 3?and 5?year sample sizes were 404 and 205, respectively. In all patients, the 1?, 3?, and 5?year OS rates were 64?9%, 26?5%, and 18?3%, respectively;the 1?, 3?, and 5?year distant metastasis?free ( DMF) rates were 86?2%, 68?9%, and 67?3%, respectively;the 1?, 3?, and 5?year local control rates were 72?7%, 53?1%, and 43?6%, respectively. The univariate analysis showed that the incidence, 3?year OS rate, and 3?year DMF rate of supraclavicular lymph node metastases in patients with cervical and upper?thoracic EC were significantly higher than those in patients with middle?thoracic and lower?thoracic EC ( 25?7% vs. 14?2%, P=0?034;24?2% vs. 11?5%, P=0?016;84?8% vs. 69?2%, P=0?007) . The multivariate analysis also showed that the number of metastatic lymph nodes was an independent prognostic factor for the OS and DMF rates in patients ( P= 0?000;P= 0?007 ) . Conclusions It is reasonable to classify upper?thoracic EC with supraclavicular lymph node metastasis into stage N1 diseases. The proposed N staging system with the factor of the number of metastatic lymph nodes is more scientific and objective than the original N staging system.

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ObjectiveTo evaluate the clinical efficacy and safety of astragalus injection on the immune function in patients with senile sepsis.Methods Sixty patients with old age sepsis in Critical Care Medicine Department of Guangdong Provincial Traditional Chinese Medicine Hospital were enrolled and randomly assigned into control and treatment groups according to the table of random numbers, 30 cases in each group. According to 2012 sepsis guidelines for treatment, including antibacterial drug, mechanical ventilation, visceral function support, etc., the therapy was given to the control group; besides the treatment in the control group, intravenous drip of 60 mL astragalus injection(10 mL per ampoule) in 250 mL 0.9% normal saline was additionally given in the treatment group, once a day for 7 days. Before and after treatment, the immunological indexes, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment(SOFA) score, duration of mechanical ventilation and time of stay in intensive care unit(ICU), 28-day mortality and adverse drug reactions were compared between the two groups.Results Before treatment, there were no statistically significant differences in CD3+, CD3+CD4+, CD3+CD8+ and T helper cells /T suppressor cells(Th/Ts)levels between the two groups(allP>0.05), while CD3-NK+ of the control group was significantly higher than that in the treatment group〔(10.47±6.22)% vs. (6.26±4.13)%,P0.05). After treatment in the treatment group, IgG was increased compared with that in the control group〔IgG(g/L): 13.07±5.43 vs. 10.10±3.96,P 0.05〕. The differences in IgA, IgM, complement(C3,C4) and total serum complement activity(CH50) in the comparisons between the two groups had no statistical significance after treatment(allP>0.05). The differences in APACHEⅡ score(13.83±6.18 vs. 15.90±7.48), SOFA score(7.38±4.66 vs. 6.89±4.19), time of stay in ICU(day: 11.63±5.13 vs. 13.62±8.08), invasive ventilation time(hour: 155.44±119.68 vs. 224.08±174.15) and noninvasive ventilation time(hour: 55.55±42.24 vs. 98.57±43.17) had no statistical significance in comparisons between the treatment group and control group after treatment(allP>0.05). The difference in 28-day mortality had no statistical significance in comparison between the treatment group and control group〔16.7%(5/30) vs. 20.0%(6/30),P>0.05〕. In 60 cases, there were 2 patients with adverse drug reaction, one diarrhea and another little rashes, the rest of the patients did not appear any drug side effect.ConclusionAstragalus injection combined with conventional western medicine therapy possibly has certain effect on adjustment of disturbance of immunologic functions in old patients with sepsis, and its therapeutic safety is well.

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Objective To evaluate the clinical effectiveness and the major toxic effect of radiotherapy combined with docetaxol and cisplatin respectively in the treatment of locally advanced non-small cell lung cancer (NSCLC).Methods 98 patients with locally advanced NSCLC were randomly divided into two groups.All of the patients were treated with 3D-CRT.One group was treated combined with docetaxel,20mg/m2,every week,totally 6 times.The other group was treated combined with cisplatin,30mg/m2,every week,totally 6 times.The total dose was 60 ～66Gy,2Gy/F,5 times each week for 5 ～7 weeks.The clinical effect and the major toxic effect between two groups were compared.Results The median survival time in group that treated with docetaxol was 17.2 months,median progression-free survival time was 13.5 months,and the 1,2 and 3-year survival rates of the patients were 78.6％,35.7％ and 19.5％ respectively.The median survival time in group that treated with cisplatin was 16 months,median progression-free survival time was 16.5 months,and the 1,2 and 3-year survival rates of the patients were 74％,34％ and 20％ respectively.The differences between two group were not stetisticelly significant( P ＞0.05 ).However,the side effect of the stomach and intestine and late radiation complication in group treated with docetaxol were slighter than those in group treated with cisplatin.Conclusion The clinical effect of radiotherapy combined with docetaxol in the treatment of locally advanced NSCLC was equal to radiotherapy combined with cisplatin.But radiotherapy combined with docetaxol has a slighter and acceptable toxic effect,which was worth the clinical application.

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Objective To evaluate the effects and toxic side-effects of radiotherapy combined with xeloda or carboplatin respectively for locally advanced esophagus carcinoma.Methods 74 cases with locally advanced esophagus carcinoma were randomly allocated into two groups.One group received radiotherapy combined with Xeloda,500mg at a time,twice a day,taken orally from the beginning of radiotherapy till end of treatment.The second group received radiotherapy combined with Carboplatin by intravenous drip at 100mg a day,for 5 days,from the first week of radiotherapy.Results The overall response rate in the radiotherapy combined with Xeloda group was 91.4％ and 89.7％ in the radiotherapy combined with Carboplatin group.The difference between the two groups was not statistically significant(P ＞0.05 ).Kaplan-Meier survival analysis showed no statistically significant differences in survival between the two groups.The toxic side-effects of gastrointestinal tract,reaction myelosuppression and late radiation reaction were notably alleviated in the Xeloda group compared with the Carboplatin group.Conclusion Compared with Carboplatin,Xeloda combined with radiotherapy had less toxic side-effects for treatment of advanced esophagus carcinoma,with an equal local control rate,which worthy of clinical application.

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Objective To observe the developmental changes of projection and termination of proprioceptive afferent fibers in the mouse spinal cord. Methods Parvalbumin (PV) immunohistochemistry was used to label the proprioceptive afferents. Single and dual immunofluorescence histochemistry were used to examine the growth pattern of proprioceptive afferents and their relationships with motoneurons in the spinal ventral horn (VH). The stained sections were observed under a confocal laserscanning microscope. Results PV-like immunoreactive (LI) proprioceptive fibers first appeared in the dorsal column on embryonic (E) day 14, then entered the gray matter on El5 and reached the intermediate gray matter and VH more obviously on E16. The number and intensity of PV-LI proprioceptive afferent fibers and punctata increased in the VH with age and reached a maximum during earlier postnatal (P) period (P0-P7). After P14, the number and intensity of proprioceptive afferents gradually decreased. The proprioceptive terminals seemed to form close relationship with motoneurons from E17. Conclusion The present study indicates that the somatotopic organization of proprioceptive afferents in the spinal cord is established during the late embryonic and early postnatal stages. These results provide evidence for understanding the development of the reflex movements.

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The present study was designed to examine the developmental changes in projection and termination of nociceptive and proprioceptive afferent fibers in the spinal cord by labeling those two fibers with calcitonion gene-related peptide (CGRP) and parvalbumin (PV)separately in mouse embryos and neonatal pups aged embryonic day 15 to posanatal day 3 (E15 -P3). CGRP-like immunoreactive (LI)nociceptive fibers first appeared in the superficial dorsal horn (DH) at E16. The afferent projections extended laterally to the DH and entered into the deep portions of the DH at E17 and E18. After birth, the projection pattern of CGRP-LI fibers remained unchanged but the intensity of afferent terminals increased in the superficial laminae and their branching patterns became more complicated. In addition,CGRP-LI collaterals that projected into the contralateral DH were also examined after E16. Around birth, the contralateral projections were also found originated from the lateral part of the DH. PV-LI proprioceptive afferents were first observed entering the gray matter at E15 and reached the intermediate gray matter (IG) and the ventral horn (VH) more obviously on E16. The number and intensity of PV-LI fibers increased in the the VH with age and reached a maximum during earlier postnatal period ( P0-P3 ). The proprioceptive terminals seemed to form close relationship with motoneurons in the VH from E17. Our results indicate that the somatotopic organization of nociceptive and proprioceptive afferents in the spinal cord both are established during the late embryonic and early postnatal stages. These results help to understand the development of the sensory transmission in more details.

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Objective:Preparated from seeds of Brassica alba, Sinapine was determinated by RP-HPLC. Methods: Seeds of Brassica alba were shattered, defatted by ether, extracted by alcohol, and crystallized by potassium thiocyanate, then ethanol and water were used to recrystallize for several times. The determination was performed by reversed-phase high performance liquid chromatography(RP-HPLC), using ZORBAX SB-Aq column 4.6 mm?250 mm, 5 ?m. The mobile phase consisted of acetonitrile-0.08 mol/L KH2P04 (20:80) at a flow rate of 1.0 ml/min, and the detection wavelength was 326 nm. Results: Pale yellow needle-like sinapine crystal was obtained, and the yield rate was 0.82%. The purity of sinapine thiocyanate crystal was over 95%. Conclusion: Preparation sinapine by this solvent extraction method was simple, high-purity, high yield, and could be used for industrial production.

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the hydrolysis temperature.7 Components had been identified from 10 separated peaks,these accounted for 99.999% of the total volatile oil.The main components were Allyl isothiocyannte(89.411%),3-Butenyl isothiocyanate(7.364%) and 3-Butenenitrile(1.275%).Conclusion:The optimum extraction conditions were:hydrolysis temperature 50,pH value of buffer solution 5.0,concentration of ascorbic acid 0.5mmol/L.The yield rate of the volatile oil of this process can reach 0.164%,and this process was stable and feasible;the main components of the volatile oil were isothiocyanates,and the volatile oil also contained a small amount of aldehydes,ethers and nitriles.

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The present study was designed to examine the morphological pattern of primary afferent projections into the spinal dorsal horn by labeling the lumbar dorsal root ganglia with carbocyanine fluorescent dye DiI in mouse embryos and neonatal pups aged embryonic day 12 to postnatal day 3 (E12-P3). Primary afferent fibers projected into dorsal funiculus at E13, but did not penetrated into gray matter of dorsal horn until E15. The afferent projections became dense and entered the spinal gray matter more deeply at E16 and E17. By E18 the intensity of primary afferent in the deep part of the dorsal horn increased and their branching patterns became more complicated. Some of these primary fibers were also observed to ramify extensively in the superficial laminae. The projection pattern of primary afferent remained unchanged after birth, but the intensity of afferent terminals increased in the superficial laminae. In addition, afferent fiber collaterals that projected into the contralateral dorsal horn were also observed. They were first examined at E16 and mainly originated from the medial and deep part of the dorsal horn. Around birth, the contralateral projections were also found to originate from the lateral part of dorsal horn. Our results indicate that laminar organization of primary afferents in the spinal dorsal horn is established during the late embryonic and early postnatal stages.This organization then undergoes further refinement to match the pattern seen in the adult.

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Objective To study the in vivo expression patterns of caspase-3 in normally aged primate brain. Methods Fresh brain tissue was taken from 4-year-old and 20-year-old female rhesus monkeys,4 for each age group. In vivo distribution of caspase-3-positive cells and its protein levels in different brain regions were investigated by immunohistochemical and immunoblot means,respectively. Results In the frontal cortex,most neurons lacked detectable caspase-3 immunoreactivity,whereas low to moderate caspase-3 immunostaining was found mainly in pyramidal cells in CA1,CA3 and CA4 subdivisions of hippocampus. And in the cerebellum,a small number of Purkinje cells were strongly stained in their cytosol and dendrites,while their nuclei lacked staining. Age-related changes in caspase-3 expression pattern were not found. Immunostaining of motor cortex in aged monkeys localized strong caspase-3 immunoreactivity to a limited number of large pyramidal cells in layer V. Immunoblotting revealed the 32 000 caspase-3 progenitor in all three brain regions. There were no differences in caspase-3 expression levels as a function of either brain region or age of animals. Conclusions These results suggest that caspase-3 is constitutively expressed in matured primate brain and there is no significant age-related change in its expression.

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Immunocytochemical staining technique by using specific antibody against 5-HT1A receptor subtype (5-HT1AR) wasused to observe the distribution of 5-HT1AR immunoreactivity in the rat nervous system. The highest level of 5-HT1AR im-munoreactivity was observed in piriform cortex, septum, ventraldorsal thalamic nucleus, reticular thalamic nucleus, basolateralamygdaloid nucleus, Purkinje cell layer, red nucleus, facial nucleus and nucleus of the trapezoid body. Considerably weaker im-munoreactivity was detected in hippocampus, frontal cortex, mediodorsal thalamic nucleus, interpeduncular nucleus, mesen-cephalic trigeminal nucleus, dorsal raphe nucleus, spinal trigeminal nucleus, the superficial layers of the spinal dorsal horn, dor-sal root and trigeminal nerve ganglia, Very weak immunoreactivity was found in the olfactory bulb, caudate putamen,globus pal-lidus, nucleus diagonal band, bed nucleus stria terminalis, habenular nucleus, substantia nigra and superior olive. The presentresults indicate that 5-HT1AR immunoreactive structures are widely distributed in the rat nervous system and might play impor-tant role in mediating the multiple effects of 5-HT in the nervous system.

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Aim To investigate the expression of vascular endothelial growth factor(VEGF) and its receptors in human hepatocellular carcinoma cell lines SMMC7721, HHCC and HepG2. Methods Immunohistochemical staining and reverse-transcriptase polymerase chain reaction(RT-PCR) were used to detect the mRNA and expression of VEGF and its receptors: VEGF-R1(Flt-1) and VEGF-R2 (KDR) in three human hepatocellular carcinoma cell lines, SMMC7721, HHCC and HepG2, as compared with ECV304 cells(human umbilical vein endothelial cells) and L929 cells(mouse fibroblast). Results All three human hepatocellular carcinoma cell lines expressed VEGF protein. Flt-1 mRNA and protein could be detected in SMMC7721 cells while KDR in HHCC and HepG2 cells. Conclusion The expressions of Flt-1 and KDR suggests that VEGF may be an autocrine growth factor for human hepatocellular carcinoma, at least for cell lines in vitro.

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Objective To observe the expression of 5-HT receptor 14 subtype mRNAs in the rat retina. Methods RT-PCR technique was used. Specific oligonucleotide primers were synthesized based on the complementary DNA sequence for each of the 14 cloned rat 5-HT receptor subtypes. Expression of 5-HT 1A、5-HT 2A、5-HT 2C、5-HT 3 and 5-HT 7 receptor subtype mRNAs were detected. Results Positive band densities of various 5-HT receptor subtypes were different in retina. The most bands were formed by 5-HT 7 and 5-HT 2A receptor subtypes, the secondary prominent bands were formed by 5-HT 2C and 5-HT 3 receptor subtypes. PCR products from each positively-detected receptor subtype were subcloned into pCRⅡ vector for sequencing and found in correspond to published complementary DNA sequences. No positive bands existed of 5-HT 1B, 5-HT 1D, 5-HT 1E, 5-HT 1F, 5-HT 2B, 5-HT 4, 5-HT 5A, 5-HT 5Band 5-HT 6receptor subtypes. Conclusions There may exist varieties of 5-HT receptor in rat retina, including 5-HT 1A, 5-HT 2A, 5-HT 2C, 5-HT 3 and 5-HT 7 receptor subtypes. It means the retina serotoninergic system may be a common feature in mammals and, by the light of the 5-HT receptor subtypes, play an important role in mediating the transmission of rod sensitive signals.

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Objective To observe the distribution of protein kinase C? subunit(PKC?) in the rat nervous system. Methods Immunocytochemical staining for PKC? by using specific antibody against PKC? was performed. Results Intensely and densely stained PKC? immunoreactive neurons were mainly observed in the cerebral cortex,hippocampus,amygdaloid complex,cerebellar cortex, ventral and dorsal cochlear nuclei, caudal spinal trigeminal nucleus and the superficial layers of the spinal dorsal horn.Conclusion\ PKC?\|containing neurons are widely located in the rat nervous system.These results provide morphological evidence for the functional roles of PKC? in the signaling transduction of the nervous system.\;[

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Objective\ To observe the expression of 5\|HT 1A and 5\|HT 2A receptor mRNAs in the rat spinal cord and dorsal root ganglion(DRG). Methods\ In situ hybridization histochemical technique. Results\ (1)5\|HT\-\{1A\} receptor mRNA positive neurons were found in all laminae of the gray matter,mainly in the superficial laminae(laminae Ⅰ and Ⅱ),laminae Ⅲ and Ⅳ of the dorsal horn.Scattered positive neurons were also observed in laminae Ⅴ\|Ⅶ and Ⅹ.Very few positive signals were found in the ventral horn(lamnina Ⅸ);(2)5\|HT\-\{2A\} receptor mRNA positive neurons were mainly found in the superficial laminae and ventral horn,while sparsely distributed positive neurons were also located in other laminae.Within the DRG:(1)About 10^4% of the total DRG cells were labeled with 5\|HT 1A receptor mRNA.The positive signals were mainly confined to a subpopulation of small\| and medium\|sized cells;(2)About 17^4% of the total DRG cells were labeled with 5\|HT 2A receptor mRNA,most of them were also small\| and medium\|sized cells. Conclusions\ 5\|HT 1A and 5\|HT 2A receptor mRNAs positive neurons distributed heterogeneously in the rat spinal cord and DRG, they may play important roles for 5\|HT in the analgesic effects at the spinal level and nociception in the periphery.\;