Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

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.

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.

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.

Objective To investigate the feasibility of CT pulmonary angiography (CTPA) with 80 kVp and contrast agent of iodixanol (270 mg I/ml) by filtered back projection(FBP) reconstruction.Methods In total,52 patients who underwent CTPA were randomly divided into two equally-sized groups,control group and experimental group.The volume computed tomography dose index (CTDIvol) and dose-length product (DLP)were recorded,and the weighted computed tomography dose index (CTDIw) and effective dose (E) were calculated.The image quality was visually evaluated and measured,and statistical analyses were performed on the image quality and the radiation dose.Results The sex,age,height,weight and body mass index (BMI) had no statistical difference between two groups (P ＞ 0.05).The average iodine dosage decreased by 22.9％ in the experimental group compared with the control group.Compared with the control group,the CTDIvol,DLP,CTDIw and E decreased by 73.5％,75.1％,73.5％ and 75.8％,respectively.The differences were statistically significant (t =＜0.001,30.5,＜ 0.001,-28.7,P ＜ 0.05).The image quality of the two groups met the requirement of diagnosis and there were no significant statistic differences between visually evaluating and objectively measuring the image quality (P ＞ 0.05).Conclusions Using 80 kVp and iodixanol for CTPA,FBP reconstruction image quality can meet diagnostic requirements.At the same time the radiation dose,the contrast agent dose and the X-ray tube wastage are reduced respectively.

Objective To investigate the characteristics of breast neoplasms on contrast-enhanced ultrasonography(CEUS) and its clinical value.Methods Two hundred and twenty-five patients with breast masses unable to be diagnosed by conventional ultrasonography were examined with CEUS.The characteristics of these masses on CEUS were analyzed and compared with the results of pathology examination.Results The typical features of breast cancers on CEUS were enlarged maximum diameter of the lesions on CEUS compared to pre-contrast ( P ＜0.05),irregular shapes,heterogeneous distribution of contrast enhancement with perfusion defect or local retention of contrast signals,tortuous,massive or penetrating vessels rapidly entering and exporting from the lesions.The sensitivity and specificity of perfusion defect for breast cancer on CEUS were 89.0％ and 91.8％,respectively; the sensitivity and specificity of local retention of contrast signals for breast cancer on CEUS were 93.4％ and 92.5％,respectively.Conclusions It is valuable for CEUS in the diagnosis and differential diagnosis of breast neoplasms clinically.

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.

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.