Analysis of Factors Associated With Synchronous Liver Metastasis in Gastroenteropancreatic Neuroendocrine Neoplasm and Establishment of A Predictive Model / 胃肠病学

Background: Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is a rare heterogeneous tumor. Liver metastasis seriously affects the prognosis of GEP-NEN. However, few tools are existed to predict GEP-NEN complicated with synchronous liver metastasis. Aims: To analyze the risk factors of synchronous liver metastasis in patients with GEP-NEN and establish a nomogram to predict synchronous liver metastasis in patients with GEP-NEN. Methods: A total of 10 973 pathologically confirmed patients with GEP-NEN from Jan. 2010 to Dec. 2017 were collected from SEER database and divided randomly into training set (n=7 511) and test set (n=3 462). Both groups were divided into liver metastasis group and non-liver metastasis group according to the occurrence of liver metastasis. Multifactorical logistic regression analysis was used to identify the risk factors of liver metastasis in patients with GEP-NEN. R software was used to establish and verify the nomogram of liver metastasis in GEP-NEN patients. Results: Liver metastasis was associated with gender, age, race, primary tumor site, degree of differentiation, tumor diameter, T3/4 stage, and lymph node metastasis in patients with GEP-NEN. The results of multivariate logistic regression analysis showed that primary tumor site (small intestine and pancreas), differentiation degree (poorly differentiated and undifferentiated), diameter of tumor ≥ 5 cm, T3/4 stage and lymph node metastasis were independent risk factors affecting liver metastasis in patients with GEP-NEN (P< 0.001). The concordance index of internal validation for nomogram was 0.838 (95% CI: 0.826-0.849), and the concordance index of external validation was 0.847 (95% CI: 0.829-0.864). Conclusions: GEP-NEN patients with primary tumor site in small intestine or pancreas, poor differentiation and undifferentiation, diameter of tumor ≥5 cm, T3/4 stage and lymph node metastasis are more likely to develop liver metastasis which suggested that such patients need to be alert for the occurrence of liver metastasis and need more aggressive treatment. The calibration curves fits are good for both the training and test sets, and can help clinicians to make individualized prediction for whether the GEP-NEN patient has synchronous liver metastasis at the initial diagnosis.

Altered Local Field Potential Relationship Between the Parafascicular Thalamic Nucleus and Dorsal Striatum in Hemiparkinsonian Rats / 神经科学通报·英文版

The thalamostriatal pathway is implicated in Parkinson's disease (PD); however, PD-related changes in the relationship between oscillatory activity in the centromedian-parafascicular complex (CM/Pf, or the Pf in rodents) and the dorsal striatum (DS) remain unclear. Therefore, we simultaneously recorded local field potentials (LFPs) in both the Pf and DS of hemiparkinsonian and control rats during epochs of rest or treadmill walking. The dopamine-lesioned rats showed increased LFP power in the beta band (12 Hz-35 Hz) in the Pf and DS during both epochs, but decreased LFP power in the delta (0.5 Hz-3 Hz) band in the Pf during rest epochs and in the DS during both epochs, compared to control rats. In addition, exaggerated low gamma (35 Hz-70 Hz) oscillations after dopamine loss were restricted to the Pf regardless of the behavioral state. Furthermore, enhanced synchronization of LFP oscillations was found between the Pf and DS after the dopamine lesion. Significant increases occurred in the mean coherence in both theta (3 Hz-7 Hz) and beta bands, and a significant increase was also noted in the phase coherence in the beta band between the Pf and DS during rest epochs. During the treadmill walking epochs, significant increases were found in both the alpha (7 Hz-12 Hz) and beta bands for two coherence measures. Collectively, dramatic changes in the relative LFP power and coherence in the thalamostriatal pathway may underlie the dysfunction of the basal ganglia-thalamocortical network circuits in PD, contributing to some of the motor and non-motor symptoms of the disease.

Effect of dopamine D1 receptor antagonist SCH23390 on electrophysiological activity of entopeduncular nuclei in parkinsonian rats / 中华神经医学杂志

Objective To study the effect of dopamine D1 receptor antagonist SCH23390 on the behavior of parkinsonian (PD) rats and on electrophysiological characteristics of the entopeduncular nucleus (EP).Methods Intracranial injection of 6-OHDA was conducted in 23 adult male Wistar rats to create PD animal models (experimental group) while the same amount of normal saline was injected in another 19 rats as a control group.(1) After intraperitoneal injection of SCH23390 at various concentrations of 0.010,0.015,0.020,0.025 and 0.030 mg/kg,the step frequency and the discontinuous moving frequency tests were carried out to determine the optimal concentration and time of intervention at 6 time points (10 main before,and 5～15,20～30,30～40,40～50 and 68～78 min after intervention) when all the rats were put on a treadmill at a speed of 8 r/min.(2) After recording electrodes were implanted into the EP in the rats,the signals of spikes in the EP in still and movement conditions were recorded simultaneously using the 16-Channel OmniPlex Neural Data Acquisition System.The spike signals collected were imported into Offiine Sorter to do cluster-sorting analysis and then into NeuroExplorer to analyze alterations in the firing pattern and firing rate of each type of neuron.(3) Frozen sections of the brain samples harvested by perfusion from the rats in the 2 groups were subjected to Nissl's staining and histological assay.Results (1) The behavioral tests showed that intraperitoneal injection of SCH23390 at 0.020 mg/kg at time points of 20～30 min and 30～40 min was optimal.The step frequency for the experimental group (24.47±1.35 step/min) was significantly decreased compared with that for the control group (30.77±2.06 step/min) (t=7.392,P=0.000).(2) After intervention by SCH23390,in movement and still conditions,the firing rate and variation coefficient of EP neurons were significantly higher in the experimental group than in the control group (P＜0.05).(3) The Nissl's staining showed a small number of lightly stained neurons were sparsely disposed in the injured cerebral substantia nigra and the histological assay found altogether 14 rats from which correct EP sites were collected.Conclusions This study demonstrated a negative regulating effect of dopamine D1 receptor antagonist SCH23390 on the behavior of PD rats,which may be exerted by changing the electrophysiological activity of EP.