Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIr^SST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIr^SST-Re tri-synaptic circuit in mediating the innate fear response.
Mice ; Animals ; Zona Incerta/metabolism* ; Neurons/metabolism* ; Fear/physiology* ; Somatostatin/metabolism*

Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2⁺) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST⁺), but not protein kinase C-δ-expressing (PKC-δ⁺), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2⁺ neurons. The SST⁺ neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST⁺ GABAergic neurons, but not PKC-δ⁺ GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeA^SST-DpMe^VGLUT2 circuit that regulates licking behavior and promotes water intake.

Objective To compare the efficacy and safety of tacrolimus with those of cyclosporine in treating idiopathic membranous nephropathy (IMN) via network meta-analysis. Methods Databases including PubMed,Embase,CENTRAL (Cochrane),Wanfang Database,CNKI,and VIP citation database were searched for relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Package Meta 4.5.0 and Gemtc 0.8.1 in R 3.3.1 were used to analyze the included studies. Results In this network meta-analysis,the complete remission rate (RR=0.98,95% CI:0.70-1.40)and the total remission rate (RR=1.00,95% CI:0.90-1.20)of idiopathic membranous nephropathy did not differ significantly between IMN patients treated with cyclosporine A or tacrolimusand,nor did the incidences of hepatic dysfunction(RR=1.40,95% CI:0.52-4.00),infection(RR=0.75,95% CI:0.18-3.10),or gastrointestinal syndrome(RR=2.1,95% CI:0.36-28.00). Conclusion Cyclosporine A seems to have similar effectiveness and safety to tacrolimus in treating IMN.

Objective: To study the difference of airway volume among the adolescent subjects with various vertical skeletal patterns. Methods: CBCT records of 88 adolescents with normal sagittal facial pattern were collected and divided into 3 groups according to their FH-MP angle. The subjects of the 3 groups were matched in age and sex. Airway volume and cross-sectional areas were compared among the 3 groups with Dolphin software. Correlation analyses of the airway dimensions with the maxillofacial variables was carried out. Results: There were statistical differences among the 3 groups in volumes of velopharynx,glossopharynx and oropharynx, minimal cross-section area of oropharynx and cross-section area on EP plane,and all the measurements decreased from low angle to normal angle to high angle groups(P ＜ 0. 05). Cross-section areas of HP plane and SP plane in low angle group were significantly larger than that of the normal angle and high angle groups(P ＜ 0. 05). The oropharyngeal airway dimensions showed negative correlation with FMA,and positive correlation with Co-Po,Ar-Gn (except cross-section area of HP). Conclusion: The pharyngeal airway volumes among different vertical skeletal patterns in adolescents are different.

Adolescent ; Adult ; Dust ; analysis ; Female ; Health Status ; Humans ; Male ; Middle Aged ; Occupational Exposure ; analysis ; Pneumoconiosis ; prevention & control ; Sentinel Surveillance ; Surveys and Questionnaires ; Welding ; Young Adult

OBJECTIVETo evaluate the influence of Fuzhenghuayu decoction on fibrotic liver tissue and activated hepatic stellate cells (HSCs) using a carbon tetrachloride (CCl4)-induced liver cirrhosis rat model system.

METHODSSixty-four Sprague-Dawley rats were randomly divided into the following groups: normal (non-model, non-drug intervention), CCl4 liver fibrosis model, and CCl4 liver fibrosis model Fuzhenghuayu drug intervention at low dose (0.75 g/kg/d) and high dose (1.5 g/kg/d). The drug intervention was administered via oral-gastric irrigation once daily for 6 times per week over a 6-week period. Four rats from each group were sacrificed at the end of week 2, 4, and 6 for serum and liver tissue collection. Liver fibrosis was evaluated by histology, and expression of a-smooth muscle actin (a-SMA) was determined by immunohistochemistry. Liver function was assessed by measuring levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil). Between-group comparisons were made by completely random design and ANOVA with Bonferroni correction.

RESULTSAt the end of weeks 2, 4 and 6, all four groups showed significantly different levels of ALT, AST, and TBil; in addition, the model group and drug intervention groups had significantly higher levels of ALT, AST, and TBil than the control group, the drug intervention groups showed significantly lower levels of ALT, AST, and TBil than the model group (P less than 0.01 or less than 0.05), and the differences between the low dose and high dose groups reached statistical significance (P less than 0.01 or less than 0.05). At the end of weeks 2, 4 and 6, the model group and drug intervention groups had significantly higher area ratio of liver fibrosis than the normal group (F = model: 18.68, low dose: 49.95, high dose: 82.44, P less than 0.01), but the two drug intervention groups had significantly less area ratio of liver fibrosis than the model group (P less than 0.05) and the high dose group showed the most robust decrease. In addition, the model group and drug intervention groups showed higher expression of a-SMA than the normal group (F = model: 18.68, low dose: 49.95, high dose: 82.44, P less than 0.01), but two drug intervention groups had significantly less a-SMA than the model group (F = model: 46.32, low dose: 40.30, high dose: 58.42, P less than 0.05) and the high dose group showed the most robust decrease.

CONCLUSIONThe Fuzhenghuayu decoction reduces the numbers of activated HSCs, thereby leading to down-regulated a-SMA expression and reduced degree of liver fibrosis; these effects may represent the mechanism by which this drug suppresses hepatic fibrosis.

Actins ; metabolism ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Hepatic Stellate Cells ; drug effects ; Liver ; drug effects ; pathology ; Liver Cirrhosis, Experimental ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVESTo evaluate the changes of the position of medulla oblongata and cerebellum following posterior fossa decompression (PFD), and to investigate their influences on the prognosis of the syringomyelia in adolescents with Chiari malformation (CM).

METHODSA retrospective review was performed on all CM patients between September 2006 and September 2011. A subset of 46 patients, including 25 male and 21 female patients, was finally enrolled according to the inclusion criteria. The initial age and duration of follow-up averaged 13.9 years (range, 10-17 years) and 13 months (range, 6-52 months), respectively. On mid-sagittal MRI, the following parameters were evaluated pre- and postoperatively (follow-up ≥ 6 months): the longitudinal and transverse position of bulbopontine sulcus, the fourth ventricle vertex, the lower extreme of cerebella tonsil, the cervico-medullary angle, the maximal syrinx/cord(S/C) ratio and the syrinx length. Changes in these parameters were analysed using the paired samples t test, and for these reaching statistical significances, an additional bivariate correlation analysis was performed to investigate their relation with syrinx resolution.

RESULTSAt the latest follow-up, upward shifting of the bulbopontine sulcus was observed in 31 patients(67.4%), with upward shifting of the lower extreme of cerebella tonsil presenting in 35 patients(76.0%). The maximal S/C ratio and the syrinx length were significantly improved postoperatively (t = 7.114 and 7.816, P = 0.000).Significant resolution of the syrinx was demonstrated in 40 patients(86.9%), and more specifically, the average improvement rates of the maximal S/C ratio and the syrinx length were 32% ± 30%and 43% ± 33%, respectively. In addition, the bivariate correlation analysis revealed that syrinx resolution was significantly correlated with the upward shifting of the bulbopontine sulcus (r = 0.332, P = 0.027) and lower extreme of cerebella (r = 0.298, P = 0.044) .

CONCLUSIONThe upward shifting of the bulbopontine sulcus and the lower extreme of cerebella tonsil might be implicated in the mechanisms of postoperative syrinx resolution.

Adolescent ; Arnold-Chiari Malformation ; complications ; surgery ; Child ; Decompression, Surgical ; Female ; Humans ; Male ; Medulla Oblongata ; pathology ; Postoperative Period ; Retrospective Studies ; Syringomyelia ; complications ; surgery ; Treatment Outcome

OBJECTIVETo explore the clinical indication of N3 lymph node biopsy during mediastinoscopy for non-small cell lung cancer (NSCLC).

METHODSCervical mediastinoscopy was performed in 89 patients with clinical stage I-IIIA non-small cell lung cancer prior to thoracotomy. Of those, 12 underwent cervical medistinoscopy combined with right scalene lymph node biopsy and 10 with anterior mediastinotomy.

RESULTSNine patients were found to have lymph node metastasis (N3 disease) during mediastinosopy. Of those, 6 had contralateral mediastinal lymph node metastasis and 3 cases with right scalene lymph node metastasis. The incidence of N3 disease in the patients with adenocarcinoma, serum CEA > 5 ng/ml and multi-station mediastinal lymph node metastasis was significantly higher than that in those with non-adenocarcinoma, CEA < 5 ng/ml and ipsilateral uni-station mediastinal lymph nodes metastasis (P < 0.05).

CONCLUSIONBiopsy of scalene lymph node or contralateral mediastinal lymph node should be performed during mediastinoscopy in order to exclude N3 disease for potentially operable NSCLC patients with adenocarcinoma, serum CEA >5 ng/ml and ipsilateral multi-station mediastinal lymph nodes metastasis.

Adenocarcinoma ; blood ; pathology ; Adult ; Aged ; Biopsy ; Carcinoembryonic Antigen ; blood ; Carcinoma, Non-Small-Cell Lung ; blood ; pathology ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; blood ; pathology ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Mediastinoscopy ; Mediastinum ; Middle Aged ; Neck Muscles ; Neoplasm Staging

OBJECTIVETo discuss the strategy of mediastinoscopy for the evaluation of mediastinal lymph node status (metastasis or not) of non-small cell lung cancer (NSCLC) prior to surgery.

METHODSFrom October 2000 to June 2007, 152 consecutive NSCLC cases pathologically proven and clinically staged I-III were enrolled in the study. Of the 152 cases, there were 118 males and 34 females. Age ranged 24-79 years old and the median age was 58. All cases underwent CT and mediastinoscopy for the evaluation of mediastinal lymph node status prior to surgery. Compared with the results of final pathology, the positive rate of mediastinoscopy and the prevalence of mediastinal lymph node metastasis were calculated in the NSCLC patients with negative mediastinal or hilar lymph nodes on CT scan (the shortest axis of mediastinal or hilar lymph nodes <1 cm). Clinical characteristics used as predictive factor including sex, age, cancer location, type of pathology, T status, cancer type (central or peripheral), size of mediastinal lymph nodes (the shortest axis <1 cm or >1 cm) on CT scan and serum CEA level were analyzed by univariate and multivariate analysis with Binary logistic regression model to identify risk factors of mediastinal metastasis.

RESULTSThe positive rate of mediastinoscopy was 11.6% (8/69) and the prevalence of mediastinal metastasis was 20.1% (14/69) in NSCLC with negative mediastinal or hilar lymph nodes on CT scan respectively. In clinical stage I (cT1-2N0M0) NSCLC the positive rate of mediastinoscopy was 11.3% (7/62), N2 accounting for 6.5% (4/62) and N3 4.8% (3/62), respectively; and the prevalence of mediastinal lymph node metastasis was 19.4% (12/62), N2 ccounting for 14.6% (9/62) and N3 4.8% (3/62), respectively. In the whole group both univariate and multivariate analysis showed that adenocarcinoma or mediastinal lymph nodes > or =1 cm in the shortest axis on CT scan was an independent risk factor to predict mediastinal lymph node metastasis. In NSCLC with negative mediastinal or hilar lymph nodes on CT scan both univariate and multivariate analysis showed that adenocarcinoma was a predictor of mediastinal lymph node metastasis. Conclusion We recommend the policy of routine mediastinoscopy in NSCLC prior to surgery if the mediastinal staging was only based on CT scan. Mediastinal lymph nodes > or =1 cm in the shortest axis on CT scan mandates preoperative mediastinoscopy. Adenocarcinoma also indicates mandatory mediastinoscopy even with negative mediastinal or hilar lymph nodes on CT scan.

Adenocarcinoma ; diagnostic imaging ; pathology ; surgery ; Adult ; Aged ; Carcinoembryonic Antigen ; blood ; Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; pathology ; surgery ; Female ; Humans ; Logistic Models ; Lung Neoplasms ; diagnostic imaging ; pathology ; surgery ; Lymph Nodes ; diagnostic imaging ; pathology ; surgery ; Lymphatic Metastasis ; diagnostic imaging ; pathology ; Male ; Mediastinoscopy ; Mediastinum ; Middle Aged ; Neoplasm Staging ; Preoperative Period ; Risk Factors ; Tomography, X-Ray Computed ; Young Adult