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Fear, a negative emotion triggered by dangerous stimuli, can lead to psychiatric disorders such as phobias, anxiety disorders, and depression. Investigating the neural circuitry underlying congenital fear can offer insights into the pathophysiological mechanisms of related psychiatric conditions. Research on innate fear primarily centers on the response mechanisms to various sensory signals, including olfactory, visual and auditory stimuli. Different types of fear signal inputs are regulated by distinct neural circuits. The neural circuits of the main and accessory olfactory systems receive and process olfactory stimuli, mediating defensive responses like freezing. Escape behaviors elicited by visual stimuli are primarily regulated through the superior colliculus and hypothalamic projection circuits. Auditory stimuli-induced responses, including escape, are mainly mediated through auditory cortex projection circuits. In this article, we review the research progress on neural circuits of innate fear defensive behaviors in animals. We further discuss the different sensory systems, especially the projection circuits of olfactory, visual and auditory systems, to provide references for the mechanistic study of related mental disorders.
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Animais , Humanos , Medo/fisiologia , Rede NervosaRESUMO
Cardiovascular disease is still the leading cause of mortality worldwide. Vascular endothelial dysfunction is viewed as the initial step of most cardiovascular diseases. Many studies have indicated that periodontal pathogens, especially Porphyromonas gingivalis, are closely correlated with vascular endothelial homeostasis, but the function of P. gingivalis and the underlying mechanisms are still elusive. To illuminate the effects and elucidate the mechanisms of P. gingivalis on endothelial structural integrity, we developed P. gingivalis infection models in vivo and in vitro. Endothelial cell proliferation, differentiation and apoptosis were detected. Here, we showed that P. gingivalis can impair endothelial integrity by inhibiting cell proliferation and inducing endothelial mesenchymal transformation and apoptosis of endothelial cells, which reduce the cell levels and cause the endothelium to lose its ability to repair itself. A mechanistic analysis showed that TLR antagonist or NF-κB signalling inhibitor can largely rescue the damaged integrity of the endothelium caused by P. gingivalis, suggesting that TLR-NF-κB signalling plays a vital role in vascular endothelial homeostasis destroyed by P. gingivalis. These results suggest a potential intervention method for the prevention and treatment of cardiovascular disease.
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Objective To investigate the effect of enhanced external counterpulsation (EECP) on plasma lipoprotein phospholipase A2 (LP-PLA2) levels, vascular endothelial diastolic function in patients with unstable angina. Methods One hundred patients with unstable angina treated in our hospital were randomly divided into routine treatment group (control group n-49) and external counterpulsation group (observation group n = 51, routine treatment plus external counterpulsation therapy, 60 min/time, a total of 30 times). All selected subjects were tested for LP-PLA2 levels on the day of enrollment and on the 30 th day after treatment, and color Doppler ultrasonography was used to detect arterial blood flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD). Results After treatment in the observation group, LP-PLA2 decreased compared with before treatment, the difference was statistically significant (P < 0.05) , but FMD, NMD were higher than those before treatment, which had statistical difference (P < 0.05). In control group treatment afterwards, LP-PLA2, endothelium-dependent vasodilatation and non-endothelium-dependent vasodilatation did not change significantly before treatment (P> 0.05). Observations between groups showed that the increase in FMD and NMD in the observation group was significantly greater than that in the control group. P < 0.01) , plasma LP-PLA2 levels in the observation group also decreased compared with the control group (P < 0.05). Conclusion Enhanced external counterpulsation can reduce the level of LP-PLA2 in patients and improve endothelial diastolic function under the action of blood flow shear stress.
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Objective To investigate the correlation of plasma heme oxygenase-1 (HO-1) level and type 2 diabetes mellitus (T2DM). Methods The outpatient with type 2 diabetes mellitus (T2DM) undergoing oral glucose tolerance test and healthy individuals with physical examination were divided into T2DM group and healthy control group, the differences between the two groups in HO-1 and methane dicarboxylic aldehyde (MDA), mean fluorescence intensity (MFI), homeostasis model assessment of insulin resistance (HOMA-IR) and fasting blood glucose (FBG) were comparatively analysed , and analyzed the correlations between HO-1 and reactive oxygen species (ROS) MFI, MDA, HOMA-IR and FBG. Results The type 2 diabetes group in MDA and MFI, the expression rate of HO-1 were higher than those of control group (P<0.05), correlation analysis of expression of HO-1 was positively correlated with MFI, MDA (r=0.489, 0.763, P<0.05) in the T2DM group, HO-1, HOMA-IR and FBG were significantly higher than the healthy control group, the difference was statistically significant(P<0.05). The expression of HO-1 and HOMA-IR and FPG levels were positively correlated in the T2DM group (r=0.271, 0.426, P <0.05). Conclusion T2DM patients with hyperglycemia and oxidative stress, plasma HO-1 expression is significantly increased, HO-1 is related to oxidative stress, insulin resistance and hyperglycaemia, which has certain value on clinical assessment of T2DM and therapeutic efficacy.
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BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) with multiple differentiation potential can be induced into osteogenic or adipogenic differentiation under certain conditions. OBJECTIVE: To review the related factors regulating the adipo-osteogenic differentiation of BMSCs. METHODS: A computer-based search of CNKI and PubMed databases was performed for literature concerning the related factors regulating the adipo-osteogenic differentiation of BMSCs published from January 2006 to August 2016. The search terms were bone marrow mesenchymal stem cells, osteogenic differentiation, adipocyte differentiation in Chinese and English, respectively. RESULTS AND CONCLUSION: Signaling pathways, transcription factors, and smal molecule compounds that are interacted are key factors in the regulation of BMSCs differentiation, so the techniques to intervene BMSCs differentiation based on these key molecules may correct bone or fat abnormality and can be applied to tissue engineering and regenerative medicine in the future. Additionally, the biological clock is also one of the most important factors for adipo-osteogenic differentiation of BMSCs by regulating signaling pathways or transcription factors.
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Objective To investigate the safety and clinical effect of laparoscopic radical parametrectomy in the treatment of unexpected cervical cancer . Methods A retrospective analysis was made on clinical characteristics of 15 patients who were diagnosed as unexpected cervical cancer from January 2008 to December 2014.The age of the patients was between 29 and 67 years old, with an average of 43.9 years old.The indications for hysterectomy were cervical intraepithelial neoplasia (CIN) grade 2-3 in 7 cases, uterine myoma in 3 cases, dysfunctional uterine bleeding in 2 cases, uterine prolapse in 2 cases and adenomyosis in 1 case. Pathological results after the hysterectomy included 13 cases of cervical squamous carcinoma and 2 cases of adenocarcinoma .The lesions were all confined to the cervix , with 4 cases of stage ⅠA2 disease and 11 cases of stage ⅠB1 .The lymph-vascular space invasion was found in 4 cases.The operation interval between the two operations was 3-7 d (mean, 4.6 d).They were all given laparoscopic radical parametrectomy . Results The operation time was 212-285 min (mean, 249.6 min), and the blood loss was 250-500 ml ( mean, 376 ml) .Postoperative pathological findings showed no residual disease .Only one patient had left pelvic lymph node mestastasis .Two patients had intraoperative complications , including 1 bladder injury and 1 ureteral injury .There were 3 cases of postoperative complications , including 2 cases of uroschesis and 1 case of lymphocyst .The follow-up time was 6-84 months ( median, 48 months).No recurrence was seen.The 1-, 3-, 5-year survival rates were 100%, 93.3%, 86.7%, respectively. Conclusions Laparoscopic radical parametrectomy in the treatment of unexpected cervical cancer is difficult to perform and has more complications . This surgical method is applicable to those who refused postoperation radiotherapy or required retaining ovarian function .
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Aim To develop LC-MS/MS method to de-termine rasagiline mesylate in human plasma and its application in a pharmacokinetics study .Methods Plasma samples were extracted using liquid-liquid ex-traction with clopidogrel as internal standard .The con-tent of rasagiline mesylate in human plasma was detec-ted by selectivelypositive ion reaction monitoring on a triple quadrupoles tandem mass spectrometer .The de-tected ions were m/z 172.3→117.1 ( rasagiline ) , m/z 322.3 →184.0 ( clopidogrel ) .The linear calibration curve was obtained in the concentration range of 0.1047~20.93 μg · L-1 .The lower limit of quantifi-cation was 0.1047 μg · L-1 .Indicators of the method validation were in line with requirements .The method was used to determine the concentration of rasagiline in human plasma after oral administration of rasagiline mesylate capsule to 24 healthy Chinese volunteers ( with half males and females ) and the results were compared statistically .Results The single oral dose of 0.5 ,1.0 and 2.0 mg presented linear pharmacokinetics in the health volunteers .No accumulation was observed with multiple doses .Meanwhile , no significant difference was identified between the gender groups . High fat postprandial has obvious effects on the peak serum con-centration of rasagiline , but there was no effect on the absorption amount and cumulative excretion .Conclu-sion The LC-MS/MS method is specific and sensi-tive, and can be successfully applied to the pharmaco-kinetic study of Rasagiline mesylate tablets in healthy Chinese volunteers .
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ObjectiveTo investigate the relationship between gastrointestinal dysfunction and both severity and prognosis in patients with heatstroke (HS).Methods A retrospective analysis was conducted. Clinical data from 39 patients with HS seeking for treatment in Department of Critical Care Medicine of Chinese PLA General Hospital from January 2013 to September 2014 were enrolled. The patients were divided into two groups: gastrointestinal dysfunction group and non-gastrointestinal dysfunction group. The acute physiology and chronic health evaluationⅡ(APACHEⅡ) score within 24 hours of admission and 28-day mortality were compared between two groups. In gastrointestinal dysfunction group, the gastrointestinal dysfunction score, the duration days of gastrointestinal dysfunction, the length of intensive care unit (ICU) stay, and the duration of mechanical ventilation were collected. Pearson correlation analysis was used to analyze the relationship between gastrointestinal function and the severity of the ailment as well as the prognosis.Results Among 39 patients with HS, 32 of them showed gastrointestinal dysfunction with an incidence of 82.05%. In gastrointestinal dysfunction group, the gastrointestinal dysfunction score was 2.3±0.8, the duration of gastrointestinal dysfunction was (17.3±15.2) days, the length of ICU stay was (37.8±25.0) days, and the duration of mechanical ventilation was (27.8±14.0) days. APACHEⅡ score in gastrointestinal dysfunction group was significantly higher than that of the non-gastrointestinal dysfunction group (26.30±6.00 vs. 17.40±6.00, t = 3.555,P = 0.001). The 28-day mortality in gastrointestinal dysfunction group was slightly higher than that of the non-gastrointestinal dysfunction group without statistically significant difference [43.75% (14/32) vs. 14.29% (1/7),P = 0.216]. It was shown by Pearson analysis that gastrointestinal dysfunction score was positively correlated with APACHEⅡ score (r = 0.727,P = 0.000), and the duration of gastrointestinal dysfunction was positively correlated with the length of ICU stay (r = 0.797,P = 0.000) and the duration of mechanical ventilation (r = 0.634,P = 0.000). Conclusion The results suggest that gastrointestinal function in patients with HS reflects the severity and prognosis of the ailment.
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To study the transport mechanisms of drugs for transplacental treatment of fetal tachyarrhythmia, MDCKII-BCRP and MDCKII cell models was used. MDCKII-BCRP and MDCKII cell monolayer model was used to investigate the bi-direction transport of sotalol, propranolol, propafenone, procainamide and flecainide. Drug concentrations were measured by HPLC-UV or chemiluminescence. The apparent permeability coefficient (P(app)), efflux rate (R(E)) and net efflux rate (R(net)) were calculated. Drugs with R(net) greater than 1.5 were further investigated using cellular accumulation experiments with or without a BCRP inhibitor. The R(net) of sotalol, propranolol, propafenone and procainamide were less than 1.5, while R(net) of flecainide with concentrations of 20 and 5 μmol x L(-1) were 1.6 and 1.9, respectively. The results showed that the transport of flecainide on MDCKII-BCRP cell monolayer could be mediated by BCRP; and the affinity increased when the concentration of flecainide decreased. Cellular accumulation experiments further suggested that accumulation of flecainide in MDCKII-BCRP cells was significantly lower than that in MDCKII cells in a concentration-dependent manner. BCRP inhibitor quercetin (50 μmol x L(-1)) significantly increased the accumulation of flecainide in MDCKII-BCRP cells (P < 0.05). Our preliminary data showed that flecainide but not sotalol, propranolol, propafenone or procainamide can be a substrate of BCRP. Thus the effect of flecainide may be affected by the BCRP in the maternal placental trophoblast membrane layer when treating fetal tachyarrhythmia.
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Objective To investigate the underlying causes, clinical characteristics, treatment and prognosis of non-traumatic pneumomediastinum (PM) in children. Methods A retrospective analysis of the clinical data of 64 children diagnosed with non-traumatic PM in Yuying Children’s Hospital Affiliated to Medical University from Jan 2003 to Dec 2013 was performed. Nineteen children with SPM and the other 45 with clear causes of non-traumatic PM were divided into two groups for comparison. According to age, 64 cases were divided into 0-6y group and 6-18y group for further comparison. Results A total of 64 patients with non-traumatic PM were collected. Nineteen of them aged 14.90±2.00 y had SPM with unknown etiology, and 84.2%were male. The other group of 45 patients aged 4.26±4.45y, and 55.6%of this group were male. The common causes were pneumonia or other lower respiratory tract infection, asthma and foreign body inspiration. The patients with SPM were always with chest pain. While the patients with clear causes of non-traumatic PM were more complained of dyspnea, coughing, subcutaneous emphysema. The treatment of patients with SPM was bed rest, oxygen uptaking, antitussive, anti-infection and other conservative therapy. All the patients with clear causes of non-traumatic PM had favorable prognosis with the treatment of actively curing primary disease and timely mediastinal air drainage, subcutaneous air drainage and thoracic close drainage. In 35 cases younger than 6 years old, the most common causes were pneumonia or other lower respiratory tract infection, none had SPM. In 29 cases older than 6 years, 19 of them had SPM. Conclusions Etiologies of pneumomediastinum varied with age in children,which should be vigilantly examined, especially for those younger than 6 years old. The key of the treatment to non-traumatic PM with clear etiologies was to treat its primary disease.
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Adipose stem cel s have been confirmed to promote the repair of soft tissue after damage, and the action mechanism is possibly related to the paracrine of adipose stem cel s, that is adipose stem cel s secrete a variety of cytokines, which may promote the restoration of damaged cel s. However, little report addressed the types of adipose stem cel s secreted factors, contents of each factor, and role in soft tissue repair after damage, especial y oral mucosa. To observe the influence of vascular endothelial growth factor, platelet-derived growth factor, and basic fibroblast growth factor in adipose stem cel-conditioned medium on the proliferation of oral mucosa fibroblasts. Protein microarray analysis was used to analyze the contents of vascular endothelial growth factor, platelet-derived growth factor, and basic fibroblast growth factor in adipose stem cel-conditioned medium. CCK8 analysis was used to analyze the effects of adipose stem cel-conditioned medium with different concentrations of vascular endothelial growth factor, platelet-derived growth factor, and basic fibroblast growth factor (0, 1, 10, 20, 50 and 100μg/L) or the neutralizing antibody of the three kinds of cytokines on the proliferation of oral mucosa fibroblast on 1, 2, 3, 4 and 5 days. High contents of vascular endothelial growth factor, platelet-derived growth factor, and basic fibroblast growth factor were contained in adipose stem cel-conditioned medium (signal value>300). Adipose stem cel-conditioned medium could promote the proliferation of oral mucosa fibroblasts, wherein, the promotion effects of platelet-derived growth factor and basic fibroblast growth factor were very significant, and the peak changes could be observed with variation of cytokines concentrations. The optimal concentrations of platelet-derived growth factor and basic fibroblast growth factor were 50μg/L and 1μg/L, respectively (P ≤ 0.05). The neutralizing antibody of platelet-derived growth factor and basic fibroblast growth factor inhibited the promotion effect of adipose stem cel-conditioned medium. On the other hand, vascular endothelial growth factor had no significant effect on the proliferation of oral mucosa fibroblasts. Adipose stem cel-conditioned medium can promote the proliferation of oral mucosa fibroblasts, platelet-derived growth factor and basic fibroblast growth factor in adipose stem cel-conditioned medium have obvious promotion effects, which are dependent on the cytokine concentrations. Therefore, we should pay attention to choose the optimal concentrations of cytokines, thereby effectively promoting the proliferation of fibroblasts.
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Along with the development of the modernization of traditional Chinese medicine (TCM), the acupunc-ture related software has also been developed. This article was aimed to combine traditional acupuncture therapy with the modern information technology in order to design software which is practical for clinical guidance in the acupoint selection and treatment according to diseases. This software provides a convenient and effective self-acupuncture treatment program for the public. It makes TCM acupuncture popular in the public and further pro-motes the development of TCM .
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<p><b>OBJECTIVE</b>To study the effect of BRCA1 in regulating the proliferation and migration of breast cancer cells stimulated by progesterone.</p><p><b>METHODS</b>Breast cancer MCF-7 and T-47D cell were transfected with a vector containing the coding sequence of BRCA1 (pFlag-CMV2-BRCA1 wt) to induce BRCA1 overexpression or with the empty vector (control). The cells were then stimulated with progesterone, and the cell proliferation and migration were observed using MTT assay and wound healing assay, respectively. The proliferation and migration of MCF-7 cells were also observed following transfection with a small interfering RNA (siRNA) for BRCA1 knockdown or with a scrambled siRNA prior to progesterone stimulation.</p><p><b>RESULTS</b>Transfection with the empty vector and with pFlag-CMV2-BRCA1 wt prior to progesterone stimulation caused significantly different proliferation rates in MCF-7 cells [(114.4∓6.0)% vs (82.1∓3.2)%, P<0.05] and in T-47D cells [(111.3∓4.3)% vs (84.2∓3.5)%, P<0.05], resulting also in significantly different cell migration rates (55.9% vs 15.8% in MCF-7 cells and 44.83% vs 10.43% in T-47D cells). Compared to the scrambled siRNA, BRCA1 siRNA transfection prior to progesterone stimulation significantly increased the proliferation rates [(114.4∓3.05)% vs (125.3∓4.0)%, P<0.05] and migration rate (39.2% vs 69.08%) of MCF-7 cells. The progesterone antagonist RU468 could antagonize the effects of BRCA1 knockdown in enhancing progesterone-stimulated MCF-7 cell proliferation and migration.</p><p><b>CONCLUSION</b>A decreased BRCA1 expression can enhance progesterone-stimulated tumor cell proliferation and migration in sporadic breast cancer.</p>