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The mechanisms behind a lack of efficient fear extinction in some individuals are unclear. Here, by employing a principal components analysis-based approach, we differentiated the mice into extinction- resistant and susceptible groups. We determined that elevated synapsin 2a (Syn2a) in the infralimbic cortex (IL) to basolateral amygdala (BLA) circuit disrupted presynaptic orchestration, leading to an excitatory/inhibitory imbalance in the BLA region and causing extinction resistance. Overexpression or silencing of Syn2a levels in IL neurons replicated or alleviated behavioral, electrophysiological, and biochemical phenotypes in resistant mice. We further identified that the proline-rich domain H in the C-terminus of Syn2a was indispensable for the interaction with synaptogyrin-3 (Syngr3) and demonstrated that disrupting this interaction restored extinction impairments. Molecular docking revealed that ritonavir, an FDA- approved HIV drug, could disrupt Syn2a- Syngr3 binding and rescue fear extinction behavior in Syn2a-elevated mice. In summary, the aberrant elevation of Syn2a expression and its interaction with Syngr3 at the presynaptic site were crucial in fear extinction resistance, suggesting a potential therapeutic avenue for related disorders., Introduction Posttraumatic stress disorder (PTSD) is a debilitating neuropsychiatric disorder (1) with complicated psychological and neurobiological mechanisms involving varied brain circuits mediating stress and fear responses (2-4), as well as [...]

BackgroundActivated hepatic stellate cells are the main source of excessive collagen deposition in liver fibrosis. Here we report the inhibitory effects of the combinational treatment of two natural products, astragalus polysaccharide (APS) and β-elemene (ELE) on the activation of human liver hepatic stellate cell line LX-2 cells.MethodsCultured LX-2 cells were treated with different concentrations of APS or ELE for 24 or 48 hours. Cell viability/apoptosis was measured by MTT assay and Annexin V/PI staining , activation related genes including α-SMA and CD44 expressions were measured by real-time PCR and western blot respectively.ResultsThe majority of LX-2 cells showed morphological change in the presence of APS or ELE for 24 hours. Treatment with APS + ELE for 24 or 48 hours significantly inhabited the cell proliferation compared with APS or ELE treatment alone on LX-2 cells. APS + ELE may block the up-regulation of α-SMA and CD44 both in mRNA and protein levels through TGF-β pathway in LX-2 cells.ConclusionAPS or ELE treatment alone on LX-2 cells could inhibit cell proliferation and induce apoptosis. The combinational treatment using APS + ELE significantly increased the killing efficiency on LX-2 cells. α-SMA and CD44 expressions was inhibited upon APS + ELE treatment through TGF-β pathway in LX-2 cells. The results indicated a novel treatment using natural products for liver diseases with anti-fibrotic effect.

To explore advantages of Chinese medicine (CM) by analyzing differences in the origin of philosophy for human health between CM and Western medicine (WM). Methodologically, a distinctive feature of CM is its systems theory, which is also the difference between CM and WM. Since the birth of CM, it has taken the human body as a whole from the key concepts of "qi, blood, yin-yang, viscera (Zang-Fu), and meridian and channel", rather than a single cell or a particular organ. WM evolves from the Western philosophic way of thinking and merely uses natural sciences as the foundation. The development of WM is based on human structures, or anatomy, and therefore, research of WM is also based on the way of thinking of decomposing the whole human body into several independent parts, which is the impetus of promoting the development of WM. The core of CM includes the holistic view and the dialectical view. Chinese herbal medicines contain various components and treat a disease from multiple targets and links. Therefore, Chinese herbal medicines treat a diseased state by regulating and mobilizing the whole body rather than just regulating a single factor, since the diseased state is not only a problem in a local part of the body but a local reflection of imbalance of the whole body.

A large amount of size tunable zeolitic imidazolate framework-67 (ZIF-67) was synthesized in a shot time with ultrasonic assisted method. The structure and morphology of synthesized materials were characterized with XRD and SEM. Nitrogen adsorption-desorption technique was also used to characterize the synthesized ZIF-67. Results showed that the ZIF-67 prepared by this method had higher crystallinity, regular rhombic dodecahedral morphology, and higher porosity and specific surface area. As supercapacitor electrode materials, cyclic voltammetry (CV) and galvanostatic charge/discharge (GCD) measurements were carried out to test the electrochemical performance of synthesized materials. The results showed that ZIF-67 synthesized by ultrasonic assisted method delivered a specific capacitance of 93 F/g at 0. 5 A/g, which was much higher than that of ZIF-67 synthesized under static condition. When current density was 1 A/g, the specific capacitance of ZIF-67 synthesized by ultrasonic assisted method could be retained to 98. 6% of the initial value after 1000 cycles, demonstrating the excellent cycling stability. [ABSTRACT FROM AUTHOR]

Three dimensional flower-like NiCo2O4 was prepared by a hydrothermal method and annealing treatment. XRD and SEM were used to characterize the crystallization, element composition and morphology of synthesized material. The results showed that: 1) The crystallinity of the synthesized NiCo2O4 material was not high. 2) The material contained Ni and Co elements with different valences. The presence of the Ni2+/ Ni3+ and Co2+/Co3+ provided two active centers for the generation of pseudocapacitance. 3) As supercapacitor electrode material, the three dimensional flower-like NiCo2O4 displayed excellent electrochemical performance. [ABSTRACT FROM AUTHOR]

This study was design to investigate preventive function of Tongxinluo (TXL) capsule on micro vascular function and endothelial survival in rats model of intestine ischemia/reperfusion (I/R) injury. We randomly divided fifty male Sprague-Dawley rats into Sham group, I/R group, TXL0.4+I/R group, TXL0.8+I/R group, TXL1.6+I/R group (10 rats each). Rat intestine I/R injury was carried out using a model of acute superior mesenteric artery occlusion with 30 min ischemia followed by 60 min reperfusion. The distribution of endothelial apoptosis in intestine was determined by CD31+TUNEL immunofluorescent double staining analysis. VE-Cadherin, ANGPTL4, HMGB1 and NF-κB were determined by immunohistochemical analysis. I/R induced massively endothelial cell apoptosis, accompanied with reduced expression of adherens junction protein VE-Cadherin and up regulation of inflammatory mediator HMGB1 and NF-κB. TXL pretreatment groups (TXL0.4+I/R, TXL0.8+I/R and TXL1.6+I/R group) significantly attenuated endothelial cell apoptosis with a dose-dependent effect. TXL pretreatment could maintain the expression of VE-Cadherin and promote the expression of ANGPTL4 which help to maintain endothelial integrity. TXL pretreatment also exert great influence in inhibiting HMGB1 expression and NF-κB expression induced by I/R. It could be concluded from this study that micro vascular dysfunction and endothelial damage play a causal role in rat intestine I/R injury. TXL pretreatment could significantly prevent the I/R induced pathology of endothelial apoptosis, micro vascular integrity disruption and inflammatory reaction.

Objective: To explore the mechanism underlying the therapeutic effect of Bushen Huoxue Decoction (BHD), a traditional Chinese medicinal preparation, on dopamine D2 receptor (DRD2) in the brain of rat models of Parkinson's disease (PD)., Methods: A total of 120 SD rats were randomized into normal control group, saline model group and BHD-treated group. In the latter two groups, PD rat models were established by direct injection of 6-OHDA to destruct the substantia nigra compact part (SNC) with corresponding treatments. The behavioral changes of the rats were observed. Radioimmunoassay was employed to determine the changes in the equilibrium dissociation constant (Kd) and maximal binding capacity (B(max)) of DRD2, and immunohistochemistry was used to observe the number of the DRD2-positive cells in the brain of the rats., Results: BHD can markedly improve the behavioral abnormalities of PD model rats. Compared with those in the saline model group, the B(max) of DRD2 in the damaged hemisphere increased while the Kd of BHD decreased significantly after BHD treatment (P<0.01). The number of DRD2-positive cells in BHD-treated group was significantly higher than that in the model group (80.9∓13.59 vs 11.15∓6.78, P<0.01), but showed no significant difference from that in the normal control group (P>0.05)., Conclusion: BHD can improve the behavioral abnormalities and increase the cerebral expression and affinity of DRD2 in PD rat models.

Objective: To study the effects of Bushenhuoxue Granules on Parkinson's disease sleep scale (PDSS) score in Parkinson's patients., Methods: 120 patients were enrolled and divided into two groups randomly,the control group were treated with placebo and treatment group with Bushenhuoxue Granules, both group based on Madopar treatment. Double-blinded clinical trial was adopted in treatment period. Follow-up period for 6 months, PDSS was adopted to measure sleep condition of PD patients at baseline time, after 3 months and after 9 months., Results: Bushenhuoxue Granules treatment group showed a higher efficacy than the placebo group in relieving the sleep disorders of Parkinson disease patients,both in treatment and follow-up period (P < 0.01). No adverse effects were found in this trial., Conclusions: Bushenhuoxue Granules can markedly improve sleep disorders in Parkinson's patients. The effects are stable and obvious along with the process of treatment.

Objective: To observe the effect of Bushen Huoxue Granule (BHG) on dopamine (DA) neurotransmitter and dopamine transporter (DAT) in the brain of patients with Parkinson's disease (PD) as an adjunctive therapy., Methods: Ninety-four PD patients were randomly assigned to two groups, 47 in each group. Madopar was given to all as the basic treatment group. The placebo was given to those in the control group while BHG was given to those in the treatment. The therapeutic course for all was three months. Before and after treatment DA levels in the brain of patients were detected by encephalofluctuograph (EFG) technique. Changes of DAT in the striatum of patients in the treatment group were detected by positron emission tomography (PET) and region of interest (ROI) analysis., Results: (1) Before treatment the DA level was lower in the two groups than the normal value, showing significant difference (P < 0.01), but with no significant difference between the two groups (P > 0.05). After treatment the DA level obviously increased in the two groups, showing significant difference from that before treatment (P < 0.01). No significant difference existed in the DA level in the two groups when compared with the normal value (P > 0.05), but with significant difference between the two groups (P < 0.05). Better results were obtained in the treatment group than in the control group. (2) The DAT radioactive accumulation inside the striatum increased obviously in the treatment group after treatment. ROI analysis showed the total ratio of striatum/cerebellum before and after treatment was 1.86 +/- 0.32 and 2.61 +/- 0.53 respectively, showing statistical difference (P < 0.05)., Conclusion: BHG could improve the DA level of PD patients, and increasing DAT contents in the striatum, thus playing a role in effectively treating PD.

Objective: To observe the effects of Bushenhuoxue Yin (BSHXY), a compound traditional Chinese herbal medicine, on nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) levels in the brain of a mouse model of Parkinson disease (PD)., Methods: Forty-five C57BL/6 mice were randomized into MPTP-induced PD model group, BSHXY treatment group and normal control group. The contents of NO and the two cytokines in the brain tissue of the mice were determined by spectroscopy and enzyme-linked immunosorbent assay, respectively., Results: The concentration of NO in the brain tissue of the PD model group was 5.93 ∓ 0.79 µmol/g.protein, significantly higher than that in BSHXY group (P<0.01) and normal control group (P<0.01). The levels of TNF-α and IFN-γ in the PD model group were 0.36 ∓ 0.11 ng/L and 0.83 ∓ 0.25 ng/L, respectively, also higher than those in the other two groups (P<0.01 or 0.001). But BSHXY group and the normal control group showed no significant differences in the levels of NO, TNF-α and IFN-γ (P>0.05)., Conclusion: The therapeutic effect of BSHXY on PD is partially attributed to decreased content of NO, TNF-α and IFN-γ in the brain.

Objective: To observe the improving effect of scalp point penetration needling on sleep quality and sleep structure for insomnia patients., Methods: Sixty-six cases of insomnia were randomly divided into a scalp point penetration needling group (observation group, 32 cases) and a routine acupuncture group (control group, 34 cases). The observation group was treated with Houshencong (EX-HN 1) penetrating to Qianshencong (EX-HN 1) and Xinhui (GV 22) penetrating to Shenting (GV 24) etc.; Baihui (GV 20), Anmian (EX- HN 22) and Neiguan (PC 6) etc. were selected in control group. The Pittsburgh Sleep Quality Index (PSQI) and micro-sensitive mattress sleep monitoring system were used to observe the sleep quality and sleep structure of the patients before and after treatment, respectively., Results: The completely improved rate of the sleep quality of 65. 6%(21/32)in observation group was superior to that of 35.3 (12/34) in control group (P < 0.05). There were significant differences between two groups in latency of falling asleep, total time of sleep, time of deep sleep stage and more than 5 min awakening times of sleep structure after treatment (all P < 0. 01), the observation group was superior to control group., Conclusion: The scalp point penetration needling has more significant effects for improving the sleep quality and sleep structure of insomnia patients than the routine needling.

Background: Insomnia has become a threat to public health, and acupuncture has shown an advantage in treatment of insomnia with good efficacy and few side effects., Objective: To observe the therapeutic effects of scalp penetration acupuncture for insomnia., Design, Setting, Participants and Interventions: A total of 70 insomnia cases meeting inclusion criteria from Department of Acupuncture and Moxibustion, General Hospital of People's Liberation Army were randomly divided into routine acupuncture group and scalp penetration acupuncture group. There were 32 cases in the scalp penetration acupuncture group, and 34 cases in the routine acupuncture group, for four cases lost to follow-up. The insomnia patients were all treated for four weeks., Main Outcome Measures: The therapeutic effects, cumulative scores of Pittsburgh Sleep Quality Index (PSQI) and contents of sleep architecture were compared before and after treatment in the two groups., Results: The total response rate of 90.6% in the scalp penetration acupuncture group was higher than 73.5% in the routine acupuncture group (P<0.05), and the improvements of PSQI cumulative scores in sleep quality, sleep time and sleep efficiency in the scalp penetration acupuncture group were superior to those in the routine acupuncture group (P<0.05, P<0.01). The total sleep time and deep sleep time of sleep architecture in the scalp penetration acupuncture group significantly increased as compared with those in the routine acupuncture group (P<0.01)., Conclusion: The therapeutic effects of scalp penetration acupuncture are better than those of routine acupuncture, especially for improving sleep quality, sleep time and sleep efficiency.

Objective: To summarize the clinical characteristics of severe acute respiratory syndrome (SARS) and observe the therapeutic effect with integrative Chinese and western medicine (ICWM) approach in treating patients with SARS., Methods: Forty-eight patients selected from the authors' hospital, whose diagnosis confirmed as SARS were analysed to sum-up the diagnostic type and basic feature of patients and the chief clinical characteristics. All the patients were randomly divided into the trial group and the control group, 24 in each. The control group was treated with the western medical therapeutic program and the trial group was treated with ICWM therapeutic program. The differences between the two groups were compared in terms of development of illness, time of using corticosteroid and absorption time of pulmonary inflammatory lesion, etc., Results: Most patients were youth and adult aged between 18 to 40 years old, the initial symptom was mainly the high fever, accompanied with general soreness, chest stuffiness and cough, etc. The hospitalization time, body temperature fluctuation sustaining time and time of using corticosteroid in the trial group were shorter than those in the control group, showing significant difference (P < 0.05). ICWM treatment showed a better effect in defervescence and inflammatory lesion absorption time, but with no statistical significance., Conclusion: Patients of SARS are mainly youth and adults in the prime of life, fever always appears as the initiation of illness and some accompanying symptoms would appear. As compared with the western treatment, ICWM treatment could evidently shorten the course of illness, prevent the rebounding of fever and reduce the time of using corticosteroid.