Objectives: To investigate whether the protective actions of ginsenoside Rb1 (Rb1) on astrocytes are mediated through the Gs-type G-protein-coupled receptor (GPCR-Gs). Methods: Primary astrocyte cultures derived from neonatal mouse brain were used. Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation (OGD/R). Cell morphology, viability, lactate dehydrogenase (LDH) leakage, apoptosis, glutamate uptake, and brain-derived neurotrophic factor (BDNF) secretion were assessed to gauge cell survival and functionality. Western blot was used to investigate the cyclic adenosine monophosphate (cAMP) and protein kinase B (Akt) signaling pathways. GPCR-Gs-specific inhibitors and molecular docking were used to identify target receptors. Results: Rb1 at concentrations ranging from 0.8 to 5 μM did not significantly affect the viability, glutamate uptake, or BDNF secretion in normal astrocytes. OGD/R reduced astrocyte viability, increasing their LDH leakage and apoptosis rate. It also decreased glutamate uptake and BDNF secretion by these cells. Rb1 had protective effects of astrocytes challenged by OGD/R, by improving viability, reducing apoptosis, and enhancing glutamate uptake and BDNF secretion. Additionally, Rb1 activated the cAMP and Akt pathways in these cells. When the GPCR-Gs inhibitor NF449 was introduced, the protective effects of Rb1 completely disappeared, and its activation of cAMP and Akt signaling pathways was significantly inhibited. Conclusion Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-Gs mediation.

Objective To study mental status of recovered two year after in shake area crowd of gansu wen-xian. Methods Fifty former disaster crowd were assessed with SCL-90, Coping Style Questionnaire and Social Support Questionnaire two year after their discharge, 50 healthy medical staffs of gan-su CTM Affiliated Hospital of logistics ensure center were assessed with same instruments as control. Results The former disaster crowd and 5 subscores of SCL-90 with higher average scores than Chinese norm and results of control, they were somatization( F =4. 31) , phobia ( F = 5. 25) , obtrude ( F =5. 91) , P＜0. 01, depression ( F = 3. 11) anxiety ( F = 3. 74) , P ＜ 0. 05; The former disaster crowd felt more objective support, used more rationalization, but were less capable in problem solving. In former disaster crowd, problem-solving, objective social support and utility of the support were negatively correlated with subscores of SCL-90 ( r = -0. 31～-0. 40, P ＜0. 05) ; while immature coping, such as fantasy, withdrawal and rationalization were positively correlated with subscores of SCL-90 ( r = 0. 40 ~ 0. 60, P ＜ 0. 05).Conclusion Former disaster crowd still have psychosomatic symptoms and need social and psychology intervene and support.

There is a bidirectional relationship between intestinal flora and bile acids,and the imbalance of intestinal flora-bile acid axis metabolism is closely related to hypertension.Based on classical TCM literature and clinical practice,this article found that"earth deficiency"is the important pathological basis of hypertension,"wood depression"is the initiating factor of hypertension,and"earth deficiency and wood depression"is the key pathogenesis of hypertension.Combined with the research results of modern medicine and molecular biology,it is considered that the imbalance of intestinal flora and abnormal bile acid metabolism are closely related to the"earth deficiency"and"wood depression"of TCM respectively,and the imbalance of intestinal flora-bile acid axis coincides with the"earth deficiency and wood depression"of TCM in the process of hypertension.It is of great theoretical and practical significance to explore the biological connotation of hypertension"earth deficiency and wood depression"from the perspective of intestinal flora-bile acid axis for guiding TCM to prevent and treat hypertension.

Hypertension is one of the most common cardiovascular diseases in clinic.TCM mostly treats it from the aspects of liver,kidney,spleen,and qi and blood,and often receives good clinical efficacy.But its modern scientific connotation still needs to be further elucidated.In recent years,it has been found that the intestinal flora is obviously related to the host's blood pressure and closely related to the function of dispersing liver-qi in TCM,so the"liver-intestine-bacteria"axis may become a new way to regulate hypertension.Based on the theory of"connection between liver and large intestine",this article discussed the correlation between liver-intestine-bacteria-hypertension with intestinal flora as the starting point,in order to provide some theoretical reference for the treatment of hypertension from liver.

Objective:To analyze the survival efficacy, prognostic factors and failure patterns of patients with esophageal squamous cell carcinoma (ESCC) underwent postoperative radiotherapy (PORT) using modified clinical target volume (CTV) based on postoperative high-frequency recurrence regions, so as to provide reference for the further optimization of CTV of PORT.Methods:The patients with ESCC underwent radical operation in Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 28, 2014 to November 29, 2018 were retrospectively analyzed. Patients with stage pT 3-4aN 0 or N +, who underwent PORT with modified CTV based on postoperative high-frequency recurrence regions, were included in the study. Kaplan-Meier method was used to calculate overall survival (OS) and locoregional recurrence free survival (LRFS) , adverse events of patients were evaluated, Cox proportional hazards model was used for univariate and multivariate survival analysis, and the failure patterns of patients after PORT were analyzed. Results:A total of 85 patients were included in this study, and the median follow-up time was 52.6 months. The median OS of the whole group was 74.1 months. The 1-year, 2-year and 3-year OS rates were 97.6%, 84.7% and 71.7% respectively. The median LRFS was not reached, and the 1-year, 2-year and 3-year LRFS rates were 92.9%, 78.6% and 71.5% respectively. The incidence of grade 3-4 adverse events was 17.6% (15/85) , mainly including lymphopenia, bone marrow suppression, gastrointestinal reaction and skin reaction. Univariate analysis of OS after PORT showed that the degree of differentiation (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=4.19, 95% CI: 1.91-9.17, P<0.001; NA+basal-like group HR=4.16, 95% CI: 1.29-13.44, P=0.017) and postoperative stage ( HR=2.19, 95% CI: 1.09-4.39, P=0.030) were the influencing factors of OS. Cox multivariate analysis showed that the degree of differentiation was an independent prognostic factor for OS after PORT (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=5.24, 95% CI: 2.30-11.93, P<0.001; NA+basal-like group HR=4.83, 95% CI: 1.33-17.62, P=0.017) . The first failure patterns analysis showed that 39 cases (45.9%) had recurrence, among which, 22 cases (25.9%) had locoregional recurrence with the median onset time of 15.2 months after operation, 19 cases (22.4%) had distant metastasis with the median onset time was 14.1 months after operation, and 2 cases (2.4%) were mixed failure mode. Among the locoregional recurrence, 16 cases (72.7%) recurred in the radiation field. Among all the local recurrence sites, the lymph node drainage regions in the supraclavicular, upper middle mediastinum and upper abdominal perigastric/celiac artery trunk areas were the most common sites. Among the distant metastatic organs, lung, bone and liver metastases were the most common. Conclusion:Patients of ESCC with high risk of recurrence after radical esophagectomy have long survival time and high safety after PORT with modified CTV according to the high-frequency recurrence regions. It is worthy of further confirmation by multicenter, large sample and prospective clinical trials.

ObjectiveTo observe the neuroprotective effects of ginsenoside Rb₁ on lipopolysaccharide （LPS）-induced neuroinflammation in mice and to preliminarily investigate its mechanism of action. MethodSeventy ICR mice were randomly divided into blank group， model group， dexamethasone sodium phosphate injection group， and low-dose， high-dose ginsenoside Rb₁ groups， with 14 mice in each group. A mouse brain neuroinflammation model was prepared using the LPS dose escalation method， starting with a dose of 1 mg·kg^-1 and administered via intraperitoneal injection every 48 h （every other morning）. Each subsequent dose increased by 2 mg·kg^-1， for a total of 7 injections， culminating in a final dose of 13 mg·kg^-1. The dexamethasone sodium phosphate injection group received an intraperitoneal injection at 5 mg·kg^-1·d^-1. The low-dose and high-dose ginsenoside Rb₁ groups were given intraperitoneal injections at 10 mg·kg^-1·d^-1 and 20 mg·kg^-1·d^-1， respectively， while the blank and model groups received the same volume of normal saline for 14 days. The behavioral activity of LPS mice was observed， anxiety-like behavior was assessed using the Y-maze and elevated plus maze， and brain levels of monocyte chemoattractant protein-1 （MCP-1）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） were measured by enzyme-linked immunosorbent assay （ELISA）. Neuronal damage of microglia， and the activation status of microglia and astrocytes in the brain were assessed using immunofluorescence staining. The protein expression of phosphatidylinositol-3-kinase （PI3K）， protein kinase B （Akt）， and nuclear factor-κB （NF-κB） in mouse brain were detected by Western blot. ResultCompared with the blank group， the model group showed significantly increased anxiety-like behavior in the Y-maze and elevated plus maze （P<0.05， P<0.01）， significantly elevated levels of MCP-1， TNF-α， and IL-1β in the brain （P<0.01）， a significant decrease in the number of neuronal positive cells in the somatosensory cortex and hippocampus CA1 region （P<0.01）， significant activation of microglia and astrocytes （P<0.01）， and a significant increase in the expression of phosphorylated PI3K， Akt， and NF-κB proteins （P<0.01）. Compared with the model group， the ginsenoside Rb₁ low-dose and high-dose groups showed significantly reduced anxiety-like behavior in the Y-maze and elevated plus maze （P<0.05， P<0.01）， significantly decreased levels of MCP-1， TNF-α， and IL-1β in the brain （P<0.01）， a significant increase in the number of neuronal positive cells in the somatosensory cortex and hippocampus CA1 region （P<0.01）， significant inhibition of microglia and astrocyte activation （P<0.05， P<0.01）， and a significant decrease in the expression of phosphorylated PI3K， Akt， and NF-κB proteins （P<0.05， P<0.01）. ConclusionGinsenoside Rb₁ has neuroprotective effects on LPS-induced inflammation in mice， which may involve the regulation of the PI3K/Akt signaling pathway.

ObjectiveTo observe the effect of intranasal ginsenoside Rb₁ against epilepsy and preliminarily explore the mechanism. MethodThe mouse model of chronic epilepsy was established by intraperitoneal injection of pentylenetetrazole （PTZ）. After successful modeling （21 d）， the epileptic mice were randomly divided into PTZ group， sodium valproate （VPA） group， and low-dose （20 mg·kg^-1） and high-dose （40 mg·kg^-1） ginsenoside Rb₁ groups. Mice in each group were given corresponding drugs intranasally for 30 days， twice a day， and the control group was given the equal volume of normal saline. During the intranasal administration， the weight change， epilepsy latency， and epilepsy stage of the mice were recorded， and the changes in the electroencephalography （EEG） were recorded wirelessly. Neuronal Nuclei （NeuN） was used to observe the damage of neurons in cerebral cortex and hippocampus. The activation of microglia and astrocytes was observed with ionized calcium binding adapter molecule-1 （IBA-1） and glial fibrillary acidic protein （GFAP）， respectively. Glutamate （Glu） transporter-1 （GLT-1） and glutamine synthetase （GS） were used to observe the key molecular changes in Glu regulation. ResultCompared with the control group， the PTZ group decreased body weight （P<0.05，P<0.01）， shortened the epilepsy latency （P<0.01）， and increased the epilepsy stage （P<0.01）. The epileptic EEG waves were increased in the PTZ group. Compared with the PTZ group， the low and high-dose ginsenoside Rb₁ groups increased body weight （P<0.05，P<0.01）， prolonged the epilepsy latency （P<0.05，P<0.01）， decreased the epilepsy stage （P<0.05，P<0.01）， and decreased epileptiform EEG waves. Immunofluorescence staining （IF） showed that ginsenoside Rb₁ significantly ameliorated PTZ-induced neuronal damage （P<0.05，P<0.01） in the motor sensory area of the cerebral cortex and hippocampal CA1 area， and significantly inhibited PTZ-induced activation of microglia （P<0.05，P<0.01） and astrocytes. Further research found that ginsenoside Rb₁ significantly improved the expressions of astrocytic GLT-1 （P<0.01） and GS （P<0.01） in the brains of epileptic mice. ConclusionIntranasal ginsenoside Rb₁ can significantly improve the symptoms of epilepsy caused by PTZ in mice， which has a clear protective effect on neuronal damage in the brains of epileptic mice and significantly inhibits the activation of brain microglia and astrocyte activation. Its anti-epileptic mechanism may be related to the regulation of GLT-1 and GS of the key molecules of astrocyte Glu metabolism.