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 explore the perioperative safety of video-assisted thoracic surgery (VATS) in Day Care Unit and the risk factors for delayed discharge under centralized management model. Methods The patients with VATS managed by the Day Care Unit of the Drum Tower Hospital Affiliated to Nanjing University Medical School in 2021 were retrospectively collected. The patients’ postoperative data and risk factors for delayed discharge were analyzed. Results A total of 383 patients were enrolled, including 179 males and 204 females with an average age of 46.09±14.82 years. Eleven (2.87%) patients developed grade 3-4 postoperative complications during the hospitalization. Eighteen (4.70%) patients visited unscheduled outpatient clinic within 7 days, and 6 (1.57%) patients were re-hospitalized within 30 days after discharge. The remaining patients had no significant adverse events during the 30-day follow-up. The average length of hospital stay was 2.27±0.35 d. The length of hospital stay was over 48 h in 48 (12.53%) patients. The independent risk factor for delayed discharge was lobectomy or combined resection (OR=3.015, 95%CI 1.174-7.745, P=0.022). Conclusion VATS can be safely conducted under the centralized management in Day Care Unit. The risk factor for delayed discharge is the extent of surgical resection.

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.

Objective To determine risk factors of postoperative pulmonary complications within 1 month in patients undergoing thoracic surgery in Day Care Unit.Methods The total of 200 patients routinely scheduled for VATS under centralized management were enrolled in this study.On the postoperative day 1,lung ultrasound(LUS)was conducted by one physician in the ward.The patients received at least once Chest X-ray or CT in outpatient department within 30 days after discharge.The composite of out-of-hospital PPCs,and the value of LUSS in predicting the PPCs was appraised.Furthermore,we identified the perioperative risk factors associated with PPCs in VATS patients.Results Of 200 recruited VATS patients eligible in the Nanjing Drum Tower Hospital,188 participants received LUS examination and finally completed the 30 days follow-up.Of whom,68 patients developed the varied types of PPCs.Multivariable Logistic regression analysis indicated that comorbidity of immune system disease(P = 0.021),lobar resection(P = 0.031)and the postoperative 24 hours LUSS(P = 0.002)were independent risk factors for PPCs within 30 days after VATS.Conclusion Comorbidity of immune system disease,lobar resection and the postoperative 24 h LUSS were independent risk factors for PPCs within 30 days after VATS.

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.

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.

Objective To investigate the principles of diagnosis and treatment of non-hereditary bilateral synchronous renal cell carcinoma.Methods This retrospective study analyzed 36 cases of non-hereditary bilateral synchronous renal cell carcinoma in our hospital from January 2008 to December 2016,including 30 males and 6 females.A total of 74 renal tumors were found,in which 34 patients had bilateral single kidney tumor and 2 patients had two tumors in one kidney.The diameter of tumors ranged from 1 cm to 11 cm,with an average of (6.8 ±4.1)cm.The patients that underwent nephron-sparing surgery(NSS) got 4-12 points,with an average of (6.1 ±3.4) points in R.E.N.A.L.score and 3-13 points,with an average of (6.9 ± 3.7) points in Zhongshan score.The patients are classified into 4 groups according to operation methods.In group A,16 patients underwent bilateral NSS,which the preoperative creatinine was 63-103 μmol/L with an average of (80.9 ± 11.4) μmol/L.In group B,7 patients underwent one side of NSS before contralateral radical nephrectomy (RN),which preoperative creatinine was 59-87 μmol/L with an average of (75.7 ± 8.9)μmol/L.In group C,7 patients underwent one side of RN before contralateral NSS,preoperative creatinine was 57-107 μmol/L,with an average of (77.6 ± 19.2) μmol/L.In group D,6 patients underwent one side of NSS or RN and spare the contralateral side,2 of which shifted from NSS to RN after finding tumor invaded pelvis and upper ureter during surgery.Of all the 16 patients with bilateral NSS,4 patients underwent surgery on the side where tumor had a higher score in the first phase and then the side where tumor had a lower score in the second phase,11 underwent surgeries in an opposite order.One patient underwent bilateral NSS simultaneously.Group A,B and C are taken into final analysis.Result All the 30 patients underwent surgery successfully.The operation time of NSS ranged from 60 to 110 min with an average of (88.6 ± 23.6) min and RN ranged from 40 to 90 min with an average of (72.3 ± 21.4) min.The warm ischemia time of NSS was 12-40 mins with an average of (29.5 ± 9.7)min.The creatinine of Group A was 62-117 μmol/L with an average of (89.4 ± 15.8) μmol/L and 57-392 μmol/L with an average of (129.6 ±74.9)μmol/L one month after the first and second surgery respectively.The creatinine of Group B was 64-115 μmol/L with an average of (94 ± 14.4) μmol/L and 93-453 μmol/L with an average of (190.4 ± 117.2)μ mol/L one month after the first and second surgery respectively.The creatinine of Group C was 84-113 μmol/L with an average of (90.1 ± 12.1) μ mol/L and 88-156 μmol/L with an average of (121.4 ± 24.8)μmol/L one month after the first and second surgery respectively.One patient in Group B and C developed lung metastases.One patient in Group B occurred oliguria after the second stage of surgery,and gradually improved after one week of hemodialysis.The creatine showed no significant difference among Group A,B and C before operation,after the first and second stage (P ＞ 0.05).Postoperative hospital stay after the first stage surgery was 3-16 days with an average of (6.7 ± 3.4) d,and 3-16 d with an average of (6.2 ± 3.2)d after the second stage,respectively.Conclusions In principle,bilateral renal tumors should be treated with NSS,wbich can protect renal functions as much as possible.Among patients who can undergo bilateral NSS,the first-stage surgery should be operated on the simpler and easier side to preserve the kidney of one side as much as possible to lay a good foundation for the second stage surgery.Among patients who undergo one side of RN and the other side of NSS,NSS is recommended for the first stage,and RN for the contralateral second stage after the renal function of the operated side was restored.

Objective To identify risk factors for postdischarge venous thromboembolism(VTE) following lung resection.Methods Patients undergoing anatomic resection for lung cancer were identified in our institution from 2005-2015.Patient demographic and clinical characteristics were evaluated for any association with post-discharge VTE.Predictors of post-discharge VTE were identified using multivariable analysis.Results VTE occurred in 1.6％ (117) of the 7 154 patients identified.43.6％ (51) VTE events occurred following hospital discharge.Undergoing pneumonectomy was associated with a threefold increased risk for post-discharge VTE compared with lobectomy(2.03％ vs.0.64％,P ＜ 0.01),as was open resection compared to minimally invasive resection(0.86％ vs.0.53％,P＜0.01).Prolonged operative time(＞75％) was also associated with increased risk for post-discharge VTE compared to shorter operative time.Multivariable analysis identified older age,obesity,pneumonectomy,and prolonged operative time as independent predictors for post-discharge VTE.Conclusion The risk for VTE extends after hospital discharge,few patients are managed with post-discharge prophylaxis.Post-discharge prophylaxis should be considered for those at high risk for VTE,particularly for older patients,those who are obese,and following extended or lengthy resections.

Objective To investigate the prognostic factors of postoperative single metastasis in patients with esophageal cancer after treatment.Methods The clinical data of patients with single lesion metastasis from 2002 to 2016 were analyzed retrospectively.Demographic and clinicopathologic data were reviewed.Predictors of PRS after definitive therapy for isolated EC recurrence were determined by the multivariable Cox proportional hazards model.Results Of the 1 016 curative esophagectomies,383 patients(37.7％) experienced recurrences(median followup 53 months).114 (11.2％) received definitive treatment of isolated EC recurrence(63 were treated surgically with or without chemotherapy-radiotherapy[CTRT] and 51 received definitive CTRT alone).Median time to recurrence(TTR) was 18 months.The 1-year and 3-year PRSs were 78.9％ and 38.6％ (median survival 28 months).On multivariable analysis;TTR was the only significant independent predictor for survival after recurrence (HR =0.982,95 ％ CI:0.95-1.03,P =0.036).No pronounced difference was found in disease-free survival or in PRS between recurrent patients treated with operation with or without CTRT and patients who received definitive CTRT.Conclusion A select subgroup of patients with isolated EC recurrence can be treated with curative intent.TTR was the best predictor for PRS.