1.GPCR-Gs mediates the protective effects of ginsenoside Rb1 against oxygen-glucose deprivation/re-oxygenation-induced astrocyte injury
Xi Wang ; Ying Liu ; Juan Li ; Jiayu Xie ; Yi Dai ; Minke Tang
Journal of Traditional Chinese Medical Sciences 2024;11(1):33-43
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.
2.Clinical significance of dynamic contrast-enhanced magnetic resonance imaging in the differential diagnosis of benign and malignant ovarian tumors
Weidong CAI ; Minke WANG ; Yong GUO ; Wangqi LUO
Chinese Journal of Primary Medicine and Pharmacy 2018;25(4):484-487
Objective To explore the value of dynamic contrast -enhanced magnetic resonance imaging in differential diagnosis of benign and malignant ovarian tumors .Methods 50 patients with benign ovarian cancer were selected as the benign group ,and 50 patients with malignant ovarian cancer were selected as the malignant group .All patients underwent dynamic contrast-enhanced magnetic resonance imaging .Results The difference of the time intensity curve ( TIC) curve between the benign group and the malignant group was no statistically significant ( P<0.05),the benign group was mainly type Ⅰ curve,and the malignant group was dominated by type Ⅲ curve.The values of Ve,Kep and Ktrans in the benign ovarian tumors [(0.492 ±0.227),(0.163 ±0.081)min-1,(0.071 ± 0.034) min-1 ] were significantly lower than those in the malignant group [( 0.686 ±0.153 ), ( 0.411 ± 0.214)min-1,(0.282 ±0.110)min-1](P<0.05).The ROC curve under the area of Ve value,Kep value,Ktrans value to identify ovarian benign and malignant were 0.707,0.942,1.000;the best differential value of Ve ,Kep, Ktransfor ovarian benign and malignant tumors were 0.118min-1,0.257min-1,0.546,respectively.The Jorden index,sensitivity,specificity,positive predictive value,negative predictive values of the diagnosis of the ovarian benign and malignant tumors were 0.446,88.84%,57.23%,63.24%and 86.12%,respectively.The Jorden index,sensitivity, specificity,positive predictive value ,negative predictive values of Kep in the diagnosis of ovarian benign and malignant tumors were 0.804,88.91%,90.87%,89.15%and 90.78%,respectively.The Jorden index,sensitivity,specificity, positive predictive value ,negative predictive values of Ktrans in the diagnosis of ovarian benign and malignant tumors were 1.000,100.0%,100.0%,100.0%,100.0%.Conclusion Dynamic contrast -enhanced magnetic resonance imaging has differential diagnosis value on benign and malignant ovarian tumors .The ovarian benign tumors are mainly type Ⅰcurve,and the ovarian malignant tumors is mainly type Ⅲcurve.Ktrans is the best for differential diagnosis of ovarian benign and malignant tumors .
3.Predictors of survival after treatment of recurrence after esophagectomy
Yulong XUAN ; Baojun CHEN ; Bin CAO ; Tao WANG ; Yong ZHOU ; Minke SHI
Chinese Journal of Thoracic and Cardiovascular Surgery 2018;34(8):477-480
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.
6.The efficiency of zero ischemia index in predicting complexity and outcomes of off-clamp nephron-sparing surgery
Hang WANG ; Yaohui LI ; Zhuoyi XIANG ; Lin ZHOU ; Minke HE ; Jianming GUO
Chinese Journal of Urology 2018;39(3):171-173
Objective To evaluate the efficacy of zero ischemia index (ZⅡ) in predicting the complexity and perioperative outcomes of off-clamp nephron-sparing surgery (NSS).Methods The patients between June 2016 and June 2017 in our institution who underwent off-clamp NSS were prospectively evaluated.ZⅡ was defined as the product of the tumor diameter and depth within renal parenchyma.The ZⅡ >6 defined as higher risk while ZⅡ ≤ 6 defined as low risk.The operating time,estimated blood loss,hospital stay,drainage,and complication rate were analyzed.Results There were 35 males and 10 females with average age of 42 y(range 23-76y).Mean tumor size was 2.4 cm (range 0.8-4.2 cm).Mini-flank approach open NSS was performed in 33 cases and laparoscopic NSS was performed in 12 cases.Off-clamp NSS was successfully performed in 44 patients except for renal artery occlusion in 1 case.Mean operative time was (95.0± 17.5) min (range 50-150 min);The average estimated blood loss was (152.4 ± 134.2) ml (range 20-600 ml);Mean postoperative drainage was (97.3 ± 59.7) ml (range 50-300 md);Mean postoperative hospital stay was (6.1 ± 1.3) d (range 5-8 d).Not severe post operative complication was observed.There were 37 patients in low risk group and 8 patients in high risk group.Operating time was significantly longer in high risk group [(118.8 ± 14.6 min) vs.(89.9±13.4) min,P<0.01].EBL [(375.0±158.1) ml vs.(104.3 ±61.4) ml,P<0.01] and drainage [(161.2±91.3)ml vs.(83.5 ±40.4)ml,P < 0.01] were also significantly higher in high risk group.But there was no significant difference in hospital stay between two groups.The postoperative pathology indicated that 35 cases of clear cell carcinomas,2 cases of chromophobe renal cell carcinomas,one case of papillary carcinoma and seven cases of angiomyolipomas.Conclusions The ZⅡ is a novel and effective measurable criterion which can help predict the risk of perioperative outcomes of off-clamp NSS.ZⅡ =6 is established as a preliminary threshold for patient selection of off-clamp NSS.
7.Exploration on the Biological Implications of"Earth Deficiency and Wood Depression"Pathogenesis of Hypertension from Intestinal Flora-bile Acid Axis
Meilong SI ; Hua JIN ; Minke LIU ; Yu WANG ; Qiuju ZHANG ; Shuangfang LIU ; Bishi LING ; Shangwen QI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):13-18
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.
8.The development of traditional Chinese medicine
Ma DANNING ; Wang SHANSHAN ; Shi YU ; Ni SHENGLOU ; Tang MINKE ; Xu ANLONG
Journal of Traditional Chinese Medical Sciences 2021;8(z1):1-9
Similar to other medicines, traditional Chinese medicine (TCM) originated from the need for various practical solutions to treat diseases. It is a knowledge system summarized and condensed by the Chinese nation in the health care practice for thousands of years. TCM continues to serve the health care system. This study summarized the history, health concept, main treatment strategies and methods, current development, and future perspectives of TCM. It may provide a more comprehensive image of the overall TCM system.
9.Efficacy of postoperative radiotherapy based on modified clinical target volume according to high-frequency recurrence regions in patients with esophageal squamous cell carcinoma
Puyuan WU ; Liang QI ; Tao WANG ; Minke SHI ; Yuwei SUN ; Lifeng WANG ; Baorui LIU ; Jing YAN ; Wei REN
Journal of International Oncology 2022;49(8):464-472
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.
10.Experience in diagnosis and treatment of non-hereditary bilateral synchronous renal carcinoma
Hang WANG ; Peirong XU ; Sihong ZHANG ; Yanjun ZHU ; Shuai JIANG ; Xiaoyi HU ; Minke HE ; Jianming GUO
Chinese Journal of Urology 2019;40(5):361-364
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.