Objective To investigate the regulatory role and mechanism of lobetyolin(LBT,a poly-acetylene glycoside isolated from the roots of Codonopsis pilosula)in the proliferation and apop-tosis of brain glioma cells based on the Akt/GSK-3β/Snail signaling pathway.Methods Human brain glioma cell line U-373MG was randomly divided into normal,SC79(Akt activator),LBT,and LBT+SC79 groups.After corresponding interventions,CCK-8 assay,colony formation assay,and flow cytometry were used to detect the proliferation and apoptosis of the cells.Western blot-ting was employed to measure the protein expression levels of the molecules related to prolifera-tion,apoptosis,and Akt/GSK-3β/Snail signaling pathway.After tumor xenograft nude mouse model of U-373MG cells was established,followed by grouping and interventions as above cell experiments,the tumor weight and volume were measured.Immunohistochemical assay and TUNEL assay were performed to detect the proliferation and apoptosis of tumor cells.Western blotting was applied to detect Akt/GSK-3β/Snail signaling pathway related proteins in the nude mouse groups.Results In the LBT+SC79 group,cell viability,number of formed colonies,pro-tein levels of cyclin D1,Bcl-2 and Snail,p-Akt/Akt and p-GSK-3β/GSK-3β,tumor weight and vol-ume,and positive ratios of Ki67,cyclin D1 and Bcl-2 in transplanted tumors were increased(P＜0.05),and cell apoptotic rate[(3.20±1.14)％vs(46.15±1.52)％,P＜0.05],Bax protein level(0.51±0.07 vs 0.89±0.06,P＜0.05),and positive ratios of TUNEL[(51.56±7.13)％vs(74.95±8.61)％,P＜0.05]and Bax[(32.71±5.43)％vs(41.86±4.90),P＜0.05]in transplanted tumors were declined when compared with the LBT group.Conclusion LBT can induce apoptosis and inhibit proliferation of brain glioma cells in vitro and in vivo by blocking activation of the Akt/GSK-3β/Snail signaling pathway.

Objective To investigate the regulatory role and mechanism of lobetyolin(LBT,a poly-acetylene glycoside isolated from the roots of Codonopsis pilosula)in the proliferation and apop-tosis of brain glioma cells based on the Akt/GSK-3β/Snail signaling pathway.Methods Human brain glioma cell line U-373MG was randomly divided into normal,SC79(Akt activator),LBT,and LBT+SC79 groups.After corresponding interventions,CCK-8 assay,colony formation assay,and flow cytometry were used to detect the proliferation and apoptosis of the cells.Western blot-ting was employed to measure the protein expression levels of the molecules related to prolifera-tion,apoptosis,and Akt/GSK-3β/Snail signaling pathway.After tumor xenograft nude mouse model of U-373MG cells was established,followed by grouping and interventions as above cell experiments,the tumor weight and volume were measured.Immunohistochemical assay and TUNEL assay were performed to detect the proliferation and apoptosis of tumor cells.Western blotting was applied to detect Akt/GSK-3β/Snail signaling pathway related proteins in the nude mouse groups.Results In the LBT+SC79 group,cell viability,number of formed colonies,pro-tein levels of cyclin D1,Bcl-2 and Snail,p-Akt/Akt and p-GSK-3β/GSK-3β,tumor weight and vol-ume,and positive ratios of Ki67,cyclin D1 and Bcl-2 in transplanted tumors were increased(P＜0.05),and cell apoptotic rate[(3.20±1.14)％vs(46.15±1.52)％,P＜0.05],Bax protein level(0.51±0.07 vs 0.89±0.06,P＜0.05),and positive ratios of TUNEL[(51.56±7.13)％vs(74.95±8.61)％,P＜0.05]and Bax[(32.71±5.43)％vs(41.86±4.90),P＜0.05]in transplanted tumors were declined when compared with the LBT group.Conclusion LBT can induce apoptosis and inhibit proliferation of brain glioma cells in vitro and in vivo by blocking activation of the Akt/GSK-3β/Snail signaling pathway.

Objective:To investigate the effects of phillyrin(PHN)on the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of glioma U251 cells by adjusting the high mobility group protein B1(HMGB1)/receptor of advanced glycation endproduct(RAGE)signaling pathway.Methods:Human glioma U251cells were assigned into the PHN-0 group(treated with 0 μmol/L PHN),the low,medium,and high-dose PHN groups(PHN-50、PHN-100、PHN-200 groups,treated with 50,100,and 200 μmol/L PHN respectively),the PHN+pcDNA-NC group(treated with 200 μmol/L PHN after transfection of pcDNA-NC plasmid),and the PHN+HMGB1 group(treated with 200 μmol/L PHN after transfection of overexpressed HMGB1 plasmid).The proliferation ability of cells in each group was detected by the CCK-8 method and the clone formation assay.The apoptosis level of cells in each group was detected by flow cytometry.The migration and invasion abilities of cells in each group were detected by the Transwell assay.ELISA was used to detect the IL-8 secretion level of cells in each group.Immunofluorescence was used to detect the positive rates of N-cadherin and E-cadherin in cells of each group.WB assay was performed to detect the expression levels of Toll like receptor 4(TLR4),nuclear factor-kappa B(NF-κ B),HMGB1,RAGE,N-cadherin,E-cadherin,cell cycle protein D1(cyclin D1),cyclin dependent kinase 2(CDK2),B-lymphoblastoma-2(Bcl-2),Bcl-2 associated X protein(BAX)proteins in cells of each group.Results:Compared with those in the PHN-0 group,the proliferation activity,the number of clone formation,the numbers of invasion and migration,IL-8 secretion levels,the positive rate and protein expression of N-cadherin,and the expressions of TLR4,NF-κB,HMGB1,RAGE,cyclin D1 and CDK2 protein in the PHN-50,PHN-100,and PHN-200 groups decreased significantly(all P<0.05);and the apoptosis rate,the positivity rate and protein expression of E-cadherin,and the BAX/Bcl-2 ratio increased significantly(all P<0.05).At the same time,overexpression of HMGB1 could reverse the inhibitory effects of PHN on the proliferation,migration,invasion and EMT of U251 cells,as well as its promoting effect on the apoptosis(all P<0.05).Conclusion:PHN inhibits the proliferation,invasion and EMT progression of glioma U251 cells through the HMGB1/RAGE signaling pathway.

Objective:To investigate the relationship between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours in primiparas using epidural analgesia.Methods:A retrospective study was conducted on the clinical data of pregnant women who delivered vaginally in the obstetrics department of the Affiliated Hospital of Jining Medical University from January 1, 2020, to December 31, 2020. The data included maternal age, pre-pregnancy body mass index (BMI), gravidity, gestational age at delivery, weight gain during pregnancy, common pregnancy complications (such as gestational hypertension, gestational diabetes, hypothyroidism, and pregnancy-related anemia), types of uterotonics, duration of each stage of labor, delivery outcomes, perineal conditions, postpartum hemorrhage within 2 hours, and neonatal birth length and weight. The exposure variable was the duration of the second stage of labor, and the outcome was the amount of postpartum hemorrhage within 2 hours. Potential risk factors were analyzed using univariate analysis. After adjusting for potential confounding factors, a generalized additive model was used for linear regression analysis, smooth curve fitting, and threshold effect analysis to observe the relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours.Results:A total of 2 067 primiparas were included in the study. The mean age of the participants was 26.5±3.6 years, the median duration of the second stage of labor was 54 min (range: 35-81 min), and the median amount of postpartum hemorrhage within 2 hours was 230 ml (range: 200-300 ml). After adjusting for factors such as maternal age, pre-pregnancy BMI, gestational age at delivery, vaginal delivery, duration of the first and third stages of labor, perineal conditions, types of uterotonics used within 2 hours postpartum, and neonatal birth length and weight, a positive relationship was found between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours ( ?=0.20, 95% CI: 0.00-0.30, P<0.05). The smooth curve fitting results showed a non-linear relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours. Threshold effect analysis indicated that the two-segment regression model (Model Ⅱ) was more suitable for fitting the correlation compared to the univariate linear regression model (Model Ⅰ), with a log-likelihood ratio test P-value of 0.001, and the inflection point was 115 min for the second stage of labor (95% CI: 99-125 min). Conclusions:In primiparas using epidural analgesia, there is a non-linear relationship and threshold effect between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours. When the second stage of labor exceeds 115 min, the extension of the second stage may increase the amount of postpartum hemorrhage within 2 hours.

Objective:To investigate the relationship between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours in primiparas using epidural analgesia.Methods:A retrospective study was conducted on the clinical data of pregnant women who delivered vaginally in the obstetrics department of the Affiliated Hospital of Jining Medical University from January 1, 2020, to December 31, 2020. The data included maternal age, pre-pregnancy body mass index (BMI), gravidity, gestational age at delivery, weight gain during pregnancy, common pregnancy complications (such as gestational hypertension, gestational diabetes, hypothyroidism, and pregnancy-related anemia), types of uterotonics, duration of each stage of labor, delivery outcomes, perineal conditions, postpartum hemorrhage within 2 hours, and neonatal birth length and weight. The exposure variable was the duration of the second stage of labor, and the outcome was the amount of postpartum hemorrhage within 2 hours. Potential risk factors were analyzed using univariate analysis. After adjusting for potential confounding factors, a generalized additive model was used for linear regression analysis, smooth curve fitting, and threshold effect analysis to observe the relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours.Results:A total of 2 067 primiparas were included in the study. The mean age of the participants was 26.5±3.6 years, the median duration of the second stage of labor was 54 min (range: 35-81 min), and the median amount of postpartum hemorrhage within 2 hours was 230 ml (range: 200-300 ml). After adjusting for factors such as maternal age, pre-pregnancy BMI, gestational age at delivery, vaginal delivery, duration of the first and third stages of labor, perineal conditions, types of uterotonics used within 2 hours postpartum, and neonatal birth length and weight, a positive relationship was found between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours ( ?=0.20, 95% CI: 0.00-0.30, P<0.05). The smooth curve fitting results showed a non-linear relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours. Threshold effect analysis indicated that the two-segment regression model (Model Ⅱ) was more suitable for fitting the correlation compared to the univariate linear regression model (Model Ⅰ), with a log-likelihood ratio test P-value of 0.001, and the inflection point was 115 min for the second stage of labor (95% CI: 99-125 min). Conclusions:In primiparas using epidural analgesia, there is a non-linear relationship and threshold effect between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours. When the second stage of labor exceeds 115 min, the extension of the second stage may increase the amount of postpartum hemorrhage within 2 hours.

Objective:To study and explore the effect and mechanism of action of Jieduhuayu granules on oxidative injury of human liver L02 cells.Methods:Human liver L02 oxidative injury model was established with 0.1 mmol/ L H 2O 2 intervention for 1 h, and treated with different concentrations of Jieduhuayu (JDHY) solution. Hepatocytes were divided into five groups: normal, H 2O 2, H 2O 2 + JDHY (0.5 mg/ml), H 2O 2 + JDHY (1 mg/ml), and H 2O 2 + JDHY (1.5 mg/ml). MTT assay was used to detect hepatocytes activity. Transmission electron microscope was used to observe mitochondrial morphology in hepatocytes. Biochemical test was used to detect the levels of superoxide dismutase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and reduced glutathione and albumin in hepatocytes. Western blot was used to detect the expression levels of rabbit anti-phosphatidylinositol 3-kinase (PI3K), AKT and mTOR in hepatocytes. One-way analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison. Results:Compared with the normal group, the cell proliferation activity ( P < 0.05), mitochondrial vacuolization, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT, and mTOR protein expression levels in the H 2O 2 group were all significantly reduced ( P < 0.05), while the content of malondialdehyde and the activities of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were significantly increased ( P < 0.05). Compared with H 2O 2 group, the cell proliferation activity ( P < 0.05), alterations in morphological remission of mitochondria, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT and mTOR protein expression levels in the H 2O 2 + JDHY (1 mg/ml) and H 2O 2 + JDHY (1.5 mg/ml) group ( P < 0.05) were all significantly increased ( P < 0.05), while malondialdehyde content and alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities were significantly decreased ( P < 0.05). Conclusion:Jieduhuayu granule can effectively improve oxidative stress and mitochondrial injury in hepatocytes, and its effect may be related to the promoting expression of PI3K/AKT/mTOR signaling pathways.

Objective:To analyze the correlation of glycosylated hemoglobin (HbA 1c) level in the late pregnancy gestational diabetes mellitus (GDM) patients and fetal weights, neonatal Apgar scores, maternal and infant adverse outcomes. Methods:One hundred and eighty-seven pregnant women who were diagnosed with GDM from January 2015 to July 2019 and delivered in Yixing People′s Hospital after standard diagnosis and treatment were divided into four groups (A group: HbA 1c<6.0%, 65 cases; B group: HbA 1c: 6.0% - 6.5%, 49 cases; C group: HbA 1c 6.6%-7.0%, 39 cases; D group: HbA 1c>7.0%, 34 cases) according to the HbA 1c examination results at 28 to 32 weeks of gestation. General data, fetal weights, neonatal Apgar scores and maternal and infant adverse outcomes were compared among the four groups. The correlation between GDM HbA 1c and fetal weights, neonatal Apgar scores and maternal and infant adverse outcomes were analyzed by unconditional Logistic regression. Results:In general data of GDM pregnant women with different HbA 1c levels, only oral glucose tolerance test (OGTT) fasting blood glucose: (4.68 ± 0.60), (4.89 ± 0.69), (5.23 ± 0.90), (6.48 ± 2.17) mmol/L; postprandial 1 h blood glucose: (9.84 ± 1.56), (10.09 ± 1.84), (10.6 ± 2.01), (12.74 ± 4.12) mmol/L; postprandial 2 h blood glucose: (8.65 ± 1.49), (8.86 ± 1.76), (9.28 ± 2.15), (11.56 ± 4.93) mmol/L, showed statistically significant differences ( P<0.05). Among the newborns of GDM pregnant women with different HbA 1c levels, there were statistically significant differences in the macrosomic infant rates: 1.54%(1/65), 10.20%(5/49), 12.82%(5/39), 17.65%(6/34); rates of neonatal Apgar scores<7 points:13.85%(9/65), 16.33%(8/49), 25.64%(10/39), 44.12%(15/34); the proportion of maternal and infant adverse outcomes: 24.62%(16/65), 24.49%(12/49), 28.21%(11/39), 50.00%(17/34), showed statistically significant differences ( P<0.05). After adjusting OGTT by unconditional Logistic regression analysis, HbA 1c (6.6%-7.0% and>7.0%) was independent risk factor for macrosomic infants: OR = 1.430, 95% CI = 1.035-1.977, P = 0.030; OR = 2.042, 95% CI = 1.311-3.180, P = 0.001; maternal and infant adverse outcomes: OR = 1.774, 95% CI = 1.130-2.874, P = 0.010; OR = 3.387, 95% CI = 1.608-7.133, P = 0.001. HbA 1c>7.0% was independent risk factors for neonatal Apgar scores<7 points: OR = 1.848 95% CI = 1.086-3.143, P = 0.023. Conclusions:There was a significant correlation between HbA 1c in GDM pregnant women in the late pregnancy and macrosomic infants, neonatal Apgar scores, and maternal and infant adverse outcomes. In particular, GDM pregnant women with HbA 1c>7.0% should be alert to the risk of macrosomic infants, neonatal Apgar score<7 points, and maternal and infant adverse outcomes.

OBJECTIVETo retrospectively analyze the clinicopathology of patients with gastric gastrointestinal stromal tumor(gGIST) who underwent radical excision within 18 years in 10 domestic medical centers in order to understand the status of domestic surgical treatment of gGIST.

METHODSClinicopathological data of gGIST patients undergoing radical excision in 10 medical centers from January 1998 to January 2016 were collected, and their operational conditions, postoperative adjuvant therapy, gene detection and survival were analyzed retrospectively.

RESULTSA total of 1 846 cases were recruited in this study, including 246 cases from Guangdong General Hospital, 331 cases from Sun Yat-sen University Cancer Center, 374 cases from Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 342 cases from Nanfang Hospital of Southern Medical University, 265 cases from Fujian Medical University Union Hospital, 148 cases from Fudan University Shanghai Cancer Center, 49 cases from West China Hospital of Sichuan University, 43 cases from Peking University Cancer Hospital and Institute, 28 cases from the 81st Hospital of Pepole's Liberation Army(PLA), 20 cases from Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute. There were 918 male (49.7%) and 928 female patients (50.3%) with median onset age of 59(18 to 95) years old. Fundus(735 cases, 39.8%) and body (781 cases, 42.3%) of stomach were the common sites of lesions. The average size of tumor was (5.3±4.6) cm. There were 1 421 cases with mitotic count ≤5(77.0%). According to the operation procedure, 924 cases (50.1%) underwent laparoscopic surgery, 759 cases (41.1%) laparotomy, 120 cases (6.5%) endoscopic surgery, and 20 cases (1.1%) laparoscopic combined with endoscopic surgery, 6 cases (0.3%) laparoscopic excision surgery through gastric wall and cavity, and 17 cases (0.9%) laparoscopy and then were transferred to laparotomy. Wedge excision were performed in 1 308 cases (70.9%), proximal gastric excision in 226 cases(12.2%), distal gastric excision in 92 cases (5.0%), total gastrectomy in 94 cases (5.1%), and local gastrectomy in 126 cases(6.8%). Multi-visceral excision was performed in 138 cases, and the splenectomy was performed in 83 cases(60.1%)with the highest ratio. According to modified NIH classification, 399 cases(21.6%) were extreme low risk, 580 cases(31.4%) were low risk, 424 cases(23.0%) were moderate risk, 443 cases (24.0%) were high risk. A total of 461 cases received postoperative imatinib adjuvant therapy, accounting for 53.2%(461/867) of patients with moderate and high risk. Among 1 846 cases, 1 402 cases (75.9%) had complete follow-up data and the median follow-up time was 33.6 (0.1 to 158) months. The 5-year survival rates of extreme low risk, low risk, moderate risk and high risk were 100%, 98.5%, 92.5%, and 79.2% with significant difference(P=0.000).

CONCLUSIONSGastric GIST occurs mostly in fundus and body of stomach in China. Wedge excision is the main operational procedure and laparoscopic operation is over 50%. General prognosis of gastric GIST is quite good.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; China ; Combined Modality Therapy ; Female ; Gastrectomy ; Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; pathology ; surgery ; Humans ; Imatinib Mesylate ; therapeutic use ; Laparoscopy ; Laparotomy ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; Retrospective Studies ; Splenectomy ; Stomach Neoplasms ; pathology ; surgery ; Survival Rate ; Young Adult

OBJECTIVETo investigate the feasibility of no nasogastric intubation and early oral feeding at will after thoracolaparoscopic esophagectomy for patients with esophageal cancer.

METHODSBetween January 2013 and January 2014, the feasibility of no nasogastric intubation and early oral feeding at postoperative day(POD) 1 after thoracolaparoscopic esophagectomy was prospectively investigated in 156 patients (trial group) with esophageal cancer in the Henan Cancer Hospital. One hundred and sixty patients previously managed in the same unit who were treated routinely after thoracolaparoscopic esophagectomy were served as control group.

RESULTSOf 156 patients of trial group, 6(3.8%) patients could not take food early as planned because of postoperative complications. The overall complication rate in trial group was 19.2%(30/156), which was 25.0%(30/160) in control group (P=0.217). The anastomotic leakage in trial group and control group was 2.6%(4/156) and 4.3%(7/160) respectively (P=0.380). Compared with control group, time to first flatus [(2.1±0.9) d vs. (3.3±1.1) d, P<0.001], bowel movement [(4.4±1.3) d vs. (6.6±1.0) d, P<0.001] and postoperative hospital stay [(8.3±3.2) d vs. (10.4±3.6) d, P<0.001] were significantly shorter in trial group.

CONCLUSIONSNo nasogastric intubation and early oral feeding postoperatively in patients with thoracolaparoscopic esophagectomy is feasible and safe. This management can shorten postoperative hospital stay and fasten postoperative bowel function recovery.

Eating ; Esophageal Neoplasms ; surgery ; Esophagectomy ; Fasting ; Feasibility Studies ; Humans ; Intubation, Gastrointestinal ; Postoperative Complications ; Postoperative Period

Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Mutation