1.Effect of AGEs on expression of mitochondrial fusion proteins Mfn1 and Mfn2 in cultured human aortic endothelial cells
Shunrong ZHANG ; Yue GAO ; Fei FENG
Chinese Journal of Pathophysiology 2016;32(9):1688-1693
AIM: To clarify whether advanced glycation end products (AGEs) can influence the expression of mitochondrial fusion proteins Mfn1 and Mfn2 in cultured human aortic endothelial cells (HAECs) in vitro.METHODS:AGE-BSA was used as AGEs.Purchased primary human aortic endothelial cell line was multiplied, and transferred to dif-ferent passages for subsequent grouping.For dose-dependent experiment, HAECs were divided into 4 groups, and the con-centrations of AGE-BSA in each group were 0 mg/L (control group), 50 mg/L, 100 mg/L and 200 mg/L, respectively. For time-dependent experiment, HAECs were divided into 5 groups with the same concentration (100 mg/L) of AGE-BSA, but the intervention time was 0 h (control group), 6 h, 12 h, 24 h and 48 h, respectively.The mRNA and protein expres-sion levels of Mfn1 and Mfn2 in the HAECs were detected by real-time PCR and Western blot, respectively.RESULTS:Exposure of the HAECs to AGEs at different concentrations for 24 h all down-regulated the mRNA and protein expression levels of Mfn1 and Mfn2.Except for 6 h intervention group, 100 mg/L AGEs intervention for 12 h, 24 h and 48 h all down-regulated the mRNA and protein expression levels of Mfn1 and Mfn2 in cultured HAECs.CONCLUSION: AGEs down-regulates the expression of mitochondrial fusion proteins Mfn1 and Mfn2 in cultured HAECs, indicating that AGEs may influence mitochondrial dynamics of human aortic endothelial cells.
2.Laparoscopic versus open surgery for D2 gastrectomy in advanced gastric cancer
Xiaoxun CHENG ; Shunrong HUANG ; Zhaoming ZHANG ; Yongchun ZHOU
Chinese Journal of General Surgery 2013;(6):413-416
Objective To evaluate laparoscopic D2 lymph node dissection gastrectomy in the treatment of advanced gastric cancer.Methods The clinical data of 239 cases of advanced gastric cancer admitted from January 2004 to June 2011 were respectively analyzed,patients were divided into laparoscopic resection group and open surgery group.Data analysis was performed by SPSS 19.0 statistical software.Results There were 102 cases in laparoscopic group,and 137 cases in open group.The length of incision,operative blood loss,recovery time of gastrointestinal function,food-taking time and postoperative hospital stay in laparoscopic operation group were (5.0 ± 1.1) cm,(70 ± 44) ml,(57 ± 14) h,(68 ± 12) h,(7.1 ± 1.4) d and in open operation group were (17.4 ± 2.1) cm,(107 ± 59) ml,(75 ± 12) h,(91 ±15) h,(9.9 ± 1.8) d respectively.There were significant differences between the two groups (t =-58.86,-5.50,-10.72,-12.58,-12.58,all P =0.00).There was no significant differences between the two groups in operative time (t =1.63,P =0.11),with operative time in laparoscopic operation group of (192 ± 32) min,and (185 ± 30) min in open group.Average proximal,distal cutting edge and the average number of lymph node harvested were (5.0 ± 1.0) cm,(4.7 ± 0.8) cm,(27.6 ± 7.2) in laparoscopic operation group,and (5.1 ±0.9) cm,(4.7 ±0.9) cm,(27.0 ±6.5) in open group (t =-0.61,0.10,0.68,P > 0.05).The 3-,5-,7 d white blood cell counts in laparoscopic group was (11.1 ± 1.3) ×109/L,(9.5 ± 1.4) × 109/L,(7.0 ± 1.5) × 109/L,and (12.8 ± 1.3) × 109/L,(11.1 ± 1.5) × 109/L,(8.6 ± 1.3) × 109/L,in open group (t =-9.83,-8.88,-9.40,all P =0.00).Complications developed in 9.8 % (10/102) in laparoscopic operation group,and 17.5 % (24/137) in open group (x2 =0.285,P =0.09).The 1-year,3-year,5-year survival rate of patients in laparoscopic group were 96.1%,74.1%,47.2%,and 95.6%,70.0%,50.9% in open group (x2=0,0.04,0.21,P >0.05).Conclusions In selected cases,laparoscopic D2 lymph node dissection gastrectomy for advanced gastric cancer is safe and effective,and long-term outcomes are satisfactory.
3.LSD1 negatively regulates the expression of tumor suppressor gene SIRT3 in pancreatic cancer cell line PANC-1
Jin XU ; Yi QIN ; Bo ZHANG ; Shunrong JI ; Wenyan XU ; Si SHI ; Jiang LIU ; Xianjun YU
China Oncology 2014;(2):87-92
Background and purpose: Lysine specific demethylase 1(LSD1) is an important chromatin modifier. It epigenetically regulates gene expression pattern through chromatin modification and participates in maintenance of tumor malignant properties, such as oncogenesis, development, invasion, migration and metabolic transformation. SIRT3 (sirtuin 3) is a mitochondria localized tumor suppressor and regulates tumor metabolic transformation and oxidative stress. The correlation between LSD1 and SIRT3 has never been reported before. This study aimed to elucidate the correlation between LSD1 and SIRT3 with gene transcriptional regulation methods. Methods: RNA interference technique, co-immunoprecipitation assay(CoIP), chromatin immune-precipitation assay(ChIP) and ifrelfy luciferase activity assay were employed to elucidate the correlation between LSD1 and SIRT3 in pancreatic cancer. Results:mRNA and protein levels of SIRT3 were signiifcantly elevated in LSD1 knock-down PANC-1 cells. LSD1 interacts with PGC-1α, an important regulator of SIRT3 gene expression. LSD1 and PGC-1αoccupied the same region in SIRT3 promoter region through ChIP analysis. Luciferase activity assay validated LSD1 as a negative regulator of PGC-1αin SIRT3 gene transcriptional regulation. Conclusion:LSD1, as an important tumor promoter, negatively regulates the expression of tumor suppressor gene SIRT3, these results provide important clues for the role that LSD1 plays in aberrant metabolism and oxidative stress.
4.Effects of different doses of dexmedetomidine on median effective end-tidal concentration of sevoflurane inhibiting responses to tracheal intubation in pediatric patients
Lin HE ; Xuan WANG ; Shan ZHENG ; Xuefeng ZHANG ; Shunrong TANG ; Yun SHI
Chinese Journal of Anesthesiology 2013;33(11):1336-1338
Objective To evaluate the effects of different doses of dexmedetomidine on median effective end-tidal concentration of sevoflurane (EC50) inhibiting responses to tracheal intubation in pediatric patients.Methods Sixty-seven ASA physical status Ⅰ or Ⅱ patients,aged 3-8 yr,with body weight not exceeding 150% of the ideal weight,scheduled for elective surgery under general anesthesia,were randomly divided into 3 groups using a random number table:control group (group C,n =22) and different doses of dexmedetomidine groups (group D1,n =23 ; group D2,n =22).Before induction of anesthesia,dexmedetomidine 1.0 and 2.0 μg/kg was infused intravenously over 10 min followed by infusion at a rate of 0.5 and 1.0 μg·kg-1 ·h-1 in D1 and D2 groups,respectively.Anesthesia was induced with inhalation of 5 % sevoflurane.After eyelash reflex disappeared,the end-tidal sevoflurane concentration was adjusted to achieve the target concentration and maintained at this level for 15 min.Tracheal intubation was then performed and the response to intubation was scored.The initial end-tidal sevoflurane concentration was 3.5%,2.5% and 1.5% in C,D1 and D2 groups,respectively.Up-and-down sequential trial was used to determine the EC50.Each time the concentration of sevoflurane increased/decreased in the next patient depending on whether or not the response to intubation was positive.The positive response to intubation was defined as intubation score > 1.The ratio of concentrations between the two consecutive patients was 1.2.The EC50 and 95% confidence interval of sevoflurane were calculated.The development of adverse cardiovascular events was recorded after dexmedetomidine administration.Results The adverse cardiovascular events were not observed in D1 group.The incidence of hypotension and brachycardia was 14% and 9% in D2 group.The EC50 (95% confidence interval) of sevoflurane was 3.54% (3.39%-3.69%),2.37% (2.24%-2.46%) and 1.41 % (1.37%-1.46 %) in C,D1 and D2 groups,respectively.Compared with group C,the EC50 of sevoflurane was significantly decreased in D1 and D2 groups (P < 0.01).Compared with group D1,the EC50 of sevoflurane was significantly decreased in group D2 (P < 0.01).Conclusion The optimum dose of dexmedetomidine is 1.0 μg/kg (loading dose) and 0.5 μg· kg-1 · h-1 (maintenance dose) when combined with sevoflurane for induction of anesthesia in pediatric patients.
5.Rectal midazolam,atropine and ketamine as premedication for infants and young children
Xuan WANG ; Hao JIANG ; Zhi-Jian ZHOU ; Xuefeng ZHANG ; Shunrong TANG ;
Chinese Journal of Anesthesiology 1994;0(01):-
Objective To determine the effectiveness of preoperative sedation with rectal midazolam and atropine alone or combined with ketamine in infants and young children.Methods One-hundred and six ASA Ⅰ or Ⅱ infants and young children aged 2 months-2 years scheduled for elective general surgical operation were studied in a double blind fashion.The patients were randomly divided into 3 groups:group M received rectal atropine 0.02 mg?kg~(-1) and midazolam 0.5 mg?kg~(-1)(n=39);group MK and MKK received rectal atropine 0.02 mg?kg~(-1), midazolam 0.5 mg?kg~(-1) and ketamine 4 mg?kg~(-1)(MK,n=34)or 8 mg?kg~(-1)(MKK,n=33).The patients were transferred from the ward to the operating room(OR)30 min after rectal administration.Depth of sedation was evaluated before and 15 min after rectal administration; when the patients were separated from their parents and on arrival in OR using De Jong's sedation score system.SpO_2 and HR were monitored in OR.Results The patients were better sedated in group MK and MKK than in group M after rectal administration.Significantly more patients were asleep on seperation from their parents and on arrival in OR in group MK and MKK than in group M. Significantly more patients were calm and not crying at venepuncture in group MKK(63%)and group MK(32%) than in group M(18%).Conclusion Rectal midazolam combined with ketamine and atropine results in better preoperative sedation than rectal midazolam alone in infants and young children.
6.Diagnostic value of 64-slice spiral CT triple-phase enhanced scan in evaluation of lymphatic metastasis of gastric cancer
Xiaoyan ZHOU ; Longbai MA ; Shunrong HUANG ; Jiawei LIN ; Dongbo WU ; Chuan LI ; Chaolong JIANG ; Ying LI ; Xiaorong ZHANG
Journal of Practical Radiology 2014;(8):1316-1319
Objective To investigate the clinical value of 64-slice spiral computed tomography(64-MSCT)triple-phase enhanced scan in diagnosis of lymphatic metastasis of gastric cancer.Methods Thirty patients with gastric cancer underwent plain and triple-phase enhanced scan by using 64-MSCT to analyze the relevant parameters of lymphatic metastasis.Results The four parameters de-termined metastatic perigastric lymph node as follows:①the short diameter ≥6 mm,②the ratio of short-to-long diameter ≥0.6,③the CT value in the portal venous phase≥ 65 HU,④the difference of CT values between portal venous phase and plain scan≥35 HU.The sensitivity and specificity of combining two parameters (①+②)in diagnosing metastatic lymph node were 90.5% and 29.0%,respectively.The sensitivity and specificity of combining three parameters (①+②+③)were 98.2% and 1 9.4%,respec-tively.The sensitivity and specificity of combining four parameters (①+②+③+④)were 99.7% and 13.2%,respectively.In ad-dition,metastatic lymph nodes were considered if they were ring-enhancement,or adhesions of several lymph nodes.Conclusion The use of 64-MSCT triple-phase enhanced scan and synthesis of various parameters of lymph nodes could lead to reliable diagnosis of lymphatic metastasis in gastric cancer with rapid,non-invasive,high sensitive and specific features.
7.The influence of E-cadherin/β-catenin on the glycolysis effect in PANC-1 cells
Yi QIN ; Dingkong LIANG ; Si SHI ; Shunrong JI ; Bo ZHANG ; Wenyan XU ; Jiang LIU ; Jin XU ; Quanxing NI ; Xianjun YU
China Oncology 2015;(2):81-86
Background and purpose:Lower expression of E-cadherin is associated with metastasis of cancer cells, however, the correlation between E-cadherin and glucose metabolism has seldom been reported. This article studied the correlation between E-cadherin and glycolysis effect in PANC-1 cells.Methods:Through treatment of transforming growth factor β (TGF-β) in PANC-1 cells to decrease E-cadherin expression, knock-down the gene of E-cadherin interaction protein β-catenin, and overexpressing of E-cadherin, the effects of E-cadherin on the glucose uptake and lactate production ability and on the expression of key glycolytic genes were assessed.Results:E-cadherin negatively regulated the glycolytic effect of PANC-1 cells by inhibiting glucose uptake and lactate production (P<0.05). Moreover, E-cadherin interacting partner β-catenin signiifcantly promoted glucose metabolism transformation in PANC-1 cells (P<0.05). Moreover, key glycolysis regulator sirtuin 3 (SIRT3) could lower E-cadherin expression.Conclusion:Lower expression of E-cadherin induced the transformation of glucose metabolism transformation in PANC-1 cells and manipulation of E-cadherin expression level could change the glycolysis effect. Moreover, through maneuver glycolysis process could inhibit high metastatic potential of pancreatic cancer cells.
8.Clinical study on Zhuang medicine Fuzheng compound in the treatment of advanced epidermal growth factor receptor sensitive mutant non-small cell lung cancer
Juanmei MO ; Shunrong ZHANG ; Xiao LIANG ; Chanjuan LI ; Hongrui ZHANG ; Zhenfei HUANG ; Haidi WEN ; Wei LIN
International Journal of Traditional Chinese Medicine 2022;44(10):1102-1106
Objective:To evaluate Zhuang medicine Fuzheng compound combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of advanced epidermal growth factor receptor (EGFR) sensitive mutant non-small cell lung cancer (NSCLC).Methods:A total of 120 patients with advanced NSCLC who met the inclusion criteria from June 2019 to May 2020 in Guangxi International Zhuang Medical Hospital were divided into 2 groups according to the random number table method, with 60 in each group. The control group was treated with TKIs, and the observation group was treated with Zhuang medicine Fuzheng compound combined with EGFR-TKIs. TCM syndrome scores were compared, and the quality of life of the patients was assessed by the Quality of Life Scale (QLQ-C30). The serum levels of carcinoembryonic antigen (CEA), squamous cell carcinoma associated antigen (SCC-Ag) and carbohydrate antigen 50 (CA50) were detected by radioimmunoassay, and the levels of CD3 +, CD4 +, and CD8 + were detected by flow cytometry, and the CD4 +/CD8 + ratio was calculated. The adverse reactions during the treatment were observed and recorded. Results:The objective remission rate in the observation group was 66.7% (40/60) and the disease control rate was 81.7% (49/60), while in the control group were 48.3% (29/60) and 63.3% (38/60), respectively.The differences were statistically significant ( χ2 values were 4.13 and 5.06, P values were 0.042 and 0.025, respectively). After treatment, the scores of chest tightness, shortness of breath, blood in sputum, mental fatigue in the observation group were significantly lower than those in the control group ( t values were 8.72, 5.02, 5.47, all Ps<0.001), After treatment, QLQ-C30 score in the observation group was significantly higher than that of the control group ( t=5.21, P<0.01). After treatment, CEA [(31.45±4.56) mU/L vs. (38.98±5.71) mU/L, t=7.98], SCC-Ag [(4.87±0.93) μg/L vs. (7.29±1.25) μg/L, t=12.03], CA50 [(58.27±7.14) U/L vs. (66.48±7.94) U/L, t=5.96] levels were significantly lower than those in the control group ( P<0.01); CD3 +[(52.43±5.01)% vs. (48.56±4.87)%, t=4.29], CD4 + [(54.89±5.03)% vs. (51.09±5.22)%, t=4.06], CD4 +/CD8 + [(1.95±0.28) vs. (1.65±0.27), t=5.97] significantly higher than those in the control group ( P<0.01), CD8 + [(28.12±2.70)% vs. (31.23±2.64)%, t=6.38] significantly lower than that of the control group ( P<0.01). During the treatment period, the incidence of adverse reactions in the observation group was 13.3% (8/60) and that in the control group was 8.3% (5/60), with a statistically significant difference between two groups ( χ 2=0.78, P=0.378). Conclusion:The Zhuang medicine Fuzheng compound combined with EGFR-TKIs can reduce the level of tumor markers in patients with advanced EGFR-sensitive mutant NSCLC, improve patients' TCM syndromes, quality of life, enhance patient immunity, and improve efficacy.
9.Complex roles of the stroma in the intrinsic resistance to gemcitabine in pancreatic cancer: where we are and where we are going.
Chen LIANG ; Si SHI ; Qingcai MENG ; Dingkong LIANG ; Shunrong JI ; Bo ZHANG ; Yi QIN ; Jin XU ; Quanxing NI ; Xianjun YU
Experimental & Molecular Medicine 2017;49(12):e406-
Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis. The nucleoside analog gemcitabine (GEM) is usually the recommended first-line chemotherapeutic agent for PDAC patients and is given alone or in combination with other agents. The mechanisms of intrinsic resistance to GEM are an active area of ongoing research. This review highlights the important role the complex structure of stroma in PDAC plays in the intrinsic resistance to GEM and discusses whether antistroma therapy improves the efficacy of GEM. The addition of antistroma therapy combined with GEM is expected to be a novel therapeutic strategy with significant survival benefits for PDAC patients.
10.Clinical features and treatment outcome of patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis
Shunrong SUN ; Min WU ; Fulati WULIPAN ; Lin SHEN ; Jiexian MA ; Pingping CHEN ; Yingwei HU ; Hongdi ZHANG ; Yanhui XIE
Chinese Journal of Hematology 2021;42(4):324-331
Objective:To investigate the clinical features and effect of prognostic factors in patients with different pathological types of non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis.Methods:We collected and analyzed the clinical data of 89 patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis who were treated at Huadong Hospital from March 2013 to May 2020. The data were analyzed via log-rank and Cox multivariate analyses.Results:The median overall survival time of the 89 cases was 10.2 months. Patients with B-cell lymphoma-associated hemophagocytic lymphohistiocytosis did not reach the median overall survival time. The median overall survival times of T-cell lymphoma-associated hemophagocytic lymphohistiocytosis and NK-cell lymphoma-associated hemophagocytic lymphohistiocytosis were 10.2 and 3.0 months, respectively. The pathological type of non-Hodgkin lymphoma (OS: P=0041, PFS: P=0.015) , ECOG score ≥ 3 (OS: P=0.031, PFS: P=0.030) , hematopoietic stem cell transplantation (OS: P=0.005, PFS: P=0.040) , lymphadenopathy (OS: P=0.007, PFS: P=0.012) , and splenomegaly (OS: P=0.276, PFS: P=0.324) were related to the overall survival and progression-free survival of patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis. Splenectomy could improve the prognosis of patients with lymphoma-associated hemophagocytic lymphohistiocytosis, especially T-cell lymphoma-associated hemophagocytic lymphohistiocytosis. Conclusion:The clinical characteristics of patients with different pathological types of non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis were similar but were different in the overall survival rate and the effect of prognostic factors. We suggested that patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis should receive more than combined chemotherapy. To improve the prognosis and survival rate of patients, those with B-cell lymphoma-associated hemophagocytic lymphohistiocytosis and NK-cell lymphoma-associated hemophagocytic lymphohistiocytosis promptly require hematopoietic stem cell transplantation. Moreover, patients with T-cell lymphoma-associated hemophagocytic lymphohistiocytosis should consider splenectomy.