1.Study on the Mechanism of DNER Promoting Malignant Progression of Gastric Cancer Cells by Inhibiting Mitochondrial Autophagy
Yongsheng FU ; Jingfen LU ; Xin ZHAO ; Wei WANG ; Qicong ZHU
Journal of Modern Laboratory Medicine 2024;39(4):50-55
Objective To investigate the role of delta/notch-like epidermal growth factor-related receptor(DNER)in gastric cancer and its regulatory mechanism.Methods The mRNA and protein levels of DNER in gastric cancer tissues and cells were detected with quantitative real time polymerase chain reaction(qRT-PCR)and Western blot.Gastric cancer cell line SGC7901 with silenced DNER expression was constructed,and cells were treated with mitochondrial dynamin-related protein 1(DRP1)inhibitor Mdivi-1.CCK-8 assay,Transwell assay,and flow cytometry were used to detect cell viability,invasion ability and apoptosis,respectively.Western blot was used to detect DNER protein levels,apoptosis-associated proteins[Cysteinyl aspartate-specific proteinase-3(Caspase-3),Bcl-2 Associated X(Bax)],autophagy associated proteins[microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ,LC3 Ⅱ/Ⅰ),p62,PTEN induced putative kinase 1(PINK1)and Parkin],and mitochondrial fission and fusion protein[DRP1,mitochondrial fission factor(MFF),mitochondrial fission protein 1(FIS1),Optic Atrophy 1(OPA1),mitofusin 1(MFN1)and MFN2]levels.Results The expression levels of DNER mRNA and protein in gastric cancer tissues were higher than those in adjacent normal tissues(t=-52.485,-46.955),while expression levels of DNER mRNA and protein in gastric cancer cells were higher than those in normal gastric epithelial cells(F=60.551,60.652),and the differences were significant(P<0.001).Silencing DNER inhibited the proliferation and invasion of SGC7901 cells,induced apoptosis,and increased the expression of apoptosis-related proteins,with significant differences(t=8.026~25.903,all P<0.05).Silenced DNER increased LC3 Ⅱ/Ⅰ ratio(t=18.086),decreased p62 protein level(t=6.747),promoted the aggregation of PINK1 and Parkin proteins in mitochondria(t=15.630,18.171),inhibited the expression of mitochondrial fusion proteins OPA1,MFN1 and MFN2(t=12.835,8.963,9.732),and promoted the expression of mitochondrial fission proteins DRP1,MFF and FIS1(t=16.034,16.939,15.971),with significant differences(all P<0.05).Mdivi-1 treatment could counteract the effects of silencing DNER on mitochondrial autophagy,proliferation,invasion and apoptosis of gastric cancer cells.Conclusion DNER can reduce mitochondrial autophagy by inhibiting mitochondrial dynamic imbalance,promote cell proliferation and invasion,and inhibit cell apoptosis,thus promoting the progression of gastric cancer.
2.Innovation and development of surgical techniques for pancreatic tumors
Yiping MOU ; Shuyou PENG ; Yun JIN ; Qicong ZHU
Chinese Journal of Surgery 2024;62(7):648-653
In recent years, great progress has been made in the diagnosis and treatment of pancreatic tumors. In terms of diagnosis, three-dimensional CT reconstruction, PET-CT scan, endoscopic ultrasound with needle biopsy are used to evaluate the benign or malignant stage and biological characteristics of the tumor, to make treatment decisions more scientific and reasonable. In terms of treatment, new technologies, such as arterial priority arterial sheath dissection and radical resection of the retroperitoneal lipo-lymphatic layer, have continuously emerged to improve radical curability of tumors. For benign or low-grade malignant pancreatic tumors, function-preserving surgery is adopted to avoid long-term complications. Minimally invasive pancreatic surgery has advanced in leaps and bounds. Both standard radical surgery and function-preserve surgery can be performed under a laparoscope or robot. Non-surgical treatment has developed quickly with each passing day; for locally advanced or metastatic pancreatic cancer, neoadjuvant therapy is expected to be down-staged or transformed into surgery. These advances in diagnosis and treatment technology have led to multidisciplinary teamwork. Based on accurate assessment, giving full play to the advantages of laparoscopic and robotic systems in diagnosis and treatment, attaching importance to comprehensive nonsurgical treatment and doctor-patient communication with care throughout the process, these are keys to improve the clinical efficacy of pancreatic tumors in the era of minimally invasive surgery.
3.The outcomes of robotic-assisted enucleation for tumors located in uncinate process of pancreas in 16 cases
Weiwei JIN ; Huizheng LU ; Jingtao CHEN ; Qicong ZHU ; Chao LU ; Yuanyu WANG ; Yiping MOU
Chinese Journal of Surgery 2024;62(10):923-928
Objective:To summarize the experience of robot-assisted enucleation of tumors located in uncinate process of pancreas.Methods:This is a retrospective case series study. The clinical data of patients with robot-assisted enucleation of tumors located in the uncinate process of pancreas at the Department of Gastroenterology and Pancreatic Surgery,Zhejiang Provincial People′s Hospital from June 2019 to December 2023 were retrospectively analyzed. A total of 16 cases were enrolled,including 10 males and 6 females,with an age( M(IQR)) of 56(21)years (range: 28 to 77 years),and body mass index of 22.4(2.3)kg/m 2 (range:19.8 to 25.6 kg/m 2). Follow-up was asked every 6 to 12 months after the first 3-month postoperative follow-up through out-patient service or via telephone. Results:In total 16 cases,there were 11 cases with pancreatic enucleation,and 5 cases with resection of the uninate process. The operation time was 70(60) minutes (range: 40 to 165 minutes),and the blood loss was 30(13)ml (range: 10 to 80 ml). The rate of pancreatic fistula was 5/16. The length of stay was 8(6)days (range: 5 to 33 days). The pathological finding included non-functional neuroendocrine tumor( n=3),insulinoma( n=2),introductal papillary mucinous neoplasm ( n=5),solid pseudopapillary neoplasm ( n=2),mucinous cystadenoma ( n=1),serous cystadenoma ( n=2),pseudocyst ( n=1). Follow-up as of March 12, 2024, the follow-up time was 16(12)months (range: 3 to 41 months). All patients had no new onset diabetes and no dyspepsia. Conclusion:Robot-assisted surgical system can be used for local resection of uncinate process tumors of pancreas,and the quality of life of patients can be improved.
4.Innovation and development of surgical techniques for pancreatic tumors
Yiping MOU ; Shuyou PENG ; Yun JIN ; Qicong ZHU
Chinese Journal of Surgery 2024;62(7):648-653
In recent years, great progress has been made in the diagnosis and treatment of pancreatic tumors. In terms of diagnosis, three-dimensional CT reconstruction, PET-CT scan, endoscopic ultrasound with needle biopsy are used to evaluate the benign or malignant stage and biological characteristics of the tumor, to make treatment decisions more scientific and reasonable. In terms of treatment, new technologies, such as arterial priority arterial sheath dissection and radical resection of the retroperitoneal lipo-lymphatic layer, have continuously emerged to improve radical curability of tumors. For benign or low-grade malignant pancreatic tumors, function-preserving surgery is adopted to avoid long-term complications. Minimally invasive pancreatic surgery has advanced in leaps and bounds. Both standard radical surgery and function-preserve surgery can be performed under a laparoscope or robot. Non-surgical treatment has developed quickly with each passing day; for locally advanced or metastatic pancreatic cancer, neoadjuvant therapy is expected to be down-staged or transformed into surgery. These advances in diagnosis and treatment technology have led to multidisciplinary teamwork. Based on accurate assessment, giving full play to the advantages of laparoscopic and robotic systems in diagnosis and treatment, attaching importance to comprehensive nonsurgical treatment and doctor-patient communication with care throughout the process, these are keys to improve the clinical efficacy of pancreatic tumors in the era of minimally invasive surgery.
5.The outcomes of robotic-assisted enucleation for tumors located in uncinate process of pancreas in 16 cases
Weiwei JIN ; Huizheng LU ; Jingtao CHEN ; Qicong ZHU ; Chao LU ; Yuanyu WANG ; Yiping MOU
Chinese Journal of Surgery 2024;62(10):923-928
Objective:To summarize the experience of robot-assisted enucleation of tumors located in uncinate process of pancreas.Methods:This is a retrospective case series study. The clinical data of patients with robot-assisted enucleation of tumors located in the uncinate process of pancreas at the Department of Gastroenterology and Pancreatic Surgery,Zhejiang Provincial People′s Hospital from June 2019 to December 2023 were retrospectively analyzed. A total of 16 cases were enrolled,including 10 males and 6 females,with an age( M(IQR)) of 56(21)years (range: 28 to 77 years),and body mass index of 22.4(2.3)kg/m 2 (range:19.8 to 25.6 kg/m 2). Follow-up was asked every 6 to 12 months after the first 3-month postoperative follow-up through out-patient service or via telephone. Results:In total 16 cases,there were 11 cases with pancreatic enucleation,and 5 cases with resection of the uninate process. The operation time was 70(60) minutes (range: 40 to 165 minutes),and the blood loss was 30(13)ml (range: 10 to 80 ml). The rate of pancreatic fistula was 5/16. The length of stay was 8(6)days (range: 5 to 33 days). The pathological finding included non-functional neuroendocrine tumor( n=3),insulinoma( n=2),introductal papillary mucinous neoplasm ( n=5),solid pseudopapillary neoplasm ( n=2),mucinous cystadenoma ( n=1),serous cystadenoma ( n=2),pseudocyst ( n=1). Follow-up as of March 12, 2024, the follow-up time was 16(12)months (range: 3 to 41 months). All patients had no new onset diabetes and no dyspepsia. Conclusion:Robot-assisted surgical system can be used for local resection of uncinate process tumors of pancreas,and the quality of life of patients can be improved.
6.Comparison of the perioperative outcomes of 2 different types of minimally invasive pancreaticoduodenectomy in elderly patients aged ≥65 years
Yufeng REN ; Qitao JIANG ; Yiping MOU ; Weiwei JIN ; Yucheng ZHOU ; Tao XIA ; Chao LU ; Yuanyu WANG ; Qicong ZHU
Tumor 2023;43(6):516-524
Objective:To compare the perioperative outcomes between robotic pancreaticoduodenectomy(RPD)and laparoscopic pancreaticoduode-nectomy(LPD)in patients aged ≥65 years. Methods:The clinical data of 130 patients aged ≥65 years who received minimally invasive pancreaticoduodenectomy(MIPD)at Department of Gastrointestinal and Pancreatic Surgery,Zhejiang Provincial People's Hospital from January 2019 to December 2022 were retrospectively analyzed.The patients were divided into the RPD group(n=66)and the LPD group(n=64)according to the operation method,and the perioperative clinical data were compared between the 2 groups. Results:Compared with the LPD group,the average age of patients in the RPD group was higher than that of the LPD group[(71.95±4.73)years vs(70.39±3.9)years,P<0.05];the RPD group had more patients with diabetes(39.4%vs 18.8%,P<0.05)and cardiopulmonary diseases(37.9%vs 17.2%,P<0.05);the RPD group had shorter operation time[(272.91± 68.38)min vs(362.81±78.24)min,P<0.05]and less intraoperative blood loss[median(range):1 00 mL(50-200 mL)vs 1 50 mL(1 00-200 mL),P<0.05)];the RPD group had higher incidence of chylous fistula(1 2.1%vs 1.6%,P<0.05)but lower incidence of surgical morbidity(37.9%vs 46.9%),serious complications(19.7%vs 34.4%),postoperative pancreatic fistula(12.1%vs 17.2%),biliary fistula(3.0%vs 3.1%),abdominal infection(10.6%vs 14.1%),postoperative bleeding(4.5%vs 4.5%),and postoperative cardiopulmonary complications(1 2.1%vs 20.3%)with no statistically significant difference(P>0.05);the RPD group waited shorter time before restarting diet[(3.97±1.59)d vs(5.34±2.56)d,P<0.05]. Conclusion:MIPD is safe and feasible in patients aged ≥65 years.The incidence of perioperative complications is similar between the 2 groups.Compared with LPD,RPD has shorter operation time,less intraoperative blood loss,and shorter duration before restarting diet after operation,which has certain clinical advantages.
7.Early experience of minimal invasive surgery for adolescent with pancreatic head tumor: a report of 15 cases
Weiwei JIN ; Chao LU ; Yiping MOU ; Yuanyu WANG ; Qicong ZHU ; Tao XIA
Chinese Journal of Surgery 2020;58(7):512-515
Objective:To summarize the characteristics and difficulties of minimal invasive surgery for adolescent with pancreatic head tumor.Methods:The data of adolescent younger than 28 years old with pancreatic head tumor treated at Department of Gastroenterology and Pancreatic Surgery, Zhejiang Province People′s Hospital from January 2014 to December 2019 were analyzed retrospectively. Fifteen cases were enrolled, included 5 males and 10 females. The median age was 20 years(range: 11 to 27 years) and the body mass index was (19.8±2.3)kg/m 2(range: 17.3 to 21.6 kg/m 2). Results:Standard pancreaticoduodenectomy was performed in 12 cases, including 9 cases of laparoscopic surgery and 3 cases of robotic-assisted surgery, and laparoscopic pancreaticoduodenectomy with resection of hepatic flexure of colon was performed on 1 case, and robotic-assisted duodenum-preserving pancreatic head resection with pancreatogastrostomy was performed on other 2 cases. The operative time was (269.0±65.1)minutes(range: 150 to 410 minutes), and the blood loss was (135.6±52.7)ml(range: 50 to 400 ml). Six patients got postoperative complications with gastrointestinal bleeding biochemical leakage and intestinal obstruction( n=1), pancreatic biochemical leakage( n=1), bile leakage( n=1), chylous leakage( n=1), wound infection( n=1), hepatic injury( n=1). The median postoperative hospital stay was 13 days(range: 9 to 22 days).The pathologic findings were solid pseudopapillary neoplasms( n=8), neuroendocrine neoplasms( n=3), introductal papillary mucinous neoplasm( n=1), cystic fibroma( n=1), serous cystadenoma( n=1), Ewing sarcoma( n=1).The median follow-up was 37 months(range: 2 to 75 months).The patient with Ewing sarcoma was diagnosed as liver metastasis at 41 months after surgery and died at 63 months after surgery.All the other patients survived without tumor.Three patients got the long-term complication of bile duct. Conclusions:Most of pancreatic head tumors for adolescent are benign or low malignant. Minimally invasive surgery be the first choice, and function-preserving surgery should be taken into account as much as possible.Perioperative management and communication is essential as the parents pay much attention to the quality of life after surgery.
8.Early experience of minimal invasive surgery for adolescent with pancreatic head tumor: a report of 15 cases
Weiwei JIN ; Chao LU ; Yiping MOU ; Yuanyu WANG ; Qicong ZHU ; Tao XIA
Chinese Journal of Surgery 2020;58(7):512-515
Objective:To summarize the characteristics and difficulties of minimal invasive surgery for adolescent with pancreatic head tumor.Methods:The data of adolescent younger than 28 years old with pancreatic head tumor treated at Department of Gastroenterology and Pancreatic Surgery, Zhejiang Province People′s Hospital from January 2014 to December 2019 were analyzed retrospectively. Fifteen cases were enrolled, included 5 males and 10 females. The median age was 20 years(range: 11 to 27 years) and the body mass index was (19.8±2.3)kg/m 2(range: 17.3 to 21.6 kg/m 2). Results:Standard pancreaticoduodenectomy was performed in 12 cases, including 9 cases of laparoscopic surgery and 3 cases of robotic-assisted surgery, and laparoscopic pancreaticoduodenectomy with resection of hepatic flexure of colon was performed on 1 case, and robotic-assisted duodenum-preserving pancreatic head resection with pancreatogastrostomy was performed on other 2 cases. The operative time was (269.0±65.1)minutes(range: 150 to 410 minutes), and the blood loss was (135.6±52.7)ml(range: 50 to 400 ml). Six patients got postoperative complications with gastrointestinal bleeding biochemical leakage and intestinal obstruction( n=1), pancreatic biochemical leakage( n=1), bile leakage( n=1), chylous leakage( n=1), wound infection( n=1), hepatic injury( n=1). The median postoperative hospital stay was 13 days(range: 9 to 22 days).The pathologic findings were solid pseudopapillary neoplasms( n=8), neuroendocrine neoplasms( n=3), introductal papillary mucinous neoplasm( n=1), cystic fibroma( n=1), serous cystadenoma( n=1), Ewing sarcoma( n=1).The median follow-up was 37 months(range: 2 to 75 months).The patient with Ewing sarcoma was diagnosed as liver metastasis at 41 months after surgery and died at 63 months after surgery.All the other patients survived without tumor.Three patients got the long-term complication of bile duct. Conclusions:Most of pancreatic head tumors for adolescent are benign or low malignant. Minimally invasive surgery be the first choice, and function-preserving surgery should be taken into account as much as possible.Perioperative management and communication is essential as the parents pay much attention to the quality of life after surgery.
9.Laparoscopic resection for gastric stromal tumors with sizes larger than 5 cm
Yunyun XU ; Xiaowu XU ; Yiping MOU ; Renchao ZHANG ; Zhenyuan QIAN ; Chaojie HUANG ; Qicong ZHU
Chinese Journal of General Surgery 2018;33(9):734-736
Objective To investigate the treatment efficacy,feasibility and safety of laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) larger than 5 cm.Methods The clinical data of 31 patients who underwent laparoscopic resection of large gastric GISTs between Jan 2010 and Jun 2017 at Sir Run Run Shaw Hospital and People's Hospital of Zhejiang Province were retrospectively analyzed.Results All operations were successful.Two patients were converted to open surgery.The mean tumor size was (7.2 ±0.5) cm.The mean operation time was (127 ± 12) min,intraoperative blood loss was (83 ±25) ml.The first flatus time was (2.2 ±0.8) days,the first diet resumption time was (2.4 ± 1.2) days,and the median postoperative hospital stay was (5.5 ± 1.5) days.The median follow-up time was 25 months.One patient developing liver metastasis 41 months after primary resection received oral mesylate imatinib therapy for 24 months and was still alive at the last follow-up.One patient died of lung cancer 33 months after primary operation without recurrence of gastric GIST.Conclusions Laparoscopic surgery for gastric GIST larger than 5 cm on laparoscopicaly accessible location is feasible and safe.
10.Efficacy of CyberKnife combined with temozolomide in treatment of brain metastasis of non-small cell lung cancer
Qicong ZHU ; Yahui WANG ; Lin YANG ; Zhengjun GUO ; Yali YUE ; Langfei HU ; Jingfen LU ; Shuyong YU
Cancer Research and Clinic 2018;30(1):17-22
Objective To analyze the efficacy and safety of CyberKnife combined with temozolomide (TMZ) in treatment of brain metastasis of non-small cell lung cancer (NSCLC). Methods From March 2013 to March 2016, 62 NSCLC patients with brain metastases in department of oncology of the 187th Hospital of PLA were divided into two groups according to the random number table method, the CyberKnife combined with TMZ group (CyberKnife + TMZ group, 31 cases) and simple CyberKnife group (CyberKnife group, 31 cases). Hypofractionated radiation of CyberKnife was given 18-36 Gy in 1-5 fractions of 5-25 Gy. CyberKnife+ TMZ group was given temozolomide 150 mg·m-2·d-1 for 5 days in first cycle, then every 28 days they received temozolomide therapy from the second to the sixth cycles: 200 mg·m-2·d-1 for 5 days. The clinical symptom remission rate after the treatment of CyberKnife in one week, the effective rate after CyberKnife in 3 months, the median intracranial progression-free survival time, overall survival, and the incidences of adverse reaction were comparatively analyzed. Results The clinical symptom remission rates of CyberKnife+TMZ group and CyberKnife group after the treatment of CyberKnife in one week were 93.6 % (29/31) and 96.8 % (30/31). There was no significant difference in the clinical symptom remission rates (χ2= 1.207, P=0.547). The effective rates of the two groups after CyberKnife in 3 months were 93.6 % (29/31) and 90.3 %(28/31). There was no significant difference in the effective rates (χ2 = 0.695, P= 0.706). The median intracranial progression-free survival time in CyberKnife + TMZ group (14.0 months) was significantly higher than that in the CyberKnife group (9 months) (χ2=8.977, P=0.003), and the median overall survival time in CyberKnife + TMZ group (15.0 months) was also significantly higher than that in the CyberKnife group (12.0 months) (χ2 = 5.190, P= 0.023). There was no significant difference in the adverse reaction of the central nervous system between the two groups (χ2=0.746, P=0.689), but the adverse reactions of the digestive system (χ2 = 6.062, P= 0.014) and the hematologic system (χ2 = 6.613, P= 0.010) in CyberKnife + TMZ group were significantly higher than those in the CyberKnife group. Systemic adverse reactions of the two groups were tolerated by most patients. Conclusions CyberKnife combined with TMZ is a feasible therapeutic option for NSCLC patients with brain metastases. This therapy can improve the median survival time to cerebral progression of the disease and the median overall survival time.

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