1.Pramlintide improves cognitive function in Alzheimer's disease mice through antioxidant stress and PI3K/Akt pathway
Yating LIU ; Jing LU ; Xiangqian FENG ; Dongling WANG ; Qirong LIAO ; Hongyan YANG ; Huadong ZHOU
Journal of Army Medical University 2025;47(16):1862-1871
Objective To investigate the effect of pramlintide,a pancreatic amyloid peptide analog,on learning and memory of Alzheimer's disease(AD)mice through antioxidant stress,and to determine the expression of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods The APP/PS1 mice were divided into a pramlintide treatment group(intraperitoneal injection of 0.5 μmol/L per day for 10 weeks)and an AD group(same dose of PBS),with 5 mice in each group.The learning and memory abilities were detected with water maze test,the pathological changes of the hippocampus were observed with HE staining and immunohistochemistry,the morphological characteristics of dendritic spines in hippocampus were observed after Golgi staining,and the ultrastructure of hippocampal neurons was observed through transmission electron microscopy(TEM).The content of malondialdehyde(MDA)and the level of superoxide dismutase(SOD)in the hippocampal tissue were detected by biochemical assay,and the levels of inflammatory factors IL-6,TNF-α and IL-1β were determined with ELISA.Western blotting was applied to measure the expression of PI3K/Akt signaling pathway related proteins in the hippocampus.In the cell experiment,SH-SY5Y cells were added with Aβ 1-42 to establish a cell model of AD.After the cells were treated with pramlintide,the levels of oxidative stress and inflammatory response were detected,and cell apoptosis was detected by immunofluorescence.Results The animal experiments showed that pramlintide treatment resulted in significantly shortened escape latency(P<0.01),increased platform crossings(P<0.01),and prolonged time to exploring hidden platform(P<0.01).In the hippocampal tissue of the pramlintide treatment group,HE staining displayed hippocampal neurons in high density and neat arrangement(P<0.05),immunohistochemical results showed significantly reduced Aβ protein(P<0.01),Golgi staining results demonstrated more dendritic spines(P<0.05),TEM revealed almost intact neuronal mitochondrial structure,with reduced vacuolization and clear and identifiable morphology.When compared with the AD group,the levels of oxidative stress and inflammatory response were decreased(P<0.01),and the relative expression of p-PI3K/PI3K and p-Akt/Akt proteins was increased(P<0.01)in the treatment group.In cell experiments,the levels of oxidative stress and inflammatory response were decreased in AD cell model after pramlintide treatment(P<0.01),and the results of immunofluorescence showed that cell apoptosis was declined(P<0.01).Conclusion Pramlintide can improve the cognitive function,reduce the hippocampal deposition of Aβ,reduce oxidative stress and inflammatory response,alleviate the pathological changes of neuronal ultrastructure,and enhance the expression of PI3K/Akt signaling pathway in AD mice.
2.Molecular mechanism of circ-Tns3/miR-671-5p/sirt1 axis mediating neuronal damage in Alzheimer's disease
Jing LU ; Yating LIU ; Xiangqian FENG ; Donglin WANG ; Qirong LIAO ; Hongyan YANG ; Huadong ZHOU
Journal of Army Medical University 2025;47(16):1872-1882
Objective To investigate the expression level of circular RNA circ-Tns3 in Alzheimer's disease(AD)mice and its role in Aβ-induced neuronal damage.Methods Five APP/PS1 transgenic AD mice and 5 wild-type(WT)mice,weighting of 23~26 g and aged 6 months were subjected in the study.Morris water maze test was used to assess learning and memory abilities,and immunohistochemical staining was performed to observe the number of Aβ plaques in the hippocampal tissue.Subsequently,total RNA was extracted from the brains to detect the differential expression of circRNAs between AD and WT mice,and the results were further analyzed with Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.The top 6 differentially expressed circRNAs were validated by real-time quantitative PCR(RT-qPCR).In in vitro experiments,Aβ1-42 was used to treat neuronal cells to establish AD cell model,and si-circ-Tns3 was transfected into Aβ1-42-treated neuronal cells to knock down circ-Tns3.RT-qPCR was used to determine the expression levels of circ-Tns3 and miR-671-5p.Cell viability and apoptotic rate were detected by CCK-8 assay and TUNEL staining,respectively.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)were measured using corresponding kits,and the levels of inflammatory factors IL-6,IL-1β,and TNF-α were detected with ELISA.The interaction between circ-Tns3 and miR-671-5p was verified by dual-luciferase reporter assay and RNA-binding protein immunoprecipitation(RIP)assay.The expression level of Sirt1 protein was detected by Western blotting.Results The 6-month-old AD mice exhibited significant cognitive impairment and Aβ deposition(P<0.01).There were 269 differentially expressed circRNAs identified between AD and WT mice,of which 159 were up-regulated and 110 down-regulated.GO and KEGG enrichment analyses showed that these differentially expressed circRNAs were mainly involved in synaptic transmission,memory,and cholinergic synapse signaling pathways.The expression of circ-Tns3 was significantly increased not only in the brain tissue of AD mice but also in neuronal cells after Aβ1-42 treatment.In cellular experiments,knockdown of circ-Tns3 significantly reduced cell viability and number of apoptotic cells in Aβ1-42-treated neuronal cells,decreased MDA content,increased SOD activity,and reduced the levels of IL-6,IL-1β,and TNF-α(P<0.01).The starBase database predicted that circ-Tns3 and miR-671-5p have complementary sequences,and dual-luciferase reporter and RIP assays confirmed their interaction.The bioinformatics database predicted that miR-671-5p and sirt1 have complementary sequences.Western blotting indicated that in neuronal cells treated with Aβ1-42,the expression of sirt1 was increased after knockdown of circ-Tns3(P<0.01).In Aβ1-42-treated neuronal cells,after knockdown of circ-Tns3,addition of miR-671-5p inhibitor significantly decreased the expression level of sirt1 protein(P<0.01).Conclusions circ-Tns3 is highly expressed in AD mice and cell model of AD.Knocking circ-Tns3 down improves neuronal damage.circ-Tns3 may be involved in the neuronal damage through regulating sirt 1 protein by binding to miR-671-5p.
3.Postoperative complications of ex vivo liver resection combined with autologous liver transplantation in treatment of advanced hepatic alveolar echinococcosis at high altitude and related prevention and treatment strategies
Qingshan TIAN ; Shaopei FENG ; Yamin GUO ; Xiumin HAN ; Shunyun ZHAO ; Chengjie YE ; Yongde AN ; Shile WU ; Xiangqian WANG ; Haibo ZHENG ; Wenjun ZHU ; Jide A ; Wei GAO ; Hongshuai PAN
Journal of Clinical Hepatology 2021;37(9):2153-2160
Objective To investigate the postoperative complications of ex vivo liver resection combined with autologous liver transplantation in the treatment of end-stage hepatic alveolar echinococcosis at high altitude and related prevention and treatment strategies. Methods Surgical data and follow-up data were collected from 11 patients with end-stage hepatic alveolar echinococcosis who underwent autologous liver transplantation in Qinghai People's Hospital from January 2013 to March 2019, and intraoperative and postoperative conditions were analyzed. Results All 11 patients underwent autologous liver transplantation successfully, without intraoperative death, among whom 2(18.18%) underwent hemi-extracorporeal hepatectomy and 9 (81.82%) underwent total extracorporeal hepatectomy. For the reconstruction of the retrohepatic inferior vena cava, 2 patients (18.18%) underwent reconstruction with the autologous great saphenous vein, 4 patients (36.36%) underwent reconstruction with artificial vessels, and the autologous retrohepatic inferior vena cava was preserved in 5 patients (45.45%). For biliary reconstruction, 8 patients (72.73%) underwent choledochoenterostomy and 3 (27.27%) underwent choledochocholedochostomy. The main postoperative complications of the 11 patients included bleeding in 2 patients (18.18%), bile leakage and abdominal infection in 4 patients (36.36%), bilioenteric anastomotic stenosis in 1 patient (9.09%), thrombus in 2 patients (18.18%), pulmonary infection and pleural effusion in 2 patients (18.18%), and echinococcosis recurrence in 1 patient (9.09%). Of all 11 patients, 2 (18.18%) died during the perioperative period, and the other 9 patients (81.82%) were improved and discharged. Conclusion Bleeding, biliary complications, and infection are the main causes of death in patients undergoing autologous liver transplantation at high altitude. An accurate understanding of surgical indication, careful multidisciplinary evaluation before surgery, superb operation during surgery, standardized surgical procedures, and fine perioperative management are the key to reducing perioperative mortality, avoiding and reducing postoperative complications, and achieving good long-term survival in patients undergoing autologous liver transplantation.
4.Next generation sequencing analysis of drug metabolism related IncRNA in children after living donor liver transplantation
Tian QIN ; Xiangqian GU ; Jianxin ZHENG ; Jinchuan LIU ; Yuanjia TANG ; Feng XUE ; Qiang XIA
Chinese Journal of Organ Transplantation 2019;40(4):219-225
Objective To employ high-throughput next generation sequencing (NGS) for analyzing the expression of lneRNAs and mRNAs in donor samples from pediatric living donor liver transplantation and search differentially expressed lncRNAs and drag metabolic gene for individualized guidance of immunosuppressive agents.Methods Between October 2016 and December 2017,10 liver tissue specimens from living donor liver transplantation children were collected and divided into fast and slow metabolic groups (n =5 each) according to the postoperative profiles of drug metabolism.Samples were assayed for high-throughput NGS.Target analysis was used for functional pathways and screening target genes prediction.Results There were differentially expressed 908 mRNAs and 1228 lncRNAs between slow metabolic and fast metabolic groups (P<0.05).According to the abundance and difference,22 up-regulated and 18 down-regulated mRNAs,13 up-regulated and 24 down-regulated lncRNAs were selected.In addition to CYP3A5,CYP2C19,CYP1A2 and UGT1A1 might affect the metabolism of tacrolimus.At the same time,NONHSAT108617.2 in differemially expressed lncRNAs might regulate the expression of CYP3A5 gene.Conclusions This study has comprehensively analyzed the expression of lncRNAs in donor liver from pediatric liver transplantation.Some differentially expressed drug metabolism related genes may affect tacrolimus metabolism in vivo and thus the postoperative use of immunosuppressive drugs.
5.Diagnosis and treatment for severe hemorrhage of portal vein system after pancreaticoduodenectomy
Jian FENG ; Xiangqian ZHAO ; Hangyu ZHANG ; Bin LIANG ; Shichun LU
Chinese Journal of Hepatic Surgery(Electronic Edition) 2018;7(6):482-485
Objective To investigate the diagnosis and treatment for severe hemorrhage of portal vein system after pancreaticoduodenectomy (PD).Methods Clinical data of 6 patients with severe portal vein hemorrhage after PD in Chinese PLA General Hospital from January 2000 to December 2017 were retrospectively analyzed.All patients were male,aged 50-70 years with a median age of 56 years.The informed consents of all patients were obtained and the local ethical committee approval was received.The primary diseases were 2 cases of distal bile duct carcinoma,2 cases of pancreatic head ductal adenocarcinoma,1 case of duodenal carcinoma and 1 case of duodenal papilla carcinoma.3 patients underwent pylorus-preserving PD and 3 underwent classic PD.Results Among the 2 149 cases undergoing PD,6 suffered from portal vein system hemorrhage after operation with an incidence of 0.28%.Portal vein hemorrhage occurred from 6 to 38 d after PD with a median of 20 d.All 6 cases were complicated with pancreatic fistula,with symptom of abdominal bleeding or hematochezia.Portal vein or superior mesenteric vein hemorrhage was confirmed by reoperation or angiography.3 patients received portal vein stent implantation and 3 underwent reoperation.After operation,4 cases survived and 2 died of hemorrhagic shock.Conclusions Massive portal vein system hemorrhage after PD is rare.Its diagnosis depends on clinical manifestations,surgical exploration and angiography.The treatments include surgical suture and interventional therapy.Portal vein stent implantation has been proven a safe and effective treatment and can be the preferred alternative treatment for the complication.
6.Expression and significance of Mnk2 and eIF4E in esophageal squamous cell carcinoma
Bo ZENG ; Yanfen FENG ; Qitao HUANG ; Jingfu CHEN ; Xin ZHANG ; Xiangqian HAN ; Shuishen ZHANG ; Jianyong ZOU ; Chunhua SU ; Zhenguang CHEN ; Honghe LUO ; Yiyan LEI
Chinese Journal of Pathophysiology 2017;33(2):349-352
AIM: To investigate the expression and significance of MAPK-interacting kinase-2 ( Mnk2 ) and eukaryotic initiation factor 4E ( eIF4E) in the patients with resected esophageal squamous cell carcinoma ( ESCC ). METHODS:The protein expression of Mnk2 and eIF4E in ESCC tissues (98 cases) and normal esophageal tissues (20 cases) were assessed by immunohistochemistry (IHC), and their correlations with clinicopathological features were statisti-cally analyzed.RESULTS:The over-expression rate of Mnk2 and eIF4E was 68.4%(67/98) and 61.2%(60/98), re-spectively.The expression of Mnk2 had a positive correlation with eIF4E (P<0.05).Clinicopathologic analysis showed that Mnk2 expression was significantly correlated with T classification ( P<0.05 ) and clinical stage ( P<0.05 ) .CON-CLUSION:The over-expression of Mnk2 was significantly related to the tumor invasive depth , TNM stages and expression of eIF4E in ESCC.Expression of Mnk2 and eIF4E may have a cooperative formation mechanism in the development of ESCC.
7.Delta-shaped anastomosis in total laparoscopic distal gastrectomy
Limin FENG ; Gang LI ; Huajie ZHANG ; Xianchun SUN ; Xiangqian GONG
Chinese Journal of General Surgery 2015;30(10):759-761
Objective To explore the feasibility of laparoscopically intracorporeal delta-shaped anastomosis in distal gastrectomy.Methods 82 consecutive patients with distal gastric cancer received laparoscopic distal gastrectomy, including intracorporeal delta-shaped anastomosis in 39 cases, and handassisted Billroth-Ⅰ anastomosis in 43 cases.The operative time, blood loss, anastomosis time were compared between the two groups.Results There were no differences between the two groups with regard to the operative time [(215 ± 24) min vs.(207 ± 13) min, t =0.406, P > 0.05] and blood loss [(56 ±21)ml vs.(65 ± 26)ml, t =1.441, P > 0.05], although the intracorporeal Delta-shaped anastomosis was more time-consuming than the extracorporeal Billroth-Ⅰ anastomosis [(17 ± 8) min vs.(12 ± 3) min, t =2.529, P < 0.05].Conclusions Demanding expertise and some skills, totally laparoscopic distal gastrectomy with intracorporeal delta-shaped anastomosis is safe and feasible.
8.Establishment of clinical nursing pathway for artificial abortion and effect assessment
Xiaomei WANG ; Yuehong LIU ; Xiangqian LIU ; Lisha LI ; Chengyun FENG
Chinese Journal of Practical Nursing 2011;27(20):5-7
Objective To build clinical nursing pathway for artificial abortion operation and explore the effect of this method. Methods The nursing pathway was designed and carried out. The satisfaction degree with nursing, status of patients' awareness about contraception and artificial abortion operation was compared before and after the nursing pathway was implemented. Results Before and after the nursing pathway was implemented,the proportion of missing item of operation record was 0.636 and 0.013, the satisfaction degree with nursing was 77.0% and 92.3%, rate of patients' awareness about contraception and artificial abortion operation was 47.6% and 96.1%. Conclusions The clinical nursing pathway for artificial abortion operation may improve the degree of satisfaction- and the status of patients' awareness about contraception and artificial abortion operation, and decline the proportion of missing item of operation note, it ensures high nursing quality and safety surgery, which is worthy of popularizing.
9.Diagnosis and treatment of 20 cases of pseudotumorous pancreatitis
Xiangqian ZHAO ; Ningxin ZHOU ; Yuquan FENG
Chinese Journal of Hepatobiliary Surgery 1998;0(06):-
Objective To investigate the diagnosis and treatment of pseudotumorous pancreatitis. Methods A retrospective clinical analysis was made on 20 cases with pseudotumorous pancreatitis in one stage from 1983.7 to 2004.5. Resulds There were 14 males and 6 females. Jaundice and abdominal pain were the major complaints. 17 cases underwent surgery, including cholangiojejunum Roux-en-Y anastomosis in 11cases, pancreatoduodenectomy in 3 cases, laparotomy and biopay in 3 cases . 3 cases underwent US-guided needle biopsy. All the 15 cases who were followed up had no jaundice at all after operation and abdominal pain relief was achieved to various degree. Conclusion It's difficult to diagnose pseudotumorous pancreatitis before operation. Hepatojejunal Roux-en-Y anastomosis was suitable for the patients with obstructive jaundice. When refractory abdominal pain was encountered or intraoperative pathologic diagnose was diffcult, pancreaticoduodenectomy should be recommended.

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