1.Linc-smad7 promotes migration and invasion of pancreatic cancer cells by targeting miR-125b/SIRT1 axis
Lili HAN ; Wenjiao DUAN ; Weixiao ZHOU ; Shuqun ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):112-118
		                        		
		                        			
		                        			Objective To explore the role of long non-coding RNA smad7(Linc-smad7)in invasion and migration of pancreatic cancer(PC)cells and its mechanisms.Methods The expression level of Linc-smad7 in PC tissues and cell lines was detected by qRT-PCR assays.Transwell assays were performed to observe the effect of Linc-smad7 overexpression on the migration and invasion abilities of PaCa-2 cells.Luciferase reporter analysis was made to detect the direct binding effect of Linc-smad7 on miR-125b and miR-125b on Sirtuin1(SIRT1).qRT-PCR assays were used to detect the regulatory effect of Linc-smad7 on miR-125b expression in PaCa-2 cells.qRT-PCR and Western blotting assays were used to detect the regulatory effect of miR-125b on SIRT1 expression.Results Linc-smad7 was significantly increased in PC tissues and cell lines.Paca-2 cells with overexpressed Linc-smad7 showed higher migration and invasion abilities,while miR-125b expression was decreased.After the expression of miR-125b was increased,the expression of SIRT1 was decreased significantly.Luciferase reporter assays results suggested that Linc-smad7 directly targeted with miR-125b,and miR-125b directly bound with SIRT1.Increased Linc-Smad7 or decreased miR-125b could reverse the effect of SIRT1 inhibition on invasion and migration of PaCa-2 cells.Conclusion Linc-smad7 promotes invasion and migration of PaCa-2 cells through miR-125b/SIRT1 axis.
		                        		
		                        		
		                        		
		                        	
2.Expression and prognostic significance of nuclear matrix protein 4 in hepatocellular carcinoma
Jinhai LI ; Huawei ZHAI ; Guangzheng SUN ; Haifeng ZHANG ; Minghui ZHU ; Yu CAI ; Shenghua PAN ; Shuqun LI
Chinese Journal of Hepatobiliary Surgery 2024;30(2):87-92
		                        		
		                        			
		                        			Objective:To investigate the expression of nuclear matrix protein 4 (NMP4) in hepatocellular carcinoma (HCC), and its relationship with clinicopathological features and survival prognosis of patients.Methods:The clinical data of 100 HCC patients who were treated with radical resection of liver cancer in the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Wenzhou Medical University from July 1, 2014 to July 1, 2019 were retrospectively analyzed. There were 63 males and 37 females, aged (58.5±10.4) years old. Immunohistochemical method was used to detect the expression of NMP4 protein in HCC cancer tissue and the corresponding adjacent normal tissue. According to the expression of NMP4 in HCC tissues, 100 patients were divided into two groups: the NMP4-positive expression group ( n=62) and the NMP4-negative expression group ( n=32). Univariate analysis was performed on the relationship between NMP4 expression and clinical pathological features as well as overall survival of HCC patients. Cox multivariate analysis was performed on the factors influencing postoperative prognosis of HCC patients. Results:Immunohistochemistry results showed that NMP4 was primarily expressed in the nucleus, the positive expression rate of NMP4 in HCC tissues was higher than that in adjacent non-cancerous tissues [62.0% (62/100) vs. 8.0%(8/100)], and the difference was statistically significant ( χ2=2.12, P=0.003). Univariate analysis revealed that the overall survival of HCC patients was correlated with the degree of tumor differentiation, tumor length, BCLC stage, number of tumor foci, vascular tumor thrombus and expression of NMP4 (all P<0.05). Cox multivariate analysis revealed that low differentiation, high BCLC stage (stage C), number of tumor foci (≥3), and positive expression of NMP4 were independent risk factors affecting postoperative survival and recurrence-free survival of HCC patients. The median overall survival and median recurrence-free survival of HCC patients in the NMP4-positive expression group were 22.3 months and 11.5 months, respectively. In contrast, that in the NMP4-negative expression group were 40.6 months and 19.4 months, respectively. The cumulative survival rate and recurrence-free survival rate of HCC patients in the NMP4-positive expression group were lower than those in the NMP4-negative expression group, and the differences were statistically significant (both P<0.05). Conclusion:Positive NMP4 expression was closely correlated with malignant biological progression and poor prognosis of HCC patients.
		                        		
		                        		
		                        		
		                        	
3.Therapeutic potential of exosome derived from remote ischemic conditioning in alleviating neurologic dysfunction after cardiac arrest in a rat model
Heng ZHAI ; Jihui WANG ; Xi CHEN ; Yang ZHANG ; Shuqun HU ; Jun WANG ; Yigen PENG ; Ningjun ZHAO ; Xianliang YAN ; Chenglei SU ; Tie XU
Chinese Journal of Emergency Medicine 2024;33(7):991-998
		                        		
		                        			
		                        			Objective:To investigate the therapeutic effect of exosomes derived from remote ischemic conditioning on neurological dysfunction after cardiopulmonary resuscitation in a rat model of cardiac arrest and the relationship with glycocalyx protection.Methods:Exosomes were isolated from the blood of healthy adult male Sprague-Dawley rats using ultracentrifugation after undergoing remote ischemic conditioning for use as intervention drugs. Nanoparticle tracking analysis technology was used for exosome detection. Thirty-six adult male Sprague-Dawley rats were randomly assigned to 3 groups ( n=12 each) :Sham group, Control group and Exosome group. Cardiac arrest was induced by asphyxia for 7 min in the Control and Exosome groups. Placebo or exosomes (1×10 10 Particles) were infused intravenously at 5 min after the rats had returned of spontaneous circulation. Neuropsychological deficit score (NDS), open field test, Y maze and Morris water maze were used to assess neurological outcomes. The levels of plasma Hyaluronic acid (HA) and syndecan-1 (Sdc-1) were detected by Elisa. The expression levels of matrix metalloproteinase-2/9 (MMP-2/9) in hippocampal CA1 region were detected by Western blot. Results:After undergoing remote ischemic conditioning, the plasma levels of exosomes were elevated in rats compared to normal rats. Compared with the control group, the behavioral experiment of rats in the exosomes group were significantly improved, as evidenced by an increase in horizontal locomotor distance (5.86±2.89 vs. 17.53±5.51, P< 0.05), an increase in the correct rate of spontaneous alternation (13.29±15.07 vs. 42.63±10.25, P< 0.05), and a shortening of avoidance latency (25.83±8.54 vs. 13.49±4.55, P< 0.05). Plasma HA and Sdc-1 levels were significantly lower 24 h after resuscitation (HA: 26.34±9.83 vs. 14.84±6.26, P< 0.05; Sdc-1: 0.05±0.03 vs. 0.02±0.02, P<0.05), along with significantly lower MMP-2/9 levels in hippocampal tissue. Conclusions:Exosomes extracted from the plasma of rats undergoing remote ischemic conditioning can improve neurological dysfunction after cardiac arrest in rats, and the mechanism may be related to the inhibition of metalloproteinases and the reduction of endothelial glycocalyx degradation.
		                        		
		                        		
		                        		
		                        	
4.Clinical significance of expression of MUC5B and PDCD4 protein in intrahepatic cholangiocellular carcinoma
Jinhai LI ; Fujing CAI ; Huawei ZHAI ; Yu YANG ; Guangzheng SUN ; Haifeng ZHANG ; Minghui ZHU ; Yue LIN ; Shenghua PAN ; Shuqun LI
Chinese Journal of Hepatobiliary Surgery 2024;30(10):755-760
		                        		
		                        			
		                        			Objective:To investigate the expression characteristics of mucin 5B (MUC5B) protein and programmed cell death factor 4 (PDCD4) protein in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram model for prognosis prediction.Methods:Clinical data of 100 patients who underwent radical surgical resection and were diagnosed as ICC by postoperative pathology from September 2009 to September 2020 in the Third Affiliated Hospital of Wenzhou Medical University were retrospectively selected, including 46 males and 54 females, aged (56.9±12.2) years old. Immunohistochemistry was used to detect the expression of MUC5B and PDCD4 protein in 100 cases of ICC and corresponding adjacent tissues respectively, and the relationship between them and clinicopathological factors of ICC patients was analyzed. Univariate and multivariate Cox regression analysis were performed to analyze the influencing factors on postoperative prognosis of ICC patients. The nomogram model was constructed using rms package and performed internal verification.Results:The positive expression rate of MUC5B protein in ICC was 76.0% (76/100), which was higher than that in para-cancer tissues 27.0%(27/100), and the difference was statistically significant ( χ2=11.33, P=0.015). While the positive expression rate of PDCD4 protein in ICC was 21.0%(21/100), which was lower than that in normal tissues 73.0% (73/100), and the difference was statistically significant ( χ2=15.57, P=0.007). Multivariate Cox regression analysis showed that ICC patients with carbohydrate antigen 19-9>37 kU/L, tumor length>5 cm, tumor TNM stage Ⅱ/Ⅲ, tumor medium/low differentiation, MUC5B positive expression, and PDCD4 negative expression had a high risk of short survival after resection (all P<0.05). The nomogram model was constructed based on the above indicators, and the C-index was 0.801. The postoperative survival calibration curve showed that the high predictive survival fit of the nomogram model, and the area under the receiver operating characteristic curve was 0.862. Conclusions:Positive expression of MUC5B protein and negative expression of PDCD4 protein in ICC tissue suggest poor prognosis of ICC patients. The nomogram model constructed on the basis of MUC5B and PDCD4 protein is well distinguished and has ideal predictive efficacy.
		                        		
		                        		
		                        		
		                        	
5.Efficacy of Lenvatinib Combined with Anti–PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study
Xiangye OU ; Junyi WU ; Jiayi WU ; Yangkai FU ; Zhenxin ZENG ; Shuqun LI ; Yinan LI ; Deyi LIU ; Han LI ; Bin LI ; Jianyin ZHOU ; Shaowu ZHUANG ; Shuqun CHENG ; Zhibo ZHANG ; Kai WANG ; Shuang QU ; Maolin YAN
Cancer Research and Treatment 2024;56(4):1207-1218
		                        		
		                        			 Purpose:
		                        			The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. 
		                        		
		                        			Materials and Methods:
		                        			This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. 
		                        		
		                        			Results:
		                        			During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. 
		                        		
		                        			Conclusion
		                        			Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects. 
		                        		
		                        		
		                        		
		                        	
6.NELFE promotes the migration and invasion of triple negative breast cancer cells by inhibiting NDRG2 expression
Lili HAN ; Weixiao ZHOU ; Shuqun ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(3):427-432
		                        		
		                        			
		                        			【Objective】 To explore the effect of negative elongation factor E(NELFE) on the invasion and migration of triple-negative breast cancer(TNBC) cells and its mechanisms. 【Methods】 qRT-PCR was used to detect the expression of negative elongation factor E(NELFE) in triple-negative breast cancer(TNBC) tissues and adjacent tissues. NELFE expression was upregulated in MDA-MB-231 cell lines via lentivirus transfection. Transwell assay was used to observe the effect of elevated NELFE expression on the migration and invasion of MDA-MB-231 cells. The RNA stability assay was used to detect the influence of NELFE on the stability of the mRNA of N-myc downstream regulated gene2(NDRG2). Western blotting analysis was used to detect the regulatory function of NELFE on NDRG2 protein expression. 【Results】 NELFE expression was increased in TNBC tissues. After the overexpression of NELFE, the migration and invasion of MDA-MB-231 cells were significantly enhanced, NDRG2 mRNA stability was decreased, and NDRG2 protein expression level was downregulated. NDRG2 expression was upregulated in MDA-MB-231 cell lines with overexpressed NELFE; cell migration and invasion abilities were decreased. 【Conclusion】 NELFE inhibited NDRG2 expression by decreasing the stability of NDRG2 mRNA and promoted the migration and invasion of TNBC cells.
		                        		
		                        		
		                        		
		                        	
7.Reverse effect of lentinanin on Sorafenib resistance in cultured hepatocellular carcinoma cells and its mechanism
Lili HAN ; Fei WU ; Lanxuan HUANG ; Shuqun ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(1):48-52,64
		                        		
		                        			
		                        			【Objective】 To investigate the effect of lentinan on Sorafenib resistance in hepatocellular carcinoma (HCC) cells BEL-7402/S and its mechanism. 【Methods】 CCK-8 method was used to detect the proliferation-toxicity of lentinan and Sorafenib on BEL-7402 and BEL-7402/S cells, and the drug resistance reversal multiple of Sorafenib. The effects of lentinan on mRNA and protein expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1α) in BEL-7402/S cells were determined by RT-qPCR and Western blotting. 【Results】 Lentinan reduced the proliferation of BEL-7402 and BEL-7402/S cells. Lentinan showed at least a partial reversal of drug resistance to sorafenib in BEL-7402/S cells and down-regulated the mRNA and protein expressions of VEGF and HIF-1α in BEL-7402/S cells. 【Conclusion】 Lentinan can partially reverse the effect of BEL-7402/S cells on Sorafenib resistance, and the mechanism may be related to the down-regulation of VEGF and HIF-1α expressions.
		                        		
		                        		
		                        		
		                        	
8.Acceptance of advanced breast cancer patients to the advance care planning and its influencing factors
Li WANG ; Fang ZHAO ; Xiaoning LI ; Yinbin ZHANG ; Weiwei WANG ; Jing WANG ; Shuqun ZHANG
Chinese Journal of Modern Nursing 2021;27(34):4694-4699
		                        		
		                        			
		                        			Objective:To explore the acceptance of advanced breast cancer patients to the advance care planning, and analyze its potential influencing factors.Methods:From October 2019 to January 2021, convenience sampling was used to select 75 advanced breast cancer patients in the Oncology Department of the Second Affiliated Hospital of Xi'an Jiaotong University as the research object. The patients were investigated with the General Information Questionnaire, Patient's Advance Care Planning Acceptance Questionnaire (ACPQ), Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC) and the Social Support Rating Scale (SSRS). Univariate analysis, Pearson correlation analysis and multiple linear regression analysis were used for data analysis.Results:A total of 75 questionnaires were distributed and 72 valid questionnaires were returned. The total ACPQ score of advanced breast cancer patients was (70.60±4.46). The results of univariate analysis showed that there were statistically significant differences in the ACPQ scores of patients with different education levels, residence, marital status, bereavement experience, hospitalization experience, and knowledge of the time of disease diagnosis ( P<0.05). Multiple linear regression analysis showed that the social support was an influencing factor of patients' acceptance of the advance care planning, and the difference was statistically significant ( P<0.01) . Conclusions:The acceptance of advanced breast cancer patients to the advance care planning is mainly related to the patient's social support. Medical and nursing staff should strengthen the understanding and utilization of patients' social support, and promote patients' participation in advance care planning.
		                        		
		                        		
		                        		
		                        	
9.Application of intraoperative red cell salvage and autologous blood transfusion in cesarean section of pregnant women with central type of placenta previa
Jian LI ; Xiang CHEN ; Juncheng XIONG ; Shuqun LIU ; Hongping ZHANG ; Yanqin WU
Chinese Journal of Primary Medicine and Pharmacy 2019;26(7):782-785
		                        		
		                        			
		                        			Objective To obsOrvO thO safOty and OffOct of intraopOrativO cOll salvagO and autologous blood transfusion during cOsarOan sOction with cOntral placOnta prOvia.Methods From April 2015 to March 2016, 25 prOg-nants with cOntral placOnta prOvia diagnosOd by MRI and ultrasound and undOrwOnt sOlOctOd caOsarOan sOction in thO POoplO′s Hospital of WOnzhou wOrO includOd. WhOn thO amount of blood in thO rOcovOry tank was 450 mL or thO obstOtrician rOquirOd, thO wash and rOtransfusion dOvicO was startOd-up. Hb and Hct wOrO mOasurOd bOforO and aftOr thO parturiOnt, and thO blood was rOcovOrOd. ThO blood loss, rOcovOry of blood, blood transfusion, allogOnOic RBC infusion and thO sidO OffOcts aftOr transfusion and 42 d of postpartum wOrO rOcordOd.Results No sOrious complica-tions wOrO rOcordOd in all prOgnants. FivO casOs(20% ) wOrO only rOcovOrOd and thO autologous blood transfusion and transfusion of thO allogOnOic RBC wOrO not carriOd out. In 14 casOs(56% ),only thO autologous blood was rOturnOd to thO puOrpOra. ThO volumO of blood transfusion was 705 mL(430,1 535). Six casOs(24% ) had massivO blOOding during thO opOration,3690 mL(1 900,8 750),and thO autologous blood transfusion volumO was 2939 mL(1 167, 4 206),and thO allogOnOic RBC transfusion was 3.5U(1.5,11.5).Conclusion Autologous blood transfusion can bO usOd safOly in thO caOsarOan sOction of thO cOntral placOnta prOvia, and can rOducO thO allogOnOic RBC transfusion.
		                        		
		                        		
		                        		
		                        	
10.The way of thinking decides exit and the innovation leads future: practice and implementation of Academician Lau Wan Yee's research ideas
Weiping ZHOU ; Feng SHEN ; Shuqun CHENG ; Tian YANG ; Gang HUANG ; Siyuan FU ; Jin ZHANG ; Kui WANG ; Dong WU ; Mengchao WU
Chinese Journal of Digestive Surgery 2018;17(1):51-54
		                        		
		                        			
		                        			Through analysis of Lau Wan Yee's published papers,monographs,conference speeches,research designs / revisions for major hospitals in China,combined with analysis of articles revised by Academician Lau in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University for the past decade,authors came up with 9 points in Academician Lau's research ideas.Academician Lau has played a huge and leading role in improving clinical skills and scientific research levels,as well as in development and internationalization of hepatobiliary and pancreatic surgery in China.To summarize the research ideas of Lau is of great importance to the future generations of surgeons.
		                        		
		                        		
		                        		
		                        	
            
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