1.Screening ferroptosis associated with glioblastoma prognosis and immunity based on bioinformatics
Hao SUN ; Zhijuan ZHAO ; Lian MENG ; Chunxia LIU
Acta Universitatis Medicinalis Anhui 2024;59(3):506-514
		                        		
		                        			
		                        			Objective To investigate the molecular mechanism of ferroptosis in glioblastoma(GBM)and to provide insights for identifying new therapeutic targets.Methods GSE108474 was selected from gene expression omnibus(GEO)database and differentially expressed genes(DEGs)in GBM were obtained by using GEO2R,compared with the gene set in the Ferroptosis database(FerrDb)to identify ferroptosis-related gene.GO and KEGG enrich-ment analyses were conducted using DAVID database.A protein-protein interaction network was created using String website.Hub genes with high connectivity were confirmed using Cytoscape software.Prognostic and immune infiltration analyses were performed using TIMER website.RNA expression levels and gene correlation analyses were carried out using GEPIA website.Differential expression of hub gene proteins was analyzed by using the HPA database.Tumor immune characteristic correlations were examined using TISIDB database.Differences in mRNA expression of hub genes between tumor cells A172 and U251MG and normal astrocytes HA1800 were compared u-sing the quantitative real-time PCR.Results Out of 5 331 differentially expressed genes,114 were related to fer-roptosis.GO and KEGG enrichment analysis suggested that these 114 genes might play roles in positive regulation of gene expression,and affect tumor progression through ferroptosis and autophagy pathways.10 hub genes were i-dentified in the protein-protein interaction network,among which cluster of differentiation 44(CD44),murine double minute 2(MDM2)and signal transducer and activator of transcription 3(STAT3)were found to be highly expressed in tumors with lower survival rates.CD44,MDM2 and STAT3 mRNA expression were higher in GBM cells compared to normal cells.Protein expression of CD44,MDM2 and STAT3 was higher in high-grade glioma tis-sues than that in normal tissues.The expression of three genes in the tumor was negatively correlated with ferropto-sis.Immune infiltration analysis revealed that CD44,MDM2 and STAT3 in the tumor were related to the infiltration of neutrophils,CD4+T cells,and dendritic cells,and the expression of three genes was related to various chemo-kines and their receptors.Conclusion CD44,MDM2 and STAT3 may play a role in tumor ferroptosis and immune regulation,which have the potential to become a therapeutic target for GBM.
		                        		
		                        		
		                        		
		                        	
2.Clinical features and outcomes of newly diagnosed follicular lymphoma concurrent with diffuse large B-cell lymphoma component
Zhijuan LIN ; Jie ZHA ; Shuhua YI ; Zhifeng LI ; Lingyan PING ; Xiaohua HE ; Haifeng YU ; Zhong ZHENG ; Wei XU ; Feili CHEN ; Ying XIE ; Biyun CHEN ; Huilai ZHANG ; Li WANG ; Kaiyang DING ; Wenyu LI ; Haiyan YANG ; Weili ZHAO ; Lugui QIU ; Zhiming LI ; Yuqin SONG ; Bing XU
Chinese Journal of Hematology 2022;43(6):456-462
		                        		
		                        			
		                        			Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.
		                        		
		                        		
		                        		
		                        	
3.Clinical blood use in Tibet Autonomous Region People′s Hospital: A respective study of 2014~2018
Aiping WANG ; Zhuoga LABA ; Chunmei ZHAO ; Zhuoga MIMA ; Zhijuan LIU ; Xuejun ZHANG
Chinese Journal of Blood Transfusion 2021;34(1):48-52
		                        		
		                        			
		                        			【Objective】 To retrospectively investigate the clinical transfusion status in Tibet Autonomous Region People′s Hospital, in order to provide data basis for further improvement of the rational and scientific blood use in our hospital. 【Methods】 Medical records of transfusion recipients in our hospital from 2014 to 2018 were investigated via HIS system, and such indicators as total clinical blood use, usage of whole blood and blood components, blood transfusion per capita, usage of blood components with different types. and the usage of red blood cells and plasma in each clinical department were retrospectively analyzed. 【Results】 The total clinical blood usage of our hospital increased from 3 930.5 U in 2014 to 4 949 U in 2018, with an annual growth rate of 5.93%. The average blood use per capita in 2014 and 2018 was 0.205 U vs 0.218 U, and incidence of blood component transfusion was 47.18% vs 99.02% The proportion of blood component (red blood cell and plasma) usage was 36.0%, 35.9%, 20.7% and 7.4% for blood type O, A, B and AB, respectively. The usage of total blood, red blood cell and plasma in internal and surgical departments were 13 883.8 U vs 7 080.8 U, 4 963.3 U vs 3 647.3 U and 6 055 U vs 1 170 U, respectively. 【Conclusion】 The total clinical blood usage and the proportion of blood component transfusion in our hospital is increasing year by year. Therefore, rational and scientific blood use should be further improved.
		                        		
		                        		
		                        		
		                        	
4.Effects of apatinib on the proliferation and apoptosis of FLT3-ITD mutant acute myeloid leukemia MV4-11 and MOLM-13 cells and their mechanisms
Jie ZHA ; Haijun ZHAO ; Manman DENG ; Yuanfei SHI ; Zhijuan LIN ; Zhifeng LI ; Bing XU
Journal of Leukemia & Lymphoma 2020;29(9):530-534
		                        		
		                        			
		                        			Objective:To explore the effects of apatinib on the proliferation and apoptosis of FLT3-ITD mutant acute myeloid leukemia (AML) cells, and to explore the related mechanisms.Methods:The logarithmic growth phase FLT3-ITD mutant AML cell lines MV4-11 and MOLM-13 were treated with different concentration of apatinib for 48 hours. The cell proliferation was detected by CCK-8 method. Flow cytometry was performed to examine the effect of apatinib on apoptosis. The cell mitochondrial membrane potential changes were detected by JC-1. Then the expression changes of vascular endothelial growth factor receptor 2 (VEGFR2) pathway-related proteins were examined by Western blot.Results:Apatinib had proliferation inhibitory effects on both MV4-11 and MOLM-13 cells, and the half-maximal inhibitory concentration (IC 50) at 48 hours was (2.23±0.42) μmol/L and (4.08±2.62) μmol/L, respectively. After exposure to apatinib with increasing concentrations (10, 20, 30, and 40 μmol/L) for 48 h hours, the percentage of apoptotic cells was significantly increased in MV4-11 cells [(81.95±1.15)%, (88.80±0.23)%, (97.46±0.49)%, and (99.29±0.05)%] and MOLM13 cells [(47.30±0.87)%, (67.00±3.71)%, (82.60±2.89)%, and (98.06±5.34)%] in a dose-dependent manner, and the differences were statistically significant ( F = 6 915.0, P < 0.01; F = 5 385.0, P < 0.01). Detection of mitochondrial membrane potential by JC-1 method showed that after MV4-11 and MOLM-13 cells were treated by 10, 20, 30, and 40 μmol/L apatinib for 24 hours, the JC-1 aggregate/monomer mean fluorescence intensity (MFI) ratios were 0.45±0.06, 0.19±0.07, 0.12±0.03, 0.09±0.01, and 0.84±0.05, 0.66±0.13, 0.35±0.11, 0.27±0.02, which were different from the control group (0.67±0.15 and 0.97±0.42), and the differences were statistically significant ( F = 372.3, P < 0.05; F = 276.4, P < 0.05). Western blot was performed to detect different concentration of apatinib (2.5, 5.0 and 10.0 μmol/L) on the MV4-11 cells for 24 hours, the results showed that apatinib could down-regulate the phosphorylation of VEGFR2, Src and Stat3 in a dose-dependent manner. Conclusions:Apatinib can inhibit cell proliferation and induce apoptosis in AML with FLT3-ITD mutation. The possible mechanism is related to the down-regulation of phosphorylation of VEGFR2 and its downstream targets Src and Stat3.
		                        		
		                        		
		                        		
		                        	
5.Application of Jiankuai psychosomatic active therapy in perioperative period of elderly patients
Jing GAO ; Xingzhi ZHAO ; Zhehao ZHANG ; Zhijuan DONG ; Jingjing SHEN ; Xiaoxiao LI ; Chunming MENG ; Xiaobao ZHANG
Chinese Journal of Practical Nursing 2020;36(26):2024-2028
		                        		
		                        			
		                        			Objective:To explore the application effect of Jiankuai psychosomatic active therapy in the elderly perioperative patients.Methods:From March 2018 to December 2019, 387 elderly patients in the urology department of the First People′s Hospital of Lianyungang City, Jiangsu Province were selected. According to the patients in two medical groups in the same ward, 193 patients in one medical group were divided into the experimental group and 194 patients in two medical groups as the control group. The experimental group was intervened by routine perioperative nursing combined with simple and fast psychosomatic active therapy, while the control group was only intervened by routine perioperative nursing. Self rating Anxiety Scale (SAS), Rosenberg Self-confidence Scale and General Self-efficacy Scale (GSEs) were used as the evaluation indexes before and after the implementation of the two groups.Results:The SAS score of the experimental group was 31.13 ± 3.64 and that of the control group was 48.45 ± 7.72 on the 7th day after operation. The difference between the two groups was statistically significant ( t value was 16.36, P < 0.05). The effective rate of self-confidence was 98.4% (190/193) and 94.8% (183/193) in the experimental group and 86.6% (168/194) and 85.1% (165/194) in the control group on the first day and the seventh day after operation, respectively. The difference between the two groups was statistically significant ( Z values were - 3.27 and 14.66, all P < 0.05). The GSEs score of the patients in the experimental group was 26.79 ± 2.17 and that of the control group was 16.86 ± 1.90. The difference between the two groups was statistically significant ( t value was 10.19, P < 0.05). Conclusions:The application of Jiankuai psychosomatic active therapy can effectively reduce the tension and anxiety of the elderly patients during the perioperative period, increase their self-confidence and self-efficacy, effectively improve the communication efficiency between doctors and patients, and promote rehabilitation.
		                        		
		                        		
		                        		
		                        	
6.Impacts of high-voltage electrical burn on serum platelet-related factors and platelet aggregation number in rats and the interventive effect of Xuebijing
Qingfu ZHANG ; Zhijuan GAO ; Ziwei ZHANG ; Xuegang ZHAO ; Jianke FENG ; Yanfen XU ; Lihong TU ; Jing ZHANG
Chinese Journal of Burns 2020;36(6):426-432
		                        		
		                        			
		                        			Objective:To explore the effect of high-voltage electrical burn on platelet function and rheological behavior in rats and the interventive effect of Xuebijing.Methods:A total of 280 Sprague Dawley rats of clean grade (aged 8-10 weeks, male and female unlimited) were divided into sham injury group, simple electrical burn group, electrical burn+ saline group, and electrical burn+ Xuebijing group according to the random number table, with 70 rats in each group. Rats in sham injury group were not conducted with electrical current to cause sham injury. Rats in the other three groups were given electrical current with output voltage of 2 kV and current intensity of (1.92 ± 0.24) A for 3 s, which caused high-voltage electrical burn wounds, each with an area of 1 cm×1 cm distributed in the left forelimb at the current inlet and the right hindlimb at the current outlet respectively. Rats in sham injury group and simple electrical burn group were not treated after injury. At post injury minute 2 and on post injury day (PID) 1, 2, 3, 4, 5, and 6, rats in electrical burn+ saline group and electrical burn+ Xuebijing group were intraperitoneally injected with 6 mL/kg saline and 6 mL/kg Xuebijing, respectively. Survival conditions of rats were recorded during the experiment. At 15 min before injury and at post injury hour (PIH) 1, 8, 24, 48, 72, and on PID 7, 10 rats in each group were respectively selected according to the random number table to sacrifice after collection of 5 mL blood under the direct vision of heart. Blood in the volume of 0.05 mL from each rat was taken to make blood smear, and platelet aggregation number was counted under 400 fold field of view using multiple projection microscope. The remaining blood samples were centrifuged to collect supernatant, and the content of platelet-derived growth factor (PDGF), thrombopoietin (TPO), and platelet activating factor (PAF) was detected by enzyme-linked immunosorbent assay. Data were statistically analyzed with analysis of variance for factorial design and Student-Newman-Keuls method.Results:All rats in sham injury group and simple electrical burn group survived during the experiment. One rat in electrical burn+ saline group died on PID 6, and one rat on PID 5 and one rat on PID 6 died in electrical burn+ Xuebijing group. The levels of all indexes among the 4 groups were close at 15 min before injury. The serum content of PDGF, TPO, and PAF and platelet aggregation number of rats in the three electrical burn groups at all time points after injury were higher or more than those in sham injury group, and the first three indexes reached the peak at PIH 8. The serum platelet aggregation number of rats in simple electrical burn group reached the peak at PIH 48, and that in electrical burn+ saline group and electrical burn+ Xuebijing group reached the peak at PIH 72. Among them, the serum content of PDGF of rats in electrical burn+ Xuebijing group at PIH 48, 72 and on PID 7 ((12.8±4.0), (11.6±4.4), (11.0±3.6) ng/mL, respectively) was close to that in sham injury group ((10.4±2.0), (10.4±2.5), (9.8±3.3) ng/mL, respectively, P>0.05). The serum content of TPO of rats in electrical burn+ Xuebijing group at PIH 24, 72 and on PID 7 ((200±52), (192±36), (193±32) ng/mL, respectively) was close to that in sham injury group ((182±30) , (184±41), (183±33) ng/mL, respectively, P>0.05). The serum content of PDGF, TPO, and PAF and platelet aggregation number of rats in electrical burn+ Xuebijing group at every time point after injury was generally lower or less than that in electrical burn+ saline group and simple electrical burn group. Conclusions:Application of Xuebijing treatment after high-voltage electrical burn can decrease the content of PDGF, TPO, and PAF in the serum and reduce the number of platelet aggregation, thereby inhibit platelet activation and improve platelet rheology.
		                        		
		                        		
		                        		
		                        	
7.lncRNA XIST promotes gastric cancer progression via regulating miR-337-3p/ HOXC8 axis
XU Longjian ; GAO Jianchao ; ZHENG Jingzhen ; ZHAO Zhijuan ; ZHONG Xuan ; SUN Jingguo ; LI Dongkun
Chinese Journal of Cancer Biotherapy 2019;26(10):1134-1141
		                        		
		                        			
		                        			 Objective: To investigate the mechanism of lncRNA XIST (XIST) on modulating gastric cancer progression via regulating miR-337-3p/HOXC8 axis. Methods: A total of 58 cases of gastric cancer tissues and corresponding para-cancerous tissues resected from March 2013 to January 2018 in Department of General Surgery, Kailuan General Hospital of Tangshan City were collected for this study; in addition, human gastric cancer cell lines (AGS, MGC803, HGC27) and human gastric mucosal GES-1 cells were also collected. qPCR was used to detect the expressions of XIST and miR-337-3p in above mentioned gastric tissues and cell lines. XIST-knockdown vectors, miR-337-3p mimics, miR-337-3p inhibitor and HOXC8-overexpression vectors were transfected into AGS cells. The proliferation and invasion of AGS cells were detected by CCK-8 and Transwell experiments respectively, and the expression levels of HOXC8, E-cadherin, N-cadherin and vimentin were detected by WB. The targeting relationships between XIST, miR337-3p and HOXC8 were verified by dual-luciferase reporter gene assay. Results: XIST was up-regulated in gastric cancer tissues and cell lines (all P<0.01). XIST knockdown significantly inhibited proliferation, invasion and EMT of AGS cells (P<0.05 or P<0.01). Moreover, XIST directly interacted with miR-337-3p and down-regulated its expression, while HOXC8 was the target gene of miR-3373p. Furthermore, XIST knockdown suppressed proliferation, invasion and EMT ofAGS cells through up-regulating the inhibitory effect of miR-337-3p on HOXC8 (P<0.05 or P<0.01). Conclusion: XIST knockdown can suppress the proliferation, invasion and EMT of AGS cells, which may be related with down-regulation of HOXC8 by targeting miR-337-3p. 
		                        		
		                        		
		                        		
		                        	
8.Correlation of serum level of tumor necrosis factor receptors with cervical cancer and cervical intraepithelial neoplasia
Shuxia HAN ; Zhijuan YANG ; Junjie ZHAO
Chinese Journal of Geriatrics 2018;37(4):431-433
		                        		
		                        			
		                        			Objective To investigate the correlation of cervical cancer and cervical intraepithelial neoplasia with expression level of serum soluble tumor necrosis factor receptor Ⅰ and Ⅱ.Methods A total of 915 recruited women in middle or advanced age were treated in our hospital from January 2015 to January 2017.Participants were assigned to one of five groups:group A (n=432) as control subjects;group B (n 89) diagnosed as cervical intraepithelial neoplasia Ⅰ;group C (n=94)as cervical intraepithelial neoplasia Ⅱ;group D (n=175) as cervical intraepithelial neoplasia Ⅲ;group E (n=125) as cervical cancer.The expression level of serum tumor necrosis factor receptor (sTNFR)was detected by enzyme linked immunosorbent assay.Results The level of sTNFR Ⅰ was much lower in the group A (0.869±0.243)μg/L than in the group B (1.127±0.435)μg/L,C (1.164±0.471)μg/L,D (1.206±0.693)μg/L,and E (1.836± 1.216)μg/L (t =7.782,8.741,8.860,and 15.523,all P<0.001).The level of sTNFR Ⅰ in the group E was much higher than in the groups B,C,and D (t=5.263,5.077,and 5.684,all P<0.001).No statistical significance was found in sTNFR Ⅰ level between B,C and D groups.The level of sTNFR Ⅱ was much lower in the group A (1.633±0.402)μg/L than in the group B (1.872±0.526)μg/L,C (1.895±0.402)μg/L,D (1.946±0.604)μg/L,and E (3.192±1.145)μg/L (t=4.824,5.254,7.446,and 23.731,all P<0.001).The level of sTNFR Ⅱ was much higher in the group E than in the groups B,C,and D (t =10.136,10.501,and 12.216,all P<0.001).There was no significant difference in sTNFR Ⅱ levels between the groups B,C,and D groups (all P > 0.05).Conclusions Cervical cancer and cervical intraepithelial neoplasia are correlated with level of serum tumor necrosis factor receptors.
		                        		
		                        		
		                        		
		                        	
9.Effects of IL10-592 locus of AA genotype on the incidence of aGVHD and survival after HLA-matched unrelated allogeneic hematopoietic stem cell transplantation
Zhiluo YANG ; Qiaocheng QIU ; Zixuan DING ; Zhijuan PAN ; Qinqin ZHAO ; Jun HE
Chinese Journal of Hematology 2016;37(5):372-376
		                        		
		                        			
		                        			Objective To explore the impact of IL10-592 (rs1800872) single nucleic acid polymorphism (SNP) on the prognosis of HLA matched unrelated hematopoietic stem cell transplantation (HSCT).Methods The polymorphism of IL10-592 in 104 recipient-donor pairs and 100 healthy volunteers was analyzed with sequence based typing (SBT).Results When the genotype of IL1 0-592 in donors and recipients matched,AA/AA genotype had higher incidence of Ⅲ-Ⅳ aGVHD than AC/AC or CC/CC genotype (47.1%,3.7%,0,P=0.002).When the genotype of IL10-592 in donors and recipients mismatched,recipients with AC genotype or donors with AA genotype,there was significant different incidence of Ⅲ-Ⅳ aGVHD among donors or recipients with different genotype (P=0.046,P=0.041).The recipients with AA genotype had higher incidence of Ⅲ-Ⅳ aGVHD than AC or CC genotype (27.8% vs 10.2%,11.1%;P=0.072),and higher incidence of intestinal aGVHD (22.2%vs 5.1%,11.1%;P=0.040),lower incidence of 2-year overall survival (OS:48.2% vs 75.1%,85.7%;P=0.002),lower incidence of 2 year disease free survival (DFS:48.5% vs 66.3%,76.2%;P=0.045).Patients had higher incidence of Ⅲ-Ⅳ aGVHD with donors of AA genotype than with donors of AC or CC genotype (26.5% vs 8.9%,0;P=0.024),and higher incidence of intestinal aGVHD (20.4% vs 4.4%,0;P=0.026).In multivariate analysis,the genotype of IL10-592AA in recipients and donors had increased risk of Ⅲ-Ⅳ aGVHD (OR=3.3,P=0.049;OR=3.9,P=0.043).There were no statistical differences on the incidence of cGVHD and relapse.Conclusion In HLA-10/10 matched unrelated HSCT,the presence of IL10-592 AA genotype in recipients and/or donors is an adverse factor for Ⅲ-ⅣaGVHD,worse OS and 2-year DFS.
		                        		
		                        		
		                        		
		                        	
10.Effect of allitridum on remodeling of the transient outward potassium current of ventricular myocytes of spontaneously hypertensive rats.
Qing DAN ; Ying ZHAO ; Zhijuan WU ; Chao ZHU ; Li LIU ; Bin XU ; Yuqi LIU ; Qi CHEN ; Yang LI
Acta Pharmaceutica Sinica 2015;50(1):39-44
		                        		
		                        			
		                        			We aimed to study the effect of allitridum (All) on the transient outward potassium current (Ito) of ventricular myocytes of spontaneously hypertensive rats (SHR). Totally 30 male SHRs were randomly divided into three groups: low-dose All group (7.5 mg·kg(-1)), high-dose All group (15.0 mg·kg(-1)) and normal saline group. The other 10 sex and age matched Wistar-kyoto rats (WKY) were also taken as control group (WKY group). All animals received i.p. administration for 8 weeks. The dual enzymatic method was used to separate single ventricular myocyte from animals. Patch-clamp technique was used to record Ito and analyze the effect of All on the current. It was shown that the left ventricular hypertrophy of SHR was reversed significantly by All. Furthermore, the density of Ito was recovered in both high and low dose All groups. The peak current densities of Ito were enhanced from 18.23±3.64 to 25.17±2.86 pA/pF (P<0.01) and 36.47±5.42 pA/pF (P<0.01) at +50 mV by All 7.5 mg·kg(-1) and 15.0 mg·kg(-1), respectively, which was not significantly different with WKY group. The effect was associated with positive shift of the steady-state, close-state inactivation, and shortened recovery from inactivation of Ito. It is concluded that All decreases the remodeling of Ito of ventricular hypertrophic myocytes of SHR.
		                        		
		                        		
		                        		
		                        	
            

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