1.Effects of COL1A1 and SYTL2 on inflammatory cell infiltration and poor extracellular matrix remodeling of the vascular wall in thoracic aortic aneurysm
Xinsheng XIE ; Ye YUAN ; Yulong HUANG ; Xiang HONG ; Shichai HONG ; Gang CHEN ; Yihui CHEN ; Yue LIN ; Weifeng LU ; Weiguo FU ; Lixin WANG
Chinese Medical Journal 2024;137(9):1105-1114
		                        		
		                        			
		                        			Background::Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods::Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results::A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain ( COL1A1) and synaptotagmin like 2 ( SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8 + T cells. In addition, single-cell analysis indicated that fibroblasts and CD8 + T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions::COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.
		                        		
		                        		
		                        		
		                        	
2.Fully protruding into the inferior vena cava deployment of braided stent in the treatment of iliac compression syndrome
Shichai HONG ; Yue LIN ; Weifeng LU ; Xiang HONG ; Gang CHEN ; Yulong HUANG ; Yihui CHEN ; Xinsheng XIE ; Lixin WANG ; Weiguo FU
Chinese Journal of General Surgery 2023;38(7):506-509
		                        		
		                        			
		                        			Objective:To evaluate the clinical efficacy of metal braided stent deployed by fully protruding into the inferior vena cava for the treatment of iliac vein compression syndrome(IVCS).Methods:The clinical data of patients with IVCS treated with interwoven nitinol mesh stent protruding into the inferior vena cava and released from Jan 2018 to May 2021 in our center were retrospectively analyzed.Results:A total of 118 patients were included in this study. Among them, 7 cases were complicated with acute thrombosis, 3 cases were complicated with post thrombotic syndrome (PTS), and 108 cases were no more thrombotic iliac vein compression. The technical success rate was 100%, with an average of 2.03±0.77 stents implanted. Of the 23 ulcer patients, 18 ulcers healed after intervention, and the healing rate was 78.26%. The postoperative CEAP grade was significantly improved ( t=11.54, P<0.01), and the primary patency rate and second patency rate were 97.46% and 98.31% at 1 year after intervention. Conclusion:The fashion of fully protruding into inferior vena cava deployment in the treatment of iliac vein compressive disease has a high patency rate and satisfactory clinical efficacy.
		                        		
		                        		
		                        		
		                        	
3.Curative effect analysis of transplantation in patients with myelodysplastic syndrome with ASXL1 gene mutation
Yupei ZHANG ; Xinsheng XIE ; Yajie SHI ; Weijie CAO ; Rong GUO ; Dingming WAN
The Journal of Practical Medicine 2023;39(23):3087-3092
		                        		
		                        			
		                        			Objective To investigate the efficacy and influencing factors of allo-HSCT in the treatment of MDS patients with ASXL1+.Methods The second-generation sequencing technique was used to detect 22 gene mutations in 247 newly diagnosed MDS patients in our hospital.The patients were divided into chemotherapy group and transplant group according to treatment style.The differences of OS and PFS between the two groups were compared,and the influencing factors of prognosis of transplant patients were analyzed.Results ASXL1+ was detected in 75 patients(30.36%),with a median mutation ratio of 42.93(18.10,58.39)%,10 received supportive treatment,43 received demethylation therapy or demethylation combined with pre-excitation therapy,and 22 received allo-HSCT.2-year PFS rate and OS rate of transplantation group were significantly higher than that of chemotherapy group(P<0.05).The 2-year OS rate in the low ASXL1 mutation load group(VAF≤42.93%)was significantly higher than that in the high ASXL1 mutation load group(VAF>42.93%)(P<0.05).In the context of allo-HSCT in patients with ASXL1+,2-year OS and PFS rates were significantly reduced in patients with RUNX1+ or ASXL1+(P<0.05);Multivariate analysis showed that high mutation load of ASXL1 or U2AF1+ were independent risk factors for OS in transplant patient(P<0.05).U2AF1+ were the risk factors for PFS(P<0.05).Conclusion allo-HSCT significantly improved the prognosis of patients with ASXL1+ MDS.High ASXL1 mutation load or U2AF1+ were independent risk factors affecting the outcome of allo-HSCT.
		                        		
		                        		
		                        		
		                        	
4.The value of three-dimension digital subtraction angiography in diagnosis and treatment of iliac vein compression syndrome
Shichai HONG ; Yihui CHEN ; Weifeng LU ; Xiang HONG ; Gang CHEN ; Yulong HUANG ; Yue LIN ; Xinsheng XIE ; Lixin WANG ; Weiguo FU
Chinese Journal of General Surgery 2022;37(5):354-357
		                        		
		                        			
		                        			Objective:To evaluate the application value of three-dimension digital subtraction angiography (3D-DSA) in the diagnosis and treatment of iliac vein compression syndrome (IVCS).Methods:A retrospective analysis was made on 171 patients with a tentative diagnosis of IVCS based on signs, symptoms, and finding of CTV or MRV, and iliac vein angiography. The diagnostic efficacy of MRV, 2D-DSA and 3D-DSA were analyzed. The imaging advantages of 3D-DSA in the diagnosis and treatment of IVCS were evaluated.Results:Ninty-three patients underwent MRV and 3D-DSA simultaneously, 101 patients had 2D-DSA and 3D-DSA simultaneously. 3D-DSA was taken as gold standard, the diagonotic sensitivity, specificity, Youden index of MRV was 75.61%, 72.73% and 0.48 respectively. The sensitivity, specificity, Youden index of 2D-DSA was 90.22%, 100% and 0.90 respectively. There are significant differences in the diagonotic sensitivity between MRV and 3D-DSA, 2D-DSA and 3D-DSA ( P<0.05). There is no significant difference in the diagonotic specificity between MRV and 3D-DSA, 2D-DSA and 3D-DSA ( P=1.000). In this study, we found that 3D-DSA has greater imaging evaluation advantages in preoperative evaluation, intraoperative guidance and immediate postoperative reexamination in the diagnosis and treatment of iliac vein disease. Conclusions:3D-DSA can improve the detection rate of IVCS, and has its advantage in imaging evaluation.
		                        		
		                        		
		                        		
		                        	
5.Clinical features and prognostic factors of 89 cases of myeloid sarcoma
Ping TANG ; Zhenkun DONG ; Rong GUO ; Haiqiong WANG ; Runqing LU ; Xinsheng XIE ; Hui SUN ; Ling SUN ; Dingming WAN ; Yanfang LIU ; Zhongxing JIANG
Chinese Journal of Organ Transplantation 2021;42(3):173-176
		                        		
		                        			
		                        			Objective:To explore the clinical characteristics, treatment and prognosis of myeloid sarcoma(MS).Methods:From January 2010 to May 2019, clinical data were reviewed for 89 MS cases. Age, gender, site of onset, type, comorbid diseases, lymphatic characteristics and disease remission status were analyzed. And 1-year survival rates were explored for different treatments including whether or not chemotherapy, transplantation and using hypomethylated drugs(HMAs)for maintenance after transplantation.Results:Among them, 21 cases had the data of chromosome karyotypic analysis and next generation sequencing and 8 patients underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT). The 1-year overall survival rates(OS)of primary MS, MS with intramedullary disease and MS relapse after leukemic remission were 16.0%, 37.5% and 36.9% respectively( P=0.013). The 1-year OS of local treatment(surgical resection, intrathecal injection and local radiotherapy), chemotherapy plus local treatment and chemotherapy plus allo-HSCT was 0, 28.1% and 72.9% respectively( P=0.003). After two courses of treatment, the 1-year OS of patients with complete and incomplete remissions were 34.9% and 10.0% respectively( P=0.008). Half(4/8)MS patients relapsed within 1 year after transplantation and had a short survival.Three patients received decitabine after HSCT and all of them survived for a long time. Conclusions:Chemotherapy plus HSCT is efficacious for MS. Decitabine maintenance treatment after transplantation may prolong recurrence-free survival. However, a larger sample size is required for further clinical verifications.
		                        		
		                        		
		                        		
		                        	
6.Prognostic significance of different IDH mutations and accompanying gene mutations in patients with acute myeloid leukemia
Ruiying WU ; Xinsheng XIE ; Yan WEI ; Zhongxing JANG ; Dandan CHEN ; Hui SUN ; Dingming WAN ; Yanfang LIU ; Ling SUN
Chinese Journal of Hematology 2021;42(1):39-44
		                        		
		                        			
		                        			Objective:To investigate the prognostic significance of different IDH mutations and accompanying gene mutations in patients with non-M 3 acute myeloid leukemia (AML) . Methods:Second-generation sequencing was performed to detect the mutations of 22 genes in 389 patients with AML in the First Affiliated Hospital of Zhengzhou University from June 2016 to December 2018, and Kaplan-Meier and Cox regression models were used to analyze the prognostic factors.Results:The mutation frequency of IDH1 and IDH2 was 6.2% and 8.7% , respectively, in all patients without co-mutation. The IDH2 mutant group had an older age, higher proportion of bone marrow primitive cells, more common normal karyotype, and more common RUNX1 and SRSF2 mutations compared with IDH2 wild-type group. Univariate analysis of variance showed that the median OS and PFS of IDH1 mutation group were significantly shorter than those of the wild-type group ( P<0.05) . IDH2 mutation as a single variable and IDH2R140 mutation had no significant effect on the prognosis, while different mutation sites had different effects. Compared with the IDH2 wild-type group, the IDH2R172 mutation group had lower complete remission (CR) rate and shorter median OS and PFS ( P<0.05) . In patients with normal karyotypes or aged ≥50 years, IDH2 mutation as a single variable had no significant effect on the prognosis, IDH1 mutation and IDH2R172 mutation were associated with poor OS and PFS ( P<0.05) , and IDH2R140 mutation had no significant effect on OS and PFS. Approximately 74.1% (43/58) of patients with IDH mutation simultaneously carried other gene mutations; however, the number of accompanying gene mutations had no significant effect on the prognosis. Among 58 patients with IDH mutation, the CR rate of patients with NPM1 mutation was significantly higher than that of patients in the NPM1 wild-type group (81.8% vs 36.4% , P=0.014) , the median OS in patients with DNMT3A mutation was lower than that of patients with DNMT3A wild type [4.0 months (95% CI 3.8-4.2) vs 6.3 months (95% CI 2.4-10.2) , P=0.041) ]. Multivariate analysis showed that age ≥60 years and white blood cell count ≥100×10 9/L were independent risk factors for OS and PFS, while CR after two courses of treatment and hematopoietic stem cell transplantation were independent prognostic favorable factors for OS and PFS. Conclusion:In patients with AML (non-M 3) , IDH gene mutations often coexisted with other gene mutations, and different subtypes and accompanying gene mutations of IDH have different prognostic significance.
		                        		
		                        		
		                        		
		                        	
7. Early antiviral therapy of abidor combined with lopinavir/ritonavir and re-combinant interferonα-2b in patients with novel coronavirus pneumonia in Zhejiang: A multicenter and prospective study
Runan WEI ; Nanhong ZHENG ; Xiangao JIANG ; Chunlian MA ; Xiaowei XU ; Shourong LIU ; Yongping CHEN ; Kaijin XU ; Hainv GAO ; Jiansheng ZHU ; Qiang SHU ; Jifang SHENG ; Xiaoqiang ZHANG ; Minghui LI ; Yan ZHANG ; Mengjie MA ; Xuan ZHANG ; Shibo LI ; Qiujing WANG ; Lingjun YING ; Yongjun ZHANG ; Yunzhen SHI ; Lingyan FAN ; Wanjun YU ; Huaying WANG ; Dandan SUN ; Xiaodong WANG ; Jichan SHI ; Yinghu CHEN ; Xinsheng XIE ; Yunqing CHEN ; Weihong WANG ; Zhaowei TONG ; Lingling TANG ; Mengfei ZHU ; Lingjian ZHANG ; Lanjuan LI
Chinese Journal of Clinical Infectious Diseases 2020;13(0):E010-E010
		                        		
		                        			 Objective:
		                        			Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province.
		                        		
		                        			Methods:
		                        			A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data.
		                        		
		                        			Results:
		                        			The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (
		                        		
		                        	
8.Early antiviral therapy of abidol combined with lopinavir/ritonavir and recombinant interferon α-2b for patients with COVID-19 in Zhejiang: A multicenter prospective study
Runan WEI ; Nanhong ZHENG ; Xiangao JIANG ; Chunlian MA ; Xiaowei XU ; Shourong LIU ; Yongping CHEN ; Kaijin XU ; Hainv GAO ; Jiansheng ZHU ; Qiang SHU ; Jifang SHENG ; Xiaoqiang ZHANG ; Minghui LI ; Yan ZHANG ; Mengjie MA ; Xuan ZHANG ; Shibo LI ; Qiujing WANG ; Lingjun YING ; Yongjun ZHANG ; Yunzhen SHI ; Lingyan FAN ; Wanjun YU ; Huaying WANG ; Dandan SUN ; Xiaodong WANG ; Jichan SHI ; Yinghu CHEN ; Xinsheng XIE ; Yunqing CHEN ; Weihong WANG ; Zhaowei TONG ; Lingling TANG ; Mengfei ZHU ; Lingjian ZHANG ; Lanjuan LI
Chinese Journal of Clinical Infectious Diseases 2020;13(1):9-15
		                        		
		                        			
		                        			Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.
		                        		
		                        		
		                        		
		                        	
9.Efficacy comparison of the second generation TKI combined with allogeneic hematopoietic stem cell transplantation or chemotherapy in the treatmeat of Philadelphia chromosome-positive acute lymphoblastic leukemia
Suping ZHANG ; Dingming WAN ; Zhongxing JIANG ; Weijie CAO ; Xue LI ; Li LI ; Xinsheng XIE ; Rong GUO ; Yanfang LIU ; Ling SUN
Chinese Journal of Organ Transplantation 2020;41(6):346-350
		                        		
		                        			
		                        			Objective:To compare the efficacy of the second generation tyrosine kinase inhibitor dasatinib combined with allogeneic hematopoietic stem cell transplantation(allo-HSCT)or chemotherapy in the treatment of Ph + acute lymphoblastic leukemia (Ph + ALL). Methods:A total of 56 Ph + ALL patients received dasatinib from January 2014 to June 2018. According to whether or not allo-HSCT was performed, they were divided into transplantation group(n=22)and chemotherapy group(n=34). The total survival rate(OS), disease-free survival rate(DFS), relapse and non-recurrence mortality(NRM)were compared between two groups. Results:The 2-year OS, DFS and cumulative recurrence rates were 69.1 % vs 47.8 %, 62.2 % vs 43.1 % and 14.6 % vs 44.1 % in transplantation and chemotherapy groups respectively. Significant inter-group differences existed in 2-year DFS, DFS and cumulative recurrence rates. The value of NRM was higher in transplantation group than that in chemotherapy group(18.6 % vs 14.1 %). However, the difference was statistically insignificant( P=0.476). Conclusions:The efficacy of dasatinib plus allo-HSCT is superior to that of dasatinib plus chemotherapy in the treatment of Ph + ALL.
		                        		
		                        		
		                        		
		                        	
10.Clinical features and prognostic factors in adult acute myeloid leukemia patients with FLT3-ITD and CEBPA gene co-mutation
Rongrong PEI ; Ronghui ZHANG ; Jifeng YU ; Zhongxing JIANG ; Hui SUN ; Dingming WAN ; Xinsheng XIE ; Yanfang LIU ; Tao LI ; Ling SUN
Chinese Journal of Hematology 2020;41(4):297-301
		                        		
		                        			
		                        			Objective:To investigate the clinical characteristics and prognosis in adult acute myeloid leukemia (AML) patients with FLT3-ITD and CEBPA double-mutated (CEBPAdm) co-mutation.Methods:Clinical data and prognostic factors were retrospectively analyzed in adult AML patients with FLT3-ITD and CEBPAdm co-mutation at The First Affiliated Hospital of Zhengzhou University from January 2016 to September 2018.Results:Among 599 non-acute promyelocytic leukemia (APL) patients, 268 received gene mutation detection, who were divided into 4 groups including 19 FLT3-ITD positive (FLT3-ITD +) and CEBPAdm positive (CEBPAdm +) cases (group A) , 84 FLT3-ITD + and CEBPAdm - cases (group B) , 95 FLT3-ITD - and CEBPAdm + cases (group C) , 70 double negative mutation cases (group D) . Gender, platelet count, FAB classification, induction treatment regimen and fusion gene mutation were comparable among four groups ( P>0.05) , while age onset, peripheral white blood cell (WBC) count, hemoglobin, percentage of blasts in peripheral blood, percentage of blasts in bone marrow, complete remission rate (CR 1 rate) after the first induction chemotherapy, the relapse rate, the median progression-free survival (PFS) time, and median overall survival (OS) time were significantly different between groups ( P<0.05) . When compared in pairs, gender, age onset, hemoglobin, platelet count, FAB classification in group A were not statistically different compared to group B, C and D ( P>0.05) , while patients in group A had higher WBC count, blasts in peripheral blood, minimal residual disease (MRD) in bone marrow. The CR 1 rates of group A, B, C, and D were 50.0%、32.4%、59.8%、39.0% respectively ( P=0.003) , and the relapse rates were 55.6%, 50.0%, 21.1%, 40.0% ( P<0.001) . As to survival, the median OS in each group was 6.25, 3.0, 15.5, 10.5 months respectively ( P<0.001) , and the median PFS was 5.0, 4.0, 10.0, 6.7 months ( P=0.032) . Conclusion:Adult AML patients with FLT3-ITD and CEBPAdm co-mutation have a higher leukemia load and low CR 1 rate, which translates into poor prognosis with high relapse rate and short survival time.
		                        		
		                        		
		                        		
		                        	
            
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