1.Mechanisms of immunogenic cell death induced by octyl ester derivative of ginsenoside Rh2 in hepatocellular carcinoma cells based on endoplasmic reticulum stress
Zhenzhen DAI ; Qingxin HUANG ; Qirui HU ; Hancheng WU ; Yao PAN ; Zeyuan DENG ; Fang CHEN
Chinese Journal of Immunology 2024;40(4):767-771,779
Objective:To investigate whether octyl ester derivative of ginsenoside Rh2(Rh2-O)can induce immunogenic cell death of Huh-7 hepatocellular carcinoma cells and possible mechanism.Methods:Huh-7 cells were cultured in vitro,and divided into control group,Rh2-O group,positive control group(mitoxantrone treatment).Viability and apoptosis of cells were detected by CCK-8 and flow cytometry,respectively.Concentrations of high mobility family protein 1(HMGB1)and adenosine triphosphate(ATP)in supernatant were detected by ELISA and chemiluminescence assay,respectively.Membrane eversion of calreticulin(CRT)was detected by immunofluorescence assay.ROS level in cells was detected by fluorescence probe DCFH-DA,and expressions of proteins associated with endoplasmic reticulum stress signaling pathway were detected by Western blot.Results:Rh2-O treatment significantly reduced cell viability,promoted apoptosis,induced secretion of HMGB1,ATP,membrane eversion of CRT,increased accumulation of ROS in cells,and enhanced expressions of endoplasmic reticulum stress-related proteins PERK,eIF2α,p-eIF2α(all P<0.05).After addition of endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA),membrane eversion of CRT induced by Rh2-O was significantly inhibited(P<0.05).Conclusion:Rh2-O can induce immunogenic cell death in hepatocellular carcinoma cells,whose mechanism may be associated with activation of endoplasmic reticulum stress and promotion of CRT membrane eversion.
2.YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling
Sui HUA ; Deng WANLI ; Chai QIONG ; Han BING ; Zhang YULI ; Wei ZHENZHEN ; Li ZAN ; Wang TING ; Feng JILING ; Yuan MAN ; Tang QINGFENG ; Xu HONGXI
Journal of Pharmaceutical Analysis 2024;14(4):525-541
The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.
3.Research advances in the roles of EGFR and targeted therapy in triple negative breast cancer
Jinming CHEN ; Qinghua JIANG ; Zhe CHEN ; Zhenzhen TIAN ; Yaguang DENG ; Yinhong SONG
Tumor 2023;43(10):829-838
In 2022,breast cancer ranks the first in incidence among all malignant tumors worldwide,and it's high recurrence and fatality rate has posed serious threat to human life and health.Triple negative breast cancer(TNBC)is known for its poor prognosis among all types of breast cancer,and is often associated with elevated expression of epidermal growth factor receptor(EGFR).EGFR is widely expressed on the surface of various cells.The signaling pathway mediated by EGFR is mainly involved in cell growth,proliferation and differentiation.EGFR overexpression is often closely related to tumor invasion,metastasis and prognosis.Therefore,elucidating the roles of EGFR in TNBC and developing prevention and treatment strategies correspondingly are helpful to prevent and control the occurrence of breast cancer,and improve patients'quality of life.This review summarizes the research progress in the roles of EGFR,the treatment strategies and drug resistance in TNBC,in order to provide more refence for treating and improving the prognosis of breast cancer.
4.Prognostic factors analysis of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction after radical resection with different surgical approaches
Yingxin DU ; Jingyu DENG ; Han LIANG ; Huifang LIU ; Weilin SUN ; Zizhen WU ; Jinyuan LIU ; Nannan ZHANG ; Zhenzhen ZHAO ; Liqiao CHEN
Chinese Journal of Digestive Surgery 2020;19(6):630-636
Objective:To investigate the prognostic factors of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) after radical resection with different surgical approaches.Methods:The retrospective case-control study was conducted. The clinicopathological data of 442 patients who were admitted to Tianjin Medical University Cancer Institute and Hospital from February 2003 to July 2011 were collected. There were 362 males and 80 females, aged from 21 to 85 years, with a median age of 64 years. Patients underwent radical resection of AEG. Observation indicators: (1) surgical situations; (2) follow-up; (3) progrostic factors analysis of AEG after radical resection; (4) survival of patients after radical resection of AEG via abdominal approach; (5) survival of patients after radical resection of AEG via thoracoabdominal approach; (6) survival of patients after radical resection of Siewert type Ⅱ type AEG; (7) survival of patients after radical resection of Siewert type Ⅲ AEG. Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients up to June 2018. Measurement data with skewed distribution were described as M (range). Count data were expressed as absolute numbers or percentages. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-rank test was used for survival analysis. Univariate analysis was conducted using the Kaplan-Meier method. Multivariate analysis was conducted using the COX proportional hazard model. Results:(1) Surgical situations: 442 patients underwent radical resection of AEG, including 204 via abdominal approach and 238 via thoracoabdominal approach. There were 391 patients with D 2 lymphadenectomy and 51 with D 2+ lymphadenectomy. (2) Follow-up: 442 patients were followed up for 8-162 months, with a median follow-up time of 37 months. All the 442 patients survived for 2-156 months, with a median survival time of 31 months. The 1-, 3-, 5-year overall survival rates were 79.2%, 42.0%, 30.0%, respectively. (3) Prognostic factors analysis of AEG after radical resection: results of univariate analysis showed that tumor diameter, Lauren type, pathological T staging, pathological N staging, pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration were related factors for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG ( χ2=4.028, 4.885, 19.435, 17.014, 34.449, 9.707, 11.866, P<0.05). Results of multivariate analysis showed that pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration were independent influencing fators for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG ( hazard ratio=1.255, 0.486, 1.454, 95% confidence interval: 1.024-1.539, 0.325-0.728, 1.096-1.928, P<0.05). (4) Survival of patients after radical resection of AEG via abdominal approach: of the 204 patients undergoing radical resection of AEG via abdominal approach, the 1-, 3-, 5-year survival rates were 83.6%, 50.4%, 37.8% for 121 patients with Siewert type Ⅱ AEG, respectively, versus 72.0%, 39.3%, 31.8% for 83 patients with Siewert type Ⅲ AEG, showing no significant difference in the survival between the two groups ( χ2=1.854, P>0.05). (5) Survival of patients after radical resection of AEG via thoracoabdominal approach: of the 238 patients undergoing radical resection of AEG via thoracoabdominal approach, the 1-, 3-, 5-year survival rates were 79.6%, 38.8%, 23.8% for 183 patients with Siewert type Ⅱ AEG, respectively, versus 79.1%, 37.6%, 29.3% for 55 patients with Siewert type Ⅲ AEG, showing no significant difference in the survival between the two groups ( χ2=0.215, P>0.05). (6) Survival of patients after radical resection of Siewert type Ⅱ AEG: of the 304 patients with Siewert typeⅡAEG, the postoperative 1-, 3-, 5-year survival rates were 83.6%, 50.4%, 37.8% for 121 patients undergoing radical resection of AEG via abdominal approach, respectively, versus 79.6%, 38.8%, 23.8% for 183 patients undergoing radical resection of AEG via thoracoabdominal approach, showing no significant difference in the survival between the two groups ( χ2=2.406, P>0.05). (7) Survival of patients after radical resection of Siewert type Ⅲ AEG: of the 138 patients with Siewert type Ⅲ AEG, the postoperative 1-, 3-, 5-year survival rates were 72.0%, 39.3%, 31.8% for 83 patients undergoing radical resection of AEG via abdominal approach, respectively, versus 79.1%, 37.6%, 29.3% for 55 patients undergoing radical resection of AEG via thoracoabdominal approach, showing no significant difference in the survival between the two groups ( χ2=0.640, P>0.05). Conclusions:Pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration are independent fators for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG. Siewert types and surgical approach are not related factors for prognosis of patients after radical resection of AEG. There is no significant difference in the survival between patients with different Siewert types of AEG undergoing radical resection via different surgical approaches.
5.Effects of nursing intervention based on story theory on negative emotions and quality of life in cancer chemotherapy patients
Jing TIAN ; Huaxia LIU ; Ting SU ; Zhenzhen DENG
Chinese Journal of Practical Nursing 2018;34(4):251-255
Objective To validate the effectiveness of nursing intervention on alleviating negative emotions and improving quality of cancer patients′ life based on story theory. Methods This study adopted the method of quasi-experimental research,100 patients with cancer chemotherapy were divided into the experimental group(50 cases),and the control group(50 cases).Based on conventional care,the experimental group received 3 weeks of nursing intervention based on story theory.The scores of mood and quality of life were collected in the 1st day and 23rd day after chemotherapy by using Profile of Mood States-Short Form(POMS-SF)and Quality of Life Questionnaire-core(QLQ-C30),thus evaluated the effect of intervention. Results The scores of POMS-SF in the 1st day and 23rd day after chemotherapy were (17.28±5.41),(35.84±12.35)points in the experimental group,and the difference was significant(t=7.54, P<0.05).The scores of QLQ-C30 in the 1st day and 23rd day after chemotherapy were(7.72±1.53),(8.17± 0.94) points in the control group, and the difference was significant(t =-4.07, P<0.05). There was no statistical difference in the scores of POMS-SF and QLQ-C30 between the 1st day and 23rd day after chemotherapy in the control group(P>0.05). Conclusions The nursing intervention based on story theory demonstrated significant improvement of negative emotions and quality of life, which is a quite practical psychological care for cancer chemotherapy patients.
6.Translation strategy of fuzzy language in traditional Chinese medicine
Zhenzhen DENG ; Yali YU ; Yi SHEN
International Journal of Traditional Chinese Medicine 2018;40(11):1079-1081
To analyze the fuzzy language and explore the translation methods of the fuzzy language in traditional Chinese medicine,examples are given and discussed in this essay.Based on the analysis of the problems in the application of the fuzzy theory to TCM translation,a flexible translation method like a combination of multiple translation method has been suggested in addition to appropriate translations such as transliteration,literal translation,free translation and borrowing translation,which can promote understanding the characteristics of the fuzzy language in TCM so as to further boosting the communication of TCM culture.
7.Effect of autophagy inhibitor chloroquine on the renal calcium oxalate crystals formation in rats
Xin MAI ; Zhenzhen KONG ; Tuo DENG ; Zhou YANG ; Yang LIU ; Yu LAN ; Xiaolu DUAN ; Wenqi WU ; Guohua ZENG
Chinese Journal of Urology 2017;38(7):542-547
Objective To investigate the effect and potential mechanism of autophagy inhibitor chloroquine on the calcium oxalate crystals formation in rats.Methods From September 2016 to October 2016,Thirty healthy male SD rats were randomly divided into 3 groups:control group,model group and chloroquine intervention group.The method to establish calcium oxalate stone model was drinking water with 1% ethylene and 1% ammonium chloride freely.The rats of chloroquine intervention group were treat with chloroquine (40mg/kg · d) by intraperitoneal injection.Modeling was finished after 28 days.The amounts of renalcalcium oxalate crystals were detected by polarizing microscope.For all groups,the amounts of autophagosome were detected by transmission electron microscope.Twenty four hour urine compositions for stone risk factors were detected.The expressions of oxidative stress injury related molecular markers (SOD,MCP-1 and 8-OHdG) and the expressions of autophagy markers (LC3 and P62) were detected by immunohistochemistry.The RNA expressions of SLC26A6 in kidney were detected by Real-time PCR.Results Compared to the model group,the amounts of renal calcium oxalate crystals were significantly reduced in chloroquine intervention group (32.37 ± 5.14 vs.4.18 ± 0.25,P < 0.05).Compared to the control group,the level of autophagy was increased in the model group.Compared to the model group,the level of autophagy was inhibited in the chloroquine intervention group.For control group,model group and chloroquine intervention group,the excretion of urinary oxalate were (3.1 ± 1.5) mmol,(22.5 ± 8.1) mmol,(2.8 ± 1.2) mmol,respectively;the excretion of urinary citrate were (63.4 ± 7.4) mmol,(45.9 ± 9.5)mmol,(15.6 ± 8.2) mmol,respectively.Compared to the control group,the amounts of urinary oxalate weresignificantly elevated in model group (P < 0.05),but citrate were significantly reduced in the chloroquineintervention group(P < 0.05).For control group,model group and chloroquine intervention group,theexpressions of SOD were 42.24 ±4.16,19.21 ± 2.25,39.08 3.53,respectively;the expressions of MCP-1 were 4.02 0.51,8.45 ± 0.55,5.52 ± 0.34,respectively;the expressions of 8-OHdG were 7.16 ± 0.54,11.21 ± 1.12,8.67 ±0.34,respectively;the RNA expressions of SLC26A6 were 0.35 ±0.07,1.02 ±0.17,0.70 ± 0.06,respectively.Compared to the control group,the expressions of SOD were significantly reduced in the model group,but the expressions of MCP-1,8-OHdG and SLC26A6 were significantly elevated(P <0.05).Compared to the model group,the expressions of SOD were significantly elevated chloroquine intervention group (P < 0.05),but the expressions of MCP-1,8-OHdG and SLC26A6 were significantly elevated(P < 0.05).Conclusions The autophagy inhibitor chloroquine could inhibit the formation of calcium oxalate crystals induced by ethylene in rat kidney via inhibit the renal autophagy level and expressions of the SLC26A6,reducing the renal oxidative stress injury and urinary oxalate excretion.
8.Optimal degree of neuromuscular blockade for inhibiting obturator nerve-muscle responses induced by transurethral resection of bladder tumor with general anesthesia
Yi ZHOU ; Zhenzhen ZHAO ; Xiaoming DENG ; Yi LIU
Chinese Journal of Anesthesiology 2016;36(12):1428-1430
Objective To evaluate the optimal degree of neuromuscular blockade for inhibiting obturator nerve-muscle responses induced by transurethral resection of bladder tumor (TURBT) with general anesthesia.Methods Ninety American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes,aged 26-64 yr,weighing 50-80 kg,scheduled for elective TURBT for lateral bladder wall tumors with general anesthesia,were divided into 3 groups (n =30 each) using a random number table:low-dose mivacurium group (group L),medium-dose mivacurium group (group M) and high-dose mivacurium group (group H).After mivacurium 0.15 mg/kg was injected intravenously during anesthesia induction,mivacurium was continuously infused at a rate of 0.2,0.3 and 0.4 mg · kg-1 · h-1 in L,M and H groups,respectively,until the end of operation.Neuromuscular blockade was continuously monitored during operation.When T1% and TOF count (TOFC) disappeared,post tetanic count (PTC) was used.ROC curve was applied to analyze the relationship between the occurrence of obturator nerve-muscle responses and degree of neuromuscular blockade.Results T1% and TOFC were recorded in 16 patients (15 cases in group L,1 case in group M) during the resection of tumor,and the obturator nerve-muscle response was observed in all of these patients.In the other 74 patients,T1% and TOFC disappeared,and PTC recorded was 10.0±3.1 (group L,n=15),6.0± 3.5 (group M,n=29) and 4.0±2.2 (group H,n=30).Among the 74 patients,the obturator nerve-muscle response was found in 18 patients (8 cases in group L,10 cases in group M).The area under the ROC curve of PTC value in predicting the occurrence of obturator nerve-muscle responses was 0.882 with a PTC cut-off of 9 (P<0.05).The sensitivity and specificity were 87.3% and 72.2%,respectively.Conclusion In order to inhibit the obturator nerve-muscle response during TURBT with general anesthesia,the optimal degree of neuromuscular blockade should be kept not more than 9 for PTC.
9.Onco-miR-24 regulates cell growth and apoptosis by targeting BCL2L11 in gastric cancer.
Haiyang ZHANG ; Jingjing DUAN ; Yanjun QU ; Ting DENG ; Rui LIU ; Le ZHANG ; Ming BAI ; Jialu LI ; Tao NING ; Shaohua GE ; Xia WANG ; Zhenzhen WANG ; Qian FAN ; Hongli LI ; Guoguang YING ; Dingzhi HUANG ; Yi BA
Protein & Cell 2016;7(2):141-151
Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR-24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3'UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.
Animals
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Apoptosis
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genetics
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Apoptosis Regulatory Proteins
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deficiency
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genetics
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Base Sequence
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Bcl-2-Like Protein 11
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Cell Line, Tumor
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Cell Movement
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genetics
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Cell Proliferation
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genetics
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Down-Regulation
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genetics
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Gene Silencing
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Male
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Membrane Proteins
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deficiency
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genetics
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Mice
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MicroRNAs
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genetics
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Proto-Oncogene Proteins
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deficiency
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genetics
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Rats
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Stomach Neoplasms
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genetics
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pathology
10.Evaluation of left ventricular diastolic function in patients with uremia by using vector flow mapping
Kaikai SHEN ; Zhenzhen WANG ; Ying DENG ; Hairu LI ; Jiawei TIAN
Chinese Journal of Ultrasonography 2015;24(11):942-947
Objective To assess the clinical application value of vector flow mapping (VFM) in evaluating the left ventricular diastolic function in patients with uremia.Methods Forty patients with uremia and forty healthy volunteers were enrolled.The quantitative parameters,including vorticity,sum total energy loss (sEL),average energy loss(aEL),and the alteration circulation were measured in the VFM imaging mode.Difference was evaluated between two groups at apical,mid and basal segments at different periods.E/e'was derived via dual-Doppler imaging technology.And correlationship was analyzed between vorticity,sEL,aEL,circulation and E/e',separately.Results ①At apex segment of isovolumetric relaxation time and at three segments of atrial systole,there were difference in vorticity,sEL,aEL between two groups (P <0.05).Circulation in rapid filling phase of anterior mitral valve and slow filling phase of posterior mitral valve were different[(15.94 ± 8.40) m2/s vs (8.36 ± 7.84) m2/s,(5.34 ± 5.24) m2/s vs (13.37 ± 10.42) m2/s,P <0.05].②In control group,vorticity,sEL and aEL were different in different segments of same phase or at different phases of same segment,and also did in the uremia group(P <0.01).③In uremia group,vorticity had a good correlation with E/e'at basal segment of rapid filling phase(r =0.34,P =0.046)and atrial systole(r =0.38,P =0.02).And sEL had a good correlation with E/e'at basal segment of rapid filling phase,isovolumetric relaxation time and at mid segment of rapid filling phase(r1 =0.44,P1 =0.008;r2 =0.48,P2 =0.003;r3 =0.50,P3 =0.002),and in time phase mentioned above,there were also the correlationship between aEL and E/e'(r1 =0.39,P1 =0.017;r2 =0.49,P2 =0.002;r3 =0.48,P3 =0.003).Conclusions VFM can be utilized to analyze left ventricular hemodynamics features of uremia patients and it may be a good supplement for assessing cardiac diastolic function.

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