1.Association between impaired sensitivity to thyroid hormones and ischemic stroke in euthyroid population with hypertension and sex difference in this association
Youyou ZHANG ; Ruirui JIA ; Long WANG ; Dong CHEN ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):763-768
Objective To investigate the associations between thyroid hormone sensitivity indices in euthyroid patients with hypertension and the risk of ischemic stroke,as well as gender difference in this association.Methods We selected 760 hypertensive patients admitted to the Geriatric Neurology Department and outpatient clinic in The Second Affiliated Hospital of Xi'an Jiaotong University between April 2021 and May 2022.We collected their basic characteristics,blood biochemical parameters,thyroid indices,and brain magnetic resonance imaging information.All the patients were divided into two groups based on the clinical manifestations and brain magnetic resonance imaging:hypertension combined with ischemic stroke(n=526)and control(n=234)groups.Independent sample t-tests or non-parametric tests were used to compare the differences in thyroid hormone sensitivity indicators between the two groups.Spearman correlation analysis was used to analyze the correlation between serum thyroid indices and ischemic stroke.Multivariate conditional Logistic regression analysis was made to estimate odds ratios(ORs)and 95%confidence intervals(CIs)for thyroid indices and ischemic stroke.Results There were statistically significant differences between the two groups in terms of age,gender,TC,LDL-c,HDL-c,systolic blood pressure,FT3/FT4,TFQI,and PTFQI(all P<0.05).However,there was no statistically significant difference between the two groups in weight,smoking,drinking,history of diabetes,TG,FBG,diastolic blood pressure,TSHI,or TT4RI(all P>0.05).The results of Spearman correlation analysis showed a negative correlation between FT3/FT4 and ischemic stroke(P<0.05),but a positive correlation of TFQI and PTFQI with ischemic stroke(P<0.05)in euthyroid patients with hypertension.Logistic regression analysis showed that FT3/FT4 was significantly associated with ischemic stroke in euthyroid patients with hypertension(P=0.001),with OR(95%CI)of 0.001(0.000,0.058).After stratifying by gender,Logistic regression analysis found that FT3/FT4,TFQI,and PTFQI were associated with an increased risk of ischemic stroke in female patients,with OR(95%CI)of 0.000(0.000,0.001),3.132(1.415,6.930),and 3.010(1.406,6.445),respectively.Conclusion Lower serum FT3/FT4 ratio is associated with an increased risk of ischemic stroke in euthyroid patients with hypertension,and the significant association of TFQI and PTFQI with the risk of ischemic stroke is found in females.
2.Study on Huangqin Decoction Regulating NEK7-NLRP3/IL-1β to Protect Vascular Endothelial Function in Obese Hyperten-sive Rats Based on Peritubular Fat Inflammatory Microenvironment
Xuan LIU ; Fusen ZHAO ; Qiyao XU ; Meng ZHANG ; Can GUO ; Zhaoyang CHEN ; Jianping SHEN ; Xin-Dong WANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(9):896-905
OBJECTIVE To explore the effect of Huangqin decoction on improving peritubular fat inflammatory microenvironment and protecting vascular endothelial function in obese hypertensive rats by regulating the NEK7-NLRP3/IL-1β inflammatory axis.METHODS Fifty 4-week-old male Wistar rats were selected,10 of which were randomly selected as the control group,and the oth-er 40 were fed a high-salt and high-fat diet to establish an obese hypertension model.The rats with successful modeling(20 rats)were randomly divided into the model group,normal-dose Huangqin decoction group,high-dose Huangqin decoction group,and IL-1β in-hibitor group,with 5 rats in each group.From the 12th week,the normal-dose group was gavaged with Huangqin decoction 2.835 g·kg-1,the high-dose group was gavaged with Huangqin decoction 5.67 g·kg-1,and the IL-1β inhibitor group was intraper-itoneally injected with 1.5 mg·kg-1 AS101,3 times a week,for 8 weeks.The rats were weighed and blood was collected 12 h after the last administration,and the thoracic aorta and perivascular fat tissue were isolated.Serum inflammatory factors were detected,patho-logical changes were observed,eNOS expression was detected by immunofluorescence,and NEK7,NLRP3,Caspase-1,ASC,and IL-1β expression levels were detected by Western blot and qPCR.RESULTS The rats in the model group had a significant increase in body weight,an increase in the area of peritubular fat lipid droplets,and severe endothelial injury;systolic blood pressure,diastolic blood pressure,serum IL-1β,IL-6,and TNF-α were significantly elevated in the model group,and the expression of eNOS was sig-nificantly reduced,and the expression levels of NEK7,NLRP3,Caspase-1,ASC,and IL-1β proteins and mRNAs were significantly elevated.Compared with the model group,rats in the Huangqin decoction and IL-1β inhibitor groups had lower body weights,reduced endothelial damage,lower systolic and diastolic blood pressures,lower serum IL-1β,IL-6,and TNF-α,and higher eNOS expression.NEK7,NLRP3,Caspase-1,ASC and IL-1β protein expression was significantly reduced in the high dose group of Huan-gqin decoction and the IL-1β inhibitor group.In addition,Huangqin decoction protected the endothelial function of obese hypertensive vessels in a dose-dependent manner,with the effect being more pronounced in the high-dose group.CONCLUSION Huangqin de-coction can improve the inflammatory microenvironment of perivascular fat and protect the vascular endothelial function in obese hyper-tension by regulating the NEK7-NLRP3/IL-1β inflammatory axis.
3.Phantom study based on MRI cine sequences: analysis of the accuracy of tumor motion range accuracy
Bing LI ; Yuan WANG ; Ronghu MAO ; Dong LIU ; Wenzheng SUN ; Xiangyue LIU ; Nan MENG ; Wei GUO ; Shuangliang CAO ; Xipan LI ; Chen CHENG ; Hui WU ; Hongyan TAO ; Dingjie LI ; Zhaoyang LOU ; Hongchang LEI ; Lingguang MENG ; Hong GE
Chinese Journal of Radiation Oncology 2024;33(12):1144-1151
Objective:To investigate the accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .
4.Remnant cholesterol is associated with triglyceride and glucose index in young and middle-aged patients with ischemic stroke
Youyou ZHANG ; Ruirui JIA ; Long WANG ; Dong CHEN ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(6):910-914
【Objective】 To investigate the association between remnant cholesterol (RC) and triglyceride and glucose (TyG) index in young and middle-aged patients with ischemic stroke. 【Methods】 A total of 268 patients were divided into two groups, namely low TyG index group (n=134) and high TyG index group (n=134). Characteristics of the study population and metabolism risk factors (TC, TG, HDL-C, LDL-C, UA) were collected from biochemical test results. Spearman correlation analysis was used to analyze the correlation between metabolism risk factors and TyG index. Multivariate conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for RC and TyG index. 【Results】 Compared with the low TyG index group, significant differences were observed for BMI, history of diabetes, history of hypertension, SBP, DBP, FBG, TC, TG, LDL-C, RC, UA, and TyG index in high TyG index group. No significant differences were observed in age, gender, smoking status, or drinking status, HDL-C between the two groups. Spearman correlation analysis indicated that significant linear associations were observed between BMI, SBP, DBP, FBG, TC, TG, HDL-C, LDL-C, RC, UA and TyG index. Logistic regression analysis revealed that the RC, BMI, hypertension, diabetes, TC, LDL-C, and UA were significantly associated with the risk of increased level of TyG index. After adjusted analysis by RC, BMI, hypertension, diabetes, TC, LDL-C, and UA, only RC was significantly associated with an increased risk of increased level of TyG index. 【Conclusion】 Remnant cholesterol was associated with an increased risk of elevated TyG index level in young and middle-aged patients with ischemic stroke.
5.Impaired sensitivity to thyroid hormones is associated with ischemic stroke in young and middle-aged euthyroid population
Youyou ZHANG ; Ruirui JIA ; Dong CHEN ; Fuhua GONG ; Long WANG ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(6):938-943
【Objective】 To investigate the association of thyroid indices with the prevalence of ischemic stroke in young and middle-aged euthyroid population. 【Methods】 For this retrospective study, 620 euthyroid patients aged from 18 to 65 years were divided into ischemic stroke group (n=308) and non-ischemic stroke group (n=312). The characteristics of the study population; serum thyroid indices, i.e., free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH), were collected from biochemical test results. Multivariate conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid indices and ischemic stroke. 【Results】 Compared with non-ischemic stroke group, significant differences were observed in age, gender, weight, smoking status, drinking status, history of hypertension and diabetes, SBP, DBP, FBG, TC, HDL-C, LDL-C, FT3, FT4, FT3/FT4, TFQI, and PTFQI in ischemic stroke patients (all P<0.05). No significant differences were observed for TG, TSH, TSHI, or TT4RI between the two groups (all P>0.05). Logistic regression analysis revealed that lower FT3 [OR (95% CI) =0.722 (0.547~0.955) , P=0.022] and FT3/FT4 ratio [OR (95% CI) =0.723 (0.600~0.870) , P=0.001] , FT4 [OR (95% CI) =1.099 (1.011~1.194) , P=0.026] were significantly associated with an increased risk of ischemic stroke. After stratified analysis by hypertension, FT4 [OR (95% CI) =1.133 (1.021~1.257) , P=0.019] , lower FT3/FT4 ratio [OR (95% CI) =0.723 (0.600~0.870) , P=0.003] , TFQI [ OR (95% CI) =1.854 (1.026~3.350) , P=0.041] , and PTFQI [OR (95% CI) =1.871 (1.065~3.288) , P=0.029] were significantly associated with an increased risk of ischemic stroke in patients combined with hypertension, while after stratified analysis by diabetes, we only found that lower FT3/FT4 ratio [OR (95% CI) =0.730 (0.559~0.953) , 0.704 (0.536~0.944) , P=0.021] and FT4 [OR (95% CI) =1.170 (1.025~1.335) , P=0.026] were significantly associated with an increased risk of ischemic stroke in patients combined with diabetes. 【Conclusion】 FT3, FT4, and FT3/FT4 ratio are associated with an increased risk for ischemic stroke in young and middle-aged euthyroid population; TFQI and PTFQ are associated with an increased risk for ischemic stroke in patients combined with hypertension.
6.Protein Kinase C Controls the Excitability of Cortical Pyramidal Neurons by Regulating Kv2.2 Channel Activity.
Zhaoyang LI ; Wenhao DONG ; Xinyuan ZHANG ; Jun-Mei LU ; Yan-Ai MEI ; Changlong HU
Neuroscience Bulletin 2022;38(2):135-148
The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.
Action Potentials
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HEK293 Cells
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Humans
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Protein Kinase C/metabolism*
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Pyramidal Cells/enzymology*
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Shab Potassium Channels/genetics*
7.CRISPR/Cas9 knockout plin1 enhances lipolysis in 3T3-L1 adipocytes.
Chenyi FENG ; Xiang XU ; Weipeng DONG ; Zhaoyang CHEN ; Jiong YAN
Chinese Journal of Biotechnology 2020;36(7):1386-1394
We used CRISPR/Cas9 to delete plin1 of 3T3-L1 preadipocyte, to observe its effect on lipolysis in adipocytes and to explore regulatory pathways. We cultured 3T3-L1 preadipocytes, and the plin1 knockout vectors were transfected by electroporation. Puromycin culture was used to screen successfully transfected adipocytes, and survival rates were observed after transfection. The optimized "cocktail" method was used to differentiate 3T3-L1 preadipocytes. The glycerol and triglyceride contents were determined by enzymatic methods. The changes in lipid droplet form and size were observed by Oil red O staining. The protein expression of PLIN1, PPARγ, Fsp27, and lipases was measured by Western blotting. RT-PCR was used to measure the expression of PLIN1 and lipases mRNA. After the adipocytes in the control group were induced to differentiate, the quantity of tiny lipid droplets was decreased, and the quantity of unilocular lipid droplets was increased and arranged in a circle around the nucleus. Compared with the control group, the volume of unilocular lipid droplets decreased, and the quantity of tiny lipid droplets increased after induction of adipocytes in the knockout group. The expression of PLIN1 mRNA and protein in the adipocytes was significantly inhibited (P<0.05); glycerol levels increased significantly (0.098 4±0.007 6), TG levels decreased significantly (0.031 0±0.005 3); mRNA and protein expression of HSL and ATGL increased (P<0.05); PPARγ and Fsp27 expression unchanged in adipocytes. The above results indicate that the knockout of plin1 enhances the lipolysis of 3T3-L1 adipocytes by exposing lipids in lipid droplets and up-regulating lipases effects.
3T3-L1 Cells
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Adipocytes
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metabolism
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Animals
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CRISPR-Cas Systems
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Gene Knockout Techniques
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Lipase
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metabolism
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Lipolysis
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genetics
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Mice
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Perilipin-1
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genetics
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metabolism
8.Investigation of attitudes toward death and hospice care in nursing students before internship
Wenli XIAO ; Chun LI ; Zhaoyang DONG ; Lu SONG ; Bing LI ; Min CAI ; Yongmei LU
Chinese Journal of Medical Education Research 2020;19(1):106-110
Objective:To investigate nursing students' attitudes toward death and hospice care before they start clinical practice, analyze the correlation between the two attitudes and compare their differences in junior and regular nursing college students.Methods:A cross-sectional study was adopted to investigate the attitudes toward death and hospice care in 232 senior nursing students at school. Instruments included the Chinese version of the Death Attitude Profile-Revised (DAP-R) and the Chinese version of the Frommelt Attitude Toward Care of the Dying Scale-Form B (FATCOD-B). Pearson correlation analysis and independent t-test were used to analyze the data.Results:The mean scores of the 5 dimensions of death attitude were neutral acceptance (4.10±0.43), fear of death (2.76±0.66), death avoidance (2.73±0.74), approach acceptance (2.61±0.58), and escape acceptance (2.48±0.75), respectively. The total score of hospice care attitude was (107.63±8.45), which was negatively correlated with fear of death ( r=-0.247, P<0.01), death avoidance ( r=-0.278, P<0.01), and escape acceptance ( r=-0.145, P<0.05) scores and positively correlated with neutral acceptance score ( r=0.405, P<0.01). The death avoidance score of regular nursing college students was significantly lower than that of junior nursing college students ( t=-2.043, P<0.05), and the hospice care attitude score of regular nursing college students was significantly higher that of junior nursing college students ( t=2.639, P<0.01). Conclusion:There is a big room to improve nursing students' attitudes toward death and hospice care. Strengthening end-of-life care education is imperative.
9.Establishment and assessment of the early maternal separation combined adult chronic unpredictable mild stress depression animal model
Chongkun SHEN ; Rong ZHANG ; Kerun CAO ; Haixin MO ; Ran YE ; Yongfei CUI ; Zhaoyang DONG ; Yafei SHI
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(5):464-470
Objective:To explore the establishment and assessment of the depression model of adult SD rats induced by early maternal infant separation stress combined with adult chronic unpredictable mild stress(CUMS), and to observe the behavior and synaptic protein expression of SD rats.Methods:Twenty-four male rats were randomly divided into three groups: control group (CON group), chronic unpredictable stress group (CUMS group), maternal infant separation combined with chronic unpredictable stress group (MS + CUMS group). The depression model of rats in cums group was established by CUMS, and the depression model of rats in MS + CUMS group was established by maternal infant separation + CUMS. The depression model was evaluated by body mass and appearance observation, sugar water preference experiment, open field test and forced swimming test.Synapse-associated proteins (PSD-95 and synaptophysin (Syn)) of the hippocampus were assayed using Western blot. Syn protein expression was measured by immunohistochemistry.Results:After modeling, compared with CON group, the rats in CUMS group and MS + CUMS group had significantly lower body mass((126.43±3.88) g, (91.04±3.85) g, (69.89±6.67) g; t=5.03, 8.03, both P<0.01), significantly lower sugar water preference((94.21±0.56)%, (79.30±1.13)%, (72.73±1.82)%; t=8.24, 11.87, both P<0.01) and significantly increased immobility time((3.50±0.84)s, (13.59±2.40)s, (15.70±2.97)s; t=3.16, 3.82, both P<0.01). Among them, the body mass and sugar water preference of MS + CUMS group were lower than those of CUMS group ( t=3.00, 3.63; both P<0.01). (2)The center time of the rats in MS+ CUMS group markedly reduced compared with that of CON group((21.41±4.65) s, (8.96±2.37) s; t=2.66, P<0.05). (3)In the immunohistochemistry experiment, compared with the CON group, the percentage of Syn positive area in hippocampus of rats in CUMS group and MS+ CUMS group decreased significantly ((24.42±0.76)%, (14.00±0.95)%, (10.38±1.38)%; t=6.93, 9.33, P<0.01). (4)The results of Western blot showed that compared with CON group, both the expression of PSD-95 ((1.18±0.02), (0.74±0.06), (0.52±0.05), t=6.29, 9.31; both P<0.05) and Syn ((1.12±0.08), (0.95±0.06), (0.90±0.07); t=3.10, 4.04; both P<0.05) in hippocampus of rats in CUMS group and MS+ CUMS group were significantly decreased.And compared with the CUMS group, the expression of PSD-95 in MS+ CUMS group was lower( t=0.93, P<0.05). Conclusion:The method of MS combined with CUMS can effectively induce depression like behavior and decrease the expression of synaptic plasticity related protein of hippocampus in rats.
10.Extracorporeal membrane oxygenation alleviating kidney damage caused by unstable circulation function following brain deaths
Runqiang YUAN ; Mancheng GONG ; Wenjing DONG ; Decheng DENG ; Zhaoyang GONG
Chinese Journal of Organ Transplantation 2018;39(4):213-216
Objective Through studying the extracorporeal membrane oxygenation (ECMO)alleviating kidney damage caused by unstable circulation function following brain deaths to improve the utilization rate of donation after brain death (DBD) for renal transplantation.Methods Randomly selected 60 DBD patients with unstable circulatory function were randomly divided into 3 groups according to the time of perfusion by ECMO.The first group used ECMO perfusion for 2 h,group 24 h and group 36 h.At the same time,20 cases of stable DBD were randomly selected as the control group.The incidence of primary graft failure,delayed graft function and acute rejection,renal function recovery time,urine volume on the first day after surgery,creatinine and urea nitrogen one year after surgery were compared between two groups.Results The incidence of delayed recovery of renal function in experimental groups 1,2,3 and control group was 10% (2/20),15% (3/20),5%(1/20) and 10% (2/20) respectively.The incidence of acute rejection in experimental groups 1,2,3 and control group was 30% (6/20),25% (5/20),35% (7/20) and 25% (5/20) respectively.There were no statistically significant differences between the experimental groups and the control group (P >0.05).The mean renal function recovery time in the experimental groups 1,2,3 and control group was (9.6 ± 2.0),(9.7 ± 2.7),(9.5 ± 1.9) and (7.3 ± 3.1) days respectively.The average urine volume in experimental groups 1,2,3 and control group was (3 405 ± 755),(3 300 ±600),(3 810±825),and (3 600 ± 80) mL respectively.In experimental groups 1,2,3 and control group,the average creatinine level was (92 ± 28),(92 ± 28),(101 ± 31),and (98 ± 30) μmol/L respectively.The average urea nitrogen in experimental groups 1,2,3 and control group was (4.2 ± 2.2),(5.6 ± 2.6),(5.2 ± 2.6) and (5.5 ± 2.5) mmol/L respectively.The recovery time of renal function in the experimental groups was longer than that in the control group (P<0.05),but there was no significant difference among the experimental groups (P>0.05).There was no statistically significant difference between the experimental groups and the control group in urine volume one day after surgery and kidney function one year after transplantation (P>0.05).Only recovery time after operation of the DBD with the unstable circulation function assisted by EMCO was slightly longer than that with stable circulation function,while the rest indexes showed no statistically significant difference.Conclusion DBD with unstable circulation function with ECMO auxiliary circulatory function can protect the renal function and increase the utilization rate of donor organs.

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