1.Changes in C3,HMGB1 and GPX4 expression in rats after cerebral ischemia-reperfusion injury
Hanting ZHU ; Ruifang XIONG ; Chengyi LI ; Xihai ZHAO ; Xiaoping TANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(6):699-703
Objective To investigate the changes in the expression of complement C3,high mobility group protein B1(HMGB1),and glutathione peroxidase 4(GPX4)in brain tissue at different time points after cerebral ischemia-reperfusion injury in rats.Methods A total 72 SPF male SD rats were randomly divided into a sham operation group(36 rats)and a model group(36 rats).A rat model of middle cerebral artery occlusion was established using thread occlusion,and then the rats from the model group were further assigned into 4 subgroups with reperfusion time for 3,6 and 24 h and 3 d,respectively,with 9 rats in each subgroup.Zea Longa scoring was used to assess neu-rological function.R2StarMap imaging,diffusion-weighted imaging(DWI),T1 weighted imaging,and T2 weighted imaging were performed on all the rats.The volume of abnormal DWI signals were detected and the volume of cerebral infarction was measured.The original R2StarMap images were post-processed to generate R2*pseudo color images,and then the R2*values of the areas with blood supply from bilateral middle cerebral artery were measured to detect iron deposition in the brain.The protein expression of C3,HMGB1,and GPX4 was detected by Western blotting.Results The sham operation group showed no neurological damage,while the model group had a significant increase in neurological function scores at 3,6 and 24 h and 3 d after modeling when compared to the sham surgery group(P<0.05).While the size of right cerebral infarct was in-creased significantly at 3,6 and 24 h and 3 d in the rats of the model group(P<0.05).The R2*value of the area with blood supply from the right middle cerebral artery in the model group was significantly higher than that in the left side at 3,6 and 24 h and 3 d(P<0.05,P<0.01),and it was also obviously higher than that in the right side of the sham operation group at these time points(P<0.05,P<0.01).The R2*ratio of the right and left blood supply areas in the model group at 3,6 and 24 h and 3 d was also statistically higher than that in the sham operation group at corresponding time points(1.82±0.82 vs 1.12±0.31,P<0.05;1.31±0.26 vs 1.04±0.14,P<0.05;1.94±0.74 vs 1.06±0.10,P<0.01;1.99±0.39 vs 1.02±0.11,P<0.01).Compared with the sham operation group,the expression levels of C3 and HMGB1 was significantly increased in the model group at 3,6 and 24 h and 3 d,while that of GPX4 was notably reduced(P<0.01).Conclu-sion Cerebral ischemia-reperfusion injury impairs the neurological function of rats and signifi-cantly affects the cerebral expression of complement C3,HMGB1,and GPX4.
2.The value of ROX index in evaluating the efficacy of high-flow nasal cannula oxygen therapy in patients with COVID-19
Wei DA ; Yuanyuan HE ; Xiaobo WANG ; Aihui XU ; Yonghuai LI ; Xihai XU ; Hong ZHANG
Chinese Journal of Emergency Medicine 2021;30(5):588-592
Objective:To assess the value of the ROX index in evaluating the efficacy of high-flow nasal cannula oxygen therapy (HFNC) in patients with coronavirus infected disease (COVID-19).Methods:This is a retrospective study. The included patients were diagnosed as COVID-19 in the intensive care unit (ICU) of the Cancer Center of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from February 15, 2020 to March 15, 2020. All the patients were treated by HFNC. According to whether the patient subsequently received non-invasive positive pressure ventilation or invasive positive pressure ventilation, patients were divided into the HFNC success group and the HFNC failure group. Parameters in the two groups such as basic characteristics, lactic acid, number of chest radiographs, APACHE II, lymphocyte count, baseline respiratory rate, baseline percutaneous oxygen saturation, baseline PaO 2/FiO 2, baseline ROX index, and ROX index after 2, 6 and 12 h HFNC treatment were analyzed with t test, Chi-square test or rank sum test. Results:A total of 57 cases were included in this study. There were no significant differences in sex, age, comorbidities, lactic acid, quadrants of chest radiograph lung infection, APACHE II, lymphocyte count, and baseline respiratory frequency, transcutaneous oxygen saturation, oxygenation index, and ROX index between the HFNC success group and the HFNC faliure group ( P>0.05). Logistic regression analysis showed that ROX index after 2 h HFNC treatment ( OR=0.069), ROX index after 6 h HFNC treatment ( OR=0.194) and ROX index after 12 h HFNC treatment ( OR=0.036) were all protective factors for the therapeutic effect of HFNC treatment in COVID-19 patients. ROC curve showed that there were significant differences in ROX index after 2 h HFNC treatment, ROX index after 6 h HFNC treatment, and ROX index after 12 h HFNC treatment ( P<0.05). In the evaluation index, the area under the ROC curve of the ROX index after 2 h HFNC treatment was 0.838, the sensitivity was 64.5%, and the specificity was 100%. After 6 h HFNC treatment, the area under the ROX index ROC curve was 0.762, the sensitivity was 64.5%, and the specificity was 92.3%. After 12 h HFNC treatment, the ROX index ROC curve area was 0.866, the sensitivity was 67.7%, and the specificity was 100%. Conclusions:The ROX index can be used to evaluate the efficacy of HFNC in COVID-19 patients in a timely, simple and real-time manner.
3.Application of the teaching mode integrated with humanistic spirit in the clinical practice teaching of gynecology
Fanling MENG ; Lianwei LI ; Xihai CHEN ; Xin NING ; Rong MA
Chinese Journal of Medical Education Research 2021;20(5):570-573
Objective:To explore the application effect of medical humanity quality education teaching mode integrated with humanistic spirit in clinical teaching of gynecology.Methods:Taking 60 undergraduate interns in gynecology department of Harbin Medical University Cancer Hospital as the experimental research objects, they were divided into experimental group and control group, with 30 students in each group. In clinical practice teaching, the experimental group adopted a teaching mode of integrating humanistic spirit, and the control group adopted a traditional teaching mode. The assessment results, teaching satisfaction and teaching effects were compared among the two groups of students. SPSS 22.0 was used for statistical analysis.Results:The students in the experimental group had higher scores of gynecological theory examination [(98.90±0.85) points] and the practical examination [(98.80±0.81) points] than the students in the control group had [(93.43±2.22) points and (92.77±2.37) points] ( P < 0.01). The teaching satisfaction of students in the experimental group was 100.00% when they leaving the department, and the satisfaction of teaching in the control group was 83.3%. The satisfaction of teaching in the experimental group was higher than that of the control group. After the internship, the experimental group was significantly superior than the control group in learning interest, problem-solving ability, self-learning ability, doctor-patient communication ability, and knowledge expansion ability ( P < 0.05). Conclusion:In the clinical teaching of gynecology, the implementation of personalized teaching and humanistic quality education mode has significantly improved the students' theoretical performance, practical performance and teaching satisfaction. The medical humanistic quality education model integrated with humanistic spirit plays an important role in clinical practice teaching.
4.The study on the segmentation of carotid vessel wall in multicontrast MR images based on U?Net neural network
Jifan LI ; Shuo CHEN ; Qiang ZHANG ; Yan SONG ; Canton GADOR ; Jie SUN ; Dongxiang XU ; Xihai ZHAO ; Chun YUAN ; Rui LI
Chinese Journal of Radiology 2019;53(12):1091-1095
Objective To investigate the value of automatic segmentation of carotid vessel wall in multicontrast MR images using U?Net neural network. Methods Patients were retrospectively collected from 2012 to 2015 in Carotid Atherosclerosis Risk Assessment (CARE II) study. All patients who recently suffered ischemic stroke and/or transient ischemic attack underwent identical, state?of?the?art multicontrast MRI technique. A total of 17 568 carotid vessel wall MR images from 658 subjects were included in this study after inclusion criteria and exclusion criteria. All MR images were analyzed using customized analysis platform (CASCADE). Randomly, 10 592 images were assigned into training dataset, 3 488 images were assigned into validating dataset and 3 488 images were assigned into test dataset according to a ratio of 6∶2∶2. Data augmentation was performed to avoid over fitting and improve the ability of model generalization. The fine?tuned U?Net model was utilized in the segmentation of carotid vessel wall in multicontrast MR images. The U?Net model was trained in the training dataset and validated in the validating dataset. To evaluate the accuracy of carotid vessel wall segmentation, the sensitivity, specificity and Dice coefficient were used in the testing dataset. In addition, the interclass correlation and the Bland?Altman analysis of max wall thickness and wall area were obtained to demonstrate the agreement of the U?Net segmentation and the manual segmentation. Results The sensitivity, specificity and Dice coefficient of the fine?tuned U?Net model achieved 0.878,0.986 and 0.858 in the test dataset, respectively. The interclass correlation (95% confidence interval) was 0.921 (0.915-0.925) for max wall thickness and 0.929 (0.924-0.933) for wall area. In the Bland?Altman analysis, the difference of max wall thickness was (0.037±0.316) mm and the difference of wall area was (1.182±4.953) mm2. The substantial agreement was observed between U?Net segmentation method and manual segmentation method. Conclusion Automatic segmentation of carotid vessel wall in multicontrast MR images can be achieved using fine?tuned U?Net neural network, which is trained and tested in the large scale dataset labeled by professional radiologists.
5. The study on the segmentation of carotid vessel wall in multicontrast MR images based on U-Net neural network
Jifan LI ; Shuo CHEN ; Qiang ZHANG ; Yan SONG ; Gador CANTON ; Jie SUN ; Dongxiang XU ; Xihai ZHAO ; Chun YUAN ; Rui LI
Chinese Journal of Radiology 2019;53(12):1091-1095
Objective:
To investigate the value of automatic segmentation of carotid vessel wall in multicontrast MR images using U-Net neural network.
Methods:
Patients were retrospectively collected from 2012 to 2015 in Carotid Atherosclerosis Risk Assessment (CARE II) study. All patients who recently suffered ischemic stroke and/or transient ischemic attack underwent identical, state-of-the-art multicontrast MRI technique. A total of 17 568 carotid vessel wall MR images from 658 subjects were included in this study after inclusion criteria and exclusion criteria. All MR images were analyzed using customized analysis platform (CASCADE). Randomly, 10 592 images were assigned into training dataset, 3 488 images were assigned into validating dataset and 3 488 images were assigned into test dataset according to a ratio of 6∶2∶2. Data augmentation was performed to avoid over fitting and improve the ability of model generalization. The fine-tuned U-Net model was utilized in the segmentation of carotid vessel wall in multicontrast MR images. The U-Net model was trained in the training dataset and validated in the validating dataset. To evaluate the accuracy of carotid vessel wall segmentation, the sensitivity, specificity and Dice coefficient were used in the testing dataset. In addition, the interclass correlation and the Bland-Altman analysis of max wall thickness and wall area were obtained to demonstrate the agreement of the U-Net segmentation and the manual segmentation.
Results:
The sensitivity, specificity and Dice coefficient of the fine-tuned U-Net model achieved 0.878,0.986 and 0.858 in the test dataset, respectively. The interclass correlation (95% confidence interval) was 0.921 (0.915-0.925) for max wall thickness and 0.929 (0.924-0.933) for wall area. In the Bland-Altman analysis, the difference of max wall thickness was (0.037±0.316) mm and the difference of wall area was (1.182±4.953) mm2. The substantial agreement was observed between U-Net segmentation method and manual segmentation method.
Conclusion
Automatic segmentation of carotid vessel wall in multicontrast MR images can be achieved using fine-tuned U-Net neural network, which is trained and tested in the large scale dataset labeled by professional radiologists.
6.Mitochondrial uncoupler BAM15 inhibits artery constriction and potently activates AMPK in vascular smooth muscle cells.
Yu TAI ; Lanjun LI ; Xuan PENG ; Junxue ZHU ; Xihai MAO ; Nan QIN ; Minghui MA ; Rong HUO ; Yunlong BAI ; Deli DONG
Acta Pharmaceutica Sinica B 2018;8(6):909-918
Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells (A10 cells). BAM15 relaxed phenylephrine (PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PE-induced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP, and niclosamide had the comparable IC value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide. BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells. BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.
7.Establishment and identification of the rat models of chondrocyte apoptosis induced by tumor necrosis factor-alpha
Houhuang CHEN ; Xiang SHAO ; Li LI ; Mingxia WU ; Xihai LI
Chinese Journal of Tissue Engineering Research 2017;21(4):527-531
BACKGROUND:Tumor necrosis factor-α(TNF-α), a main cytokine inducing chondrocyte apoptosis of osteoarthritis, plays a regulatory role in the process of osteoarthritis. OBJECTIVE:To compare the rat models of chondrocyte apoptosis induced by different mass concentrations of TNF-α, thus providing theoretical basis for further study on the regulation of drugs on chondrocyte apoptosis. METHODS:Chondrocytes were isolated from the knee cartilage of 4-week-old Sprague-Dawley rats of clean grade by mechanical l col agenase digestion and were then incubated with different mass concentrations of TNF-αto induce apoptosis. The morphology of chondrocytes was observed under inverted phase contrast microscope, cel s were identified using immunohistochemical staining of type II col agen, as wel as the cel viability and apoptosis were detected by MTT and DAPI, respectively. RESULTS AND CONCLUSION:(1) In vitro, the cytoplasm of chondrocytes was stained brown-yel ow by using immunohistochemical staining of type II col agen. (2) At 48 hours, the apoptosis rate of chondrocytes induced by 10, 20 and 30μg/L TNF-αwas significantly higher than that of the 0μg/L TNF-α(P<0.01), and the apoptosis rate of chondrocytes induced by 40μg/L TNF-αwas significantly higher than that of the 10μg/L TNF-α(P<0.01). (3) The viability of chondrocytes induced by 10, 20 and 40μg/L TNF-αwas significantly lower than that of the 0μg/L TNF-α(P<0.01). In detail, the viability of chondrocytes induced by 20μg/L TNF-αwas lower than that of the 10μg/L TNF-α(P<0.05);the viability of chondrocytes induced by 40μg/L TNF-αwas significantly lower than that of the 10 and 20μg/L TNF-α(P<0.01, P<0.05). (4) These results suggest that 20μg/L TNF-αcan successful y induce the chondrocyte apoptosis model.
8.Electroacupuncture delays articular cartilage degeneration in osteoarthritisvia Ras-Raf-MEK1/2-ERK1/2 signaling pathway
Changlong FU ; Houhuang CHEN ; Dingyu ZHU ; Zhuile WU ; Xin XU ; Chunsong ZHENG ; Li LI ; Xianxiang LIU ; Xihai LI ; Mingxia WU
Chinese Journal of Tissue Engineering Research 2017;21(24):3790-3795
BACKGROUND:Previous studies have found that electroacupuncture can delay articular cartilage degeneration mediated by JAK-STAT signaling pathway through upregulating the expression level of transforming growth factor β1 as well as mRNA expression levels of STAT3, Smad3 and LepR. In the meanwhile, electroacupuncture can inhibit the mRNA expression of p38 and Fas mRNA mediated by MAPK signaling pathways, further inhibiting the apoptosis of chondrocytes. OBJECTIVE: To explore the effect of electroacupuncture on the degeneration of articular cartilage in rats with knee osteoarthritis based on Ras-Raf-MEK1/2-ERK1/2 signaling pathway. METHODS:120 male healthy Sprague-Dawley rats aged 2 months olds were selected and randomly divided into normal, model, 15-minite electroacupuncture and 30-minute electroacupuncture groups (n=30 per group). The rats in the latter three groups received the intra-articular injection of 4% papain bilaterally, and the remaining rats received no intervention. At 2 weeks after modeling, the latter two groups were respectively given 15- and 30-minute electroacupuncture, five times weekly for consecutive 12 weeks. The morphology of the cartilage was observed by hematoxylin-eosin staining, the expression level of interleukin-1β in the synovium was detected by ELISA assay, and the protein expression levels of Ras, Raf, MEK1/2, ERK1/2, C-MYC, C-FOS, and C-JUN were detected by western blot analysis. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that: in the model group, the cartilage surface was rough, the cartilage layer became thinner, and the cartilage structure was damaged with incomplete tidal line; in the 15- and 30-minute electroacupuncture groups, the cartilage structure was complete with clear layers and complete tidal line. ELISA showed that the expression level of interleukin-1β in the model group was significantly higher than that in the normal group (P< 0.01), and the level in the 15- and 30-minute electroacupuncture groups was significantly lower than that in the model group (P < 0.05). Western blot assay found that compared with the normal group, the protein expression levels of Ras, Raf, MEK1/2, ERK1/2, C-MYC, C-FOS, and C-JUN were increased in the model group. However, all above protein levels except ERK1/2 in the 15- and 30-minute electroacupuncture groups were significantly lower than those in the model group (P < 0.01,P < 0.05). To conclude, electroacupuncture inhibits the degeneration of articular cartilage in osteoarthritisvia Ras-Raf-MEK1/2-ERK1/2 signaling pathway and downregulating the expression level of interleukin-1β.
9.Influences of statin treatment on MR vessel wall imaging-observed characteristics of atherosclerotic plaque in the thoracic aorta in the elderly
Changwu ZHOU ; Cheng LI ; Xihai ZHAO ; Fang DU ; Wei WANG ; Huiyu QIAO ; Le HE ; Rui LI ; Huijun CHEN ; Qiang ZHANG ; Chun YUAN
Chinese Journal of Geriatrics 2017;36(4):412-416
Objective To evaluate the influences of statin treatment on MR vessel wall imagingobserved characteristics of atherosclerotic plaque in the thoracic aorta of the elderly.Methods Elderly subjects (≥ 60 years) without any serious cerebro-cardiovascular diseases were recruited.Thoracic aorta was imaged on MR scanner for all the subjects.The plaque burden was calculated quantitatively,the composition of plaque in thoracic aorta was evaluated qualitatively,and the contributions of statin treatment to these characteristics were also compared by image interpretation personals.The thoracic aorta was divided into three segments (AAO:ascending aorta;AOA:aortic arch,and DOA:descending aorta)on the imaging.Results Totally 55 recruited subjects had atherosclerotic plaque in thoracic aorta,with 24 subjects receiving statin treatment,and 50 % (12/24) male,aged 73.8±6.3 years.The level of LDL C[(2.4±0.7)mmol/L vs.(3.1±0.8)mmol/L(P< 0.01)]and total cholesterol[(4.4±0.6)mmol/L vs.(5.1 ±1.0)mmol/L(P<0.01)]were significantly lower in statin group than in non-statin group.The lumen area,wall area,and total vessel area in all three segments of thoracic aorta were significantly smaller in statin group(all P<0.05)than in nonstatin group.The average wall thickness in segment of AOA[(2.7±0.3)mm vs.(2.8±0.4)mm(P<0.01)]and DAO[(2.5±0.4)mm vs.(2.6±0.5)mm(P<0.01)]were smaller in statin group than in non-statin group.The incidence rate of intraplaque hemorrhage / mural thrombus [6 cases (25.0%) vs.8 cases(25.8 %)]in thoracic aorta was a little lower in statin group than in non-statin group,with no significant difference(P>0.05).Conclusions Statin treatment decreases LDL-C level,reduces the burden of atherosclerotic plaque in thoracic aorta,and maintains the atherosclerotic plaque stability.
10.Characteristics of Atherosclerotic Plaque in Thoracic Aorta in the Elderly Evaluated by Magnetic Resonance Vessel Wall Imaging
Changwu ZHOU ; Xihai ZHAO ; Cheng LI ; Huiyu QIAO ; Le HE ; Chun YUAN
Chinese Journal of Medical Imaging 2017;25(8):588-592
Purpose The thoracic aortic atherosclerotic plaque is an important source of ischemic stroke embolism in the elderly.This study aims to explore the characteristics of vulnerable plaque of atherosclerosis in the thoracic aorta in the elderly by using three-dimensional multi-contrast magnetic resonancewall imaging technique,so as to actively prevent the occurrence of cardiovascular and cerebrovascular complications.Materials and Methods Fifty-three cases of elderly subjects (>60 years old) without serious cerebrovascular diseases were recruited in this prospective study.All subjects were divided into A and B groups (60-74 and 75-90 years old).All subjects underwent MRI of multiple contrast sequences of the aortic wall.The thoracic aorta was divided into three segments of ascending aorta,aortic arch and descending aorta,and the characteristics of the atherosclerotic plaque were evaluated.The load characteristics of thoracic aortic atherosclerotic plaques in the elderly were calculated quantitatively,and the compositional characteristics were evaluated qualitatively.Results The incidence of intraplaque hemorrhage in the thoracic aortic atherosclerotic plaque in the elderly was 26.4% (14/53),and the incidence of lipid nucleus was 94.3% (50/53).Meanwhile,the maximum wall thickness of three segments of ascending aorta,aortic arch and descending aorta in group B was significantly higher than that in group A [(3.1±0.6) mm vs (3.0±0.4) mm,P<0.05;(3.2±0.7) mm vs (3.1 ±0.7) mm,P<0.05;(3.0±0.8) mm vs (2.9±0.7) mm,P<0.001];the normalized wall index of the three segments in group B was significantly higher than that in group A [(26.9±3.5)% vs (26.7±2.9)%,P<0.001;(31.9±5.1)% vs (31.0±5.1)%,P<0.001;(34.6±5.0)% vs (34.1 ±4.6)%,P<0.001)].Conclusion The incidence of hemorrhage in the atherosclerotic plaque in the thoracic aorta in the elderly is higher,and the plaque load increases with age.Therefore,early screening of vulnerable plaque in the thoracic aorta in the elderly using magnetic resonance wall imaging will be helpful for prevention and treatment of stroke.

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