1.FGF19 alleviates inflammatory injury in vascular endothelial cells by activating the Nrf2/HO-1 signaling pathway.
Yan-Jun ZHANG ; Fei-Fei XIAO ; Xiao-Hua LI ; Shen-Hua TANG ; Yi SANG ; Chao-Yue LIU ; Jian-Chang LI
Chinese Journal of Contemporary Pediatrics 2025;27(5):601-608
OBJECTIVES:
To investigate the role and mechanism of fibroblast growth factor (FGF) 19 in inflammation-induced injury of vascular endothelial cells caused by high glucose (HG).
METHODS:
Human umbilical vein endothelial cells (HUVECs) were randomly divided into four groups: control, HG, FGF19, and HG+FGF19 (n=3 each). The effect of different concentrations of glucose and/or FGF19 on HUVEC viability was assessed using the CCK8 assay. Flow cytometry was utilized to examine the impact of FGF19 on HUVEC apoptosis. Levels of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured by ELISA. Real-time quantitative PCR and Western blotting were used to determine the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2 related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Cells were further divided into control, siRNA-Nrf2 (siNrf2), HG, HG+FGF19, HG+FGF19+negative control, and HG+FGF19+siNrf2 groups (n=3 each) to observe the effect of FGF19 on oxidative stress injury in HUVECs induced by high glucose after silencing the Nrf2 gene.
RESULTS:
Compared to the control group, the HG group exhibited increased apoptosis rate, increased IL-6, iNOS and MDA levels, and increased VEGF mRNA and protein expression, along with decreased T-SOD activity and decreased mRNA and protein expression of Nrf2 and HO-1 (P<0.05). Compared to the HG group, the HG+FGF19 group showed reduced apoptosis rate, decreased IL-6, iNOS and MDA levels, and decreased VEGF mRNA and protein expression, with increased T-SOD activity and increased Nrf2 and HO-1 mRNA and protein expression (P<0.05). Compared to the HG+FGF19+negative control group, the HG+FGF19+siNrf2 group had decreased T-SOD activity and increased MDA levels (P<0.05).
CONCLUSIONS
FGF19 can alleviate inflammation-induced injury in vascular endothelial cells caused by HG, potentially through the Nrf2/HO-1 signaling pathway.
Humans
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NF-E2-Related Factor 2/genetics*
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Signal Transduction
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Human Umbilical Vein Endothelial Cells/drug effects*
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Fibroblast Growth Factors/pharmacology*
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Heme Oxygenase-1/physiology*
;
Apoptosis/drug effects*
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Glucose
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Inflammation
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Interleukin-6/analysis*
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Vascular Endothelial Growth Factor A/genetics*
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Nitric Oxide Synthase Type II/analysis*
;
Cells, Cultured
2.Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures (version 2025)
Yong YANG ; Xiaoguang ZHOU ; Qixin CHEN ; Jian CHEN ; Jian DONG ; Liangjie DU ; Shunwu FAN ; Jin FAN ; Zhong FANG ; Haoyu FENG ; Shiqing FENG ; Haishan GUAN ; Aiguo GAO ; Yanzheng GAO ; Yong HAI ; Da HE ; Dengwei HE ; Haiyi HE ; Dianming JIANG ; Xuewen KANG ; Bin LIN ; Baoge LIU ; Changqing LI ; Fang LI ; Li LI ; Fangcai LI ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Xinyu LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Fei LUO ; Yuhai MA ; Keya MAO ; Xuexiao MA ; Bin MENG ; Xu NING ; Limin RONG ; Hongxun SANG ; Jun SHU ; Tiansheng SUN ; Dasheng TIAN ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Qingde WANG ; Qinghe WANG ; Lan WEI ; Jigong WU ; Baoshan XU ; Youjia XU ; Guoyong YIN ; Jinglong YAN ; Feng YAN ; Cao YANG ; Huilin YANG ; Qiang YANG ; Bin ZHAO ; Jie ZHAO ; Yue ZHU ; Jianguo ZHANG ; Wenzhi ZHANG ; Zhongmin ZHANG ; Zhaomin ZHENG ; Yan ZENG ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(7):613-626
Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.
3.Simultaneous,rapid,and precise prediction of main quality control indicators of typhae pollen based on near-infrared spectroscopy technology
Yuning DONG ; Mengjiao SANG ; Xiaoying REN ; Mengting QIN ; Yingying XIE ; Weiliang CUI ; Fei XUE ; Yongqiang LIN ; Bing WANG
Drug Standards of China 2025;26(3):325-331
Objective:To establish a rapid quantitative model for the determination of moisture,extractives,and content in Pollen Typhae.Methods:Near-infrared spectra of 91 batches of Pollen Typhae samples were collected.Spectral preprocessing was performed using S-G,MSC,SNV,and CWT methods.Variable selection was conducted using CARS,SPA,and VIP methods,and compared with full-spectrum modeling.Partial least squares(PLS)mod-els were established for the quantitative determination of moisture,total ash,extractives,and content.The model performance was evaluated by calculating the coefficient of determination for the calibration set and validation set(R2 c,R2v),root mean square error of calibration and validation(RMSEc,RMSEv),and residual prediction devia-tion(RPD).Results:The PLS models for moisture,extractives,and content in Pollen Typhae showed R2c and R2v values greater than 0.9,RMSEc and RMSEv values approaching 0,and RPD values greater than 3.Conclusion:In this study,near-infrared spectroscopy was used to construct quantitative prediction models for moisture,extractives,typhaneoside,and isorhamnetin-3-O-neohesperidoside content in Pollen Typhae.This method enables rapid detection of the main quality control indicators of Pollen Typhae,providing strong technical support for its quality supervision.
4.Simultaneous,rapid,and precise prediction of main quality control indicators of typhae pollen based on near-infrared spectroscopy technology
Yuning DONG ; Mengjiao SANG ; Xiaoying REN ; Mengting QIN ; Yingying XIE ; Weiliang CUI ; Fei XUE ; Yongqiang LIN ; Bing WANG
Drug Standards of China 2025;26(3):325-331
Objective:To establish a rapid quantitative model for the determination of moisture,extractives,and content in Pollen Typhae.Methods:Near-infrared spectra of 91 batches of Pollen Typhae samples were collected.Spectral preprocessing was performed using S-G,MSC,SNV,and CWT methods.Variable selection was conducted using CARS,SPA,and VIP methods,and compared with full-spectrum modeling.Partial least squares(PLS)mod-els were established for the quantitative determination of moisture,total ash,extractives,and content.The model performance was evaluated by calculating the coefficient of determination for the calibration set and validation set(R2 c,R2v),root mean square error of calibration and validation(RMSEc,RMSEv),and residual prediction devia-tion(RPD).Results:The PLS models for moisture,extractives,and content in Pollen Typhae showed R2c and R2v values greater than 0.9,RMSEc and RMSEv values approaching 0,and RPD values greater than 3.Conclusion:In this study,near-infrared spectroscopy was used to construct quantitative prediction models for moisture,extractives,typhaneoside,and isorhamnetin-3-O-neohesperidoside content in Pollen Typhae.This method enables rapid detection of the main quality control indicators of Pollen Typhae,providing strong technical support for its quality supervision.
5.Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures (version 2025)
Yong YANG ; Xiaoguang ZHOU ; Qixin CHEN ; Jian CHEN ; Jian DONG ; Liangjie DU ; Shunwu FAN ; Jin FAN ; Zhong FANG ; Haoyu FENG ; Shiqing FENG ; Haishan GUAN ; Aiguo GAO ; Yanzheng GAO ; Yong HAI ; Da HE ; Dengwei HE ; Haiyi HE ; Dianming JIANG ; Xuewen KANG ; Bin LIN ; Baoge LIU ; Changqing LI ; Fang LI ; Li LI ; Fangcai LI ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Xinyu LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Fei LUO ; Yuhai MA ; Keya MAO ; Xuexiao MA ; Bin MENG ; Xu NING ; Limin RONG ; Hongxun SANG ; Jun SHU ; Tiansheng SUN ; Dasheng TIAN ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Qingde WANG ; Qinghe WANG ; Lan WEI ; Jigong WU ; Baoshan XU ; Youjia XU ; Guoyong YIN ; Jinglong YAN ; Feng YAN ; Cao YANG ; Huilin YANG ; Qiang YANG ; Bin ZHAO ; Jie ZHAO ; Yue ZHU ; Jianguo ZHANG ; Wenzhi ZHANG ; Zhongmin ZHANG ; Zhaomin ZHENG ; Yan ZENG ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(7):613-626
Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.
6.Predictive value of controlling nutritional status score in the prognosis of patients with advanced diffuse large B-cell lymphoma
Huirong SHAN ; Xicheng CHEN ; Hao ZHANG ; Yuqing MIAO ; Fei WANG ; Yuye SHI ; Ling WANG ; Jingjing YE ; Ziyuan SHEN ; Wei SANG ; Hongfeng GE
Journal of Leukemia & Lymphoma 2024;33(2):104-109
Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.
7.Effect of PDCA cycle on improving the completion rate of sepsis bundle treatment
Xiaoming SANG ; Yuli LI ; Yuping HAN ; Na LI ; Zhenmei ZHANG ; Fei WANG
Chinese Journal of Practical Nursing 2024;40(21):1614-1620
Objective:To analyze the effect of analysis plan, do, check, and action (PDCA) cycle in improving the completion rate of sepsis bundle treatment in sepsis patients and the knowledge-attitude-practice of sepsis bundle treatment in medical staff.Methods:Using the historical control method, sepsis patients admitted to the Emergency Trauma Intensive Care Unit of Shandong Provincial Hospital Affiliated to Shandong First Medical University were selected as the research objects by convenience sampling. The 35 patients admitted from January to December 2021 will be included in the control group; from June 2022 to June 2023, 28 patients were admitted to the observation group. The control group received routine nursing care, while the observation group received intervention based on the PDCA cycle. The completion rate of sepsis bundle treatment before and after PDCA cycle implementation was compared. The 27 nurses and 5 doctors working in trauma care unit were investigated by using a self-designed questionnaire on their knowledge and practice level of sepsis bundle treatment. The completion rate of sepsis bundle treatment before and after the implementation of PDCA cycle was compared.Results:The control group included 19 males and 16 females, aged (61.77 ± 8.64) years. The observation group included 13 males and 15 females, aged (60.61 ± 10.20) years. After the implementation of PDCA cycle, the completion rate of 3h bundle treatment for sepsis in the observation group was 89.29% (25/28), which was higher than 31.42% (10/35) in the control group, with a statistically significant difference ( χ2=23.22, P<0.05). The completion rate of sepsis bundle treatment within 6 hours in the observation group was 11/11, which was higher than 5/9 in the control group, with a statistically significant difference ( χ2=6.11, P<0.05). Moreover, after the implementation of PDCA cycle, the total score and sub-scale scores of the knowledge-attitude-practice among medical staffs increased from 86.60 ± 10.33, 21.00 ± 4.74, 18.00 ± 1.58, and 47.60 ± 4.10 to 100.00 ± 5.20, 27.60 ± 2.51, 19.60 ± 0.55, and 52.80 ± 2.28 respectively, with statistically significant differences ( t values were -5.10 - -3.14, all P<0.05). Conclusions:PDCA cycle can improve the completion rate of sepsis bundle treatment and improve the level of knowledge, attitude and practice of medical staff.
8.Residual neural network-101-feature pyramid network model based on CT for differentiating benign and malignant lung nodules
Gang LIU ; Xiaoting XIE ; Hui HE ; Fei LIU ; Xu MAO ; Jingyao SANG ; Haiyun YANG ; Yueyong XIAO
Chinese Journal of Interventional Imaging and Therapy 2024;21(7):414-417
Objective To observe the value of residual neural network(ResNet)-101-feature pyramid network(FPN)model based on CT for differentiating benign and malignant lung nodules.Methods Totally 2 040 lung nodules in 2 000 patients were retrospectively enrolled,including 1 150 benign and 890 malignant nodules.The nodules were divided into training set(n=1 632)and test set(n=408)at the ratio of 8∶2,the former including 881 benign and 751 malignant ones,while the latter including 269 benign and 139 malignant ones,respectively.Taken ResNet-101 as the backbone network,combined with FPN,a classification model was established based on chest CT,and the efficiency of this model alone and combined with evaluation of physicians for differentiating benign and malignant lung nodules were evaluated.Results Among 269 benign lung nodules in test set,ResNet-101-FPN model alone correctly diagnosed 214 nodules(214/269,79.55%),while combined with evaluation of physicians correctly diagnosed 230 ones(230/269,85.50%).For 139 malignant nodules in test set,ResNet-101-FPN model alone correctly diagnosed 124 nodules(124/139,89.21%),while combined with evaluation of physicians correctly diagnosed 131 ones(131/139,94.24%).The sensitivity,accuracy and precision of ResNet-101-FPN model combined with evaluation of physicians for distinguishing benign and malignant lung nodules were all higher,while the specificity of the combination was lower than those of ResNet-101-FPN model alone,but the differences were not significant(all P>0.05).Conclusion ResNet-101-FPN model could be used to distinguish benign and malignant lung nodules based on CT.Combining with evaluation of physicians could improve diagnostic efficiency of this model.
9.Cardiovascular protective effects of SGLT-2 inhibitors on patients with type 2 diabetic nephropathy
Ya-Fei SANG ; Jing-Ya YUAN ; Qian ZHAO ; Jia-Lin WANG ; Yu-Jin MA ; Hong-Yun WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(4):449-455
Objective:To explore the clinical efficacy and cardiovascular protective effect of sodium-glucose co-transporter 2 inhibitor(SGLT-2i)on patients with type 2 diabetic nephropathy(T2DN).Methods:A total of 376 T2DN patients admitted in our Department of Endocrinology and Department of Cardiology from January 2018 to December 2021 were selected.According to therapeutic program,they were divided into control group(n=177,re-ceived routine treatment program)and SGLT-2i group(n=199,received SGLT-2i based on routine treatment program),both groups were continuously treated for 1 year.Blood glucose,blood pressure,blood lipids,uric acid,body mass index,renal function-related indexes and the occurrence of major adverse cardiovascular events were compared between the two groups after 12 months,as well as the adverse drug reactions.Results:After 12-month treatment,compared with control group,there were significant reductions in levels of blood pressure,fasting blood glucose(FBG),glycosylated hemoglobin A1e(HbA1c),urinary albumin/creatinine ratio(UACR),creatinine(Cr),blood urea nitrogen(BUN),total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and uric acid(UA),and significant rise in estimated glomerular filtration rate(eGFR),levels of high density lipoprotein cholesterol(HDL-C),albumin(Alb)and alanine aminotransferase(ALT)in SGLT-2i group(P<0.05 or<0.01).Incidence rates of acute myocardial infarction(1.51%vs.6.21%)and heart failure caused-readmission(2.51%vs.6.78%)in SGLT-2i group were significantly lower than those of control group,and inci-dence rate of urinary system infection(8.54%vs.1.69%)was significantly higher than that of control group(P<0.05 all).Conclusion:SGLT-2i can not only effectively control blood glucose,but also reduce body weight and blood pressure,improve blood lipids,reduce uric acid,improve renal hyperfiltration,reduce urinary protein and possess unique cardiovascular benefits,but risk of urinary system infection calls for attention.
10.Effects of the ROCK1 gene on proliferation and migration of and related molecular expression in keloid fibroblasts
Pengfei SANG ; Mingsong FANG ; Xuan LI ; Lin CAO ; Lingling ZHAO ; Chang LIU ; Zhiyong JIANG ; Fei ZHU
Chinese Journal of Dermatology 2023;56(3):222-228
Objective:To investigate effects of the ROCK1 gene on proliferation and migration of and related molecular expression in keloid fibroblasts.Methods:Immunohistochemical technique was used to detect ROCK1 protein expression in human keloids and normal skin tissues, and Western blot analysis was performed to detect the expression of ROCK1, transforming growth factor β1 (TGF-β1) and E-cadherin in keloid tissues. In vitro cultured human keloid fibroblasts (HKFs) were divided into 4 groups: ROCK1 gene overexpression control group (ROCK1 NC group) transfected with ROCK1 gene overexpression control vectors, ROCK1 gene overexpression group (ROCK1 OE group) transfected with ROCK1 gene overexpression vectors, ROCK1 gene knockdown control group (sh NC group) transfected with ROCK1 gene knockdown control vectors, and ROCK1 gene knockdown group (shROCK1 group) transfected with ROCK1 gene knockdown vectors. Cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ROCK1 gene on the survival rate of HKFs, Transwell assay to evaluate the effect on the migration of HKFs, and real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis were conducted to determine the mRNA and protein expression of ROCK1, TGF-β1 and E-cadherin, respectively. Results:Immunohistochemical study showed that ROCK1 protein expression decreased significantly in the human keloid tissues compared with the normal tissues ( t = 6.47, P = 0.003) ; Western blot analysis showed that the expression levels of ROCK1 and E-cadherin significantly decreased ( t = 14.02, 162.20, respectively, both P < 0.001), while TGF-β1 expression significantly increased ( t = 76.01, P < 0.001) in the keloid tissues compared with the expression levels of corresponding proteins in the normal tissues. CCK8 assay showed that the cell activity was significantly lower in the ROCK1 OE group than in the ROCK1 NC group after 24-hour transfection ( t = 3.25, 3.78, P = 0.031, 0.019, respectively), and significantly higher in the shROCK1 group than in the sh NC group ( t = 3.12, 2.79, P = 0.036, 0.049, respectively). Transwell assay showed that the number of migratory cells was significantly lower in the ROCK1 OE group than in the ROCK1 NC group ( t = 5.17, P = 0.004), and significantly higher in the shROCK1 group than in the sh NC group ( t = 9.28, P < 0.001). Compared with the ROCK1 NC group, the ROCK1 OE group showed significantly increased mRNA and protein expression levels of ROCK1 and E-cadherin ( P < 0.05 or < 0.001), but decreased mRNA and protein expression levels of TGF-β1 (both P < 0.001) ; compared with the sh NC group, the shROCK1 group showed significantly decreased mRNA and protein expression levels of ROCK1 and E-cadherin ( P < 0.05 or < 0.001), but significantly increased mRNA and protein expression levels of TGF-β1 ( P = 0.005 or < 0.001) . Conclusions:The ROCK1 gene can inhibit the proliferation and migration of HKFs. Overexpression of the ROCK1 gene can down-regulate the TGF-β1 gene expression and up-regulate the E-cadherin gene expression in HKFs.

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