1.Resveratrol activates extracellular-regulated protein kinase 5 signaling protein to promote proliferation of mouse MC3T3-E1 cells
Yongkang NIU ; Zhiwei FENG ; Yaobin WANG ; Zhongcheng LIU ; Dejian XIANG ; Xiaoyuan LIANG ; Zhi YI ; Hongwei ZHAN ; Bin GENG ; Yayi XIA
Chinese Journal of Tissue Engineering Research 2025;29(5):908-916
BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.
2.3D Pulse Image Detection and Pulse Pattern Recognition Based on Subtle Motion Magnification Technology.
Chongyang YAO ; Yongxin CHOU ; Zhiwei LIANG ; Haiping YANG ; Jicheng LIU ; Dongmei LIN
Chinese Journal of Medical Instrumentation 2025;49(3):255-262
To address the problem of large reconstruction errors in 3D pulse signals caused by excessively small out-of-plane displacement of the contact membrane in the existing traditional Chinese medicine fingertip tactile binocular vision detection technology, this study proposes a 3D pulse image detection method based on subtle motion magnification technology and explores its application in pulse pattern recognition. Firstly, a 3D pulse image detection system based on binocular vision to obtain pulse image signals is developed as experimental data. Then, the phase motion video magnification algorithm is used to amplify the original signals, and the amplified signals are reconstructed in three dimensions to obtain 3D pulse signals. On this basis, nine features are extracted from the 3D pulse signals and features selection is performed using a two-sample Kolmogorov-Smirnov test. Finally, machine learning algorithms such as decision trees and random forests are used to identify the five types of pulse conditions: deep pulse, intermittent pulse, flooding pulse, slippery pulse, and rapid pulse. The experimental results show that compared to the methods without subtle motion magnification technology, the proposed method significantly improves waveform clarity, amplitude stability, and periodic regularity. Meanwhile, the average accuracy in pulse pattern recognition reaches 96.29%±0.26%.
Algorithms
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Imaging, Three-Dimensional/methods*
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Pattern Recognition, Automated
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Medicine, Chinese Traditional
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Motion
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Humans
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Pulse
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Signal Processing, Computer-Assisted
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Machine Learning
3.SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.
Tongzhu JIN ; Huiying GAO ; Yuquan WANG ; Zhiwei NING ; Danyang BING ; Yan WANG ; Yi CHEN ; Xiaomu TIAN ; Qiudi LIU ; Zhihui NIU ; Jiayu GUO ; Jian SUN ; Ruoxuan YANG ; Qianqian WANG ; Shifen LI ; Tianyu LI ; Yuhong ZHOU ; Wenxin HE ; Yanjie LU ; Yunyan GU ; Haihai LIANG
Acta Pharmaceutica Sinica B 2025;15(6):3041-3058
Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.
4.Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis
Zonglong LI ; Jialu CHEN ; Yue TANG ; Delong QIN ; Chen CHEN ; Yinghe QIU ; Hong WU ; Yu HE ; Xianhai MAO ; Wenlong ZHAI ; Jingdong LI ; Xiao LIANG ; Chuandong SUN ; Kai MA ; Zhimin GENG ; Zhaohui TANG ; Zhiwei QUAN
Chinese Journal of Surgery 2024;62(7):685-696
Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.
5.Clinical analysis of complete left bundle branch block after transcatheter closure of ventricular septal defect in 25 children
Bingyu MA ; Yifan LI ; Dongpo LIANG ; Ling SUN ; Xu HUANG ; Shaoying ZENG ; Shusheng WEN ; Shushui WANG ; Zhiwei ZHANG ; Yumei XIE
Chinese Journal of Applied Clinical Pediatrics 2024;39(10):743-749
Objective:To summarize the clinical treatment of complete left bundle branch block (CLBBB) after the transcatheter closure of ventricular septal defect (VSD).Methods:A case series study was conducted on the treatments and outcomes of 25 children with CLBBB after transcatheter VSD closure in Guangdong Provincial People′s Hospital from January 2010 to December 2023.Paired sample t test was used to evaluate the effect of occlude removal. Results:Among the 25 patients, 12 were males (48%), and 13 were females (52%).The age at surgery was 3.18 (2.51-3.86) years, the height before surgery was 95.0 (90.0-97.5) cm, and the weight before surgery was 13 (12-15) kg.Fourteen children were early-onset cases (≤ 1 month), while the other 11 were late-onset cases (> 1 month).The mean follow-up time was (6.63±3.93) years.Of the 14 early-onset cases, 6 children underwent occluder removal within 1 month and restored normal heart rhythm or incomplete right bundle branch block; 4 children underwent occluder removal after 1 month, of whom 2 recovered, 1 remained CLBBB, and 1 had complete atrioventricular block (CAVB); the other 4 children received drug treatment, of whom 2 had normal heart rhythm, 1 had left anterior fascicular block, and 1 died of cardiac shock and heart failure.All the 11 late-onset cases were first treated by drugs, of whom 3 recovered, and the other 8 remained CLBBB.One of the 8 cases received occluder removal at 8 months after surgery and recovered, 1 had CAVB, and the other 6 remained CLBBB.Conclusions:For patients with CLBBB after transcatheter closure of VSD, drug therapy is not always effective, and CLBBB is easy to recur.Therefore, occluder removal is recommended to be done immediately after CLBBB is discovered.Patients with persistent CLBBB should be followed up regularly, and pacemaker implantation may be performed if necessary.
6.Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis
Zonglong LI ; Jialu CHEN ; Yue TANG ; Delong QIN ; Chen CHEN ; Yinghe QIU ; Hong WU ; Yu HE ; Xianhai MAO ; Wenlong ZHAI ; Jingdong LI ; Xiao LIANG ; Chuandong SUN ; Kai MA ; Zhimin GENG ; Zhaohui TANG ; Zhiwei QUAN
Chinese Journal of Surgery 2024;62(7):685-696
Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.
7.Design and experimental study of pressure control system in spacecraft airlock module
Yuan ZHANG ; Xuan YANG ; Jianqiang XUAN ; Feifei JIAO ; Bin ZHANG ; Peng SUN ; Pisheng ZHAO ; Zhiwei LIANG
Space Medicine & Medical Engineering 2024;35(1):56-59
Air lock module pressure control is a necessary step to balance the pressure inside and outside the spacecraft cabin and achieve the transfer of materials or personnel inside and outside the spacecraft cabin.The two main functions of the air lock module pressure control system are to reduce the pressure when leaving the chamber and increase the pressure when returning to the chamber.There are some methods such as releasing the gas in the chamber to vacuum or storing the gas in the chamber using containers.The control equipment for releasing gas is simple,but the gas is wasted.Gas storage requires temperature control and gas compressing equipment,but the gas is saved.There are some methods such as releasing gas from high-pressure vessels or releasing gas from nearby chamber.This article theoretically analyzes airlock module pressure controlling and provides several technical solutions for designing module pressure control systems.Releasing the gas to vacuum is suitable for spacecraft with a single sealed cabin while storing the gas is suitable for spacecraft with multi sealed cabins.Combined methods are also used in specific conditions.
8.Research of intelligent model for automatically counting the number of vertebral ossification center below the end of conus medullaris
Zhiwei GUO ; Huaxuan WEN ; Dandan LUO ; Bocheng LIANG ; Guanghua TAN ; Hongjie ZHANG ; Ying TAN ; Ying YUAN ; Shengli LI
Chinese Journal of Ultrasonography 2024;33(8):677-682
Objective:To develop and test the intelligent model for automatically counting the number of vertebral ossification centers below the end of conus medullaris.Methods:From January 2021 to October 2022, 3 000 ultrasound images of the sacrococcygeal spinal middle sagittal plane were retrospectively selected from Shenzhen Maternal and Child Healthcare Hospital and Zhuhai People′s Hospital. The vertebral ossification center and spinal conus medullaris were artificially fine-marked in 2, 800 images for segmentation training. Yolov8 algorithm was used to build the segmentation model for segmentation training, and the fitting and automatic counting of vertebral ossification centers were carried out by post-processing. In the other 200 planes, the counting was performed by the artificial intelligence (AI) model, attending physician (D1), and junior physician (D2), and the accuracy of their performance were evaluated by a specialist physician. The accuracy and the time spent between D1, D2, and AI were compared.Results:The accuracy of AI model segmentation fitting and counting reached 95.00% (190/200) by the specialist physician evaluation, which was almost equal to 94.50%(189/200) by D1( P=0.823) and higher than that of 88.50% by D2(177/200)( P=0.012). The counting time spent for D1, D2, and AI model were 5.00 (4.25, 6.00)s, 7.00 (7.00, 8.00)s, 0.09 (0.08, 0.10)s, respectively, showing that the time spent by AI model was significantly shorter than that of doctors(all P<0.001). Conclusions:The trained artificial intelligence model can efficiently and accurately complete the vertebral ossification center counting below the end of conus medullaris, equivalent to the level of attending physicians. This study is expected to be further applied in the screening of fetal spina bifida and improve the automation and intelligence level of prenatal ultrasound screening.
9.Preliminary study of quantitative parameters from gastric tumor and spleen CT to predict the clinical stage of gastric cancer
Dongbo LYU ; Pan LIANG ; Mengru LIU ; Pengchao ZHAN ; Zhiwei HU ; Bingbing ZHU ; Songwei YUE ; Jianbo GAO
Chinese Journal of Radiology 2024;58(9):923-928
Objective:To investigate the value of CT quantitative parameters of tumor and spleen in predicting the clinical stage of gastric cancer (Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage).Methods:This study was a case-control study. The data of 145 patients with gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from February 2019 to June 2021 were retrospectively collected, including 70 cases of Ⅰ/Ⅱ stage and 75 cases of Ⅲ/Ⅳ stage. On the baseline CT images, the tumor related parameters, including tumor thickness, length of tumor, CT attenuation of tumor unenhanced phase, CT attenuation of tumor arterial phase, CT attenuation of tumor venous phase were measured. The spleen related parameters, including splenic thickness, CT attenuation of splenic unenhanced phase, CT attenuation of splenic arterial phase, CT attenuation of splenic venous phase, and standard deviation of CT attenuation (CTsd) in splenic unenhanced phase were also measured. The independent sample t test or Mann-Whitney U test was used to compare the parameters between the Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage patients. The multi-factor logistic regression analysis was used to find the independent predictors of gastric cancer clinical stage, and establish the combined parameters. The efficiency to the diagnosis of gastric cancer stage of single and combined parameters was evaluated using the operating characteristic curve, and the DeLong test was used to compare the differences of area under the curve (AUC). Results:There were significant differences in tumor thickness, length of tumor, CT attenuation of tumor venous phase, CT attenuation of splenic unenhanced phase, CT attenuation of splenic venous phase, CTsd in splenic unenhanced phase between the Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage of gastric cancer ( P<0.05). Multivariate analysis showed that tumor thickness ( OR=1.073, 95% CI 1.026-1.123, P=0.002), CT attenuation of splenic venous phase ( OR=1.040, 95% CI 1.011-1.070, P=0.006) and CTsd in splenic unenhanced phase ( OR=1.625, 95% CI 1.330-1.987, P<0.001) were independent risk factors for the clinical stage of gastric cancer and the combined parameters were established. The AUC values of tumor thickness, CT attenuation of splenic venous phase, CTsd in splenic unenhanced phase and combined parameters were 0.655, 0.614, 0.749 and 0.806, respectively. The AUC of combined parameters was higher than those of tumor thickness and CT attenuation of splenic venous phase, and the differences were statistically significant ( Z=3.37, 3.82, both P<0.001). Conclusion:Tumor thickness, CT attenuation of splenic venous phase and CTsd in splenic unenhanced phase are independent risk factors for the clinical stage of gastric cancer, and combined parameters can improve the diagnostic efficiency.
10.Clinical and CT radiomics features for predicting microsatellite instability-high status of gastric cancer
Pengchao ZHAN ; Liming LI ; Dongbo LYU ; Chenglong LUO ; Zhiwei HU ; Pan LIANG ; Jianbo GAO
Chinese Journal of Medical Imaging Technology 2024;40(1):77-82
Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P<0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P<0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

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