1.Diagnostic efficacy of AI in rib fracture under CT images with different reconstruction slice thickness
Ping AO ; Li ZHU ; Zhigang XIU ; Han XIAO ; Weimin LI
Chongqing Medicine 2024;53(5):723-726
Objective To investigate the diagnostic efficiency of artificial intelligence(AI)in rib frac-ture under the computed tomography(CT)images with different reconstruction slice thickness.Methods The first CT images of 100 patients with rib fractures were selected,and the interval-free recon-struction was carried out with the thickness of 0.625 mm,1.250 mm,2.500 mm and 5.000 mm,respectively.The rib fracture screening function of AI was used to automatically detect the CT images of four groups,and the diagnostic efficiency of AI for rib fracture under different reconstruction thickness conditions was com-pared.Results The sensitivity of AI in the diagnosis of rib fracture at 0.625 mm,1.250 mm,2.500 mm and 5.000 mm thickness was 99.32%(436/439),98.41%(432/439),89.52%(393/439)and 83.60%(367/439),respectively.The false positive rate was 4.80%(22/458),0.92%(4/436),0.76%(3/396)and 0.27%(1/368).The diagnostic sensitivity of AI in 0.625 mm and 1.250 mm thickness was higher than that in 2.500 mm and 5.000 mm,and the difference was statistically significant(P<0.05),while there was no significant difference in the thickness of 0.625 mm and 1.250 mm.The false positive rate of AI in the diagnosis of 0.625 mm slice thickness was higher than that of 1.250 mm,2.500 mm and 5.000 mm,and the difference was sta-tistically significant(P<0.05),while there was no significant difference in the thickness of 1.250 mm,2.500 mm and 5.000 mm(P>0.05).Conclusion The diagnostic efficiency of AI in 1.250 mm CT images is better than that in 0.625 mm,2.500 mm and 5.000 mm CT images.
2.Finite element analysis of femoral neck fracture treated by internal fixation of femoral neck system under nonanatomical reduction
Jizhai JIA ; Guikun YIN ; Hui XIE ; Weimin FU ; Shun HAN ; Yingjie MA ; Zhun WEN ; Benjie WANG
Chinese Journal of Tissue Engineering Research 2024;28(21):3319-3325
BACKGROUND:Irreducible femoral neck fracture was difficult to obtain anatomic reduction.As a new type of internal fixation,the femoral neck system is still blank for the treatment of non-anatomical reduced femoral neck fractures. OBJECTIVE:To explore the biomechanical stability of femoral neck system internal fixation under nonanatomical reduction in the treatment of femoral neck fractures based on finite element analysis. METHODS:CT data of the hip joint of a healthy female adult were obtained.Anatomical reduction of femoral neck fracture models with Pauwels angles of 30°,50°,and 70° were established using Mimics 21.0,Geomagic Wrap 2021,and SolidWorks 2020.The fracture proximal ends of the three anatomical reduction models were shifted upward by 2 mm along the fracture line,and three positive buttress models with different Pauwels angles were obtained.In the same way,three negative buttress models were acquired by shifting downward by 2 mm.SolidWorks 2020 was used to make the femoral neck system internal fixation,and the nine femoral neck fracture models were assembled with the femoral neck system.Then Ansys 19.0 was used for finite element analysis.The displacement distribution and maximum displacement,stress distribution and maximum stress of the femur and femoral neck system were recorded under 2100 N stress. RESULTS AND CONCLUSION:(1)When Pauwels angles were 30°,50°,and 70°,the maximum stresses of the femoral neck system appeared to be concentrated at the junction of the sliding hip screw and anti-rotation screw.The maximum femur stresses appeared to be concentrated in the medial cortex of the femur.The maximum displacement was concentrated at the upper of the femoral head and femoral neck system.(2)When Pauwels angles were 30° and 50°,the maximum displacement and maximum stress of the femoral neck system and femur were:negative buttress>anatomical reduction>positive buttress.(3)When Pauwels angle was 70°,the maximum displacement and maximum stress of the femoral neck system were:negative buttress>anatomical reduction>positive buttress;the maximum displacement and maximum stress of the femur were:negative buttress>positive buttress>anatomical reduction.(4)With the increase of Pauwels angle,the biomechanical advantage of the positive buttress was weakening.However,it was better than a negative buttress.When Pauwels angle was 30°,positive buttress was more stable than anatomical reduction.When Pauwels angle was 50°,the biomechanical difference between positive buttress and anatomical reduction became smaller.When Pauwels angle was 70°,the stability of anatomical reduction was slightly better than positive buttress.(5)If it was difficult to achieve anatomical reduction of femoral neck fracture during operation,but the positive buttress had been displaced within 2 mm,the femoral neck system could be used to offer stable mechanical fixation.It is necessary to avoid negative buttress reduction.
3.Effect of blood flow restriction combined with low-intensity plyometric jump training on functional ankle instabil-ity
Xinwen LIANG ; Yabing HAN ; Shilin WANG ; Weimin PAN ; Yingpeng JIANG ; Xiaoyu WEI ; Yan HUANG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(3):352-361
Objective To investigate the effect of blood flow restriction combined with low-intensity plyometric jump training(LI-PJT+BFR)on lower limb dynamic postural control of functional ankle instability(FAI)in college students. Methods From March to May,2023,40 FAI college students were recruited from Xi'an Physical Education University,and randomly divided into high-intensity plyometric jump training(HI-PJT,n = 14)group,low-intensity plyomet-ric jump training(LI-PJT,n = 13)group and LI-PJT+BFR group(n = 13).All the groups finished the six-week corresponding training.The maximum voluntary isometric contraction(MVIC)of tibialis anterior,peroneus lon-gus,lateral head of gastrocnemius,gluteus maximus,vastus lateralis,biceps femoris and semitendinosus were measured,and the root mean square(RMS)of electromyography of these muscles was measured during the sin-gle-leg landing(SLL),using wireless surface electromyography before and after intervention.Moreover,they were assessed with Y-balance test and Cumberland Ankle Instability Tool(CAIT). Results MVIC and RMS of the target muscles improved after intervention in all the groups(t>2.218,P<0.05),except MVIC and RMS of peroneus longus,gluteus maximus,biceps femoris and semitendinosus in LI-PJT group,and RMS of peroneus longus in LI-PJT+BFR group;and MVIC and RMS of the target muscles were the least in LI-PJT group(F>3.262,P<0.05),except those of peroneus longus.The extension scores of Y-balance test and the total score improved after intervention(t>2.485,P<0.05),and they were the least in LI-PJT group(F>5.042,P<0.05).The CAIT score improved after intervention(t>5.227,P<0.001),and it was the least in LI-PJT group(F = 4.640,P<0.05). Conclusion LI-PJT+BFR could improve lower limb dynamic postural control of FAI college students,which is similar to HI-PJT.
4.Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study
Weiyu ZHANG ; Huixin LIU ; Ming LIU ; Shi YING ; Renbin YUAN ; Hao ZENG ; Zhenting ZHANG ; Sujun HAN ; Zhannan SI ; Bin HU ; Simeng WEN ; Pengcheng XU ; Weimin YU ; Hui CHEN ; Liang WANG ; Zhitao LIN ; Tao DAI ; Yunzhi LIN ; Tao XU
Chinese Medical Journal 2024;137(11):1324-1331
Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.
5.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
6.Effect of hip neuromuscular training on anterior cruciate ligament injury risk for female soccer players
Yabing HAN ; Shaoqing LIU ; Xintong LI ; Xinwen LIANG ; Jing LUO ; Ting LI ; Weimin PAN
Chinese Journal of Rehabilitation Theory and Practice 2023;29(7):770-776
ObjectiveTo explore the effect of hip neuromuscular training on reducing the risk of anterior cruciate ligament (ACL) injury in female soccer players. MethodsFrom March to May, 2022, 39 female soccer players from Xi'an Physical Education University were randomly divided into control group (n = 19) and experimental group (n = 20). On the basis of daily training, the control group received sham intervention, and the experimental group received hip neuromuscular training, for six weeks. Before and after training, they were measured dynamic knee valgus (DKV) angle and assessed with Landing Error Score System (LESS); while they were also measured the maximal voluntary isometric contraction (MVIC) and root mean square (RMS) of electromyography as single leg landing of gluteus medius and gluteus maximus. ResultsAll the indexes varied little after training in the control group (|t| < 1.178, P > 0.05), while the indexes improved in the experimental group (|t| > 2.288, P < 0.05), except sagittal score of LESS; and all the indexes improved more in the experimental group than in the control group (|t| > 2.609, P < 0.05), except sagittal score of LESS and MVIC of gluteus maximus. ConclusionHip neuromuscular training can reduce the risk of ACL injury in female soccer players.
7.Efficacy of celecoxib in the treatment of refractory lymphatic anomalies
Yuan WANG ; Tao HAN ; Jie CUI ; Weimin SHEN
Chinese Journal of Plastic Surgery 2023;39(1):60-64
Objective:To determine the efficacy of treatment of refractory lymphatic anomalies with celecoxib.Methods:The authors retrospectively analyzed the characteristics, treatments and complications of patients treated with celecoxib in Children’s Hospital of Nanjing Medical University from September 2020 to January 2022. Treatment was started after poor response to other method or pain, which consisted of a continuous dosing schedule of oral celecoxib at 5 mg.kg -1.d -1, twice daily, for 6 months. Efficacy and safety were evaluated according to radiologic assessment, quality of life and incidence of adverse events. The efficacy was divided into complete response, partial response, stablizing response and non-responsive. SPSS 21.0 was used for data analysis. The data were expressed by M( Q1, Q3). Wilcoxon test was used to compare the lesion volume and PedsQL score before and after treatment. P<0.05 indicated that the difference was statistically significant. Results:A total of 12 patients with lymphatic malformation were enrolled, including 7 males and 5 females aging from 1 year and 5 months to 9 years and 9 months. Eight patients kept stable disease while two patients achieve partial response and two patients presented progressive disease. The median volume of lesions before treatment was 59.13(38.19, 107.15) cm 3 and was 66.08(37.37, 119.98) cm 3 after the treatment. There was no significant difference in volume changes ( Z=0.40, P=0.686). The PedsQL score was 30.5 (29.0, 32.0) before and 29.0(28.0, 30.0) after the treatment. There was no significant difference in the change of PedsQL score( Z=1.73, P=0.084). The side effects occurred in one patient as poor sleeping. Conclusion:Celecoxib can not reduce the lesion but may be helpful for improving life quality in lymphatic malformations.
8.Effects of Notch signaling pathway on the adipogenic differentiation of infantile hemangioma-derived mesenchymal stem cells
Weidong WANG ; Weimin SHEN ; Tao HAN ; Yuan WANG ; Sheng CHEN ; Jiawei LIN
Chinese Journal of Plastic Surgery 2023;39(7):762-769
Objective:To study the effects and potential mechanisms of Notch signaling pathway on the adipogenic differentiation of infantile hemangioma-derived mesenchymal stem cells.Methods:From January 2021 to June 2021, 10 infantile hemangioma specimens (6 males and 4 females, aged 2 months to 6 months, average age 3.5 months) were collected from the Department of Burns and Plastic Surgery of the Children’s Hospital of Nanjing Medical University. Hem-MSCs were isolated from hemangioma in the proliferating phase by adherent screening and identified by flow cytometry. Adipogenic induction was performed after successful identification. Real-time quantitative fluorescence PCR was used to detect the expression of Notch1, Jagged1 and Hes1 genes after 14 days of adipogenesis induction of Hem-MSCs. The Notch signaling pathway inhibitor DAPT, PI3K/Akt signaling pathway agonist 740Y-P and solvent DMSO were added to Hem-MSCs, and adipogenesis induction was performed. The cells were divided into six groups: control group, adipogenic induction group, adipogenic induction+ DMSO group, adipogenic induction+ DAPT group, adipogenic induction+ 740Y-P group, and adipogenic induction+ 740Y-P+ DAPT group. After 14 days of adipogenic induction, real-time quantitative fluorescence PCR was used to detect the expression of PPARγ and C/EBPα genes in the key transcription factors of adipogenic differentiation in the above six groups. Oil red O staining was applied to identify the adipogenic differentiation capabilities; after adipogenic induction for 7 days, the expression levels of p-PI3K, PI3K, p-AKT, and AKT proteins in the adipogenic induction+ DMSO group, adipogenic induction+ DAPT+ 740Y-P group were detected by western blotting. In comparing the two groups, an unpaired Student’s t-test was used to assess the differences, and analysis of variance was applied for the analysis of the mean values among multiple groups. and P<0.05 was considered statistically significant. Results:The expression levels of Notch1, Jagged1 and Hes1 decreased gradually during the adipogenic induction of Hem-MSCs, and the differences were statistically significant ( tNotch1=8.99, PNotch1=0.008; tJagged1=9.49, PJagged1=0.007; tHes1=7.74, PHes1=0.015). After the addition of Notch signaling pathway inhibitor DAPT during the adipogenic induction of Hem-MSCs, the expression of proteins associated with PI3K/AKT signaling pathway decreased, and the difference was statistically significant ( qp-PI3K=4.78, Pp-PI3K=0.014; qp-AKT=5.04, Pp-AKT=0.010) and the expression of adipogenesis indexes increased( qOil red O=6.07, POil red O=0.003; qPPARγ=17.34, PPPARγ<0.001; qC/EBPα=14.8, PC/EBPα<0.001). There was no significant change in adipogenesis indexes after addition of PI3K/Akt signaling pathway agonist 740Y-P ( qOil red O=1.82, POil red O=0.786; qPPARγ=0.97, PPPARγ=0.981; qC/EBPα=1.98, PC/EBPα=0.654). The expression of adipogenesis indexes decreased after adding DAPT and 740Y-P( qOil red O=5.22, POil red O=0.013; qPPARγ=9.78, PPPARγ<0.001; qC/EBPα=16.74, PC/EBPα<0.001). Conclusion:The inhibition of Notch signaling pathway can promote the adipogenic differentiation of Hem-MSCs by reducing the activity of PI3K/Akt signaling pathway.
9.Efficacy of celecoxib in the treatment of refractory lymphatic anomalies
Yuan WANG ; Tao HAN ; Jie CUI ; Weimin SHEN
Chinese Journal of Plastic Surgery 2023;39(1):60-64
Objective:To determine the efficacy of treatment of refractory lymphatic anomalies with celecoxib.Methods:The authors retrospectively analyzed the characteristics, treatments and complications of patients treated with celecoxib in Children’s Hospital of Nanjing Medical University from September 2020 to January 2022. Treatment was started after poor response to other method or pain, which consisted of a continuous dosing schedule of oral celecoxib at 5 mg.kg -1.d -1, twice daily, for 6 months. Efficacy and safety were evaluated according to radiologic assessment, quality of life and incidence of adverse events. The efficacy was divided into complete response, partial response, stablizing response and non-responsive. SPSS 21.0 was used for data analysis. The data were expressed by M( Q1, Q3). Wilcoxon test was used to compare the lesion volume and PedsQL score before and after treatment. P<0.05 indicated that the difference was statistically significant. Results:A total of 12 patients with lymphatic malformation were enrolled, including 7 males and 5 females aging from 1 year and 5 months to 9 years and 9 months. Eight patients kept stable disease while two patients achieve partial response and two patients presented progressive disease. The median volume of lesions before treatment was 59.13(38.19, 107.15) cm 3 and was 66.08(37.37, 119.98) cm 3 after the treatment. There was no significant difference in volume changes ( Z=0.40, P=0.686). The PedsQL score was 30.5 (29.0, 32.0) before and 29.0(28.0, 30.0) after the treatment. There was no significant difference in the change of PedsQL score( Z=1.73, P=0.084). The side effects occurred in one patient as poor sleeping. Conclusion:Celecoxib can not reduce the lesion but may be helpful for improving life quality in lymphatic malformations.
10.Effects of Notch signaling pathway on the adipogenic differentiation of infantile hemangioma-derived mesenchymal stem cells
Weidong WANG ; Weimin SHEN ; Tao HAN ; Yuan WANG ; Sheng CHEN ; Jiawei LIN
Chinese Journal of Plastic Surgery 2023;39(7):762-769
Objective:To study the effects and potential mechanisms of Notch signaling pathway on the adipogenic differentiation of infantile hemangioma-derived mesenchymal stem cells.Methods:From January 2021 to June 2021, 10 infantile hemangioma specimens (6 males and 4 females, aged 2 months to 6 months, average age 3.5 months) were collected from the Department of Burns and Plastic Surgery of the Children’s Hospital of Nanjing Medical University. Hem-MSCs were isolated from hemangioma in the proliferating phase by adherent screening and identified by flow cytometry. Adipogenic induction was performed after successful identification. Real-time quantitative fluorescence PCR was used to detect the expression of Notch1, Jagged1 and Hes1 genes after 14 days of adipogenesis induction of Hem-MSCs. The Notch signaling pathway inhibitor DAPT, PI3K/Akt signaling pathway agonist 740Y-P and solvent DMSO were added to Hem-MSCs, and adipogenesis induction was performed. The cells were divided into six groups: control group, adipogenic induction group, adipogenic induction+ DMSO group, adipogenic induction+ DAPT group, adipogenic induction+ 740Y-P group, and adipogenic induction+ 740Y-P+ DAPT group. After 14 days of adipogenic induction, real-time quantitative fluorescence PCR was used to detect the expression of PPARγ and C/EBPα genes in the key transcription factors of adipogenic differentiation in the above six groups. Oil red O staining was applied to identify the adipogenic differentiation capabilities; after adipogenic induction for 7 days, the expression levels of p-PI3K, PI3K, p-AKT, and AKT proteins in the adipogenic induction+ DMSO group, adipogenic induction+ DAPT+ 740Y-P group were detected by western blotting. In comparing the two groups, an unpaired Student’s t-test was used to assess the differences, and analysis of variance was applied for the analysis of the mean values among multiple groups. and P<0.05 was considered statistically significant. Results:The expression levels of Notch1, Jagged1 and Hes1 decreased gradually during the adipogenic induction of Hem-MSCs, and the differences were statistically significant ( tNotch1=8.99, PNotch1=0.008; tJagged1=9.49, PJagged1=0.007; tHes1=7.74, PHes1=0.015). After the addition of Notch signaling pathway inhibitor DAPT during the adipogenic induction of Hem-MSCs, the expression of proteins associated with PI3K/AKT signaling pathway decreased, and the difference was statistically significant ( qp-PI3K=4.78, Pp-PI3K=0.014; qp-AKT=5.04, Pp-AKT=0.010) and the expression of adipogenesis indexes increased( qOil red O=6.07, POil red O=0.003; qPPARγ=17.34, PPPARγ<0.001; qC/EBPα=14.8, PC/EBPα<0.001). There was no significant change in adipogenesis indexes after addition of PI3K/Akt signaling pathway agonist 740Y-P ( qOil red O=1.82, POil red O=0.786; qPPARγ=0.97, PPPARγ=0.981; qC/EBPα=1.98, PC/EBPα=0.654). The expression of adipogenesis indexes decreased after adding DAPT and 740Y-P( qOil red O=5.22, POil red O=0.013; qPPARγ=9.78, PPPARγ<0.001; qC/EBPα=16.74, PC/EBPα<0.001). Conclusion:The inhibition of Notch signaling pathway can promote the adipogenic differentiation of Hem-MSCs by reducing the activity of PI3K/Akt signaling pathway.

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