1.The Effect of Fluvastatin on Ventricular Remodeling and VWF in Heart Failure Rats
Shikai WANG ; Haiyan WANG ; Yanju XUE ; Jiangjiu LIANG
Tianjin Medical Journal 2013;(8):802-805
Objective To study the protective effect of fluvastatin on cardiac remodeling and cardiac function, and to investigate its effect on Von Willebrand factor (VWF). Methods The rat model of cardiac heart failure (CHF) was in-duced by isoproterenol injection (170 mg/kg) via subcutaneous. Eighteen model rats were randomly divided into fluvastatin (20 mg ·kg-1·d-1) group, placebo group and control group. Rats were treated with normal saline in placebo group and control group. After 6-week treatment, the structure and function of hearts were measured by echocardiography in three groups. The ventricular weight index, the serum levels of VWF and B-type natriuretic peptide (BNP) were measured by ELISA assay. The levels of VWF mRNA in cardiac muscle were measured by RT-PCR. Results Compared with control group, the val-ues of left ventricular end-diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly increased in placebo group and fluvastatin group, while values of left ventricular ejection fraction (LVEF) and left ventricular ejection fraction shortening (LVFS) were significantly decreased (P<0.05). The values of left ventricular wet weight/body weight (LVRW) and right ventricular wet weight/body weight (RVRW) were increased in placebo group and fluvastatin group. The expression of VWF mRNA in cardiac tissues was enhanced significantly (P<0.01). Compared with placebo group, the values of LVEDD, LVRW and RVRW were significantly decreased in fluvastatin group. The expression of VWF mRNA in cardiac tissues was significantly decreased (P<0.01), and the values of LVEF and LVFS were significant increased in fluvas-tatin group (P<0.05). The level of VWF was positively corrected with BNP(r=0.996). Conclusion Fluvastatin could im-prove the cardiac function and cardiac remodeling, which may be by reducing the level of VWF and improving endothelial function.
2.Effect of human umbilical cord mesenchymal stem cells on the proliferative characteristics of cervical cancer Hela cells
Shikai LIU ; Lili SONG ; Saitian ZENG ; Liang ZHANG
Chinese Journal of Tissue Engineering Research 2015;(45):7274-7278
BACKGROUND:Mesenchymal stem cels have the specific chemotaxis to the inflammation and tumor tissue, but the effect of mesenchymal stem cels on the growth of cervical cancer cels becomes an urgent problem. OBJECTIVE:To investigate the effect of human umbilical cord mesenchymal stem cels on the proliferation of cervical cancer Hela cels. METHODS:Hela cels were co-cultured with human umbilical cord mesenchymal stem cels at different number or its conditioned medium at different concentrations for 3 days. Then, cel counting kit-8 was used to detect the proliferation of Hela cels. RESULTS AND CONCLUSION:When Hela cels were co-cultured with human umbilical cord mesenchymal stem cels at ratios of 1:3, 1:2, 1:1, 2:1, 4:1, 8:1, the relative proliferation inhibition rates were 67.12%, 47.18%, 31.15%, 27.61%, 15.55% and 15.95%, respectively. When the Hela cels were co-cultured with human umbilical cord mesenchymal stem cel conditioned medium at 5, 10, 20, 40, 60, 100 mg/L, the relative proliferation inhibition rates were 0.61%, 40.1%, 63.47%, 80.61%, 93.56%, 90.65%, respectively. These findings indicate that the proliferation of Hela cels can be inhibited by co-culture with human umbilical cord mesenchymal stem cels at a certain concentration-dependent manner.
3.Prediction of Venous Trans-Stenotic Pressure Gradient Using Shape Features Derived From Magnetic Resonance Venography in Idiopathic Intracranial Hypertension Patients
Chao MA ; Haoyu ZHU ; Shikai LIANG ; Yuzhou CHANG ; Dapeng MO ; Chuhan JIANG ; Yupeng ZHANG
Korean Journal of Radiology 2024;25(1):74-85
Objective:
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology associated with venous sinus stenosis. This study aimed to develop a magnetic resonance venography (MRV)-based radiomics model for predicting a high trans-stenotic pressure gradient (TPG) in IIH patients diagnosed with venous sinus stenosis.
Materials and Methods:
This retrospective study included 105 IIH patients (median age [interquartile range], 35 years [27– 42 years]; female:male, 82:23) who underwent MRV and catheter venography complemented by venous manometry. Contrast enhanced-MRV was conducted under 1.5 Tesla system, and the images were reconstructed using a standard algorithm. Shape features were derived from MRV images via the PyRadiomics package and selected by utilizing the least absolute shrinkage and selection operator (LASSO) method. A radiomics score for predicting high TPG (≥ 8 mmHg) in IIH patients was formulated using multivariable logistic regression; its discrimination performance was assessed using the area under the receiver operating characteristic curve (AUROC). A nomogram was constructed by incorporating the radiomics scores and clinical features.
Results:
Data from 105 patients were randomly divided into two distinct datasets for model training (n = 73; 50 and 23 with and without high TPG, respectively) and testing (n = 32; 22 and 10 with and without high TPG, respectively). Three informative shape features were identified in the training datasets: least axis length, sphericity, and maximum three-dimensional diameter.The radiomics score for predicting high TPG in IIH patients demonstrated an AUROC of 0.906 (95% confidence interval, 0.836– 0.976) in the training dataset and 0.877 (95% confidence interval, 0.755–0.999) in the test dataset. The nomogram showed good calibration.
Conclusion
Our study presents the feasibility of a novel model for predicting high TPG in IIH patients using radiomics analysis of noninvasive MRV-based shape features. This information may aid clinicians in identifying patients who may benefit from stenting.
4.A study of the dynamic evolution of macrophage infiltration behavior after acute carotid artery thrombosis
Shikai LI ; Jia LIANG ; Yanyan HE ; Qianhao DING ; Chenqing LI ; Yang LIU ; Yingpu FENG ; Wenli ZHAO ; Yumeng HUANG ; Lina SUO ; Tianxiao LI ; Yingkun HE
Chinese Journal of Cerebrovascular Diseases 2024;21(7):433-443
Objective To explore the changes in macrophage infiltration behavior during the dynamic evolution of thrombi following the formation of acute carotid artery thrombosis occlusion(ACTO).Methods 15 healthy male New Zealand rabbits were selected to establish an ACTO model by causing injury to the rabbit carotid artery using surgical sutures treated with ferric chloride.All rabbits were randomly divided into 5 groups according to the end-point time using the random number table method,namely 24-hour group,1 week group,4week group,8 week group,and 12week group postoperatively,with 3 rabbits in each group.At 24 hours post-operation,the ACTO model was examined by DS A.At 24 hours,1 week,4 weeks,8 weeks,and 12 weeks post-operation,samples were taken from the thrombotic arterial segment of the 3 rabbits in each group and embedded in paraffin.The thrombus samples were stained with hematoxylin-eosin(HE)and Martius scarlet blue(MSB)to analyze changes in thrombus morphology and composition(including red blood cells,fibrin and collagen fibers).Orbit Imaging Analysis software was used for semi-quantitative analysis of the thrombus composition components.Using immunohistochemistry to detect the distribution of MO and M2 macrophages in thrombi,aimed to summarize the dynamic evolution of thrombus morphology,composition,and macrophage infiltration behavior at different stages following ACTO occurrence.Results The 24-hour DSA results indicated that all experimental rabbits successfully established the ACTO model.(1)HE staining showed a continuous increase in thrombus size from 24 hours to 1 week.By 4 weeks,signs of thrombus dissolution appeared,and at 8 weeks,neovascularization was observed within the thrombus.By 12 weeks,signs of fibrosis were evident in the thrombus.(2)MSB staining revealed that during the acute phase of thrombus formation(within 24 hours after surgery),red blood cells were the predominant component initially,but after this period,fibrin and collagen fibers became the main components.(3)The detection results of MO macrophages showed that 24 hours after surgery,MO macrophages in the thrombus were not evenly distributed throughout the thrombus,but mainly gathered at the thrombus edge;at 1 week after surgery,the positive area percentage of MO macrophage in the thrombus increased compared with 24 hours after surgery(thrombus edge:[41.7±27.0]%vs.[24.6±16.7]%,thrombus core:[35.7±19.6]%vs.[11.1±10.4]%,all P<0.001),and evenly distributed within the thrombus;at 4 weeks after surgery,MO macrophages in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.7±6.1]%vs.[41.7±27.0]%,thrombus core:[12.1±8.5]%vs.[35.7±19.6]%,all P<0.001),the differences were statistically significant.At 4,8,and 12 weeks after surgery,MO macrophages within the thrombus did not change significantly with time(thrombus edge:[10.7±6.1]%,[8.0±7.7]%,and[8.9±5.3]%;thrombus core:[12.1±8.5]%,[9.5±4.2]%,and[15.7±11.0]%),and the differences were not statistically significant(all P>0.05).In addition,at 12 weeks after surgery,MO macrophages at the thrombus edge was less than the thrombus core([8.9+5.3]%vs.[15.7±11.0]%,P<0.01).The detection results of M2 macrophages showed that 24 hours after surgery,M2 macrophages in the thrombus were widely distributed throughout the thrombus;at 1 week after surgery,the positive area percentage of M2 macrophages in the thrombus increased compared with 24 hours after surgery(thrombus edge:[22.1±11.3]%vs.[11.4±8.7]%,P<0.001;thrombus core:[24.5±9.8]%vs.[7.6±6.0]%,P<0.001);at 4 weeks after surgery,M2 macrophage in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.6±3.7]%vs.[22.1±11.3]%,P<0.001;thrombus core:[9.2±4.3]%vs.[24.5±9.8]%,P<0.001);at 8 weeks after surgery,M2 macrophages in the thrombus increased compared with 4 weeks after surgery([17.9±8.8]%vs.[9.2±4.3]%,P<0.001),and the differences were statistically significant.However,M2 macrophages in the thrombus did not change significantly from 8 weeks to 12 weeks after surgery(thrombus edge:[9.4±6.3]%vs.[8.5±5.3]%,P>0.05;thrombus core:[17.9±8.8]%vs.[14.4±10.0]%,P>0.05).In addition,at 8 and 12 weeks after surgery,M2 macrophages in the thrombus core was greater than the thrombus edge(8 weeks after surgery:[17.9±8.8]%vs.[9.4±6.3]%,P<0.001;12weeks after surgery:[14.4±10.0]%vs.[8.5±5.3]%,P<0.001).Conclusions This study successfully established an ACTO animal model and demonstrated for the first time the dynamic evolution of macrophages within 12 weeks post-thrombus formation.Macrophages may played a significant role in both thrombus formation and fibrinolysis,as well as in the promotion of thrombus dissolution and the formation of new blood vessels within the thrombus which may potentially promote the spontaneous reperfusion of the occluded vessels.The results of this study need further verification.
5.Radiotherapy for and prognosis of breast cancer patients with isolated chest wall recurrence after mastectomy
Liang XUAN ; Xuran ZHAO ; Huiru SUN ; Jun YIN ; Yu TANG ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Shikai WU ; Yexiong LI ; Shulian WANG ; Bing SUN
Chinese Journal of Radiation Oncology 2021;30(9):898-902
Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.
6.Radiotherapy and prognostic analysis of breast cancer patients with isolated regional recurrence after mastectomy
Xuran ZHAO ; Liang XUAN ; Jun YIN ; Yu TANG ; Huiru SUN ; Shikai WU ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Yexiong LI ; Bing SUN ; Shulian WANG
Chinese Journal of Radiation Oncology 2021;30(10):1030-1035
Objective:To analyze the prognosis of patients with isolated regional recurrence (RR) after mastectomy, and evaluate the efficacy of radiotherapy and identify the optimal radiation target volumes.Methods:Clinical data of 144 patients with first isolated RR after mastectomy between 2001 and 2018 were retrospectively analyzed. All patients had not received post-mastectomy radiotherapy. The primary endpoints consisted of the subsequent locoregional recurrence (sLRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS).Results:With a median follow-up of 82.5 months after RR, the 5-year sLRR, DM, PFS and OS rates for the entire group were 42.1%, 71.9%, 22.9% and 62.6%, respectively. Local plus systemic therapy was an independent favorable prognostic factor for sLRR ( P<0.001) and PFS ( P=0.013). The sLRR rate in the surgery plus radiotherapy group was the lowest ( P<0.001). Surgery plus radiotherapy significantly reduced the 5-year risk of recurrence within the initially involved nodal regions ( P<0.001). Patients with chest wall irradiation obtained the 5-year subsequent chest wall recurrence rate of 12.1% compared to 14.8%( P=0.873) for those without chest wall irradiation. The subsequent supraclavicular recurrence rate was lower in patients with prophylactic supraclavicular irradiation than that without prophylactic supraclavicular irradiation (9.9% vs. 23.8%, P=0.206). The incidence rates of initially uninvolved axillary and internal mammary nodal recurrence were below 10% regardless of prophylactic irradiation or not. Conclusions:Patients with RR alone have an optimistic 5-year OS in the contemporary era. Comprehensive locoregional treatment including surgery and radiotherapy combined with systemic therapy is recommended. The chest wall, axillary and internal mammary nodal prophylactic irradiation should not be routinely performed for all patients with RR. The value of supraclavicular prophylactic irradiation remains to be evaluated.
7.Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy
Xuran ZHAO ; Liang XUAN ; Jun YIN ; Yu TANG ; Huiru SUN ; Shikai WU ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Yexiong LI ; Bing SUN ; Shulian WANG
Chinese Journal of Oncology 2021;43(11):1203-1208
Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.
8.Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy
Xuran ZHAO ; Liang XUAN ; Jun YIN ; Yu TANG ; Huiru SUN ; Shikai WU ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Yexiong LI ; Bing SUN ; Shulian WANG
Chinese Journal of Oncology 2021;43(11):1203-1208
Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.