Objective To explore the correlations of serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with grading of myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPN). Methods Ninety patients with Philadelphia chromosome negative (Ph-)MPN were selected as MPN group. According to the grading criteria for myelofibrosis by the World Health Organization (WHO) in 2016, MPN patients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases; another 50 healthy volunteers were selected as the control group. Levels of serum VEGF, MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay, and the ratio of TIMP-1 to MMP-9 (TIMP-1/MMP-9) was calculated. Spearman rank correlation test was used to analyze the correlations of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 with MF grading. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of each indicator alone or their combination for diagnosing MPN or distinguishing MF grading. Results Compared with the control group, the serum levels of VEGF, MMP-9 and TIMP-1 in the MPN group increased significantly (P < 0.05). Values of area under the curve (AUC) of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0, 834, 0.745, 0.923 and 0.618 respectively; the AUC of the combined diagnosis of MPN by VEGF, MMP-9 and TIMP-1 was 0.960; when the optimal cut-off value was 0.627, the sensitivity was 85.56%, and the specificity was 92.00%. Compared with the pre-fibrosis or early fibrosis group, the serum levels of VEGF, TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly (P < 0.05). Spearman correlation analysis showed that VEGF (r=0.378, P=0.001), TIMP-1 (r=0.512, P < 0.001) and TIMP-1/MMP-9 (r=0.353, P=0.001) were positively correlated with the MF grading of MPN patients (P < 0.05). ROC curve analysis showed that the values of AUC of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723, 0.523, 0.802 and 0.708 respectively; the AUC of the combined detection of VEGF, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838; when the optimal cut-off value was 0.530, the sensitivity was 72.22%, and the specificity was 85.19%. Conclusion Serum VEGF, TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients, and the combined detection of these indicators can predict the MF degree of MPN patients.

Objective:To investigate the feasibility of surface-guided hypo-fractionated radiotherapy for intracranial metastasis with open face mask immobilization.Methods:Nineteen patients treated with hypo- fractionated radiotherapy for intracranial metastasis in our hospital were included. Before the start of treatment, each patient underwent simulation with open face mask immobilization. During the treatment, cone-beam CT(CBCT)images were collected for verification each time. Laser-guided positioning was used for the first time in the treatment, and surface images were captured after six-dimensional position correction as the reference images for subsequent treatment. Subsequent treatment was randomly divided into laser-guided positioning group(LG, 85/F)and optical surface-guided positioning group(SG, 101/F). The six-dimensional error data of patients with two positioning methods were compared and expressed as mean ± standard deviation. Meanwhile, the correlation and consistency between the optical surface error data and the gold standard CBCT error data were compared in the laser-guided fraction. GraphPad Prism 6.0 software was used for data processing and mapping, and SPSS 21.software was used for mean analysis and normality test. Pearson correlation analysis was used to analyze the correlation, and Bland-Altman plot analysis was used to test the coincidence between two methods.Results:Compared with the laser-guided positioning, the 3D error of optical surface-guided positioning was reduced from(0.35±0.16)cm to(0.14±0.07)cm. The Pearson coefficient of correlation along all three directions was less than 0.01,R 2 was 0.91,0.70 and 0.78 on Lat, Lng and Vrt, and R 2 was 0.75,0.85 and 0.77 on Pitch, Roll and Rtn(all P<0.01), respectively. The measurement results of two methods were positively correlated. The Bland-Altman plot analysis showed that the 95% limits of agreement were within preset 3 mm tolerance([-0.29 cm, 0.19 cm], [-0.25 cm, 0.25 cm], [-0.27 cm, 0.19 cm]), and the 95% limits of agreement were within preset 3° tolerance(Pitch[-1.76°,1.76°], Roll[-1.54°,1.60°], ROT[-2.18°,1.69°]), indicating agreement between two methods. Conclusions:The optical surface-guided positioning can reduce the setup errors in the hypo-fractionated radiotherapy for intracranial metastasis with open face mask immobilization. The optical surface error and CBCT error have good correlation and agreement.

Objective:To evaluate the application of visual feedback coaching method, which is embedded in an optical surface monitoring system, in deep inspiration breath holding during the radiotherapy in left breast cancer patients after breast-conserving surgery.Methods:Thirty patients with left breast cancer, who were scheduled to receive the whole breast radiotherapy after breast-conserving surgery, met the requirements of deep inspiration breath holding after respiratory coaching with the visual feedback coaching module in the optical surface monitoring system. Active breathing control equipment was used to control breath-holding state and CT simulation was performed. During treatment, optical surface monitoring system was used to guide radiotherapy. All patients were randomly divided into two groups. In group A ( n=15), visual feedback respiratory training method was utilized and not employed in group B ( n=15). In group A, the visual feedback coaching bar of the optical surface monitoring system was implemented, while audio interactive method was employed to guide patients to hold their breath. Real-time data of optical body surface monitoring were used to compare the interfraction reproducibility and intrafraction stability of breath holding fraction between two groups. Besides, the number of breath holding and treatment time per fraction were also compared. GraphPad prism 6.0 software was used for data processing and mapping, and SPSS 21.0 software was used for analyzing mean value and normality testing. Results:Compared with the control group, the reproducibility in the experiment group was reduced from 1.5 mm to 0.7 mm, the stability was reduced from 1.1 mm to 0.8 mm, the mean number of breath holding required per fraction was decreased from 4.6 to 2.4, the mean beam-on time per fraction from 336 s to 235 s, and the treatment time per fraction was shortened from 847 s to 602 s (all P<0.05), respectively. Conclusions:The application of visual feedback coaching method can improve the reproducibility and stability of breath holding during radiotherapy for left breast cancer, and it can also effectively reduce the number of breath holding and shorten the treatment time per fraction.

By using optical surface guided radiotherapy technology, the principle of three-dimensional body surface imaging is employed to obtain body surface images in a real-time manner. By comparing with reference images, it can verify the position before treatment, and realize real-time monitoring and gated treatment during treatment. It is a non-invasive and non-radiation technology, which is mainly applied in the treatment of intracranial, head and neck, chest and abdomen, breast, extremities and pediatric tumors. The research progresses consist of four aspects including less body surface markers, less restraint fixation, safer collision prediction and more accurate real-time tracking.

Objective:To establish the basic procedures of the application of optical surface monitoring system (OSMS) in the deep inspiration breath hold (DIBH) radiotherapy for patients with left sided breast cancer and compare the performance of OSMS and cone-beam CT (CBCT) in the determination of the set-up errors of DIBH radiotherapy for patients with left sided breast cancer.Methods:Twenty patients with left sided breast cancer received DIBH radiotherapy. Through the registration of CBCT images with the planning CT images, and the registration of OSMS radiography images with the outer contour of the body surface, translational set-up errors and rotational errors were determined along the lateral-medial ( Rx), superior-inferior ( Ry) and anterior-posterior ( Rz) directions. Pearson correlation analysis was performed to evaluate the correlation of the set-up errors determined by two methods, and Bland- Altman plot analysis was used to assess the coincidence of these two methods. Results:Two methods were positively correlated. The Rz volume was 0.84, 0.74 and 0.84 in the x, y and z directions, and 0.65, 0.41 and 0.54 in the Rx, Ry and Rz directions, respectively (all P<0.01). The 95% CI of agreement were within preset 5 mm tolerance (-0.37-0.42cm, -0.39-0.41cm, -0.29-0.49cm ) in x, y and z directions for two methods. The 95% CI of agreement were within preset 3 ° tolerance -2.9°-1.4°, -2.6°-1.4°, -2.4°-2.5°in Rx, Ry and Rz directions for two methods. The system errors of 20 patients with left sided breast cancer receiving DIBH radiotherapy were <0.18cm and the random errors were <0.24cm. Conclusions:OSMS is equivalent to CBCT in the determination and stimulation of set-up errors for patients with left sided breast cancer receiving DIBH radiotherapy. The combination of CBCT and OSMS is a safe and reliable method.

Objective:To evaluate the incidence of early cardiac injury in patients with left-sided breast cancer receiving hypofractionated radiotherapy after breast conserving surgery, and to investigate the correlation between cardiac injury and hypofractionated radiotherapy dose.Methods:We prospectively enrolled 103 breast cancer patients who received whole breast with or without regional nodal irradiation after breast conserving surgery using either deep inspiration breath-hold (DIBH) or free breathing (FB) radiotherapy technique. Cardiac examinations that included N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and myocardial perfusion imaging were performed routinely before and after radiotherapy. The effects of heart dose, systemic therapy and individual factors (Framingham score) on the incidence of cardiac events were analyzed.Results:The median age was 48 years. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) were 4.0, 16.9, 6.3, and 4.4 Gy, respectively. With a median follow-up of 13.4 months, no patient had clinical cardiac abnormalities. The incidence rates of subclinical cardiac events at 1- 6- and 12-month were 23.5%, 31.6%, and 41.3%, respectively. The DIBH group had a lower mean dose, maximum dose, and V5-V40 in the heart, LAD, LV, and RV than the FB group ( P<0.001). Univariate analysis showed an increased incidence of subclinical cardiac events with heart Dmean >4 Gy, LAD V40 > 20%, LV Dmean >6 Gy, RV Dmean >7 Gy, or cumulative doses of anthracycline or taxane > 300 mg/m 2 (All P<0.05). Anti-HER2 targeted therapy, endocrine therapy and Framingham score were not associated with the incidence of subclinical cardiac events (all P>0.05). Multivariate analysis demonstrated that Dmean of LV and RV were independently associated with the increased incidence of subclinical cardiac events. Conclusions:Early subclinical heart injury are found in patients with left-sided breast cancer after hypofractionated radiotherapy. The increased incidence of subclinical cardiac events after radiotherapy is positively associated with the cardiac radiation doses.

Objective:To investigate the effects of microRNA-451 on proliferation, invasion and migration of multiple myeloma RPMI-8226 cells and its mechanism.Methods:RPMI-8226 cells cultured in vitro were divided into blank control group (untransfected), negative control (NC) group and miR-451 mimic transfected (miR-451) group. The expression of miR-451 was detected by real-time quantitative PCR (qRT-PCR), cell proliferation was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) array and clone formation experiment, cell invasion and migration were detected by Transwell, and the expressions of c-Myc, MMP-2 and MMP-9 proteins were detected by western blot. The targeting relationship between miR-451 and c-Myc was detected by double luciferase reporter gene assay. Results:Compared to the blank control group, the expression level of miR-451 was increased (2.85±0.27 vs 1.02±0.06), while the cell survival rate [(47.28±3.15)% vs (93.65±6.52)%], cloning formation rate [(15.03±1.34)% vs (28.48±2.12)%], invasive cell number (86.65±5.58 vs 135.47±9.85), migrating cell number (106.36±6.48 vs 165.28±11.05) and the expression level of c-Myc(0.35±0.03 vs 0.66±0.05), MMP-2 (0.20±0.02 vs 0.48±0.03) and MMP-9 (0.28±0.03 vs 0.59±0.06) protein were significantly decreased in the miR-451 group ( P<0.05). In the negative control group, the expression level of miR-451, cell viability, clone formation rate, invasive cell number, migrating cell number, c-Myc protein, MMP-2 protein and MMP-9 protein were 0.94±0.05, (95.16±5.04)%, (27.55±2.26)%, (128.96±8.32) and (158.65±8.76), 0.68±0.06, 0.51±0.03, 0.54±0.03, respectively. There were no significant differences between the blank control group and the NC group ( P>0.05). Double luciferase reporter gene experiment confirmed that c-Myc was a potential target gene of miR-451. Conclusion:miR-451 can inhibit the proliferation, invasion and migration of RPMI-8226 cells by targeting c-Myc.

Objective:To evaluate the incidence of early cardiac injury in patients with left-sided breast cancer receiving hypofractionated radiotherapy after breast conserving surgery, and to investigate the correlation between cardiac injury and hypofractionated radiotherapy dose.Methods:We prospectively enrolled 103 breast cancer patients who received whole breast with or without regional nodal irradiation after breast conserving surgery using either deep inspiration breath-hold (DIBH) or free breathing (FB) radiotherapy technique. Cardiac examinations that included N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and myocardial perfusion imaging were performed routinely before and after radiotherapy. The effects of heart dose, systemic therapy and individual factors (Framingham score) on the incidence of cardiac events were analyzed.Results:The median age was 48 years. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) were 4.0, 16.9, 6.3, and 4.4 Gy, respectively. With a median follow-up of 13.4 months, no patient had clinical cardiac abnormalities. The incidence rates of subclinical cardiac events at 1- 6- and 12-month were 23.5%, 31.6%, and 41.3%, respectively. The DIBH group had a lower mean dose, maximum dose, and V5-V40 in the heart, LAD, LV, and RV than the FB group ( P<0.001). Univariate analysis showed an increased incidence of subclinical cardiac events with heart Dmean >4 Gy, LAD V40 > 20%, LV Dmean >6 Gy, RV Dmean >7 Gy, or cumulative doses of anthracycline or taxane > 300 mg/m 2 (All P<0.05). Anti-HER2 targeted therapy, endocrine therapy and Framingham score were not associated with the incidence of subclinical cardiac events (all P>0.05). Multivariate analysis demonstrated that Dmean of LV and RV were independently associated with the increased incidence of subclinical cardiac events. Conclusions:Early subclinical heart injury are found in patients with left-sided breast cancer after hypofractionated radiotherapy. The increased incidence of subclinical cardiac events after radiotherapy is positively associated with the cardiac radiation doses.

Objective:To investigate the effects of microRNA-451 on proliferation, invasion and migration of multiple myeloma RPMI-8226 cells and its mechanism.Methods:RPMI-8226 cells cultured in vitro were divided into blank control group (untransfected), negative control (NC) group and miR-451 mimic transfected (miR-451) group. The expression of miR-451 was detected by real-time quantitative PCR (qRT-PCR), cell proliferation was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) array and clone formation experiment, cell invasion and migration were detected by Transwell, and the expressions of c-Myc, MMP-2 and MMP-9 proteins were detected by western blot. The targeting relationship between miR-451 and c-Myc was detected by double luciferase reporter gene assay. Results:Compared to the blank control group, the expression level of miR-451 was increased (2.85±0.27 vs 1.02±0.06), while the cell survival rate [(47.28±3.15)% vs (93.65±6.52)%], cloning formation rate [(15.03±1.34)% vs (28.48±2.12)%], invasive cell number (86.65±5.58 vs 135.47±9.85), migrating cell number (106.36±6.48 vs 165.28±11.05) and the expression level of c-Myc(0.35±0.03 vs 0.66±0.05), MMP-2 (0.20±0.02 vs 0.48±0.03) and MMP-9 (0.28±0.03 vs 0.59±0.06) protein were significantly decreased in the miR-451 group ( P<0.05). In the negative control group, the expression level of miR-451, cell viability, clone formation rate, invasive cell number, migrating cell number, c-Myc protein, MMP-2 protein and MMP-9 protein were 0.94±0.05, (95.16±5.04)%, (27.55±2.26)%, (128.96±8.32) and (158.65±8.76), 0.68±0.06, 0.51±0.03, 0.54±0.03, respectively. There were no significant differences between the blank control group and the NC group ( P>0.05). Double luciferase reporter gene experiment confirmed that c-Myc was a potential target gene of miR-451. Conclusion:miR-451 can inhibit the proliferation, invasion and migration of RPMI-8226 cells by targeting c-Myc.

Objective To investigate the clinical and pathologic features of patients with gastric neuroendocrine neoplasms (g-NENs).Methods A total of 50 cases of g-NENs diagnosed by pathology in the First Hospital of Jilin University from May 2012 to January 2016 were retrospective analyzed to summarize the clinical manifestations and pathological features.The location of lesion,gross morphology,maximum diameter,lymph node metastasis rate,distant metastasis rate,and survival time between patients with neuroendocrine tumors and neuroendocrine carcinomas were compared.Results Among the 50 patients,34 were males and 16 were females with a male to female ratio of 2.125 ∶ 1.Their age ranged from 33 to 77 years with an mean age of 60± 11 years.There were 13 cases (26％) of neuroendocrine tumors,31 (62％) neuroendocrine carcinomas,and 6 (12％) mixed adenoneuroendocrine carcinomas.The maximum diameter of lesion was less than 2 cm in 8 cases (16％),and equal or greater than 2 cm in 42 cases (84％).There was single lesion in 48 cases (96％) and multiple lesions in 2 cases (4％).There were 19 cases (38％) located in gastric antrum,16 (32％) in gastric body,11 (22％) in gastric fundus or cardia,3 (6％) in gastric angle,and 1 (2％) in the junction of gastric antrum and body.Thirty-two patients (64％) had metastasis,including 20 cases of lymph node metastasis and 12 cases of distant metastasis.The clinical symptoms of the patients were different,mainly were digestive system symptoms and tumor occupying symptoms,and no carcinoid syndrome was reported.The gross morphology (x2 =24.446.P =0.000).maximum diameter (t =-4.044,P =0.001),lymph node metastasis rate (x2=4.435,P =0.035),and survival time (t =2.925,P =0.000) were significantly differences between 13 cases of neuroendocrine tumors and 37 cases of neuroendocrine carcinoma.But the location of lesion (x2 =6.921,P=0.082) and distant metastasis rate (x2 =0.715,P =0.389) were no statistically different between the two groups.Conclusion Gastric neuroendocrine neoplasms can occur in any part of stomach,majority of tumor is single lesion and lack of specific clinical manifestations.The mostly gross morphology of gastric neuroendocrine carcinoma and mixed adenoneuro-endocrine carcinoma are ulcer type with a large diameter and poor prognosis.