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@#<b>Objective</b> To investigate the dosimetric differences between volumetric modulated arc therapy (VMAT) with a flattening filter (FF) and flattening filter-free (FFF) VMAT in fractionated stereotactic radiotherapy for brain metastases. <b>Methods</b> Seventeen patients with brain metastases were divided into FF-VMAT group (VMAT plans with the FF mode) and FFF-VMAT group (VMAT plans with the FFF mode). The two groups were compared in terms of target volume dose parameters (<i>D</i><sub>98%</sub>, <i>D</i><sub>2%</sub> and <i>D</i><sub>mean</sub>), the conformal index (<i>CI</i>), the gradient index (<i>GI</i>), the gradient, normal brain tissue dose parameters (<i>V</i><sub>5Gy</sub>, <i>V</i><sub>10Gy</sub>, <i>V</i><sub>12Gy</sub> and <i>D</i><sub>mean</sub>), monitor units, and beam-on time. <b>Results</b> Compared with the FF-VMAT group, the FFF-VMAT group had significantly lower <i>GI</i> (3.33 ± 0.37 <i>vs</i> 3.27 ± 0.35, <i>P</i> = 0.001), a significantly lower gradient [(0.85 ± 0.20) cm <i>vs</i> (0.84 ± 0.19) cm, <i>P</i> = 0.002], a significantly shorter beam-on time [(177.05 ± 62.68) s <i>vs</i> (142.71 ± 34.59) s, <i>P</i> = 0.001], and significantly higher <i>D</i><sub>2%</sub> [(65.69 ± 2.15) Gy <i>vs</i> (66.99 ± 2.03) Gy, <i>P</i> = 0.001] and <i>D</i><sub>mean</sub> [(58.77 ± 1.60) Gy <i>vs</i> (59.95 ± 1.43) Gy, <i>P</i> <0.001]. There were no significant differences in the <i>CI</i>, the<i> D</i><sub>98% </sub>of the target volume, the <i>V</i><sub>5Gy</sub>, <i>V</i><sub>10Gy</sub>, <i>V</i><sub>12Gy</sub> and <i>D</i><sub>mean</sub> of the normal brain tissue, and monitor units between FFF-VMAT and FF-VMAT. <b>Conclusion</b> FFF-VMAT can better protect the normal tissue around the target volume, reduce the beam-on time, and improve treatment efficiency.
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Objective To investigate the dose calculation accuracy of two algorithms in Monaco TPS for self-made phantoms with different cavity thickness, and analyze the influence of phantoms with different cavity thickness on dose verification of upper esophageal cancer. Methods The phantoms with different cavity thickness were placed on the simulated CT positioning machine to scan and acquire images. In Monaco TPS, the irradiation fields with energy of 6 MV, 100 MU and different square field sizes were added to the acquired images. The dose of the cavity of the ionization chamber was calculated by two algorithms, and measured on the accelerator by dosimeter under the same conditions. At the same time, 20 patients with upper esophageal cancer who received dynamic intensity modulation in fixed field were randomly selected and included in the study, and two algorithms were used for dose verification on phantoms with different cavity thickness. The results were statistically analyzed by SPSS 22.0 software. Results The maximum deviations between the calculated values and the measured values were 0.66% and −1.8%, in the calculation of phantoms with different cavity thickness by algorithms of Monte Carlo and Pencil Beam. In Monte Carlo algorithm, the result of RD pair t test is P > 0.05. Paired t test of AD (0 mm, 10 mm), (5 mm, 10 mm) and (10 mm, 20 mm) groups showed no significant difference (P < 0.05). The maximum deviation was 1.1%, and the rest groups were not statisticely significant (P > 0.05); In Pencil Beam algorithm the t test results of RD (0 mm, 20 mm) and (5 mm, 20 mm) pairs were (P < 0.05), the maximum deviation was 0.58%, and the rest groups were (P > 0.05). In AD group, (P < 0.05), the maximum deviation was 2.78%; The paired t test between the two algorithms was (P < 0.05), and the maximum deviations in RD and AD groups were 2.49% and 4.14%, respectively. Conclusion Monte Carlo algorithm has accurate calculation and high gamma pass rate of dose verification, and there is no clinical difference in gamma pass rate of dose verification among phantoms with different cavity thickness, pencil Beam algorithm is not recommended in cavity phantom calculation.
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Objective:To investigate the predictive value of serum histone deacetylase 3(HDAC3) on major adverse cardiovascular events (MACE) in patients with stable coronary artery disease after percutaneous coronary intervention (PCI).Methods:Eighty patients with stable coronary artery disease who underwent PCI in Jinshan Branch of Shanghai Sixth People′s Hospital from October 2017 to October 2018 were selected as the research subjects, which were divided into the MACE group (26 cases) and non-MACE group (54 cases) according to the occurrence of MACE. The clinical data, blood lipid index, HDAC3, C-reactive protein(CRP) and other indicators of the patients between two groups were compared, independent risk factors for MACE after PCI were analyzed by Logistic regression analysis, and the predictive value of various indicators on MACE were analyzed by receiver operating characteristic(ROC) curve.Results:There were no statistical differences between the two groups in general information such as gender, age, body mass index (BMI), smoking history, drinking history, history of heart failure, hypertension, hyperlipidemia, diabetes and vascular lesion count ( P>0.05). The Gensini scores in the MACE group was significantly higher than that in the non-MACE group [(18.47 ± 3.23) vs. (14.46 ± 3.62)]( P<0.05). There were no statistical differences in total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterin(LDL-C), high density lipoprotein cholesterin (HDL-C) levels between the two groups ( P>0.05). The levels of HDAC3 and CRP in the MACE group were significantly higher than those in the non-MACE group [(3.93 ± 0.50) mg/L vs. (2.92 ± 0.56) mg/L, (22.06 ± 4.56) mg/L vs. (17.56 ± 3.28) mg/L] ( P<0.05). Logistic multivariate regression analysis showed that HDAC3, CRP and Gensini scores were independent risk factors for MACE in patients with stable coronary artery disease after PCI ( P<0.05). ROC curve analysis showed that the area under the curve (AUC) of serum HDAC3,CRP and Gensini scores predicted MACE in patient with stable coronary artery disease after PCI were 0.924, 0.785, 0.803. The diagnostic efficacy of serum HDAC3 was significantly higher than that of CRP and Gensini scores ( Z=2.019, 2.147, P<0.05). Conclusions:The up-regulation of serum HDAC3 expression has correlation with MACE in patients with stable coronary artery disease after PCI, which can be used as a predictor of MACE.
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Objective To study the proliferation and apoptosis and investigate the expression of Indian hedgehog (Ihh),parathyroid hormone-related peptide (PTHrp),smoothened (Smo) protein and mRNA in the cultured rat primary chondrocytes exposed to different doses of NaF.Methods The third generation articular chondrocytes of neonate rat were cultured in vitro and treated with 0 (control),5,10,20 and 40 mg/L of fluoride.The proliferation activities of cells at different times (24,48 and 72 h) were tested by Thiazolyl Blue Tetrazolium Bromide (MTT).The apoptosis rate was determined by flow cytometry.The expressions of protein and mRNA of Ihh,Smo and PTHrp at 48 h were determined by Western blotting and semi-quantitative RT-PCR,respectively.Results After exposed to 5 mg/L of fluoride for 24,48 and 72 h,the proliferation rates were significantly increased [(1.17 ± 0.07)％,(1.20 ±0.06)％,(1.16 ± 0.08)％] compared with those of control group [(1.10 ± 0.08)％,(1.13 ± 0.08)％,(1.15 ± 0.08)％],but the proliferation activity at 48 and 72 h in 40 mg/L group [(0.72 ± 0.11)％,(0.68 ± 0.04)％] was significantly lower than those in control group (all P ＜ 0.05).Compared with the control group,apoptosis rate of cartilage cell in fluoride treatment group increased gradually [(1.47 ± 0.05)％,(19.87 ± 3.03)％,(25.30 ± 1.28)％,(45.73 ± 4.63)％,F =123.328,P ＜ 0.01].Western blot analysis and RT-PCR results showed that the Ihh,PTHrp,Smo mRNA and protein expression increased in the fluoride groups at 48 h (Ihh protein:0.77 ± 0.08 vs.0.98 ±-0.07,1.23 ± 0.06,1.37 ±0.07,1.34 ± 0.07;PTHrp protein:0.68 ± 0.04 vs.0.89 ± 0.05,0.83 ± 0.05,1.29 ± 0.05,1.16 ± 0.08;Smo protein:0.37 ± 0.01 vs.0.64 ± 0.06,0.67 ± 0.03,0.96 ± 0.06,0.69 ± 0.06;Ihh mRNA:0.77 ± 0.05 vs.0.98 ± 0.05,1.09 ±0.05,1.27 ± 0.03,1.46 ± 0.06;PTHrp mRNA:0.67 ± 0.07 vs.0.97 ± 0.05,1.07 ± 0.08,1.37 ± 0.05,1.45 ± 0.05;Smo mRNA:0.45 ± 0.03 vs.0.63 ±-0.04,0.71 ± 0.05,0.81 ± 0.01,1.00 ± 0.02,all P ＜ 0.05).Conclusions Low doses of fluoride can promote the proliferation of chondrocytes cultured in vitro,and high doses of fluoride can promote the apoptosis of chondrocytes cultured in vitro.The expression of Ihh signaling pathway RNAs and proteins of the cartilage cells are increased following increased levels of fluoride.The results suggest that fluorine has activated the Ihh signaling pathway in chondrocytes and promoted the proliferation and apoptosis processes which might be involved in chondrocytes injury.
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Objective To explore the role of Janus kinase/signal transduction and transcriptional activation (JAK/STAT) pathway in rat liver damaged by excessive fluorine.Methods Thirty-six healthy Sprague-Dawley (SD) rats were randomized by weight and divided into three groups (6 males and 6 females per group):a control group (drunk water containing NaF ＜1 mg/L) and two fluorosis groups (drunk water containing NaF of 5 mg/L and 50 mg/ L).After 6 months of experiment treatment,the fluorine contents of urine and bone were detected by fluorine-ion electrode method.The rats liver function was determined by automatic blood chemical analyzer.The protein expression of Janus kinase (JAK1),signal transducer and activator of transcription (STAT3),B-cell lymphoma/ leukemia-2 (Bcl-2) and Bcl-associated x protein (Bax) were detected by immunohistochemistry (IHC) and protein imprinting (Western blotting).The activity of superoxide dismutase (SOD),glutathione peroxidase (GSH-PX) and the content of lipid peroxide (LPO) in liver tissue were determined with oxidative stress kit.Results The fluorine contents in the urine and bone in low-[(1.90 ± 0.12)mg/L,(210.37 ± 15.81)mg/kg] and high-dose [(2.20 ± 0.17)mg/L,(222.84 ± 10.21)mg/kg] fluoride groups were higher than those of control group [(1.74 ± 0.11)mg/L;(165.48 ± 10.37) mg/kg,F =33.840,69.149,P ＜0.05];the activity of serum alanine aminotransferase (ALT) and aspartate transaminase (AST) in high-dose fluorosis group [(69.83 ± 11.18),(167.56 ± 50.85) U/L] was higher than those of control group [(42.67 ± 7.07),(126.31 ± 16.76)U/L,F =32.135,4.984,all P ＜0.05];the protein expression of JAK1,STAT3 and Bax (1.56 ± 0.31,1.49 ± 0.49,1.41 ± 0.55) in high-dose fluorosis group were significantly higher than those of control group(1.01 ± 0.11,1.04 ± 0.15,0.87 ± 0.21,F=10.923,5.361,5.009,all P＜0.05),and Bcl-2 (0.61 ± 0.15) was significantly lower in high-dose fluorosis group than control group (1.04 ± 0.17,F =16.017,P ＜0.05);the activities of SOD and GSH-PX [(7.22 ± 0.88),(7.23 ± 2.47)U/mg prot] were significantly lower in high-dose fluorosis group than control group [(9.52 ± 1.51),(12.01 ± 5.16)U/mg prot,F =11.627,4.824,all P ＜0.05],and the contents of LPO [(9.23 ± 2.24)μmol/g prot] was significantly higher in high-dose fluorosis group than control group [(6.09 ± 1.55)μmol/g prot,F =7.457,P ＜0.05].Conclusion JAK/STAT signaling pathway and the oxidative stress,apoptosis may be the pathogenesis of liver damage in chronic fluorosis.
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Objective To investigate the effects of silencing Smo gene on proliferation and apoptosis of rat prima-ry chondrocyte in vitro.Methods The primary chondrocyte was obtained by mechanical-enzyme digestion and identified by Immunohistochemical cells ( ColⅡ) .The animals were divided into control group , control siRNA group and Smo siRNA 1 ~3 group.The siRNA was transfected into chondrocytes by lentivirus vector .After 72 h, the cell viability was detected by MTT, Smo expression was detected by RT-PCR and Western blot, and the apoptosis of chondrocyte was assessed by flow cytometry .Results All types of siRNA were transfected into primary chondrocyte by vectors, the Smo siRNA 1 ~3 may inhibit the expression of Smo mRNA and protein in chondrocytes, and Smo siRNA2 had the highest silencing rate ( the expressions of Smo mRNA and protein were 0.19 ±0.03 and 0.39 ±0.07 ) .The cell viability in Smo siRNA2 group was lowest ( 77.38% ±7.19%) , while the apoptosis rate of Smo siRNA2 was highest ( 21.43%±2.97%) .Conclusions Silencing Smo gene in primary chondrocytes may inhibit proliferation and promote apoptosis , Smo may have a protecting role from apop-tosis of the chondrocyte.
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Integrin alphavbeta3 plays a major role in various signaling pathways, cell apoptosis, and tumor angiogenesis. To examine the functions and roles of alphavbeta3 integrin, a stable CHO-677 cell line expressing the murine alphavbeta3 heterodimer (designated as "CHO-677-malphavbeta3" cells) was established using a highly efficient lentiviral-mediated gene transfer technique. Integrin subunits alphav and beta3 were detected at the gene and protein levels by polymerase chain reaction (PCR) and indirect immunofluorescent assay (IFA), respectively, in the CHO-677-malphavbeta3 cell line at the 20th passage, implying that these genes were successfully introduced into the CHO-677 cells and expressed stably. A plaque-forming assay, 50% tissue culture infective dose (TCID50), real-time quantitative reverse transcription-PCR, and IFA were used to detect the replication levels of Foot-and-mouth disease virus (FMDV) in the CHO-677-malphavbeta3 cell line. After infection with FMDV/O/ZK/93, the cell line showed a significant increase in viral RNA and protein compared with CHO-677 cells. These findings suggest that we successfully established a stable alphavbeta3-receptor-expressing cell line with increased susceptibility to FMDV. This cell line will be very useful for further investigation of alphavbeta3 integrin, and as a cell model for FMDV research.
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Animals , Mice , Animals, Suckling , CHO Cells , Cloning, Molecular , Cricetulus , DNA, Complementary/genetics , Disease Susceptibility/virology , Foot-and-Mouth Disease/genetics , Foot-and-Mouth Disease Virus/physiology , Integrin alphaVbeta3/geneticsABSTRACT
ObjectiveTo study the expression and significance of NDRG1(N-myc downstream regulated gene-1), p53 and VEGF in esophageal squamous cell carcinoma (ESCC). MethodsNDRG1, p53 and VEGF protein were detected by immunohistochemistry (IHC, SP method) in 20 cases of normal esophageal squamous epithelium and 78 cases of ESCC.ResultsThe results of IHC shows that in normal esophageal squamous epithelium and esophageal squamous cell carcinoma,the positive rate of NDRG1 was 100.0 ％(20/20) and 55.1％ (43/78) respectively, p53 was 0 (0/20) and 65.4 ％ (51/78) respectively, VEGF was 30.0 ％(6/20)and 67.9 ％(53/78)respectively,all had statistical significance.There was inverse correlationof NDRG1 expression and lymphatic invasion(r =-0.237,P = 0.036).However expression of NDRG1 was no statistical significance with patient' s age,gender,grade,TNM stage,patient' s five year survival.The expression of p53 was inverse correlated with NDRG1,and the expression of VEGF was inverse correlated with NDRG1 (r =-0.331, P = 0.003). ConclusionNDRG1 may be a new tumor suppress gene and play an important role in the development and metastasis of ESCC.
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OBJECTIVE:To investigate the efficacy and safety of carvedilol in patients with chronic heart failure(CHF). METHODS:46patients with CHF were randomly divided into carvedilol group(n=26)and control group(n=20),thareinto,standard therapeutic scheme is used in control group,standard therapeutic scheme+carvedilol is used in carve diol greup.The treatment courses were6months in both groups.RESULTS:Left ventricular end-diastolic diameter(LVEDD)reduced and left ventricular ejection fraction(LVEF)increased in carvedilol group with significant difference comparing with control group(P