ObjectiveTo investigate the expression of family with sequence similarity 162 member A （Fam162a）， a mitochondrial inner membrane protein， in the fibrosis of cardiac fibroblasts and its regulatory role in modulating the fibrotic phenotype of cardiac fibroblasts. MethodsFam162a protein expression was detected in myocardial samples from patients with heart failure （HF） and mice with transverse aortic constriction （TAC）-induced myocardial remodeling. Primary neonatal mouse cardiac fibroblasts （mCFs） were isolated and cultured， and a cell model of angiotensin Ⅱ （Ang Ⅱ）-induced myocardial fibrosis was established to determine Fam162a protein expression. Recombinant adenovirus was used to mediate Fam162a overexpression， while small interfering RNA （si-RNA） was employed for Fam162a knockdown. Western blot was performed to detect the expression of fibrosis-related proteins， including COL1A1， COL3A1， and α-SMA. EdU staining assay was used to evaluate cell proliferation capacity， and scratch assay combined with Transwell assay was conducted to assess cell migration ability. Immunofluorescence assay was applied to measure mitochondrial membrane potential for reflecting mitochondrial dysfunction； reactive oxygen species （ROS） detection was performed to evaluate cellular oxidative stress status； MitoSox assay was used to reflect the degree of mitochondrial oxidative damage； and ATP detection was conducted to assess the overall cellular energy metabolism. ResultsFam162a expression was significantly downregulated in the myocardium of HF patients and TAC mice， and Ang Ⅱ-treated mCFs， accompanied by increased expression of COL1A1， COL3A1， and α-SMA （all P＜0.05）. Adenovirus-mediated overexpression of Fam162a significantly inhibited Ang Ⅱ-induced upregulation of fibrosis-related genes， as well as cell proliferation and migration. Accordingly， silencing Fam162a aggravated the fibrotic phenotypes of mCFs treated with Ang II. Further studies revealed that the inhibitory effect of Fam162a overexpression on Ang Ⅱ-induced fibrotic phenotype was suppressed following the addition of rotenone （a mitochondrial oxidative respiratory chain inhibitor）， which was accompanied by mitochondrial membrane potential depolarization， excessive ROS production， and insufficient ATP generation. ConclusionFam162a exerts its inhibitory effect on the fibrotic phenotype of cardiac fibroblasts by maintaining mitochondrial membrane potential， promoting ATP production， reducing reactive oxygen species （ROS） generation， and suppressing Smad3 signaling activation.

[Objective]To investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A(IDH3A)on cardiomyocyte hypertrophy.[Methods]The expression of IDH3A in the myocardium of healthy volunteers(n=10)and patients with heart failure(HF)(n=10),and in the myocardium of mice subjected to transverse aortic constriction(TAC)surgery and sham operation,as well as in phenylephrine(PE)-induced neonatal rat ventricular cardiomyocytes(NRVCs),was assessed by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot assay.The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated.The effect of IDH3A on NRVCs area was examined by phalloidin staining assay.A mutant of IDH3A with abolished enzymatic activity,IDH3A_D208A,was generated through site-directed mutagenesis.The impact of this IDH3A mutant on the hypertrophic phenotype,ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity.The effect of exogenous α-ketoglutaric acid(AKG)on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay,respectively.[Results]IDH3A was significantly decreased in the myocardium of HF patients,in the myocardium of TAC-operated mice,and in PE-induced NRVCs(P=0.005 2,P=0.026 6,P=0.041 3 and P=0.006 6,respectively).Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs(P<0.000 1,P=0.000 1 and P=0.000 2,respectively).The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs(P=0.001 2 and P<0.000 1,respectively),whereas the enzymatically inactive IDH3A mutant lacked this effect.Exogenous AKG provision could,but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy.[Conclusion]IDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level,providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

Objective:To design a semi-spherical applicator for delivery of semi-spherical dose distributions and assess its dosemetric characteristics.Methods:The applicator was designed in the following way. First, the scattering angle and dose rate of the electron beam having passed through a series of scattering foils of different thicknesses were calculated to determine the thickness of the scattering foil. And then, a series of location model was designed, and the variances of the mean electron energy on the surface of these models were calculated to determine the foil location. Finally, the relationship between the geometric characteristics of the layer and the surface dose on the applicator was established to design the modulator. Monte Carlo (MC) codes EGSnrc/BEAMnrc and EGS4/DOSXYZ were employed to model the head of the Mobetron, the location model, the layer, the semi-spherical applicator, and to calculate the dose distributions.Results:A semi-spherical applicator was designed for electron beam of energy 12 MeV, which consisted of a 2.5 cm diametre cylindrical collimator with 0.5 cm thick wall made of 0.3 cm thick steel and 0.2 cm thick water equivalent material (WEM), a 0.14 cm-thick foil made of tansgen, and a 2.5 cm diametre hollow semi-sphere containing a crescent modulator made of WEM. The dose rate was about 160 cGy/min, and the depth of the 50% isodose curve was 0.85 cm.Conclutions:We designed and performed a MC simulation of a semi-spherical applicator to deliver a semi-spherical dose distribution from a high energy electron beam.

Objective To analyze the expression and predictive value of serum tumor markers spectrum and chemokine protein in lung cancer and predictive value.Methods One hundred and fifty patients with lung cancer were selected as the observation group and contemporaneous 150 individuals undergoing physical examination served the control group.The levels of ProGRP,CEA,SCC and Cyfra21-1 were measured by chemiluminescence microparticle immunoassay.The chemokine protein was determined by multiple immunofluorescent assay.Results The levels of CCL28,LIF,LIGHT and GRO in the observation group were significantly higher than those in the control group (P＜0.05).The levels of CCL28,LIF,LIGHT and GRO in the observation group were higher than those in the control group.The levels of CCL28,NAP-2 and MDC in the observation group were lower than those in the control group (P＜0.05).Conclusion The regular detection of serum tumor markers spectrum and chemokine protein can predict the treatment prognosis and evaluate the clinical curative effect.