Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Automatic segmentation of organs at risk for nasopharyngeal carcinoma with Smart Segmentation and MIM Atlas / 中华放射医学与防护杂志

Objective@#To compare the accuracy of two automatic segmentation softwares (Smart Segmentation and MIM Atlas) in organs at risk (OARs) contouring for nasopharyngeal carcinoma (NPC).@*Methods@#Totally 55 NPC patients were retrospectively reviewed with manually contoured OARs on CT images, in which 30 cases were randomly selected to create a data base in the Smart Segmentation and MIM Atlas. The remaining 25 cases were automatically contoured with Smart Segmentation and MIM as test cases. The automatic contouring accuracies of two softwares were evaluated with Dice coefficient(DSC), Hausdorff distance(HD), and absolute volume difference(△V) using manual contours as a golden standard.@*Results@#The overall DSC, HD and △V of all organs contoured by MIM Atlas and Smart Segmentation were (0.79±0.13) vs. (0.62±0.24) (t=14.06, P<0.05), (5.50±3.84)mm vs.(8.38±4.88)mm (t=-11.40, P<0.05), and (1.52±2.46) cm3 vs. (2.38±3.57) cm3 (t=-4.70, P<0.05), respectively. The average DSC of 11 organs (brain stem, optic chiasm, bilateral lens, bilateral optic nerve, bilateral eyeballs, bilateral parotid gland, spinal cord) delineated by MIM Atlas was statistically greater than that of Smart Segmentation (t=5.27, 4.41, 6.34, 5.70, 10.62, 7.45, 3.96, 4.26, 6.25, 5.42, 7.23, P<0.05). The average HD of 10 organs (brain stem, optic chiasm, bilateral lens, bilateral optic nerve, bilateral eyeballs, left parotid gland, spinal cord) delineated by MIM Atlas was statistically less than that of Smart Segmentation (t=-4.51, -4.49, -3.92, -3.45, -5.36, -5.56, -3.89, -3.90, -3.60, -3.68, P<0.05). The average △V of 6 organs (brain stem, optic chiasm, left len, bilateral optic nerve, right eyeball) delineated by MIM Atlas was statistically less than that of Smart Segmentation (t=-2.83, -3.39, -2.56, -2.27, -2.43, -2.51, P<0.05).@*Conclusions@#Both softwares have reasonable contouring accuracy for larger organs. The accuracy decreased with the decrease of organ volumes and blurred boundary. Generally, MIM Atlas′s performs better than Smart Segmentation does.

Automatic segmentation of organs at risk for nasopharyngeal carcinoma with Smart Segmentation and MIM Atlas / 中华放射医学与防护杂志

Objective To compare the accuracy of two automatic segmentation softwares ( Smart Segmentation and MIM Atlas) in organs at risk ( OARs) contouring for nasopharyngeal carcinoma ( NPC) . Methods Totally 55 NPC patients were retrospectively reviewed with manually contoured OARs on CT images, in which 30 cases were randomly selected to create a data base in the Smart Segmentation and MIM Atlas. The remaining 25 cases were automatically contoured with Smart Segmentation and MIM as test cases. The automatic contouring accuracies of two softwares were evaluated with Dice coefficient( DSC) , Hausdorff distance( HD) , and absolute volume difference(△V) using manual contours as a golden standard. Results The overall DSC, HD and △V of all organs contoured by MIM Atlas and Smart Segmentation were (0.79±0.13) vs. (0.62±0.24) (t= 14.06, P<0.05),(5.50±3.84)mm vs.(8.38±4.88)mm ( t=-11. 40, P<0. 05 ) , and ( 1. 52 ± 2. 46 ) cm3 vs. ( 2. 38 ± 3. 57 ) cm3 ( t = -4. 70, P<0. 05 ) , respectively. The average DSC of 11 organs ( brain stem, optic chiasm, bilateral lens, bilateral optic nerve, bilateral eyeballs, bilateral parotid gland, spinal cord) delineated by MIM Atlas was statistically greater than that of Smart Segmentation ( t=5. 27, 4. 41, 6. 34, 5. 70, 10. 62, 7. 45, 3. 96, 4. 26, 6. 25, 5. 42, 7. 23, P<0. 05) . The average HD of 10 organs ( brain stem, optic chiasm, bilateral lens, bilateral optic nerve, bilateral eyeballs, left parotid gland, spinal cord) delineated by MIM Atlas was statistically less than that of Smart Segmentation ( t=-4. 51, -4. 49, -3. 92, -3. 45, -5. 36, -5. 56, -3. 89, -3. 90,-3. 60, -3. 68, P<0. 05). The average △V of 6 organs (brain stem, optic chiasm, left len, bilateral optic nerve, right eyeball) delineated by MIM Atlas was statistically less than that of Smart Segmentation ( t=-2. 83, -3. 39, -2. 56, -2. 27, -2. 43, -2. 51, P<0. 05 ) . Conclusions Both softwares have reasonable contouring accuracy for larger organs. The accuracy decreased with the decrease of organ volumes and blurred boundary. Generally, MIM Atlas's performs better than Smart Segmentation does.

Cardioprotection by hypoxia-induced rat adipose-derived stem cells through paracrine mechanisms / 中国组织工程研究

BACKGROUND: Adipose-derived stem cells (ADSCs) represent one of the promising cell sources for myocardial regeneration due to their easy accessibility and efficacy in the improvement of cardiac function following myocardial infarction. However, previously reported studies on the underlying mechanism of ADSCs-mediated cardioprotective effect mainly focused on the ADSCs cultured at room air. OBJECTIVE: To test the paracrine actions and anti-apoptotic effect of ADSCs under hypoxic conditions. METHODS: After isolation and culture, neonatal rat myocardial cells were injured by hydrogen peroxide and co-cultured with rat ADSCs under normoxia and hypoxia (10% O2) conditions. Ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in the cell pellet and levels of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and basic fibroblast growth factor (bFGF) were tested by ELISA. Expression of apoptotic proteins Bax and Bcl-2 were determined by western blot. RESULTS AND CONCLUSION: GSH/GSSG, VEGF, IGF-1, and bFGF were decreased in neonatal rat myocardial cells injured by hydrogen peroxide. ADSCs significantly attenuated hydrogen peroxide-induced myocardial apoptosis by increasing the ratio of GSH/GSSG and the secretion of VEGF, IGF-1 and bFGF. ADSCs also down-regulated Bax expression and up-regulated Bcl-2 expression. To conclude, hypoxic conditions can enhance the anti-apoptosis and cardioprotective effects of ADSCs through the paracrine mechanism.

Application of deep inspiration breath hold in postoperative radiotherapy for left-side breast cancer / 中华放射医学与防护杂志

Objective To investigate the dosimetric differences among three types of breath hold mode ( free breath:FB, thoracic deep inspiration breath hold: T-DIBH, abdomen deep inspiration breath hold:A-DIBH) and to explore the optimal breath hold method in the postoperative radiotherapy of left-side breast cancer patients with minimum dose to normal tissues and organs at risk. Methods A total of eighteen patients with left-side breast cancer patients who underwent postoperative radiotherapy were enrolled in this study. Three CT simulation scans with three different breath hold method ( FB, T-DIBH, and A-DIBH ) were performed for each patient. Dosimetric differences were compared among plans generated on these three different CT image sets. Results There was no significant difference in the volume, mean dose, and homogeneity of planning target volume ( PTV) among plans generated from three different image sets (P>0. 05). The mean heart dose, mean LAD dose and mean ipsilateral lung dose in plans generated from CT image sets with FB, T-DIBH and A-DIBH were (3. 21 ± 1. 02), (1. 74 ± 0. 51), (1. 31 ±0. 41) Gy (W =171, P <0. 05), (34. 61 ± 13. 51), (14. 38 ±10. 20), (9. 21 ± 6. 53) Gy (W=171, P<0. 05), and (8. 31 ±2. 75), (7. 46 ±1. 96), (6. 89 ±1. 79) Gy (W=171, P<0. 05), respectively. Conclusions Compared with plans with FB, plans with DIBH ( T-DIBH and A-DIBH ) achieved lower cardiac, LAD and pulmonary doses. A-DIBH achieved a better normal dose reduction than T-DIBH.

An analysis on spatial and temporal distribution of highly pathogenic avian influenza H5 N1 / 预防医学

Objective To investigate the spatial and temporal distribution of highly pathogenic avian influenza H5N1 based on Geography Information System (GIS),and to learn the mechanism of the occurrence and spread of H5N1.Methods A total of 2 069 officially confirmed cases of H5N1 outbreak reported to WHO and World Organization for Animal Health (OIE)from 2003 to 2012 were analyzed using a GIS based approach.Hot spot analysis (Getis-Ord Gi*)was used in the spatial and temporal analysis.Results From 2003 to 2012,2 069 cases of H5N1 outbreak was reported in Vietnam (1 055),Bangladesh (528)and Indonesia (209).The most of the outbreaks were reported in Ganges Delta,Mekong Delta,areas around Dacca and West Java.The occurrence,spread and distribution pattern of the disease varied within different spatial scale,and the epidemic showed a bipolar distribution in Vietnam,aradial distribution in Bangladesh and a shrinking pattern in Indonesia.Conclusion Highly pathogenic avian influenza H5N1 was first emerged in city and then spread through poultry trading or transportation,and finally caused epidemic in regions with high density poultry and intensive agriculture.Hot spot analysis had a great application value in disease surveillance and early warning.

Analysis of dosimetric results of postoperative intensity modulated radiation therapy using single-energy or mixed-energy photons in invasive thymoma patients / 中华放射医学与防护杂志

Objective To compare the dosimetric results of postoperative intensity modulated radiation therapy (IMRT) using single-energy or mixed-energy photons in invasive thymoma patients.Methods Simulation CT images were acquired and clinical target volume (CTV),planning target volume (PTV) and organs at risk (OARs) were defined.Three sets of fixed-field IMRT planning were generated using 6 MV,10 MV and mixed 6/10 MV photons for each case.Monitor Units (MUs) for each plan were recorded after optimization,and parameters of PTV such as conformity index (CI),homogeneity index (HI) and dose to OARs were evaluated on dose-volume histograms.Results Near-Maximal dose (D2％) received by PTV was better in mixed-energy IMRT as compared with 6 MV(t =3.107,P ＜0.05).HI was better in mixed-energy than in 6 MV(t =2.924,P ＜0.05).There were statistically significant differences in CI among three IMRT plans.MU was higher in 6 MV than in both 10 MV and mixed-energy IMRT.The percentages of lung volumes receiving 5 Gy (V5),10 Gy(V10),20 Gy (V20),30 Gy (V30) and the mean lung dose (D) were also significantly different in most plans.V30 and V40 of the heart were comparable between 6 MV and mixed energy plans but better than in 10 MV plan.Conclusions If the reasonable choice of beam angles and number,and capability of energy selection according to beam directions,with combined advantages of low and high energy photons,mixed IMRT plans can improve the quality of IMRT plans in general and has clinical potential for postoperative radiotherapy of invasive thymomas.

Relationship between vimentin and glucocorticoid-induced cataract / 国际眼科杂志(Guoji Yanke Zazhi)

Long-term use of systemic or topical glucocorticoid can cause posterior subcapsular opacities ( PSO ) , named glucocorticoid-induced cataract ( GIC ) . There are many hypotheses on the pathogenesis of GIC. However, no one has well explained the formation of PSO, which leads to no effective approaches in the prevention and/or treatment. A new opinion is that hormones might affect lens epithelial cells through GR - mediated vimentin changes, which eventually result in the formation of GIC. Therefore, the association between vimentin and lens epithelial cell proliferation and differentiation, maybe a new direction for further studies in the pathogenesis of GIC.

THE STUDY OF NEUROPROTECTION OF bcl-2 GENE BY TRANSFECTING IT INTO PC12 CELL LINE / 解剖学报

Objective To investigate the biological effects of bcl-2 gene on neurons. Methods The recombinant expression plasmid pc DNA3-bcl-2 was constructed from pSFFV-bcl-2,then it was introduced into PC12 cell line by liposome method.Western blotting and immunohistochemistry in situ were applied to exam the exogenous gene expression.The two groups of cells(Group A,PC12 transfected by pcDNA3-bcl-2 and Group B,PC12 transfected by pcDNA3) were exposed to cisplatin with the concentration of 10*!?mol/L,50*!?mol/L, and 100*!?mol/L 72 hours later,the survival cells were estimated.Cell cycle indexes between these two groups were also studied by FCM. Results The recombinant expression plasmid pcDNA 3-bcl-2 was constructed successfully and PC12 cell line transfected by the plasmid could express Bcl-2 protein effectively.Compared with the control(25 79%),there was a significant decrease of cells from the S phase in PC12 with bcl-2 gene(8.81%).After exposed with 10*!?mol/L,50*!?mol/L,and 100*!?mol/L cisplatin,the surviving cells in group A were 276?13,185?11 and 108?10 respectively,which increased much more than in group B while they were 100?9,12?3 and 2?2 accordingly.Conclusions bcl-2 can protect PC12 cells against cytotoxic insults of cisplatin,and it suggested that it might act via cell cycle controlling.