1.Synthesis and classification of pulmonary nodules using two-stage-based generative adversarial network incorporating contextual transformer
Zhixian YIN ; Kewen XIA ; Zhao ZHANG ; Ziping HE
Chinese Journal of Medical Physics 2024;41(12):1517-1531
A two-stage-based generative adversarial network incorporating contextual transformer is proposed for synthesis and multiclass classification of pulmonary nodules.Contextual transformer adopts a channel-enhanced multi-head contextual transformer mechanism which combines channel attention and multi-head contextual transformer to better deal with the complex semantic relationship in the feature space,thereby effectively enhancing the feature extraction capability of the model.A two-stage-based generative adversarial network framework is used to achieve the injection of pulmonary nodules in the designated lung area,and divide the synthesis task into two stages.In the first stage,pulmonary nodule regions of interest images are generated and then fused with designated lung parenchyma through a Poisson blending module to generate preliminary samples;in the second stage,an improved CycleGAN model is used to fine-tune the preliminary samples.Meanwhile,the skip layer excitation module and auxiliary classifier are introduced into the discriminator for realizing the re-correction of the feature channel and the classification of pulmonary nodules.Experiments on LIDC-IDRI dataset reveal that the proposed method has a FID,IS and KID of 115.153,2.619±0.095 and 0.062 on pulmonary nodule synthesis,and achieves an accuracy,sensitivity,F1 value and AUC of 70.23%,68.66%,68.92%and 87.59%on pulmonary nodule malignancy classification,respectively,outperforming GAN-based classification models such as ADGAN,as well as benchmark networks such as VGG16.
2.Synthesis and classification of pulmonary nodules using two-stage-based generative adversarial network incorporating contextual transformer
Zhixian YIN ; Kewen XIA ; Zhao ZHANG ; Ziping HE
Chinese Journal of Medical Physics 2024;41(12):1517-1531
A two-stage-based generative adversarial network incorporating contextual transformer is proposed for synthesis and multiclass classification of pulmonary nodules.Contextual transformer adopts a channel-enhanced multi-head contextual transformer mechanism which combines channel attention and multi-head contextual transformer to better deal with the complex semantic relationship in the feature space,thereby effectively enhancing the feature extraction capability of the model.A two-stage-based generative adversarial network framework is used to achieve the injection of pulmonary nodules in the designated lung area,and divide the synthesis task into two stages.In the first stage,pulmonary nodule regions of interest images are generated and then fused with designated lung parenchyma through a Poisson blending module to generate preliminary samples;in the second stage,an improved CycleGAN model is used to fine-tune the preliminary samples.Meanwhile,the skip layer excitation module and auxiliary classifier are introduced into the discriminator for realizing the re-correction of the feature channel and the classification of pulmonary nodules.Experiments on LIDC-IDRI dataset reveal that the proposed method has a FID,IS and KID of 115.153,2.619±0.095 and 0.062 on pulmonary nodule synthesis,and achieves an accuracy,sensitivity,F1 value and AUC of 70.23%,68.66%,68.92%and 87.59%on pulmonary nodule malignancy classification,respectively,outperforming GAN-based classification models such as ADGAN,as well as benchmark networks such as VGG16.
3.Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer.
Juanjuan FENG ; Zhengke LIAN ; Xinting XIA ; Yue LU ; Kewen HU ; Yunpeng ZHANG ; Yanan LIU ; Longmiao HU ; Kun YUAN ; Zhenliang SUN ; Xiufeng PANG
Acta Pharmaceutica Sinica B 2023;13(3):1145-1163
MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.
4.Genetic characteristics of breakthrough varicella-zoster virus infection during the varicella outbreaks in Minhang District of Shanghai
Jia LU ; Yan DU ; Xi WANG ; Ye WANG ; Baofang JIN ; Kewen MEI ; Xia TIAN ; Liping ZHANG
Chinese Journal of Microbiology and Immunology 2016;36(4):271-276
Objective To analyze the genetic characteristics of breakthrough varicella-zoster virus infection during the varicella outbreaks in Minhang District of Shanghai in 2013-2014. Methods Samples of the varicella-zoster liquid were collected from patients with chickenpox in Minhang District in 2013-2014 and used for the extraction of genomic DNA. The open reading frame ( ORF) of 22 and 62 regions were se-quenced and further analyzed by using bioinformatics methods. Results A total of 24 samples were success-fully collected and sequenced, and all of them were wild strains. Among the 24 varicella-zoster virus strains, 23 strains were highly homologous to the parental strain ( P-Oka) and the vaccine strain ( V-Oka) , indica-ting that they belonged to J genotype. Only one strain, whose genotype was between M and E, was highly ho-mologous to the mosaic( M) CA123 strain ( M1 genotype) , indicating that it might belong to M1 genotype. Conclusion The epidemic strains of varicella-zoster virus in Minhang District were mainly J genotype. Lo-cal epidemic of M and other genotypes of varicella-zoster virus also existed. There were some gene variations in different strains of J genotype. These varicella-zoster virus strains of non-vaccine genotypes might be one of the reasons causing the breakthrough cases of chicken pox.
5.Effect of ditching for drain on control of Oncomelania hupensis snail in beaches of Dongting Lake
Wangyuan WEI ; Kaimin BU ; Kailin WEI ; Zhihong LUO ; Guanghui REN ; Xianglin CHEN ; Jianmin YI ; Yu LIU ; Yang XIANG ; Kewen TANG ; Jianhui YAN ; Meng XIA ; Liang DING ; Xianjiang LU ; Dongsong NIE ; Yaun LI
Chinese Journal of Schistosomiasis Control 2015;(3):241-245
Objective To evaluate the effect of ditching for drain on the control of the breed of Oncomelania hupensis snails in beaches of Dongting Lake. Methods From November,2009 to November,2012,an O. hupensis snail infested beach of the Yueyang jail and an O. hupensis snail infested beach of Junshan District were selected as research fields in the eastern Dongting Lake area,and the former,as the intervention field,was performed with the ditching for drain by excavators and the latter,as the control field,was not. Results Before the project implemented,the average soil moisture contents on the beaches in dry seasons of the two fields were both about 35.56%. After the project implemented,in the intervention field,the average soil mois?ture content was 26.53%which was significantly lower than that(35.56%)in the control field(F=6.53,P<0.05). The under?ground water levels in different heights in the intervention field were lower than those in the control field (χ2 = 33.33,P <0.05). Before the project implemented,the natural death rates of the snails were 0.98%and 0.89%in the two research fields re?spectively(P>0.05),and after the project implemented(in 2012),no adult and young snails were found in the interventional field,but in the control field,the average densities of living snails and young snails were 29.37 snails/0.1 m2 and 213±108.45 snails/0.1 m2 respectively. Conclusion The intervention of ditching for drain can decrease the soil moisture contents quickly and change the ecological condition,therefore,can control the breed of O. hupensis snails in the beaches of Dongting Lake.
6.The comparison of cognitive potential P300 in major depressive disorder between with and without family history
Dongmei YAN ; Yan REN ; Kewen WU ; Zixuan ZHOU ; Jiao JIA ; Xia LIU ; Hong YANG
Chinese Journal of Behavioral Medicine and Brain Science 2012;21(8):699-701
ObjectiveTo explore the character of cognitive potential P300 in major depressive disorder ( MDD ) patients between with and without family history and compare the cognitive function between them.MethodsSixty-seven MDD patients with family history and sixty-seven MDD patients without family history were assigned to research group,sixty-seven healthy volunteers were assigned to control group,and ERP P300 detections were conducted in all subjects.Results①To compare with control group ( ( 189.33 ± 51.13 ) ms) and MDD without family history group( ( 193.55 ± 40.01 )ms),the N2 latency was prolonged more significantly in MDD with family history group ( ( 208.40 ± 33.05 ) ms ) (P < 0.05 ).②Compared with control group ( ( 3.38 ± 5.52 ) μV ),the N2 amplitude was decreased more significantly in MDD without ( ( 2.47 ± 1.87 ) μV ) and with family history ( ( 2.36 ± 2.10) μV ),(P < 0.05 ).ConclusionThere is an obvious cognitive function damaged in the MDD patients with and without family history and the MDD patients with family history are more serious.
7.Effects of diazoxide on ?-calpain activation, c-Fos and c-Jun expres sion in neonatal hypoxic-ischemic rat brain
Kewen JIANG ; Quanxiang SHUI ; Zhezhi XIA ; Yin ZHANG
Chinese Journal of Pathophysiology 1986;0(01):-
AIM: To investigate the effects of diazoxide, an ATP-sensitive K + channel opener on the ?-calpain activation, c-Fos and c- Jun expression in neonatal hypoxic-ischemic rat brain. METHODS:The animal model of hypoxic-ischemic brain injury (HIBI) was made in the 7-day -old SD rats. Diazoxide was injected into the left lateral ventricle prior or po st hypoxic-ischemia (HI) insults. Western blot was applied to detect the integra ted density (ID) of the nuclear c-Fos and c-Jun at 4h, and the cleavage of cytos olic ?-calpain at 24 h after HI insults. RESULTS: Low c-Fos and c-Jun expressions from cortical and hippocampal samples were observed in the tw o diazoxide groups, and significant differences in their expressions were found by comparison with the HI controls (P

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