Objective:To investigate the relationship between SET domain bifurcated 1(SETDB1)expression and trefoil factor 1(TFF1)gene methylation,along with its clinical significance.Methods:Fifty-five lung adenocarcinoma samples and normal tissues of distant cancer were collected from the Affiliated Hospital of Chengde Medical College Hebei Province.TFF1 gene methylation levels were measured by pyrosequencing,relative TFF1 mRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR),and TFF1 and SETDB1 protein expression were quantified via immunohistochemistry.The clinical significance and correlation between TFF1 methyla-tion levels and SETDB1 protein expression were analyzed statistically.In vitro,SETDB1 siRNA or negative control siRNA was transfected into A549 cells.Following transfection,SETDB1 mRNA expression was analyzed using qRT-PCR,and SETDB1 protein expression was evaluated via Western blot.TFF1 methylation was reassessed via pyrosequencing.Results:In lung adenocarcinoma and normal tissues of distant cancer,TFF1 gene methylation rates were(70.16±6.32)%and(12.46±2.22)%,respectively.TFF1 mRNA relative expression levels were 0.56±0.17 for cancer tissues and 1.56±0.22 for the normal tissues of distant cancer.All detected differences were statistically significant(all P<0.05).TFF1 protein expression rates were 29.09%(16/55)for cancer tissues and 65.45%(36/55)for the normal tissues of distant cancer.Additionally,relative positivity rates for SETDB1 protein expression were 74.55%(41/55)and 23.64%(13/55),respectively,and all differences were stat-istically significant(all P<0.05).Western blot analysis showed that SETDB1 protein expression was significantly higher in cancer tissues(72.89±5.27)%,compared to normal tissues of distant cancer(24.27±2.37)%.In contrast,TFF1 protein expressed was markedly lower in can-cer tissues(15.38±2.33)%than in normal tissues of distant cancer(72.72±4.48)%.All differences were statistically significant(all P<0.05).TFF1 methylation and SETDB1 expression were associated with lung adenocarcinoma(r=0.486,P<0.05).Both TFF1 methylation and SETDB1 expression were closely associated with tumor TNM stage,tissue differentiation,and lymph node metastasis(P<0.05).Furthermore,TFF1 methylation increased following SETDB1 downregulation(P<0.05).Conclusions:During lung adenocarcinoma progression,SETDB1 expres-sion correlates with TFF1 methylation,and the highly expressed SETDB1 may play a role in catalyzing TFF1 methylation.

Objective:To investigate the relationship between SET domain bifurcated 1(SETDB1)expression and trefoil factor 1(TFF1)gene methylation,along with its clinical significance.Methods:Fifty-five lung adenocarcinoma samples and normal tissues of distant cancer were collected from the Affiliated Hospital of Chengde Medical College Hebei Province.TFF1 gene methylation levels were measured by pyrosequencing,relative TFF1 mRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR),and TFF1 and SETDB1 protein expression were quantified via immunohistochemistry.The clinical significance and correlation between TFF1 methyla-tion levels and SETDB1 protein expression were analyzed statistically.In vitro,SETDB1 siRNA or negative control siRNA was transfected into A549 cells.Following transfection,SETDB1 mRNA expression was analyzed using qRT-PCR,and SETDB1 protein expression was evaluated via Western blot.TFF1 methylation was reassessed via pyrosequencing.Results:In lung adenocarcinoma and normal tissues of distant cancer,TFF1 gene methylation rates were(70.16±6.32)%and(12.46±2.22)%,respectively.TFF1 mRNA relative expression levels were 0.56±0.17 for cancer tissues and 1.56±0.22 for the normal tissues of distant cancer.All detected differences were statistically significant(all P<0.05).TFF1 protein expression rates were 29.09%(16/55)for cancer tissues and 65.45%(36/55)for the normal tissues of distant cancer.Additionally,relative positivity rates for SETDB1 protein expression were 74.55%(41/55)and 23.64%(13/55),respectively,and all differences were stat-istically significant(all P<0.05).Western blot analysis showed that SETDB1 protein expression was significantly higher in cancer tissues(72.89±5.27)%,compared to normal tissues of distant cancer(24.27±2.37)%.In contrast,TFF1 protein expressed was markedly lower in can-cer tissues(15.38±2.33)%than in normal tissues of distant cancer(72.72±4.48)%.All differences were statistically significant(all P<0.05).TFF1 methylation and SETDB1 expression were associated with lung adenocarcinoma(r=0.486,P<0.05).Both TFF1 methylation and SETDB1 expression were closely associated with tumor TNM stage,tissue differentiation,and lymph node metastasis(P<0.05).Furthermore,TFF1 methylation increased following SETDB1 downregulation(P<0.05).Conclusions:During lung adenocarcinoma progression,SETDB1 expres-sion correlates with TFF1 methylation,and the highly expressed SETDB1 may play a role in catalyzing TFF1 methylation.

ObjectiveTo investigate the effects and underlying mechanism of Yinxing Mihuan oral solution （YM） on neovascularization and vascular remodeling in chemical photothrombosis-induced focal cerebral ischemia model in mice. MethodFifty SPF C57BL/6J mice were randomly divided into sham group， model group， ginaton group （12.5 mg·kg^-1）， and low- （YM-L， 412 mg·kg^-1） and high-dose （YM-H， 824 mg·kg^-1） YM groups， with 10 mice in each group. The focal cerebral ischemia model was established by chemical photothrombosis method. Drugs in each group were administered by gavage for 14 consecutive days after operation. The modified neurological severity score （mNSS） and measurement of forelimb grasping were used to evaluate the neurologic impairment of mice. The vascular density of infarct border-zone （IBZ） was measured by fluorescein labelled dextran （FITC-dextran） method. The morphology of IBZ was evaluated and observed by hematoxylin-eosin （HE） staining. The expression of proteins related to neovascularization and vascular remodeling in brain tissues， including vascular endothelial growth factor （VEGF）， platelet and endothelial cell adhesion molecule 1 （CD31）， hypoxia-inducible factor-1α （HIF-1α）， von Willebrand factor （vWF）， and angiogenin （ANG）， was detected by Western blot. ResultCompared with the sham group， the model group showed manifest neurological deficits （P<0.01）， weakened forelimb grasping （P<0.01）， increased vascular density of IBZ （P<0.01）， and obvious pathological changes， such as neuronal necrosis and gliocyte proliferation. After treatment for 14 days， compared with the model group， the YM-H group showed improved neurological deficits （P<0.01）， and the YM-L group and the YM-H group showed strengthened forelimb grasping （P<0.01）. Moreover， the YM-L group displayed increased vascular density of IBZ （P<0.05）， reduced pathological damage， and up-regulated protein expression of CD31， ANG， HIF-1α， and vWF （P<0.05， P<0.01）. ConclusionYM could improve motor function and pathological morphological impairment in chemical photothrombosis-induced focal cerebral ischemia mouse model， and the underlying mechanism might be related to the promotion of neovascularization and vascular remodeling in IBZ.

OBJECTIVE: To establish an algorithm based on 3D convolution neural network to segment the organs at risk (OARs) in the head and neck on CT images. METHODS: We propose an automatic segmentation algorithm of head and neck OARs based on V-Net. To enhance the feature expression ability of the 3D neural network, we combined the squeeze and exception (SE) module with the residual convolution module in V-Net to increase the weight of the features that has greater contributions to the segmentation task. Using a multi-scale strategy, we completed organ segmentation using two cascade models for location and fine segmentation, and the input image was resampled to different resolutions during preprocessing to allow the two models to focus on the extraction of global location information and local detail features respectively. RESULTS: Our experiments on segmentation of 22 OARs in the head and neck indicated that compared with the existing methods, the proposed method achieved better segmentation accuracy and efficiency, and the average segmentation accuracy was improved by 9%. At the same time, the average test time was reduced from 33.82 s to 2.79 s. CONCLUSIONS The 3D convolution neural network based on multi-scale strategy can effectively and efficiently improve the accuracy of organ segmentation and can be potentially used in clinical setting for segmentation of other organs to improve the efficiency of clinical treatment.
Head ; Humans ; Image Processing, Computer-Assisted ; Neck ; Neural Networks, Computer ; Organs at Risk ; Tomography, X-Ray Computed

Objective To analyze the differences between the semi-quantitative RT-PCR and real time quantitative fluorescence RT-PCR assays for detecting XDH/XO mRNA expression in various organ tissues of rhesus monkey, and provide useful reference in methodology of experimental studies.Total RNA was extracted from the myocardium, kidney, testis, skin, and liver tissues, respectively, for detecting XDH/XO mRNA expression in rhesus monkey by semi-quantitative RT-PCR and real time quantitative fluorescence RT-PCR assays.The sensitivity and specificity of the two assays were compared with each other using the same primer sequences and reference genes.Results The expression of XDH/XO mRNA in different organ tissues were detected by both the two PCR assays.The sensitivity of quantitative fluorescence real-time RT-PCR for the XDH/XO mRNA expression in the liver tissue was 39 times higher than that by semi-quantitative RT-PCR.Conclusions Both the quantitative and semi-quantitative fluorescence RT-PCR assays can be used to detect the expression of XDH/XO mRNA in different organ tissues of rhesus monkey.The sensitivity of quantitative fluorescence real-time PCR assay is more sensitive than that of the semi-quantitative RT-PCR assay.

In this paper are proposed four heartbeat models which correspond to two different positions of the ectopic pacemaker and two coupling styles of the sinus and ectopic pacemakers. The models computed are based on the modified Ikeda phase resetting model. Most of the heartbeat modes are periodic; they exhibit "Arnold's tongue" structure in parameter plane of perturbing frequency and strength. When the ectopic pacemaker is located in the ventricle, there are bistable dynamic modes. The abnormal hearbeat rhythms of bigeminy and trigeminy in clinical medicine have been observed when coupling strength is weaker in odd resetting or refractory time is longer in even resetting.
Cardiac Pacing, Artificial ; methods ; Computer Simulation ; Electrocardiography ; Heart Rate ; physiology ; Humans ; Models, Cardiovascular ; Sinoatrial Node ; physiology

Metabolic nuclear receptors consist of a group of nuclear hormone receptor transcription factors including peroxisome proliferator-activated receptors(PPARs),liver X-activated receptors(LXRs) and farnesoid X-activated receptors(FXRs).They have been identified and drawn enormous attention due to key roles in regulating adipogenesis,lipid metabolism,energy metabolism,insulin sensitivity,inflammation,blood pressure,cell growth and differentiation.Growing evidences support a causative relationship between these three metabolic nuclear receptors and the metabolic syndrome,which is characterized by insulin resistance,glucose intolerance or type II diabetes,obesity,dyslipidemia,hypertension,and microalbuminuria.These receptors have also been implicated in pathogenesis of atherosclerosis.Here we review the literature pertaining to the action and physiological role of metabolic nuclear receptors with particular emphasis on their pathogenic roles in the metabolic syndrome.