Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective Network pharmacology and molecular docking and molecular dynamics techniques were used to investigate the mechanism of action of Alhagi sparsifolia Shap.in the treatment of sepsis and to perform animal experimental verification.Methods First,we screened the effective ingredients and their action targets of Alhagi sparsifolia Shap.,meanwhile,screened relevant action targets for the treatment of sepsis,constructed a protein interaction(PPI)network,and performed topology analysis to draw a TCM disease target network diagram.Second,Kyoto Encyclopedia of genes and genomes enrichment analysis was performed for core targets in the network diagram,along with gene ontology functional enrichment analysis.This was followed by molecular docking and molecular dynamics simulation experiment validation of the core targets.Finally,mice were used for the verification of animal experiments.Results Thirty active components of Alhagi sparsifolia Shap.were screened out,and the top 5 ranked by degree value were quercetin,(-)-epigallocatechin,(-)-Epigallocatechin Gallate,genistein,kaempferol and epigallocatechin with 196 action targets;2144 disease-related targets for sepsis,105 targets for Alhagi sparsifolia Shap.-sepsis intersection,and the core targets were TNF,IL-6,AKT1,VEGFA,CASP3,IL-1β Et al.PI3K-Akt,TNF,HIF-1,AGE-RAGE,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert therapeutic effects on sepsis.Molecular docking results showed that camelina flavanoids bound equally well to each key target,among which the conformations with the lowest binding energy were(-)-Epigallocatechin Gallate-IL-6 and quercetin-IL-6.Molecular dynamics simulations were performed on the two pairs of complexes,and the results indicated that the stable binding could be achieved through a combination of electrostatic,van der Waals potential,and hydrogen bonding interactions.Animal experiments confirmed that Alhagi sparsifolia Shap.could inhibit the activation of PI3K/Akt signaling pathway,decrease the protein expression of Caspase-3,VEGF and reduced peripheral blood inflammatory factors secretion of TNF-α、IL-1βand IL-6,alleviating inflammatory injury in tissues and organs.Conclusion The therapeutic effect of Alhagi sparsifolia Shap.on sepsis is achieved through multi biological processes,multi targets,and multi pathways.It provides a certain theoretical basis for the clinical application of camel spines as well as sepsis treatment.

When applying deep learning to the automatic segmentation of organs at risk in medical images, we combine two network models of Dense Net and V-Net to develop a Dense V-network for automatic segmentation of three-dimensional computed tomography (CT) images, in order to solve the problems of degradation and gradient disappearance of three-dimensional convolutional neural networks optimization as training samples are insufficient. This algorithm is applied to the delineation of pelvic endangered organs and we take three representative evaluation parameters to quantitatively evaluate the segmentation effect. The clinical result showed that the Dice similarity coefficient values of the bladder, small intestine, rectum, femoral head and spinal cord were all above 0.87 (average was 0.9); Jaccard distance of these were within 2.3 (average was 0.18). Except for the small intestine, the Hausdorff distance of other organs were less than 0.9 cm (average was 0.62 cm). The Dense V-Network has been proven to achieve the accurate segmentation of pelvic endangered organs.
Algorithms ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Neural Networks, Computer ; Organs at Risk ; Pelvis ; Tomography, X-Ray Computed

Objective:To resolve the issue of poor automatic segmentation of the bowel in women with pelvic tumors, a Dense V-Network model was established, trained and evaluated to accurately and automatically delineate the bowel of female patients with pelvic tumors.Methods:Dense Net and V-Net network models were combined to develop a Dense V-Network algorithm for automatic segmentation of 3D CT images. CT data were collected from 160 patients with cervical cancer, 130 of which were randomly selected as the training set to adjust the model parameters, and the remaining 30 were used as test set to evaluate the effect of automatic segmentation.Results:Eight parameters including Dice similarity coefficient (DSC) were utilized to quantitatively evaluate the segmentation effect. The DSC value, JD, ΔV, SI, IncI, HD (cm), MDA (mm), and DC (mm) of the small intestine were 0.86±0.03, 0.25±0.04, 0.10±0.07, 0.88±0.05, 0.85±0.05, 2.98±0.61, 2.40±0.45 and 4.13±1.74, which were better than those of any other single algorithm.Conclusion:Dense V-Network algorithm proposed in this paper can deliver accurate segmentation of the bowel organs. It can be applied in clinical practice after slight revision by physicians.

The QUASAR Penta-guide Phantom with fiducial markers was scanned, and the CT images were transferred to Pinnacle workstation. Skin and target volumes were contoured and transferred to TomoPlan treatment planning system. The phantom was scanned with Megavoltage CT (MVCT). MVCT images were matched to the planning CT. Automatic adjustment of treatment couch was completed. It was found that the green laser coincided with the etched center crosshairs in lateral and longitudinal directions with an error less than 2 mm. However 2 mm vertical tabletop lag was found, but could be eventually corrected. Verifications for specific patients with head and pelvic tumors were also completed, the residual setup error were analyzed. The automatic movement of tabletop after image match is satisfactory.
Humans ; Radiotherapy Planning, Computer-Assisted ; instrumentation ; methods ; Radiotherapy, Intensity-Modulated ; instrumentation ; methods ; Tomography, Spiral Computed ; instrumentation ; methods

Objective To analyze the effect of clinical temporomandibular joint (TMJ) functional training for prevention of trismus in nasopharyngeal carcinoma (NPC) patients treated with radiotherapy.Methods According to the performance of patients clinical TMJ functional training, 43 NPC patients treated with three-dimensional conformal radiation therapy (3DCRT) and 82 NPC patients treated with general twodimensional radiation therapy were assigned respectively to the study group and the contrast group. The clinical TMJ functional training on patients of the study group was performed regularly and intensively under good guidance and supervision from the beginning of radiotherapy. The clinical TMJ functional training on patients of the contrast group was performed without such strict supervison after the first guidance. The size of the distance was measured between the incisors of the patients of the study group and the contrast group before radiotherapy and the final follow-up within two years after radiotherapy. Results The reduction of the distance between the incisors were [(0.64±0.59) cm] in the study group of 3DCRT in contrast to the [(0.81±0.64) cm] in the contrast group (P ＞0.05). The incidence of trismus was 8.1% in the study group of 3DCRT in contrast to the 21.1% in the contrast group (P ＞0.05); The reduction of the distance between the incisors were [(0.72±0.65) cm] in the study group of general two-dimensional radiotherapy in contrast to the [(1.64±0.73) cm] in the contrast group (P ＜0.01). The incidence of trismus was 19.0% in the study group of general two-dimensional radiotherapy in contrast to the 47.5% in the contrast group (P ＜0.01). Conclusion TMJ Functional training method is the good method that can lower the severity and the incidence of trismus in NPC patients treated with radiotherapy. It is more evident and more important for patients with general twodimensional radiotherapy.