Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To explore the predictive value of 3D quantitative shape features based on enhanced CT for disease-free survival(DFS)of primary gastric gastrointestinal stromal tumors(GIST)patients receiving curative resection.Methods From January 2010 to December 2016,a total of 154 patients with primary gastric GIST who received curative resection in Zhongshan Hospital,Fudan University were retrospectively collected.The conventional CT imaging features and 3D quantitative shape features of tumors were evaluated,and the influencing factors of DFS were analyzed by univariate and multivariate Cox regression.Cut-off values were extracted,and Kaplan-Meier curves were used for survival analysis.Results Maximum 3D diameter(HR=1.829,95% CI 1.389-2.408,P＜0.001)and spherical disproportion(HR=2.153,95% CI 1.474-3.146,P＜0.001)were independent risk factors for DFS in primary gastric GIST.Kaplan-Meier curves showed that patients with maximum 3D diameter＞90.5 mm and spherical disproportion＞1.5 showed shorter DFS after curative resection(P＜0.001).Conclusion Maximum 3D diameter and spherical disproportion based on preoperative enhanced CT are valuable in the diagnosis of postoperative DFS in primary gastric GIST.

To explore the application of humanistic care in children's fever clinics,the children's fever clinics of Guangzhou Women and Children's Medical Center conducted relevant research using narrative medicine as a guiding concept.This paper elaborated on the medical humanistic dilemmas and narrative care needs in children's fever clinics,and focused on exploring the practice paths of narrative medicine in pediatric with Chinese characteristics from five dimensions,including the cultivation of nursing staff's abilities of professional narrative and humanistic care,the establishment of health lectures featuring narrative patient education,the alleviation of medical anxiety for children and their families,related support of narrative nursing,and caring services.The aim was to improve the narrative care ability of nurses in children's fever clinics,develop methods for pediatric patients that can eliminate the fear of seeking medical treatment,and protect children's physical and mental health.A carrier of care,support,and emotional expression can be provided for parents.The foundation for nursing staff to achieve professional growth through narrative reflection can be laid.Thus,it can assist in establishing a life narrative community relationship between doctors and patients,and jointly explore the meaning of life.

Objective:To propose a model that could improve image quality of cone-beam computed tomography(CBCT),which based on region-discriminative generative adversarial networks(GAN),in radiotherapy for cervical cancer,so as to meet the requirements of self-adaptive radiotherapy for image quality.Methods:We employed a region-discriminative strategy and a generative adversarial networks idea to construct a model of improving CBCT image quality that could focus on local details of the images of radiotherapy for cervical cancer,which discriminator could improve the quality of generating local details of images.This model of image quality was applied to CBCT images of radiotherapy for cervical cancer.And then,the effects of processing image were evaluated through quantitative indicators and visualization.Results:Both texture clarity and contrast were significantly enhanced after CBCT image quality was improved.The signal to noise ratio of peak value of images was increased by 47.2%,and the indicator of similarity of structure was enhanced to>0.838.Compared with other model,both visualization and indicators can appear better efficiency of model.Compared with Unet network and CycleGAN network,the similarities of structure were respectively increased by 11.88% and 19.54%,and the signal to noise ratios were respectively increased by 19.75% and 25.99%.Conclusion:The GAN bases on region-discrimination can significantly improve the quality of generating integral and detailed CBCT image of radiotherapy for cervical cancer,which can provide new technical pathway for image quality of CBCT with low dose,and can play an important role for improving safety and effectiveness of radiotherapy.It has importantly clinical value for formulating and executing radiotherapy plan.

Objective:To develop a machine learning algorithm based on habitat imaging(HI),which can be used in the grading of gliomas by using multimodal magnetic resonance imaging(MRI),so as to construct the model of support vector machine(SVM)and the visualized heterogeneous regions of gliomas.Methods:A total of 335 glioma patients were collected from the 2019 brain tumor segmentation(BraTS)challenge competition of World Health Organization(WHO),which included 259 cases with high-grade gliomas(HGG)and 76 cases with low-grade gliomas(LGG).Subregions were divided based on HI technology.The PyRadiomics open-source package was used to extract the image features of region of interest(ROI),and to screen the features that stronger correlated with the high and low-grade gliomas.An SVM model was used to classify and predict the screened feature data.The heterogeneity of gliomas in images was analyzed through visualized characterization.The efficacy of glioma grading was assessed by using the area under curve(AUC)of the receiver operating characteristic(ROC)curve.Results:The AUC of test set exceeded 90%.The average accuracy of the performance indicators of test set was(92.74±2.88)%,and the average sensitivity was(93.90±2.10)%,and the average specificity was(90.36±4.59)%,and the average F1 score was(95.24±0.66)%when the tumors were divided into six habitat regions.The SVM model could showed important sub-regions in glioma grading in three-dimensional space.Conclusion:The study method based on HI has significant advantages in glioma grading,which can effectively realize visualized heterogeneity of tumor and construct model of the heterogeneity of tumor.

Objective:To explore the clinical effects of a 3D-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy (DC).Methods:This study is a retrospective cohort analysis. The clinical data of 35 patients who underwent DC at Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, from September 2020 to September 2023 were reviewed. The cohort included 24 males and 11 females, with an age of (48.7±14.9) years (range:17 to 74 years). Nineteen patients (experimental group) received the intracranial pressure balancing device fixed to the bone defect site post-DC. This device was made using medical-grade dicyanamide resin and was three dimensional printed based on postoperative CT scans of the patients. The remaining 16 patients (control group) did not receive the intracranial pressure balancing device, while other treatments and procedures were consistent with the experimental group. Data were compared using the χ2 test or Fisher′s exact probability method. Results:Out of the 35 patients, 30 cases (85.7%) experienced complications following DC. Specific complications included cerebral infarction in 3 cases (8.6%), intracerebral hemorrhage in 1 case (2.9%), subdural effusion in 27 cases (77.1%) with a median onset of (8.8±6.5) days (range: 1 to 23 days), brain tissue protrusion in 15 cases (42.9%) with a median onset of ( M(IQR)) 7.0 (21.0) days (range:2 to 106 days), and hydrocephalus in 6 cases (17.14%) with a median onset of 34.5 (111.0) days (range: 22 to 136 days). There were no significant differences in the occurrence of complications(all P>0.05). However, there was a significant reduction in the incidence of subdural effusion in the experimental group prior to cranioplasty ( P=0.013). No significant differences were noted in mRS scores between the two groups after cranioplasty ( P>0.05). Conclusions:The intracranial pressure balancing device has the effect of prevention and treatment of subdural effusion. However, it did not significantly improve patient prognosis post-DC, warranting further investigation.

Objective:To explore the clinical effects of a 3D-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy (DC).Methods:This study is a retrospective cohort analysis. The clinical data of 35 patients who underwent DC at Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, from September 2020 to September 2023 were reviewed. The cohort included 24 males and 11 females, with an age of (48.7±14.9) years (range:17 to 74 years). Nineteen patients (experimental group) received the intracranial pressure balancing device fixed to the bone defect site post-DC. This device was made using medical-grade dicyanamide resin and was three dimensional printed based on postoperative CT scans of the patients. The remaining 16 patients (control group) did not receive the intracranial pressure balancing device, while other treatments and procedures were consistent with the experimental group. Data were compared using the χ2 test or Fisher′s exact probability method. Results:Out of the 35 patients, 30 cases (85.7%) experienced complications following DC. Specific complications included cerebral infarction in 3 cases (8.6%), intracerebral hemorrhage in 1 case (2.9%), subdural effusion in 27 cases (77.1%) with a median onset of (8.8±6.5) days (range: 1 to 23 days), brain tissue protrusion in 15 cases (42.9%) with a median onset of ( M(IQR)) 7.0 (21.0) days (range:2 to 106 days), and hydrocephalus in 6 cases (17.14%) with a median onset of 34.5 (111.0) days (range: 22 to 136 days). There were no significant differences in the occurrence of complications(all P>0.05). However, there was a significant reduction in the incidence of subdural effusion in the experimental group prior to cranioplasty ( P=0.013). No significant differences were noted in mRS scores between the two groups after cranioplasty ( P>0.05). Conclusions:The intracranial pressure balancing device has the effect of prevention and treatment of subdural effusion. However, it did not significantly improve patient prognosis post-DC, warranting further investigation.

Mechanosensitive channels (MSCs) are special membrane proteins that can convert mechanical stimulation into electrical or chemical signals. These channels have become potential targets for ultrasonic neuromodulation due to their properties. The good spatial resolution and focusing effect of ultrasound make it theoretically possible to achieve non-invasive whole-brain localization. Therefore, ultrasonic neuromodulation is a promising method for performing physical neuromodulation and treating neurological disorders. To date, only a few ion channels have been reported to be activated by ultrasound, while recent research has identified more channels with mechanosensitive properties. Moreover, the opening process and mechanism of MSCs under ultrasound excitation remain unknown. This review provides an overview on recent research advances and applications in MSCs, including large conductance mechanosensitive channels, transient receptor potential channels, degenerated protein/epithelial sodium channels, two-pore potassium channels, and piezo channels. These findings will facilitate future studies and applications of ultrasonic neuromodulation.
Ultrasonics ; Ion Channels/metabolism*

Objective:To explore the correlation of the dose of capecitabine with the efficacy and cardiotoxicity in patient-derived tumor xenograft (PDX) model of mice with colorectal cancer.Methods:The fresh cancer tissues of 1 colorectal cancer patient were transplanted into the bilateral axillary subcutaneous of immunodeficient NOG mice to establish PDX model and passage stably. And then the morphology of tumor cells in primary generation and the second-generation tumor tissues was observed by using HE staining. The expression of tumor markers was detected by using immunohistochemistry method, and the model was evaluated. Mice were intragastrically infused with 200, 300 and 400 mg/kg capecitabine once a day, which were treated as low, middle and high dose groups respectively, 5 rats in each group; in the control group, 0.9% NaCl solution was perfused into the stomach; 14 d in total, use stop for 7 d, consecutively administered in this way. The body weight was measured every day and the tumor volume was measured every 3 days. After 100 days of observation, the mice were killed, and the tumor tissue was taken to measure the tumor weight and then the tumor volume, tumor volume inhibition rate and tumor inhibition rate were calculated. The morphology of tumor tissues was observed by using HE staining. The protein levels of anti-tumor effect indexes like rasP21, cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), cardiac troponin Ⅰ (cTn-Ⅰ) and brain natriuretic peptide (BNP) in serum of mice were detected by using enzyme linked immunosorbent assay (ELISA).Results:PDX model of mice with colorectal cancer was successfully constructed, and the histological characteristics of the primary tumor in the model were well preserved. During administration, 1 mouse died in the capecitabine high dose group; a slow down in tumor volume growth could be found with the increased dose of capecitabine. There was no statistically significant difference in body weight among 4 groups until all mice were killed ( P > 0.05). The tumor volume and tumor weight in the low, middle and high dose groups were lower than those in the control group (all P < 0.05), and the tumor volume and tumor weight showed an obvious decrease with the increase in dose. The tumor volume inhibition rates of low, middle and high dose groups were 42.61%, 67.61% and 77.27%, respectively, and the tumor inhibition rates were 35.53%, 67.77% and 75.09%, respectively. The serum anti-tumor effect indexes rasP21, COX2 and PGE2 in the middle and high dose groups were decreased compared with those in the control group (all P < 0.05), while cTn-Ⅰ and BNP levels were increased compared with those in the control group (all P < 0.05). Conclusions:The established PDX model of mice with colorectal cancer can better retain the histological characteristics of the original tumor. After treatment of middle and high dose of capecitabine, the tumor inhibition effect is obvious, but the risk of myocardial damage should be noticed.

Objective:To investigate the clinical efficacy of trigeminal neuralgia treatment in elderly patients with percutaneous balloon compression assisted by a robotic surgical navigation and positioning planning system.Methods:Eleven elderly patients with trigeminal neuralgia admitted to the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University between August 2021 and August 2022 were retrospectively analyzed.Three-dimensional time-of-flight magnetic resonance angiography, a three-dimensional fast spin-echo sequence with variable flip angles and thin-slice CT scans were performed before the procedure, and multimodal image fusion was performed by a robot workstation.The volume of Meckel's cave was calculated.Two paths were set up in the surgical planning: an actual puncture path, targeting the anterior inner quadrant of the internal foramen ovale, and a virtual path, used to plan the insertion depth of the balloon.The actual puncture path was completed under the guidance of the robotic arm adapter, and the virtual path for depth measurement was completed under lateral X-ray views of digital subtraction angiography.The balloon was placed at the predetermined depth and was inflated to form a pear shape to complete the procedure.The visual analogue scale(VAS)score was used to evaluate preoperative pain, and the Barrow Neurological Institute(BNI)facial numbness score was used to evaluate postoperative facial numbness.The patients were followed up for 1-12 months and the results were analyzed.Results:In all of the 11 patients, puncturing the foramen ovale and entry into the Meckel's cave were successfully conducted and the balloon was inflated to form a pear shape.Ten patients(90.9%)achieved complete remission immediately after the procedure, and 1 patient had delayed healing at 5 days after the procedure.There were no serious complications related to the procedure.There was no recurrence of pain during the follow-up, and the BNI numbness grading was between 2-3.The ratio between the inflated balloon volume and the preoperative volume of the Meckel's cave was approximately 1.7.Conclusions:Robot-assisted percutaneous balloon compression is safe and effective for the treatment of trigeminal neuralgia in elderly patients.