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*

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg^-1） groups， and a trimetazidine group （0.002 g·kg^-1）. By intragastric administration of vitamin D₃ and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

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 investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.

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 investigate the effects of computerized cognitive remediation therapy (CCRT) combined with social skill training on the improvement of negative symptoms of schizophrenia.Methods:A total of 102 schizophrenic patients who received treatment in Shanxi Province Social Welfare Kangning Psychiatry Hospital from March 2019 to June 2021 were included in this study. They were randomly divided into an intervention group and a control group ( n = 51/group). During the intervention process, because of the reasons such as midway discharge, only 93 patients were included in the final analysis, consisting of 47 patients in the intervention group and 46 patients in the control group. All patients received social skills training. Patients in the intervention group received 8-week CCRT. The Positive and Negative Syndrome Scale and Social Skills Checklist were used to evaluate curative effect in the two groups. Results:After treatment, total score of the Positive and Negative Syndrome Scale and the score of negative symptoms in the intervention group were (46.36 ± 9.33) points and (11.15 ± 3.53) points, respectively, which were significantly lower than (51.06 ± 10.26) points and (16.42 ± 4.75) points in the control group ( t = 2.07, 5.41, both P < 0.05). The total score of Social Skills Checklist, conflict resolution ability score and relationship building ability score in the intervention group were (16.05 ± 6.85) points, (3.36 ± 1.65) points and (3.14 ± 1.83) points, respectively, which were significantly lower than (21.08 ± 8.24) points, (5.92 ± 2.35) points and (6.75 ± 2.51) points, respectively ( t = 2.87, 5.34, 7.00, all P < 0.01). Conclusion:CCRT combined with social skill training can effectively improve the negative symptoms of patients with schizophrenia.

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.

Objective    To evaluate the clinical value of in vitro fenestration and branch stent repair in the treatment of thoracoabdominal aortic aneurysm in visceral artery area assisted by 3D printing. Methods    The clinical data of 7 patients with thoracoabdominal aortic aneurysm involving visceral artery at the Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University from March 2016 to May 2019 were analyzed retrospectively. There were 5 males and 2 females with an average age of 70.2±3.9 years. Among them 4 patients had near-renal abdominal aortic aneurysm, 3 had thoracic aortic aneurysm, 4 had asymptomatic aneurysm, 2 had acute symptomatic aneurysm and 1 had threatened rupture of aneurysm. According to the preoperative CT measurement and 3D printing model, fenestration technique was used with Cook Zenith thoracic aortic stents, and branch stents were sewed on the main stents in vitro, and then the stents were modified by beam diameter technique for intracavitary treatment. Results    All the 7 patients completed the operation successfully, and a total of 18 branch arteries were reconstructed. The success rate of surgical instrument release was 100.0%. The average operation time was 267.0±38.5 min, the average intraoperative blood loss was 361.0±87.4 mL and the average hospital stay was 16.0±4.2 d. Immediate intraoperative angiography showed that the aneurysms were isolated, and the visceral arteries were unobstructed. Till May 2019, there was no death, stent displacement, stent occlusion, ruptured aneurysm or loss of visceral artery branches. Conclusion    3D printing technology can completely copy the shape of human artery, intuitively present the anatomical structure and position of each branch of the artery, so that the fenestration technique is more accurate and the treatment scheme is more optimized.

Background/Aims: Mean nocturnal baseline impedance (MNBI) is a new reflux metric for mucosal integrity. It remains unclear whether MNBI can help identify evidence against pathological reflux by the Lyon Consensus in patients with refractory gastroesophageal reflux disease (GERD) symptoms. Methods: Three hundred and forty-nine patients with refractory GERD symptoms enrolled in this study were subjected to high-resolution manometry, 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring, and endoscopy. Conventional indexes (ie, reflux events and acid exposure time) and the novel index (MNBI) of MII-pH monitoring were extracted and analyzed. The value of MNBI in diagnosing patients with evidence against pathologic reflux was evaluated by receiver-operating-characteristic analysis. Results: There were 102 (29.2%) patients with evidence against pathologic reflux, 149 (42.7%) with inconclusive or borderline evidence and 98 (28.1%) with conclusive evidence for pathologic reflux. The MNBI was significantly higher while the proportion of pathological MNBI was significantly lower in subjects with evidence against pathologic reflux than in patients with inconclusive or borderline evidence and in patients with conclusive evidence for pathologic reflux (2444.3 [1977.9-2997.4] vs 1992.8 [1615.5-2253.6] and vs 1772.3 [758.6-2161.3], both P < 0.001; 42.2% vs 79.7% and vs 80.0%, both P < 0.05). When identifying evidence against pathologic reflux in patients with refractory GERD symptoms, the MNBI yielded an area under the curve of 0.749 (P < 0.001) at a cutoff value of 1941.8 Ω. Conclusions The MNBI has a good diagnostic value for evidence against pathological reflux in patients with refractory GERD symptoms. For its simplicity and reproducibility, we believe that MNBI should be referred to in reports of impedance-pH tracings by physicians.

Objective:To study the correlation between third lumbar skeletal muscle index(LSMI) and inflammatory factors and other factors in peripheral blood in gastric cancer patients.Methods:From October 2017 to December 2019, patients with gastric cancer admitted to West China Hospital Sichuan University were included. The LSMI of patients was obtained by dividing the area of skeletal muscle at the third lumbar vertebra level by the square of the height based on preoperative abdominal imaging data. The correlation between preoperative LSMI and inflammatory factors and other factors in peripheral blood were analyzed by person correlation analysis.Results:This study included 132 patients with gastric cancer. Among them, 39 were classified as stage Ⅰ, 36 were stage Ⅱ, and 57 were stage Ⅲ, respectively. Pearson correlation analysis suggested that the LSMI of gastric cancer patients was positively correlated with peripheral red blood cell count( P<0.01), hemoglobin( P<0.01), and prealbumin( P<0.01), and negatively correlated with interleukin-6(IL-6, P=0.027) and C-reactive protein(CRP, P= 0.014). Conclusion:Our study suggested that LSMI can be used as a nutritional index in gastric cancer patients and IL-6 and CRP played an important in the occurrence and development of sarcopenia in gastric cancer patients.