Objective To investigate the correlation between peripheral blood CD14+CD16+monocytes and IgG N-glycosyl levels and disease activity in patients with systemic lupus erythematosus(SLE).Methods A total of 109 SLE patients admitted to Xingtai Cental Hospital from August 2021 to November 2024 were retrospectively selected as the study objects.According to SLE disease activity index(SLE-DAI),the patients were divided into active group(n=52)and stable group(n=57).In addition,56 patients who underwent physical examination during the same period were selected as the control group.Clinical data of patients were collected,CD14+CD16+mononuclear cells were detected by flow cytometry(FCM),and IgG N-glycosyl levels were detected by hydrophilic interaction chromatography-mass spectrometry.Logistic regression analysis was performed to analyze the influencing factors of SLE-DAI,and multicollinearity test[variance inflation factor(VIF)]was performed for independent variables.The prediction model of disease activity was constructed.The effectiveness of the predictive model was evaluated by describing the recviver operator characteristic(ROC)curve and calculating the area under the curve(AUC)value.Hosmer-Lemeshow goodness-of-fit test predicted the calibration degree of the model.Results The levels of WBC,Hb,PLT,ALB,complement C3 and complement C4 in control group were higher than those in SLE group(t=8.917～22.171),and the levels of CRP were lower than those in SLE group(t=-17.359),with differences were statistical significance(all P<0.05).The CRP level and the proportion of CD14+CD16+mononuclear cells in the active group were higher than those in the stable group,and the differences were statistically significant(t=5.449,11.112,all P<0.05).The IgG glycosylation characteristics of galactosylation,sialylation and N-acetylglucosamine modification were lower than those in the stable group,and the differences were statistical significance(Z=-2.432～-0.158,all P<0.05).Spearman correlation analysis showed that the proportion of CD14+CD16+monocytes was significantly negatively correlated with IgG galactosylation,sialylation level and bisection N-acetylglucosamine modification(r=-0.656,-0.531,-0.608,all P<0.01).CD14+CD16+monocyte ratio was positively correlated with SLE-DIA(r=0.581,all P<0.01).IgG galactosylation,sialylation levels and bisection N-acetylglucosamine modification were negatively correlated with SLE-DIA(r=-0.645,-0.609,-0.503,all P<0.01).Logistic regression analysis showed that CRP>8.21mg/L,CD14+CD16+≥16.17%,sialylation<22.05%and isotropic N-acetylglucosamine modification<16.53%were independent risk factors for disease activity in SLE patients(Wald χ2=4.471～12.811,all P<0.05).The VIF values of the above independent variables were all less than 10.By establishing the Logistic regression prediction model and drawing the ROC curve,the AUC value for diagnosing SLE disease activity was 0.821(95%CI:0.733～0.905),the sensitivity,specificity and the Yodon index were 85.37%,75.67%,0.677,respectively.and the P values of Hosmer-Lemeshow goodness-of-fit test models were 0.568,respectively.Conclusion The proportion of CD14+CD16+monocytes in peripheral blood of SLE patients increase significantly,and the level of IgG glycosylation characteristics decrease,both of which are correlated with SLE-DIA.The predictive model constructed based on the two had a good ability to distinguish SLE-DIA from inactive state,with high sensitivity and moderate specificity conducive to early clinical recognition,and the model fitting effect is good.SLE-DIA can be evaluated more accurately.

Objective To evaluate the application value of stereotactic robotic surgery driven by a multi scenario AI system in the elderly with severe hypoperfusion in the internal capsule area and minor HTH.Methods A retrospective analysis was conducted on 101 minor HTH patients com-plicated with severe hypoperfusion in the internal capsule area identified by an AI diagnostic sys-tem in our department from January to October 2024.Among them,48 cases who underwent ster-eotactic robotic drainage with AI system support were assigned into the study group,and 53 cases of conventional drug treatment were into the control group.The general clinical data were com-pared between the two group.Improvement rate of rCBF 14 d after treatment,effective rate 90 d after treatment,favorable prognosis rate,and incidence of shunt dependent hydrocephalus were compared between the two groups to evaluate the application value of AI-assisted stereotactic ro-botic surgery in these patients.Results The study group had significantly higher improvement rate of rCBF 14 d after treatment,better effective rate and larger ratio of favorable prognosis 90 d after treatment when compared with the control group(60.4％vs 39.6％,P＜0.05;62.5％vs 41.5％,P＜0.05;64.6％vs 43.4％,P＜0.05).Conclusion Stereotactic robotic assisted drainage driven by multi scenario AI system can significantly improve the prognosis of the elderly minor HTH patients complicated with severe hypoperfusion in the internal capsule area.

Objective To evaluate the application value of stereotactic robotic surgery driven by a multi scenario AI system in the elderly with severe hypoperfusion in the internal capsule area and minor HTH.Methods A retrospective analysis was conducted on 101 minor HTH patients com-plicated with severe hypoperfusion in the internal capsule area identified by an AI diagnostic sys-tem in our department from January to October 2024.Among them,48 cases who underwent ster-eotactic robotic drainage with AI system support were assigned into the study group,and 53 cases of conventional drug treatment were into the control group.The general clinical data were com-pared between the two group.Improvement rate of rCBF 14 d after treatment,effective rate 90 d after treatment,favorable prognosis rate,and incidence of shunt dependent hydrocephalus were compared between the two groups to evaluate the application value of AI-assisted stereotactic ro-botic surgery in these patients.Results The study group had significantly higher improvement rate of rCBF 14 d after treatment,better effective rate and larger ratio of favorable prognosis 90 d after treatment when compared with the control group(60.4％vs 39.6％,P＜0.05;62.5％vs 41.5％,P＜0.05;64.6％vs 43.4％,P＜0.05).Conclusion Stereotactic robotic assisted drainage driven by multi scenario AI system can significantly improve the prognosis of the elderly minor HTH patients complicated with severe hypoperfusion in the internal capsule area.

Objective:To evaluate the effect of ultrasound-guided high ankle block (HAB) on the quality of postoperative recovery of patients undergoing foot and ankle surgery.Methods:In this randomized controlled trial, 90 patients of either sex, aged 18-64 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, scheduled for elective foot and ankle surgery, were divided into 2 groups ( n=45 each) using a random number table method: HAB group and spinal anesthesia group (SA group). Patients underwent ultrasound-guided HAB on the affected side in HAB group, while patients received spinal anesthesia in SA group. The Quality of Recovery-15 (QoR-15) scores were recorded at 24 and 48 h postoperatively. Additional data collected included anesthesia preparation and operation time, sensory and motor grading after anesthesia, anesthetic effect grading, surgery duration, intraoperative tourniquet time, block duration, time to first ambulation, and postoperative length of hospital stay. The time of first rescue analgesia and requirement for rescue algesia within 48 h postoperatively and the occurrence of adverse reactions such as hypotension, headache, nausea and vomiting, and urinary retention after anesthesia were also recorded. Results:Compared to SA group, QoR-15 scores and motor grading after anesthesia were significantly increased, the time to first ambulation and postoperative length of hospital stay were shortened, the duration of block and anesthesia preparation and operation time were prolonged at 24 h postoperatively, the rate of rescue analgesia wthin 48 h after operation and incidence of adverse reactions after anesthesia were decressed, and the time to first rescue analgesia was pronlonged in HAB group ( P<0.05). There were no significant differences between the two groups in sensory grading after anesthesia, anesthetic effect grading, intraoperative use of tourniquet time, and QoR-15 scores at 48 h postoperatively ( P>0.05). Conclusions:Ultrasound-guided HAB provides better quality of postoperative recovery than spinal anesthesia for the patients undergoing foot and ankle surgery.

Objective:To evaluate the effect of ultrasound-guided high ankle block (HAB) on the quality of postoperative recovery of patients undergoing foot and ankle surgery.Methods:In this randomized controlled trial, 90 patients of either sex, aged 18-64 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, scheduled for elective foot and ankle surgery, were divided into 2 groups ( n=45 each) using a random number table method: HAB group and spinal anesthesia group (SA group). Patients underwent ultrasound-guided HAB on the affected side in HAB group, while patients received spinal anesthesia in SA group. The Quality of Recovery-15 (QoR-15) scores were recorded at 24 and 48 h postoperatively. Additional data collected included anesthesia preparation and operation time, sensory and motor grading after anesthesia, anesthetic effect grading, surgery duration, intraoperative tourniquet time, block duration, time to first ambulation, and postoperative length of hospital stay. The time of first rescue analgesia and requirement for rescue algesia within 48 h postoperatively and the occurrence of adverse reactions such as hypotension, headache, nausea and vomiting, and urinary retention after anesthesia were also recorded. Results:Compared to SA group, QoR-15 scores and motor grading after anesthesia were significantly increased, the time to first ambulation and postoperative length of hospital stay were shortened, the duration of block and anesthesia preparation and operation time were prolonged at 24 h postoperatively, the rate of rescue analgesia wthin 48 h after operation and incidence of adverse reactions after anesthesia were decressed, and the time to first rescue analgesia was pronlonged in HAB group ( P<0.05). There were no significant differences between the two groups in sensory grading after anesthesia, anesthetic effect grading, intraoperative use of tourniquet time, and QoR-15 scores at 48 h postoperatively ( P>0.05). Conclusions:Ultrasound-guided HAB provides better quality of postoperative recovery than spinal anesthesia for the patients undergoing foot and ankle surgery.

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 develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

Objective To explore the anatomical landmarks and segmentation method for the intraoperative identification of the cervical segment of the internal carotid artery by studying cadaveric dissections with an endoscopic transoral medial pterygomandibular fold approach and to investigate its clinical significance.Methods The head specimens of five fresh frozen cadavers were dissected in the anatomical laboratory of the Surgical Treatment Technology Innovation Unit of Nasal Skull Base Tumor in Eye&ENT Hospital of Fudan University.The parapharyngeal space was dissected layer by layer through the endoscopic transoral medial pterygomandibular fold approach,and the location marks of parapharyngeal internal carotid artery(ppICA)and adjacent structures of ppICA were anatomically studied.The anatomical landmarks associated with ppICA were observed and characterized,and the ppICA was segmented anatomically according to its adjacent structures.Then,the length of each ppICA segment was measured.Results Muscle structures were essential anatomical landmarks for an endoscopic transoral pterygoid medial approach that identifies mandibular folds.The first layer of muscles included the superior pharyngeal constrictor,tensor veli palatini,and medial pterygoid muscles.The second layer includes the stylopharyngeus,styloglossus,longus capitis,and levator veli palatini muscles.The stylopharyngeal and levator veli palatini muscles were close to the ppICA and were reliable landmarks for locating the ppICA.Furthermore,the ppICA was divided into three segments according to their positional relationship with the ppICA.The first segment of ppICA(P1 ICA)was located between the greater horn plane of the hyoid bone and the intersection plane between the upper margin of stylopharyngeal muscle and ppICA.The second segment of ppICA(P2 ICA)was between the plane where the upper edge of the stylopharyngeal muscle intersected with the ppICA and the plane where the projection of inferior edge of the levator veli palatini muscle intersected with the ppICA.The third segment of ppICA(P3 ICA)was between the intersection of the lower margin projection of the levator veli palatini muscle and ppICA and the external orifice of the carotid canal.The P2 ICA was within an anatomical region bounded by the levator veli palatini muscle,longus capitis muscle,and stylopharyngeus muscle.This region was termed"ICA window"in this paper measured under the cadaver head specimen,the lengths of P1 ICA,P2 ICA,and P3 ICA were(36.5±7.3)mm,(15.5±1.6)mm,(7.4±1.7)mm respectively.Conclusion The muscular structure refers to the relatively constant anatomical reference landmarks within the endoscopic transoral medial pterygomandibular fold.The stylopharyngeus and levator veli palatini muscles are reliable landmarks for precisely locating and segmenting the ppICA,thus having essential clinical implications.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*