Objective: To investigate the correlation among α2, 6-sialyltransferase (ST6Gal-Ⅰ), CD36 desialylation, and caveolin-1 (Cav-1) in phorbol ester (PMA)-induced MEG-01 cell model, as well as their potential mechanism in immune thrombocytopenia (ITP). Methods: MEG-01 cells were treated with 10 ng/mL PMA for 48 hours (control group: 0.1% DMSO). Flow cytometry was used to detect cell surface markers: desialylation (CD41 RCA ) and α2, 6-sialylation (CD41 SNA ). Western blot was performed to analyze the protein expressions of ST6Gal-Ⅰ, CD36, and Cav-1. Results: Flow cytometry analysis revealed that, compared with the control group (set as 100%), the proportion of CD41 RCA positive cells in the MEG-01 cells after PMA intervention significantly increased to (127.79±2.01)%, while the proportion of CD41 SNA positive cells significantly decreased to (78.09±1.76)% (both P<0.05). Western blot analysis results showed that, compared with the control group, PMA intervention significantly downregulated the expression of ST6Gal-Ⅰ protein (0.602±0.023 vs 0.768±0.068) and Cav-1 protein (1.012±0.028 vs 1.253±0.068) (both P<0.05), while significantly upregulating the expression of CD36 protein (0.936±0.033 vs 0.694±0.070, P<0.05). Conclusion: PMA can significantly inhibit the expression of ST6Gal-Ⅰ, accompanied by increased desialylation (β-galactose exposure), elevated CD36, and downregulated Cav-1. These changes suggest that the increased exposure of CD36 antigen and the disorder of membrane microenvironment may be involved in the pathological process of ITP, providing a new direction for mechanism research.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective To explore the diagnostic value of non-contrast chest CT in acute pulmonary thromboembolism(APTE).Methods A total of 187 patients with suspected APTE who underwent non-contrast chest CT and computed tomography pulmonary angiography(CTPA)within 2 h were included.Among 187 patients,there were 89 patients with APTE(APTE group)and 98 patients without APTE(control group).The clinical characteristics and chest CT features between the APTE group and the control group were compared.The sensitivity and specificity of non-contrast chest CT findings in the diagnosis of central APTE and peripheral APTE were analyzed.Results Chest CT showed pulmonary artery hyperdensity sign in 35 cases in the APTE group and none in the control group,with the difference was statistically significant(χ2=47.414,P<0.001);Subpleural shadow appeared in 33 cases in the APTE group and 11 cases in the control group,with the difference was statistically significant(χ2=17.327,P<0.001).The sensitivity and specificity of pulmonary artery hyperdensity sign in the diagnosis of central APTE and peripheral APTE were 72.92%,100%and 0%,100%,respectively.The sensitivity and specificity of sub-pleural shadow in the diagnosis of central APTE and peripheral APTE were 39.58%,88.78%and 34.15%,88.78%,respectively.The difference was not statistically significant in pleural effusion,pulmonary artery diameter,or pulmonary artery diameter to aorta diameter ratio between the two groups.Conclusion The pulmonary artery hyperdensity sign on non-contrast chest CT is a useful sign of APTE,which can avoid CTPA examination.

Objective:To elucidate the prognostic differences and risk factors associated with different patterns of recurrence and metastasis following pancreatic cancer (PC) resection.Methods:This is a retrospective case series study. Clinicopathological data and follow-up information were retrospectively collected from 210 patients who underwent surgery for PC at the Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, between January 2014 and December 2023. There were 114 males and 96 females; the age was (64.5±10.3) years (range: 29 to 89 years). Survival functions based on different times to recurrence and metastasis and different patterns of recurrence and metastasis were estimated using the Kaplan-Meier method, and survival differences among groups were compared using the Log-rank test. Identifying the optimal cutoff for time to postoperative recurrence/metastasis predicting overall survival (OS) in pancreatic cancer patients via the minimum p-value approach. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS following pancreatectomy.Results:A total of 210 patients met the inclusion and exclusion criteria. Among them, 71 patients remained free of recurrence and metastasis, while 139 developed recurrence and metastasis. The patterns included local recurrence ( n=34), liver metastasis ( n=39), lung metastasis ( n=11), peritoneal metastasis ( n=13), multiple sites metastasis ( n=38), bone metastasis ( n=3), and kidney metastasis ( n=1). OS was significantly shorter in the group with postoperative recurrence and metastasis compared to the group without recurrence/metastasis (23.07 months vs.not reached, P<0.01). The optimal cut-off time distinguishing early from late recurrence and metastasis was 13 months. There was a significant difference in post-recurrence survival between patients with early and late recurrence and metastasis (16.03 months vs. 52.40 months, P=0.009). The Kaplan-Meier survival curve showed that different postoperative recurrence and metastasis patterns had different impacts on OS, with lung metastasis showing the best prognosis compared to local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastasis ( P<0.01). Multivariate Cox analysis revealed that Eastern Cooperative Oncology Group (ECOG) score 1, postoperative carcinoembryonic antigen (CEA) ≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for postoperative recurrence and metastasis (all P<0.05). Conclusions:Considerable prognostic heterogeneity exists in postoperative PC patients depending on the site and pattern of recurrence or metastasis. Specifically, lung metastasis portends a significantly more favorable prognosis than liver metastasis, peritoneal metastasis, local recurrence, or multiple sites metastases. ECOG score 1, postoperative CEA≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for OS in postoperative PC patients.

Objective To investigate the relationship between between the levels of serum malondialdehyde(MDA)and superoxide dismutase(SOD),the balance of oxidative/antioxidant stress,and the prognostic nu-tritional index(PNI)and the risk of early neurological deterioration in patients with acute ischemic stroke(AIS).Methods A total of 95 patients with suspected AIS admitted to the Second People's Hospital of Fos-han,Foshan from January to April 2023 were selected as the research subjects.Among them,71 patients who were finally diagnosed with AIS were included in the stroke group,and the remaining 24 non-AIS patients were included in the control group.According to the National Institutes of Health Stroke Rating Scale(NIH-SS)score,the stroke group was divided into the moderate-severe stroke group and the mild stroke group.Ac-cording to whether early neurological deterioration(END)occurred,it was divided into the END group and the non-END group.To analyze the correlations between the levels of serum SOD and MDA,SOD/MDA,and the PNI and the severity of stroke.The receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of each index for the risk of END.By fitting the indicators with high diagnostic efficacy,a Fisher discriminant function model for evaluating the risk of END was established to verify the overall accura-cy rate.Results The levels of serum MDA and SOD,SOD/MDA and the PNI in the moderate to severe stroke group were statistically different from those in the mild stroke group(P＜0.05).There were statistically sig-nificant differences in the levels of serum MDA and SOD,SOD/MDA and the PNI among the END group,the non-END group and the control group(P＜0.05).The areas under the curve(AUC)of SOD,MDA,SOD/MDA and PNI for evaluating END were 0.692,0.727,0.777 and 0.819,respectively.The Fisher discriminant function model established by fitting the NIHSS score,the SOD/MDA and the PNI has an overall accuracy rate of 85.9％.Conclusion The END risk prediction model established by applying the Fisher discriminant function can provide early and objective reference basis for clinical prediction of END risk and has certain practical value.

[Objective]To evaluate the feasibility of animal model of simulated adenoid hypertrophy by combining animal model of allergic rhinitis and chronic pharyngitis from the perspective of predictive validity.[Methods]Forty SD rats were randomly divided into blank group,model control group,montelukast group and traditional Chinese medicine(TCM)group,with 10 rats in each group.The model control group,montelukast group and TCM group all established rat model of allergic rhinitis and the rat model of chronic pharyngitis was also established in the same time,which combined the simulated adenoid hypertrophy rat model,while the blank group was replaced the equivalent amount of 0.9%sodium chloride solution.After molding,the montelukast group was gavaged with montelukast sodium particles,the TCM group was gavaged with Yunpi Huatan Tongqiao Decoction,model control group and blank group received equal amount of 0.9%sodium chloride solution,the course of treatment would all be 8 weeks.After molding and after the course of treatment,the symptom performance of model animals was assessed by animal behavioral score and the eosinophil percentage(EOS%),interleukin-4(IL-4),immunoglobulin E(IgE)and hypoxia-inducible factor-1α(HIF-1α)levels in blood serum and nasopharyngeal mucosal tissues were tested,and the pathomorphological changes of nasal and pharyngeal mucosa were observed by hematoxylin-eosin(HE)staining.[Results]After molding,the levels of animal behavioral score,EOS%,serum and tissue IL-4,IgE,and HIF-1α level in model control group,montelukast group and TCM group were significantly upregulated compared with blank group(P<0.01),and the nasal and pharyngeal mucosa showed different degrees of disease-related histopathological changes.After treatment,the levels of each index in montelukast group and TCM group were lower compared with that before treatment,and were also lower than that in model control group,all differences were statistically significant(P<0.05,P<0.01),and the histopathological damage was relieved than before the treatment.[Conclusion]The simulated rat model is similar to adenoid hypertrophy in terms of symptom manifestations and pathological changes,and effective drugs used clinically have similar efficacy in simulated rat models.In terms of predictive validity,the animal model of simulated adenoid hypertrophy can be made by combining animal model of allergic rhinitis and chronic pharyngitis,but it still needs further exploration and improvement.