Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought to play a role in such cases. Despite being a long-debated issue in the field of DRE, the mechanisms underlying neuroinflammation have yet to be fully elucidated. The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes, such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis. The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems. We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application. We hope to provide an insightful overview to advance the quest for better DRE treatments.
Humans ; Drug Resistant Epilepsy/metabolism* ; Neuroinflammatory Diseases/immunology* ; Animals ; Brain/pathology* ; Nerve Net/pathology*

Objective To compare the long-term prognosis differences between surgical radical resection and endoscopic resection for early gastric cancer patients based on the SEER database. Methods A total of 1 437 patients with stage Tis to T_1b gastric adenocarcinoma were selected from the SEER database from January 1, 2004 to December 31, 2013. They were divided into a surgery group (n=1 257) and an endoscope group (n=180) according to the treatment method. Kaplan-Meier survival curve and Cox regression model were used to analyze survival outcomes. Results The patients in the surgery group were younger than those in the endoscope group ([67.63±12.97] years old vs [71.29±10.82] years old), with higher rates of T₁ stage (97.45% vs 87.78%) and lymph node metastasis (19.73% vs 5.00%, all P＜0.001). The median follow-up time for all patients was 37 (15, 66) months, and the mortality rate of gastric cancer in the endoscope group was lower than that in the surgery group (23.33% vs 27.13%, P＜0.001). Univariate Cox analysis showed that treatment modality, age, sex, T stage, lymph node metastasis were all associated with early gastric cancer mortality (all P＜0.05), and the risk of death in the endoscope group was 43% of that in the surgery group (HR=0.43, P=0.015). After adjusting for multiple factors, there was no statistically significant difference in mortality risk between the two groups (P=0.067), but after excluding lymph node positive patients, the mortality risk in the endoscope group was 46% of that in the surgery group (HR=0.46, P=0.048). Conclusions For early gastric cancer patients with negative lymph nodes, endoscopic resection may provide better survival benefits than surgical procedures, suggesting that it can be the preferred treatment strategy for patients with low risk of lymph node metastasis.

Objective To explore the optimization strategy of Qishen Granules in treating coronary heart disease with heart failure(CHD-HF)based on data mining and the pathogenic"toxin"theory,and to predict its active components and mechanisms using network pharmacology.Methods Literature on traditional Chinese medicine(TCM)for treating CHD-HF was collected from relevant databases,and prescriptions were screened and established into a database according to inclusion and exclusion criteria.Frequency,association rules,and hierarchical clustering analyses were performed using the Ancient and Modern Medical Case Cloud Platform.Network pharmacology techniques were applied to screen potential targets of the optimized combination for treating CHD-HF,and carry out the targets and pathways enrichment analysis.Results A total of 336 articles and 339 prescriptions involving 191 herbs were included,with 12 herbs used more than 100 times.The core drug combinations for treating CHD-HF included Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,etc,while commonly used detoxifying herbs included Leonuri Herb,Coptidis Rhizoma,etc.Association rule analysis yielded 10 two-item associations and 17 three-item associations;clustering analysis grouped the data into 5 categories.Based on data mining and the pathogenic"toxin"theory,the combination for treating CHD-HF was optimized to include Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Aconiti Lateralis Radix Praeparata,Glycyrrhizae Radix et Rhizoma,Coptidis Rhizoma,and Taraxaci Herba.Network pharmacology analysis identified 366 common targets between the optimized combination and CHD-HF,with 16 core targets screened out.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed significant enrichment in pathways such as cancer pathways,lipid and atherosclerosis,Rap1 signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway,Ras signaling pathway,and mitogen-activated protein kinase(MAPK)signaling pathway.Conclusion TCM treatment for CHD-HF primarily focuses on replenishing qi and warming yang,activating blood circulation and resolving fluid retention.Based on data mining results and the pathogenic"toxin"theory,the formulation strategy of Qishen Granules for treating CHD-HF was optimized,potentially exerting therapeutic effects through anti-inflammatory,anti-apoptotic,and anti-hypoxia physiological processes.

Objective To discuss the causes and the therapeutic strategy of acute cardiac tamponade(ACT)occurring as a complication of transcatheter aortic valve replacement(TAVR)so as to improve the success rate of the surgery and to make a further understanding of this complication.Methods The general clinical data,surgical procedures,and postoperative follow-up results of five patients,who received TAVR at the Affiliated Northern Jiangsu People's Hospital of Yangzhou University of China and developed ACT from March 2018 to September 2024,were retrospectively analyzed.Results After developing ACT,all the 5 patients received pericardiocentesis together with other adjuvant therapies including blood volume expansion with infusion,vasopressors,heparin neutralization,and blood transfusion.However,due to no obvious reduction in drainage volume and unstable hemodynamics all the 5 patients had eventually to receive open-chest surgery to identify the source of bleeding and to make hemostasis.Surgical exploration revealed that the perforation or rupture of cardiac structures caused by the temporary pacemaker lead or a super-stiff guide wire during the procedure was the main cause of ACT.Finally,after active treatment four patients recovered and discharged,and one patient died.The discharged patients were followed up for 3-12 months,and no procedure-related complications such as acute coronary artery occlusion,severe arrhythmia,exacerbation of heart failure symptoms,valve displacement,or stroke occurred.Conclusion As a severe complication occurring during the TAVR procedure,ACT requires to get a rapid diagnosis and management.Improvement of surgical techniques and operative methods,comprehensive preoperative assessment,and close intraoperative monitoring are crucial points for the prevention of ACT.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:To explore the application value of histogram and texture feature analysis based on CT images in distinguishing long bone osteosarcoma (OS) from Ewing sarcoma (ES).Methods:A retrospective collection of 25 patients with long bone osteosarcoma and 25 patients with Ewing sarcoma confirmed by surgery and pathology in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Qilu Hospital of Shandong University and Nanjing Drum Tower Hospital, Nanjing University Medical School, from March 2018 to May 2023 was conducted. All patients were randomly divided into a training set (21 cases of OS and 19 cases of ES) and a validation set (4 cases of OS and 6 cases of ES) in an 8∶2 ratio. The region of interest (ROI) on CT images to extract texture feature parameters was manually sketched. Random forest and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature screening. Logistic regression (LR), random forest (RF), support vector machine (SVM) and K-nearest neighbor (KNN) classifiers were used to establish models respectively. Receiver operating characteristic (ROC)curve was drawn and area under the curve (AUC) was calculated to evaluate the diagnostic efficiency of the four models.Results:A total of 100 texture parameters were extracted from CT images, and 8 feature parameters (maximum 3D diameter, 10th percentile, kurtosis, maximum pixel intensity value, inverse normalization, grayscale level variance, long range high grayscale emphasis, and low grayscale area emphasis) were obtained through screening. Four classifiers were used to establish models, and the AUC values of the four models (LR, RF, SVM, KNN) in the validation group were 0.92, 0.79, 0.83, and 0.73, respectively. LR and SVM classifier algorithm trains models had high diagnostic efficiency, with an accuracy of 90%, sensitivity of 83%, specificity of 100%, and AUC of 92% for the LR classifier validation set; the accuracy of SVM classifier validation set was 80%, sensitivity was 67%, specificity was 100%, and AUC was 83%.Conclusions:LR and SVM models have high value in distinguishing OS and ES.

OBJECTIVE: To evaluate the surgical methods for treating distal urethral stricture. METHODS: The clinical data of 80 patients with distal urethral stricture in Beijing Jishuitan Hospital, Captial Medical University between January 2018 and December 2022 were retrospectively collected. Including male genital lichen sclerosus (MGLS) 33 cases, iatrogenic injury 25 cases, postoperative hypospadias 12 cases, and other causes such as trauma 10 cases. Among these cases, strictures involved the urethral meatus in 54 instances, of which 38 were treated with meatotomy (MO), 7 with penile skin flap urethroplasty (PSFU), and 9 with oral mucosa graft urethroplasty (OMGU). There were also 26 instances where strictures involved both the navicular fossa and meatus; one case underwent PSFU while 25 underwent OMGU. Based on different surgical methods used for treatment purposes we divided the patients into MO group, PSFU group and OMGU group. The age of the three groups was (48.8±20.0) years, (53.3±21.8) years and (44.5±16.4) years. The mean±SD body mass index (BMI) was (28.6±3.9) kg/m², (29.6±3.2) kg/m² and (29.2±4.8) kg/m². The preoperative maximum flow rate was (5.8±2.3) mL/s, (6.8±2.4) mL/s and (5.7±3.1) mL/s. RESULTS: All the operations were successfully completed without Clavien Ⅲ or Ⅳ complications. The median length of strictures (measured intraoperatively) in the three groups were 1.1 (1.0, 1.6), 1.5 (1.1, 2.0) and 4.0 (2.5, 5.0) cm. The median operation time was 60.0 (60.0, 75.0), 85.0 (75.0, 112.5) and 180.0 (75.0, 330.0) min. The median estimated blood loss was 5.0 (2.0, 10.0), 15.0 (5.0, 42.5) and 180.0 (135.0, 216.3) mL. The median postoperative hospital stay was 3.5 (2.0, 5.0), 6.5 (3.5, 7.0) and 7.5 (7.0, 11.3) days. The median follow-up duration was 40.0 (26.3, 57.3), 55.0 (18.8, 62.8) and 52.5 (30.5, 64.0) months. The median postoperative maximum flow rate was 18.3 (15.5, 19.8), 19.2 (16.1, 20.1) and 17.2 (14.2, 19.6) mL/s. Among the 38 patients with MO, 33 cases had normal urination without reintervention, and 5 cases experienced recurrent strictures and required regular urethral dilation. Among the 8 patients with PSFU, 7 cases had normal urination without reintervention, and one case developed a urinary fistula, for which intervention was recommended but the patient opted to maintain the status quo. Among the 34 patients with OMGU, 28 cases had normal urination without reintervention. There were 6 instances of stenosis recurrence, with 5 cases requiring regular urethral dilations and one case requiring reconstructive surgery. The overall success rate of operation was 85.0%, and the reintervention rate was 15.0%. Statistical analysis revealed significant differences in etiologies among the three groups (P=0.002), as well as in stricture locations (P < 0.001), length of strictures (P < 0.001), operation time (P < 0.001), estimated blood loss (P < 0.001) and postoperative hospital stays (P < 0.001). However, no significant differences were observed in terms of age, BMI, history of previous urethral stricture surgeries, preoperative maximum flow rate, follow-up duration, postoperative maximum flow rate and reintervention rate. Univariate and multivariate Logistic regression analyses indicated that a history of previous urethral stricture surgeries was a risk factor for postoperative reintervention (P=0.026). CONCLUSION MO and PSFU are primarily suitable for treating short-segment (≤1.5 cm) distal penile urethral strictures, whereas OMGU is more appropriate for longer segment strictures. MO and OMGU can both be utilized in managing MGLS cases. PSFU and OMGU are more conducive to improving the appearance of the urethral meatus. The success rate of surgical management of distal penile urethral stricture is 85.0%, 15.0% of the patients still require surgical intervention after surgery, and having history of previous urethral stricture surgeries is a risk factor for postoperative reintervention.
Humans ; Urethral Stricture/surgery* ; Male ; Retrospective Studies ; Middle Aged ; Adult ; Urethra/surgery* ; Surgical Flaps ; Penis/surgery* ; Mouth Mucosa ; Urologic Surgical Procedures, Male/methods* ; Plastic Surgery Procedures/methods* ; Lichen Sclerosus et Atrophicus/surgery* ; Operative Time ; Skin Transplantation/methods* ; Aged

To preliminarily understand the pathogenic mechanism of Mycoplasma genitalium (Mg) GroEL protein, we used bioinformatics tools to predict the structure and function of Mg GroEL protein and then constructed the recombinant plasmid pET-28a-GroEL. The protein expression was induced by 0.2 mmol/L IPTG, and the expressed protein was purified by Ni-iminodicitic acid (IDA) column affinity. Tohoku Hospital Pediatrics-1 (THP-1) cells were exposed to 2 μg/mL Mg rGroEL. The levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the cell supernatant were measured by ELISA, and that of IL-6 was measured by an automatic chemiluminescence instrument. The activation of the nuclear factor-kappa B (NF-κB) signaling pathway was visualized by immunofluorescence and Western blotting. The results showed that Mg GroEL was a stable hydrophilic protein composed of 543 amino acid residues, with the relative molecular mass of 58.44 kDa, an isoelectric point of 5.68, and a molecular formula of C₂₅₆₈H₄₃₀₀N₇₀₀O₈₂₅S₈. The secondary structure was mainly composed of α-helices and random coils. Mg GroEL contained 12 B-cell dominant epitopes and 10 T-cell dominant epitopes. It exhibited high homology with the GroEL proteins from Mycoplasma pneumoniae, M. agalactiae, M. arthritidis, M. hyopneumoniae, and M. bovis. Mg rGroEL activated the NF-κB signaling pathway and promoted the secretion of IL-1β, IL-6, and TNF-α in THP-1 cells. These results suggest that Mg GroEL exhibits substantial antigenicity and possesses the capability of triggering inflammation in host cells. This study establishes a theoretical basis for future investigations pertaining to the role and pathogenic mechanisms of Mg GroEL.
Mycoplasma genitalium/metabolism* ; Chaperonin 60/metabolism* ; Computational Biology ; Bacterial Proteins/genetics* ; Humans ; NF-kappa B/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-1beta/genetics* ; Inflammation ; Interleukin-6/genetics* ; Recombinant Proteins/genetics* ; THP-1 Cells ; Signal Transduction ; Escherichia coli/metabolism*