Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

The incidence rate of thyroid cancer has been rising in recent years. How to accurately distinguish malignant and benign thyroid nodules before surgery has become an important research direction. Ultrasound, as a non-invasive and fast examination method, has been widely used in clinical practice. Some typical ultrasound features, such as calcification, unclear boundaries, multiple lesions, low echo, and aspect ratio>1, can indicate the occurrence of thyroid cancer before surgery. Further analysis of these ultrasound features is still a focus of current research. This article will review the expression and distribution of calcification, a typical ultrasound feature, in benign and malignant thyroid nodules, in order to provide a basis for predicting the malignancy of thyroid nodules based on the characteristics of calcification under preoperative ultrasound.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective:To assess the clinical value of global RNA N6-methyladenosine (m 6A) and perilipin 2 (PLIN2) mRNA site-specific (chr9:19116312) m 6A modification in peripheral blood as novel molecular biomarkers of coronary artery disease (CAD). Methods:Seventy-four patients with coronary artery disease diagnosed at the Eastern Theater General Hospital from June to December 2023, and 60 age-and sex-matched healthy controls during the same period were selected for a retrospective case-control study. The global RNA m 6A modification level in peripheral blood was detected by RNA methylation quantitative detection kit as a preliminary validation, and PLIN2 site-specific (chr9:19116312) m 6A modification level was further detected using the qPCR quantification technique with single-base elongation and ligation as a rescreening validation. Lipid indicators such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), routine blood indicators such as neutrophil count and platelet count were detected, and the coronary lesion characteristics were further evaluated by using the Gensini score and SYNTAX score systems in conjunction with coronary arteriography results.The CAD group was divided into a single-branch (25 cases) and a multi-branch lesion subgroup (49 cases) according to the number of vascular lesion branches on coronary angiography. The potential value of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood of patients for the adjunctive diagnosis and assessment of coronary artery disease was explored using Spearman correlation analysis, subject operating characteristic (ROC) curves, and logistic regression analysis. Results:Compared with the control group, the levels of global RNA m 6A modification and PLIN2 site-specific (chr9∶19116312) m 6A modification in peripheral blood were significantly decreased in the CAD group (both P<0.05). The levels of global RNA m 6A modification in peripheral blood was also significantly decreased in the single-branch and multi-branch lesion subgroups ( P<0.05), and PLIN2 site-specific (chr9:19116312) m 6A modification in peripheral blood was significantly decreased in the multi-branch lesion subgroup only ( P<0.05). Spearman correlation analysis showed that in both the CAD group and the multi-branch lesion subgroup, global RNA m 6A modification level in peripheral blood was positively correlated with HDL-C ( r=0.246, 0.289, P<0.05) and negatively correlated with SYNTAX score ( r=-0.261, -0.322, P<0.05) and neutrophil count ( r=-0.246, -0.466, P<0.05). In the single-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with Gensini score ( r=-0.566, P<0.05). In the multi-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with platelet count ( r=-0.313, P<0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood for distinguishing CAD and coronary artery multi-branch lesions were 0.915 and 0.918, with specificity of 83.3% and 95.0%, and sensitivity of 85.1% and 75.5%, respectively. The multivariate logistic regression analysis showed that after adjusting confounding factors such as age, sex, proportion of diabetes and hypertension, and TC, the levels of global RNA m 6A modification ( OR=0.691, P<0.001; OR=0.694, P<0.01), and PLIN2 site-specific (chr9:19116312) m 6A modification levels ( OR=0.345, P<0.05; OR=0.143, P<0.01) in peripheral blood remained independently associated with CAD and coronary artery multi-branch lesions, respectively. Conclusions:The analysis of global RNA m 6A in combination with PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood is valuable for the adjunctive diagnosis and assessment of patients with CAD and coronary artery multi-branch lesions.

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.

Objective:To assess the clinical value of global RNA N6-methyladenosine (m 6A) and perilipin 2 (PLIN2) mRNA site-specific (chr9:19116312) m 6A modification in peripheral blood as novel molecular biomarkers of coronary artery disease (CAD). Methods:Seventy-four patients with coronary artery disease diagnosed at the Eastern Theater General Hospital from June to December 2023, and 60 age-and sex-matched healthy controls during the same period were selected for a retrospective case-control study. The global RNA m 6A modification level in peripheral blood was detected by RNA methylation quantitative detection kit as a preliminary validation, and PLIN2 site-specific (chr9:19116312) m 6A modification level was further detected using the qPCR quantification technique with single-base elongation and ligation as a rescreening validation. Lipid indicators such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), routine blood indicators such as neutrophil count and platelet count were detected, and the coronary lesion characteristics were further evaluated by using the Gensini score and SYNTAX score systems in conjunction with coronary arteriography results.The CAD group was divided into a single-branch (25 cases) and a multi-branch lesion subgroup (49 cases) according to the number of vascular lesion branches on coronary angiography. The potential value of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood of patients for the adjunctive diagnosis and assessment of coronary artery disease was explored using Spearman correlation analysis, subject operating characteristic (ROC) curves, and logistic regression analysis. Results:Compared with the control group, the levels of global RNA m 6A modification and PLIN2 site-specific (chr9∶19116312) m 6A modification in peripheral blood were significantly decreased in the CAD group (both P<0.05). The levels of global RNA m 6A modification in peripheral blood was also significantly decreased in the single-branch and multi-branch lesion subgroups ( P<0.05), and PLIN2 site-specific (chr9:19116312) m 6A modification in peripheral blood was significantly decreased in the multi-branch lesion subgroup only ( P<0.05). Spearman correlation analysis showed that in both the CAD group and the multi-branch lesion subgroup, global RNA m 6A modification level in peripheral blood was positively correlated with HDL-C ( r=0.246, 0.289, P<0.05) and negatively correlated with SYNTAX score ( r=-0.261, -0.322, P<0.05) and neutrophil count ( r=-0.246, -0.466, P<0.05). In the single-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with Gensini score ( r=-0.566, P<0.05). In the multi-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with platelet count ( r=-0.313, P<0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood for distinguishing CAD and coronary artery multi-branch lesions were 0.915 and 0.918, with specificity of 83.3% and 95.0%, and sensitivity of 85.1% and 75.5%, respectively. The multivariate logistic regression analysis showed that after adjusting confounding factors such as age, sex, proportion of diabetes and hypertension, and TC, the levels of global RNA m 6A modification ( OR=0.691, P<0.001; OR=0.694, P<0.01), and PLIN2 site-specific (chr9:19116312) m 6A modification levels ( OR=0.345, P<0.05; OR=0.143, P<0.01) in peripheral blood remained independently associated with CAD and coronary artery multi-branch lesions, respectively. Conclusions:The analysis of global RNA m 6A in combination with PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood is valuable for the adjunctive diagnosis and assessment of patients with CAD and coronary artery multi-branch lesions.

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.