Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

Objectives:To preliminarily investigate the safety and efficacy of same-day discharge(SDD)following radiofrequency catheter ablation for arrhythmia.Methods:A total of 50 consecutive patients who underwent radiofrequency catheter ablation for arrhythmia in the SDD strategy at Fuwai Hospital from 8 July 2024 to 18 September 2024 were included in this analysis.The study evaluated the immediate success rate of the ablation,the rate of all-cause and arrhythmia-related readmission,outpatient or emergency visits and incidence of complications within 30 days post ablation,and recurrence rate of arrhythmias over a 3-month follow-up period.Results:The average age of the 50 patients was(47.2±16.1)years old,32 patients(64.0%)were male.Radiofrequency catheter ablation was performed in 47 patients(94.0%),including 18(36.0%)atrial fibrillation(AF)ablation.Three patients(6.0%)underwent electrophysiological study only.The immediate success rate for ablation patients was 100%(47/47).None of the patients developed vascular puncture-related or ablation-related complications.The average hospital stay and postoperative observation time were(6.84±1.13)hours and(3.40±1.12)hours,respectively.The all-cause and arrhythmia-related readmission,outpatient or emergency visits rates within 30 days were 12.0%(6/50)and 2.0%(1/50),respectively.Two patients(4.0%)post ablation experienced AF recurrence during the 3-months follow-up period.Conclusions:Radiofrequency catheter ablation for arrhythmias in SDD strategy is safe,effective,and feasible.

Objective:To investigate the clinical efficacy and safety of laser ablation and closure for the treatment of sacrococcygeal pilonidal disease (SPD) and to analyze risk factors for postoperative recurrence in male patients.Methods:A retrospective observational study was conducted to collect clinical data of 369 patients with SPD who underwent laser ablation and closure in the Anorectal Department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine between March 2019 and December 2024. Perioperative outcomes and postoperative recurrence were analyzed. The cohort included 313 males and 56 females, with 43 patients aged ≤18 years. The median body mass index was 26.3 (IQR: 22.9, 29.6) kg/m2, and the median disease duration was 28 months (IQR: 4, 76). Among them, 218 male SPD patients who underwent surgery received preoperative sex hormone testing. A logistic regression model was used to analyze the risk factors for recurrence.Results:All patients completed the surgery. The median intraoperative ablation energy delivered was 426.8 (IQR: 243.9, 683.9) J, with no occurrence of major intraoperative complications. Postoperatively, a total of 31 patients (8.4%) required analgesic medication. Within the first postoperative week, 12 patients experienced wound oozing/bleeding; hemostasis was achieved by compression alone in 5 cases, while the remaining 7 instances required suture hemostasis after failed compression attempts. No other complications were observed. The median postoperative hospital stay was 6 (IQR: 4, 8) days, and the median time to return to regular work and life was 7 (IQR: 5, 12) days. The wound healing rate was 100%, with a median wound healing time of 35 (IQR: 30, 42) days. Postoperative recurrence occurred in 19 patients (5.1%), all of whom were male. Multivariate logistic regression analysis identified age ≤18 years (OR = 4.764, 95%CI: 2.424-34.905, P = 0.008) and a history of previous SPD surgery (OR = 5.078, 95%CI: 1.431-18.019, P = 0.012) as independent risk factors for recurrence after SPD laser ablation and closure surgery. Conclusion:Laser ablation and closure are safe, effective, and minimally invasive treatments for SPD. However, particular attention should be paid to the risk of recurrence in young male patients and those with a history of previous SPD surgery.

Objective:To investigate affinity of monoclonal antibody(MAb)of different cardiac troponinⅠ(cTnⅠ)epi-topes to cTnⅠ-troponin C(cTnⅠ-TnC)antigen,and to screen novel cTnⅠ-specific antibodies for clinical detection kit development.Methods:Based on technology platform of microarray chemiluminescence immunoassay,cTnⅠ-TnC antigen spot sample hard matrix chip was used,mouse derived cTnⅠ MAb was used as antibody to be detected,HRP-sheep-anti-mouse-IgG was used as antibody to detect,and experimental conditions were optimized for anti-origin solution,antigen spot sample concentration and antibody to be detected concentration.Affinity of cTnⅠ MAb with different antigenic epitopes to cTnⅠ-TnC was detected by competition method.Graded concentrations of cTnⅠ-TnC were added to experimental group,and diluents of equal volume were added to control group.Reaction signals of different cTnⅠ MAb were detected and affinity constants were calculated.Results:Antigen spot sample liquid was P105,antigen spot sample concentration was 0.1 mg/ml,and antibody concentration to be detected was 80 ng/ml were optimal experi-mental conditions.20c6cc and 7B9cc MAb containing TnC antibodies had the best affinity,and 20c6cc MAb reached 3.18×106 L/mol.cTnⅠ MAb located at C-end of peptide chain in a.a.r 130～145,169～178 and 190～196 regions showed good affinity,among which MAb 625(a.a.r 169～178)was 6.37×105 L/mol,showing the strongest affinity among cTnⅠ MAb.Conclusion:MAb has good affinity with cTnⅠ-TnC antigen at C-end of cTnⅠ peptide chain a.a.r 130～145,169～178,190～196 and TnC region.Designing a new type of cTnⅠ complement antibody targeting this region can be a new way to solve negative interference of autoantibody and peptide proteolysis.

Lung cancer is the leading cause of death worldwide. With the prevalence of CT screening and early diagnosis and treatment of lung cancer in China, more and more patients with early-stage lung cancer characterized with ground-glass opacity are discovered and urgently require treatment, which poses a significant challenge to surgeons. As an emerging technology, three dimensional reconstruction technology plays a crucial auxiliary role in clinical work. This review aims to briefly introduce this technology, focusing on its latest advances in surgical applications in early lung cancer screening, malignant risk assessment, and perioperative period application and medical education.

OBJECTIVE: To explore the current status, evolution, hot topics, and future research trends in the field of burn-related sepsis research through a visual analysis of literature. METHODS: A bibliometric method was employed to retrieve articles related to burn-related sepsis from January 1, 1994, to May 16, 2024, in the China National Knowledge Infrastructure (CNKI) and the Web of Science database. The CiteSpace 6.3.R1 software was used to analyze the retrieved literature. The number of publications, authors, countries, and institutions in both Chinese and English literature was statistically analyzed. Co-occurrence analysis, clustering analysis, and co-citation analysis of keywords were performed. RESULTS: A total of 1 090 articles from the CNKI database and 1 143 articles from the Web of Science database were retrieved. Over the past 20 years, the volume of Chinese publications has remained stable, although there has been a slight decline in the past two years. In contrast, the number of English publications, after a period of growth, showed a sharp decline over the past three years. In Chinese literature, 1 457 authors published articles on burn-related sepsis as first authors, with 14 core authors publishing four or more articles. In English literature, 98 authors published articles on burn-related sepsis as first authors. Research on burn-related sepsis was conducted by 76 countries, with the United States having the most collaborations and publications. Globally, 1 349 institutions published articles on burn-related sepsis, with the top institutions being the First Affiliated Hospital of the PLA General Hospital (8 articles) for Chinese literature and the University of Texas Medical Branch (57 articles) for English literature. In the co-occurrence analysis, 208 Chinese keywords and 211 English keywords were included. Excluding keywords related to search terms, the top five most frequent keywords in Chinese literature were burn, sepsis, infection, severe burn, and procalcitonin; the top five most frequent keywords in English literature were sepsis, septic shock, mortality, injury, and burn injury. Chinese keyword analysis identified six clusters, with the largest being sepsis, followed by procalcitonin, infection, and severe burn. English keyword analysis identified seven clusters, with the largest being expression, followed by epidemiology, inhalation injury, and acute kidney injury. The persistent clusters in Chinese literature were procalcitonin, with recent emerging nodes being severe burn, inflammatory response, platelets, and predictive value. In English literature, the persistent clusters were inhalation injury and nitric oxide, with recent emerging nodes being continuous renal replacement therapy, hemorrhagic shock, and early enteral nutrition. The longest-lasting emergent keyword in Chinese literature was delayed resuscitation (2003-2010), with the highest emergent strength being severe burn. In English literature, the longest-lasting emergent keywords, each lasting five years, were nitric oxide (2007-2012), management (2019-2024), and impact (2019-2024), with the highest emergent strength being thermal injury. CONCLUSIONS Research on burn-related sepsis has shifted from focusing on early studies on pathogenesis and mortality to focus on prevention, treatment, and early diagnosis. Future research is expected to focus on early diagnosis and risk factors of burn-related sepsis.
Burns/complications* ; Sepsis/etiology* ; Humans ; Bibliometrics ; China

Platelet lipid rafts are dynamic nanodomains enriched in cholesterol and sphingolipids within the plasma membrane. As pivotal hubs for signal transduction, membrane trafficking, and intercellular interactions, they have garnered significant attention in recent years for their roles in regulating platelet function and related disease mechanisms. This article reviews the structural characteristics and molecular composition of platelet lipid rafts, as well as their central roles in signal transduction and cytoskeletal reorganization. It particularly focuses on the functional abnormalities and pathological contributions of lipid rafts in diseases such as atherosclerosis, antiphospholipid antibody syndrome, and ANCA-associated vasculitis. Research indicates that lipid rafts coordinate platelet activation, inflammatory responses, and immunomodulatory processes by integrating receptor clustering, enrichment of signaling proteins, and regulation of metabolites. Finally, the article discusses the future prospects of lipid raft-targeted nanotherapeutic strategies and addresses challenges in translational research, providing a theoretical foundation and novel perspectives for understanding platelet biology and intervening in thrombo-inflammatory diseases.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective:To report the blood group antigen and antibody specificity identification methods for a patient with high-frequency antibodies, and the process of finding and providing compatible blood for the patient.Methods:A patient sent from the Blood Transfusion Department of Shanxi Provincial People′s Hospital to Taiyuan Blood Center in November 2022 was selected for the study. Classical serological methods were used to determine the patient′s blood type, screen for unexpected antibodies, identify antibodies, and perform crossmatching. High-frequency antibody identification was carried out using red blood cells treated with various enzymes. Blood group genotyping was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) and Sanger sequencing. Multiple strategies were employed to address the patient′s blood source problem. The study was approved by the Medical Ethics Committee of Taiyuan Blood Center [Ethics No. 2024 Ethics Review No.(2)].Results:①The patient′s blood type was B, RhD positive. Initial screening of the patient′s serum with multiple screening cells and antibody identification cells in saline medium was negative, but positive in antiglobulin medium. The patient′s serum showed varying reaction intensities with red blood cells treated with different enzymes. ②MALDI-TOF mass spectrometry and Sanger sequencing revealed a homozygous nonsense variant c. 376C>T (p.Gln126Ter) in the ABCG2 gene, resulting in the Jr(a-) phenotype. During family donor selection, the patient′s son was found to have a heterozygous variant c. 376C>T (p.Gln126Ter), and another heterozygous variant c. 421C>A (p.Gln141Lys), which predicted a Jr(a+ w) phenotype. ③Crossmatch tests confirmed the compatibility of blood from the patient′s son, which was used to address the urgent blood requirement. Later, rare blood from a Jr(a-) donor from the Guangzhou Blood Center was used for the patient′s ongoing treatment, saving the patient′s life. Conclusion:Combining classic serological testing with blood group gene typing techniques successfully identified the rare Jr(a-) blood type and high-frequency anti-Jra antibodies. Enzyme-treated red blood cell identification methods confirmed the presence of anti-Jra antibodies. By searching within the family and seeking help from other blood centers, compatible blood was found. This approach may provide insights for resolving similar complex blood matching problems in the future.