Panyu District Central Hospital

Status epilepticus (SE) is a severe type of epileptic seizure and induces molecular and cellular changes in the brain tissues which contribute to neuron injury. Here we used RNA sequencing to determine changes in hippocampal gene expression in pilocarpine-induced SE mice at 3-hour (SE-3h) and 24-hour (SE-24h) time points, a crucial stage of SE-induced brain acute damage. A total of 366 differentially expressed genes (DEGs) were identified from the SE-3h hippocampus and 570 DEGs from the SE-24h hippocampus, and most of them were up-regulated upon SE induction. Bioinformatical analyses showed that, compared to SE-3h up-regulated genes with poor scores in functional and pathway enrichment, the SE-24h up-regulated genes were predominantly enriched in inflammatory and immune response, positive regulation of response to external stimuli and inflammatory response (GO function), and Microglia pathogen phagocytosis pathway and Tyrobp causal network in microglia (WikiPathway). Specifically, a subset of DEGs such as Tyrobp, C1qc, Itgb2, Ncf2, and Nckap1l involved in the two pathways are present in the inflammatory and immune cascades. Therefore, this study delineates early altered transcriptional profiles in the hippocampus after SE, and highlights up-regulation of a subset of genes might be involved in the activation of microglia-mediated inflammatory and immune responses linked to the early pathogenesis of SE-induced brain injury.

The significant heterogeneity and complex morphology of invasive pulmonary adenocarcinoma (IPA) make grading challenging for pathologists. However, thorough investigations into radiopathomics features extracted from computed tomography (CT) and whole slide images (WSIs) for IPA grading and their biological significance remain limited. We aim to integrate multi-omics analysis to establish a robust grading model for IPA and reveal its biological significance. This multicenter study encompassed 988 patients who underwent radical surgical resection and received a pathological confirmation of IPA. Through integrated analysis of radiomics and pathomics, we constructed and validated an optimal ensemble learning grading model, which integrates multi-scale and multi-modal characteristics, achieved AUCs of 0.885, 0.920, 0.833, and 0.905 in the internal and external validation sets. Further systematic analysis of paired CT, WSIs, and RNA sequencing, two co-expression modules, 23 hub genes, and 680 significant pathways associated with grading were identified. Moreover, the reproducibility of the radiopathomics phenotypes, linked to multiple biological pathways-including signal transduction, cell differentiation, DNA damage and repair, cell proliferation and growth, metabolism, and metastasis and invasion-has been validated. In conclusion, the integration of radiological and pathological characteristics enhances the accuracy in differentiating high-grade IPA, offering a robust approach for grading. Multi-scale imaging biomarkers may promote personalized treatment.

BACKGROUNDDiabetic foot ulcers (DFUs) affect approximately 18.6 million people worldwide every year. Patients with DFU often present with symptoms such as lower limb infections, ulcers, and deep tissue damage. Platelet-rich plasma (PRP) is a concentrated platelet product that can trigger the release of growth factors and cytokines, which stimulate tissue healing and regeneration and thus alleviates DFU. At present, no comprehensive study has been conducted to verify the effect of PRP in both in vitro and clinical settings for treating DFUs.AIMTo perform the in vitro and clinical evaluation of PRP combined with endovascular angioplasty in treating diabetic foot.METHODSThis study focused on both in vitro and clinical settings. In the in vitro study, human umbilical vein endothelial cells (HUVECs), human dermal fibroblasts (HSFs), and human immortalized keratinocytes (HaCaTs) were treated with PRP. Experiments involving proliferation, migration, tubule formation, and angiogenesis signaling pathways were conducted. In this clinical study, patients who visited the Affiliated Panyu Central Hospital of Guangzhou Medical University from 2020 to 2024 and met enrollment criteria were randomly assigned to 2 groups using prospective block randomization. In the control group, the DFU was treated with endovascular angioplasty and wound debridement. In the PRP + endovascular angioplasty group, PRP was evenly used on the surface of superficial ulcers, followed by endovascular angioplasty to treat vascular occlusion. The key outcomes were measured, including the Rutherford scale, Wagner scale, foot skin temperature, and ulcer repair area before and after treatment.RESULTSIn the in vitro study, 6% PRP could promote the proliferation and migration of HUVECs, HSFs, and HaCaTs in a high-glucose environment. Additionally, it promoted tubule formation in HUVECs by activating signaling proteins such as Ak strain transforming and extracellular regulated protein kinases 1/2. In the clinical study, a total of 208 patients participated. After 12 months of treatment, the ulcer repair area (14.95 ± 0.16 cm2) and ulcer healing rate were improved in the PRP + endovascular angioplasty group than in the control group (P < 0.05).CONCLUSIONThe combination of 6% activated PRP and endovascular angioplasty may improve the microcirculation and tissue repair in DFUs. This study offers a novel treatment option for patients with diabetic foot.

Cardiopulmonary resuscitation (CPR) is physically demanding and may result in work-related musculoskeletal injuries in healthcare providers. We report a case of triangular fibrocartilage complex (TFCC) and dorsal distal radioulnar ligament injuries sustained by an orthopedic resident during prehospital CPR events, to increase awareness of this underrecognized occupational hazard. A 31-year-old orthopedic resident performed prolonged CPR twice in one shift and subsequently developed marked tenderness, instability, and pain in the left wrist with pronation, as well as a sensation of clicking subluxation. A second physician recalled persistent wrist pain after CPR in previous years. Imaging demonstrated a tear of the TFCC and dorsal distal radioulnar ligament as well as joint effusion and extensor carpi ulnaris sheath edema in the affected wrist. The retrospective magnetic resonance imaging of the second physician indicated chronic TFCC change. Conservative management with nonsteroidal anti-inflammatory drugs, plaster splint immobilization, and subsequent wrist bracing was implemented for the resident; self-treatment with nonsteroidal anti-inflammatory drugs and wrist brace was reported by the second physician. The orthopedic resident achieved resolution of instability after 6 weeks with restoration of full wrist motion and strength by 2 years. The second physician's symptoms persisted for 2 years before mostly resolving. Musculoskeletal injuries, including TFCC and distal radioulnar ligament tears, may occur in CPR providers but are often underrecognized and underreported. Early recognition, appropriate management, and preventive strategies such as alternating roles, prompt initiation of automated compression devices, and ergonomic device placement may mitigate injury risks. Encouraging timely reporting and self-care among healthcare professionals is essential for provider well-being and care quality.

NCT03928119.

Chronic kidney disease (CKD) is a condition that affects people on a global scale. After various stages of progression, CKD is finally characterized by renal fibrosis. As the most pervasive and well-studied epigenetic modification, DNA methylation has recently been associated with the development of renal fibrosis. Gaining a better understanding of the link between DNA methylation and CKD would provide new targets or enable the development of epigenetic therapies for CKD. This review discusses the mechanisms by which DNA methylation regulates gene expression during the pathological process of CKD, including the role of DNA methyltransferases (DNMTs). This review summarizes DNA methylation in CKD, particularly its crucial role in CKD-related conditions, such as diabetic kidney disease (DKD) and chronic allograft injury. Conventional demethylating agents have been discussed as well as the need for less toxic demethylating agents for clinical applications. Finally, some of the problems and obstacles specified in previous DNA methylation studies have been considered. This information aims to promote further investigations into the role of DNA methylation in CKD by providing novel insights into the mechanism by which methylation affects the progression and regression of CKD, which would result in the development of alternate treatments.

In this study, we assessed the pharmacokinetics, safety, and bioequivalence of trimetazidine tablets from 2 different manufacturers in healthy Chinese individuals under both fasting and fed conditions. Twenty-eight healthy Chinese volunteers were included in each fasting and fed group. They were randomly assigned to fasting and fed arms in a single-center, randomized, open-label, crossover trial with a 2-period, 2-sequence design. Plasma trimetazidine levels were determined using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined using a nonatrioventricular model. The pharmacokinetic parameters were obtained by the concentration-time profiles, including the area under the plasma concentration-time curve from time 0 to 24 hours, area under the concentration-time curve from time 0 to infinity, maximum concentration, time to achieve maximum concentration, and elimination half-life. Both trimetazidine preparations were bioequivalent under fasting and fed states, with all parameters within the acceptable limits. All recorded adverse events were mild. Overall, the test trimetazidine formulation was bioequivalent to the reference formulation and safe for use in healthy Chinese subjects in both the fasting and fed states.