Objective To explore the non-invasive diagnostic criteria of magnetocardiography (MCG) for coronary microvascular dysfunction (CMVD), and its value in dynamically assessing drug treatment for CMVD. Methods Patients who presented with chest tightness or chest pain at Zhongshan Hospital, Fudan University from September 2024 to March 2025 were consecutively enrolled, and all of whom had non-obstructive coronary arteries on angiography. Using the coronary angiography-derived index of microcirculatory resistance (caIMR) as the gold standard, patients were divided into a normal microcirculation group (caIMR≤40 U) and a CMVD group (caIMR＞40 U). MCG testing was performed using a domestic device (MD-U041001, Mind Medical). Patients in the CMVD group received adenosine treatment and underwent repeat MCG after medication. Differences in MCG parameters between the two groups were analyzed, and a diagnostic model was established. The value of the diagnostic model was analyzed using receiver operating characteristic (ROC) curves. Results A total of 311 patients were included, with 135 in the normal microcirculation group and 176 in the CMVD group. The CMVD group had a significantly higher proportion of males (61.9% vs 47.4%, P＝0.012), and lower high-density lipoprotein cholesterol (HDL-C) levels ([1.16±0.31] mmol/L vs [1.24±0.29] mmol/L, P＝0.029) than the normal group. Eleven MCG parameters showed significant differences between the two groups (P＜0.05), among which increased values of mfm_QR_epav, mfm_RS_epmse, space_zeroRTrot, as well as decreased value of mfm_QR_v1 were independent predictors of CMVD. The diagnostic model based on these 11 MCG parameters yielded an area under the curve (AUC) of 0.688 (95%CI 0.629-0.747). The integrated diagnostic model combining clinical risk factors (male, smoking history, HDL-C) with MCG parameters had an AUC of 0.701 (95%CI 0.643-0.759). After adenosine treatment, patients in the CMVD group showed significant decreases in mfm_QR_epav (P＝0.010), mfm_RS_sad (P＝0.013), and mfm_RS_epmse (P＝0.046). Conclusions The model based on MCG parameters demonstrates good diagnostic ability for CMVD; dynamic changes in MCG parameters following adenosine intervention may serve as potential objective indicators for evaluating microcirculatory treatment efficacy.

ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

Doxorubicin (DOX)-induced cardiotoxicity and sepsis-induced myocardial injury (SIMI) represent significant clinical challenges in patients undergoing chemotherapy, sharing a common pathological basis of oxidative stress and mitochondrial dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide (LPS)-induced SIMI. This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis, identifying ferroptosis as a central common pathway. DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4 (GPX4) activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin. LPS, by activating pattern recognition receptors and related inflammatory signaling pathways, provokes a cytokine storm and mitochondrial dysfunction. Both can disrupt the core regulatory axis of cysteine-glutathione (GSH)-GPX4, synergistically promoting ferroptosis in cardiomyocytes. Moreover, epigenetic regulation plays a key role in DOX- and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target. A deeper understanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related cardiotoxicity and improve outcomes in cancer patients with concurrent infections.

Objective To investigate the role and regulatory mechanism of LINC00657 in the progression of cervical cancer. Methods Bioinformatics analysis predicted potential binding sites between LINC00657 and miR-30a-5p and between miR-30a-5p and Skp2. These sites were verified by using RNA immunoprecipitation and dual-luciferase reporter experiments. LINC00657, miR-30a-5p, and Skp2 mRNA expression levels in cervical cancer tissues and cell lines were assessed by utilizing RT-qPCR. Western blot analysis was employed to examine the protein levels of Skp2 in cells and subcutaneous xenograft tumor models in nude mice. Immunohistochemistry was applied to analyze Skp2 expression in animal tissues. The cellular processes of cervical cancer cell lines were evaluated through CCK-8, scratch, and Transwell assays. Results LINC00657 and Skp2 presented binding sites for miR-30a-5p. In cervical cancer, LINC00657 and Skp2 showed high expression levels (P<0.05), whereas miR-30a-5p displayed low expression (P<0.05). Functional experiments demonstrated that linc00657 upregulates Skp2 expression, a process that is dependent on its sequestration of miR-30a-5p. Conclusion LINC00657 promoted the malignant progression of cervical cancer by upregulating Skp2 expression through specifically sequestering miR-30a-5p, thereby relieving its inhibitory effect on the target gene Skp2.

With a growing public emphasis on oral health, efficacy-focused toothpastes have become mainstream. By combining chemical active ingredients with mechanical cleaning, these products deliver multifunctional benefits, such as caries prevention, dentin hypersensitivity relief, whitening, and anti-inflammation. This article systematically reviews recent advances in key efficacious ingredients across four functional domains: fluoride, often supplemented with calcium-phosphorus compounds, probiotics, and herbal preparations, primarily prevents caries; antibacterial and anti-inflammatory effects arise from multi-ingredient synergy; anti-hypersensitivity works via physical occlusion and nerve inhibition, with herbal extracts as natural alternatives; and whitening involves mechanical abrasion, chemical action, and optical modification. However, current research remains fragmented and repetitive, lacking a systematic evidence base. This complicates evidence-based consumer choice, while studies on precision and personalized formulations are still limited. Future efforts should establish comprehensive efficacy evaluation systems, investigate multi-component synergies, and advance precision toothpaste development tailored to individual oral microbiomes and needs. By summarizing ingredients, mechanisms, efficacy, and safety elements, this review aims to support optimized toothpaste formulation and clinical application, thereby contributing to oral healthcare precision.

BACKGROUND: Over 20 million colonoscopies are performed in China annually. An automatic clinical decision support system (CDSS) with accurate semantic recognition of colonoscopy reports and guideline-based is helpful to relieve the increasing medical burden and standardize the healthcare. In this study, the CDSS was built under a hierarchical-label interpretable classification framework, trained by a state-of-the-art transformer-based model, and validated in a multi-center style. METHODS: We conducted stratified sampling on a previously established dataset containing 302,965 electronic colonoscopy reports with pathology, identified 2041 patients' records representative of overall features, and randomly divided into the training and testing sets (7:3). A total of five main labels and 22 sublabels were applied to annotate each record on a network platform, and the data were trained respectively by three pre-training models on Chinese corpus website, including bidirectional encoder representations from transformers (BERT)-base-Chinese (BC), the BERT-wwm-ext-Chinese (BWEC), and ernie-3.0-base-zh (E3BZ). The performance of trained models was subsequently compared with a randomly initialized model, and the preferred model was selected. Model fine-tuning was applied to further enhance the capacity. The system was validated in five other hospitals with 3177 consecutive colonoscopy cases. RESULTS: The E3BZ pre-trained model exhibited the best performance, with a 90.18% accuracy and a 69.14% Macro-F1 score overall. The model achieved 100% accuracy in identifying cancer cases and 99.16% for normal cases. In external validation, the model exhibited favorable consistency and good performance among five hospitals. CONCLUSIONS The novel CDSS possesses high-level semantic recognition of colonoscopy reports, provides appropriate recommendations, and holds the potential to be a powerful tool for physicians and patients. The hierarchical multi-label strategy and pre-training method should be amendable to manage more medical text in the future.
Humans ; Colonoscopy/methods* ; Deep Learning ; Decision Support Systems, Clinical ; Female ; Male

Colorectal polyps are important early markers of colorectal cancer, and their early detection is crucial for cancer prevention. Although existing polyp segmentation models have achieved certain results, they still face challenges such as diverse polyp morphology, blurred boundaries, and insufficient feature extraction. To address these issues, this study proposes a parallel coordinate fusion network (PCFNet), aiming to improve the accuracy and robustness of polyp segmentation. PCFNet integrates parallel convolutional modules and a coordinate attention mechanism, enabling the preservation of global feature information while precisely capturing detailed features, thereby effectively segmenting polyps with complex boundaries. Experimental results on Kvasir-SEG and CVC-ClinicDB demonstrate the outstanding performance of PCFNet across multiple metrics. Specifically, on the Kvasir-SEG dataset, PCFNet achieved an F1-score of 0.897 4 and a mean intersection over union (mIoU) of 0.835 8; on the CVC-ClinicDB dataset, it attained an F1-score of 0.939 8 and an mIoU of 0.892 3. Compared with other methods, PCFNet shows significant improvements across all performance metrics, particularly in multi-scale feature fusion and spatial information capture, demonstrating its innovativeness. The proposed method provides a more reliable AI-assisted diagnostic tool for early colorectal cancer screening.
Humans ; Colonic Polyps/diagnostic imaging* ; Colorectal Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Early Detection of Cancer

BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.