Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

ObjectiveTo investigate the effect and mechanism of Yangxin Dawayimicol honey ointment （YXDW） in improving cardiac function in rats after myocardial infarction. MethodsRats were divided into the sham group， model group， fosinopril sodium tablet group， and YXDW low， medium， and high-dose groups. A rat myocardial infarction model was established by left anterior descending branch ligation. The YXDW groups were administered doses of 0.27， 0.54， and 1.08 g·kg^-1·d^-1， while the fosinopril sodium tablet group was given 3.60 mg·kg^-1·d^-1. The sham group and model group were treated with an equal amount of 0.5% sodium carboxymethyl cellulose solution. After continuous gavage for 4 weeks， the effects of YXDW on the signs and cardiac indices of the rats were observed. Echocardiography was used to assess cardiac function， and pathological examination was used to evaluate heart morphology. Enzyme-linked immunosorbent assay （ELISA） was used to assess changes in interleukin-1β （IL-1β）， IL-6， N-terminal pro-brain natriuretic peptide （NT-proBNP）， and tumor necrosis factor-α （TNF-α）. The expression of voltage-dependent anion-selective channel protein 1 （VDAC1）， nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 （NLRP3）， B-cell lymphoma -2 （Bcl-2）， and Bcl-2-associated X protein （Bax） was detected by reverse transcription-polymerase chain reaction （Real-time PCR） and Western blot. ResultsThe survival status of rats in all YXDW groups was generally improved. Echocardiographic results showed that， compared to the sham group， the model group exhibited a significant decrease in left ventricular ejection fraction （LVEF） and left ventricular short axis shortening rate （LVFS）， with statistical significance （P<0.01）. Compared to the model group， rats in the treatment groups showed varying degrees of improvement in LVEF and LVFS， with statistical significance （P<0.01）. Pathological examination revealed reduced myocardial cell degeneration， less inflammatory infiltration， intact myofilaments， regular shape， and significantly fewer myocardial fiber disruptions in the treatment groups compared to the model group. Electron microscopy results showed that， compared to the model group， the mitochondria of myocardial cells in the YXDW groups had clear ultrastructure， intact membranes， denser cristae， a clear matrix， and regular arrangement of myofilaments and intercalated discs. ELISA results showed that， compared to the sham group， serum levels of IL-6， IL-1β， and TNF-α were significantly higher in the model group， with statistical significance （P<0.01）. However， in the treatment groups， the serum levels of IL-6， IL-1β， and TNF-α were significantly reduced， with statistical significance （P<0.01）. NT-proBNP levels were significantly higher in the model group compared to the sham group （P<0.01）， but significantly lower in the treatment groups （P<0.01）. Furthermore， Real-time PCR and Western blot results showed that compared to the sham group， the levels of VDAC1， NLRP3， and Bax/Bcl-2 were significantly higher in the model group （P<0.05）. In the treatment groups， these levels were significantly lower than the model group （P<0.05）. ConclusionYXDW significantly improved cardiac function in rats after myocardial infarction. Its mechanism of action may involve the VDAC1/NLRP3/Bax/Bcl-2 pathway to improve mitochondrial structure and function and inhibit the inflammatory response， thereby improving cardiac function.

Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. In vivo experiments were conducted using 8-week-old SPF male C57BL/6J mice. The T2DM animal model was established by high-fat and high-sugar diet combined with intraperitoneal injections of streptozotocin (STZ), in compliance with the ethical guidelines set by the Animal Welfare Committee of Beijing University of Chinese Medicine (approval number: BUCM-2022021503-1134). In vitro experiments employed human liver cancer HepG2 cells, which were induced with tunicamycin (TM) to establish the ERS cell model. Transcriptomic sequencing was used to analyze changes in gene expression in the liver samples of T2DM mice following ISL treatment. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the regulatory effects of ISL on key ERS genes. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunofluorescence techniques were used to evaluate ISL's effects on ERS-related proteins. Results indicate that ISL significantly downregulates the expression of ERS-related genes, reduces the level of glucose-regulated protein 78 (GRP78), and inhibits the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), thereby alleviating abnormal ERS induced by T2DM. Additionally, ISL increases the protein levels of insulin receptor substrate (IRS) 1 and IRS2 and enhances the phosphorylation of protein kinase B (Akt), thereby improving insulin sensitivity. In conclusion, ISL is able to alleviate T2DM associated symptoms by improving abnormal ERS and enhancing insulin sensitivity.

ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.

Objective To evaluate the effectiveness of thermal tomography in breast cancer (BC) screening. Methods We conducted a general population-based BC screening in three regions of Hubei Province (Xiantao, Hongan, and Yangxin Districts). Participants underwent a questionnaire-based interview for baseline data collection. They then received a physical examination, thermal tomography, and ultrasound from doctors and technicians. We compared the efficacies, including sensitivity, specificity, and false-positive rates, of ultrasound and thermal tomography in BC screening. Results A total of 59 712 eligible women were included in this screening program. The BI-RADS 1, 2, 3, 4, and 5 accordance rates between the two screening methods were 0.9549, 0.8047, 0.9037, 0.3352, and 0, respectively. The overall accordance rate was 0.933 1. The kappa consistency results showed that the Cicchetti-Allison and Fleiss-Cohen kappa values were 0.7970 and 0.8583, respectively. Although the two methods had equal sensitivities, specificity was higher in thermal tomography than in ultrasound. The false-positive rate was lower in thermal tomography than in ultrasound. The area under the receiver operating characteristic (ROC) curve of thermal tomography was significantly larger than that of ultrasound. Conclusion The general consistency between thermal tomography and ultrasound in BC screening was high. Thermal tomography outperformed ultrasound in terms of specificity and diagnostic efficiency. Therefore, thermal tomography has a high application value for general population-based BC screening.

This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.
Humans ; Cerebral Small Vessel Diseases/pathology* ; Inflammation/pathology* ; Cerebral Amyloid Angiopathy/pathology* ; Vasculitis, Central Nervous System/pathology* ; Vasculitis/pathology*

Tripartite motif-containing (TRIM) family proteins are crucial E3 ubiquitin ligases that have garnered significant attention for their regulatory roles in bone metabolism in recent years. This article reviews the function and regulatory mechanisms of TRIM family proteins in bone metabolism, focusing on their dual roles in bone formation and resorption. It also provides a detailed analysis of signaling pathways and molecular mechanisms by which TRIM family members regulate the activities of osteoblasts and osteoclasts. Research findings suggest that modulating the expression or activity of TRIM family proteins could be beneficial for treating bone diseases such as osteoporosis. This review highlights the molecular mechanisms of TRIM family members in bone physiology and pathology, aiming to provide theoretical basis and scientific guidance for developing novel therapeutic strategies for bone diseases.
Humans ; Ubiquitin-Protein Ligases/physiology* ; Bone and Bones/metabolism* ; Animals ; Tripartite Motif Proteins/physiology* ; Osteoclasts/metabolism* ; Osteoblasts/metabolism* ; Signal Transduction/physiology* ; Osteogenesis/physiology*

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Objectives: This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle. Patients and Methods: Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery. Results: Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively). Conclusion The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.