Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.

Objective:To report the preclinical trial results of the application of a domestic high-flow percutaneous left ventricular assist device (pLVAD) in patients with low cardiac output syndrome (LCOS) following cardiac surgery.Methods:Six patients who developed LCOS after direct cardiac surgery were implanted with a domestic high-flow pLVAD. Clinical outcomes, including hemodynamic changes, complications, and survival rates were observed post-implantation.Results:Four patients underwent pLVAD implantation under digital subtraction angiography (DSA) guidance, while two patients had the procedure performed under ultrasound guidance. The implantation process was straightforward, rapid, and uneventful, with no instances of bleeding or arrhythmias. The flow rate at the initiation of pLVAD support was 3.8-5.0 (4.22±0.44)L/min, and the flow rate during pump removal was 1.0-1.3(1.18±0.15)L/min. The duration of pLVAD support was 16.5-165.0(101.3±60.65)h. Hemodynamic parameters showed immediate improvement following pLVAD support: mean arterial pressure increased from (62.67±4.46)mmHg to (80.50±18.96)mmHg (1 mmHg=0.133 kPa, P=0.049), cardiac output increased from (2.45±0.66)L/min to (4.35±1.32)L/min( P=0.01), cardiac index improved from (1.95±0.21)L·min -1·m -2 to (2.77±0.33)L·min -1·m -2( P<0.001), pulmonary artery diastolic pressure decreased from (27.50±1.87) mmHg to(18.33±4.18)mmHg( P=0.001), and left ventricular ejection fraction improved from 0.27±0.04 to 0.37±0.06 ( P=0.004). No visible hemoglobinuria was noted during the support period. No malignant arrhythmias or cerebrovascular complications occurred. One patient required transition to surgical LVAD implantation, while the other five patients had the pLVAD successfully removed and were discharged. Three months later, all six patients were alive, with functional status classified as New York Heart Association (NYHA) Class Ⅰ-Ⅱ. Conclusion:The implantation of a domestic high-flow pLVAD provides a safe and effective therapeutic option for patients with LCOS following cardiac surgery.

Objective:To explore the key factors affecting health-related quality of life in children with brain tumors following initial diagnosis and to analyze its impact on survival and prognosis.Methods:Seventy-eight pediatric brain tumor patients who participated in a prospective cohort study between June 1st，2016 and June 30th，2021 were included for health-related quality of life assessment and long-term follow-up（median follow-up duration：52 months）.Results:The male-to-female ratio among the 78 children was 1.1：1，with a median age of 7.0（4.0，10.0）years. The scores of the Pediatric Quality of Life Inventory? 4.0 Generic Core Scales（PedsQL? 4.0）were（67.40±18.26）for parent proxy reports and（67.87±20.40）for child self-reports. Cronbach's α coefficients ranged from 0.790 to 0.927，with the intraclass correlation coefficient（ICC）was 0.673. According to the PedsQL? 4.0，impaired quality of life was observed in 50.0% of children by parent proxy report and 52.8% by child self-report，primarily affecting physical and role functioning. In addition，70% of caregivers reported impaired quality of life，with worry being the most prominent issue. Key factors affecting children's quality of life included radiotherapy，tumor stage，annual family income，and parents' marital status，while caregivers' quality of life was influenced by radiotherapy and the child's IgA levels（all P<0.05）. Children with decreased total scores，impaired physical functioning，or impaired emotional functioning on the PedsQL? 4.0 parent proxy report exhibited an increased risk of mortality（all P<0.05）. In multivariate Cox regression analysis，independent prognostic factors included a decrease in the total score on the PedsQL? 4.0 parent proxy report（ HR=6.702，95% CI：1.442-31.151， P<0.05），presence of hydrocephalus（ HR=33.602，95% CI：4.354-259.333， P<0.05），tumor recurrence（ HR=16.846，95% CI：3.158-89.852， P<0.05），and absence of hydrocephalus shunt surgery（ HR=13.428，95% CI：1.761-102.394， P<0.05）. Conclusion:The quality of life of newly diagnosed children with brain tumors is lower than that of healthy children，and quality of life is an important prognostic factor. Quality of life assessment should be an integral component of a comprehensive management program for children with brain tumors.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To report the preclinical trial results of the application of a domestic high-flow percutaneous left ventricular assist device (pLVAD) in patients with low cardiac output syndrome (LCOS) following cardiac surgery.Methods:Six patients who developed LCOS after direct cardiac surgery were implanted with a domestic high-flow pLVAD. Clinical outcomes, including hemodynamic changes, complications, and survival rates were observed post-implantation.Results:Four patients underwent pLVAD implantation under digital subtraction angiography (DSA) guidance, while two patients had the procedure performed under ultrasound guidance. The implantation process was straightforward, rapid, and uneventful, with no instances of bleeding or arrhythmias. The flow rate at the initiation of pLVAD support was 3.8-5.0 (4.22±0.44)L/min, and the flow rate during pump removal was 1.0-1.3(1.18±0.15)L/min. The duration of pLVAD support was 16.5-165.0(101.3±60.65)h. Hemodynamic parameters showed immediate improvement following pLVAD support: mean arterial pressure increased from (62.67±4.46)mmHg to (80.50±18.96)mmHg (1 mmHg=0.133 kPa, P=0.049), cardiac output increased from (2.45±0.66)L/min to (4.35±1.32)L/min( P=0.01), cardiac index improved from (1.95±0.21)L·min -1·m -2 to (2.77±0.33)L·min -1·m -2( P<0.001), pulmonary artery diastolic pressure decreased from (27.50±1.87) mmHg to(18.33±4.18)mmHg( P=0.001), and left ventricular ejection fraction improved from 0.27±0.04 to 0.37±0.06 ( P=0.004). No visible hemoglobinuria was noted during the support period. No malignant arrhythmias or cerebrovascular complications occurred. One patient required transition to surgical LVAD implantation, while the other five patients had the pLVAD successfully removed and were discharged. Three months later, all six patients were alive, with functional status classified as New York Heart Association (NYHA) Class Ⅰ-Ⅱ. Conclusion:The implantation of a domestic high-flow pLVAD provides a safe and effective therapeutic option for patients with LCOS following cardiac surgery.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.