Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

ObjectiveThis paper aims to explore the action and molecular mechanism of modified Tongluo Tangtai Formula（MTLTT） on myelin damage in diabetic peripheral neuropathy （DPN） based on network pharmacology and in vitro experiments. MethodsThe chemical components of the MTLTT were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database and literature， and the component targets were collected from the SwissTargetPrediction database. The targets of DPN were collected from the GeneCards， OMIM， Disgenet， and GEO databases. Gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses were performed using the Metascape database， and a network diagram was constructed using Cytoscape software. The binding actions of core components with glycogen synthase kinase 3 beta （GSK-3β） and β-catenin were analyzed by Autodock Vina. An in vitro DPN model was established by high glucose-induced Schwann cells and dorsal root ganglion cells （SCs/DRGs）. The ultrastructural morphological changes of SCs and DRGs were observed by scanning electron microscope（SEM）， and the expressions of myelin-associated glycoprotein （MAG） and myelin basic protein （MBP） were detected by immunofluorescence staining. The mRNA and protein expression levels of MAG， MBP， myelin protein 0 （P0）， peripheral myelin protein 22 （PMP22）， and Wnt/β-catenin signaling pathway-related protein β-catenin， GSK-3β， Wnt family member 3α （Wnt3α）， and Wnt inhibitory factor-1 （Wif-1） were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot. ResultsNetwork pharmacology analysis revealed that MTLTT components may treat DPN via the Wnt signaling pathway， involving key proteins such as GSK-3β， β-catenin and Wif-1. The molecular docking results indicate that atropine， apigenin， baicalein， isoflavanone， and albiflorin have good binding activity with GSK-3β， and that all 13 core components have stable binding activity with β-catenin. Cell experiments showed that compared with the blank group， SCs and DRGs in the model group exhibited severe morphological and structural abnormalities such as disintegration， shrinkage and axonal rupture， while these abnormal changes were improved after MTLTT intervention. Immunofluorescence results indicated that the fluorescence intensity of MAG and MBP was markedly decreased in the model group relative to the blank group（P<0.01）， while MTLTT treatment obviously upregulated the expression of MAG and MBP compared with the model group （P<0.01）. Real-time PCR and Western blot assays revealed that the expression levels of myelin-related molecules MAG， MBP， P0 and PMP22 were significantly reduced in the model group （P<0.05，P<0.01）， and MTLTT remarkably increased their expression levels （P<0.05）. In the Wnt/β-catenin signaling pathway， the mRNA levels of GSK-3β， Wif-1 and Wnt3α were elevated and β-catenin mRNA expression was declined in the model group （P<0.01）. Meanwhile， the protein expressions of GSK-3β and Wif-1 were upregulated， whereas those of Wnt3α and β-catenin were downregulated （P<0.01）. Compared with the model group， MTLTT at different doses reduced the mRNA and protein levels of GSK-3β and Wif-1 to varying degrees （P<0.05）， and distinctly enhanced the protein expression of Wnt3α and β-catenin（P<0.01）. ConclusionMTLTT can alleviate high glucose-induced myelin damage. Its protective mechanism may promote myelin repair by upregulating the expression of MAG， MBP， P0 and PMP22， and the therapeutic effect is possibly associated with the activation of Wnt/β-catenin signaling pathway.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

The incomplete degradation of tumour cells by macrophages(Mφ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mφ is mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mφ to degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mφ to degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mφ phagosomes,causing Mφ to produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mφ by liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subse-quently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mφ cannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mφ to degrade tumour cells by suppressing NOX2.

Objective:To investigate the optimization of inferior vena cava imaging using dual-layer spectral detector CT (DLCT) virtual monoenergetic images (VMI) combined with multiphase scanning.Methods:A retrospective analysis was conducted on the imaging data of 184 patients who underwent inferior vena cava imaging using dual-layer detector spectral CT at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2021 to October 2024. Each patient underwent multiphase scanning (60, 80, and 120 s after contrast injection were referred to as the first, second, and third phases, respectively). The images were reconstructed into conventional 120 kVp polyenergetic image (PI) and VMIs at 40, 50, 60, 70, and 80 keV. Image quality of 120 kVp PI and VMI for each phase was evaluated. The objective image quality indicators included CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and noise. Comparisons of the above indictors within the same phase were performed using repeated measures ANOVA or the Friedman test, while comparisons between different phases were conducted using one-way ANOVA or the Kruskal-Wallis test.Results:At the same phase, the CT value, SNR, and CNR of the 40 keV VMI were higher than those of other energy level VMIs and PI (all P<0.001). The SNR of the 40 keV VMI in the third phase was significantly higher than in the first phase ( P<0.05), while there was no significant difference between the first and second phases ( P>0.05). The standard deviation (SD) of the 40 keV VMI in the third phase was significantly lower than that in the first and second phases (all P<0.05). The subjective scores for the 40 keV VMI were higher than those for other energy level VMIs and PI at the same phase ( P<0.001). The subjective scores for the 40 keV VMI in the third phase were higher than those in the second and first phases ( P<0.001). The percentage of scores≥4 in the third phase (77.17%,142/184) was significantly higher than those in the first phase (28.26%,52/184) and second phase (61.96%,114/184) ( P<0.001). Conclusion:In inferior vena cava imaging, the 40 keV VMI, combined with the optimal phase (120 s delay), effectively optimizes image quality.

Objective To investigate the clinical characteristics and prognostic factors of Staphylococcus aureus bloodstream infections in adult patients for improving clinical treatment and identifying potential interventions.Methods Clinical data of inpatients diagnosed with S.aureus bloodstream infection confirmed by blood culture in a hospital from January 2016 to December 2023 were retrospectively reviewed.The data included patient age,gender,history of hospital admission,department of admission,underlying diseases,primary infection,quick Pitt bacteremia score(qPitt),invasive treatment,empirical anti-infective treatment,and treatment outcomes.Patients were assigned to case group or control group according to whether they died in hospital in order to identify the prognostic factors of patient outcomes.Binary logistic regression analysis was used to identify independent prognostic factors.Results A total of 233 cases of S.aureus bacteremia were identified.Multivariate logistic regression analysis showed that age ≥ 70 years old(OR=4.725,95％CI:1.228-18.173,P=0.024),diabetes mellitus(OR=8.161,95％CI:1.954-34.086,P=0.004),Charlson comorbidity index(CCI)≥ 5(OR=7.672,95％CI:1.901-30.963,P=0.004),hospital infection(OR=7.853,95％CI:1.588-38.832,P=0.012),and qPitt ≥ 2(OR=23.189,95％CI:4.461-120.552,P＜0.001)were independent prognostic factors for poor outcome of patients with S.aureus bacteremia,while catheter-associated infection(OR=0.051,95％CI:0.005-0.579,P=0.016)was negatively correlated with mortality.Conclusions Advanced age,diabetes mellitus,high CCI,hospital infection,and high qPitt were independent prognostic factors for poor outcomes of patients with S.aureus bacteremia.The patients should be well managed by timely removal of eradicable lesions to improve patient outcomes.

Objective Exploring the clinical diagnosis and treatment status of epilepsy patients at the epilepsy specialty clinic in a single-center comprehensive hospital in the Lhasa area of the Tibetan Plateau.Methods Epilepsy patients who visited the epilepsy specialty clinic of the Department of Neurology at the Tibet Autonomous Region People's Hospital from September 2021 to June 2023 were continuously enrolled.Data such as clinical characteristics and diagnosis and treatment conditions of the enrolled patients was analyzed.Results A total of 121 patients were enrolled in this study,with 33.9%(41/121 cases)being new patients at our hospital and 6.6%(8/121 cases)being referred to our hospital.Non-adherence to treatment,with patients self-reducing or stopping medication without medical advice,accounted for 8.3%(10/121 cases)of the cases.The majority of epilepsy patients were in the young and middle-aged group,with 51.2%(62/121 cases)being between 18 and 44 years old.There were significant differences in the distribution of epilepsy patients across different age groups(P<0.001),while there was no significant difference in gender distribution(49.6%male vs.50.4%female,P>0.05).Generalized seizures were the predominant type of seizure(75.2%,91/121 cases),and 73.6%(89/121 cases)of the patients had an unknown etiology for their epilepsy,with symptomatic epilepsy accounting for 26.4%(32/121 cases)and structural causes being the most common at 24.8%(30/121 cases).Monotherapy was the main treatment for epilepsy(55.4%,67/121 cases),with sodium valproate being the most frequently prescribed drug for monotherapy at 22.3%(27/121 cases).Conclusion In the epilepsy specialty clinic in the plateau region,newly diagnosed patients account for about one-third,and over one-tenth of revisiting patients have not been receiving standardized treatment.The majority of our epilepsy patients are young to middle-aged adults.Generalized seizures are the predominant type.The etiology is unknown in the majority of cases,with structural causes being a common etiology in symptomatic epilepsy.Sodium valproate is the most frequently used antiseizure medication(ASM)in monotherapy in the plateau area.

Radiotherapy plays a critical role in the management of borderline resectable and unresectable locally advanced pancreatic cancer. Conventional radiotherapy improves local control in pancreatic cancer but has not significantly enhanced overall survival. Stereotactic body radiotherapy (SBRT), which employs single high-dose fractions or a hypofractionated regimen, enhances the biologically effective dose and has demonstrated remarkable efficacy in cancer treatment combined with systemic therapy. Due to the extremely high precision requirements of SBRT for spatial tumor targeting, precise organ motion management and image-guided radiotherapy technologies are essential for its successful implementation. The integration of MR-guided online adaptive radiotherapy with SBRT enables real-time assessment of anatomical changes during each treatment session, allowing online adaptive replanning to optimize dose delivery. This approach significantly improves treatment accuracy. The comprehensive application of these cutting-edge radiotherapy technologies holds promise for establishing groundbreaking therapeutic paradigms in pancreatic cancer.

Pediatric tumors differ significantly from adult cancers, possessing unique developmental origins, histological features, and molecular genetic changes. With the rapid advancement of multi-omics technologies, such as genomics, transcriptomics, proteomics, and epigenetic analyses, the molecular characteristics of pediatric tumors have been extensively revealed, providing new possibilities for precision medicine. Concurrently, the integration of artificial intelligence and digital pathology has effectively enhanced diagnostic accuracy, presenting a broad scope for future development. While this progress positively impacts the pathological diagnosis of pediatric tumors, it also presents challenges related to data complexity, technology integration, and the promotion of clinical applications. This article aims to discuss the influence of molecular and artificial intelligence, as well as multimodal integrated pathological models on diagnosis and prognostic prediction of pediatric tumor, with the goal of fostering further exploration and in-depth research.