Onco-critical care has emerged as an important subspecialty at the intersection of critical care medicine and oncology, attracting increasing attention in recent years. With continuous innovations in cancer therapies, patient survival has improved significantly; however, the incidence of associated critical complications has also increased. The reasons for cancer patients requiring intensive care unit admission are diverse and can be broadly categorized into three groups: progression of the underlying malignancy, treatment-related complications, and coexisting classical critical illnesses. Traditional critical care concepts and practices face limitations in addressing the multidimensional and heterogeneous challenges of onco-critical care. Based on the core mechanism of critical illness development—host/organ unregulated response (HOUR)—this article systematically elaborates on how this framework advances understanding and clinical practice into onco-critical care, with emphasis on its manifestations in neuroendocrine, immune-inflammatory, and coagulation-metabolic pathways. The review summarizes recent advances in clinical assessment and phenotyping systems for onco-critical illness and discusses a multidisciplinary, integrated management strategy centered on the "Disease Control, Host Response Modulation, Organ Support" triad. Finally, major challenges and future directions in this field are outlined. By integrating existing evidence and theoretical insights, this review aims to provide new perspectives and a theoretical foundation for the clinical management of onco-critical illness, thereby promoting its evolution toward precision and standardization.

Portal vein thrombosis （PVT） is a common and severe complication of liver cirrhosis. Anticoagulant therapy for PVT in these patients is particularly challenging due to the coexistence of abnormal coagulation function and bleeding risk. This article reviews recent research findings， domestic and international guidelines， and expert consensus regarding anticoagulant therapy for liver cirrhosis complicated by PVT. The review focuses on four key aspects: the underlying causes of the high incidence of PVT， its clinical manifestations and diagnosis， anticoagulant treatment decision-making （including determining indications， timing， and course selection）， and rational drug use. The evidence indicates that the high incidence of PVT in patients with liver cirrhosis results from the interplay of multiple factors. Currently， portal venous stasis， a systemic hypercoagulable state， and vascular endothelial damage are widely recognized as the three primary risk factors for PVT formation. The clinical manifestations of liver cirrhosis complicated by PVT are diverse，diagnosis requires comprehensive evaluation based on clinical context， imaging examination， and laboratory tests， with imaging examination as the cornerstone. Anticoagulant therapy can significantly improve the thrombus recanalization rate in PVT， reduce the risk of thrombus progression， and does not increase the risk of portal hypertension-related bleeding. Regarding treatment timing， initiating anticoagulation within six months of diagnosis， particularly within two weeks， can significantly enhance the recanalization rate. Commonly used anticoagulants in clinical practice for liver cirrhosis with PVT include heparins， vitamin K antagonists （VKAs）， and direct oral anticoagulants （DOACs）. Among these， substantial evidence supports low-molecular-weight heparin as a first-line agent. DOACs have demonstrated favorable efficacy and safety in patients with compensated liver cirrhosis and PVT； however， their use in patients with decompensated liver cirrhosis and PVT warrants extra caution. A treatment duration of at least six months is generally recommended. Long-term anticoagulation should be considered for patients with liver cirrhosis and PVT who have mesenteric vein involvement， are awaiting liver transplantation， or have an inherited thrombophilia.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

In this study, the reductive amination method was used to label IR783 on Astragalus polysaccharides(APS) for the first time, which was verified by ultraviolet-visible spectroscopy and infrared spectroscopy. Quantitative analysis methods of APS-IR783 in plasma and various tissue were established using a multifunctional microplate reader. The pharmacokinetics and tissue distribution of APS-IR783 in mice were investigated after a single intravenous injection of 30 mg·kg~(-1) APS-IR783, and pharmacokinetic parameters were calculated using DAS 2.0 software. The results showed that the APS used had a mass fraction of 93.69%, a relative molecular weight of 1.55×10~5, and a polydispersity index(PDI, M_w/M_n) of 1.73, close to a homogeneous polysaccharide. The IR783 labeling yield reached 86.50%, and the content of IR783 in APS-IR783 was 0.72%. After a single intravenous injection of 30 mg·kg~(-1), the pharmacokinetic parameters of APS in mouse plasma were as follows: T_(max) was(0.67±0.26) h; C_(max) was(1 599.29±159.30) mg·L~(-1); T_(1/2α) and T_(1/2β) were(2.29±3.06) h and(0.44±0.05) h, respectively; AUC_(0-t) was(23 398.91±2 907.03) mg·h·L~(-1); AUC_(0-∞) was(27 710.55±3 506.55) mg·h·L~(-1); MRT_(0-∞) was(34.38±12.59) h; CL was 0.001 L·h~(-1)·kg~(-1); V_z was(0.042±0.017) L·kg~(-1). The in vivo biodistribution study demonstrated that the in vivo exposure ratios of APS in different tissue were in the following order: spleen > liver > kidney > lung > heart > small intestine > muscle > large intestine > brain > stomach, where the top five tissue accounted for 87.54% of the total area under the curve(AUC). This study successfully labeled APS with a water-soluble near-infrared fluorescent probe of IR783 for the first time and revealed the pharmacokinetics and tissue distribution of APS in mice. The paper provides detailed in vivo behavior of APS after intravenous injection, which lays the foundation for the development and utilization of APS and related natural medicines.
Animals ; Mice ; Polysaccharides/chemistry* ; Tissue Distribution ; Astragalus Plant/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Fluorescent Dyes/pharmacokinetics* ; Female

Ulcerative colitis(UC) is a recurrent, chronic, nonspecific inflammatory bowel disease. The longer the course of the disease, the higher the risk of cancerization. In recent years, the incidence and mortality rates of colon cancer in China have been increasing year by year, seriously threatening the life and health of patients. Therefore, studying the mechanism of "inflammation cancer transformation" in UC and conducting early intervention is crucial. The "Kenang" theory is an important component of traditional Chinese medicine(TCM) theory of phlegm and blood stasis. It is based on the coexistence of phlegm and blood stasis in the body and deeply explores the pathogenic syndromes and characteristics of phlegm and blood stasis. Kenang is a pathological product formed when long-term Qi stagnation leads to the internal formation of phlegm and blood stasis, which is hidden deep within the body. It is characterized by being hidden, progressive, and difficult to treat. The etiology and pathogenesis of "inflammation cancer transformation" in UC are consistent with the connotation of the "Kenang" theory. The internal condition for the development of UC "inflammation cancer transformation" is the deficiency of healthy Qi, with Qi stagnation being the key pathological mechanism. Phlegm and blood stasis are the main pathogenic factors. Phlegm and blood stasis accumulate in the body over time and can produce cancer toxins. Due to the depletion of healthy Qi and a weakened constitution, the body is unable to limit the proliferation and invasion of cancer toxins, eventually leading to cancer transformation in UC. In clinical treatment, the focus should be on removing phlegm and blood stasis, with syndrome differentiation and treatment based on three basic principles: supporting healthy Qi to strengthen the body's foundation, resolving phlegm and blood stasis to break up the Kenang, and regulating Qi and blood to smooth the flow of energy and resolve stagnation. This approach helps to dismantle the Kenang, delay, block, or even reverse the cancerization process of UC, reduce the risk of "inflammation cancer transformation", improve the patient's quality of life, and provide new perspectives and strategies for early intervention in the development of colon cancer.
Humans ; Colitis, Ulcerative/immunology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Cell Transformation, Neoplastic

Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

Gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinase are key drivers of most gastrointestinal stromal tumor (GIST). The continuous development of tyrosine kinase inhibitors, such as imatinib, sunitinib, anlotinib, regorafenib, ripretinib and avapritinib, has greatly improved the overall survival of patients with advanced GIST. This article reviewed the efficacy (including objective response rate, disease stability rate, median progression free survival) and common adverse events of representative tyrosine kinase inhibitors in the treatment of advanced GIST in recent years, aiming to provide a clinical basis for the treatment options of patients with advanced GIST.

Gastric polyps, as a common digestive system disease, have shown an increasing detection rate and are regarded as one of the precancerous states of gastric cancer. In TCM, gastric polyps can be classified as diseases such as "stomachache" and "fullness and distension in the stomach". TCM holds that the disease is often related to the accumulation of pathogenic factors such as phlegm and blood stasis in the body to form "kenang", which has the characteristics of insidiousness, stubbornness, and recurrence. Deficiency of healthy qi and disorder of qi movement can lead to the adhesion of phlegm and blood stasis, which highly aligns with the etiology and pathogenesis of gastric polyps. The treatment principles are promoting blood circulation to remove blood stasis, regulating qi movement, and strengthening the body resistance to consolidate the essence. Understanding the etiology, pathogenesis, and treatment principles of gastric polyps from the theory of "kenang" has important guiding significance for clinical diagnosis and treatment, providing new ideas and methods for the treatment of gastric polyps.

Osteoporosis(OP)is a refractory metabolic bone disease,with decreased bone mineral mass,weakened bone strength,and systemic bone pain as typical clinical manifestations.Shenzhen Pingle Guo's Orthopedics,an important branch of the Pingle Guo's Orthopedics,has developed their distinct therapeutic approaches to the prevention and treatment of OP:the fifth-generation inheritor,Mr.Guo Chunyuan,advocated for the simultaneous regulation of qi and blood and formulated Shudi Zhuanggu Formula(composed of Rehmanniae Radix Praeparata,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Poria,Angelicae Sinensis Radix,Paeoniae Radix Alba,Chuanxiong Rhizoma,Dipsaci Radix,and Achyranthis Bidentatae Radix);the sixth-generation inheritor,Professor Yang Zejin,emphasized zang-fu syndrome differentiation and established Yang's Guwei Formula,which simultaneously tonifies the liver,spleen,and kidney,and simultaneously treats deficiency and blood stasis(composed of Astragali Radix,Rehmanniae Radix Praeparata,Achyranthis Bidentatae Radix,Epimedii Folium,Cistanches Herba,Cuscutae Semen,Drynariae Rhizoma,Angelicae Sinensis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Corydalis Rhizoma,and Paeoniae Radix Alba);the seventh-generation inheritor,Professor Gong Chunzhu,proposed a three-stage clinical treatment strategy and stressed the principle of reinforcing acquired foundation of life(i.e.,reinforcing spleen and stomach),and formulated the modified Shudi Zhuanggu Formula with Lingnan characteristics(composed of Rehmanniae Radix Praeparata,Corni Fructus,Dioscoreae Rhizoma,Alismatis Rhizoma,Poria,Moutan Cortex,Astragali Radix,Dipsaci Radix,Cyathulae Radix,Acanthopanacis Cortex,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,and Chaenomelis Fructus).During the evolution,Shenzhen Pingle Orthopedic Hospital has continuously integrated modern medical achievements,passed down and enriched the clinical experience,and then the theoretical framework of traditional Chinese medicine in the prevention and treatment of OP has been developed.