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.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

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.

Negative logarithm of the acid dissociation constant(pKa)significantly influences the absorption,dis-tribution,metabolism,excretion,and toxicity(ADMET)properties of molecules and is a crucial indicator in drug research.Given the rapid and accurate characteristics of computational methods,their role in predicting drug properties is increasingly important.Although many pKa prediction models currently exist,they often focus on enhancing model precision while neglecting interpretability.In this study,we present GraFpKa,a pKa prediction model using graph neural networks(GNNs)and molecular finger-prints.The results show that our acidic and basic models achieved mean absolute errors(MAEs)of 0.621 and 0.402,respectively,on the test set,demonstrating good predictive performance.Notably,to improve interpretability,GraFpKa also incorporates Integrated Gradients(IGs),providing a clearer visual description of the atoms significantly affecting the pKa values.The high reliability and interpretability of GraFpKa ensure accurate pKa predictions while also facilitating a deeper understanding of the relation-ship between molecular structure and pKa values,making it a valuable tool in the field of pKa prediction.

Objective:To observe the effect of quadrato motor training(QMT)training on the balance of stroke patients under two conditions(single and dual-task).Method:The eligible stroke patients were randomly divided into three groups:the control group(n=15),the gait training group(n=15),and the QMT group(n=15).All groups received routine rehabilitation training.The gait training group received additional gait training,while the QMT group received QMT training.The Prokin Balance Assessment System,Berg balance scale,timed up and go test(TUGT),仃ail making test(TMT),dual-task cost,and specific activity balance confidence scale were used to evaluate the static and dy-namic balance function,attention and executive function,dual-task performance,and self-efficacy of balance before and after treatment in the three groups.Result:Before treatment,there were no significant differences in the assessment indicators among the three groups(P＞0.05).After treatment,only the TUGT test showed a significant difference compared to before treat-ment in the control group,while the other indicators showed no significant differences(P＞0.05).In the gait training group,only the average swing speed in the ML direction during the eyes-open test,the average swing speed in the AP direction during the eyes-closed test,and the movement length did not improve com-pared to before treatment,while the other indicators showed significant differences compared to before treat-ment(P＜0.05).In the QMT group,all indicators showed improvement compared to before treatment(P＜0.05).The QMT group showed significantly better results than the control group in terms of the average swing speed in the AP direction during the eyes-open test,the movement ellipse area,and ABC(P＜0.01).In the eyes-closed test,the QMT group showed better results than both the control group and the gait training group in terms of the average swing speed in the ML direction,the movement length,the average swing speed in the AP direction,the movement ellipse area,Berg Balance Scale,TUG,TUGT cognitive,DTC,TMTA,TMTB,and TMTB-A(P＜0.05).Conclusion:As an interactive exercise cognitive training,QMT training was found to be more effective in im-proving attention and executive function,dynamic and static balance function,and reducing dual-task costs than single exercise training in stroke patients.

Objective:To investigate the expression of transcription factor Zinc finger and BTB domain-containing 4 (ZBTB4) in papillary thyroid carcinoma and its relationship with the clinicopathological features of the tumor.Methods:Immunohistochemistry (IHC) was used to assess ZBTB4 protein of cancerous tissues and paired-normal tissues extracted from surgical samples of 60 patients with papillary thyroid carcinoma (30 classical and 30 with Hashimoto’s thyroiditis) . Fresh tissue samples were collected from above patients, and the expression of ZBTB4 gene mRNA and ZBTB4 protein in cancerous tissues was detected by qRT-PCR and Western blot methods. SPSS statistical software was used to analyze the relationship between the expression level of this gene in tumor tissues, clinicopathological features and tumor prognosis.Results:Immunohistochemical results showed that the expression of ZBTB4 protein in papillary thyroid carcinoma tissues was significantly higher than that in normal thyroid tissues (25.0% vs. 3.3%, P=0.001) . The results of qRT-PCR showed that the expression of ZBTB4 gene mRNA in tumor tissues was significantly higher than that in normal thyroid tissues ( P<0.001) . There was no significant difference in the expression level of ZBTB4 between patients with classical papillary carcinoma and those with Hashimoto’s thyroiditis. Multivariate analysis showed that the patients with higher expression of ZBTB4 had relatively smaller tumor diameter ( t=2.31, P=0.025) and less lateral cervical lymph node metastasis ( t=4.13, P=0.042) . Conclusions:Patients with higher ZBTB4 expression level have better outcome, as reflected in smaller tumor diameter and lower rates of lateral cervical lymph node metastasis. The molecular mechanism of ZBTB4 gene in papillary thyroid carcinoma needs further study.