Histone lactylation is a recently identified post-translational modification, wherein lactate mediates the enzymatic addition of lactyl groups to lysine residues on histones. Since its discovery, extensive research has demonstrated that histone lactylation is widely present in human tissues and plays a pivotal role in regulating the transcription of specific genes. Subsequent studies have further established this modification as a widespread epigenetic mark with significant physiological implications. With advancing research, accumulating evidence confirms that lactylation at distinct histone sites elicits diverse biological effects—such as promoting cell proliferation, driving inflammatory responses, and enhancing fibrosis—all of which profoundly influence disease progression and serve as key drivers of disease onset and development. Conversely, inhibiting histone lactylation can alter disease outcomes, positioning histone lactylation as a promising therapeutic target. Moreover, studies have revealed crosstalk between histone lactylation and other post-translational modifications, such as acetylation and methylation, which collectively regulate disease progression. Notably, lactylation occurs not only on histones but also on non-histone proteins. Histone lactylation activates specific gene transcription and reshapes metabolic epigenetics, while non-histone lactylation directly modulates enzyme activity, signal transduction, and protein stability. These two facets form a synergistic network through shared lactate pools, common modifying enzyme systems, and pathway crosstalk, thereby constructing a multi-dimensional regulatory framework—namely, the “histone lactylation-metabolism hub-non-histone lactylation” axis. This architecture bridges metabolism and epigenetics, and deciphering its topological structure may provide novel targets for precise intervention in diseases driven by lactate-mediated signaling hijacking. Traditional Chinese medicine (TCM), grounded in clinical practice, has been shown to regulate histone lactylation by modulating lactate metabolism and lactylation-related enzymes, thereby influencing disease progression. Moreover, certain TCM formulations exhibit potential as alternative therapies for drug-resistant diseases, underscoring the significance of further exploring TCM-mediated regulation of histone lactylation in future therapeutic strategies. This review aims to elucidate the mechanisms underlying histone lactylation, systematically delineate the associations between site-specific histone lactylation and various diseases, present a comprehensive landscape of the “lactate-histone lactylation and functional protein lactylation” axis, and summarize the mechanistic basis and research advances in TCM-mediated regulation of histone lactylation for disease treatment. Additionally, we discuss current challenges in histone lactylation research and propose future directions, ultimately aiming to deepen understanding and broaden perspectives on the roles and therapeutic potential of histone lactylation in disease.

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.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

With the rapid advancement of hemodynamic indices and monitoring technologies, their classification methods and application processes have become increasingly complex. Currently, no unified standard hasbeen established, making it difficult to fully meet the clinical requirements for hemodynamic management. To assist in hemodynamic monitoring assessment and therapeutic decision-making in critically ill patients, the Critical Hemodynamic Therapy Collaborative Group, in conjunction with the Critical Ultrasound Study Group, has jointly developed the Standard for the Application of Hemodynamic Monitoring Techniques in Critical Care. The first part of this standard systematically categorizes hemodynamic indicators into flow indicators, pressure and its derivative indicators, and tissue perfusion indicators, while elaborating on the clinical application of each. The second part establishes a standardized clinical implementation pathway for hemodynamic monitoring. It proposes a tiered monitoring strategy-comprising basic, advanced, indication-specific, and special scenario monitoring-tailored to different clinical settings. It emphasizes the central role of critical care ultrasound across all levels of monitoring and establishes hemodynamic assessment standards for organs such as the brain, kidneys, and gastrointestinal tract. This standard aims to provide a unified framework for clinical practice, teaching, training, and research in critical care medicine, thereby promoting standardized development within the discipline.

The intelligent oxygen management system is a software designed with various algorithms to automatically titrate inhaled oxygen concentration according to specific patterns. This system can be integrated into various ventilator devices and used during assisted ventilation processes, aiming to maintain the patient's blood oxygen saturation within a target range. This paper employs a scoping review methodology, focusing on research related to intelligent oxygen management systems in neonatal intensive care units. It reviews the fundamental principles, application platforms, and clinical outcomes of these systems, providing a theoretical basis for clinical implementation.
Humans ; Intensive Care Units, Neonatal ; Infant, Newborn ; Oxygen/administration & dosage* ; Oxygen Inhalation Therapy/methods* ; Respiration, Artificial

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

Objective To observe the feasibility of transesophageal echocardiography(TEE)combined with agitated saline contrast echocardiography(ASCE)for identifying morphological characteristics of high-risk patent foramen ovale(PFO)and evaluating the risk of PFO related stroke.Methods Totally 212 PFO patients diagnosed by TEE combined with ASCE were enrolled,including 100 cases with cryptogenic stroke(CS)(CS group)and 112 without CS(non-CS group).Anatomical morphological characteristics of PFO were comparatively analyzed between groups to screen the independent factors of CS.Results In CS group,the left and right atrial opening diameters of PFO were all larger than those in non-CS group in both resting-state and stimulated state.The aortic root diameter in CS group was larger than that in non-CS group,and the incidence of atrial septal aneurysm(ASA),high activity of the atrial septum,inferior vena cava valve or Chiari network,large amount of right-to-left-shunt(RLS)in stimulated state,and multiple outlets of the oval valve in CS group were all higher than those in non-CS group(all P＜0.05).Logistic regression analysis showed that ASA,high atrial septal activity,large amount of RLS and multiple oval valve outlets were all independent factors associated with CS(OR=0.211,0.384,0.999,0.199,all P＜0.05).Conclusion TEE combined with ASCE could identify anatomical characteristics of high-risk PFO and assess the risk of PFO related stroke.

Objective:To explore the optimization potential of clinical target volume (CTV) delineation proposed in the guidelines of the Oncology Group (RTOG), the Francophone Group of Urological Radiotherapy (GFRU), and the European Society for Radiotherapy and Oncology (ESTRO) based on prostate bed local occurrence patterns after radical prostatectomy identified using prostate-specific membrane antigen positron emission tomography (PSMA PET).Methods:A retrospective analysis was conducted on patients with local prostate bed recurrence after radical prostatectomy who underwent PSMA PET at the Department of Nuclear Medicine, Peking University First Hospital from September 2021 to February 2024. The central point of each recurrence was marked. A six-zone method was established based on prostate bed anatomy and the characteristics of cross-sectional imaging. Then, the positional relationships (within or outside) were recorded with respect to recurrences and CTV defined by the RTOG, GFRU, and ESTRO (CTV RTOG, CTV GFRU, and CTV ESTRO), followed the analysis of the recurrence rates and distribution characteristics of various zones. Results:A total of 63 patients with prostate bed recurrence after radical prostatectomy were enrolled in this study, including 97 recurrences. The recurrence rates in the six zones were as follows: 10% of zone 1, 22% of zone 2, 29% of zone 3, 2% of zone 4, 12% of zone 5a, 18% of zone 5b, and 7% of zone 6. Among these zones, zones 2 and 3 showed the highest and second-highest recurrence rates, respectively. CTV GFRU and CTV ESTRO completely covered zones 2 and 3, while CTV RTOG covered zone 2 completely and zone 3 partially. Zone 4, characterized by a low recurrence rate, was not covered by CTV GFRU and CTV ESTRO but was entirely covered by CTV RTOG. Zone 5a, with a recurrence rate of 12%, was completely covered by CTV RTOG but was partially covered by CTV GFRU and CTV ESTRO. The range of 1.3 cm in front of the posterior wall of the bladder covered all recurrences in zone 5a. Conclusions:For CTV delineation of the prostate cancer surgical bed, zone 4, the anterior half of the bladder above the pubic symphysis midpoint, should be contracted due to the low recurrence rate in this zone. In contrast, the anterior boundary above the pubic symphysis midpoint should extend to 1.3 cm in front of the posterior wall of the bladder to completely cover the recurrence zones.

Undifferentiated spindle cell sarcoma of the prostate is clinically rare. This article reports a case of a 29-year-old male who presented on February 7，2022，with a two-week history of localized pain in the perineal area and spermatic cord. The diagnosis of prostatic undifferentiated spindle cell sarcoma was confirmed by imaging studies and prostate needle biopsy pathology. After consultation by the urologic oncology multidisciplinary team and considering the patient's preference，a treatment plan of radical radiotherapy combined with chemotherapy，immunotherapy，and targeted therapy was adopted，Partial stereotactic body radiotherapy（P-SBRT）was delivered to the tumor center with a total dose of 74.4 Gy，combined with cisplatin and pembrolizumab. Lung metastasis progression occurred 1.5 months after radiotherapy，and treatment was switched to a combination of pirarubicin，ifosfamide，pembrolizumab，and bevacizumab. After 39 months of follow-up，the disease remained well-controlled with preserved organ function and long-term survival. This case，utilizing a multidisciplinary comprehensive diagnosis and treatment model，provides a reference for organ-preserving non-surgical management in patients with prostate soft tissue sarcoma.