OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

This article provides a systematic interpretation and review of the Society of Critical Care Medicine 2024 Guidelines on Adult ICU Design. Developed based on the Grading of Recommendations Assessment, Development and Evaluation methodology, the guideline address five core themes: ICU layout, room design, infection control, infrastructure, and staff spaces, and put forward 17 evidence-based recommendations, including 5 good practice statements. This article briefly introduces the guideline development methods and evidence characteristics, and focuses on summarizing key recommendations, including high-visibility layouts, single-bed ward settings, natural lighting and noise reduction strategies, integrated infection prevention and control design, remote monitoring, and flexible capacity expansion capabilities. Furthermore, it delves into the applicability and localized implementation pathways within China's healthcare environment, analyzing limitations in terms of evidence quality, specialty applicability, and cost-effectiveness. Furthermore, by integrating the Chinese Guidelines for the Construction and Development of Critical Care Medicine (2025 Edition) and current domestic practices, the article proposes tiered and phased implementation recommendations. This article aims to provide domestic healthcare institutions with a scientific reference that balances international cutting-edge concepts with China's real-world conditions for the construction and renovation of ICUs, thereby promoting the development of intensive care environments centered on patient safety, healthcare worker well-being, and infection control.

Objective: To validate the performance of the Procleix UltrioPlex E assay (Grifols, Spain) on the Procleix Panther automated nucleic acid detection platform, which employs the TMA method to simultaneously detect HIV-1/HIV-2/HCV/HBV/HEV viruses, and to evaluate its value for screening transfusion-associated infectious diseases. Methods: In accordance with the requirements of ISO15189"Application of the Guidelines for the Accreditation of Quality and Capabilities of Medical Laboratories in the Field of Molecular Diagnostics (CNAS-CL02-A009: 2018)", "Guidelines for Performance Validation of Molecular Diagnostic Testing Procedures (CNAS-GL039: 2019)", and the "Technical Operating Procedures for Blood Banks (2019 Edition)", this study validated the reagent's performance in terms of analytical sensitivity validation, performance consistency validation, interference resistance, and cross-contamination resistance. Results: Probit analysis revealed that the 95% detection limits (95% confidence interval) for HBV, HCV, HIV, and HEV were 2.0 IU/mL, 1.5 IU/mL, 18.0 IU/mL and 3.7 IU/mL, respectively, which were consistent with the minimum detection limits stated in the kit's package insert and were comparable to the Procleix Ultrio Elite kit. Both kits were used to test the performance validation serum plate simultaneously, yielding results consistent with the serum plate (Kappa=1), indicating stable performance. Detection of medium-and low-concentration lipemia and weakly positive hemolysis samples demonstrated good interference resistance. Cross-contamination performance validation showed that the kit exhibited excellent cross-contamination resistance. Conclusion: The Procleix UltrioPlex E nucleic acid detection kit enables combined detection of HIV-1, HIV-2, HCV, HBV, and HEV, allowing single-test screening for multiple viruses in donor blood. The kit's analytical performance is stable and meets basic laboratory requirements, making it suitable for screening transfusion-associated infectious diseases in blood banks.

The herb pair Hedysari Radix-Angelicae Sinensis Radix is a classic combination embodying the theory of replenishing Qi and tonifying blood in traditional Chinese medicine. The two herbs are often used together to achieve the effects of replenishing Qi， tonifying blood， activating blood， and unblocking collaterals. Clinically， this herb pair is widely applied in the treatment of blood deficiency syndrome and hematopoietic dysfunction disorders such as myelosuppression induced by radiotherapy and chemotherapy. Modern research indicates that Hedysari Radix-Angelicae Sinensis Radix and their active components can synergistically promote hematopoiesis through multiple targets and pathways. At the cellular level， the active components directly activate hematopoietic stem cells （HSCs） and hematopoietic progenitor cells （HPCs）， promoting their proliferation and differentiation， while simultaneously stimulating the production and release of peripheral blood cells. Regarding molecular regulation， this herb pair can regulate the expression of various hematopoietic-related cytokines， such as stem cell factor and erythropoietin. Additionally， it modulates key signaling pathways， including phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） and Wnt/β-catenin， providing signal support for the hematopoietic process. Furthermore， Hedysari Radix-Angelicae Sinensis Radix can improve the hematopoietic microenvironment， protect bone marrow stromal cells， and eliminate free radicals through antioxidant effects， thereby reducing damage to hematopoietic cells. Furthermore， this herb pair regulates apoptosis-related proteins to inhibit excessive apoptosis of hematopoietic cells and increase their survival rate. Its material basis primarily includes active components such as Hedysarum polybotrys polysacchcrides and flavonoids， as well as Angelica sinensis polysaccharides and ferulic acid， which synergistically contribute to its hematopoietic-promoting effects. By elaborating on the active components and mechanisms of Hedysari Radix-Angelicae Sinensis Radix in promoting hematopoiesis， this paper aims to elucidate the molecular mechanisms underlying their hematopoietic effects and provide a reference for further research and clinical application.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

ObjectiveTo elucidate the critical role of rehabilitation medical records (including electronic records) in rehabilitation medicine's clinical practice and management, comprehensively analyzed the structure, core content and data standards of rehabilitation medical records, to develop a standardized medical record data architecture and core dataset suitable for rehabilitation medicine and to explore the application of rehabilitation data in performance evaluation and payment. MethodsBased on the regulatory documents Basic Specifications for Medical Record Writing and Basic Specifications for Electronic Medical Records (Trial) issued by National Health Commission of China, and referencing the World Health Organization (WHO) Family of International Classifications (WHO-FICs) classifications, International Classification of Diseases (ICD-10/ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), this study constructed the data architecture, core content and data standards for rehabilitation medical records. Furthermore, it explored the application of rehabilitation record summary sheets (home page) data in rehabilitation medical statistics and payment methods, including Diagnosis-related Groups (DRG), Diagnosis-Intervention Packet (DIP) and Case Mix Index. ResultsThis study proposed a systematic standard framework for rehabilitation medical records, covering key components such as patient demographics, rehabilitation diagnosis, functional assessment, rehabilitation treatment prescriptions, progress evaluations and discharge summaries. The research analyzed the systematic application methods and data standards of ICD-10/ICD-11, ICF and ICHI Beta-3 in the fields of medical record terminology, coding and assessment. Constructing a standardized data structure and data standards for rehabilitation medical records can significantly improve the quality of data reporting based on the medical record summary sheet, thereby enhancing the quality control of rehabilitation services, effectively supporting the optimization of rehabilitation medical insurance payment mechanisms, and contributing to the establishment of rehabilitation medical performance evaluation and payment based on DRG and DIP. ConclusionStructured rehabilitation records and data standardization are crucial tools for quality control in rehabilitation. Systematically applying the three reference classifications of the WHO-FICs, and aligning with national medical record and electronic health record specifications, facilitate the development of a standardized rehabilitation record architecture and core dataset. Standardizing rehabilitation care pathways based on the ICF methodology, and developing ICF- and ICD-11-based rehabilitation assessment tools, auxiliary diagnostic and therapeutic systems, and supporting terminology and coding systems, can effectively enhance the quality of rehabilitation records and enable interoperability and sharing of rehabilitation data with other medical data, ultimately improving the quality and safety of rehabilitation services.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

Objective To analyze the distribution of occupational hazard factors (OHFs) in key enterprises in Foshan City. Methods A total of 373 enterprises from 11 key industries in Foshan City in 2022 were selected as the research subjects using the purposive sampling method. Monitoring data of OHFs in workplaces were obtained and analyzed from the "Workplace Occupational Hazards Monitoring Information System" under "China Disease Prevention and Control Information System". Results Among the 373 enterprises, small and micro-sized enterprises, and large and medium-sized enterprises accounted for 85.5% and 14.5% respectively. A total of 24 137 sampling points in the workplaces were monitored for OHFs, with the national standard compliance rate of 92.1%. Among different OHFs, the compliance rates ranked from highest to lowest were chemical agents, dust, and noise (98.0% vs 89.3% vs 52.0%, P<0.01). A total of 63 131 workers were employed in 373 enterprises, among whom 29 753 were exposed to OHFs, yielding an overall exposure rate of 47.1%. Exposure rates of OHFs by enterprise scale, from highest to lowest, were micro-sized, small-sized, medium-sized, and large-sized enterprises (69.2% vs 52.7% vs 47.3% vs 39.0%, P<0.01). The proportion of workers participated in occupational medical examination was 85.1%, with re-examination proportion of 62.5% and the abnormality detection rate of 2.1%. Conclusion In key enterprises in Foshan City, the risk of noise exposure is relatively high, and the exposure rate of OHFs is highest in micro-sized enterprises. The occupational health supervision and management department needs to strengthen the governance of noise hazards in a targeted manner and urge enterprises (especially micro-sized enterprises) to fulfill their primary responsibilities in occupational disease prevention and control.