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Complementary therapies are gaining interest in palliative care. This study investigated the implementation of a complementary and integrative medicine (CIM) service on a palliative care unit of a Tertiary Care Center in Switzerland. This study aims to explore how health care professionals, patients, and family members perceive complementary medicine in specialized palliative care, identify related challenges and opportunities, and develop strategies for their effective and sustainable implementation into routine practice. In a first step, to check acceptability, in 2016, an interview study was carried out by conducting qualitative interviews with nurses, physicians and patients, and their relatives. In a second step, based on the results of the structured interviews, CIM experts developed complementary nursing interventions followed by an educational program and establishing CIM service on the ward. Eight nurses, six doctors, four patients, and three relatives were interviewed. The interviews revealed a generally positive attitude among all stakeholders with high acceptability. Key challenges faced by medical staff included time management, training needs, and interdisciplinary communication. Patients and relatives emphasized the need for CIM to alleviate symptoms, improve quality of life, and enhance confidence in integrated care. The developed nursing interventions include selected measures (wraps/compresses and rhythmic embrocations) targeting common symptoms like pain, nausea, anxiety, and respiratory distress. To ensure quality control and sustainability, the concept also features an organizational framework, regular specialist training, and a detailed manual and accessible videos, along with guidelines for documentation and quality assurance. Medical professionals, patients, and relatives viewed the implementation of complementary nursing interventions as beneficial for enhancing symptom management in palliative care. Establishing appropriate framework conditions based on current implementation research is essential, and further research on effectiveness and long-term implementation is needed.
Post-influenza bacterial infection is associated with higher severity and mortality rates. Qingfei Paidu decoction (QFPDD) has demonstrated efficacy as an anti-inflammatory therapeutic agent specifically for influenza. However, its role in bacterial secondary infection remains unclear. This study aimed to investigate the protective effects and underlying mechanisms of QFPDD in a mouse model of post-influenza bacterial infection. A mouse model of post-influenza bacterial infection was established to evaluate the therapeutic effects of QFPDD. QFPDD was administered prior to the full establishment of secondary bacterial infection. Body weight, body temperature, lung indexes and pulmonary bacterial load were evaluated by lung weighing and colony counting of lung tissue homogenates. Single-cell ribonucleic acid sequencing (scRNA-seq) was performed to characterize immune cell populations and cytokine expression levels in lung tissues. Neutrophil activation, neutrophil extracellular trap (NET) formation and coagulation-related markers were examined using molecular and biochemical approaches. In vitro, pam3cys-ser-lys4 (Pam3CSK4)-stimulated macrophages were used to assess cytokine production, while the expression of phagocytic receptors was evaluated in macrophages and neutrophils following Pam3CSK4 or heat-killed Staphylococcus aureus stimulation. In addition, phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils were utilized to assess the production of reactive oxygen species (ROS) and the activation of signaling pathways. QFPDD prevented body weight loss, reduced lung indexes, decreased lung bacterial load and alleviated hypothermia in secondary infected mice. ScRNA-seq analysis revealed decreased cytokine scores in the lungs following QFPDD treatment, with neutrophils exhibiting the highest cytokine scores among the 18 identified cell populations. QFPDD downregulated inflammatory mediators in neutrophils. Furthermore, QFPDD reduced the expression of xanthine oxidase, myeloperoxidase, citrullinated histone H3, and peptidyl arginine deiminase 4, accompanied by decreased S100 calcium-binding protein A8 and S100 calcium-binding protein A9 levels, suggesting that QFPDD can be associated with the reduced formation of NETs. QFPDD also decreased platelet activation and hypercoagulation markers. In vitro, QFPDD inhibited cytokine and chemokine production in macrophages and suppressed ROS generation and extracellular signal-regulated protein kinase phosphorylation in neutrophils. In addition, QFPDD significantly enhanced the expression of phagocytic receptors in macrophages and neutrophils. QFPDD confers protection against post-influenza bacterial infection by inhibiting the formation of NETs and cytokine storm, highlighting its potential as a candidate for further investigation in the prevention and treatment of this condition. Please cite this article as: Mu JW, Cheng T, Hu L, Lei B, Ma YH, Cui Y, Peng YC, Huang WB, Ge YW, Ho LP, Zheng YJ. Qingfei Paidu decoction, a compound Chinese herbal medicine, protects against post-influenza bacterial infection by inhibiting the formation of neutrophil extracellular traps and cytokine storm. J Integr Med. 2026; Epub ahead of print.
Postmastectomy pain syndrome (PMPS) is a prevalent chronic pain condition that occurs after breast cancer surgery, often impairing quality of life in survivors of breast cancer. Despite its prevalence, no standardized treatment has been established. Acupuncture has been reported to be an efficacious intervention for the management of chronic pain and may be an effective treatment for PMPS. This study aims to explore the effectiveness and safety of integrative treatment of acupuncture-based intervention for PMPS. This is a single-center, single-arm, prospective interventional study. Eligible participants are patients with breast cancer who experience chronic postoperative pain in the chest, neck, or shoulder with a numerical rating scale (NRS) score ≥4, are at least 6 months postcurative treatment, have no evidence of disease recurrence, and are not receiving anticancer treatment at enrollment. Participants will receive the intervention once weekly for 12 sessions, followed by a 4-week observation period. The primary end point is the change in the average pain NRS score from baseline to week 16. The study commenced in October 2023 and is scheduled to continue through March 31, 2027. The first participant was enrolled on October 24, 2023. As of the manuscript submission, 24 patients have been enrolled. This study will explore the potential role of an integrative treatment of acupuncture-based intervention in the management of PMPS. The results will contribute to the evidence base for acupuncture in PMPS and inform the design of future clinical studies.
Several artificial intelligence (AI) governance frameworks have emerged to help health systems (HS) address AI-related risks. However, most fail to capture the multidimensional and evolving nature of real-world governance. This systematic review aimed to synthesize existing AI governance frameworks for HS and to propose an integrative AI governance model identifying key components to guide AI-related policy, practice, and research in HS. A comprehensive search was conducted in 8 academic databases (PubMed, MEDLINE, Embase, ACM Digital Library, Web of Science, Scopus, Social Sciences Abstracts, and PsycINFO), gray literature databases, and international organization web portals in October 2024 (updates: July 2025 and March 2026) and limited to studies published from November 2014 to March 2026 in English, French, Spanish, or Portuguese. Eligible documents included peer-reviewed articles and reports proposing AI governance frameworks for HS. Two reviewers independently selected the frameworks, assessed their quality using the Appraisal of Guidelines for Research and Evaluation for Health Systems, and extracted data. Results were synthesized using thematic analysis. The research retrieved 10,175 records, among which 19 AI governance frameworks were identified. Most were published between 2022 and 2024 (n=13, 68%), half (n=10, 53%) were developed by authors based in North America, and only one-third (n=6, 32%) were derived from primary studies. The frameworks focused on 4 levels of AI governance: international (n=3, 16%), national (n=5, 26%), local (n=3, 16%), and organizational (n=8, 42%). All of them underline the crucial role of multidisciplinary bodies in the structure of AI governance in HS. Six key AI governance processes in HS emerged as critical: (1) need and/or problem identification (n=14, 74%), (2) data governance (n=17, 89%), (3) risk assessment and management (n=17, 89%), (4) validation and/or evaluation (n=18, 95%), (5) maintenance and monitoring (n=16, 84%), and (6) integration (n=9, 47%). Additionally, 4 pivotal relational mechanisms were identified: (1) ethical principles and/or values (n=17, 89%), (2) education and training (n=14, 74%), (3) communication (n=12, 63%), and (4) standards and regulations (n=13, 68%). Our study provides a comprehensive synthesis of existing AI governance frameworks for HS across 4 levels (local, regional, national, and international), underpinned by a quality assessment of the 19 identified frameworks. It differs from existing studies that concentrate on specific dimensions or settings by contributing an integrative AI governance model for HS comprising 2 dimensions and 4 relational mechanisms across the 4 levels, explicitly modeling their interactions. Future research should test and operationalize the proposed model to enhance its practical applicability. Strengthening the methodological rigor of AI governance frameworks will be essential for the responsible integration of AI in HS. As the framework is primarily grounded in Global North and English-language literature, validation in other contexts is warranted.
Artificial intelligence (AI) technology is advancing rapidly with algorithms and models for diverse applications, such as virtual disease biologist agents, target and drug discovery, and multimodal diagnosis and treatment, emerging at an increasingly rapid pace. The development and application of AI can effectively address long-standing challenges in the research and application of traditional Chinese medicine (TCM), including the difficulty of mining classic texts, insufficient standardization of diagnosis and treatment, and lengthy drug development cycles. This creates new opportunities for the development of TCM and further propels its transition from empirical medicine to precision medicine. To seize the opportunities presented by AI development, it is necessary to build a tripartite innovation system centered on "data-algorithms-computing power," to establish a research paradigm suited to the characteristics of TCM, and to achieve a deep integration of traditional wisdom with modern technology, thereby driving high-quality development of the TCM industry. Please cite this article as: Chen KX. Artificial intelligence empowers the innovation of traditional Chinese medicine. J Integr Med. 2026; 24(4):467-470.
This study aimed to develop pilot clinical skills assessment (CSA) modules for Korean medicine-specific procedures and to examine their preliminary appropriateness, perceived necessity, and feasibility as a foundation for future licensing-related assessment development. A participatory action research framework, supplemented by qualitative interviews, was used to develop 4 CSA modules-acupuncture, Chuna manual therapy, pulse diagnosis, and constitutional diagnosis-in collaboration with expert evaluators, students, and standardized patients. The modules were implemented as formative examinations for third-year Korean medicine students, after which semi-structured interviews were conducted to obtain feedback on module content, implementation processes, and scoring procedures. Each module was also reviewed using the RUMBA checklist (Realistic, Understandable, Measurable, Behavioral, and Achievable), together with ratings of perceived necessity and feasibility for possible future use in licensing-related assessment. Interview data were analyzed inductively at the level of individual responses and then compared across modules and participant groups. Qualitative analysis yielded 3 themes: content and scoring criteria, physical environment or simulators, and education or training. Participants emphasized the need to make key aspects of performance more observable, improve authenticity through simulators or task trainers, and strengthen the capacity of scoring systems to distinguish between levels of student performance. Across all modules, mean RUMBA scores were high in the understandable, behavioral, and achievable domains, whereas measurability was more problematic, especially for pulse diagnosis. These pilot findings clarify both the strengths and the limitations of Korean medicine-specific CSA modules. The modules received favorable ratings for understandability and achievability, whereas lower ratings for measurability and realism identified priorities for refinement before wider use. This study provides preliminary guidance for the continued development and broader evaluation of Korean medicine-specific performance assessments.
Radiation oncology has long paired precision with compassion, technical excellence with daily human connection. Integrative oncology extends that legacy, advancing a shift from reactive symptom management to proactive, coordinated care; from fragmented referrals to integrated pathways; and from isolated pilot efforts to implementation-ready science. In this volume of Seminars in Radiation Oncology international experts reflect on the collective toolbelt of integrative oncology, the maturation of the science, and the exciting opportunity before us in radiation oncology. By integrating complementary approaches alongside conventional treatment, integrative oncology seeks to improve symptom control, functional outcomes, treatment adherence, and quality of life, with emerging evidence supporting benefits in disease-free and overall survival in select settings. Integrative approaches include nutrition and the microbiome, physical activity, mind-body and nature-based interventions, acupuncture and East Asian medicine, Ayurveda, massage and manual therapy, yoga, tai chi, qi gong, music therapy, stress management, sleep medicine, herbs and supplements, psycho-oncology, and supportive care. Across this collection, three central themes emerge: (a) patient-centered care targeting symptoms that matter most to patients and caregivers; (b) data-driven practice grounded in clinical trials, guidelines, and mechanistic science; and (c) operational compatibility with radiation oncology workflows. We hope readers leave with two clear outcomes: practical integrative strategies applicable to patients beginning radiation therapy tomorrow, and a sharper understanding of the research and systems infrastructure required to make integrative oncology a standard and equitable component of care. The work presented here signals a structural evolution -aligning tumor control and survival with symptom science, biologic insight, and whole-person care. In doing so, radiation oncology is uniquely positioned not merely to participate in, but to lead the redefinition of integrative cancer care for the decades ahead.
To investigate brain activation and functional connectivity in the prefrontal and motor regions during observation, imagery and execution tasks of Tai Chi Yunshou in healthy adults using functional near-infrared spectroscopy (fNIRS). This cross-sectional study enrolled 100 healthy adults (48 males and 52 females; aged 26.23 ± 6.84 years) without a history of neurological, psychiatric or chronic diseases. All participants completed observation, imagery and execution tasks of Tai Chi Yunshou: (1) in the observation task, participants watched videos of the Tai Chi Yunshou movement; (2) in the imagery task, participants repeatedly imagined performing the Tai Chi Yunshou movement following verbal instructions; and (3) in the execution task, participants physically performed the Tai Chi Yunshou movement. The forty-channel wearable fNIRS system was utilized to evaluate the real-time cortical responses during the tasks. Cortical activation was analyzed using a general linear model, functional connectivity was assessed by Pearson correlation, and directional interactions between brain regions were examined using Granger causality analysis (GCA). During the observation task, right dorsolateral prefrontal cortex (DLPFC) and frontopolar area (FPA) were deactivated (P < 0.05). During the imagery task, right DLPFC, primary motor cortex (PMC) and premotor and supplementary motor cortex (PSMC) areas were activated. The bilateral Broca's areas, bilateral DLPFC, bilateral orbitofrontal areas, right FPA, right PMC, right PSMC and right primary somatosensory cortex were activated during the execution task. Execution of Tai Chi Yunshou showed strong functional connectivity within prefrontal cortex (PFC), within sensorimotor area as well as between PFC and sensorimotor area. The results of GCA suggested that Tai Chi Yunshou execution engaged more robust and widespread causal interactions among cortical areas compared to observation and imagery tasks. Different activation patterns were found among observation, imagery and execution of Tai Chi Yunshou. Compared with observation and imagery of Tai Chi Yunshou, execution of Tai Chi Yunshou activated and coordinated more brain regions in the PFC and sensorimotor areas, offering evidence that the practice of Tai Chi has the effect of harmonizing both the body and the mind. Please cite this article as: Fu H, Fan J, Liu XB, Li YX, Zhang JM, Xue C, Zhang J, Xie C, Zheng Z, Jiang LB, Li J, Zhong DL, Jin RJ. Brain cortical activation and functional connection of Tai Chi Yunshou during different tasks: An fNIRS study. J Integr Med. 2026; Epub ahead of print.
Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and remains a leading cause of cancer-related mortality worldwide. Aberrant glycosylation contributes to tumor progression by regulating receptor signalling, immune evasion, and metastatic. However, the prognostic and therapeutic relevance of glycosylation-related genes (GRGs) in LUAD has not been comprehensively defined. Therefore, this study aimed to comprehensively evaluate GRG-associated molecular subtypes and their clinical and therapeutic relevance in LUAD. Methods: GRGs were curated from multiple public databases and integrated with transcriptomic and clinical data from The Cancer Genome Atlas LUAD cohort (TCGA-LUAD) with validation in Gene Expression Omnibus (GEO) datasets. Consensus clustering, pathway enrichment, and immune profiling were used to identify glycosylation-associated subtypes. A glycosylation activity scoring (Glyco. marker) was developed to quantify glycosylation features. Drug response prediction was analyzed using OncoPredict and the Genomics of Drug Sensitivity in Cancer (GDSC) database. Single-cell RNA sequencing (scRNA-seq) was analyzed to evaluate cell-type-specific GRG expression. Selected proteins were by immunohistochemistry (IHC) in LUAD tissue microarrays. Results: GRG expression stratified 513 LUAD patients into four molecular clusters with distinct clinical and immune characteristics. The Glyco.High group showed elevated expression of MGAT5 (mannosyl (α-1,6)-glycoprotein β-1,6-N-acetylglucosaminyltransferase), ST6GAL1 (β-galactoside α-2,6-sialyltransferase 1), GALNT7 (polypeptide N-acetylgalactosaminyltransferase 7), and FUT8 (fucosyltransferase 8), frequent tumor protein p53 (TP53) mutations, increased immune checkpoint expression, and enrichment of regulatory T cells. The Glyco. marker score predicted overall survival and was associated with stemness signatures. Drug response prediction suggested reduced sensitivity to platinum chemotherapy and epidermal growth factor receptor (EGFR) inhibitors but increased sensitivity to phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) inhibitors. Conclusion: GRG-based molecular stratification identifies clinically distinct LUAD subtypes associated with immune regulation, tumor stemness, and therapeutic response. The Glyco. marker system provides a potential framework for prognostic assessment and precision oncology strategies in LUAD.
Nonpharmacological strategies are advocated as evidence-based treatment options for pain, yet these are rarely offered within the emergency department (ED) setting. Understanding how ED providers perceive these strategies can guide implementation efforts. The objective of this study was to qualitatively examine ED provider perceptions of conventional and complementary nonpharmacological pain strategies. Nine ED physicians from a single academic medical center completed a semi-structured interview conducted by a trained qualitative researcher. The interview focused on the provider's current pain management approach and perceived benefits, barriers, and facilitators of nonpharmacological pain treatments. Each interview was audio-recorded, transcribed verbatim, and analyzed using an iterative deductive-inductive approach. Findings were organized into themes and subthemes to inform a conceptual model of nonpharmacological intervention implementation. Six major themes emerged: 1) institutional context around intervention implementation, 2) professional beliefs about nonpharmacological pain interventions, 3) patient characteristics as a modifying factor, 4) intervention characteristics as a modifying factor, 5) process of implementation, and 6) engagement. Providers acknowledged benefits of nonpharmacological strategies, particularly for patients with chronic pain or history of opioid use. However, perceived barriers included negative patient perceptions of mind-body therapies, minimal ED provider training or education, limited time or care coordination support, and lack of physical space. Possible facilitators for integration included provider education, leadership support, and intervention tailoring. ED providers recognize the potential value of nonpharmacological pain treatment strategies. However, both broad healthcare and ED-specific barriers to implementation may limit routine use in the ED. Future efforts for improving pain management in the ED should identify strategies to address implementation barriers of evidence-based nonpharmacological interventions.
Refractive surgery can unmask or accelerate transforming growth factor-β-induced (TGFBI)-related corneal dystrophies that are undetectable by routine slit-lamp examination, creating a clear need for a rapid, standardized, preoperative genetic screening. We developed a multiplex, allele-specific real-time quantitative polymerase chain reaction (qPCR) panel targeting five high-frequency TGFBI hotspots (R124C/L/H, R555W/Q) and built a statistics-driven analytical framework to optimize assay decisions. Receiver operating characteristic (ROC) analysis defined locus-specific cycle threshold (CT) cut-offs that were harmonized to a single decision threshold (CT=36) to simplify deployment. Analytical sensitivity was established by Probit modeling of serial two-fold dilutions, and confirmed by ≥20 replicates per level. In a 158-sample validation set (38 mutation-positive; 120 negative), qPCR agreed perfectly with Sanger sequencing (Cohen's kappa coefficient (κ)=1.0). Probit analysis yielded locus-specific limit of detection (LoD) values ranging from 0.035 to 0.200 ng/µL; at 0.200 ng/µL, the detection rate was over 95%. Repeatability and intermediate precision were high (CT coefficient of variation (CV) 0.34%-1.21%). No cross-reactivity was observed against non-target TGFBI variants or other ophthalmic genes, and interference from blood, oral flora/rinse, or toothpaste produced small, bounded shifts (approximately -7.8% to +2.8%). Calibration with serial dilutions demonstrated linear CT-log(copy) relationships suitable for routine quality control. Prospective screening of 10 055 refractive surgery candidates identified six TGFBI carriers (0.06%) harboring R124H (including one homozygote), R124L, R124C, or R555W mutation, all confirmed by Sanger sequencing. This study established a clinically applicable, statistically optimized multiplex qPCR platform that integrated ROC-derived cut-offs and Probit-defined LoD with rigorous evaluations of precision, specificity, and robustness, enabling large-scale population implementation. Positive screening results guide clinical decision-making through a standardized post-screening workflow, and the targeted hotspot screening strategy serves as a cost-effective first-tier high-throughput approach for preoperative risk assessment. The framework provides a transparent, reproducible path to standardize preoperative TGFBI screening and reduce iatrogenic risk in refractive surgery candidates. TGFBI基因突变是导致角膜营养不良的重要病因，也是屈光手术术前必须排查的遗传风险因素。然而，目前仍缺乏稳定、灵敏且可标准化的多重检测体系。本研究构建了一套整合分析与统计框架，用于优化针对TGFBI高频突变位点的多重等位基因特异性定量聚合酶链反应（qPCR）检测方法，并系统评估其临床应用价值。通过条件优化、阈值确定、重复性与特异性验证，建立了可同时检测R124C/L/H、R555W/Q等关键突变的多重qPCR体系。统计分析结果表明，该方法扩增效率良好、重复性高且检出限低，在梯度稀释样本中表现出稳定的定量能力，且无明显非特异性扩增。受试者工作特征曲线（ROC）与概率单位（Probit）分析进一步验证了体系的准确性与可靠性，能够有效检出微量模板中突变序列。将该体系应用于大规模屈光手术候选者术前筛查，成功检出了低频TGFBI突变携带者，且结果与Sanger测序完全一致。上述结果证实，基于整合分析与统计优化的多重qPCR体系，能够高效、可靠地用于TGFBI突变筛查，为屈光手术提供标准化的术前遗传风险评估工具，也为其他遗传病位点的多重检测优化提供了可借鉴的统计与方法学框架。.
"Santé en 2050" is the first medical conference in France dedicated to the adaptation of healthcare systems to environmental constraints. Organized in 2024 and 2025 by healthcare professionals within The Shifters, a non-profit association committed to raising public awareness of the dual carbon challenge, the conference provided both a scientific platform for research on mitigation and adaptation in health and a forum to enhance professional competencies on these cross-cutting issues. Over its two successful editions, the event mapped the emerging disease landscape driven by environmental exposures and climate change, affecting both communicable and non-communicable diseases due to shifting temperatures, precipitation patterns, mass population movements, unhealthy lifestyles, and increasing pollution. Climate change also poses indirect threats to health by straining infrastructure, disrupting supply chains, and triggering crises that practitioners must address with ever-scarcer resources. The conference underscored the urgent need for a systemic overhaul of healthcare to build resilient, sustainable care pathways. It provided attendees with practical tools to integrate ecodesigned care, integrative medical approaches, and non-pharmacological interventions into their daily practice. The conference further explored pressing ethical and philosophical dilemmas, examining how technology, research priorities, and innovation must evolve in response to environmental constraints and the broader responsibility of medicine at a population level. Here we summarize the topics discussed during the two editions of the conference. By equipping healthcare workers with skills in epidemiology, disease prevention, and continuity of care amid accelerating environmental change, "Santé en 2050" aims to prepare the medical community for the challenges of tomorrow.
Integrative oncology interventions for patients undergoing radiation therapy (RT) may relieve symptoms (including procedural anxiety) and improve quality of life, though gaps remain in the evidence base to adequately guide implementation efforts. In this article we review clinical trials specifically for psychological (ie, mindfulness), physical (ie, exercise, acupuncture), and combination approaches (ie, yoga, tai chi, and qigong), in which several symptom-based clinical outcomes are impacted (ie, fatigue, sleep disturbance, pain, mood, and xerostomia). We identified at least 90 clinical trials and 15 systematic reviews and meta-analyses related to this topic, but note the predominance of early-phase investigations and some heterogeneity in study findings. We also assess opportunities across the radiation treatment continuum, noting most interventions were targeted during active radiation treatment. Future research ought to leverage novel hybrid study designs and multi-center community-based clinical settings (including cooperative groups) to confirm effectiveness and generalizability of findings of existing earlier phase clinical trials. Meanwhile, opportunities to improve clinical trial efficiency such as integrating advanced practice providers and patient-reported outcomes in routine care should be considered. As a field with procedural elements, established symptom trajectories, and often daily patient engagement, radiation oncology is poised to develop and implement interventions that advance symptom science and clinical outcomes for patients with cancer.
Severe COVID-19 is a global health concern despite continuous vaccination campaigns because current therapies, such as dexamethasone and remdesivir, do not considerably improve immune function, especially in high-risk individuals. SARS-CoV-2-specific T cells (CoV-2-STs) from vaccinated or convalescent donors are a promising new treatment that can enhance clinical outcomes and viral-specific immunity. CoV-2-STs improve T cell proliferation and recovery without raising safety concerns, according to randomized studies. Targeting patients for immunotherapy is made more difficult by the variability in COVID-19 progression brought on by variables like age and comorbidities. In order to further enable precision medicine and patient care, machine learning techniques are being used to analyze clinical data, predict disease severity, and optimize treatment. However, their use in guiding the treatment of novel therapies like CoV-2-STs using early cellular immunology data is limited and requires improvement. The purpose of this research was to stratify high-risk individuals using early immunological and clinical indicators, and to develop a prediction tool to enable individualized treatment decisions, either with standard of care (SoC) or with a combination of CoV-2-STs and SoC. A randomized phase 1-2 trial enrolled 87 patients with severe COVID-19 (CoV-2-STs+SoC: n=57; SoC only: n=30). We performed a post hoc machine learning analysis. Clinical and biomarker data from days 0 and 5 were analyzed longitudinally. Shrinkage linear discriminant analysis was used to create arm-specific prognostic models, and stratified cross-validation assessed performance (area under the receiver operating characteristic curve, area under the precision-recall curve, sensitivity, specificity, F1-score, and Brier score). To investigate arm-swap scenarios, Monte Carlo simulations (4 variance models) generated hypothetical early-treatment trajectories. Day 5 analysis revealed a significant difference in CD3+, CD8+, CD56+, and CoV-2-STs between the 2 treatment groups (CoV-2-STs+SoC vs SoC). At Day 60, 64.9% (37/57) of patients with CoV-2-STs+SoC survived, compared with 40% (12/30) of patients with only SoC, resulting in a crude odds ratio of 2.8 (95% CI 1.1-6.9) for recovery. SoC-only models had an area under the curve between 0.72 and 0.76, while CoV-2-STs+SoC models had an area under the curve between 0.86 and 0.88. Area under the precision-recall curve values for CoV-2-STs+SOC models were 0.74-0.78, with sensitivity ranging from 0.89 to 0.91 and specificity from 0.83 to 0.87, compared with SoC-only models with a sensitivity of approximately 0.95 and a specificity of 0.58-0.62. Simulation studies indicate that CoV-2-STs+SoC may benefit up to 30% (approximately 9/30) of patients receiving SoC alone. Misclassifying candidates with CoV-2-STs+SoC as SoC-only could increase critical outcomes by up to approximately 22%. A robust computational tool for severe COVID-19 risk stratification and treatment selection is presented. Precision medicine and early treatment outcome prediction are supported by clinical and immunological data integration. Prospective studies are needed to confirm its clinical utility.
Acute ischemic stroke (AIS) remains a leading cause of long-term disability, with approximately 70% of survivors suffering from motor, sensory, and language impairments that significantly affect their daily functioning and quality of life. Recent advances in neuroimaging have provided a more precise assessment of changes in brain gray matter volume (GMV) and functional connectivity (FC), both of which are closely correlated with disease severity, prognosis, and rehabilitation outcomes. Acupuncture, as a complementary therapy, has demonstrated potential in alleviating motor and language deficits following stroke. By integrating structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) data with comprehensive clinical evaluations, this research aims to objectively investigate the neural mechanisms underlying acupuncture-induced brain plasticity. Our goal is to explore how acupuncture may augment conventional AIS treatments by promoting neuroplasticity, offering a scientific basis for its integration into standard therapeutic protocols. The findings aim to advance our understanding of the neurobiological basis for integrative rehabilitation strategies, ultimately contributing to improved prognostic evaluation and optimized recovery trajectories for AIS patients. A total of 54 AIS patients with motor dysfunction were allocated to receive either acupuncture combined with western medicine treatment (AWT) group or WT group alone. The acupuncture points used included: Neiguan (PC6), Renzhong (DU26), Sanyinjiao (SP6), Weizhong (BL40), Zusanli (ST36), Fenglong (ST40), Taichong (LR3), and Yanglingquan (GB34). Patients in AWT groups received treatment 5 times per week for 8 weeks. National Institutes of Health Stroke Scale (NIHSS), the Fugl-Meyer assessment (FMA) and structural and fMRI data were collected at three time points: baseline (on the day of enrollment), week 8 (at the end of the acupuncture intervention), and week 12 (after a 12-week follow-up period post-intervention). GMV and FC analysis was performed to investigate the potential mechanism of acupuncture treatment by comparing differences in brain cortical structure and function between treatments. GMV: The AWT group manifested an increased GMV in the ipsilesional supplementary motor area (SMA) and contralesional anterior cingulate gyrus (ACG) by week 8. In contrast, the WT group witnessed a substantial decline in GMV within the ipsilesional median cingulate and paracingulate gyrus (DCG). At the 12-week follow-up, the AWT group further demonstrated a significantly greater increase in GMV in the ipsilesional superior temporal gyrus (STG) when compared to week 8. The between-group comparisons at week 8 disclosed that the AWT group had a significantly elevated GMV in the postcentral gyrus (PoCG) and contralesional inferior temporal gyrus (ITG) (p  = 0.005) in contrast to the WT group. By week 12, the AWT group also presented a marked increase in GMV in the ipsilesional ITG relative to the WT group. In the spearman correlation analysis, a positive correlation was identified in the AWT group between the GMV of the ipsilesional SMA at 8 weeks post-enrollment and the FMA score at week 12 (p  = 0.016, R = 0.487). Moreover, the GMV in the contralesional ACG exhibited a positive correlation with the FMA score at week 12 (p = 0.006, R = 0.540). Additionally, a negative correlation was also detected in the WT group between the GMV of contralesional PoCG and the NIHSS score at week 8 (p = 0.004, R = -0.540). FC: At 8 weeks post-enrollment, the AWT group exhibited significantly increased FC between the ipsilesional SMA and the contralesional middle temporal gyrus (MTG), between the contralesional PoCG and the ACG, and between the contralesional PoCG and the ipsilesional pallidum (PAL). In the WT group, increased FC was observed between the ipsilesional SMA and the contralesional STG, and between the contralesional PoCG and the ipsilesional middle occipital gyrus (MOG). No significant positive FC regions were identified in the between-group comparisons at either 8 weeks post-enrollment or the 12-week follow-up. In the spearman correlation analysis, the enhanced FC between the ipsilesional SMA and the contralesional MTG in the AWT group was positively correlated with the post-acupuncture FMA score (p = 0.043, R = 0.417). In the WT group, the enhanced FC between the contralesional PoCG and the ipsilesional MOG was positively correlated with the FMA score (p = 0.003, R = 0.567). The increased in GMV and enhanced FC in AIS patients following acupuncture intervention are correlated with improvements in neurological and motor functions. Acupuncture may promote neural network remodeling and the coordinate of brain structure and function. These findings suggest potential neurobiological mechanisms through which acupuncture can improve clinical outcomes in patients.
To study the associations of dietary intake of A and E vitamins, as well as plasma retinols, carotenoids, and tocopherols in relation to development of islet autoimmunity and progression to T1D. The Environmental Determinants of Diabetes in the Young (TEDDY) Study followed 7659 newborns with genetic susceptibility to T1D for 6 years in the USA, Finland, Germany, and Sweden. Dietary vitamin intake was assessed repeatedly with 3-day food-records in full cohort at ages 6 months to 6 years. Plasma retinols, carotenoids, and tocopherols were analysed in a nested case-control setting with 359 children with islet autoimmunity and 1033 matched controls. In the full cohort analyses, dietary intake of retinol, β-carotene, and vitamin E was not associated with the risk of islet autoimmunity or progression to T1D. Further, none of the plasma retinol, carotenoid, and tocopherol biomarkers were associated with islet autoimmunity or T1D in the full nested case-control analyses. We observed effect modification by country, breastfeeding, sex, and follow-up time for both intake and biomarkers of vitamins on the risk of islet autoimmunity or T1D, and some subgroup associations. Finally, a plasma carotenoid metabolite (likely zeinoxanthin) (OR 0.61, 95% CI 0.39, 0.95, p = 0.03) and γ-carotene at 6 months (OR 0.65, 95% CI 0.45, 0.94, p = 0.02) were inversely associated with the odds of developing GADA-first. Retinol, carotenoids and tocopherols were not consistently associated with islet autoimmunity. This study adds to the understanding of factors and their interactions related to T1D development.
Lung adenocarcinoma (LUAD) is a prevalent and lethal malignancy. The three-dimensional (3D) chromatin architecture significantly influences tumor progression, yet the contribution of 3D chromatin structure-related genes (3DCRGs) in LUAD remains unclear. This study was designed to explore the role of 3DCRGs in postoperative recurrence of early-stage LUAD, response to Sorafenib therapy in advanced LUAD, tumor progression, and the regulation of the tumor microenvironment (TME). Based on prior studies of chromatin 3D architecture, we curated 49 3DCRGs. Differential expression analysis in the TCGA-LUAD cohort identified 21 3D differentially expressed genes (3DDEGs) between tumor and adjacent normal tissues. Seven GEO datasets (GSE31210, GSE30219, GSE33072, GSE27389, GSE115002, GSE83836 and GSE31428) were used to screen key genes associated with early recurrence, Sorafenib response, and LUAD stage progression through integrated machine learning approaches, and the selected genes were validated in independent datasets. TME characteristics in high-risk early-stage LUAD patients were assessed using IOBR 2.0. Single-cell transcriptomic analysis (GSE200972) was utilized to identify cell populations enriched with the core genes, while spatial transcriptomics was employed to validate their spatial localization. Virtual single-gene perturbation analysis was performed using scTenifoldKnk to assess the functional convergence of core 3DCRGs in tumor proliferating cells. We identified 21 3DDEGs (|log2FC|≥ 0.5, q < 0.05). Machine-learning integration consistently highlighted SMC3, RAD21, FOXM1, MYBL2, and MTA3 as key regulators in postoperative recurrence in early-stage LUAD, response to Sorafenib treatment in advanced LUAD, and tumor progression across different stages of LUAD. Models constructed using these genes demonstrated robust performance and were validated in independent cohorts. IOBR analysis revealed that patients with high recurrence risk exhibited co-activation of glycolysis and oxidative phosphorylation, along with significantly increased infiltration of myeloid-derived suppressor cells (MDSCs) (P = 0.0001). Single-cell transcriptomic analysis demonstrated a significant enrichment of these genes within tumor proliferating cells (TPCs), and spatial transcriptomics confirmed their robust expression in epithelial hotspots regions. Virtual single-gene perturbation analysis using scTenifoldKnk revealed that all five core genes convergently regulate cell cycle, DNA replication, and mismatch repair pathways in tumor proliferating cells. Immunohistochemistry results confirmed that SMC3 protein expression was significantly higher in tumor tissues compared to adjacent normal tissues. This study identified five 3DCRGs (SMC3, RAD21, FOXM1, MYBL2 and MTA3) that significantly influence postoperative recurrence in early-stage LUAD, Sorafenib treatment response in advanced tumors, and clinical staging. These genes are enriched in TPCs and may promote tumor evolution and therapeutic resistance by coordinating stemness maintenance and metabolic-immune crosstalk. Our findings highlight the significance of chromatin 3D architecture in LUAD and provide a theoretical foundation for its application in cancer precision medicine and therapeutic intervention.
This study examined longitudinal associations between spirituality and quality of life (QoL) in women newly diagnosed with breast cancer and undergoing chemotherapy at a large tertiary cancer center. Women (N = 114) completed measures of spirituality (3 subscales of the Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being Scale: Meaning, Peace, and Faith) and health-related QoL (36-Item Short Form Health Survey) at study entry and 3- and 15-months later. Bias-corrected bootstrap tests were used to examine whether baseline Faith was indirectly associated with mental and physical QoL 15 months later via Meaning and Peace at 3 months. Baseline Faith was positively associated with Meaning (β = .31, p = .001) and Peace (β = .38, p < .001) at 3 months. Both Meaning [n = 94, effect = .07 (95% CI: .002, .17)] and Peace [n = 93, effect = .13 (95% CI: .02, .28)] mediated the association between Faith and mental QoL at 15 months. When baseline Meaning was controlled, the indirect effect of baseline Faith on mental QoL remained significant, [n = 94, effect = .07 (95% CI: .001, .18)], and increases in Meaning over the first 3 months became an even stronger predictor of later mental QoL (β = .36, p = .004), suggesting that change in meaning during active treatment is an especially important predictor of mental QoL. Overall, findings demonstrate that Faith is indirectly associated with long-term QoL through early increases in Meaning and Peace. Because 90% of participants were within 6 weeks of diagnosis, the study provided a unique perspective on spirituality during the early treatment period. Clinically, results highlight the importance of early assessment of spiritual well-being and suggest that meaning-focused interventions may enhance long-term QoL for women undergoing chemotherapy.
Sham acupuncture control is essential for evaluating the specific efficacy of acupuncture. However, the complex nature of acupuncture components presents challenges in designing an inert sham acupuncture control while maintaining blinding. Currently, no standardized guidance exists for the design of sham acupuncture controls. This study aimed to propose guidelines for optimizing the design of sham acupuncture in randomized controlled trials. The initial draft of the guidelines was developed through a literature review and expert interviews. The items in the guidelines were revised and finalized through consensus meetings. The resulting Recommendations for the DesIgn of sham acupuncture in RandomizEd Controlled Trials (the DIRECT guidelines) include issues to consider prior to adopting a sham acupuncture control, a five-stage framework for designing sham acupuncture, which addresses feasibility, risks, and recommendations for the implementation of sham acupuncture in clinical trials. These guidelines offer practical recommendations for establishing appropriate sham acupuncture controls and optimizing their implementation in randomized controlled trials of acupuncture. Please cite this article as: Chen Y, Liu XY, Liu ZS, Guo Y, Zhou KH, Bian ZX, Wu M, Tian RH, Yang F, Zhang LY, Lu Y, Lao LX, He LY, Liu CZ, Liu BY, Yan SY. Recommendations for the DesIgn of sham acupuncture in RandomizEd Controlled Trials (the DIRECT guidelines). J Integr Med. 2026; Epub ahead of print.
Approximately 40% of women stop endocrine therapy for hormone-receptor-positive breast cancer within the first 5 years of prescribed treatment because of side effects. Musculoskeletal complaints are among the most frequently reported side effects. The Cancer Of the BReast Asanas (COBRA) study examines the effect of an 18-week yoga programme on endocrine therapy-associated musculoskeletal complaints in women with breast cancer. In total, 140 women will be randomised in a 1:1 ratio to the intervention or waitlist control group. The intervention programme consists of two times a week 1-hour supervised Hatha or (easy) Vinyasa yoga classes at a yoga or sports centre for 18 weeks and once per week a half-hour at home using videos. The waitlist control group is asked to maintain their habitual lifestyle during the first 18 weeks and will participate in a similar yoga programme to the intervention group for the following 18 weeks. The control group yoga programme is offered live-remote. The primary outcome (musculoskeletal complaints) is assessed with the Brief Pain Inventory questionnaire at baseline and 18 weeks (primary comparison) and additionally at 36 weeks. Secondary outcomes include lower and upper extremity joint complaints, menopausal symptoms, fatigue, sleep, quality of life, anxiety and depression, cognitive complaints and habitual physical activity (all patient-reported), vital signs and anthropometrics, physical fitness, blood biomarkers, medication use, safety data and patient and teacher experiences. At baseline and 18 weeks, cognitive complaints are also assessed with an online neuropsychological test battery. The COBRA study was approved by the Medical Ethical Committee of the University Medical Center Utrecht. The study started on 8 October 2024, and 65 participants have been included (20 January 2026). Results will be submitted to an international peer-reviewed journal. NCT06480513.