Malignant tumors represent a major threat to global health. Conventional anti-tumor pharmacotherapy often encounters challenges such as drug resistance, highlighting an urgent need for the development of novel therapeutic strategies. Fatty acid synthase (FASN), the key enzyme catalyzing de novo fatty acid synthesis, is subject to precise regulation at multiple levels, including transcriptional control, various post-translational modifications such as ubiquitination and phosphorylation, as well as modulation by diverse signaling pathways. Recent studies have revealed that FASN is aberrantly overexpressed in various malignant tumors and is closely associated with tumor progression and poor patient prognosis. FASN is a homodimer composed of seven functional domains that catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to generate saturated fatty acids, primarily palmitic acid. Its stability is regulated by multiple ubiquitin ligases and deubiquitinating enzymes. Additionally, FASN is subject to upstream regulation via neural precursor cell-expressed developmentally downregulated 8 (Nedd8) modification and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, thereby establishing a metabolic-signaling positive feedback loop. As a core executor of metabolic reprogramming, FASN promotes tumorigenesis through dual mechanisms. First, its fatty acid synthesis product, palmitate, participates in membrane phospholipid synthesis, lipid raft formation, and protein palmitoylation, thereby activating several key oncogenic signaling pathways, including PI3K/AKT/mTOR, wingless-type MMTV integration site family member (Wnt)/β‑catenin, and signal transducer and activator of transcription 3 (STAT3)/matrix metalloproteinase (MMP), leading to tumor development and progression. Second, FASN plays a pivotal role in modulating the anti-tumor functions of immune cells and remodeling the tumor immune microenvironment. Specifically, FASN enhances immune checkpoint inhibition by inducing programmed death-ligand 1 (PD-L1) palmitoylation, suppresses the activation of cytotoxic T lymphocytes and natural killer cells, and promotes the polarization of M2-type macrophages, consequently facilitating tumor immune evasion and malignant progression. Precisely due to its significant overexpression in tumor cells, its critical functional role, and its differential expression compared to normal cells, FASN has emerged as a highly promising target for anti-tumor drug development. Highly selective small-molecule inhibitors, notably represented by TVB-2640, have advanced to clinical trial stages and demonstrated favorable anti-tumor activity. Furthermore, the combination of FASN inhibitors with other chemotherapeutic agents or targeted drugs can overcome the limitations of monotherapy through synergistic effects or by resensitizing tumor cells to conventional drugs, achieving a “1+1>2” therapeutic outcome. With the advancement of modern traditional Chinese medicine (TCM), numerous active ingredients derived from TCM have been confirmed to exert anti-tumor effects by modulating FASN-related pathways. This integrated approach leverages the precision of Western medicine while simultaneously harnessing the holistic regulatory benefits of TCM to alleviate the side effects of radiotherapy and chemotherapy. Despite the promising prospects of FASN-targeted therapies, challenges remain, including tumor cell metabolic plasticity, tumor context-dependent responses, and heterogeneity. This review systematically summarizes the molecular structure, physiological functions, and mechanisms of FASN in tumorigenesis, as well as recent advances in targeted therapies. Future directions—including the precise identification of responsive patient populations using spatial transcriptomics, the development of novel combination regimens, and the active exploration of integrative strategies combining traditional Chinese and Western medicine—will facilitate the clinical translation of FASN-targeted therapies and open new avenues for improving the quality of life and prognosis of cancer patients.

Lung cancer， with persistently high incidence and mortality rates， remains a significant global health challenge. By taking the study on the experience in diagnosis and treatment of lung cancer with phlegm-dampness and blood stasis syndrome by distinguished traditional Chinese medicine physicians of the Sichuan School as an example， the diagnosis and treatment system for lung cancer with phlegm-dampness and blood stasis syndrome， which was formed in response to the humid and foggy environment of the Sichuan Basin， possesses unique value. However， traditional inheritance modes face challenges such as fragmentation， lack of standardization， and insufficient quantification， which hinder the promotion and application of this experience. This research focused on how to leverage multimodal data and artificial intelligence-generated content （AIGC） to achieve precise analysis， intelligent inheritance， and clinical innovation of the experience in diagnosis and treatment of lung cancer with phlegm-dampness and blood stasis syndrome by distinguished traditional Chinese medicine physicians of the Sichuan School. By integrating multimodal data （encompassing four diagnostic methods of traditional Chinese medicine， modern medical imaging， clinical laboratory tests， molecular biology， and regional environmental information）， a precise diagnosis and treatment system integrating macro and micro perspectives for the "disease， syndrome， and pathogenesis" was constructed. The research yielded the following results： （1） In precise syndrome differentiation， the objective quantification of the phlegm-dampness and blood stasis syndrome was achieved. By constructing a "four diagnostic methods， imaging， and molecule" correlation model， the study revealed intrinsic links between tongue and pulse parameters and the tumor microenvironment， as well as between regional climatic factors and syndrome characteristics， enabling real-time dynamic monitoring of efficacy. （2） In elucidating patterns， the study systematically explored the syndrome differentiation thoughts of Sichuan School physicians， such as the timing of purgation and tonification. A "pathogenesis， syndrome complex， and prescriptions and herb" network model was constructed， which accurately elucidated the synergistic action mechanisms of core herb pairs and quantified the dynamic compatibility patterns of reinforcing healthy Qi and eliminating pathogenic factors. （3） In intelligent empowerment， an auxiliary system integrating intelligent syndrome differentiation， treatment plan generation， and efficacy evaluation was built. This system can fuse regional characteristics with individual data， dynamically generate and optimize personalized prescriptions aligned with the experience of Sichuan School， and predict efficacy trends and potential adverse reactions. The integration of multimodal data and AIGC can effectively facilitate the structured inheritance and clinical translation of distinguished physicians' experience. The established intelligent diagnosis and treatment model integrating traditional Chinese medicine and Western medicine demonstrates clear potential in prolonging patients' progression-free survival， alleviating symptoms， and reducing adverse reactions to treatment. This study provides a referential methodological framework for the traditional Chinese medicine experience in diagnosis and treatment of lung cancer， especially the empirical inheritance and modernized development of regional academic schools. It contributes to advancing clinical diagnosis and treatment toward greater precision and personalization.

Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO₂), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective: To investigate the association of physical activity and screen time with overweight and obesity among children and adolescents with special needs in Tianjin, so as to provide scientific evidence for childhood obesity prevention and intervention measures in the population. Methods: From January 2022 to June 2024, 296 children and adolescents with intellectual disabilities and autism spectrum disorders aged 2-18 years were recruited from special education schools and institutions in Tianjin. Height and weight were measured, and a standardized questionnaire was used to assess physical activity and screen time. Binary Logistic regression analysis was carried out to investigate the association of physical activity and screen time with overweight and obesity. Results: The prevalence of overweight and obesity among children and adolescents with special needs in Tianjin were 17.2% and 21.6%, respectively, and the combined prevalence of overweight and obesity was 38.9%. The median of moderatetovigorous physical activity (MVPA) time was 0.20 h/d, and physical activity sufficiency rate was 7.8%. The median of screen time was 1.79 h/d, and the screen time compliance rate was 68.2%. The binary Logistic regression results showed that lower levels of MVPA time and increased screen time were associated with a higher risk of overweight and obesity among children and adolescents with special needs [OR(95%CI)=1.80(1.06-3.07), 2.40(1.42-4.07),P<0.05]. Conclusions Insufficient physical activity and excessive screen time are associated with an increased risk of overweight and obesity among children and adolescents with special needs. Therefore, comprehensive intervention measures should be implemented as early as possible to prevent and reduce the incidence of overweight and obesity in this population.

Objective:To explore the impact of Epstein-Barr Virus(EBV) infection on treatment response and survival in newly diagnosed multiple myeloma(MM).Methods:The clinical data of 196 patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from June 1st, 2019 to February 25th,2021 were analyzed retrospectively and divided into EBV-positive group (106 cases) and negative group (90 cases) according to the primary EBV DNA results in peripheral blood mononuclear cells.To analyse the distribution of EBV positive rates in each type and in each stage of the Revised International Staging System (R-ISS), and to compare EBV DNA loads in EBV-positive patients among R-ISS stages.Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis between the two groups.The clinical prognosis of EBV-positive patients was summarized through survival analysis and Cox regression.Results:The EBV positive rate in patients with newly diagnosed MM was 54% (106/196), with the highest rate in patients with κ light chain type (9/12).Patients with R-ISS stage Ⅲ had a significantly higher positive rate than with stage Ⅰ ( χ2=4.68, P=0.031) and stage Ⅱ ( χ2=6.04, P=0.014), but there was no significant difference in EBV DNA loads between EBV-positive MM patients by stage ( Z=3.27, P=0.195).Serum creatinine (Scr) and β 2-microglobulin (β 2-MG) levels were higher in the EBV-positive group than in the EBV-negative group ( Z=1.98, P=0.048 and Z=2.08, P=0.038), and the occurrence of t(4;14) was also higher in the EBV-positive group ( χ2=3.93, P=0.047).The proportion of complete response (CR)/stringent complete response(sCR) and very good partial response(VGPR) after completion of the fourth chemotherapy were significantly lower in the EBV-positive group than in the EBV-negative group ( χ2=12.82, P=0.001 and χ2=8.30, P=0.004), and a higher rate of progressive disease (PD) occurred in the EBV-positive group ( χ2=4.48, P=0.046).The 2-year progression-free survival (PFS) of MM patients was shorter in the EBV-positive group compared to that in the EBV-negative group ( Z=-4.50, P0.01).Cox regression analysis showed that R-ISS stage Ⅲ ( HR=5.38, 95% CI 1.28-22.56, P=0.021), failure to achieve VGPR after the fourth chemotherapy ( HR=3.02, 95% CI 1.42-6.46, P=0.004), EBV-positive ( HR=1.98, 95% CI 1.02-3.87, P=0.045), with 1q21 amplification ( HR=2.35, 95% CI 1.16-4.75, P=0.017) and 13q14 deletion ( HR=1.93, 95% CI 1.01-3.67, P=0.046) were independent risk factors for PFS in newly diagnosed MM. Conclusions:EBV infection is an independent risk factor for poor prognosis, which has important clinical implications for the outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Objective To develop a decision support system for clinical nursing plans based on nursing diagno-sis and explore its application effects,in order to provide references for optimizing the clinical nursing process and improving the quality of nursing.Methods A multidisciplinary research team was established to construct a clini-cal nursing plan decision support system framework from 3 aspects,namely nursing diagnosis,nursing interventions,and outcome tracking.The system built a clinical nursing diagnosis decision knowledge base through 3 dimensions,namely basic nursing diagnoses,specialty disease nursing diagnoses,and nursing-related technical diagnoses.Deep learning-based artificial intelligence capture technology was developed to achieve intelligent matching and generate clinical nursing plan forms.Implemented in a tertiary hospital in Yichang City,Hubei Province,a control group(June to August 2024)and an experimental group(October to December 2024)were compared regarding nursing diagnosis implementation rate,nursing plan documentation accuracy,and clinical nursing quality scores.Results This research showed a significant improvements for nursing diagnosis implementation rate increased from 94.88％to 97.25％,and nursing plan documentation accuracy improved from 90.38％to 95.33％.Compared with the control group,the experimental group demonstrated statistically significant enhancements in deep vein thrombosis preven-tion,fall prevention,pressure injury management,unplanned extubation control,bloodstream infection control,catheter-related infection prevention,and key specialty nursing quality indicators(all P＜0.05).Conclusion The nursing di-agnosis-based clinical decision support system effectively improves nurses'diagnostic implementation rates,enhances documentation accuracy of nursing plans,and elevates overall clinical nursing quality.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.