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

Objective: To summarize the treatment methods and efficacy of a patient with pure red cell aplasia (PRCA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to accumulate relevant case data. Methods: The clinical treatment and laboratory test data of a patient with PRCA after allo-HSCT in our hospital were retrospectively collected. The therapeutic strategy, monitoring parameters, and treatment outcomes were summarized. Results: Upon suspicion of post-transplant PRCA, the patient was promptly treated with intravenous injection of human immunoglobulin and three sessions of plasma exchange. The titer of blood group antibodies in the patient decreased, and the hemolytic symptoms were relieved. Over one year post-transplantation, the patient exhibited a sustained impairment of erythropoiesis, necessitating continued red blood cell transfusions. After treatment with intravenous daratumumab (400 mg twice weekly for 4 weeks), the pateint's hemoglobin (Hb) and reticulocyte (Ret) levels normalized rapidly, the ABO blood type converted from the recipient to the donor type, and the titer of IgM blood group antibodies returned to normal. The patient was successfully weaned off red blood cell transfusions, indicating the clinical efficacy of the treatment. Conclusion: Daratumumab shows effectiveness in the treatment of refractory PRCA after allo-HSCT in the case. It is essential to monitor Hb, Ret and the titer of blood group antibodies during treatment. Nevertheless, the interference of daratumumab with the titer of blood group antibodies should be considered.

Endometriosis(EMs)is a common estrogen-depend-ent clinical disease with the pathological characteristics of malig-nant tumors,which has great impact on women's physical and mental health.In recent years,experimental exploration has re-vealed that ectopic foci are in a hypoxic environment outside the uterine cavity,and mitochondria,as the"functional factories"of the cells,play an important role in the process of planting and in-vasion,and the mitochondrial quality control system,which in-cludes mitochondrial oxidative stress,kinetics,autophagy,bio-genesis and calcium homeostasis,is a key mechanism for the e-quilibrium of the mitochondrial function.The mitochondrial quality control system,including mitochondrial oxidative stress kinetics,autophagy,biogenesis and calcium homeostasis,is a key mechanism for mitochondrial functional balance.Therefore,to clarify the role of the mitochondrial quality control system in the development of EMs with the help of rational and rigorous experi-mental and clinical studies can not only help to clarify the patho-genesis of the disease,but also explore the key targets in the prevention and treatment of the disease.Therefore,this article summarizes the research progress of mitochondrial quality control system in endometriosis,with a view to providing reference and theoretical basis for the etiology,pathogenesis and prevention strategies of EMs.

The cribriform fascia is formed by the fusion of deep and superficial fascias in the axilla,and it forms the base of the axilla together with the subcutaneous tissue and skin,which is a key part of the system of the membranous anatomy of breast surgery.The loose anatomical structure of the cribriform fascia makes it an important anatomical landmark in the axillary region,which plays an important role in accurate localization of lymph nodes.The sentinel lymph node biopsy through cribriform fascia has less intraoperative blood loss and shorter catheterization time compared with the traditional axillary fold approach.However,the anatomical structure of the cribriform fascia and its significance in the membranous anatomy of breast surgery have not been fully elucidated.This article analyzes the anatomical structure of the cribriform fascia and its adjacent tissues,and emphasizes the anatomical structure that needs to be paid attention to in sentinel lymph node biopsy through the axillary cribriform fascia,so as to provide a reference for clinicians to fully understand the cribriform fascia structure.

AIM To study the chemical constituents from the leaves of Drynaria fortunei(Kunze)J.Sm.and their antioxidant activity.METHODS ODS-AG-HG,Sephadex LH-20 and semi-preparative HPLC were used for separation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH mothod.RESULTS Fifteen compounds were isolated and identified as kaempferol-3-O-neohesperidoside(1),dihydrodehydrodiconiferyl alcohol(2),kaempferol-3,7-di-O-α-L-rahmnoside(3),astragalin(4),loliolid(5),trichothecene analogue(6),2,2-[bis-4-(2,3-dihydroxypropoxy)phenyl]propane(7),maculatin(8),trichothecin(9),4-[(Z)-but-2-enoyloxy]-8-chloro-12-hydroxy-7,13-epoxytrichothec-9-ene(10),8-deoxy-trichotecin(11),β-sitosterol(12),daucosterol(13),afzelin(14),samwinol(15).The IC50 values of the leaf and rhizome extracts against DPPH free radicals were(0.072±0.005),(0.287±0.012)mg/mL,respectively.CONCLUSION Compounds 1,2,5-11,15 are isolated from this plant for the first time.The leaves of D.fortunei exhibit strong antioxidant activity.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective To propose a novel identification algorithm based on ensemble learning for assessing the severity of acute respiratory distress syndrome(ARDS)to achieve continuous monitoring of the disease severity.Methods Firstly,leve-raging the open-source MIMIC-Ⅳ database,a variety of non-invasive physiological parameters of patients were extracted and subjected to preliminary preprocessing.A multivariate feature selection algorithm was employed to rank these parameters and calculate feature importance scores through weighted computation.Secondly,based on the feature importance scores,a subset search algorithm was utilized to identify the subset of features that could yield optimal performance across four machine learning algorithms:neural networks,logistic regression,AdaBoost and XGBoost.Finally,a soft voting ensemble method was designed using a generalized linear regression model to integrate the results of each single machine learning algorithm,and a multivariate ensemble learning algorithm was proposed by combining the optimal feature subsets.The algorithm proposed when used to identify the severity of ADRS was evaluated with MIMIC-Ⅳ database,and compared with the traditional algorithms.Results The sensitivity,specificity,accuracy and AUC of the algorithm were 87.15％,89.23％,88.34％and 0.923 4,respectively,all of which outperformed those of the traditional algorithms.Conclusion The ARDS severity identification algorithm based on ensemble learning is capable of achieving continuous and real-time monitoring of the severity of ARDS,thereby offering robust support for the early identification and warning of ARDS in patients.[Chinese Medical Equipment Journal,2025,46(2):1-9]

Neuroinflammatory responses play an important role in the pathogenesis of various diseases, particularly those affecting the central nervous system. Inhibition of neuroinflammation is a crucial therapeutic strategy for the management of central nervous system disorders. The intestinal microbial-gut-brain axis serves as a key regulatory pathway that modulates neuroinflammatory processes. Intestinal flora metabolites such as short-chain fatty acids, indoles and their derivatives, lipopolysaccharides, trimethylamine oxide, and secondary bile acids exert direct or indirect effects on neuroinflammation. Studies have shown that electroacupuncture (EA) modulates the composition of the intestinal microbiota and its metabolites, while also suppressing neuroinflammation by targeting the TLR4/NF- κ B, NLRP3/caspase-1, and microglial cell M2-type transformation pathways. This review discusses the mechanisms by which EA regulates neuroinflammation via intestinal microbiota and its metabolites, providing information and a foundation for further investigation of the precise therapeutic mechanisms of EA in neurological disorders.
Humans ; Gastrointestinal Microbiome ; Electroacupuncture ; Neuroinflammatory Diseases/metabolism* ; Animals

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*