Background Carbendazim (CBZ), a widely used benzimidazole fungicide, has raised increasing concerns regarding the health risks associated with its residues. However, the toxic effects and associated mechanisms of CBZ on the skeletal system have not been reported. Objective To elucidate the effects of carbendazim on osteogenic differentiation and its underlying mechanisms. Methods MC3T3-E1 mouse pre-osteoblastic cells were treated with 1, 10, and 100 μmol·L⁻¹ CBZ for 24 h to examine cell viability, alkaline phosphatase (ALP) activity, bone nodule formation, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and nitric oxide synthase (NOS) activity. Transcriptomics was used to identify differentially expressed genes (DEGs) in osteoblasts exposed to CBZ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were employed to analyze the potential biological pathways of DEGs. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to validate changes in gene and protein expression. Results Exposure to 10 and 100 μmol·L⁻¹ CBZ significantly reduced osteoblast viability, ALP activity, bone nodule formation, and NOS activity, while increasing intracellular ROS levels. CBZ at 100 μmol·L⁻¹ concentration significantly elevated MDA level (P < 0.05). The transcriptomic analysis revealed that 1 μmol·L⁻¹ CBZ treatment resulted in 385 significantly DEGs. The KEGG enrichment analysis revealed that CBZ significantly affects hormone regulation pathways (including parathyroid hormone, growth hormone, dopamine, and oxytocin), mitogen-activated protein kinase (MAPK) and cyclic GMP-dependent protein kinase G (cGMP-PKG) signaling pathways, focal adhesion and adherens junction, as well as the NOD-like receptor signaling pathway and the mRNA surveillance (NMD) pathway. The results of GSEA showed that CBZ significantly inhibited the bile acid metabolism and the Wnt/β-catenin pathway in osteoblasts. The validation results demonstrated that CBZ significantly suppressed the mRNA expression of Wnt3a and β-catenin, as well as the protein expression of Runx2 and Osterix in the Wnt/β-catenin pathway. Conclusion CBZ exposure exhibits potential skeletal toxicity, and its mechanism is through promoting oxidative stress, interfering with the Wnt/β-catenin pathway in osteogenic differentiation, thereby inhibiting the bone formation function of osteoblasts.

ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Medical cross-modal retrieval aims to achieve semantic similarity search between different modalities of medical cases, such as quickly locating relevant ultrasound images through ultrasound reports, or using ultrasound images to retrieve matching reports. However, existing medical cross-modal hash retrieval methods face significant challenges, including semantic and visual differences between modalities and the scalability issues of hash algorithms in handling large-scale data. To address these challenges, this paper proposes a Medical image Semantic Alignment Cross-modal Hashing based on Transformer (MSACH). The algorithm employed a segmented training strategy, combining modality feature extraction and hash function learning, effectively extracting low-dimensional features containing important semantic information. A Transformer encoder was used for cross-modal semantic learning. By introducing manifold similarity constraints, balance constraints, and a linear classification network constraint, the algorithm enhanced the discriminability of the hash codes. Experimental results demonstrated that the MSACH algorithm improved the mean average precision (MAP) by 11.8% and 12.8% on two datasets compared to traditional methods. The algorithm exhibits outstanding performance in enhancing retrieval accuracy and handling large-scale medical data, showing promising potential for practical applications.
Algorithms ; Semantics ; Humans ; Ultrasonography ; Information Storage and Retrieval/methods* ; Image Processing, Computer-Assisted/methods*

Online hashing methods are receiving increasing attention in cross modal medical image retrieval research. However, existing online methods often lack the learning ability to maintain semantic correlation between new and existing data. To this end, we proposed online semantic similarity cross-modal hashing (OSCMH) learning framework to incrementally learn compact binary hash codes of medical stream data. Within it, a sparse representation of existing data based on online anchor datasets was designed to avoid semantic forgetting of the data and adaptively update hash codes, which effectively maintained semantic correlation between existing and arriving data and reduced information loss as well as improved training efficiency. Besides, an online discrete optimization method was proposed to solve the binary optimization problem of hash code by incrementally updating hash function and optimizing hash code on medical stream data. Compared with existing online or offline hashing methods, the proposed algorithm achieved average retrieval accuracy improvements of 12.5% and 14.3% on two datasets, respectively, effectively enhancing the retrieval efficiency in the field of medical images.
Semantics ; Humans ; Algorithms ; Information Storage and Retrieval/methods* ; Diagnostic Imaging ; Image Processing, Computer-Assisted/methods*

Small cell lung cancer (SCLC) is the thoracic malignant tumor and accounts for about 15% of lung malignancies and transfer often occurs by the time of diagnosis. Extensive stage-small cell lung cancer (ES-SCLC) accounts for about 2/3 of all SCLC. For many years, radiotherapy has occupied an important position in the treatment of SCLC, especially in the treatment of ES-SCLC, because SCLC is more sensitive to radiotherapy. However, in recent years, immune checkpoint inhibitor has shown more excellent antitumor activity in the treatment of ES-SCLC and become the mainstream argument for the treatment of ES-SCLC. However, will radiotherapy be buried by the times among the therapeutic approaches for ES-SCLC? In this article, we will review the clinical progress of radiotherapy, immunotherapy and combination therapy for ES-SCLC.
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Humans ; Small Cell Lung Carcinoma/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Neoplasm Staging ; Radiotherapy/methods* ; Combined Modality Therapy

ObjectiveTo explore the biological mechanism of bone loss caused by perfluorooctanoic acid (PFOA) through transcriptomic analysis, and to provide new insights into regulating perfluoroalkyl substances (PFAS) applications and the prevention of hazards affecting bone health. MethodsMouse embryonic osteoblast precursor cells (MC3T3-E1) were exposed to 0.1, 1, 10, and 100 μmol·L^-¹ PFOA for 24 hours to assess the effects on cell viability and alkaline phosphatase (ALP) activity, and to determine the critical concentration of PFOA toxicity. The transcriptome sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) induced by PFOA. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted to identify significantly affected gene pathways. Additionally, Seahorse XF metabolic phenotyping and reverse transcription polymerase chain reaction (RT-PCR) were used to validate the key pathways. ResultsExposure to 10 and 100 μmol·L^-¹ PFOA significantly reduced the cell viability and ALP activity of MC3T3-E1 cells. Therefore, the results of transcriptomic analysis for 10 μmol‧L^-1 PFOA exposure found that a total of 80 DEGs were identified, including 32 upregulated genes and 48 downregulated genes. According to GO analysis, PFOA mainly affected cellular components such as mitochondrion and nucleus, molecular functions involving GTPase activity and GTP binding, as well as biological process related to mRNA processing. GSEA identified the downregulation of the β-oxidation of fatty acid pathway in mitochondria. Metabolic phenotyping reserches showed that PFOA indeed reduced mitochondrial aerobic respiration capacity and adenosine triphosphate (ATP) production, and the ratio of ATP production from cellular aerobic respiration to glycolysis was significantly decreased as well. The mRNA expression of glucose metabolism-related genes (GK, G6PD, and CS), as well as fatty acid metabolism-related genes (CPT1A and CPT2), were significantly downregulated. ConclusionPFOA reduces bone formation by inhibiting energy metabolism and β-oxidation of fatty acid pathways in osteoblasts, whihc lays the foundation for revealing the mechanism of PFOA exposure induced bone loss.

OBJECTIVE To explore the clinical efficacy of Wuhuang Shengji decoction irrigation combined with inci-sion and hanging suture in patients with perianal abscess.METHODS A total of 121 patients with perianal abscess admitted to the Anorectal Department of Ningbo Traditional Chinese Medicine Hospital from Jan.2022 to Jan.2024 were selected as the study subjects.According to the treatment methods,they were divided into a control group(n=37),a positive control group(n=41)anda research group(n=43).The control group was treated with incision and hanging suture,the positive control group was treated with recombinant human epidermal growth factor combined with incision and hanging suture,and the research group was treated with Wuhuang Shengji Decoction irrigation combined with incision and hanging suture.The clinical efficacy,the time of necrotic tissue shedding,new skin appearing,wound itch disappearing and wound healing and the recurrence rate were ob-served.The visual analogue scale(VAS),wound secretion score and expression levels of vascular endothelial growth factor(VEGF)and platelet-derived endothelial cell growth factor(PD-ECGF)in wound secretions were compared before and 14 days after treatment in the three groups.RESULTS The clinical efficacy of the study group(90.70%)was higher than that of the positive control group(87.80%)and control group(70.27%);the recur-rence rate of the study group(2.33%)was lower than that of the positive control group(9.76%)and the control group(18.92%),and the differences were statistically significant(P<0.05).The time required for necrotic tissue shedding,new skin appearing,wound itch disappearing and wound healing followed the trend of study group

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To construct multimorbidity patterns among elderly individuals with chronic diseases and to explore the relationship between these patterns and frailty.Methods:A cross-sectional study was conducted involving 4, 706 elderly participants aged 60 years and older from selected prefecture-level cities in Shaanxi Province.Data were collected on general information, chronic diseases, and frailty status.The average age of the participants was 69.9±6.7 years, with males comprising 47.3%(2, 255 cases)and females comprising 52.7%(2, 481 cases)of the sample.Latent class analysis(LCA)was employed to identify multimorbidity patterns, while multivariate logistic regression analysis was utilized to examine the associations between these patterns and frailty.Results:The prevalence of multimorbidity within the study population was found to be 43.6%(2, 052 cases out of 4, 706 cases).The highest rates of multimorbidity were observed in anxiety and depression(100%, 23 cases out of 23 cases), dementia(100%, 6 cases out of 6 cases), and Parkinson's disease(100%, 11 cases out of 11 cases).Stroke followed closely with a rate of 96.8%(597 cases out of 617 cases), while rheumatoid arthritis exhibited the lowest rate of multimorbidity with other chronic diseases at 50%(4 cases out of 8 cases).Five distinct multimorbidity patterns were identified through LCA: the complex multimorbidity class(123 cases), the stroke-respiratory class(546 cases), the sleep disorders-osteoarticular class(488 cases), the cardiovascular-metabolic class(987 cases), and the relatively healthy class(2, 562 cases).When compared to the relatively healthy class, the complex multimorbidity class( OR=2.317, 95% CI: 1.573-3.412), stroke-respiratory class( OR=2.279, 95% CI: 1.862-2.788), sleep disorders-osteoarticular class( OR=1.370, 95% CI: 1.111-1.691), and cardiovascular-metabolic class( OR=1.185, 95% CI: 1.003-1.400)were all found to be significantly associated with frailty. Conclusions:The cardiovascular-metabolic class is the most prevalent among elderly individuals.Various patterns exhibit distinct associations with frailty, with the complex multimorbidity class and the stroke-respiratory class being the most significant, as they markedly elevate the risk of frailty.