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.

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

Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

OBJECTIVE: This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules (QFG) in inhibiting colitis-associated colorectal cancer (CAC) development via RNA sequencing (RNA-seq) and 16S ribosomal RNA (rRNA) correlation analysis. METHODS: CAC was induced in BALB/c mice using azoxymethane (AOM) and dextran sulfate sodium (DSS), and QFG was administered orally to the treatment group. The effects of QFG on CAC were evaluated using disease index, histology, and serum T-cell ratios. RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change. Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence. The link between microbiota and CAC-related markers was explored using linear discriminant analysis effect size and Spearman correlation analysis. RESULTS: Long-term treatment with QFG prevented AOM/DSS-induced CAC formation, reduced levels of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), IL-6, and interferon γ (IFN-γ), and increased CD3⁺ and CD4⁺/CD8⁺ T cells ratio, without causing hepatic or renal toxicity. A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances. Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/nuclear factor kappa-B (NF-κB) pathway as key for QFG's treatment against CAC. Furthermore, QFG decreased the abundance of Bacilli, Bacillales, Staphylococcaceae, Staphylococcus, Lactobacillales, Aerococcus, Alloprevotella, and Akkermansia, while increasing Clostridiales, Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Muribaculaceae, which were highly correlated with CAC-related markers or NOD2/NF-κB pathway. CONCLUSION By mapping the relationships between CAC, immune responses, microbiota, and key pathways, this study clarifies the mechanism of QFG in inhibiting CAC, highlighting its potential for clinical use as preventive therapy.

Objective To investigate the changes and clinical value of inflammatory derived indices re-lated to myelosuppression caused by chemotherapy in patients with solid tumors.Methods The clinical data of 189 patients with malignant tumor who received chemotherapy in Jiangxi Cancer Hospital from January 2022 to August 2023 were retrospectively analyzed.According to the grade of myelosuppression,they were di-vided into 0 degree(n=35),Ⅰ degree(n=23),Ⅱ degree(n=31),Ⅲ degree(n=21),Ⅳ degree non-infec-tion(n=51)and Ⅳ degree infection(n=28).The levels of inflammatory index[monocyte(MO),lympho-cyte(LY)],reticulocyte(RET),prealbumin(PA),albumin(ALB),inflammatory infection index[C reactive protein(CRP)and serum amyloid A(SAA)]and complex derived inflammatory index[neutrophil to lym-phocyte ratio(NLR),systemic immunoinflammatory index(SII),systemic inflammatory response index(SI-RI),lymphocyte to C reactive protein ratio(LCR),C reactive protein to albumin ratio(CAR)]were collected and compared in patients with different degrees of myelosuppression.The correlation between each index and myelosuppression score was analyzed,and the influencing factors of myelosuppression after chemotherapy in tumor patients were analyzed by multivariate logistic regression.Results With the severity of myelosuppres-sion,the levels of MO,LY,SII,SIRI and LCR decreased gradually and showed a downward trend(P＜0.05).The levels of CRP,SAA and CAR were increased gradually(P＜0.05).RET and PA levels were decreased when myelopathic depression reached Ⅲ degree or above(P＜0.05).When myelosuppression reached gradeⅣ and above,the level of NLR decreased(P＜0.05).CRP,SAA and CAR were positively correlated with my-elosuppression degree,while MO,LY,RET,PA,NLR,SII,SIRI and LCR were negatively correlated with my-elosuppression degree(P＜0.05).The results of multivariate logistic regression analysis showed that LY and NLR were the influencing factors of myelosuppression caused by chemotherapy in tumor patients(P＜0.05).Conclusion Myelosuppression caused by solid tumor chemotherapy can lead to a continuous decline in the body's anti-tumor immunity.Deep myelosuppression is unfavorable to the prognosis of patients,and infection can promote the development of tumors and lead to poor prognosis.

Objective:To develop and evaluate a nomogram prediction model for poor outcome of lower extremity motor function in patients with acute ischemic stroke (AIS) at 90 days after onset.Methods:Patients with AIS admitted to Guangzhou Province Hospital of Chinese Medicine from January to October 2024 were included retrospectively. At 90 days after onset, Functional Ambulation Category (FAC) was used for outcome evaluation. ≥4 was defined as good outcome and <4 was defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent predictive factors for poor outcome of lower extremity motor function, and develop a nomogram prediction model. The area under the receiver operating characteristic curve, calibration curve, and clinical decision curve were used to evaluate the predictive model. Results:A total of 325 patients with AIS were enrolled, including 214 males (65.8%), median aged 62 years (interquartile range, 54-71 years); 158 patients (48.6%) had poor outcome of lower extremity motor function. Multivariate logistic regression analysis showed that older age (odds ratio [ OR] 1.037, 95% confidence interval [ CI] 1.011-1.065]; P=0.007) and a higher baseline National Institutes of Health Stroke Scale (NIHSS) score ( OR 1.472, 95% CI 1.336-1.637; P<0.001) were the independent predictors of poor outcome, while intravenous thrombolysis ( OR 0.195, 95% CI 0.080-0.443; P<0.001) and early rehabilitation intervention ( OR 0.444, 95% CI 0.231-0.850; P=0.014) were the independent predictors of good outcome. The area under the receiver operating characteristic curve of the nomogram prediction model developed using the above factors was 0.906 (95% CI 0.872-0.940), indicating that the model had good discriminability. The calibration curve fits well with the ideal curve. The clinical decision curve showed that the model had stronger clinical practicality. Conclusion:The nomogram developed by age, intravenous thrombolysis, early rehabilitation intervention, and baseline NIHSS score can effectively predict the risk of poor outcome of lower extremity motor function in patients with AIS and has higher clinical value.

Objective To analyze the research literature on fire needling therapy published on China National Knowledge Infrastructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and China Science and Technology Journal Database(VIP)in the last 20 years,and to explore the current status and the hotspots of the research,thus to summarize and analyze the spectrum of the dominant diseases and technological transformations of fire needling therapy.Methods CiteSpace and VOSviewer were applied to analyze the keywords,authors and institutions,to draw the scientific knowledge map,and to summarize the disease spectrum.Results A total of 4 226 literature were included,from 2000 to 2023,the number of publications on fire needling therapy research showed an increasing trend,with each of the four periods showing its own characteristics of the times.The"filiform fire needling"and"pricking of fire needling"were widely used as acupuncture tools and acupuncture techniques in the studies,the emergence of high-frequency disease keywords such as"shingles""vitiligo"and"acne"indicates that research on the treatment of skin diseases with fire needling has attracted much attention.The disease spectrum of fire needling therapy was enlarged,involving a total of 356 diseases distributed in 20 disease systems.Conclusion Skin diseases and arthralgia became the dominant diseases of fire needling therapy,the rise of research hot words such as"acne vulgaris""vitiligo""stroke""chronic eczema""filiform fire needling"and"Lingnan fire needling"indicates that fire needling therapy is developing towards research standardization,theoretical diversification and disease diversification.