BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

ObjectiveTo detect the proportion of splenic follicular helper T （Tfh） cells and their functionally related cytokine expression levels in the incomplete embryo implantation disorder （EID） model mice， and to explore the immunological mechanism of Tfh in infertility caused by embryo implantation disorder. MethodsSixteen female Kunming mice were randomly divided into two groups， with eight mice in each group. On day 4 of pregnancy， an incomplete EID mouse model was established by oral gavage of mifepristone suspension， while an equal volume of saline was administered to the control group. On day 8 of pregnancy， the mice were euthanized. Flow cytometry was used to detect the levels of Tfh cells in the spleen lymphocytes of both incomplete EID mice and normal control mice. qRT-PCR was performed to measure the mRNA levels of B-cell lymphoma 6 （Bcl-6） and C-X-C chemokine receptor type 5 protein （CXCR5） in the spleen lymphocytes of both groups. Western blot was employed to assess the protein expression levels of Bcl-6 and CXCR5 in the spleen lymphocytes of both groups. Serum levels of interleukin-4 （IL-4）， IL-6， and IL-21 were measured by ELISA. Immunohistochemistry （IHC） was used to observe the expression levels of progesterone receptor （PR）， Bcl-6， and CXCR5 proteins in the uterine endometrial tissue of mice in both groups. ResultsIncomplete-type EID mice had a reduced number of embryo implantation points and reduced endometrial PR expression. Flow assay results showed that the proportion of CD4⁺CXCR5⁺Tfh cells in splenic lymphocytes of incomplete-type EID mice was significantly higher than that of normal controls （P<0.05）. Compared with the normal control group， Bcl-6 and CXCR5 mRNA levels and protein levels were elevated in splenic lymphocytes of incomplete EID mice， with statistically significant differences （P<0.05）； serum IL-4， IL-6， and IL-21 levels were elevated in incomplete EID mice， and Bcl-6 and CXCR5 proteins in the endometrium were significantly elevated （P<0.05）. ConclusionThe increase of Tfh cells and their associated cytokines Bcl-6 and CXCR5 is associated with the development of incomplete EID， and may be involved in the development of female immune infertility.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

SMYD5 is a ribosomal methyltransferase with SET and MYND structural domains， which is a member of the SMYD family and is expressed in a variety of tissues， including ovary and testis. This enzyme participates in biological processes such as gene expression regulation， cell development and differentiation， and maintenance of genomic stability through ribosomal protein methylation modification. In recent years， research on SMYD5 has increased in cancers including hepatocellular carcinoma， gastric adenocarcinoma， and lung cancer. Studies have revealed that SMYD5 exhibits high expression levels in various diseases including hepatocellular carcinoma， gastric adenocarcinoma， lung cancer， and inflammatory bowel disease， influencing the progression of these conditions. This review summarizes the role of SMYD5 in hepatocellular carcinoma， inflammatory bowel disease， and other biological functions， aiming to provide a reference for related disease research.

Objective This study aims to evaluate the diagnostic efficacy of multi-slice spiral CT in early lung cancer and provide evidence for clinical differentiation. Methods A retrospective analysis was conducted on the clinical data of 86 patients with early-stage lung cancer admitted to our hospital between March 2020 and February 2025. All patients underwent MSCT examination. Using pathological examination as the gold standard, the consistency between MSCT and the gold standard was analyzed. CT sign differences among patients with different pathological types of lung cancer were compared. Pearson correlation analysis was used to analyze the relationships between CT signs and the degree of adenocarcinoma infiltration. Results MSCT examination showed positive findings in 75 cases of adenocarcinoma, with a sensitivity of 97.40%, a specificity of 88.89%, a positive predictive value of 98.68%, a negative predictive value of 80.00%, an accuracy of 96.51%, and a Kappa value of 0.823. Significant differences were found in the proportions of tumor maximum diameter > 2 cm, vacuole sign, ground-glass opacity sign, lobulation sign, spiculation sign, air bronchogram sign, pleural indentation sign, and vascular convergence sign (P<0.05), and these proportions increased progressively from carcinoma in situ to minimally invasive adenocarcinoma to invasive adenocarcinoma. Pearson correlation analysis showed that tumor maximum diameter, vacuole sign, ground-glass opacity sign, and pleural indentation sign were positively correlated with adenocarcinoma, while spiculation sign and vascular convergence sign were negatively correlated with adenocarcinoma (P<0.05). Conclusion MSCT demonstrates high diagnostic efficiency for early-stage lung adenocarcinoma and can provide a reference for early clinical evaluation.

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

Objective To investigate the expression levels of micro RNA-651(miR-651)and the transcrip-tion factor Forkhead Box N2(FOXN2)in lung cancer tissues and to analyse their relationship with patients' prognosis after lobectomy.Methods A total of 98 patients with lung cancer who underwent lobectomy from January 2020 to December 2021 in Nantong Cancer Hospital were selected as research objects,the lung cancer tissue specimens and corresponding paracancerous tissue specimens of patients were collected,the expression levels of miR-651 and FOXN2 were detected by real-time fluorescence quantitative PCR(qPCR),and their re-lationship with the prognosis of patients after lobectomy was analyzed.Results At 2-year follow-up,19(19.39％)of 98 patients had recurrent metastasis,and the median time to recurrent metastasis was 20 months(95％CI:18.626--21.374).qPCR assay showed that the expression levels of miR-651 and FOXN2 in lung cancer tissues were significantly lower than those in paracancerous tissues(P＜0.05).miR-651 and FOXN2 expression levels were significantly correlated with clinicopathological features such as tumour size,TNM stage and lymph node metastasis(P＜0.05).The results of univariate Cox regression analysis showed that the percentages of maximum tumor diameter ≥3 cm,TNM stage Ⅱ,lymph node metastasis,miR-651 low ex-pression and FOXN2 low expression were higher in the poor prognosis group than those in the good prognosis group(P＜0.05).Multifactorial Cox regression analysis showed that maximum tumor diameter ≥ 3 cm(HR=3.185,95％CI:1.105-9.182),TNM stage Ⅱ(HR=5.167,95％CI:1.939-13.771),lymph node metastasis(HR=2.860,95％CI:1.115-7.338),low miR-651 expression(HR=5.345,95％CI:1.845-15.483)and low FOXN2 expression(HR=5.404,95％CI:1.744-16.745)were independent risk factors for the prognosis of lung cancer patients after lobectomy(P＜0.05).Conclusion The expression levels of miR-651 and FOXN2 were reduced in the tissues of lung cancer patients,and both were associated with tumour size,TNM stage,lymph node metastasis,and patients' prognosis after lobectomy.

Objective To investigate the mechanism of autophagy induced by House dust mites(HDM)on airway epithelial tight junction through β-catenin-Snail signaling pathway.Methods Human bronchial epithelial cells(16HBE)were stimulated with HDM at different time points(0,3,6,12,24,48 h)and different concen-trations(0,40,100,200 μg/mL)to screen the appropriate stimulation concentration and stimulation time.16HBE cells were treated with oxidative stress inhibitor N-acetylcysteine(NAC),autophagy inhibitor 3-methylad-enine(3-MA),HDM,and their combinations.Cells were transfected with mCherry-EGFP-LC3B,Beclin-1-siRNA,and ATG14-siRNA lentivirus and then stimulated with NAC and HDM.Immunofluorescence was used to detect the expression levels of autophagy-related protein LC3B,tight junction-related proteins Occludin,and ZO-1 in airway epithelial cells.The level of reactive oxygen species(ROS)was detected by using DCFH-DA in each group.The protein expression levels of Occludin,ZO-1,LC3B,Beclin-1,ATG5,ATG14,P62,Snail,β-catenin and p-β-catenin were detected by Western blot method.Results Immunofluorescence results showed that compared with the control group,200 μg/mL HDM stimulation induced cellular autophagy,increased the expression level of LC3B protein,and promoted the level of ROS,all with statistical significances(all P<0.05).Compared with the HDM group,the HDM+3-MA,HDM+ATG14-si,and HDM+Beclin-1-si groupsall showed significantincreases in the expression levels of tight junction-related proteins Occludin and ZO-1(P<0.05).The HDM+NAC group demonstrated significant decreases both in the level of ROS andin the expression level of LC3B protein.Western blot results revealed that compared with HDM,3-MA and autophagy protein low-expression beads(Beclin-1-si,ATG14-si)attenuated HDM-induced cellular autophagy(P<0.05),inhibited HDM-induced upregulation of Snail and p-β-catenin expression,and improved HDM-induced decreases in Occludin and ZO-1(P<0.05).Moreover,compared with the HDM group,the NAC+HDM group exhibited significant decreases both in the conversion of LC3BⅠ to LC3BⅡ(P<0.001)in the protein levels of Snail,p-β-catenin,Beclin-1 and ATG14(P<0.01),but significant increases in the protein levels of Occludin and ZO-1(P<0.05).Conclusion HDM affects the tight connections between airway epithelial cells by inducing autophagy,which may be attributed to the β-catenin-Snail signaling pathway.

Objective:To explore the related risk factors of neonatal necrotizing enterocolitis (NEC) by constructing and comparing nine regression models.Methods:All NEC patients admitted to the neonatal internal medicine department, neonatal surgery department, and neonatal intensive care unit of Shanxi Provincial Children's Hospital (Shanxi Provincial Maternity and Child Health Center) from 2020 to 2022 were included as the case group. A control group consisted of children admitted during the same period based on the inclusion and exclusion criteria. The NEC data collected were used for feature selection by using the Boruta algorithm. Logistic regression, multi-decision tree gradient boosting, efficient gradient one-sided sampling, random forest, decision tree, gradient boosting decision tree (GBDT), neural network, support vector machine, and K-nearest neighbor models were constructed. The optimal model was selected through rigorous comparison and Shap explainable analysis was performed on the GBDT model.Results:Thirteen key factors were identified through screening for nine regression models construction. After strict comparison and analysis, the GBDT model showed higher stability compared with other eight regression models. In the validation set, the area under the receiver operating characteristic curve of the GBDT model was 0.958, with an accuracy of 0.925, and sensitivity and specificity of 0.827 and 0.950, respectively. Shap explainable analysis on the GBDT model revealed that suffering from anemia, non-invasive ventilator use, procalcitonin use, premature birth, and low birth weight increased the risk for NEC, while breastfeeding and probiotics decreased the risk for NEC.Conclusion:This study identified the risk factors and protective factors for NEC by using the GBDT model, which provided evidnce for the prevention and treatment of NEC.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. The advancement of its precise diagnosis and therapeutic development urgently requires in vitro models that can highly recapitulate the pathophysiological characteristics of human tissues. Organ-on-a-chip has emerged as a novel technological platform that integrates microfluidic engineering, biomaterials, and other engineering strategies with organoid culture. This platform enables precise control over the cellular microenvironment, thereby closely mimicking the three-dimensional structure and physiological functions of human organs in vitro. Organ-on-a-chip systems demonstrate significant advantages in cancer research, developmental biology, and disease modeling, as they not only preserve the heterogeneity and pathological features of patient samples but also support co-culture of various cell types to reconstruct the tumor microenvironment (TME). However, standardized construction methods and integrated analytical strategies for this technology in lung cancer research remain to be further refined. This review systematically elaborates on the key technical principles of organ-on-a-chip and its recent advances in lung cancer modeling, drug screening, and immunotherapy research. It aims to provide a theoretical foundation and technical perspective for promoting the deeper application of organ-on-a-chip in precision medicine and translational research for lung cancer.
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Humans ; Lung Neoplasms/drug therapy* ; Organoids/drug effects* ; Lab-On-A-Chip Devices ; Animals ; Tumor Microenvironment