Objective: To assess the causal association between specific oral microbiota and the risk of oral leukoplakia (OLK) using a Mendelian randomization (MR) approach, and to elucidate the potential mediating role of immune cells. Methods: Summary statistics from genome-wide association studies (GWAS) of the oral microbiome, GWAS data for immune cell phenotypes, and GWAS summary statistics for OLK from FinnGen were used. The inverse variance weighted (IVW) method was adopted as the primary approach, and it was supplemented by MR Egger regression, simple mode, weighted median, and weighted mode methods for additional analyses, to investigate the causal relationship between 3 117 types of tongue coating and salivary microbiota, as well as 731 immune cell traits, and OLK. Furthermore, a two-step MR approach was applied to explore the potential mediating role of immune cells in the association between oral microbiota and OLK. Results: IVW analysis revealed causal associations between 15 oral microbial genera and OLK. Among these, Streptococcus, Neisseria, and Catonella were associated with a reduced risk of OLK, with Fusobacterium showing the most significant protective effect (OR = 0.41, P = 0.023). In contrast, genera, including Microbacterium, Campylobacter, and Haemophilus_A, were linked to an increased risk of OLK, with Lancefieldella exhibiting the strongest risk effect (OR = 2.66, P = 0.006). Eleven immune cell phenotypes with potential causal associations with OLK were identified, including four protective and seven risk-increasing factors. Mediation analysis further identified four key mediating pathways: pathogenic genera, particularly Campylobacter_A and Lancefieldella, may promote the development and progression of OLK by upregulating highly activated pro-inflammatory immune subsets such as activated monocytes, B cells, and myeloid cells. Conversely, the potentially protective genus Catonella appeared to exert inhibitory effects on OLK by significantly downregulating dendritic cell subsets. Conclusion This study is the first to reveal, at the genetic level, causal pathways through which specific oral microbial genera influence the risk of OLK by mediating immune cell responses. These findings provide novel insights into the immunopathological mechanisms underlying OLK and offer potential targets for intervention strategies aimed at modulating specific microbial genera or immune cell subsets.

To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

To explore the effects of different exercise prescriptions on glycemic metabolism in East Asian patients with type 2 diabetes mellitus (T2DM) and to compare the differences in the impact of population characteristics and exercise components on glycemic metabolism.

OBJECTIVES: To investigate the inhibitory effect of pirfenidone (PFD) on growth of bladder cancer xenograft and its regulatory effect on Treg cells in tumor-bearing mice. METHODS: Thirty-two C57BL/6 mice bearing ectopic bladder tumors were randomized into control and PFD groups (n=16). In PFD group, PFD was administered orally at the daily dose of 500 mg/kg, and tumor growth and survival of the mice were monitored. After treatment for 21 days, the tumors and vital organs were harvested for analysis. Immunohistochemistry was used to assess CD3, CD4, CD8, and FOXP3 expressions in the tumors. Flow cytometry and RT-qPCR were used to analyze the percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells and IL-2, IL-10, and IL-35 expressions in the tumors and spleens; organ damage of the mice was examined with HE staining. RESULTS: Compared with the control group, the PFD-treated mice exhibited significantly lower tumor growth rate with smaller tumor volumes at day 21, along with improved survival at day 28. Immunohistochemistry revealed no significant differences in the infiltration of CD3⁺ and CD8⁺ cells between the two groups, but the percentages of CD4⁺ and FOXP3⁺ cells were significantly lower in the tumors of PFD-treated mice. Flow cytometric analysis confirmed a decrease in CD4⁺CD25⁺FOXP3⁺ Treg cells in the tumors from PFD-treated mice, which also had reduced expression levels of IL-2, IL-10 and IL-35 mRNAs in the tumors. No significant differences were found in Treg cell populations or cytokine expressions in the spleen tissues between the two groups. HE staining showed obvious organ damage in neither of the groups. CONCLUSIONS PFD inhibits bladder cancer growth and enhances survival of tumor-bearing mice possibly by suppressing Treg cells in the tumor microenvironment.
Animals ; Urinary Bladder Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory/metabolism* ; Mice, Inbred C57BL ; Interleukins/metabolism* ; Interleukin-10/metabolism* ; Cell Line, Tumor ; Interleukin-2/metabolism* ; Xenograft Model Antitumor Assays ; Female

Objective:To discuss the effects of bone marrow-derived mesenchymal stem cells(BMSCs)transplantation on mitophagy in the vascular dementia(VaD)rats through reactive oxygen species(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)signaling,and to clarify its mechanism.Methods:Forty-five male adult SD rats were randomly divided into sham operation group,model group,unloaded group,BMSCs group,and MSCs+ML385(Nrf2 inhibitor)group(combination group),and there were 9 rats in each group.After intraperitoneal anesthesia,the VaD models were established in all groups except sham operation group.Morris water maze test was used to detect the learning and memory abilities of the rats in various groups;HE staining was used to observe the histopathological morphology of brain tissue of the rats in various groups;Nissl staining was used to observe the changes of Nissl bodies in hippocampus region of brain tissue of the rats in various groups;transmission electron microscope was used to observe the ultrastructure of hippocampus region of the rats in various groups;fluorescence probe method was used to detect the ROS levels in hippocampus neurons in various groups;Western blotting method was used to detect the expression levels of Nrf2,heme oxygenase-1(HO-1),PTEN-induced putative kinase 1(PINK1),parkin RBR E3 ubiquitin protein ligase(Parkin),Beclin-1,ubiquitin-binding protein p62(P62),and microtubule-associated protein 1A/1B-light chain 3(LC3-Ⅱ/LC3-Ⅰ)ratio in brain tissue of the rats in various groups.Results:The Morris water maze results showed that compared with sham operation group,the escape latency of the rats in model group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).Compared with model group,the escape latency of the rats in BMSCs group was significantly decreased(P<0.01),while the number of crossing time and residence time were significantly increased(P<0.01).Compared with BMSCs group,the escape latency of the rats in combination group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).The HE staining results showed that hippocampus neurons of the rats in sham operation group were normal in quantity and morphology,with uniform staining and clear structure.Compared with sham operation group,the hippocampus tissue of the rats in model group showed sparse arrangement,disordered structure,reduced neuronal quantity,varied morphology,uneven staining,nuclear pyknosis,and partial neuronal necrosis.Compared with model group,the neuronal damage of the rats in hippocampus regio in BMSCs group was alleviated,with restored morphology and improved neuronal loss.Compared with BMSCs group,the neurons of the rats in hippocampus region in combination group showed irregular morphology,disordered structure,unclear cell boundaries,uneven staining,and nuclear pyknosis.The Nissl staining results showed that the hippocampal neurons in sham operation group were tightly arranged with intact morphology,obvious nucleoli,and abundant darkly stained Nissl bodies.Compared with sham operation group,the neurons in hippocampus region of the rats in model group showed pyknosis,vacuolization,and sparse Nissl bodies.Compared with model group,the BMSCs group showed reduced neuronal pyknosis,relatively intact morphology,and increased Nissl bodies.Compared with BMSCs group,the combination group showed neuronal pyknosis,loss of morphological integrity,and fragmented Nissl bodies.The transmission electron microscope results showed that mitochondria in sham operation group exhibited oval shape with intact double-membrane structure and cristae.Compared with sham operation group,the mitochondria in model group showed swelling,disrupted membranes,broken cristae,and numerous autophagosomes.Compared with model group,the BMSCs group showed improved mitochondrial structure and reduced autophagosomes.Compared with BMSCs group,the combination group showed swollen mitochondria,disrupted membranes,broken cristae,and visible autophagosomes.The fluorescence probe results showed that compared with sham operation group,the ROS levels in the hippocampus neurons in brain tissue of the rats in model group were significantly increased(P<0.01);compared with model group,the ROS levels in hippocampus neurons in brain tissue of the rats in BMSCs group were significantly decreased(P<0.01);compared with BMSCs group,the ROS levels in hippocampus neurons in brain tissue of the rats in combination group were significantly increased(P<0.01).The Western blotting results showed that compared with sham operation group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in model group were significantly decreased(P<0.01);compared with model group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in BMSCs group were significantly increased(P<0.01);compared with BMSCs group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in combination group were significantly decreased(P<0.01);compared with sham operation group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,and LC3-Ⅱ/LC3-Ⅰ ratio of the rats in model group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01);compared with model group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in BMSCs group were significantly decreased(P<0.01),while the expression level of P62 protein was significantly increased(P<0.01);compared with BMSCs group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in combination group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01).Conclusion:BMSCs can alleviate the hippocampal neuronal pathological changes and improve cognitive function in the VaD rats,and its mechanism may be related to the regulation of ROS/Nrf2 signaling pathway to inhibit mitophagy.

Objective:To investigate the moyamoya disease (MMD) -related mitochondrial genes and to elucidate potential regulatory mechanisms.Methods:The GSE157628 and GSE189993 datasets of MMD from the Gene Expression Omnibus (GEO) database were downloaded as the training set and validation set, respectively. Mitochondrial-related gene sets were obtained from the MitoCarta 3.0 database. Weighted gene co-expression network analysis was used to screen the pathogenic module genes of MMD. Venn analysis was used to identify differentially expressed genes related to mitochondria. Functional enrichment analysis was used to elucidate potential molecular functions. Mitochondrial genes were screened using three machine learning methods, receiver operator characteristic (ROC) curve, and validation set expression analysis. A diagnostic nomogram model of MMD related features was developed based on diagnostic genes. The correlation between the identified genes and MMD immune infiltration characteristics, the biological pathways involved, and potential therapeutic drugs with interactions were analyzed.Results:A total of 15 differentially expressed mitochondria-related genes were identified based on GSE157628 dataset, involving the processes related to small molecule metabolism and mitochondrial function. Three machine learning algorithms, ROC curves and expression analysis finally identified two mitochondria-related diagnostic genes: NUDT8 and RDH13. The diagnostic nomogram model developed based on these two genes had good diagnostic ability for MMD. Immune infiltration analysis showed that there was significant difference in plasma cells between the MMD group and the control group. In addition, the two diagnostic genes interacted with several therapeutic drugs. Conclusion:NUDT8 and RDH13 are identified as potential mitochondrial-related genes of MMD, and they may serve as therapeutic targets for progressive vascular occlusion in MMD.

Skeletal maturity can reflect an individual's developmental status and predict their future growth potential, provide clinicians with valuable diagnostic information. In recent years, significant progress has been made in imaging techniques for assessing skeletal maturity. This article aims to review the application status and research progress of X-ray, MRI and ultrasound in assessing skeletal maturity in adolescents and children, with a view of providing clinical reference.

BACKGROUND:In recent years,with the improvement of living standards,non-alcoholic fatty liver disease has a gradually increasing trend.miRNA-122 is one of the most abundant microRNAs in the liver,which plays an important role in maintaining the environmental stability and differentiation of the liver.Exercise training is a non-drug treatment for non-alcoholic fatty liver disease,which may improve liver lipid metabolism by regulating the expression of miRNA-122. OBJECTIVE:To review the effects of miRNA-122 on the pathological factors related to non-alcoholic fatty liver disease as well as the effects of exercise on the expression of miRNA-122 and the occurrence and development of nonalcoholic fatty liver disease. METHODS:The first author searched the databases of CNKI,WanFang,VIP,PubMed,Geenmedical,EBSCO,Medline,Web of Science,and Elsevier using"non-alcoholic fatty liver disease,microRNA,microRNA-122,lipid metabolism,inflammatory response,insulin resistance,exercise,physical exercise,exercise training"as the English and Chinese search terms for all relevant literature published before June 5,2022.All included documents were screened,summarized,and analyzed.Finally,68 documents were included for review. RESULTS AND CONCLUSION:Compared with the healthy control group,the expression of circulating miRNA-122 is increased in patients with non-alcoholic fatty liver disease.The level of miRNA-122 may show different expression levels at different stages of non-alcoholic fatty liver disease.miRNA-122 can regulate the expression of downstream-related proteins,influence lipid metabolism,inflammatory response,insulin resistance and other pathogenic factors in non-alcoholic fatty liver disease by targeting base complementary pairing sites on mRNA or directly acting as physiological ligands of some RNA receptors.Different exercise modes can improve non-alcoholic fatty liver disease.Therefore,patients with non-alcoholic fatty liver disease need to complete at least 120 minutes of moderate-intensity exercise every week to have a positive effect.For patients who can tolerate various exercises,priority should be given to the combination of aerobic and resistance exercises 4-5 times a week.The exercise intensity should be 50%-70%of the maximum heart rate and the exercise should last for>3 months.For patients with poor tolerance,resistance exercise may be more feasible than aerobic exercise.In addition,patients with non-alcoholic fatty liver disease can also choose proper exercise modes according to their own disease conditions(such as liver enzymes and lipid levels).Exercise can be used as a feasible strategy to prevent non-alcoholic fatty liver disease,reduce liver steatosis,and alleviate liver inflammatory response and insulin resistance.Exercise training can regulate the expression of miRNA-122,but in patients with non-alcoholic fatty liver disease,the effect of exercise on miRNA-122 and its related signal pathways remains to be studied.

Objective To study the unqualified items in the reported quality control tests of linear accelerators, analyze the issues in quality control tests, and propose the key points and development directions for accelerator quality control test in China. Methods A literature review was conducted using the CNKI database to analyze the qualified rates of test items and the issues in quality control tests. Results In the literature on the quality control tests of linear accelerators, except for a few provinces where the qualified rates of all test items were 100%, unqualified items were reported in most of the literature. There were unqualified items related to X-ray and electron beam in different reports. Error of dose indication was the unqualified item with the highest occurrence rate in X-ray test, and the item with the lowest qualified rates in X-ray and electron beam tests. The lowest qualified rate of X-ray dose indication error was 73.5% in 2016, and the lowest qualified rate of electron beam dose indication error was 46.2% in 2017. Conclusion Tests should be carried out strictly according to the items and intervals specified by the quality control test standards. Hospitals, radiation health technology service institutions, and health administrative departments should each fulfill their respective responsibilities, work together, and place emphasis on ensuring effective quality control tests of linear accelerators to further enhance the overall quality control standards for these devices.

Skeletal maturity can reflect an individual's developmental status and predict their future growth potential, provide clinicians with valuable diagnostic information. In recent years, significant progress has been made in imaging techniques for assessing skeletal maturity. This article aims to review the application status and research progress of X-ray, MRI and ultrasound in assessing skeletal maturity in adolescents and children, with a view of providing clinical reference.