BACKGROUND: Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear. METHOD: We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing. RESULTS: There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect. CONCLUSIONS These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans ; DNA, Mitochondrial ; DNA Methylation ; Male ; Adult ; Noise, Occupational/adverse effects* ; Middle Aged ; Occupational Exposure/adverse effects* ; Biomarkers/blood* ; Female

Objective To study the oral health status of officers and soldiers in a certain unit,so as to provide a basis for the formulation and implementation of oral health support plans.Methods A total of 437 officers and soldiers in a certain unit were enrolled to assess their oral health status through questionnaire survey and clinical examination.Results The prevalences of dental caries and periodontal diseases were 87.6%(383/437)and 90.4%(395/437),respectively;the detection rates of impacted third molars,recurrent aphthous stomatitis,other mucosal diseases,and temporomandibular joint disorders were 12.6%(55/437),54.2%(237/437),29.5%(129/437),and 19.2%(84/437),respectively.In terms of oral medical needs,23.3%(102/437)patients did not need treatment,66.1%(289/437)required elective treatment,9.2%(40/437)required early treatment,and 1.4%(6/437)required urgent treatment.Conclusion Officers and soldiers in this study have a variety of oral diseases,with periodontal diseases having the highest prevalence.Supportting plans should be formulated based on the characteristics of the prevalence of oral diseases among them,and regular oral diagnosis and treatment should be carried out to prevent the development and progression of oral diseases.

Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00～50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046～0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505～8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191～8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.

Objective To investigate risk factors for residual lesions after initial transurethral resection of bladder tumors(TURBT)and risk factors for tumor recurrence after second TURBT in patients with non-muscle-invasive bladder cancer(NMIBC)in order to provide reference for clinical management.Methods A case-control study design was adopted to include 120 NMIBC patients who underwent initial TURBT and then second surgery within 2～8 weeks in our department from January 2017 to January 2025.Based on the presence of residual lesions after the initial TURBT or not,the patients were divided into a residual lesion group(n=34)and a non-residual lesion group(n=86).Chi-square test and multivariate logistic regression analysis were performed to identify potential risk factors for residual lesions following the initial TURBT.Univariate and multivariate Cox regression models were used to analyze potential risk factors for tumor recurrence after the second TURBT.Results The residual lesion rate after initial TURBT was 28.33％.Chi-square test analysis revealed that tumor stage T1(Chi-square=5.756,P=0.016)and broad tumor base(Chi-square=4.331,P=0.037)were factors influencing residual lesions after initial TURBT.Multivariate logistic regression analysis identified tumor stage T1(OR=3.047,95％CI:1.128～8.226,P=0.028)as an independent risk factor for residual lesions after initial TURBT.The tumor recurrence rate after second TURBT was 17.5％.Multivariate Cox regression analysis identified tumor stage T1(OR=4.258,95％CI:1.248～14.532,P=0.021),intravesical chemotherapy instillation after second TURBT(OR=3.539,95％CI:1.284～9.752,P=0.015),history of urinary system tumors(OR=3.002,95％CI:1.145～7.873,P=0.025)and high platelet-to-lymphocyte(PLR)ratio(OR=2.798,95％CI:1.115～7.023,P=0.028)as independent risk factors for tumor recurrence after second TURBT.Conclusion Tumor stage T1 and broad tumor base are risk factors for residual lesions after initial TURBT,while tumor stage T1,intravesical chemotherapy instillation after second TURBT,history of urinary system tumors and high PLR ratio are risk factors for tumor recurrence after second TURBT.Comprehensive analysis on above 4 indicators can effectively assess the risk of tumor recurrence in NMIBC patients following second TURBT,and timely early medical intervention is beneficial for improving patient outcomes.

Compared to traditional machine learning algorithms,which often suffer from low feature extraction efficiency,insufficient nonlinear pattern recognition capabilities and slow training speeds,the broad learning system(BLS)enhances the learning ability and efficiency by horizontally expanding the network structure.BLS offers advantages such as a simple structure,fast training speed,and strong generalization capabilities.While BLS has demonstrated potential in various fields,but its application in identification of complex samples has not been fully explored.This research investigated the feasibility of using BLS algorithm for identification of complex samples based on physicochemical indicators.Using the iris,wine,and breast cancer datasets,the length and width of petals and sepals of iris flowers,the physicochemical properties of wine,and the nuclear characteristics of breast cancer cells were used as input variables to establish BLS models for identifying iris species,wine varieties,and benign versus malignant nucleus.The model performance was evaluated by confusion matrices,accuracy,and runtime.Compared with partial least squares-discriminant analysis(PLS-DA),soft independent modeling of class analogies(SIMCA),and artificial neural networks(ANN),the results indicated that BLS demonstrated significant advantages in computational efficiency and recognition accuracy.Thus,BLS was an efficient and reliable method for identification of complex samples.

Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.

AIM To explore the effects and mechanism of verbascoside on adenine-induced infertility in rats.METHODS Rats randomly divided into the blank group,the model group,the positive control group(100 mg/kg Compound Xuanju Capsule)and low and high dose groups of verbascoside(50 and 100 mg/kg)were given 150 mg/kg adenine daily for 14 days to establish the rat model of infertility,except those of the blank group,followed by the 28 days corresponding gavage of the drugs.The rats had their general activities observed;their indexes levels of liver,kidney,testis and epididymis calculated;their sperms checked under the microscope;their pathological morphology of the liver,the kidney and the testis observed by HE staining;their spermatogenesis evaluated using the Johnsen scoring method;their serum levels of T,LH,FSH and GnRH detected by ELISA;and their testicular mRNA and protein expressions of mTOR,LC3B and ULK1 detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group displayed increased index level of the kidney(P＜0.05),decreased sperm count,sperm activity rate and sperm index level(P＜0.05),decreased serum levels of T and GnRH(P＜0.05),increased levels of LH and FSH(P＜0.05),obviously pathological damage of the kidney and testis,increased testicular expressions of mTOR mRNA and protein(P＜0.05),decreased expressions of LC3B and ULK1 mRNA and protein(P＜0.05),and decreased expression of p-mTOR protein(P＜0.05).Compared with the model group,the high-dose verbascoside group demonstrated decreased renal index level(P＜0.05),increased sperm count and sperm activity rate(P＜0.05),increased serum T level(P＜0.05),decreased LH and FSH levels(P＜0.05),improved pathological damage of the kidney and the testis at different levels,decreased testicular expressions of mTOR mRNA and protein(P＜0.05),increased expressions of LC3B,ULK1 mRNA and protein(P＜0.05),and increased expression of p-mTOR protein(P＜0.05).The high-dose verbascoside group displayed the same effects as those of the positive control Compound Xuanju Capsule.CONCLUSION Verbascoside can effectively improve the sperm quality,sex hormone disorder,reproductive function and pathological damage of kidney and testis in infertile rats,and its mechanism may be related to the enhanced positive regulation of autophagy and regulated hypothalamus-pituitary-testis axis disorder.

AIM: To investigate the role of histidine-rich glycoprotein(HRG)in the neovascularization of diabetic retinopathy in rats.METHODS: Streptozocin(STZ)-induced diabetic Sprague-Dawley(SD)rats were utilized as an experimental model, the protein expression of HRG and vascular endothelial growth factor(VEGF)in the retinas of normal(Wild type, WT)and diabetic(diabetic mellitus, DM)groups was detected using Western blot(WB). The protein expression of HRG in high-glucose-induced human retinal microvascular endothelial cells(hRMECs)was verified by WB after transfection with HRG small interfering RNA(siRNA)low-expression sequences. The optimal si-HRG#298 sequence was selected for further experiments. In the animal experiment, HRG gene silencing was achieved using an adeno-associated virus(AAV)vector, with AAV2-sh-NC and AAV2-sh-HRG#298 serving as the HRG gene silencing group and the HRG empty vector control group, respectively. The protein expression of HRG and VEGF in each group was then detected by WB following the verification of HRG protein expression. Retinal structural changes were observed by HE staining, and neovascularization changes were observed by PAS staining.RESULTS: HE staining found that the retinal structure in the DM group was disordered, the number of cells in the ganglion cell layer decreased, the number of cells in the inner and outer nuclear layers decreased, and the total retinal thickness also decreased(P<0.05); cellular capillaries were significantly increased in DM rats observed by PAS staining(P<0.05); the protein expression of HRG and angiogenesis factor VEGF was up-regulated in the retina of DM group(P<0.05); the protein expression of HRG was significantly downregulated in high glucose-induced hRMECs(P<0.05); the inhibition of neovascularization in diabetic retinas and the downregulation of VEGF protein expression were achieved through HRG gene silencing(P<0.05).CONCLUSION: HRG promotes neovascularization in the retinas of diabetic rats, and HRG gene silencing can inhibit neovascularization.

This article elaborates on the complex cross-talk and close relationship between muscles and bones involved in this disease,as well as its pathogenesis.It also summarizes that the difficulty of its treatment lies in the need to simultaneously consider both muscles and bones.And elaborated on the key role of the Hedgehog signaling pathway in embryonic development,tissue morphology establishment,and human tissue regeneration and repair.Investigated the remodeling effect of the Hedgehog signaling pathway on skeletal muscle from three aspects:Proliferation and differentiation of muscle stem cells,precursor cell and muscle fiber generation,inhibition of inflammation,and regulation of immunity;this article elucidates the role of the Hedgehog signaling pathway in bone reconstruction from two aspects.

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.