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

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.

Objective To investigate the therapeutic effects of upper limb rehabilitation robot training combined with intermittent theta burst stimulation(iTBS)on upper limb motor and neurological function in stroke patients with hemiplegia.Methods This study retrospectively consecutive enrolled 46 stroke hemiparetic patients from the Department of Rehabilitation Medicine,Nanjing Pukou People's Hospital.The patients were randomly assigned to a control group and an experimental group(23patients in each)using a random number table.Baseline data,including sex,age,disease duration,side of hemiplegia,and stroke type,were collected from patients enrolled.All patients received conventional treatment.The control group received upper limb rehabilitation robot training combined with iTBS sham stimulation(coil placed perpendicular to the skull),while the experimental group received upper limb rehabilitation robot training combined with iTBS real stimulation(coil placed parallel to the skull).Both groups underwent treatment for 3 weeks.Upper limb motor function was assessed using the Fugl-Meyer upper extremity(FMA-UE)scale and Wolf motor function test(WMFT);while neurological function was evaluated using the motor-evoked potentials(MEP)latency,amplitude,and central motor conduction time(CMCT)of the affected thumb abductor muscle.Activities of daily living were assessed using the modified Barthel index(MBI).Results(1)No significant differences in baseline data were found between the two groups(all P＞0.05).(2)Before treatment,the FMA-UE and WMFT scores in the experimental group were 27.48±7.87 and 28.22±3.87,respectively;and in the control group were 26.35±4.78 and 28.35±3.33,respectively;there were no significant differences in both FMA-UE and WMFT scores between the two groups(all P＞0.05).After 3weeks of treatment,the FMA-UE and WMFT scores in the experimental group were 40.35±8.96 and 37.74±4.11,respectively;and in the control group were 32.78±4.50 and 32.57±4.11,respectively;there were significant interaction effects of time and group(Ftime×group values of 19.613 and 31.522,both P＜0.01),main effects of group(Fgroup values of 5.401 and 5.897,both P＜0.05),and main effects of time(Ftime values of 176.516 and 211.478,both P＜0.01).(3)Before treatment,the MEP latency,amplitude,and CMCT in the experimental group were(24.39±3.56)ms,(137.77±42.67)μV,and(10.62±2.76)ms,respectively;and in the control group were(24.64±2.77)ms,(136.74±48.77)μV,and(10.73±1.84)ms,respectively,there were no significant differences between the two groups(all P＞0.05).After 3weeks of treatment,the MEP latency,amplitude,and CMCT in the experimental group were(20.39±1.83)ms,(239.91±43.70)μV,and(6.58±1.23)ms,respectively,and in the control group were(22.53±3.53)ms,(198.54±50.37)μV,and(9.19±1.60)ms,respectively,there were significant interaction effects of time and group(Ftime×group values of 7.270,15.554,and 20.110,all P＜0.05)and main effects of time(Ftime values of 76.540,256.706,and 100.629,all P＜0.01),the main effect of group for CMCT was significant(Fgroup=7.406,P＜0.01),but there were no significant difference in the main effect of group on MEP latency,amplitude between two groups(Fgroup values of 2.145,2.778,both P＞0.05).(4)Before treatment,the MBI score in the experimental group was 42.83±7.36,and in the control group was 43.91±6.56,with no significant difference between two groups(P＞0.05).After 3 weeks of treatments,the MBI score in the experimental group was 67.83±12.69,and in the control group was 54.13±5.57,there were significant interaction effects of time and group(Ftime×group=39.862,P＜0.01),main effects of group(Fgroup=8.083,P=0.007),and main effects of time(Ftime=226.241,P＜0.01).Conclusions Upper limb rehabilitation robot training combined with iTBS can improve upper limb motor function and neurological function and enhance the daily living activity ability of stroke patients.Real iTBS combined with robot training has a more significant effect than sham iTBS.

Objective:To investigate human factors underlying radiotherapy planning safety incidents and quantitatively explore their interrelationships.Methods:A total of 1 619 safety incidents recorded in the automated plan checking system developed by West China Hospital of Sichuan University were utilized. Human factors were identified and statistically analyzed using the Human Factors Analysis and Classification System (HFACS). A Bayesian network model was developed and combined with sensitivity analysis for quantitative assessment.Results:Key contributing factors included organizational processes (12.89%), inadequate supervision (11.85%), and personnel factors (13.50%). Utilizing the established HFACS Bayesian network hybrid model in conjunction with sensitivity analysis, it has been found that the most significant influences on skill‐based errors and decision errors were condition of operators and environmental factors, with corresponding indices of 0.96 and 0.76. Additionally, personnel factors had the greatest impact on routine, with an index of 3.51.Conclusions:Key contributing factors span all HFACS levels, with organizational processes, supervision, personnel, and condition of operators each playing a significant role. Upstream factors — such as organizational climate, environment factors, and personnel factors — strongly influence downstream risks. These offer actionable insights for developing targeted safety protocols.

Objective To evaluate the diagnostic performance of the minimum-cost-path-based CT angiography-derived fractional flow reserve(MCP-FFR)and the deep learning-driven CT angiography-derived fractional flow reserve(DeepCL-FFR),and to particularly explore the potential value of the DeepCL algorithm in improving diagnostic accuracy within the"gray zone."Methods A retrospective analysis was conducted on 151 coronary vessels from 109 patients with coronary artery disease,who were hospitalized at the General Hospital of the People's Liberation Army between January 2020 and June 2021.Pearson correlation and Bland-Altman plots were employed to assess the correlation and agreement of the two CT-FFR methods with invasive FFR.A CT-FFR range of 0.70-0.80 was defined as the diagnostic"gray zone."The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value for detecting hemodynamic abnormalities were calculated and analyzed.The DeLong test was used to compare the areas under the receiver operating characteristic curves(AUC)between the two CT-FFR calculation methods.Results Both CT-FFR methods exhibited a positive correlation with invasive FFR(MCP-FFR:r=0.75,P＜0.001;DeepCL-FFR:r=0.86,P＜0.001)and showed good agreement(MCP-FFR:mean difference=0.010,P=0.351;DeepCL-FFR:mean difference=-0.003,P=0.772).Both DeepCL-FFR(AUC 0.97,95％CI 0.94-0.99)and MCP-FFR(AUC 0.92,95％CI 0.88-0.97)demonstrated favorable diagnostic performance for detecting hemodynamic abnormalities(P=0.122).In the"gray zone"for hemodynamic abnormality,the diagnostic accuracy of MCP-FFR was 68.8％,whereas DeepCL-FFR increased it to 89.7％.DeepCL-FFR also exhibited superior diagnostic performance(AUC 0.89,95％CI 0.73-0.99)within the"gray zone,"which was significantly higher than that of MCP-FFR(AUC 0.71,95％CI 0.54-0.87)(P＜0.001).Conclusions The deep learning-driven coronary centerline extraction algorithm,DeepCL,demonstrates superior diagnostic performance in CT-FFR for detecting hemodynamic abnormalities,particularly by significantly improving diagnostic accuracy in the"gray zone."

Objective To investigate the effects of m6A methylation modification and changes in oxidative stress levels on the progression of colorectal cancer(CRC)in Apemin/+mice with normal and high-fat diets.Methods C57BL/6J mice and Apcmin/+mice were fed with a normal or high-fat diet(60％fat)for 2(S group),6(M group),or 12 weeks(L group),respectively.Food intake,body mass,and the size,number,and volume of small intestinal polyps and colon tumors were then measured.Protein expression levels of the cancer markers Ki-67 and proliferating cell nuclear antigen in colon tissues were detected by immunohistochemical staining and the serum levels or activities of the antioxidant enzymes catalase,reduced glutathione,and lipid peroxide malondialdehyde were detected using appropriate kits.mRNA expression levels of m6A methylation-related enzymes in colon tissues were detected by RT-qPCR and total levels of m6A methylation modification in colon tissues were detected.Results(1)Apcmin/+mice showed rapid tumor growth from the early to middle stages of cancer.Tumor proliferation from the middle to late stages of cancer was slowed in mice fed a normal diet,while a high-fat diet promoted the further development of cancer.(2)Decreased m6A methylation levels and enhanced antioxidant capacity may have delayed advanced tumor development in Apcmin/+mice fed a normal diet.(3)In contrast,a high-fat diet may have promoted the sustainable development of CRC by increasing the total level of m6A methylation,while the enhanced antioxidant capacity may have been insufficient to resist the promoting effect of m6A methylation on CRC.Conclusions A high-fat diet may promote the advancement of CRC compared with a normal diet by affecting m6A methylation modification.Both normal and high-fat diets enhanced the antioxidant capacity,suggesting that antioxidant effects may initiate self-protection mechanisms during cancer progression.

Objective:To explore the equity and driving path of primary healthcare human resource allocation across 31 provinces in China,providing references for optimizing such allocations.Methods:Using data from the 2022 primary healthcare human resources in 31 provinces in China,the Health Resource Density Index(HRDI)was used to measure the equity of primary healthcare human resource allocation.The fuzzy-set Qualitative Comparative Analysis(fsQCA)was applied to construct configurational pathways influencing on allocation patterns.Results:In 2022,the HRDI for primary healthcare human resources in China was 2.349 0 in the East,1.198 6 in the Central region,and 0.775 2 in the West.Configurational analysis revealed three paths that promote high equity:the internal-external balance-driven model(H1),the government-led model(H2),and the economic-demand combined model(H3),with overall consistency and coverage of 0.955 and 0.794,respectively.Seven paths lead to low equity:internal-external constraint models(L1,L2),economic constraint models(L3),and demand constraint models(L4,L5,L6,L7),with overall consistency and coverage of 0.967 and 0.795,respectively.Conclusions:Significant regional disparities exist in the equity of primary healthcare human resource allocation in China.Population density is a critical factor influencing allocation equity.The collaboration of various factors contributes to enhancing the equity of primary healthcare human resources distribution.Therefore,future efforts to enhance equity should focus on promoting inter-regional mobility and resource sharing,while precisely addressing regional shortcomings to achieve high equity in primary healthcare human resource allocation.

AIM:To investigate the impact of mitochondrial carrier homologous protein 2(MTCH2)on the metastasis of oral squamous cell carcinoma and to elucidate its underlying mechanisms.METHODS:Human tongue squamous cell carcinoma CAL-27 cells were selected as the study model.An MTCH2 inhibition and overexpression model was established using small interfering RNA(siRNA)technology and overexpression plasmids.Based on the experimental design,cells were categorized into the following groups:siRNA negative control(siRNA-NC)group,MTCH2 siRNA(siRNA-MTCH2)group,empty vector(OE-NC)group,and MTCH2 overexpression(OE-MTCH2)group.Transwell as-says and wound healing assays were conducted to assess the invasion and migration capabilities of cells in each group.The morphological changes and distribution of actin microfilaments were examined using a red fluorescent probe.The mito-chondrial membrane potential was evaluated using a mitochondrial membrane potential detection kit.The levels of reactive oxygen species(ROS)were measured using a ROS detection kit.Adenosine triphosphate(ATP)production levels were assessed with an ATP detection kit.The protein expression levels of MTCH2 and matrix metalloproteinase 14(MMP14)were analyzed through cell fluorescence and Western blot techniques.RESULTS:The number of invasive cells in the siRNA-MTCH2 group was significantly reduced,and the cell migration rate was notably decreased.Conversely,the OE-MTCH2 group exhibited a significant increase in both the number of invasive cells and the cell migration rate(P<0.01).The fluorescence intensity of F-actin and MTCH2 in the siRNA-MTCH2 group was significantly diminished,while these in-tensities were markedly elevated in the OE-MTCH2 group(P<0.01).The ROS levels in the siRNA-MTCH2 group were significantly higher than those in the siRNA-NC group,whereas the levels of ATP and mitochondrial membrane potential were significantly lower.Conversely,the ROS levels in the OE-MTCH2 group were significantly lower than those in the OE-NC group,with corresponding increases in ATP levels and mitochondrial membrane potential(P<0.01).The expres-sion levels of MTCH2 and MMP14 proteins in the siRNA-MTCH2 group were significantly lower than those in the siRNA-NC group,while the OE-MTCH2 group showed significantly higher expression levels compared to the OE-NC group(P<0.01).CONCLUSION:The MTCH2 is associated with the development of oral squamous cell carcinoma and may facili-tate the metastasis of CAL-27 cells by regulating mitochondrial function and MMP14 protein expression.Therefore,MTCH2 may represent a novel therapeutic target for the treatment of oral cancer.

AIM:To investigate the impact of mitochondrial carrier homologous protein 2(MTCH2)on the metastasis of oral squamous cell carcinoma and to elucidate its underlying mechanisms.METHODS:Human tongue squamous cell carcinoma CAL-27 cells were selected as the study model.An MTCH2 inhibition and overexpression model was established using small interfering RNA(siRNA)technology and overexpression plasmids.Based on the experimental design,cells were categorized into the following groups:siRNA negative control(siRNA-NC)group,MTCH2 siRNA(siRNA-MTCH2)group,empty vector(OE-NC)group,and MTCH2 overexpression(OE-MTCH2)group.Transwell as-says and wound healing assays were conducted to assess the invasion and migration capabilities of cells in each group.The morphological changes and distribution of actin microfilaments were examined using a red fluorescent probe.The mito-chondrial membrane potential was evaluated using a mitochondrial membrane potential detection kit.The levels of reactive oxygen species(ROS)were measured using a ROS detection kit.Adenosine triphosphate(ATP)production levels were assessed with an ATP detection kit.The protein expression levels of MTCH2 and matrix metalloproteinase 14(MMP14)were analyzed through cell fluorescence and Western blot techniques.RESULTS:The number of invasive cells in the siRNA-MTCH2 group was significantly reduced,and the cell migration rate was notably decreased.Conversely,the OE-MTCH2 group exhibited a significant increase in both the number of invasive cells and the cell migration rate(P<0.01).The fluorescence intensity of F-actin and MTCH2 in the siRNA-MTCH2 group was significantly diminished,while these in-tensities were markedly elevated in the OE-MTCH2 group(P<0.01).The ROS levels in the siRNA-MTCH2 group were significantly higher than those in the siRNA-NC group,whereas the levels of ATP and mitochondrial membrane potential were significantly lower.Conversely,the ROS levels in the OE-MTCH2 group were significantly lower than those in the OE-NC group,with corresponding increases in ATP levels and mitochondrial membrane potential(P<0.01).The expres-sion levels of MTCH2 and MMP14 proteins in the siRNA-MTCH2 group were significantly lower than those in the siRNA-NC group,while the OE-MTCH2 group showed significantly higher expression levels compared to the OE-NC group(P<0.01).CONCLUSION:The MTCH2 is associated with the development of oral squamous cell carcinoma and may facili-tate the metastasis of CAL-27 cells by regulating mitochondrial function and MMP14 protein expression.Therefore,MTCH2 may represent a novel therapeutic target for the treatment of oral cancer.

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.