ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.

This study investigated the infection status,drug resistance,and molecular characteristics of Shiga toxin-producing Escherichia coli(STEC)in domestic goats in Chengkou county,Chongqing.In August 2023,283 fecal samples were collected from households in Chengkou county.After enrichment with EC broth and inoculation onto selective media,samples that tested positive for stx1/stx2 were selected for further isolation.The positive strains were investigated with antimicrobial susceptibility testing and whole genome sequencing.According to the whole genomic sequences,the stx subtypes,serotypes,multi-locus sequence types,virulence genes,drug resistance genes,and phylogenetic relationships of the STEC strains were analyzed.Forty-six strains of STEC were isolated from 283 goat fecal samples,thus resulting in a detection rate of 16.25%.The 46 STEC strains were categorized into 12 O∶H serotypes,among which O76∶H19 and O8∶H7 predominated,each represented by 9 strains.Five STEC strains were identified as serotype O157∶H7.The 46 STEC strains were categorized into 11 sequence types(STs),among which ST675 and ST196 predominated,each represented by nine strains,accounting for a 19.57%proportion.The strains were categorized into 7 stx subtypes,among which stx1c(26/46,56.52%),followed by stx2k(9/46,19.57%)predominated.All nine Stx2k-STEC strains were identified as serotype O8∶H7 and sequence type ST196.In antimicrobial susceptibility testing,2 STEC strains were resistant to ampicillin,one strain was resistant to ampicillin/sulbactam,one strain was resistant to cefazolin,and one strain was resistant to cefoxitin.Nine Stx2k-STEC strains were found to carry the beta-lactam resistance gene blaEC-18.Antimicrobial sensitivity tests revealed that the nine Stx2k-STEC strains were sensitive to all 15 tested antibiotics.Moreover,phylogenetic analysis indicated that the 9 Stx2k-STEC strains were remarkably similar but showed high genetic diversity with respect to that of the Stx2k-STEC strains isolated from other regions in China.Goatsare an important animal reservoir for STEC in theChengkou district of Chongqing,and novel sequence type Stx2k-STEC strains distinct from those found in other regions of China were identified in this region.

Objective To investigate the value of serum micro ribonucleic acid-335-5p(miR-335-5p)and endothelial cell-specific molecule-1(ESM1)in the early diagnosis and prognosis of patients with esophageal cancer.Methods A total of 81 patients diagnosed with esophageal cancer by pathological examination were selected from April 2019 to April 2023 as the esophageal cancer group,and 81 healthy volunteers who underwent physical examination in our hospital were selected as the control group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the levels of miR-335-5p and ESM1.According to the follow-up results,46 cases were grouped into the good prognosis group and 35 cases in the poor prognosis group.Pearson correlation analysis was used to analyze the relationship between serum miR-335-5p and ESM1 in patients with esophageal cancer.Receiver operating characteristic(ROC)curve was plotted to analyze the value of serum miR-335-5p and ESM1 levels in diagnosing esophageal cancer and the value in evaluating the prognosis of esophageal cancer patients.Results Compared with the control group,the serum level of miR-335-5p in the esophageal cancer group was greatly reduced,the level of ESM1 was greatly increased(P＜0.05).MiR-335-5p had binding sites with ESM1.Pearson correlation analysis showed that serum miR-335-5p was negatively correlated with ESM1 level in patients with esophageal cancer(r=-0.538,P＜0.001).Compared with the individual diagnosis,the AUC of the combination of serum levels of miR-335-5p and ESM1 in the diagnosis of esophageal cancer was greatly higher(ZmiR-335-5p～miR5-335-5p+ESM1=2.625,P=0.009;ZESM1～miR-335-5p+ESM1=4.156,P＜0.001).The levels of miR-335-5p and ESM1 were correlated with TNM stage,lymph node metastasis and differentiation(P＜0.05).Compared with the good prognosis group,the serum level of miR-335-5p in the poor prognosis group was greatly reduced,and the ESM1 level was greatly increased(P＜0.05).Compared with the individual diagnosis,the AUC of combination of serum miR-335-5p and ESM1 levels in the prognostic assessment of esophageal cancer patients was greatly higher(ZmiR-335-5p～miR-335-5p+ESM1=2.128,P=0.033;ZESM1～miR-335-5p+ESM1=2.440,P=0.015).Conclusion MiR-335-5p is low expressed and ESM1 is highly expressed in the serum of esophageal cancer patients,they have certain clinical value for early diagnosis and prognostic evaluation of esophageal cancer patients.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.

Objective To propose an EBT3 film technology-based quality control measurement method for the INTRABEAM PRS500 intraoperative radiotherapy equipment to solve the problems of the traditional methods in cumbersome operation and setup error.Methods According to HJ 1198-2021 Requirements of radiation safety and protection for radiotherapy and GBZ 121-2020 Requirements for radiological protection in radiotherapy,the environmental radiation testing of the INTRABEAM PRS500 intraoperative radiotherapy equipment was carried out point by point by means of the radiation inspection instrument.The INTRABEAM PRS500 intraoperative radiotherapy equipment was characterized by a point X-ray source(XRS),and the XRS was detected in terms of the probe linearity,radiation dose,dynamic deviation,isotropy and dose rate.The EBT3 film technology was used to verify the symmetry and isotropy of the XRS planar dose of INTRABEAM PRS500 intraoperative radiotherapy equipment.Results The X-γ dose equivalent rate of each monitoring site of the INTRABEAM PRS500 intraoperative radiotherapy device was lower than the method detection limit(MDL).The results of SQA quality control showed that the INTRABEAM PRS500 intraoperative radiotherapy equipment XRS met the quality control requirements in terms of the probe linearity,radiation dose,dynamic deviation and etc,and the isotropy differences in the+X,-X,+Y,and-Y axis directions ranged from-1.40％to 1.79％,which were all within the allowable range of measurement tolerance(5.60％to 5.65％).The results of measuring the isotropy of the INTRABEAM PRS500 intraoperative radiotherapy equipment based on the EBT3 film technology showed that the dose distribution of the XRS in the directions of the+X,-X,+Y,and-Y axes at the same plane was well isotropic,and that the doses in the directions of the X and Y axes were symmetrically distributed,and that the maximum skewness value for the isotropy of the XRS in the XY plane was-1.581％,which met the requirements of AAPM TG61 report on the reference dosimetry of low-energy and medium-energy X-rays for radiotherapy and radiobiology of≤±5.3％.Conclusion The EBT3 film technology-based measurement method gains high simplicity and feasibility for the isotropy of the INTRABEAM PRS500 intraoperative radiotherapy equipment in the directions of the+X,-X,+Y,and-Y axes at the same planet,which realizes the dynamic monitoring of the dosimetric changes and facilitates the whole-process quality control management of the intraoperative radiotherapy equipment.[Chinese Medical Equipment Journal,2025,46(6):47-53]

Objective To investigate the value of serum micro ribonucleic acid-335-5p(miR-335-5p)and endothelial cell-specific molecule-1(ESM1)in the early diagnosis and prognosis of patients with esophageal cancer.Methods A total of 81 patients diagnosed with esophageal cancer by pathological examination were selected from April 2019 to April 2023 as the esophageal cancer group,and 81 healthy volunteers who underwent physical examination in our hospital were selected as the control group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the levels of miR-335-5p and ESM1.According to the follow-up results,46 cases were grouped into the good prognosis group and 35 cases in the poor prognosis group.Pearson correlation analysis was used to analyze the relationship between serum miR-335-5p and ESM1 in patients with esophageal cancer.Receiver operating characteristic(ROC)curve was plotted to analyze the value of serum miR-335-5p and ESM1 levels in diagnosing esophageal cancer and the value in evaluating the prognosis of esophageal cancer patients.Results Compared with the control group,the serum level of miR-335-5p in the esophageal cancer group was greatly reduced,the level of ESM1 was greatly increased(P＜0.05).MiR-335-5p had binding sites with ESM1.Pearson correlation analysis showed that serum miR-335-5p was negatively correlated with ESM1 level in patients with esophageal cancer(r=-0.538,P＜0.001).Compared with the individual diagnosis,the AUC of the combination of serum levels of miR-335-5p and ESM1 in the diagnosis of esophageal cancer was greatly higher(ZmiR-335-5p～miR5-335-5p+ESM1=2.625,P=0.009;ZESM1～miR-335-5p+ESM1=4.156,P＜0.001).The levels of miR-335-5p and ESM1 were correlated with TNM stage,lymph node metastasis and differentiation(P＜0.05).Compared with the good prognosis group,the serum level of miR-335-5p in the poor prognosis group was greatly reduced,and the ESM1 level was greatly increased(P＜0.05).Compared with the individual diagnosis,the AUC of combination of serum miR-335-5p and ESM1 levels in the prognostic assessment of esophageal cancer patients was greatly higher(ZmiR-335-5p～miR-335-5p+ESM1=2.128,P=0.033;ZESM1～miR-335-5p+ESM1=2.440,P=0.015).Conclusion MiR-335-5p is low expressed and ESM1 is highly expressed in the serum of esophageal cancer patients,they have certain clinical value for early diagnosis and prognostic evaluation of esophageal cancer patients.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.

Background and Aims:Conversion therapy offers initially unresectable hepatocellular carcinoma(HCC)patients a chance for curative resection.However,the optimal margin width following conversion remains unclear.This study aimed to evaluate the impact of surgical margin width on prognosis and identify independent prognostic factors in HCC patients undergoing hepatectomy after conversion therapy.Methods:A retrospective analysis was performed on 413 patients with initially unresectable HCC who received conversion therapy and underwent radical resection at Cancer Prevention and Control Center of Sun Yat-sen University between February 2015 and June 2022.According to the intraoperatively measured pathological margin,patients were classified into two groups:tumor margin<1 cm and≥1 cm,and further divided into subgroups with margins of 0 cm,0.1 cm,and>0.1 cm to compare survival differences among groups.The Kaplan-Meier method and Cox proportional hazards model were used to evaluate disease-free survival(DFS),overall survival(OS),and their influencing factors.Results:The 3-year OS and DFS showed no significant difference between the<1 cm and≥1 cm groups(both P>0.05).However,patients with a 0 cm margin had significantly worse OS than those with a 0.1 cm margin(P=0.048).No significant survival difference was observed in OS and DFS between the 0.1 cm and>0.1 cm groups(both P>0.05).Multivariate analysis identified multiple tumors,poor differentiation,and microvascular invasion as independent adverse prognostic factors for both OS and DFS(all P<0.05),whereas targeted therapy was an independent protective factor for DFS(P=0.014).Conclusion:A pathological margin≥0.1 cm provides comparable survival to wider margins and can be considered a safe threshold for HCC patients undergoing hepatectomy after conversion therapy.The conventional 1 cm margin standard offers no additional benefit.Multiple tumors,poor differentiation,and microvascular invasion predict poor prognosis,while targeted and immunotherapy during conversion may improve long-term outcomes.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Background and Aims:Conversion therapy offers initially unresectable hepatocellular carcinoma(HCC)patients a chance for curative resection.However,the optimal margin width following conversion remains unclear.This study aimed to evaluate the impact of surgical margin width on prognosis and identify independent prognostic factors in HCC patients undergoing hepatectomy after conversion therapy.Methods:A retrospective analysis was performed on 413 patients with initially unresectable HCC who received conversion therapy and underwent radical resection at Cancer Prevention and Control Center of Sun Yat-sen University between February 2015 and June 2022.According to the intraoperatively measured pathological margin,patients were classified into two groups:tumor margin<1 cm and≥1 cm,and further divided into subgroups with margins of 0 cm,0.1 cm,and>0.1 cm to compare survival differences among groups.The Kaplan-Meier method and Cox proportional hazards model were used to evaluate disease-free survival(DFS),overall survival(OS),and their influencing factors.Results:The 3-year OS and DFS showed no significant difference between the<1 cm and≥1 cm groups(both P>0.05).However,patients with a 0 cm margin had significantly worse OS than those with a 0.1 cm margin(P=0.048).No significant survival difference was observed in OS and DFS between the 0.1 cm and>0.1 cm groups(both P>0.05).Multivariate analysis identified multiple tumors,poor differentiation,and microvascular invasion as independent adverse prognostic factors for both OS and DFS(all P<0.05),whereas targeted therapy was an independent protective factor for DFS(P=0.014).Conclusion:A pathological margin≥0.1 cm provides comparable survival to wider margins and can be considered a safe threshold for HCC patients undergoing hepatectomy after conversion therapy.The conventional 1 cm margin standard offers no additional benefit.Multiple tumors,poor differentiation,and microvascular invasion predict poor prognosis,while targeted and immunotherapy during conversion may improve long-term outcomes.