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.

To address the growing challenge of an increasing number of elderly lung cancer patients amidst China's aging population and to fill the gap in quality control standards for surgical treatment in this special population, this study aimed to develop a standardized surgical evaluation system for elderly lung cancer patients tailored to China's national conditions. The system was established through a literature review, integrated the pathophysiological characteristics of elderly patients, and was constructed following review, feedback, and revision by experts from multiple thoracic surgery centers. Employing a 100-point scoring system, it comprises three primary domains: physical infrastructure and geriatric adaptability foundational conditions (10 points); management level and perioperative care models (20 points); and technical proficiency and clinical outcomes (70 points). The system places a strong emphasis on geriatric adaptability, proposing specific, quantifiable indicators for age-friendly facility modifications, control of elderly-specific complications, multidisciplinary collaboration, and standardized perioperative management. It provides a convenient and measurable assessment tool for quality control in the surgical treatment of elderly lung cancer in China, which is expected to promote the standardization and homogenization of diagnosis and treatment.

Objective Using cockroach surveillance data in Nanjing from 2017 to 2024, we have descriptively analyzed population characteristics and changes in insecticide resistance among Blattella germanica, and have established a seasonal Autoregressive Integrated Moving Average (ARIMA) model to predict monthly population densities in Nanjing spanning the year 2025. Methods B. germanica density and infestation rate were monitored using the sticky trap method, and insecticide resistance was assessed using the residual contact method. Our ARIMA model was applied to fit and estimate cockroach density fluctuations over time. Results From 2017 to 2024, B. germanica accounted for 94.90% of all cockroach specimens captured in Nanjing, with an average density of 0.37 cockroaches per trap and an average infestation rate of 5.56%. Significant differences in density and infestation rate were observed among different habitats (P＜0.001). Significant downward annual trends in both density and infestation rate were found (P＜0.05). ARIMA was found to be the optimal model for fitting the density data from 2017 to 2024 (0, 1, 1) × (0, 1, 1)1 2. Conclusions From 2017 to 2024, B. germanica was overwhelmingly the dominant cockroach species in Nanjing, with both its density and infestation rate declining annually. A positive correlation was observed between the amount and proportion of insecticide use and the development of insecticide resistance (P＜0.05). The established model demonstrated good performance in predicting monthly B. germanica densities in Nanjing throughout 2025, providing a valuable reference for future surveillance and control efforts.

Objective To discuss the efficacy of transcatheter arterial chemoembolization(TACE)in combination with targeted therapy and immune checkpoint inhibitors for advanced hepatocellular carcinoma(HCC),and to identify the influencing factors.Methods A total of 60 patients with advanced HCC,who were admitted to the Air Force Medical Center of China from January 2016 to December 2022,were enrolled in this study.Thirty patients received TACE combined with targeted therapy and immune checkpoint inhibitors(TACE-L-P group),and the other 30 patients received TACE combined with targeted therapy(TACE-L group).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and objective response rate(ORR)were compared between the two groups.Results In the TACE-L group and TACE-L-P group,the median PFS(mPFS)was 7 months and 10 months respectively(P=0.011),the median OS(mOS)was 15.5 months and 29 months respectively(P=0.014).Child-Pugh class B(HR=3.89,95％CI:1.27-11.94,P=0.018)and Barcelona Clinic Liver Cancer(BCLC)stage C(HR=2.83,95％CI:1.32-6.03,P=0.007)were the independent risk factors for OS,while micro wave ablation(HR=0.21,95％CI:0.07-0.63,P=0.005)and TACE-L-P(HR=0.09,95％CI:0.03-0.3,P=0.001)were the independent protection factors for OS.Besides,elevated bilirubin level(HR=1.03,95％CI:1-1.06,P=0.032)and elevated gamma-glutamyl transferase(GGT)level(HR=1.01,95％CI:1-1.01,P=0.002)were the independent risk factors for disease progression,and TACE-L-P(HR=0.27,95％CI:0.09-0.79,P=0.017)was the independent protection factor for disease progression.The ORR and DCR in TACE-L-P group were remarkably higher than those in TACE-L group,which were 43.4％vs 13.3％and 63.4％vs 23.3％respectively,the differences between the two groups were statistically significant(both P＜0.05).Conclusion In treating advanced HCC,TACE combined with targeted therapy and immune checkpoint inhibitors is superior to TACE combined with targeted therapy in therapeutic efficacy.

Objective To investigate the predictive value of pan-immune inflammatory values(PIV)in the prognosis of patients with ischemic stroke(AIS)treated with intravascular intervention combined with tirofiban.Methods 102 AIS cases admitted to the Department of Neurology of the First People's Hospital of Zhaotong from January 2019 to December 2023 and treated with intravascular intervention combined with Tirofiban were selected as the study objects.The patients were divided into the mild group(n=9),moderate group(n=45)and severe group(n=48)according to the score of NIHSS after the admission.According to the mRS 90 days after the treatment,the cases were divided into the good prognosis group(n=63)and poor prognosis group(n=38).Data were collected and analyzed.The predictive value of PIV level in patients with ischemic stroke treated with intravascular intervention combined with tirofiban was evaluated by ROC.The risk factors of adverse outcomes in patients with ischemic stroke treated with intravascular intervention combined with tirofiban were investigated by multivariate Logistic regression.Results A total of 102 patients with ischemic stroke were included.The PIV level in the good prognosis group 331.1(221.9,662.7)was lower than that in the poor prognosis group 1 025.7(451.5,1 841.3)(P<0.05).PIV level in the severe group was higher than that in the mild and moderate groups,and PIV level in the moderate group was higher than that in the mild group(P<0.05).The AUC(95％CI)of PIV for predicting adverse outcomes of intravascular intervention combined with tirofiban in patients with ischemic stroke was 0.750(95％CI 0.654～0.831),the cut-off point was 834.92,the specificity was 85.71％and the sensitivity was 65.79％.NIHSS score>18(OR=5.944 95％CI 2.011～19.137),PIV>834.92(OR=4.863,95％CI 1.410～18.685)were the risk factors for the poor outcome of intravascular intervention combined with tirofiban in patients with ischemic stroke(P<0.05).Conclusion Elevated PIV is closely related to the poor outcomes in patients with ischemic stroke treated with intravascular intervention combined with Tirofiban.High PIV and NIHSS scores are both risk factors for the poor prognosis in patients with ischemic stroke,and can be used as the sensitive indicators for the early identification.

Drynaria fortunei,commonly known as"bone setting herb",has been widely included in various traditional Chinese herb-al classics for treating bone injuries.It is used medicinally from its rhizome,which has a bitter taste and warm property.It is known to nourish the kidneys,strengthen bones,and alleviate pain from injuries.The chemical constituents mainly include flavonoids,phenylpro-panoids,triterpenoids,phenolic acids,lignans,and sterols.Modern medical research indicates that Drynaria fortunei has anti-osteoporo-sis effects,promotes fracture healing,has anti-inflammatory properties,and benefits dental health.This article reviews the historical use of Drynaria fortunei and recent research on its chemical composition and pharmacological effects,summarizing some of the mechanisms of action.The aim is to provide a reference for further research on this medicinal herb.

Objective To investigate the application effect of three-dimensional CT-assisted pedicle measurement in elderly patients undergoing percutaneous vertebroplasty(PVP).Methods A total of 80 osteoporotic patients with L1 vertebral compression fracture who were treated in People's Hospital of Qujiang District in Shaoguan from March 2021 to March 2023 were selected as the study subjects.Three-dimensional CT-assisted pedicle measurement was performed before surgery,including L1 axial effective angle,axial effective pedicle transverse,oblique sagittal effective angle,oblique sagittal effective longitudinal diameter,and pedicle transverse diameter,and their differences between different genders were analyzed.Four patients with an effective pedicle diameter of less than 3 mm were included into the bilateral group,and the rest of the patients were divided into the unilateral group(received unilateral-approach PVP)and the bilateral group(received bilateral-approach PVP)according to the random number table method.The perioperative conditions of patients in the two groups were collected.The follow-up was performed for six months after surgery,and the visual analogue scale(VAS)score and Oswestry dysfunction index(ODI)score of patients between the two groups were compared before surgery,1 month after surgery and 6 months after surgery.X-ray examinations were performed before and after surgery to evaluate the recovery of Cobb angle and cement leakage.Results No significant difference was observed in axial universal effective angle or universal oblique sagittal effective angles between genders(P>0.05).The male patients showed greater axial lateral effective angle,axial lateral effective pedicle transverse,axial universal effective pedicle transverse,lateral oblique sagittal effective angle,lateral oblique sagittal effective longitudinal diameter,universal oblique sagittal effective longitudinal diameter,and pedicle transverse as compared to female patients,with statistically significant differences(P<0.05).The intraoperative fluoroscopy times and bone cement injection volume of patients in the unilateral group were less/lower than those in the bilateral group,with statistically significant differences(P<0.05).There was no significant difference in the operation time of patients between the two groups(P>0.05).During the follow-up period,3 patients were lost to follow-up in the unilateral group and 4 patients in the bilateral group.One patient in the unilateral group had cement leakage.There were no significant differences in the VAS scores,ODI scores before surgery and 1 month after surgery or Cobb angles before and after surgery between the two groups(P>0.05).The VAS and ODI scores of patients in the unilateral group 6 months after surgery were significantly higher than those in the bilateral group,with statistically significant differences(P<0.05).Conclusion In the treatment of osteoporotic vertebral compression fractures,three-dimensional CT-assisted pedicle measurement before PVP can help to achieve accurate puncture,and improve the safety and effectiveness of the surgery.

Objective To explore the role and possible mechanism of adenosine monophosphate(AMP)-dependent protein kinase(AMPK)/insulin receptor(IR)/insulin receptor substrate(IRS1)pathway in myocardial insulin resistance in diabetic mice.Methods Thirty C57BL/6J mice were randomly divided into control group,diabetes group and AMPK-activated group according to the experimental design,with 10 mice in each group.Fasting blood glucose(FBG)was detected by a dynamic blood glucose detector detected.Glycosylated hemoglobin kit(HbA1c)was used to detect the level of HbA1c in mice.Fasting insulin(FINS)was detected by insulin detection kit in mice.Heart rate(HR),left ventricular end-systolic diameter(LVIDd),left ventricular end-diastolic diameter(LVIDs),ejection fraction(EF)and left ventricular fractional shortening(LVFS)were measured by echocardiography.Masson staining was used to detect myocardial collagen deposition in mice.The levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),glutathione(GSH),malondialdehyde(MDA)and reactive oxygen species(ROS)were detected by ELISA kit.The protein levels of AMPK,IR and IRS1 in myocardial tissue were detected by Western blotting(WB).RT-qPCR detected the mRNA levels of AMPK,IR and IRS1 in myocardial tissue.Results Compared with the control group,the levels of FBG,HbA1c,FINS,TC,TG and LDL-C in diabetic group were increased(t=14.94～63.46),the cardiac function indexes HR,EF and LVFS decreased(t=56.62,199.00,42.50),LVIDd increased(t=176.80),and the differences were statistically significant(all P<0.05),and there was no significant difference in LVIDs(t=3.46,P>0.05).The collagen deposition around small blood vessels in myocardial interstitial was increased,and the serum GSH level was decreased(t=5.75),ROS and MDA levels increased(t=22.60,15.18),the expression levels of AMPK,IR,IRS1 protein(t=7.00,4.33,3.66)and mRNA(t=2.61,5.17,6.79)in myocardial tissue decreased,and the differences were statistically significant(all P<0.05).Compared with diabetic group,the levels of FBG,HbA1c,FINS,TC,TG and LDL-C in AMPK activated group were decreased(t=9.14～56.34),the cardiac function indexes HR,EF and LVFS increased(t=135.90,152.00,41.99),LVIDd decreased(t=203.20),and the differences were statistically significant(all P<0.05),and there was no significant difference in LVIDs(t=1.58,P>0.05).Perivascular collagen deposition decreased and serum GSH level increased(t=19.60),ROS and MDA levels decreased(t=32.90,23.44),the expression levels of AMPK,IR,IRS1 protein(t=15.14,29.44,17.15)and mRNA(t=11.52,9.67,8.49)in myocardial tissue increased,and the differences were statistically significant(all P<0.05).Conclusion Activation of AMPK can improve the cardiac function structure,reduce blood glucose and lipid levels and reduce oxidative stress levels in diabetic mice.The mechanism of action may be related to insulin resistance mediated by AMPK/IR/IRS1 pathway.

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

Objective:To investigate the adjunctive diagnostic value of retinal imaging structural parameters combined with apolipoprotein E (ApoE) gene polymorphisms for Alzheimer′s disease (AD).Methods:It was a case-control study, 71 confirmed AD patients who attended the Department of Neurology in Sichuan Provincial People′s Hospital from May 2023 to June 2024 and 156 healthy medical checkups who participated in medical checkups in the Health Management Center were continuously with convenience sampling method; the subjects were included as the AD case group and healthy control group, respectively. Optical coherence tomography (OCT) was used to measure the structural parameters of retinal imaging such as the thickness of the retinal nerve fiber layer (RNFL) and the retinal nerve fiber layer-inner plexiform layer (RNFL-IPL) in the study subjects. Information on demographic characteristics and disease history of the study participants were collected through a questionnaire, and venous blood was collected to test for ApoE gene polymorphisms. The retinal imaging structural parameters, ApoE gene polymorphisms and other related indicators were included in a multifactorial logistic regression model to analyze the main factors affecting the risk of AD. Based on the results of the multifactorial analysis, the receiver operating characteristic (ROC) curves were plotted and the areas under the curve (AUC) were calculated to evaluate the efficacy of different models in the adjunctive diagnosis of AD.Results:Of the 227 study subjects included in the analysis, 153 were females and 74 were males; there were 71 cases in the AD case group with a mean age of (66.73±8.83) years, and there were 156 subjects in the healthy control group with an average age of (61.95±8.21) years. Educational attainment of elementary school and below ( OR=4.683, 95% CI: 2.133-10.282), living visual acuity<0.5 ( OR=2.716, 95% CI: 1.12-6.583), and carrying ≥1 ApoE ε4 genes ( OR=5.331, 95% CI: 2.309-11.891) were positively correlated with the risk of AD. RNFL thickening ( OR=0.923, 95% CI: 0.854-0.998) was negatively associated with the risk of AD (all P<0.05). The AD risk assessment model (Model 4), which included fundus imaging features and ApoE gene polymorphisms, had the highest predictive efficacy (AUC=0.857, P<0.001). Conclusion:Retinal imaging structural parameters differ significantly between AD patients and healthy examinees, and a risk assessment model combining retinal imaging structural parameters and ApoE gene polymorphisms has high predictive value and is expected to serve as an auxiliary diagnostic tool for AD.