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.

Objective:To explore the effect of exercise on glycemic control and physical indicators among community-dwelling persons with type 2 diabetes mellitus (T2DM).Methods:A total of 42 T2DM patients undergoing regular follow-up at a community health center were divided into a control group and an exercise group. To minimize confounding factors, 1∶1 propensity score matching was performed, resulting in 21 patients in each group. Both groups received standardized diabetes management, including medication, dietary guidance and diabetes health education. The exercise group additionally performed exercises which integrated sports and medical care models. The experiment lasted 8 weeks. Before and after the intervention, glycosylated hemoglobin A1c (HbA1c) levels, body weight, body mass index (BMI), fat mass, visceral fat area (VFA), fat mass index (FMI) and appendicular skeletal muscle mass index (ASMI) were recorded and compared between the two groups. Moreover, the actual exercise compliance of the exercise group was observed, along with any adverse events such as hypoglycemia or exercise-related injuries, as well as changes in antidiabetic medication dosage.Results:After the intervention, significant improvement was observed in both groups in all of the measurements, but with the average HbA1c, BMI, fat mass, VFA and FMI values of the exercise group then significantly better than the control group′s averages. The average compliance rate in the exercise group was 60%. No cases of hypoglycemia or exercise-related injuries were reported during the intervention, and there were no changes in the use of anti-diabetes medications.Conclusions:Exercise effectively improves glycemic control and physical indicators among community-dwelling T2DM patients. However, exercise compliance needs improving.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Objective To estimate the prevalence of calcified nodule(CN)among patients with coronary artery disease(CAD)and identify the possible risk factors associated with an increased CN risk.Methods Databases include PubMed,Web of Science and Embase was conducted to identify studies reporting the prevalence and/or risk factors of CN.For this databases,the search was from inception to January 1,2024.Data analyses was performed using R statistical Software 4.2.2.Results A total of 46 studies involving 17 926 patients were included.Among them,13 studies with 4 187 patients reported both the prevalence and associated risk factors.The overall prevalence of CN was found to be 5.72％(95％CI 4.47％-7.31％),while in studies reporting both the prevalence and risk factors,the CN prevalence was slightly higher at 8.72％(95％CI 6.43％-11.71％).Hypertension(OR 1.75,95％CI 1.29-2.37),diabetes(OR 1.84,95％CI 1.46-2.33),chronic kidney disease(OR 2.50,95％CI 1.67-3.74),and hemodialysis(OR 7.77,95％CI 4.77-12.67)were associated with an elevated CN risk(all P＜0.001).Conversely,obesity(OR 0.39,95％CI 0.18-0.83)and history of smoking(OR 0.61,95％CI 0.47-0.80)were linked to a decreased CN risk(both P＜0.05).Conclusions The overall prevalence of CN is relatively low among patients with CAD.However,the prevalence of CN is influenced by a variety of clinical factors.Further research is warranted to elucidate the underlying mechanisms.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To estimate the prevalence of calcified nodule(CN)among patients with coronary artery disease(CAD)and identify the possible risk factors associated with an increased CN risk.Methods Databases include PubMed,Web of Science and Embase was conducted to identify studies reporting the prevalence and/or risk factors of CN.For this databases,the search was from inception to January 1,2024.Data analyses was performed using R statistical Software 4.2.2.Results A total of 46 studies involving 17 926 patients were included.Among them,13 studies with 4 187 patients reported both the prevalence and associated risk factors.The overall prevalence of CN was found to be 5.72％(95％CI 4.47％-7.31％),while in studies reporting both the prevalence and risk factors,the CN prevalence was slightly higher at 8.72％(95％CI 6.43％-11.71％).Hypertension(OR 1.75,95％CI 1.29-2.37),diabetes(OR 1.84,95％CI 1.46-2.33),chronic kidney disease(OR 2.50,95％CI 1.67-3.74),and hemodialysis(OR 7.77,95％CI 4.77-12.67)were associated with an elevated CN risk(all P＜0.001).Conversely,obesity(OR 0.39,95％CI 0.18-0.83)and history of smoking(OR 0.61,95％CI 0.47-0.80)were linked to a decreased CN risk(both P＜0.05).Conclusions The overall prevalence of CN is relatively low among patients with CAD.However,the prevalence of CN is influenced by a variety of clinical factors.Further research is warranted to elucidate the underlying mechanisms.

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Objective To propose a lead attention network-based ST-T change recognition algorithm to detect ECG ST-T changes accurately.Methods Firstly,heartbeat signals were extracted through R-wave localization,and a 12-lead heartbeat matrix was generated by correlation-based screening and merging to realize data augmentation.Secondly,a lead attention module was constructed by combining depthwise convolution(DWConv)with the channel attention squeeze-and-excitation block(SE-block)structure to perceive the differences in ST-T status among electrocardiogram leads.Thirdly,the mapping output by two independent attention modules was fused and splicing with the original signal residual was carried out,so that attention information extraction and original information transfer were enhanced effectively.Finally,SE-ResNet was used as the backbone network to extract signal features to complete the classification and identification of ST-T changes.To validate the recognition performance of the proposed algorithm for ST-T changes in ECG,the 12-lead ECG data of 97 472 patients containing different ECG rhythms were collected for ablation and comparison experiments at the First Affiliated Hospital of Army Medical University.Results The proposed algorithm achieved an AUC of 0.965 with a sensitivity of 90.51%,specificity of 90.23%,positive predictive value of 89.24%and overall accuracy of 90.36%on an independent test set.Comparative analysis demonstrated superior performance to four benchmark architectures,including VGG16,ResNet18,MobileNetV3-Small and ShuffleNet,in terms of both classification accuracy and computational efficiency.Conclusion The algorithm designed can accurately detect ST-T changes and can be used for wearable ECG automatic analysis to assist in the early warning of cardiovascular diseases in both acute and chronic patients and highland residents.[Chinese Medical Equipment Journal,2025,46(7):1-11]

Background and Aims:Pancreatic cancer is one of the most aggressive malignancies of the digestive system and is associated with an inferior prognosis.In recent years,its incidence has shown a trend toward younger onset.Early-onset pancreatic cancer(EOPC),defined as pancreatic cancer diagnosed at≤50 years of age,has been increasing annually and may possess distinct biological and prognostic characteristics.Given the limited data from China,this study aimed to investigate the clinicopathological features and prognostic outcomes of EOPC patients.Methods:Clinical data of 113 patients with EOPC admitted to Xiangya Hospital,Central South University,from January 2017 to December 2023 were retrospectively analyzed.Variables included demographic characteristics,clinicopathological features,and survival information.Kaplan-Meier survival curves were plotted,and differences in survival between the surgical and non-surgical groups were compared.Results:The median age at diagnosis was 46(42-49)years,and males accounted for 65.49%of cases.Blood type A(40.71%)and type O(34.51%)were most common.The main presenting symptoms were abdominal pain(69.91%),weight loss(62.83%),jaundice(43.36%),and abdominal distension(36.28%).Imaging findings showed bile duct dilation in 32.74%,pancreatic duct dilation in 39.82%,vascular invasion in 59.29%,and distant metastasis in 52.21%of patients.Histopathology revealed that adenocarcinoma and ductal adenocarcinoma accounted for 93.81%of all cases,with predominantly moderate or poor differentiation(76.10%).Tumors were the most frequently located in the pancreatic head(65.42%).TNM staging showed lymph node metastasis in 77.88%and stage Ⅳ disease in 52.21%.Laboratory tests demonstrated markedly elevated CA19-9 levels.Kaplan-Meier analysis indicated a median overall survival of 18.6 months for the entire cohort,with significantly longer survival in the surgical group compared with the non-surgical group(29.4 months vs.13.8 months,P=0.001 5).Conclusion:EOPC predominantly affects males and tends to arise in the pancreatic head.It is often diagnosed at an advanced stage or with distant metastasis and is characterized by poor differentiation and strong invasiveness.Surgical resection markedly improves survival and remains the key to prolonged prognosis.Young individuals presenting with unexplained abdominal pain,weight loss,or jaundice should be carefully evaluated through imaging to enable early diagnosis and timely surgical intervention.Future multicenter,large-sample prospective studies are warranted to validate these findings further.

In 2025,the International Association of Pancreatology(IAP),in collaboration with the American Pancreatic Association,European Pancreatic Club,Indian Pancreas Club,and Japan Pancreas Society,released the International Association of Pancreatology revised guidelines on acute pancreatitis 2025.This edition represents a comprehensive revision of the 2013 guidelines,based on high-quality evidence accumulated over the past decade,particularly randomized controlled trials.The guidelines encompass 18 key areas-including pain management,fluid therapy,nutritional support,management of infected necrosis,complication control,discharge and follow-up,and recurrence prevention-offering a total of 96 recommendations that emphasize individualized treatment.These updates provide important guidance for standardizing clinical practice and improving outcomes in acute pancreatitis,while also indicating future research directions such as the development of targeted therapies.However,some recommendations remain limited by lower evidence quality,uncertain applicability in specific clinical settings,and insufficient consideration of economic burden and cost-effectiveness.