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 compare the risk of pneumonitis and interstitial lung disease （ILD） associated with different antibody-drug conjugates （ADC） in the treatment of breast cancer. METHODS CNKI， VIP， PubMed， Embase and other Chinese and English databases， and ClinicalTrials.gov were searched from the inception to June 15， 2025. Randomized controlled trials （RCT） about pneumonitis and ILD associated with ADC （T-DM1， T-DXd， SG， Dato-DXd， SHR-A1811，ARX788， and T-Duo） in the treatment of breast cancer were included. After literature screening， data extraction， and quality assessment， a network meta-analysis was conducted using Stata 17.0 software， and the surface under the cumulative ranking curve（SUCRA） of all interventions were ranked. RESULTS A total of 19 RCTs involving 10 556 patients were included. The overall incidence of pneumonitis with ARX788 and T-DXd was significantly higher than that with T-DM1， T-DM1 plus TPC（T-DM1combined with pertuzumab or atezolizumab）， TPC（treatment of primary care）， and SG （ P ＜0.05）， for grade 1-2 pneumonitis， ARX788 and T-DXd showed significantly higher incidence than T-DM1， T-DM1 plus TPC， and TPC （ P ＜0.05）. For both indicators， ARX788 and T-Duo were ranked as the top two by SUCRA. For the incidence of grade ≥3 pneumonitis， T-DXd and T-DM1 were significantly higher than SG （ P ＜0.05）， T-Duo and Dato-DXd were ranked as the top two by SUCRA. For overall incidence of ILD， ARX788 was significantly higher than T-DM1， SHR-A1811， TPC， and SG （ P ＜0.05）， for the incidence of grade 1-2 ILD， ARX788 was significantly higher than T-DM1， SHR-A1811， and TPC （ P ＜0.05）， for the incidence of grade ≥3 ILD， ARX788 was significantly higher than TPC （ P ＜0.05）. For three indicators above， ARX788 and T-DXd combined with pertuzumab were ranked as the top two by SUCRA. CONCLUSIONS Compared with other ADCs， ARX788 and T-Duo are associated with a higher risk of pneumonitis and ILD in patients with breast cancer.

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the clinical and pathological characteristics, prognostic factors, and treatment outcomes of bladder adenocarcinoma.Methods:The data of 177 bladder adenocarcinoma patients treated at Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2003 to December 2023, and 2 687 bladder adenocarcinoma patients from the SEER database (2000—2021) were reviewed retrospectively. The clinicopathological and prognostic characteristics were compared between the two cohorts. Patients with urachal adenocarcinoma or primary bladder adenocarcinoma were included, while metastatic bladder adenocarcinoma from other sites and urothelial carcinoma with glandular components were excluded. The Chi-square test was used for comparison of categorical data, and propensity score matching (1∶1) was applied to match baseline data between the Renji and SEER cohorts. Kaplan-Meier survival curves were generated, and log-rank tests were used for comparisons. Univariate and multivariate Cox regression analyses were performed using the survival R package, with P-values calculated via Wald tests. Results:The proportion of localized bladder adenocarcinoma was significantly higher in the Renji cohort than in the SEER cohort [61.0% (108/177) vs. 19.4% (521/2 687), P<0.001], and mucinous adenocarcinoma was more common in Renji cohort [33.3% (59/177) vs. 22.6% (607/2 687), P<0.001]. After matching for baseline factors, including SEER stage and pathological grade, survival analysis revealed that the Renji cohort patients had slightly better survival compared to the SEER cohort [median survival: 55.4 (24.1, 196.2) months vs. 39.2 (13.6, 137.4)months, P=0.033]. Multivariate Cox analysis identified SEER stage [Renji cohort: HR=3.83 (95% CI 1.62-9.07), P=0.002; SEER cohort: HR=3.67 (95% CI 3.13-4.31), P<0.001] and pathological grade [Renji cohort: HR = 2.76 (95% CI 1.54-4.95), P=0.001; SEER cohort: HR=1.46 (95% CI 1.29-1.65), P<0.001] as independent prognostic factors. In the Renji cohort, no significant differences were observed in the median progression-free survival [40.1 (19.5, 91.6) months vs. 40.9 (12.8, not reached)months, P=0.976] and overall survival [79.3 (37.1, 195.8) months vs. 53.9 (16.4, 129.5)months, P=0.374] between patients receiving adjuvant chemotherapy and those not receiving it. However, among patients with lymph node-positive bladder adenocarcinoma, adjuvant chemotherapy significantly improved both progression-free survival [40.1 (38.2, 75.4) months vs. 12.2 (3.1, 12.2)months, P=0.004] and overall survival [68.2 (46.2, 84.5)months vs. 28.1 (4.3, 28.3)months, P=0.006]. Conclusions:Bladder adenocarcinoma is rare and associated with poor prognosis. Compared to the SEER cohort, Renji cohort patients had more localized disease, with no significant differences in other features. SEER stage and pathological grade were independent prognostic factors in both cohorts. Lymph node-positive bladder adenocarcinoma patients in the Renji cohort benefited significantly from adjuvant chemotherapy.

Germplasm degeneration occurs during the long-term cultivation of root-and rhizome-derived traditional Chinese medicine(RR-TCM), which seriously restricts the high-quality development of their industry. Therefore, it is urgent to solve the problem of germplasm degeneration through variety breeding. In this paper, based on previously published research articles, monographs, and news reports, the research progresses on the number and origins, breeding methods, and selection of new varieties of RR-TCM listed in the Chinese Pharmacopoeia(Edition 2020) were summarized and analyzed. The results show that there are 169 kinds of RR-TCM listed in the Chinese Pharmacopoeia(Edition 2020), originated from 223 origins with three breeding methods(i.e., seed propagation, vegetative reproduction, and tissue culture), and there are 215 species derived from seed propagation, 177 species derived from vegetative reproduction, and 164 species derived from tissue culture. To date, there are 62 origins breeding new varieties through conventional breeding, cross breeding, mutation breeding, ploidy breeding, or modern biotechnology breeding methods, including 57 origins breeding 145 new varieties through conventional breeding, 10 origins breeding 43 new varieties through mutation breeding, and seven origins breeding 12 new varieties through cross breeding method. They are used mainly to improve yield, disease resistance, and active ingredient content, but only a few new varieties have been widely used. This review will provide useful references in variety breeding, quality breeding, and standardized planting of RR-TCM.
Plant Breeding/methods* ; Plant Roots/growth & development* ; Rhizome/growth & development* ; Drugs, Chinese Herbal ; Plants, Medicinal/classification* ; Medicine, Chinese Traditional

OBJECTIVE: To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods. METHODS: Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords. RESULTS: Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc. CONCLUSION Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans ; Diabetic Foot/physiopathology* ; Biomechanical Phenomena ; Bibliometrics

Objective To develop a novel protective ventilator circuit component and to verify its performance by water seal and anti-splash experiments.Methods A novel protective ventilator circuit component had a design scheme with the multifunctional joint,and consisted of a tee connection tube,an isolation sleeve and a stop sleeve,of which,the tee connection tube was made of polyethylene polymer material and the others were made of silicone material.The tee connection tube had a T-shaped structure with two standard connection ports,which was composed of an adapter,a sealing cap,a plug and a sealing ring;the isolation sleeve was in the shape of a cylinder with a raised bottom,which was inserted into the adapter;the stop sleeve was located in the isolation sleeve,with an inverted frustum of a cone at the bottom and a rounded hole in the middle of the inverted frustum.An open ventilator circuit tube was involved in the performance verification of the circuit component developed.In the water seal experiment,sputum aspiration was simulated and the heights of the liquid level drop in the L-shaped tubes were compared after sputum aspiration.In the anti-splash experiment,the infection rates on the surfaces of the sterile hole towels and gloves were calculated.Results Water seal experiment showed after sputum aspiration the open ventilator circuit tube had the liquid level at the L-shaped tube higher significantly than that of the circuit component;the anti-splash experiment indicated sputum aspiration resulted in the occurance of the splashing out of the secretion and 77.5%infection rate by the open ventilator circuit tube,while no splashing out and 0%infection rate by the circuit component developed.Conclusion The novel protective ventilator circuit component behaves well in sealing and anti-splashing,and thus is worthy of clinical application for sputum aspiration.[Chinese Medical Equipment Journal,2025,46(4):113-117]

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.