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 evaluate the efficacy and safety of super-mini percutaneous nephrolithotomy(SMP)and standard percutaneous nephrolithotomy(sPCNL)in the treatment of 2-4 cm renal calculi, so as to provide reference for the management of medium-sized renal calculi. Methods A retrospective analysis was conducted on 168 patients with 2-4 cm renal calculi who underwent either SMP or sPCNL at our hospital during Sep. 2020 and Mar. 2025. The patients were divided into the SMP group(n=85)and sPCNL group(n=83). The baseline characteristics, stone features, operation time, perioperative complications, transfusion rate, postoperative hemoglobin drop, pain score, hospital stay, and stone-free rate(SFR)were compared between the two groups. Results There were no significant differences in baseline characteristics, stone features, and SFR between the two groups(P＞0.05). Compared to the sPCNL group, the SMP group had a longer operation time [(71.76±22.49)vs.(64.22±15.01)min, P=0.034]. However, it had lower postoperative pain score [(2.51 ±0.85)vs.(4.11±0.47), P＜0.001], shorter hospital stay [(3.16±1.45)vs.(4.30±1.06)days, P＜0.001], lower hospitalization costs [(19982.67±4267.80)vs.(21688.53±4575.74)RMB, P=0.004], a slighter decrease in hemoglobin [(6.64±10.56)vs.(12.22±11.50)g/L, P=0.032], and a significantly higher tubeless rate(83.53% vs. 0%, P＜0.001). There was no statistically significant difference in the overall complication rate between the two groups(P＞0.05). Conclusion For 2—4 cm renal calculi, SMP achieves a comparable SFR as sPCNL. Although the operation time with SMP is slightly longer, it offers significant advantages, including reduced postoperative pain, shorter hospitalization, lower costs, less bleeding, and a higher tubeless rate. SMP is a valuable technique worthy of broader clinical application.

Objective To explore the clinical features, diagnosis, treatment and prognosis of testicular Ewing sarcoma(ES), so as to enhance the understanding and differential diagnosis of this disease. Methods A retrospective analysis was conducted on the clinical manifestations, auxiliary examinations and pathological findings of a case of left-sided ES treated at our hospital, supplemented by a review of relevant literature. Results A 24-year-old male patient presented with left testicular enlargement with pain. Magnetic resonance imaging suggested a neoplastic lesion, with a high likelihood of testicular germ cell tumor. A radical left orchiectomy was performed. Postoperative pathology revealed testicular ES. The patient subsequently completed 8 cycles of VDC/IE chemotherapy and showed no evidence of recurrence at 10 months of follow-up. Analysis of literature on 5 previously reported cases of testicular ES had testicular enlargement as the primary presentation. All patients underwent surgery and 4 received adjuvant therapy. Follow-up revealed 1 death at 9 months postoperatively, with no recurrence or progression seen in the remainder. Conclusion ES occurring in the testis is extremely rare.Testicular ES is a poorly differentiated small round-cell malignant tumor that primarily presents as testicular enlargement. Current treatment mainly surgical resection combined with adjuvant chemotherapy.

Ulcerative colitis(UC) is a recurrent, chronic, nonspecific inflammatory bowel disease. The longer the course of the disease, the higher the risk of cancerization. In recent years, the incidence and mortality rates of colon cancer in China have been increasing year by year, seriously threatening the life and health of patients. Therefore, studying the mechanism of "inflammation cancer transformation" in UC and conducting early intervention is crucial. The "Kenang" theory is an important component of traditional Chinese medicine(TCM) theory of phlegm and blood stasis. It is based on the coexistence of phlegm and blood stasis in the body and deeply explores the pathogenic syndromes and characteristics of phlegm and blood stasis. Kenang is a pathological product formed when long-term Qi stagnation leads to the internal formation of phlegm and blood stasis, which is hidden deep within the body. It is characterized by being hidden, progressive, and difficult to treat. The etiology and pathogenesis of "inflammation cancer transformation" in UC are consistent with the connotation of the "Kenang" theory. The internal condition for the development of UC "inflammation cancer transformation" is the deficiency of healthy Qi, with Qi stagnation being the key pathological mechanism. Phlegm and blood stasis are the main pathogenic factors. Phlegm and blood stasis accumulate in the body over time and can produce cancer toxins. Due to the depletion of healthy Qi and a weakened constitution, the body is unable to limit the proliferation and invasion of cancer toxins, eventually leading to cancer transformation in UC. In clinical treatment, the focus should be on removing phlegm and blood stasis, with syndrome differentiation and treatment based on three basic principles: supporting healthy Qi to strengthen the body's foundation, resolving phlegm and blood stasis to break up the Kenang, and regulating Qi and blood to smooth the flow of energy and resolve stagnation. This approach helps to dismantle the Kenang, delay, block, or even reverse the cancerization process of UC, reduce the risk of "inflammation cancer transformation", improve the patient's quality of life, and provide new perspectives and strategies for early intervention in the development of colon cancer.
Humans ; Colitis, Ulcerative/immunology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Cell Transformation, Neoplastic

Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
.
Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Ferroptosis is a form of cell death that occurs when there is an excess of reactive oxygen species (ROS), lipid peroxidation, and iron accumulation. The precise regulation of metabolic pathways, including iron, lipid, and amino acid metabolism, is crucial for cell survival. This type of cell death, which is associated with oxidative stress, is controlled by a complex network of signaling molecules and pathways. It is also implicated in various respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), lung cancer, pulmonary fibrosis (PF), and the coronavirus disease 2019 (COVID-19). To combat drug resistance, it is important to identify appropriate biological markers and treatment targets, as well as intervene in respiratory disorders to either induce or prevent ferroptosis. The focus is on the role of ferroptosis in the development of respiratory diseases and the potential of targeting ferroptosis for prevention and treatment. The review also explores the interaction between immune cell ferroptosis and inflammatory mediators in respiratory diseases, aiming to provide more effective strategies for managing cellular ferroptosis and respiratory disorders.

OBJECTIVE: To explore the role of CDGSH iron-sulfur domain 2 (CISD2) in patients with sepsis-related myocardial injury (SMI) and its predictive value for 28-day prognosis and myocardial damage through clinical studies and cell experiments. METHODS: A retrospective study was conducted. Adult patients diagnosed with sepsis admitted to the critical care medicine of Third Affiliated Hospital of Qiqihar Medical University from January 2023 to January 2024 were enrolled. The clinical data, laboratory indicators, expression level of CISD2 mRNA in peripheral blood mononuclear cells (PBMC) 24 hours after admission, and 28 days prognosis were collected. Patients were divided into SMI group [left ventricular ejection fraction (LVEF) < 0.50 or LVEF decreased by ≥ 10% from baseline] and sepsis non-myocardial injury group based on LVEF. The expression levels of CISD2 mRNA were compared between the two groups, and the correlation between CISD2 and myocardial injury was analyzed. Patients were divided into the low-expression group (CISD2 mRNA < 0.5 copy/μL) and the high-expression group (CISD2 mRNA ≥ 0.5 copy/μL) based on the expression of CISD2 mRNA, and into the survival group and the death group based on the prognosis at 28 days. The clinical characteristics were analyzed between the groups. Multivariate Logistic regression was used to analyze the independent predictors of 28-day mortality in patients with sepsis. The predictive value of CISD2 for myocardial damage and 28-day prognosis in patients with sepsis were evaluated by using the receiver operator characteristic curve (ROC curve). In addition, in vitro experiments using human AC16 cardiomyocytes was conducted. The cells were divided into control group, lipopolysaccharide (LPS) group, the LPS+transfection group with overexpression of CISD2 plasmid (LPS+p-CISD2 group), and the LPS + transfection group with negative control plasmid (LPS+p-NC group). The mRNA expression of CISD2 in cells were detected by real-time quantitative polymerase chain reaction (RT-qPCR), the protein expression of CISD2 in cells were detected by Western blotting, and the cell viability was determined by cell counting kit-8 (CCK-8). RESULTS: A total of 85 sepsis patients were included, with 32 developing myocardial injury and 53 without myocardial injury. There were 40 cases of low expression of CISD2 and 45 cases of high expression of CISD2. At 28 days, 60 cases survived and 25 cases died. The mRNA expression of CISD2 in the SMI group was significantly lower than that in the sepsis non-myocardial injury group (copy/μL: 0.41±0.09 vs. 0.92±0.13, P < 0.05). CISD2 was significantly correlated with myocardial injury in patients with sepsis (r = 0.729, P < 0.05). The proportion of LVEF < 0.50 (67.50% vs. 11.11%), sequential organ failure score (SOFA: 15.63±2.15 vs. 11.12±1.52), and acute physiology and chronic health evaluation II (APACHEII: 29.49±3.51 vs. 22.41±2.61) in the CISD2 low-expression group were significantly higher than those in the CISD2 high-expression group (all P < 0.05), while there were no significantly differences in other indicators. The Kaplan-Meier survival curve showed that the 28-day survival time of sepsis patients with in the CISD2 low-expression group was significantly shorter than that in the CISD2 high-expression group (Log-rank test: χ ² = 5.601, P < 0.05). The proportion of CISD2 low-expression and the proportion of LVEF < 0.50 in the survival group were both higher than those in the death group (80.00% vs. 33.33%, 64.00% vs. 26.67%, both P < 0.05), while there were no significantly differences in other indicators. Multivariate Logistic regression analysis showed that CIDS2 and LVEF were independent predictive factors for 28-day mortality in patients with sepsis [CIDS2: odds ratio (OR) = 3.400, 95% confidence interval (95%CI) was 1.026-11.264, P = 0.045; LVEF: OR = 2.905, 95%CI was 1.029-8.199, P = 0.044]. ROC curve analysis showed that when CISD2 was expressed at a low level, patients with sepsis were at high risk of death within 28 days and myocardial injury. The sensitivity of CISD2 in predicting the 28-day mortality of patients with sepsis was 80.00%, and the specificity was 66.67%, and the area under the curve (AUC) was 0.733 (95%CI was 0.626-0.823). The sensitivity of CISD2 in predicting myocardial injury in patients with sepsis was 83.87%, the specificity was 74.07%, and the AUC was 0.790 (95%CI was 0.688-0.871). In addition, compared with the control group, the mRNA and protein expressions of CISD2 as well as the cell activity in the LPS group were significantly decreased. The mRNA and protein expressions of CISD2 and the activity of cardiomyocytes transfected with p-CISD2 were significantly increased. CONCLUSIONS CISD2 plays a protective role in sepsis-associated myocardial injury and has good predictive value for 28-day prognosis and myocardial injury.
Humans ; Sepsis/metabolism* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; RNA, Messenger/genetics* ; Aged ; Myocardium/metabolism*

The biological nitrogen removal technology utilizing heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria has shown effectiveness in wastewater treatment. However, the nitrogen removal efficiency of HN-AD bacteria significantly decreases as the salinity increases. To tackle the challenge of treating high-salt and high-nitrogen wastewater, we isolated a moderately halophilic HN-AD strain 5505 from a salt lake in Xinjiang. The strain was identified based on morphological, physiological, and biochemical characteristics and the 16S rRNA gene sequence. Single-factor experiments were carried out with NH₄⁺-N, NO₃^--N, and NO₂^--N as sole or mixed nitrogen sources to study the nitrifying effect, denitrifying effect, and nitrogen metabolism pathway of the strain. The strain was identified as Halomonas sp.. It can grow in the presence of 1%-25% (W/V) NaCl and exhibited efficient nitrogen removal ability in the presence of 3%-8% NaCl. At the optimal NaCl concentration (8%), the strain showed the NH₄⁺-N, NO₃^--N and NO₂^--N removal rates of 100.0%, 94.11% and 74.43%, respectively. Strain 5505 removed inorganic nitrogen mainly by assimilation, which accounted for over 62.68% of total nitrogen removal. In the presence of mixed nitrogen sources, strain 5505 showed a preference for utilizing ammonia, with a potential HN-AD pathway of NH₄⁺→NH₂OH→NO₂^-→NO₃^-→NO₂^-→NO/N₂O/N₂. The findings provide efficient salt-tolerant bacterial resources, enhance our understanding of biological nitrogen removal, and contribute to the nitrogen removal efficiency improvement in the treatment of high-salt and high-nitrogen wastewater.
Halomonas/classification* ; Nitrogen/isolation & purification* ; Denitrification ; Nitrification ; Wastewater/microbiology* ; Aerobiosis ; Biodegradation, Environmental ; Salinity