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 investigate the effect of altitude on the risk of pre-eclampsia (PE).Methods:This cross-sectional study included 19 246 pregnant women who delivered in Gansu Provincial Hospital from January 2016 to December 2020. General clinical data, pregnancy outcomes and neonatal outcomes were collected. The diagnosis of PE was based on the disease diagnosis coding of medical record information system and the Chinese guidelines for the diagnosis and treatment of hypertensive disorders in pregnancy (2020). According to the altitude of residence, the subjects were divided into low altitude group (9 931 cases), middle altitude group (9 068 cases) and high altitude group (247 cases). Univariate and multivariate logistic regression analyses were used to evaluate the relationship between altitude and the risk of PE, after adjusting for confounding factors such as age, ethnicity, mode of conception, gestational diabetes mellitus, and hemoglobin level.Results:(1) Among the 19 246 pregnant women, 752 (3.91%, 752/19 246) were diagnosed with PE. The incidence of PE in the low altitude group, middle altitude group and high altitude group was 2.95% (293/9 931), 4.91% (445/9 068) and 5.67% (14/247), respectively. With the increase of living altitude, the incidence of PE increased significantly ( P<0.001). (2) The results of univariate logistic analysis showed that compared with the low altitude area, the risk of PE in pregnant women living in the middle altitude area and high altitude area increased by 70% ( OR=1.70, 95% CI: 1.46-1.97; P<0.001) and 98% ( OR=1.98, 95% CI: 1.14-3.43; P=0.016). (3) The results of multivariate logistic regression analysis showed that after fully adjusting for confounding factors, the risk of PE increased by 40% for every 500 meters of elevation ( OR=1.40, 95% CI: 1.25-1.57; P<0.001). Compared with those living in low altitude areas, the risk of PE in pregnant women living in middle altitude and high altitude areas increased by 72% ( OR=1.72, 95% CI: 1.47-2.00; P<0.001) and 100% ( OR=2.00, 95% CI: 1.07-3.74; P=0.030). Conclusion:In the high-altitude environment of Gansu Province, the risk of PE gradually increases with the increase of altitude.

Objective:To study the risk factors for combined bacterial/fungal infections in patients with severe fever with thrombocytopenia syndrome (SFTS) and to develop a novel and validated prediction model.Methods:The basic data and the results of the first laboratory examination after admission were retrospectively collected from patients diagnosed with SFTS who were hospitalized in the First Affiliated Hospital, Nanjing Medical University from January 2018 to December 2022. The patients were categorized into co-infected and non-co-infected groups according to whether they had co-infections with bacterial/fungal infections or not.Independent risk factors were screened by multivariate logistic regression analyses. A novel prediction model was constructed, and the predictive value of the model was assessed using receiver operating characteristic curve. Non-parametric tests and chi-square test were used for statistical analysis.Results:A total of 294 patients were included, and 62 cases were in the combined infection group including 39 cases of simple respiratory tract infections, 11 cases of simple bloodstream infections, four cases of simple urinary tract infections, four cases of respiratory tract combined with bloodstream infection, and four cases of respiratory tract combined with urinary tract infection. Acinetobacter baumannii was mostly found in bacterial infections, with a total of 19 strains, followed by Escherichia coli and Pseudomonas aeruginosa, both with seven strains. Aspergillus were mostly common in fungi, with a total of 16 strains which were all collected from patients with pulmonary infections. Compared with the non-co-infected group, patients in the co-infected group had longer hospital stays, with statistically significant differences ( Z=-6.18, P<0.001). The patients also had higher frequencies of bleeding symptoms, neurological symptoms, severe illness, and death, with statistically significant differences ( χ2=23.91, 16.37, 15.51 and 15.58, respectively, all P<0.001). The aspartate transaminase-to-platelet ratio index (APRI) was also higher in patients with coinfection, with a statistically significant difference ( Z=-4.64, P<0.001). Multivariate binary logistic regression showed that severe illness (odds ratio ( OR)=2.567, 95% confidence interval ( CI) 1.344 to 4.904, P=0.004), blood glucose level higher than 7.782 mmol/L ( OR=4.766, 95% CI 2.493 to 9.109, P<0.001), procalcitonin level higher than 0.228 μg/L ( OR=2.487, 95% CI 1.289 to 4.799, P=0.007), and APRI value higher than 6.268 ( OR=3.032, 95% CI 1.404 to 6.548, P=0.005) were the independent risk factors for co-infections in SFTS patients. Disease severity, blood glucose, procalcitonin, and APRI were combined to construct a novel predictive model: Infect-risk score=-3.331+ 0.654×severity (severe=1, non-severe=0)+ 0.160×blood glucose+ 0.066×procalcitonin+ 0.013×APRI. The AUC for this score was 0.764 (95% CI 0.698 to 0.830, P<0.001), with Youden index of 0.416, sensitivity of 0.839, and specificity of 0.578. Conclusions:Severe illness, blood glucose levels higher than 7.782 mmol/L, procalcitonin levels above 0.228 μg/L, and APRI values above 6.268 are independent risk factors for bacterial/fungal coinfection in SFTS patients. The constructed Infect-risk score model has good predictive value for bacterial/fungal coinfection in SFTS patients.

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

Cardiovascular damage caused by cancer treatment has become an important cause of death for tumor survivors. With the recognition of cardiovascular diseases and cancer therapy-related cardiovascular toxicity (CTR-CVT) in tumor patients, noninvasive imaging technologies play pivotal roles in the risk stratification, early diagnosis, monitoring and follow-up for CTR-CVT. In recent years, the field of cardio-oncology has witnessed continual updates in diagnostic and therapeutic strategies, with several pertinent guidelines and expert consensus documents issued in China and abroad. However, there remains a conspicuous absence of systematic guidance documents on the application of imaging techniques in the clinical practice of cardio-oncology. Therefore, the Chinese Anti-Cancer Association Society of Integrative Cardio-oncology, the Ultrasound Branch of the Chinese Medical Association, and the Chinese Society of Echocardiography convened experts to formulate the "Chinese guideline for the clinical application of noninvasive imaging technology in accessing cancer therapy-related cardiovascular toxicity". Building upon the systematic evaluation of guidelines and the latest evidence-based medical research in the field of cardio-oncology domestically and abroad, and in conjunction with data derived from evidence-based medical research in China, this guideline proposes noninvasive imaging examination methods and monitoring strategies for CTR-CVT, aiming to further standardize and guide the clinical practice of multidisciplinary physicians specializing in cardio-oncology in China.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.
Animals ; Organoids/metabolism* ; Mice ; Humans ; Wound Healing ; Frostbite/metabolism* ; Skin/pathology* ; Induced Pluripotent Stem Cells/cytology* ; Cicatrix/pathology* ; Fibroblasts/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Extracellular Matrix/metabolism* ; Male

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.