Aging has emerged as a cutting edge and hotspot in global life science field， with anti-aging and geriatric disease prevention and treatment becoming critical issues urgently demanding solutions in international medical communities. In the face of the challenge of accelerating global population aging， in-depth exploration of aging mechanisms and the development of effective intervention strategies hold significant scientific and clinical value. This study supported by the national key research and development program of China， employed the essence-Qi-spirit theory of Qiluo doctrine as its guiding framework， focusing on the key scientific issue of the core traditional Chinese pathogenesis of aging， namely "depletion of kidney essence， deficiency of primordial Qi， and impairment of body and spirit". The treatment principle of "tonifying the kidney to replenish essence， harmonizing Yin and Yang， warming and invigorating primordial Qi， and nourishing the body and spirit" was established. Centered on holistic aging， systemic aging， and aging-related diseases， the research integrated multidisciplinary research approaches to construct multi-modal aging models and a multi-dimensional evaluation system， and it utilized multi-omics technologies to deeply analyze aging mechanisms. By systematically reviewing historical kidney-tonifying and anti-aging formulas and combining big data with artificial intelligence technologies， an information database of anti-aging traditional Chinese medicine substance was developed to reveal the differences and synergistic effects of various treatment methods and formulas on anti-aging. Based on this treatment method， the research integrated two millennia of kidney-tonifying medicinal experience to develop the innovative anti-aging traditional Chinese medicine， namely Bazhi Bushen capsules. It was validated that this capsule can delay holistic and systemic aging through multiple targets and mechanisms， thereby elucidating the scientific connotation of the essence-Qi-spirit theory of Qiluo doctrine in guiding anti-aging research from multiple dimensions and providing robust support for leveraging the advantages of traditional Chinese medicine to occupy the commanding heights of international anti-aging research.

Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.

Objective:To investigate the effect of miR-1-3p on mitophagy in human esophageal squamous cell carcinoma (ESCC) cells and the related mechanisms.Methods:The differentially expressed miRNAs in ESCC were screened using the GEO database. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure miR-1-3p expression in normal esophageal epithelial cells (HET-1A) and ESCC cell lines (TE1, KYSE30, KYSE150, KYSE410, Eca109). Bioinformatics tools were utilized to predict target genes of miR-1-3p, subcellular localization was confirmed by fluorescence in situ hybridization. The targeting relationship between miR-1-3p and SLC7A11 was validated using dual-luciferase reporter assay. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Furthermore, experimental validation demonstrated that overexpression of SLC7A11 rescued the presence of the miR-1-3p/SLC7A11 axis. Confocal microscopy was used to detect changes in mitochondrial autophagic lysosomes, while transmission electron microscopy was employed to observe mitophagy and morphological alterations. Western blot was conducted to evaluate the expression of autophagy-related proteins LC3 and P62. Flow cytometry was used to measure mitochondrial membrane potential and reactive oxygen species (ROS). Immunohistochemistry was applied to assess SLC7A11 expression in 133 ESCC patient tissues and 115 normal esophageal epithelial tissues. The correlation between SLC7A11 expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for multivariate analysis.Results:The expression of miR-1-3p in ESCC cells was significantly lower than that in HET-1A cells ( P＜0.05). SLC7A11 was a target gene of miR-1-3p. Transfection of miR-1-3p mimic inhibited the proliferation of ESCC cells. CCK-8 assay results showed that the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic group (absorbance values: 2.88±0.24 and 2.88±0.18, respectively) was significantly lower than that in the miRNA mimic negative control (NC) group (3.94±0.27, P＜0.001; 4.20±0.21, P＜0.001). Meanwhile, the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic+SLC7A11-overexpression (OE) group (absorbance values: 3.57±0.15 and 3.60±0.13, respectively) was significantly higher than that in the miR-1-3p mimic +empty vector (EV) group (2.54±0.10, P＜0.001, 2.36±0.16, P＜0.001). Additionally, transfection of miR-1-3p mimic promoted apoptosis. Flow cytometry results demonstrated that the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic group [(9.22±0.05)% and (6.55±0.37)%, respectively] were significantly higher than those in the miRNA mimic NC group [(0.81±0.17)%, P＜0.001); (1.04±0.12)%, P＜0.001]. Conversely, the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic + SLC7A11-OE group [(0.73±0.04)% and (1.19±0.05)%, respectively] were significantly lower than those in the miR-1-3p mimic+EV group [(9.83±0.41)%, P＜0.001); (6.09±0.17)%, P＜0.00)]. MiR-1-3p mimic downregulated SLC7A11 protein expression and the LC3Ⅱ/LC3I ratio ( P＜0.05), upregulated P62 protein expression ( P＜0.05), this phenomenon can be rescued by overexpressing SLC7A11 ( P＜0.05). Additionally, miR-1-3p mimic increased ROS levels and decreased mitochondrial membrane potential (JC-1 aggregate/monomer ratio), this phenomenon can be rescued by overexpressing SLC7A11 ( P＜0.05). SLC7A11 expression was higher in ESCC tissues compared to normal esophageal epithelial tissues ( P＜0.001), and SLC7A11 serves as an independent prognostic factor in ESCC ( HR=2.15, 95% CI: 1.27-3.65, P=0.004). Conclusion:miR-1-3p inhibits mitophagy in esophageal squamous cell carcinoma by targeting SLC7A11.

To clarify the current situation of ketosis in dairy cattle on large-scale pastures in China and provide new insights,a questionnaire survey was conducted to analyze the incidence,preven-tion,treatment methods,and associated costs of ketosis in 79 large-scale pastures.The results showed that the average incidence of ketosis in dairy cows was 3.97％,with a cure rate of 92.40％.The order of importance of methods for preventing and controlling ketosis was as follows:feed for-mulation optimization＞blood ketone monitoring＞negative energy balance monitoring＞feed in-take monitoring＞milk yield monitoring.The most important treatment methods are intravenous glucose＞propylene glycol butyl phosphate＞vitamins＞choline.The most important diagnostic methods are blood ketone testing＞milk ketone testing＞negative energy balance testing＞clinical symptoms＞blood glucose testing.Economic analysis revealed that treatment costs were lower on larger farms and higher milk yields farms.Continuous optimization of feeding management,preven-tion,and control measures should be implemented on large-scale farms in China to reduce the oc-currence of ketosis in dairy cows.Additionally,more effective diagnostic and treatment methods should be employed to improve the cure rate and overall farm income.

To clarify the current situation of ketosis in dairy cattle on large-scale pastures in China and provide new insights,a questionnaire survey was conducted to analyze the incidence,preven-tion,treatment methods,and associated costs of ketosis in 79 large-scale pastures.The results showed that the average incidence of ketosis in dairy cows was 3.97％,with a cure rate of 92.40％.The order of importance of methods for preventing and controlling ketosis was as follows:feed for-mulation optimization＞blood ketone monitoring＞negative energy balance monitoring＞feed in-take monitoring＞milk yield monitoring.The most important treatment methods are intravenous glucose＞propylene glycol butyl phosphate＞vitamins＞choline.The most important diagnostic methods are blood ketone testing＞milk ketone testing＞negative energy balance testing＞clinical symptoms＞blood glucose testing.Economic analysis revealed that treatment costs were lower on larger farms and higher milk yields farms.Continuous optimization of feeding management,preven-tion,and control measures should be implemented on large-scale farms in China to reduce the oc-currence of ketosis in dairy cows.Additionally,more effective diagnostic and treatment methods should be employed to improve the cure rate and overall farm income.

Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.

Objective:To investigate the effect of miR-1-3p on mitophagy in human esophageal squamous cell carcinoma (ESCC) cells and the related mechanisms.Methods:The differentially expressed miRNAs in ESCC were screened using the GEO database. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure miR-1-3p expression in normal esophageal epithelial cells (HET-1A) and ESCC cell lines (TE1, KYSE30, KYSE150, KYSE410, Eca109). Bioinformatics tools were utilized to predict target genes of miR-1-3p, subcellular localization was confirmed by fluorescence in situ hybridization. The targeting relationship between miR-1-3p and SLC7A11 was validated using dual-luciferase reporter assay. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Furthermore, experimental validation demonstrated that overexpression of SLC7A11 rescued the presence of the miR-1-3p/SLC7A11 axis. Confocal microscopy was used to detect changes in mitochondrial autophagic lysosomes, while transmission electron microscopy was employed to observe mitophagy and morphological alterations. Western blot was conducted to evaluate the expression of autophagy-related proteins LC3 and P62. Flow cytometry was used to measure mitochondrial membrane potential and reactive oxygen species (ROS). Immunohistochemistry was applied to assess SLC7A11 expression in 133 ESCC patient tissues and 115 normal esophageal epithelial tissues. The correlation between SLC7A11 expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for multivariate analysis.Results:The expression of miR-1-3p in ESCC cells was significantly lower than that in HET-1A cells ( P＜0.05). SLC7A11 was a target gene of miR-1-3p. Transfection of miR-1-3p mimic inhibited the proliferation of ESCC cells. CCK-8 assay results showed that the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic group (absorbance values: 2.88±0.24 and 2.88±0.18, respectively) was significantly lower than that in the miRNA mimic negative control (NC) group (3.94±0.27, P＜0.001; 4.20±0.21, P＜0.001). Meanwhile, the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic+SLC7A11-overexpression (OE) group (absorbance values: 3.57±0.15 and 3.60±0.13, respectively) was significantly higher than that in the miR-1-3p mimic +empty vector (EV) group (2.54±0.10, P＜0.001, 2.36±0.16, P＜0.001). Additionally, transfection of miR-1-3p mimic promoted apoptosis. Flow cytometry results demonstrated that the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic group [(9.22±0.05)% and (6.55±0.37)%, respectively] were significantly higher than those in the miRNA mimic NC group [(0.81±0.17)%, P＜0.001); (1.04±0.12)%, P＜0.001]. Conversely, the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic + SLC7A11-OE group [(0.73±0.04)% and (1.19±0.05)%, respectively] were significantly lower than those in the miR-1-3p mimic+EV group [(9.83±0.41)%, P＜0.001); (6.09±0.17)%, P＜0.00)]. MiR-1-3p mimic downregulated SLC7A11 protein expression and the LC3Ⅱ/LC3I ratio ( P＜0.05), upregulated P62 protein expression ( P＜0.05), this phenomenon can be rescued by overexpressing SLC7A11 ( P＜0.05). Additionally, miR-1-3p mimic increased ROS levels and decreased mitochondrial membrane potential (JC-1 aggregate/monomer ratio), this phenomenon can be rescued by overexpressing SLC7A11 ( P＜0.05). SLC7A11 expression was higher in ESCC tissues compared to normal esophageal epithelial tissues ( P＜0.001), and SLC7A11 serves as an independent prognostic factor in ESCC ( HR=2.15, 95% CI: 1.27-3.65, P=0.004). Conclusion:miR-1-3p inhibits mitophagy in esophageal squamous cell carcinoma by targeting SLC7A11.

Objective To explore the effect of miR-1-3p on the malignant biological behavior of human esophageal squamous cell carcinoma cells and the potential mechanisms.Methods The Gene Expression Omnibus(GEO)database was analyzed to screen differentially expressed miRNAs in esophageal squamous cell carcinoma(ESCC).qRT-PCR was used to detect the expression of miR-1-3p in human ESCC cell lines(KYSE30,KYSE150,KYSE410,KYSE510,and Eca109)and normal esophageal epithelial cell line HET-1A.CCK-8,wound healing,Transwell assays,and flow cytometry were applied to detect the effect of miR-1-3p on the proliferation,migration,invasion,and apoptosis of ESCC cells.Bioinformatics tool was used to predict the target genes of miR-1-3p.A Kaplan-Meier survival curve was drawn to analyze the correlation between STC2 expression and overall survival of patients in the ESCC cohort of the TCGA database.Fluorescence in situ hybridization was performed to verify the subcellular location of miR-1-3p in ESCC cells,and dual-luciferase reporter gene assay was performed to validate the regulation of miR-1-3p on stanniocalcin 2(STC2).RNA immunoprecipitation assays were used to detect the binding of miR-1-3p and STC2.Western blot assay was performed to determine the effect of miR-1-3p on the expression of STC2 and endoplasmic reticulum stress pathway-related proteins,including p-PERK,p-eIF2α,and ATF4.CCK-8,wound healing,Transwell assays,and flow cytometry were applied to detect the effect of STC2 overexpression and knockdown on the proliferation,migration,invasion,and apoptosis of ESCC cells.Results The expression of miR-1-3p was lower in ESCC cell lines than in HET-1A cells(all P<0.05).The transfection of miR-1-3p mimic decreased the proliferation,invasion,and migration of ESCC cells(all P<0.05)and promoted the apoptosis of ESCC cells(all P<0.001).Bioinformatics tool showed that STC2 was a target gene of miR-1-3p.The expression of STC2 in ESCC tissues was higher than that in normal esophageal epithelial tissues in the ESCC cohort of TCGA database and was negatively correlated with prognosis(all P<0.05).miR-1-3p was located in the cytoplasm and can directly bind to STC2 mRNA.The transfection of miR-1-3p mimic downregulated the expression of STC2,p-PERK,p-eIF2α,and ATF4(all P<0.05).The overexpression of STC2 promoted the proliferation,invasion,and migration(all P<0.05)and inhibited the apoptosis of ESCC cells(all P<0.05).Knockdown of STC2 inhibited the proliferation,invasion,and migration(all P<0.05)and promoted the apoptosis of ESCC cells(all P<0.05).Conclusion miR-1-3p inhibits the malignant biological behavior and promotes the apoptosis of esophageal squamous cell carcinoma cells by regulating STC2 possibly by suppressing the endoplasmic reticulum stress.

In recent years， the research method of Mendelian randomization based on genome-wide association studies has been widely used for etiological exploration in the medical field， which can effectively overcome the confounding biases and interference of reverse causalities in traditional observational researches with its unique advantages of the distributive randomness and timing priority of genetic variants. This article reviews the method of Mendelian randomization and its application in liver cancer， in order to provide new ideas for the research on causal association in liver cancer.

Objective Based on the efficacy of Ranae Oviductus in reinforcing the kidney and replenishing essence,a biological titer assay for Ranae Oviductus was developed using anti-ageing vitality as an indicator,and this was used to evaluate the quality of Ranae Oviductus from different origins and to provide a reference for improving its quality standard.Methods MRC-5 cells were used as the study target and H2O2 was used as the acute senescence model-inducing drug to verify the anti-aging effect of Ranae Oviductus by cell viability and β-galactosidase staining rate.Vc was selected as the reference and CCK-8 method was used as the biological titer assay for Ranae Oviductus.Results In the cell viability assay,compared to the model group,the Ranae Oviductus group was able to up-regulate cell viability,with the best effect at 250.0 μg·mL-1,up-regulating by 20.01％.The percentage of SA-β-gal positive cells was reduced by 17.70％in the cells pretreated with Ranae Oviductus.The results of the biological titer of anti-aging determination showed that the biological titer of anti-aging of Ranae Oviductus from different origins ranged from 218.03 to 1152.04 U·mg-1,with an extreme difference of 934.01 U·mg-1.Conclusion The established biological titer assay for Ranae Oviductus can clearly distinguish the differences in the quality of Ranae Oviductus and provide a certain reference for the quality evaluation and control of Ranae Oviductus.