Objective:To understand the epidemiological characteristics of injury deaths in local residents in Nanjing from 2009 to 2023, and provide evidence for the development of injury prevention and control strategies.Methods:The injury mortality data in Nanjing from 2009 to 2023 were analyzed based on the death cause surveillance system. In the recorded 33 542 injury death cases, 19 906 (59.35%) were men, and 13 636 (40.65%) were women. The crude mortality rate, age-standardized mortality rate, age-specific mortality rate, cause-eliminated life expectancy (CELE), potential gains in life expectancy (PGLEs) and life loss rate, were calculated. Joinpoint 5.0 software was used to estimate the average annual percentage change (AAPC) and its 95% CI to assess temporal trends of injury deaths. Results:In Nanjing, the crude injury mortality rate showed an upward trend (AAPC=2.11%), while the age-standardized mortality rate exhibited a downward trend (AAPC=-1.27%) from 2009 to 2023. The ranking of injury deaths in all causes of death declined from the 4 th in 2009 to the 6 th in 2023. The crude and age-standardized injury mortality rates in men were consistently higher than those in women. The primary cause of injury deaths was fall (31.42%). Drowning was the primary cause of injury deaths in age group 0-14 years (35.94%), while traffic accident was the primary cause in age group 15-64 years. For residents aged ≥65 years, fall was the primary cause of injury deaths. From 2009 to 2023, the CELE (AAPC=0.61%, 95% CI: 0.34%-0.89%, P<0.05) and the PGLEs (AAPC=1.73%, 95% CI: 0.21%-3.29%, P<0.05) showed increasing trends. The PGLEs and life loss rate due to injury were consistently higher in men than in women, but the AAPC of PGLEs and life loss rate was higher in women. Conclusions:From 2009 to 2023, the age-standardized injury mortality rate decreased, but the life loss due to injury deaths showed an upward trend in Nanjing, indicating that injury still has non-negligible negative impact on life expectancy.

Objective:To investigate the association between serum uric acid trajectories and the risk of renal function decline and diabetic kidney disease(DKD) incidence in elderly patients with type 2 diabetes mellitus.Methods:This retrospective cohort study included 5 037 elderly patients with type 2 diabetes mellitus aged 60 years and above who underwent at least three health examinations between 2019 and 2023, with 2019 as the baseline. Latent growth mixture modeling(LGMM) was employed to identify distinct serum uric acid trajectories. Renal function changes and DKD incidence were followed from 2020 to 2023. Binary logistic regression models were used to assess the association between serum uric acid trajectories and the risks of renal function decline and DKD.Results:Two distinct serum uric acid trajectory groups were identified based on model selection criteria: A stable group( n=4 485, 89.04%) and an inverted U-shaped group( n=552, 10.96%). After adjusting for potential confounders, compared with the stable trajectory group, the inverted U-shaped group showed a significantly increased risk of estimated glomerular filtration rate(eGFR) <60 mL·min -1·(1.73 m 2) -1, ≥25% decline in eGFR, doubling of serum creatinine, and DKD events, with OR(95% CI) of 1.99(1.28-3.09), 2.27(1.65-3.13), 1.52(1.09-3.02), and 1.52(1.27-1.82), respectively(all P<0.05). In addition, multivariate analysis indicated that elevated baseline serum uric acid levels were also associated with an increased risk of adverse renal outcomes and DKD incidence; However, the magnitude of the associations was lower than that observed for serum uric acid trajectory groups. Conclusions:An inverted U-shaped serum uric acid trajectory is significantly associated with an increased risk of renal function progression and DKD in elderly patients with type 2 diabetes mellitus. These findings highlight the importance of long-term dynamic monitoring of serum uric acid levels to facilitate early identification and intervention for high-risk individuals.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Objective To find out whether photobiomodulation(PBM)can mitigate cognitive dysfunction caused by chronic stress by affecting levels of adenosine triphosphate(ATP)and adenosine receptors.Methods Twenty-four C57BL/6J mice were randomly divided into a control group,a stress group,and a treatment group.Chronic unpredictable mild stress was used to establish a mouse model of stress.Six weeks into modeling,the treatment group was subjected to one week of PBM interventions.Behavioral tests were conducted to observe behavioral changes in the mice.Western blotting(WB)was used to detect the expressions of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex of mice in the three groups.Twelve C57BL/6J mice were randomly divided into a control group and an intervention group.The intervention group received a week of PBM interventions and underwent behavioral testing.WB was used to detect the expression changes of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex in both groups.Immunofluorescence assay was adopted to detect the expression of c-Fos in the hippocampus of mice in the two groups.The ATP assay kit made by Beyotime Biotechnology Co.,Ltd.was used to measure changes in ATP contents in the hippocampus and prefrontal cortex tissues of mice.Cell experiments were conducted to verify the effect of PBM on intracellular ATP contents.Results Mice in the stress group covered a similar distance to the control group,but finished far fewer platform crossings.There was no significant difference between the treatment group and the control group in the number of times of platform crossings,but compared favorably with the stress group where the levels of adenosine receptors in the hippocampus and prefrontal cortex were lower,but were increased by PBM.After PBM interventions in normal mice,platform crossings were increased significantly compared to the control group.PBM also raised adenosine receptor levels and ATP contents in the hippocampus and prefrontal cortex,and increased hippocampal c-Fos expressions.In vitro,PBM elevated intracellular ATP levels.Conclusion PBM may improve chronic stress-induced cognitive dysfunction by regulating ATP levels and adenosine receptor expressions,thereby modulating neuronal responsiveness in the hippocampus.

Objective:To understand the epidemiological characteristics of injury deaths in local residents in Nanjing from 2009 to 2023, and provide evidence for the development of injury prevention and control strategies.Methods:The injury mortality data in Nanjing from 2009 to 2023 were analyzed based on the death cause surveillance system. In the recorded 33 542 injury death cases, 19 906 (59.35%) were men, and 13 636 (40.65%) were women. The crude mortality rate, age-standardized mortality rate, age-specific mortality rate, cause-eliminated life expectancy (CELE), potential gains in life expectancy (PGLEs) and life loss rate, were calculated. Joinpoint 5.0 software was used to estimate the average annual percentage change (AAPC) and its 95% CI to assess temporal trends of injury deaths. Results:In Nanjing, the crude injury mortality rate showed an upward trend (AAPC=2.11%), while the age-standardized mortality rate exhibited a downward trend (AAPC=-1.27%) from 2009 to 2023. The ranking of injury deaths in all causes of death declined from the 4 th in 2009 to the 6 th in 2023. The crude and age-standardized injury mortality rates in men were consistently higher than those in women. The primary cause of injury deaths was fall (31.42%). Drowning was the primary cause of injury deaths in age group 0-14 years (35.94%), while traffic accident was the primary cause in age group 15-64 years. For residents aged ≥65 years, fall was the primary cause of injury deaths. From 2009 to 2023, the CELE (AAPC=0.61%, 95% CI: 0.34%-0.89%, P<0.05) and the PGLEs (AAPC=1.73%, 95% CI: 0.21%-3.29%, P<0.05) showed increasing trends. The PGLEs and life loss rate due to injury were consistently higher in men than in women, but the AAPC of PGLEs and life loss rate was higher in women. Conclusions:From 2009 to 2023, the age-standardized injury mortality rate decreased, but the life loss due to injury deaths showed an upward trend in Nanjing, indicating that injury still has non-negligible negative impact on life expectancy.

Objective:To investigate the association between serum uric acid trajectories and the risk of renal function decline and diabetic kidney disease(DKD) incidence in elderly patients with type 2 diabetes mellitus.Methods:This retrospective cohort study included 5 037 elderly patients with type 2 diabetes mellitus aged 60 years and above who underwent at least three health examinations between 2019 and 2023, with 2019 as the baseline. Latent growth mixture modeling(LGMM) was employed to identify distinct serum uric acid trajectories. Renal function changes and DKD incidence were followed from 2020 to 2023. Binary logistic regression models were used to assess the association between serum uric acid trajectories and the risks of renal function decline and DKD.Results:Two distinct serum uric acid trajectory groups were identified based on model selection criteria: A stable group( n=4 485, 89.04%) and an inverted U-shaped group( n=552, 10.96%). After adjusting for potential confounders, compared with the stable trajectory group, the inverted U-shaped group showed a significantly increased risk of estimated glomerular filtration rate(eGFR) <60 mL·min -1·(1.73 m 2) -1, ≥25% decline in eGFR, doubling of serum creatinine, and DKD events, with OR(95% CI) of 1.99(1.28-3.09), 2.27(1.65-3.13), 1.52(1.09-3.02), and 1.52(1.27-1.82), respectively(all P<0.05). In addition, multivariate analysis indicated that elevated baseline serum uric acid levels were also associated with an increased risk of adverse renal outcomes and DKD incidence; However, the magnitude of the associations was lower than that observed for serum uric acid trajectory groups. Conclusions:An inverted U-shaped serum uric acid trajectory is significantly associated with an increased risk of renal function progression and DKD in elderly patients with type 2 diabetes mellitus. These findings highlight the importance of long-term dynamic monitoring of serum uric acid levels to facilitate early identification and intervention for high-risk individuals.

Objective To investigate the effect of MALAT1 expressions on cell proliferation and apoptosis in astrocytes by regulating mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK1,2)pathway.Methods The MALAT1 gene was knocked down and over-expressed in C8-D1A cells by lentiviral and plasmid vectors,respectively.The expressions of MALAT1,cell proliferation-related markers(Ki67,MCM2,PCNA)and apoptosis-related proteins(Caspase-3,Bax,Bcl-2)were detected by quantitative real-time polymerase chain reaction(qPCR).CCK-8 assay and flow cytometry were used for cell proliferation and apoptosis in C8-D1A cells.Immunofluorescence was adopted to detect the protein expressions of Caspase-3 and Ki67.Western blotting was used to detect the protein expressions of Caspase-3,Bax,Bcl-2,ERK1/2,p-ERK1/2,p38MAPK and p-p38MAPK.Results Compared with the control group,over-expressed MALAT1 inhibited cell proliferation and induced cell apoptosis in C8-D1A cells while the knockdown of MALAT1 significantly enhanced cell proliferation and anti-apoptotic ability in C8-D1A cells.The proportion of C8-D1A cells in G0/G1-phase and G2/M-phase was higher than in the control group as evidenced by flow cytometry,but was lower in S-phase.Meanwhile,data showed that Caspase-3 was increased while p-ERK1/2 was decreased in terms of protein levels.The mRNA expressions of Ki67 and PCNA were decreased.After knockdown of MALAT1,the proportion of C8-D1A cells in S-phase was higher,but was lower in G2/M-phase.The protein expressions of Caspase-3 and Bax decreased while those of p-ERK1/2 and p-p38MAPK increased.The mRNA expressions of Ki67,MCM2 and PCNA were increased.The differences were all statistically significant(P＜0.05).Conclusion MALAT1 promotes astrocyte apoptosis and inhibits proliferation by regulating the MAPK/ERK1,2 signaling pathway.

Currently, the types of kidney stones before surgery are mainly identified by human beings, which directly leads to the problems of low classification accuracy and inconsistent diagnostic results due to the reliance on human knowledge. To address this issue, this paper proposes a framework for identifying types of kidney stones based on the combination of radiomics and deep learning, aiming to achieve automated preoperative classification of kidney stones with high accuracy. Firstly, radiomics methods are employed to extract radiomics features released from the shallow layers of a three-dimensional (3D) convolutional neural network, which are then fused with the deep features of the convolutional neural network. Subsequently, the fused features are subjected to regularization, least absolute shrinkage and selection operator (LASSO) processing. Finally, a light gradient boosting machine (LightGBM) is utilized for the identification of infectious and non-infectious kidney stones. The experimental results indicate that the proposed framework achieves an accuracy rate of 84.5% for preoperative identification of kidney stone types. This framework can effectively distinguish between infectious and non-infectious kidney stones, providing valuable assistance in the formulation of preoperative treatment plans and the rehabilitation of patients after surgery.
Humans ; Kidney Calculi/classification* ; Deep Learning ; Neural Networks, Computer ; Tomography, X-Ray Computed ; Imaging, Three-Dimensional ; Radiomics

Metabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.
Chromatin ; DNA Methylation ; Epigenesis, Genetic ; Epigenomics ; Histones/metabolism* ; Humans ; Neoplasms/therapy*

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*