Mitochondria are the convergence point of multiple pathways that trigger programmed cell death (PCD). Mitochondrial-associated PCD (mtPCD) is involved in the pathogenesis of several diseases. However, the role of mtPCD in the prognostic prediction of cancers including non-small-cell lung cancer (NSCLC) remains to be investigated. Here, 12 mtPCD patterns were analyzed in transcriptomics, genomics, and clinical data collected from 4 datasets containing 977 patients. A risk-score assessment system containing 18 genes was established. We found that NSCLC patients with a high-risk score had a poorer prognosis. A nomogram was constructed by incorporating the risk score with clinical features. The risk score was further associated with clinicopathological information, tumor-mutation frequency, and immunotherapy responses. NSCLC patients with a high risk score had more Treg cells infiltration. However, these patients had higher tumor-mutation burden scores and may be more sensitive to immunotherapy. Moreover, receptor-interacting serine/threonine protein kinase 2 (RIPK2) was selected from mtPCD gene model for validation. We found that RIPK2 exhibited oncogenic function, and its expression level was inversely associated with the overall survival of NSCLC. Taken together, our results indicated the accuracy and practicability of the mtPCD gene model and RIPK2 in predicting the prognosis of NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Prognosis ; Male ; Female ; Nomograms ; Middle Aged ; Mitochondria/metabolism* ; Apoptosis/genetics* ; Mutation ; Biomarkers, Tumor/genetics* ; Aged

The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.
Humans ; Lung Neoplasms/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Gene Expression Regulation, Neoplastic ; Disease Progression ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Chromatin Assembly Factor-1/metabolism* ; Animals ; Mice ; Male ; Female

OBJECTIVES: This study investigated the seasonal impact of diurnal temperature range (DTR) on hospitalization rates for intracerebral hemorrhage (ICH) in middle-aged and elderly adults. METHODS: We collected data on the DTR and hospitalization records of ≥45-year-old patients with ICH in 2019 in Hunan Province, central China. Time-series analyses were performed using a distributed lag non-linear model. RESULTS: Overall, 54,690 hospitalizations for ICH were recorded. DTR showed a non-linear relationship with ICH hospitalization in both middle-aged and elderly populations (45-59 and ≥60 years, respectively). During spring, a low DTR coupled with persistently low temperatures increased ICH risk in both age groups, while a high DTR was associated with an increased risk in the middle-aged group only (relative risk [RR], 1.24; 95% confidence interval [CI], 1.21 to 1.27). In the summer, a low DTR combined with persistently high temperatures was linked to a higher risk exclusively in the middle-aged group. A high DTR in the autumn was correlated with increased risk in both age groups. In winter, either a low DTR with a continuously low temperature or a high DTR elevated the risk solely in the elderly population (RR, 1.37; 95% CI, 1.00 to 1.69). In the elderly group, the impact of DTR on hospitalization risk manifested within a 5-day period. CONCLUSIONS The impact of DTR on ICH hospitalization risk differed significantly across seasons and between age groups. Elderly individuals demonstrated greater sensitivity to the impact of DTR. Weather forecasting services should emphasize DTR values, and interventions targeting sensitive populations are needed.

OBJECTIVES: This study investigated the seasonal impact of diurnal temperature range (DTR) on hospitalization rates for intracerebral hemorrhage (ICH) in middle-aged and elderly adults. METHODS: We collected data on the DTR and hospitalization records of ≥45-year-old patients with ICH in 2019 in Hunan Province, central China. Time-series analyses were performed using a distributed lag non-linear model. RESULTS: Overall, 54,690 hospitalizations for ICH were recorded. DTR showed a non-linear relationship with ICH hospitalization in both middle-aged and elderly populations (45-59 and ≥60 years, respectively). During spring, a low DTR coupled with persistently low temperatures increased ICH risk in both age groups, while a high DTR was associated with an increased risk in the middle-aged group only (relative risk [RR], 1.24; 95% confidence interval [CI], 1.21 to 1.27). In the summer, a low DTR combined with persistently high temperatures was linked to a higher risk exclusively in the middle-aged group. A high DTR in the autumn was correlated with increased risk in both age groups. In winter, either a low DTR with a continuously low temperature or a high DTR elevated the risk solely in the elderly population (RR, 1.37; 95% CI, 1.00 to 1.69). In the elderly group, the impact of DTR on hospitalization risk manifested within a 5-day period. CONCLUSIONS The impact of DTR on ICH hospitalization risk differed significantly across seasons and between age groups. Elderly individuals demonstrated greater sensitivity to the impact of DTR. Weather forecasting services should emphasize DTR values, and interventions targeting sensitive populations are needed.

OBJECTIVES: This study investigated the seasonal impact of diurnal temperature range (DTR) on hospitalization rates for intracerebral hemorrhage (ICH) in middle-aged and elderly adults. METHODS: We collected data on the DTR and hospitalization records of ≥45-year-old patients with ICH in 2019 in Hunan Province, central China. Time-series analyses were performed using a distributed lag non-linear model. RESULTS: Overall, 54,690 hospitalizations for ICH were recorded. DTR showed a non-linear relationship with ICH hospitalization in both middle-aged and elderly populations (45-59 and ≥60 years, respectively). During spring, a low DTR coupled with persistently low temperatures increased ICH risk in both age groups, while a high DTR was associated with an increased risk in the middle-aged group only (relative risk [RR], 1.24; 95% confidence interval [CI], 1.21 to 1.27). In the summer, a low DTR combined with persistently high temperatures was linked to a higher risk exclusively in the middle-aged group. A high DTR in the autumn was correlated with increased risk in both age groups. In winter, either a low DTR with a continuously low temperature or a high DTR elevated the risk solely in the elderly population (RR, 1.37; 95% CI, 1.00 to 1.69). In the elderly group, the impact of DTR on hospitalization risk manifested within a 5-day period. CONCLUSIONS The impact of DTR on ICH hospitalization risk differed significantly across seasons and between age groups. Elderly individuals demonstrated greater sensitivity to the impact of DTR. Weather forecasting services should emphasize DTR values, and interventions targeting sensitive populations are needed.

OBJECTIVES: This study investigated the seasonal impact of diurnal temperature range (DTR) on hospitalization rates for intracerebral hemorrhage (ICH) in middle-aged and elderly adults. METHODS: We collected data on the DTR and hospitalization records of ≥45-year-old patients with ICH in 2019 in Hunan Province, central China. Time-series analyses were performed using a distributed lag non-linear model. RESULTS: Overall, 54,690 hospitalizations for ICH were recorded. DTR showed a non-linear relationship with ICH hospitalization in both middle-aged and elderly populations (45-59 and ≥60 years, respectively). During spring, a low DTR coupled with persistently low temperatures increased ICH risk in both age groups, while a high DTR was associated with an increased risk in the middle-aged group only (relative risk [RR], 1.24; 95% confidence interval [CI], 1.21 to 1.27). In the summer, a low DTR combined with persistently high temperatures was linked to a higher risk exclusively in the middle-aged group. A high DTR in the autumn was correlated with increased risk in both age groups. In winter, either a low DTR with a continuously low temperature or a high DTR elevated the risk solely in the elderly population (RR, 1.37; 95% CI, 1.00 to 1.69). In the elderly group, the impact of DTR on hospitalization risk manifested within a 5-day period. CONCLUSIONS The impact of DTR on ICH hospitalization risk differed significantly across seasons and between age groups. Elderly individuals demonstrated greater sensitivity to the impact of DTR. Weather forecasting services should emphasize DTR values, and interventions targeting sensitive populations are needed.

Objective To investigate the nutritional knowledge,attitudes,and behaviors of air crew in a sanatorium from 2020 to 2022,and analyzing their nutritional management methods.Methods A total of 118 air crew members in a sanatorium from 2020 to 2022 were included in this study.A questionnaire survey on nutritional knowledge,attitude and behavior was conducted to collect basic information.The scores of nutritional knowledge,attitude and behavior were compared among air crew of different types of job,ages,genders and diseases.Nutritional management methods were adopted according to the survey results,and the scores of nutritional knowledge,attitude and behavior were compared before and after nutritional management.Results Before nutritional management,the scores of nutrition knowledge,attitude and behavior of fighters were higher than those of transport planes and bombers(P<0.05);there were no significant differences in the nutritional knowledge,attitude or behavior scores between air crew members of different genders(P>0.05).After nutritional management,there were no significant difference in the nutritional knowledge,attitude,or behavior scores among air crew of different aircraft types,ages,genders,or disease conditions(P>0.05).The nutritional knowledge,attitude,and behavior scores were increased after nutritional management in all the air crew members(P<0.05).The nutritional knowledge,attitude,and behavior of air crew members were positively correlated with each other(P<0.05).Conclusion The air crew in a sanatorium from 2020 to 2022 have low scores of nutritional knowledge,attitude and behavior.Their knowledge,attitude,and behavior in nutrition management are mutually influenced.Nutrition management measures can improve their nutrition knowledge level,enhance their attitude towards nutrition management,and promote their healthy nutrition behavior.

Objective To identify inflamm-aging related biomarkers in osteoarthritis(OA).Methods Microarray gene profiles of young and aging OA patients were obtained from the Gene Expression Omnibus(GEO)database and aging-related genes(ARGs)were obtained from the Human Aging Genome Resource(HAGR)database.The differentially expressed genes of young OA and older OA patients were screened and then intersected with ARGs to obtain the aging-related genes of OA.Enrichment analysis was performed to reveal the potential mechanisms of aging-related markers in OA.Three machine learning methods were used to identify core senescence markers of OA and the receiver operating characteristic(ROC)curve was used to assess their diagnostic performance.Peripheral blood mononuclear cells were collected from clinical OA patients to verify the expression of senescence-associated secretory phenotype(SASP)factors and senescence markers.Results A total of 45 senescence-related markers were obtained,which were mainly involved in the regulation of cellular senescence,the cell cycle,inflammatory response,etc.Through the screening with the three machine learning methods,5 core senescence biomarkers,including FOXO3,MCL1,SIRT3,STAG1,and S100A13,were obtained.A total of 20 cases of normal controls and 40 cases of OA patients,including 20 cases in the young patient group and 20 in the elderly patient group,were enrolled.Compared with those of the young patient group,C-reactive protein(CRP),interleukin(IL)-6,and IL-1β levels increased and IL-4 levels decreased in the elderly OA patient group(P＜0.01);FOXO3,MCL1,and SIRT3 mRNA expression decreased and STAG1 and S100A13 mRNA expression increased(P＜0.01).Pearson correlation analysis demonstrated that the selected markers were associated with some indicators,including erythrocyte sedimentation rate(ESR),IL-1β,IL-4,CRP,and IL-6.The area under the ROC curve of the 5 core aging genes was always greater than 0.8 and the C-index of the calibration curve in the nomogram prediction model was 0.755,which suggested the good calibration ability of the model.Conclusion FOXO3,MCL1,SIRT3,STAG1,and S100A13 may serve as novel diagnostic biomolecular markers and potential therapeutic targets for OA inflamm-aging.

Background The risks of unhealthy working mood and physical and mental health problems are high in the workers of petrochemical enterprises. Resilience is a positive psychological factor, which can provide positive ability to manage stress and job burnout, relieve tension, depression, anxiety, and other psychological discomfort. Objective To explore the moderating or mediating effect of resilience on the association between job burnout and sleep disorders in workers of petrochemical enterprises. Methods A survey with questionnaire of general information, resilience, job burnout (including exhaustion, cynicism, and professional efficacy), and sleep disorders was conducted among 1087 workers who were selected by cluster sampling from a petrochemical enterprise in Henan Province in April 2022. Mann-Whitney U test and Kruskal-Wallis H test were used to test the differences of scores among different demographic groups. Resilience, job burnout (including exhaustion, cynicism, and professional efficacy), and sleep disorder scores were analyzed by partial correlation analysis. The moderating effect of resilience was examined by linear regression analysis, and the mediating effect of resilience by Bootstrap method. Results A total of 861 questionnaires were collected, of which 857 were effective, and the effective rate was 99.5%. The M (P₂₅, P₇₅) of job burnout score was 1.24 (0.65, 2.22) and the incidence of job burnout was 36.4% (312/857); the scores [M (P₂₅, P₇₅)] of exhaustion, cynicism, and professional efficacy were 1.40 (0.80, 3.00), 1.00 (0.20, 1.60), and 5.50 (4.00, 6.00), respectively. The M (P₂₅, P₇₅) of resilience score was 36.00 (30.00, 41.00). The M (P₂₅, P₇₅) of sleep disorder score was 11.00 (7.00, 15.00). The partial correlation analysis results showed that job burnout, exhaustion, and cynicism were negatively correlated with resilience (r=−0.387, −0.248, −0.247, P<0.01), and positively correlated with sleep disorders (r=0.455, 0.445, 0.357, P<0.01); professional efficacy was positively correlated with resilience (r=0.366, P<0.01) and negatively correlated with sleep disorders (r=−0.184, P<0.01); resilience was negatively correlated with sleep disorders (r=−0.349, P<0.01). The linear regression analysis results found that job burnout, exhaustion, and cynicism elevated the risk of sleep disorders (P<0.01), resilience lowered the risk of sleep disorders (P<0.01); but the relationship between job burnout (exhaustion, cynicism, and professional efficacy) and sleep disorders was not moderated by resilience (P＞0.05). The mediating effect test showed that resilience played a partial mediating role in the associations of job burnout, exhaustion, cynicism, and professional efficacy with sleep disorders, the mediating effects were 0.522 (95%CI: 0.283-0.777), 0.310 (95%CI: 0.188-0.453), 0.364 (95%CI: 0.228-0.524), −0.542 (95%CI: −0.741-−0.366) and the mediating effects accounted for 17.31%, 14.12%, 19.24%, and 64.72% of the total effects, respectively. Conclusion The relationship between job burnout and sleep disorders is partially mediated by resilience among workers in the selected petrochemical company, but no moderating effect is found.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*