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.

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*

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.
Carcinoma, Renal Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Humans ; Immunity, Innate ; Kidney Neoplasms/pathology* ; Lectins/metabolism* ; Prognosis ; Receptors, Cell Surface/metabolism*