Unraveling the immunogenic cell death pathways in gastric adenocarcinoma: A multi-omics study.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal (GI) system. However, the lack of reliable biomarkers has made its diagnosis, prognosis, and treatment challenging. Immunogenic cell death (ICD) is a type of programmed cell death that is strongly related to the immune system. However, its function in GC requires further investigation. METHOD: We used multi-omics and multi-angle approaches to comprehensively explore the prognostic features of ICD in patients with stomach adenocarcinoma (STAD). At the single-cell level, we screened genes associated with ICD at the transcriptome level, selected prognostic genes related to ICD using weighted gene co-expression network analysis (WGCNA) and machine learning, and constructed a prognostic model. In addition, we constructed nomograms that incorporated pertinent clinical features and provided effective tools for prognostic prediction in clinical settings. We also investigated the sensitivity of the risk subgroups to both immunotherapy and drugs. Finally, in addition to quantitative real-time polymerase chain reaction, immunofluorescence was used to validate the expression of ICD-linked genes. RESULTS: Based on single-cell and transcriptome WGCNA analyses, we identified 34 ICD-related genes, of which 11 were related to prognosis. We established a prognostic model using the least absolute shrinkage and selection operator (LASSO) algorithm and identified dissimilarities in overall survival (OS) and progression-free survival (PFS) in risk subgroups. The nomograms associated with the ICD-related signature (ICDRS) demonstrated a good predictive value for clinical applications. Moreover, we detected changes in the tumor microenvironment (TME), including biological functions, mutation landscapes, and immune cell infiltration, between the high- and low-risk groups. CONCLUSION: We constructed an ICD-related prognostic model that incorporated features related to cell death. This model can serve as a useful tool for predicting the prognosis of GC, targeted prevention, and personalized medicine.

Development and validation of the patient-reported outcome for older people living with HIV/AIDS in China (PROHIV-OLD).

BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.

A clinical prediction model based on interpretable machine learning algorithms for prolonged hospital stay in acute ischemic stroke patients: a real-world study.

Objective: Acute ischemic stroke (AIS) brings an increasingly heavier economic burden nowadays. Prolonged length of stay (LOS) is a vital factor in healthcare expenditures. The aim of this study was to predict prolonged LOS in AIS patients based on an interpretable machine learning algorithm. Methods: We enrolled AIS patients in our hospital from August 2017 to July 2019, and divided them into the "prolonged LOS" group and the "no prolonged LOS" group. Prolonged LOS was defined as hospitalization for more than 7 days. The least absolute shrinkage and selection operator (LASSO) regression was applied to reduce the dimensionality of the data. We compared the predictive capacity of extended LOS in eight different machine learning algorithms. SHapley Additive exPlanations (SHAP) values were used to interpret the outcome, and the most optimal model was assessed by discrimination, calibration, and clinical utility. Results: Prolonged LOS developed in 149 (22.0%) of the 677 eligible patients. In eight machine learning algorithms, prolonged LOS was best predicted by the Gaussian naive Bayes (GNB) model, which had a striking area under the curve (AUC) of 0.878 ± 0.007 in the training set and 0.857 ± 0.039 in the validation set. The variables sorted by the gap values showed that the strongest predictors were pneumonia, dysphagia, thrombectomy, and stroke severity. High net benefits were observed at 0%-76% threshold probabilities, while good agreement was found between the observed and predicted probabilities. Conclusions: The model using the GNB algorithm proved excellent for predicting prolonged LOS in AIS patients. This simple model of prolonged hospitalization could help adjust policies and better utilize resources.

A neural network model was constructed by screening the potential biomarkers of aortic dissection based on genes associated with pyroptosis.

BACKGROUND: Aortic dissection (AD) is one of the crucial and common cardiovascular diseases, and pyroptosis is a novel cell delivery mechanism that is probably involved in the pathogenesis of various cardiovascular diseases. However, no study has investigated the role of pyroptosis in AD. METHODS: We obtained two AD datasets, GSE153434 and GSE190635, from the Gene Expression Omnibus database. The differential expression of AD-related genes was determined by differential analysis, and their enrichment analysis was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Additionally, a protein-protein interaction network was established. Next, potential biomarkers were screened by Lasso regression analysis, and a neural network model was constructed. Finally, the potential biomarkers were validated by constructing a mouse model of AD. RESULTS: A total of 1033 differentially expressed related genes were distinguished and these genes were mainly associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase signaling pathways. The Lasso regression results showed five potential biomarkers, namely platelet endothelial cell adhesion molecule-1 (PECAM1), caspase 4 (CASP4), mixed lineage kinase domain-like pseudokinase (MLKL), APAF1-interacting protein (APIP), and histone deacetylase 6 (HDAC6) and successfully constructed a neural network model to predict AD occurrence. The results showed that CASP4 and MLKL were highly expressed, whereas PECAM1 and HDAC6 were lowly expressed in AD samples, and no statistically significant difference was observed in APIP expression in AD samples. CONCLUSION: Pyroptosis plays a crucial role in AD occurrence and development. Moreover, the five potential biomarkers identified in the present study can act as targets for the early diagnosis of AD in patients.

Magnoflorine Ameliorates Collagen-Induced Arthritis by Suppressing the Inflammation Response via the NF-κB/MAPK Signaling Pathways.

Objective: Magnoflorine (Mag) has been reported to have anxiolytics, anti-cancer, and anti-inflammatory properties. In this study, we aim to investigate the effects of Mag on the rheumatoid arthritis (RA) and explore the underlying mechanism using a collagen-induced arthritis (CIA) mouse model and a lipopolysaccharide (LPS)-stimulated macrophage inflammation model. Methods: The in vivo effects of Mag on CIA were studied by inducing CIA in a mouse model using DBA/1J mice followed by treatment with vehicle, methotrexate (MTX, 1 mg/kg/d), and Mag (5 mg/kg/d, 10 mg/kg/d, and 20 mg/kg/d), and the in vitro effects of Mag on macrophages were examined by stimulation of RAW264.7 cells line and peritoneal macrophages (PMs) by LPS in the presence of different concentrations of Mag. Network pharmacology and molecular docking was then performed to predict the the binding ability between Mag and its targets. Inflammatory mediators were assayed by quantitative real-time PCR and enzyme linked immunosorbent assay (ELISA). Signaling pathway changes were subsequently determined by Western blotting and immunohistochemistry (IHC). Results: In vivo experiments demonstrated that Mag decreased arthritis severity scores, joints destruction, and macrophages infiltration into the synovial tissues of the CIA mice. Network pharmacology analysis revealed that Mag interacted with TNF-α, IL-6, IL-1ß, and MCP-1. Consistent with this, analysis of the serum, synovial tissue of the CIA mice, and the supernatant of the cultured RAW264.7 cells and PMs showed that Mag suppressed the expression of TNF-α, IL-6, IL-1ß, MCP-1, iNOS, and IFN-ß. Furthermore, Mag attenuated the phosphorylation of p65, IκBα, ERK, JNK, and p38 MAPKs in the synovial tissues of the CIA mice and LPS-stimulated RAW 264.7 cells. Conclusion: Mag may exert anti-arthritic and anti-inflammatory effects by inhibiting the activation of NF-κB and MAPK signaling pathways.

Signaling pathways of oxidative stress response: the potential therapeutic targets in gastric cancer.

Gastric cancer is one of the top causes of cancer-related death globally. Although novel treatment strategies have been developed, attempts to eradicate gastric cancer have been proven insufficient. Oxidative stress is continually produced and continually present in the human body. Increasing evidences show that oxidative stress contributes significantly to the development of gastric cancer, either through initiation, promotion, and progression of cancer cells or causing cell death. As a result, the purpose of this article is to review the role of oxidative stress response and the subsequent signaling pathways as well as potential oxidative stress-related therapeutic targets in gastric cancer. Understanding the pathophysiology of gastric cancer and developing new therapies for gastric cancer depends on more researches focusing on the potential contributors to oxidative stress and gastric carcinogenesis.

Emerging role of substance and energy metabolism associated with neuroendocrine regulation in tumor cells.

Cancer is the second most common cause of mortality in the world. One of the unresolved difficult pathological mechanism issues in malignant tumors is the imbalance of substance and energy metabolism of tumor cells. Cells maintain life through energy metabolism, and normal cells provide energy through mitochondrial oxidative phosphorylation to generate ATP, while tumor cells demonstrate different energy metabolism. Neuroendocrine control is crucial for tumor cells' consumption of nutrients and energy. As a result, better combinatorial therapeutic approaches will be made possible by knowing the neuroendocrine regulating mechanism of how the neuroendocrine system can fuel cellular metabolism. Here, the basics of metabolic remodeling in tumor cells for nutrients and metabolites are presented, showing how the neuroendocrine system regulates substance and energy metabolic pathways to satisfy tumor cell proliferation and survival requirements. In this context, targeting neuroendocrine regulatory pathways in tumor cell metabolism can beneficially enhance or temper tumor cell metabolism and serve as promising alternatives to available treatments.

Identification and validation of ferroptosis-related genes and immune infiltration in ischemic cardiomyopathy.

Background: Cardiomyocyte death is an important pathophysiological basis for ischemic cardiomyopathy (ICM). Many studies have suggested that ferroptosis is a key link in the development of ICM. We performed bioinformatics analysis and experiment validation to explore the potential ferroptosis-related genes and immune infiltration of ICM. Methods: We downloaded the datasets of ICM from the Gene Expression Omnibus database and analyzed the ferroptosis-related differentially expressed genes (DEGs). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction network were performed to analyze ferroptosis-related DEGs. Gene Set Enrichment Analysis was used to evaluate the gene enrichment signaling pathway of ferroptosis-related genes in ICM. Then, we explored the immune landscape of patients with ICM. Finally, the RNA expression of the top five ferroptosis-related DEGs was validated in blood samples from patients with ICM and healthy controls using qRT-PCR. Results: Overall, 42 ferroptosis-related DEGs (17 upregulated and 25 downregulated genes) were identified. Functional enrichment analysis indicated several enriched terms related to ferroptosis and the immune pathway. Immunological analysis suggested that the immune microenvironment in patients with ICM is altered. The immune checkpoint-related genes (PDCD1LG2, LAG3, and TIGIT) were overexpressed in ICM. The qRT-PCR results showed that the expression levels of IL6, JUN, STAT3, and ATM in patients with ICM and healthy controls were consistent with the bioinformatics analysis results from the mRNA microarray. Conclusion: Our study showed significant differences in ferroptosis-related genes and functional pathway between ICM patients and healthy controls. We also provided insight into the landscape of immune cells and the expression of immune checkpoints in patients with ICM. This study provides a new road for future investigation of the pathogenesis and treatment of ICM.

Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system, the most common type of dementia in old age, which causes progressive loss of cognitive functions such as thoughts, memory, reasoning, behavioral abilities and social skills, affecting the daily life of patients. The dentate gyrus of the hippocampus is a key area for learning and memory functions, and an important site of adult hippocampal neurogenesis (AHN) in normal mammals. AHN mainly consists of the proliferation, differentiation, survival and maturation of newborn neurons and occurs throughout adulthood, but the level of AHN decreases with age. In AD, the AHN will be affected to different degrees at different times, and its exact molecular mechanisms are increasingly elucidated. In this review, we summarize the changes of AHN in AD and its alteration mechanism, which will help lay the foundation for further research on the pathogenesis and diagnostic and therapeutic approaches of AD.

The Efficacy and Hemorheological Indexes of Ginseng and Its Active Components for Patients with Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Non-small cell lung cancer (NSCLC) is still a slightly less orphan disease after immunotherapy, and routine treatment has low efficiency and adverse events. Ginseng is commonly used in the treatment of NSCLC. The purpose of this study is to assess the efficacy and hemorheological indexes of ginseng and its active components in patients with non-small cell lung cancer. Methods: A comprehensive literature search was performed in PubMed, the Cochrane Library, Medline (Ovid), the Web of Science, Embase, CKNI, Wan Fang, VIP, and SinoMed up to July 2021. Only randomized controlled trials evaluating ginseng in combination with chemotherapy versus chemotherapy alone in NSCLC patients were included. Primary outcomes included patients' condition after using ginseng or its active components. Secondary outcomes included changes in immune cells, cytokines, and secretions in serum. Data were extracted by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was applied for the included studies. Systematic review and meta-analysis were performed by RevMan 5.3 software. Results: The results included 1480 cases in 17 studies. The results of the integration of clinical outcomes showed that the treatment of ginseng (or combination of ginseng with chemotherapy) can improve the quality of life for patients with NSCLC. Analysis of immune cell subtypes revealed that ginseng and its active ingredients can upregulate the percentages of antitumor immunocyte subtypes and downregulate the accounts of immunosuppressive cells. In addition, a reduction of the inflammatory level and an increase of antitumor indicators in serum were reported. Meta-analysis showed that Karnofsky score: WMD = 16, 95% CI (9.52, 22.47); quality-of-life score: WMD = 8.55, 95%CI (6.08, 11.03); lesion diameter: WMD = -0.45, 95% CI (-0.75, -0.15); weight: WMD = 4.49, 95% CI (1.18, 7.80); CD3+: WMD = 8.46, 95% CI (5.71, 11.20); CD4+: WMD = 8.45, 95% CI (6.32, 10.57)+; CD8+: WMD = -3.76, 95% CI (-6.34, -1.18); CD4+/CD8+: WMD = 0.32, 95% CI (0.10, 0.53); MDSC: WMD = -2.88, 95% CI (-4.59, -1.17); NK: WMD = 3.67, 95% CI (2.63, 4.71); Treg: WMD = -1.42, 95% CI (-2.33, -0.51); CEA: WMD = -4.01, 95% CI (-4.12, -3.90); NSE: WMD = -4.00, 95% CI (-4.14, -3.86); IL-2: WMD = 9.45, 95% CI (8.08, 10.82); IL-4: WMD = -9.61, 95% CI (-11.16, -8.06); IL-5: WMD = -11.95, 95% CI (-13.51, -10.39); IL-6: WMD = -7.65, 95% CI (-8.70, -6.60); IL-2/IL-5: WMD = 0.51, 95% CI (0.47, 0.55); IFN-γ: WMD = 15.19, 95% CI (3.16, 27.23); IFN-γ/IL-4: WMD = 0.91, 95% CI (0.85, 0.97); VEGF: WMD = -59.29, 95% CI (-72.99, -45.58); TGF-α: WMD = -10.09, 95% CI (-12.24, -7.94); TGF-ß: WMD = -135.62, 95% CI (-147.00, -124.24); TGF-ß1: WMD = -4.22, 95% CI (-5.04, -3.41); arginase: WMD = -1.81, 95% CI (-3.57, -0.05); IgG: WMD = 1.62, 95% CI (0.18, 3.06); IgM: WMD = -0.45, 95% CI (-0.59, -0.31). All results are statistically significant. No adverse events were reported in the included articles. Conclusion: It is a reasonable choice to use ginseng and its active components as adjuvant therapy for NSCLC. Ginseng is helpful for NSCLC patients' conditions, immune cells, cytokines, and secretions in the serum.

Relapse After Drug Withdrawal in Patients with Epilepsy After Two Years of Seizure-Free: A Cohort Study.

Background and Study Aims: Antiepileptic drugs are the first choice of treatment for patients with epilepsy. However, the withdrawal of antiepileptic drugs after seizure-free remains a significant focus for the majority of patients with epilepsy and their families. In this study, we evaluated the risk factors associated with relapse after drug withdrawal in patients with seizure free for 2 years. We aimed to guide patients in seizure-free to assess the risk of drug withdrawal. Patients and Methods: Through screening, 452 patients with epilepsy were included in the study.Patients were followed up for at least 2 years or more. Analyzed their clinical data by applying the χ2-test, Kaplan-Meier survival analysis and multivariate Cox regression analysis. Results: 423 patients completed follow-up, of which 304 cases recurred (71.9%).Related recurrence factors include age of onset, type of seizure, number of AEDs, seizure-free time before withdrawal, and electroencephalogram (EEG) results before drug withdrawal (P<0.05). The results of correlation analysis showed that age of onset, seizure frequency, seizure type, number of AEDs, the period from AEDs treatment to a seizure-free status, EEG results before drug withdrawal, and pre-medication course, were all significantly related to the recurrence of seizures after drug reduction and withdrawal (P<0.05). We identified a range of independent risk factors, including onset age, seizure frequency, Multiple AEDs and the period from AEDs treatment to a seizure-free status. Conclusion: The overall recurrence rate of epilepsy in our patient cohort was high, and the peak recurrence period was within one-year of drug withdrawal. Patients with partial seizures, a short seizure-free time before withdrawal, severe EEG abnormalities before drug reduction, and a long course of the disease, are prone to relapse. Patients with an older age at onset and a high frequency of attack, those taking multi-drug combination therapy, and those that take a long time to gain control, should be managed carefully to AEDs withdrawal.

The mediating role of appraisal on health-related quality of life in adolescent and young adult cancer survivors.

BACKGROUND: Adolescent and young adult (AYA) cancer survivors (first diagnosed with cancer at age 15-39) are distinct within the cancer community due to their unique challenges and diverse psycho-behavioral characteristics. This study aimed to analyze psycho-behavioral pathways and further explore the mediating role of cognitive appraisals on AYA cancer survivors' quality of life (QoL). METHODS: Three hundred and eighty-nine AYA cancer survivors were eligible for analyses and recruited to self-administer questionnaires on QoL (the Chinese version of EORTC Quality of Life Questionnaire-C30 v3.0), resilience, coping, and appraisal on site. This study performed structural equation modeling (SEM) to examine pathways on QoL based on the Rapkin & Schwartz QoL Appraisal Model. RESULTS: The average age of participants (47.6% female) was 32.7 ± 4.1 years. The SEM results closely fit the measured data (RMSEA = 0.053, GFI = 0.955, CFI = 0.964, SRMR = 0.052). The final model showed direct negative effects of later clinical-stage, more comorbidities, and more Acceptance-Resignation coping on QoL; indirect positive effects of better resilience on QoL through less Acceptance-Resignation coping (ß = 0.286, P = 0.002). Appraisal mediated the effects of treatment and resilience on QoL (ß = -0.024, P = 0.038). Further, Calm, Peaceful, and Active appraisal patterns were associated with improved Cognitive Functioning (ß = 0.119, P = 0.009). CONCLUSION: Appraisal, coping, and resilience could significantly mediate the effects of cancer and its treatment on the QoL of AYA cancer survivors. Future interventions targeting cognitive appraisals and psycho-behaviors will be helpful. Figuring out what matters to such a unique population and how they appraise a cancer diagnosis through treatment trajectories could help nurses adjust support.

Investigation of the relationship between MBP gene polymorphisms and delayed encephalopathy after acute carbon monoxide poisoning.

Increasing evidence reveals that delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) results from the combined effects of environmental and genetic factors. The main pathological feature of DEACMP was generalized demyelination of cerebral white matter. Myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) and serum samples from DEACMP patients were elevated. This study investigated the association of MBP single nucleotide polymorphisms(SNPs) (rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336) with DEACMP. We genotyped 416 DEACMP patients and 785 age, educational level, and sex-matched ACMP patients for rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336 SNPs using the Agena MassArray. There were no significant differences in the allele frequency distribution, four genetic models, and genotype distributions between the DEACMP and ACMP groups for rs470555, rs470724, rs4890785, and rs595997. However, significant differences were observed for rs76452994 and rs921336. This study revealed that the MBP polymorphisms, rs470555, rs470724, rs4890785, and rs595997, were not associated with DEACMP. Based on the codominant, dominant, and overdominant genetic inheritability patterns, the MBP rs76452994 and rs921366 polymorphisms were associated with DEACMP. Furthermore, the G allele of rs76452994 and T allele of rs921336 could lead to higher DEACMP risk.

HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis.

HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in the clinical setting. However, the mechanism of action of HJ11 components remains unclear. Ferroptosis is a critical factor that promotes myocardial I/R injury, and the pathophysiological ferroptosis-mediated lipid peroxidation causes I/R injury. Therefore, this study explored whether HJ11 decoction ameliorates myocardial I/R injury by attenuating ACSL4-mediated ferroptosis. This study also explored the effect of ACSL4 expression on iron-dependent programmed cell death by preparing a rat model of myocardial I/R injury and oxygen glucose deprivation/reperfusion (OGD/R)-induced H9c2 cells. The results showed that HJ11 decoction improved cardiac function; attenuated I/R injury, apoptosis, oxidative stress, mitochondrial damage, and iron accumulation; and reduced infarct size in the myocardial I/R injury rat model. Additionally, HJ11 decoction suppressed the expression of ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase-2 (COX2)] but promoted the expression of ferroptosis-inhibiting proteins [ferritin heavy chain 1 (FTH1) and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4)] in the myocardial tissues of the I/R injury rat model. Similar results were found with the OGD/R-induced H9c2 cells. Interestingly, ACSL4 knockdown attenuated iron accumulation, oxidative stress, and ferroptosis in the OGD/R-treated H9c2 cells. However, ACSL4 overexpression counteracted the inhibitory effect of the HJ11 decoction on OGD/R-triggered oxidative stress and ferroptosis in H9c2 cells. These findings suggest that HJ11 decoction restrained the development of myocardial I/R injury by regulating ACSL4-mediated ferroptosis. Thus, HJ11 decoction may be an effective medication to treat myocardial I/R injury.

Prognostic Assessment of Oxidative Stress-Related Genes in Colorectal Cancer and New Insights into Tumor Immunity.

Oxidative stress is crucial to the biology of tumors. Oxidative stress' potential predictive significance in colorectal cancer (CRC) has not been studied; nevertheless here, we developed a forecasting model based on oxidative stress to forecast the result of CRC survival and enhance clinical judgment. The training set was chosen from the transcriptomes of 177 CRC patients in GSE17536. For validation, 65 samples of colon cancer from GSE29621 were utilized. For the purpose of choosing prognostic genes, the expression of oxidative stress-related genes (OXEGs) was found. Prognostic risk models were built using multivariate Cox regression analysis, univariate Cox regression analysis, and LASSO regression analysis. The outcomes of the western blot and transcriptome sequencing tests were finally confirmed. ATF4, CARS2, CRP, GPX1, IL1B, MAPK8, MRPL44, MTFMT, NOS1, OSGIN2, SOD2, AARS2, and FOXO3 were among the 14 OXEGs used to build prognostic characteristics. Patients with CRC were categorized into low-risk and high-risk groups according on their median risk scores. Cox regression analysis using single and multiple variables revealed that OXEG-related signals were independent risk factors for CRC. Additionally, the validation outcomes from western blotting and transcriptome sequencing demonstrated that OXEGs were differently expressed. Using 14 OXEGs, our work creates a predictive signature that may be applied to the creation of new prognostic models and the identification of possible medication candidates for the treatment of CRC.

Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma.

Background: Cuproptosis, a newly described method of regulatory cell death (RCD), may be a viable new therapy option for cancers. Long noncoding RNAs (lncRNAs) have been confirmed to be correlated with epigenetic controllers and regulate histone protein modification or DNA methylation during gene transcription. The roles of cuproptosis-related lncRNAs (CRLs) in Colon adenocarcinoma (COAD), however, remain unknown. Methods: COAD transcriptome data was obtained from the TCGA database. Thirteen genes associated to cuproptosis were identified in published papers. Following that, correlation analysis was used to identify CRLs. The cuproptosis associated prognostic signature was built and evaluated using Lasso regression and COX regression analysis. A prognostic signature comprising six CRLs was established and the expression patterns of these CRLs were analyzed by qRT-PCR. To assess the clinical utility of prognostic signature, we performed tumor microenvironment (TME) analysis, mutation analysis, nomogram generation, and medication sensitivity analysis. Results: We identified 49 prognosis-related CRLs in COAD and constructed a prognostic signature consisting of six CRLs. Each patient can be calculated for a risk score and the calculation formula is: Risk score =TNFRSF10A-AS1 * (-0.2449) + AC006449.3 * 1.407 + AC093382.1 *1.812 + AC099850.3 * (-0.0899) + ZEB1-AS1 * 0.4332 + NIFK-AS1 * 0.3956. Six CRLs expressions were investigated by qRT-PCR in three colorectal cancer cell lines. In three cohorts, COAD patients were identified with different risk groups, with the high-risk group having a worse prognosis than the low-risk group. Furthermore, there were differences in immune cell infiltration and tumor mutation burden (TMB) between the two risk groups. We also identified certain drugs that were more sensitive to the high-risk group: Paclitaxel, Vinblastine, Sunitinib and Elescloml. Conclusions: Our findings may be used to further investigate RCD, comprehension of the prognosis and tumor microenvironment infiltration characteristics in COAD.

Associated factors on physical activity among childhood cancer survivors in Mainland China: a qualitative exploration applied health belief model.

PURPOSE: Regular physical activity (PA) is essential for childhood cancer survivors (CCS), yet most CCS have difficulty participating in it. The level of PA participation among CCS in China is lower than those of western countries, leading to a worse long-term survival of CCS in China. Here, the study aims to explore the associated factors on the PA performance among CCS. METHODS: From September to December 2020, the study used purposive sampling to recruit 35 families (88.9%) as sampling units among two hospitals in Hangzhou City, China. The data collection conducted two designs on semi-structured interviews with different roles under family structure - children (n = 35) and parents (n = 35) - respectively. The design of predetermined questions relied on the health belief model (HBM) as a thematic framework. The qualitative analysis applied codebook thematic analysis and used the deductive approach to finalize the main findings. RESULTS: The study only presented preliminary conclusions from interviews with CCS, which resulted in four themes (changes in PA performance; perceptions on participating PA; cognitions of PA; impacts from others) with eight sub-themes. In particular, CCS replied diversity changes in PA, but most of them mentioned the inactive PA after diagnosis, especially the decline of moderate-to-vigorous PA (MVPA). As for the "perceptions of PA," almost all CCS had substantial perceived benefits about PA, specifically on their physical well-being. All children also expressed perceived barriers to PA, including the side effects of disease and treatment, fatigue, academic burden, changes in psychological status, and lack of companions. On the cognitions of PA, the CCS had limited realizations of regular PA and low self-efficacy on MVPA. Furthermore, CCS expressed their need for support from their parents, school teachers, and healthcare providers. But in reality, they recieved less support on PA from these important people. CONCLUSION: The changes in PA after illness among CCS are apparent and unavoidable because of the interaction impacts from internal factors (e.g., personal characters, cognization, perceptions of PA) and external factors (e.g., disease effects, interpersonal supports). The findings explained the main elements under HBM but also provided explored views as the evidence on developing theories and guiding motivations and practices on PA among CCS. IMPLICATIONS FOR CANCER SURVIVORS: In this exploratory study of 35 CCS, we identified the current situation of PA among CCS in China and explored the associated factors. As the first qualitative study on the CCS in mainland China, the study considered particular effects on social culture and living environment.

Development of an exosome-related and immune microenvironment prognostic signature in colon adenocarcinoma.

Background: The correlation between exosomes and the tumor immune microenvironment has been proved to affect tumorigenesis and progression of colon adenocarcinoma (COAD). However, it remained unclear whether exosomes had an impact on the prognostic indications of COAD patients. Methods: Expression of exosome-related genes (ERGs) and clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The ERGs associated with prognosis were identified and exosome-related prognostic signature was constructed. Patients in two risk groups were classified according to the risk score calculation formula: Risk score = 1.0132 * CCKBR + 0.2416 * HOXC6 + 0.7618 * POU4F1. The expression of three ERGs was investigated by qRT-PCR. After that, we developed a nomogram predicting the likelihood of survival and verified its predictive efficiency. The differences of tumor immune microenvironment, immune cell infiltration, immune checkpoint and sensitivity to drugs in two risk groups were analyzed. Results: A prognostic signature was established based on the three ERGs (CCKBR, HOXC6, and POU4F1) and patients with different risk group were distinguished. Survival analysis revealed the negative associated of risk score and prognosis, ROC curve analyses showed the accuracy of this signature. Three ERGs expression was investigated by qRT-PCR in three colorectal cancer cell lines. Moreover, risk score was positively correlated with tumor mutational burden (TMB), immune activities, microsatellite instability level, the expression of immune checkpoint genes. Meanwhile, the expression level of three ERGs and the risk score were markedly related with the sensitive response to chemotherapy. Conclusion: The novel signature composed of three ERGs with precise predictive capabilities can be used to predict prognosis and provide a promising therapeutic target for improving the efficacy of immunotherapy.

Ferroptosis and its Role in Gastric Cancer.

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Currently, surgery is the treatment of choice for GC. However, the associated expenses and post-surgical pain impose a huge burden on these patients. Furthermore, disease recurrence is also very common in GC patients, thus necessitating the discovery and development of other potential treatment options. A growing body of knowledge about ferroptosis in different cancer types provides a new perspective in cancer therapeutics. Ferroptosis is an iron-dependent form of cell death. It is characterized by intracellular lipid peroxide accumulation and redox imbalance. In this review, we summarized the current findings of ferroptosis regulation in GC. We also tackled on the action of different potential drugs and genes in inducing ferroptosis for treating GC and solving drug resistance. Furthermore, we also explored the relationship between ferroptosis and the tumor microenvironment in GC. Finally, we discussed areas for future studies on the role of ferroptosis in GC to accelerate the clinical utility of ferroptosis induction as a treatment strategy for GC.

The efficacy and safety of Wulingsan modified formulas for chronic heart failure patients: a systematic review and meta-analysis.

Background: Chronic heart failure (CHF) is one of the most common cardiovascular diseases, which has caused huge economic burden worldwide. Wulingsan modified formulas have been historically used for CHF in China. However, the efficacy of its treatment for CHF has not been summarized by scholars and lacks of clinical evidence. This study aimed to assess the efficacy and safety of Wulingsan modified formulas for patients with CHF. Methods: A comprehensive literature search was performed in the PubMed, EMBASE, Cochrane Library, Web of Science, Medline (Ovid), China National Knowledge Infrastructure, WanFang, China Science and Technology Journal Database, and SinoMed databases from the date of their inception up to 1st November, 2021. Only randomized controlled trials evaluating Wulingsan modified formulas in patients with CHF were included. The primary outcome of this study was efficacy of Wulingsan modified formulas in the treatment of CHF, and the secondary outcomes included brain natriuretic peptide, left ventricular ejection fractions, and any other changes in the patients' condition. The risk ratio was applied to evaluate efficiency, and the weighted mean difference (WMD) and 95% confidence interval (CI) were used to merge the continuous variables. The I2 statistic was used to assess the heterogeneity. Sensitivity analysis was used to evaluate whether the single research affected the whole results. Data were extracted by two independent investigators. The Cochrane Risk of Bias tool (version 2.0) was utilized to evaluate the included studies, STATA (version 15.0) was applied for sensitivity analysis, and RevMan 5.3 software was used to conduct the systematic review and meta-analysis. Results: Nineteen studies with a total of 1,631 were included in this meta-analysis. The meta-analysis results were as follows: efficiency, the risk ratio =1.21, 95% CI: 1.15, 1.27; brain natriuretic peptide, WMD =-269.14, 95% CI: -349.25, -189.04; and left ventricular ejection fractions, WMD =8.80, 95% CI: 5.93, 11.68. All of these findings were statistically significant. No statistically significant adverse events were reported in the included articles. Discussion: Wulingsan modified formulas are a reasonable and relatively safe adjuvant therapy for the treatment of CHF.