Ferroptosis is a protective factor for the prognosis of cancer patients: a systematic review and meta-analysis.

BACKGROUND: Cancer is a leading global cause of death. Conventional cancer treatments like surgery, radiation, and chemotherapy have associated side effects. Ferroptosis, a nonapoptotic and iron-dependent cell death, has been identified and differs from other cell death types. Research has shown that ferroptosis can promote and inhibit tumor growth, which may have prognostic value. Given the unclear role of ferroptosis in cancer biology, this meta-analysis aims to investigate its impact on cancer prognosis. METHODS: This systematic review and meta-analysis conducted searches on PubMed, Embase, and the Cochrane Library databases. Eight retrospective studies were included to compare the impact of ferroptosis inhibition and promotion on cancer patient prognosis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Studies lacking clear descriptions of hazard ratios (HR) and 95% confidence intervals for OS and PFS were excluded. Random-effects meta-analysis and meta-regression were performed on the included study data to assess prognosis differences between the experimental and control groups. Meta-analysis results included HR and 95% confidence intervals. This study has been registered with PROSPERO, CRD 42023463720 on September 27, 2023. RESULTS: A total of 2,446 articles were screened, resulting in the inclusion of 5 articles with 938 eligible subjects. Eight studies were included in the meta-analysis after bias exclusion. The meta-analysis, after bias exclusion, demonstrated that promoting ferroptosis could increase cancer patients' overall survival (HR 0.31, 95% CI 0.21-0.44) and progression-free survival (HR 0.26, 95% CI 0.16-0.44) compared to ferroptosis inhibition. The results showed moderate heterogeneity, suggesting that biological activities promoting cancer cell ferroptosis are beneficial for cancer patient's prognosis. CONCLUSIONS: This systematic review and meta-analysis demonstrated that the promotion of ferroptosis yields substantial benefits for cancer prognosis. These findings underscore the untapped potential of ferroptosis as an innovative anti-tumor therapeutic strategy, capable of addressing challenges related to drug resistance, limited therapeutic efficacy, and unfavorable prognosis in cancer treatment. REGISTRATION: CRD42023463720.

Diagnostic Performance of Node Reporting and Data System Magnetic Resonance Imaging Score in Detecting Metastatic Cervical Lymph Nodes of Nasopharyngeal Carcinoma.

Background: The Node Reporting and Data System (Node-RADS) is a recently proposed classification system for the categorization of lymph nodes in radiological images. This study was conducted to retrospectively evaluate the diagnostic accuracy of the Node-RADS score for metastatic cervical lymph nodes on magnetic resonance imaging (MRI) of patients with nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed cervical lymph nodes of NPC cases. Two radiologists independently evaluated each lymph node on the MRI scans using Node-RADS. Interobserver agreement between 2 radiologists for Node-RADS score assessment was evaluated by linear weighted kappa statistics. The correlation between metastasis and the Node-RADS score of each lymph node was analyzed using multivariate regression analysis. To investigate the diagnostic performance of the Node-RADS score, we further conducted receiver operating characteristic curve analysis. Correspondently, the sensitivity, specificity, positive predictive value, and negative predictive value of each different cutoff (>1, >2, >3, and >4) were computed. Results: In all, 119 patients with NPC were assessed, including 203 cervical lymph nodes consisting of 140 (69%) of 203 metastatic and 63 (31%) of 203 benign. The kappa agreement between the 2 readers for the Node-RADS score was 0.863 (95% CI = 0.830-0.897, P < .001). Node-RADS score on MRI scan was shown to be an independent predictive factor of lymph node metastasis after multivariate regression analysis (odds ratio [OR] = 6.745, 95% CI = 3.964-11.474, P < .001). Node-RADS achieved an area under the curve (AUC) of 0.950 (95% CI = 0.921-0.979) in diagnosing metastatic lymph nodes. When Node-RADS >2 was identified as the best cutoff based on balanced values, the sensitivity and positive predictive value were 0.92 and 0.94, respectively. Conclusions: Our study suggests that the Node-RADS score has high accuracy in predicting NPC cervical lymph node metastasis. Nevertheless, this conclusion requires confirmation in a larger cohort of patients with NPC.

Development and validation of a point-of-care nursing mobile tool to guide the diagnosis of malnutrition in hospitalized adult patients: a multicenter, prospective cohort study.

Malnutrition is a prevalent and severe issue in hospitalized patients with chronic diseases. However, malnutrition screening is often overlooked or inaccurate due to lack of awareness and experience among health care providers. This study aimed to develop and validate a novel digital smartphone-based self-administered tool that uses facial features, especially the ocular area, as indicators of malnutrition in inpatient patients with chronic diseases. Facial photographs and malnutrition screening scales were collected from 619 patients in four different hospitals. A machine learning model based on back propagation neural network was trained, validated, and tested using these data. The model showed a significant correlation (p < 0.05) and a high accuracy (area under the curve 0.834-0.927) in different patient groups. The point-of-care mobile tool can be used to screen malnutrition with good accuracy and accessibility, showing its potential for screening malnutrition in patients with chronic diseases.

Accumulation of TOX high mobility group box family member 3 promotes the oncogenesis and development of hepatocellular carcinoma through the MAPK signaling pathway.

Microvascular invasion (MVI) has been widely valued in the field of liver surgery because MVI positivity indicates poor prognosis in hepatocellular carcinoma (HCC) patients. However, the potential molecular mechanism underlying the poor prognosis of MVI-positive HCC patients is unclear. Therefore, this study focused on identifying the key genes leading to poor prognosis in patients with a high degree of malignancy of HCC by examining the molecular signaling pathways in MVI-positive HCC patients. Through RNA sequencing, TOX high mobility group box family member 3 (TOX3) was demonstrated to be significantly highly expressed in MVI-positive HCC tissues, which was associated with poor prognosis. The results of in vivo and in vitro showed that TOX3 can promote the oncogenesis and development of HCC by targeting key molecules of the MAPK and EMT signaling pathways. The IP-MS results indicated that proteasome degradation of TOX3 in HCC cells is potentially mediated by a tripartite motif containing 56 (TRIM56, an E3 ligase) in HCC cells. Inhibiting TRIM56 enhances TOX3 protein levels. Overall, our study identified TOX3 as a key gene in the MAPK and EMT signaling pathways in HCC, and its overexpression confers significant proliferation and invasiveness to tumor cells.

Artificial Intelligence Applications in the Treatment of Colorectal Cancer: A Narrative Review.

Colorectal cancer is the third most prevalent cancer worldwide, and its treatment has been a demanding clinical problem. Beyond traditional surgical therapy and chemotherapy, newly revealed molecular mechanisms diversify therapeutic approaches for colorectal cancer. However, the selection of personalized treatment among multiple treatment options has become another challenge in the era of precision medicine. Artificial intelligence has recently been increasingly investigated in the treatment of colorectal cancer. This narrative review mainly discusses the applications of artificial intelligence in the treatment of colorectal cancer patients. A comprehensive literature search was conducted in MEDLINE, EMBASE, and Web of Science to identify relevant papers, resulting in 49 articles being included. The results showed that, based on different categories of data, artificial intelligence can predict treatment outcomes and essential guidance information of traditional and novel therapies, thus enabling individualized treatment strategy selection for colorectal cancer patients. Some frequently implemented machine learning algorithms and deep learning frameworks have also been employed for long-term prognosis prediction in patients with colorectal cancer. Overall, artificial intelligence shows encouraging results in treatment strategy selection and prognosis evaluation for colorectal cancer patients.

Efficacy of e-health interventions for smoking cessation management in smokers: a systematic review and meta-analysis.

Background: Smoking is one of the major risk factors for shortened lifespan and disability, while smoking cessation is currently the only guaranteed method to reduce the harm caused by smoking. E-health is a field that utilizes information and communication technology to support the health status of its users. The emergence of this digital health approach has provided a new way of smoking cessation support for smokers seeking help, and an increasing number of researchers are attempting to use e-health for a wide range of effective smoking cessation interventions. We conducted a systematic review and meta-analysis of studies that used e-health as a smoking cessation support tool. Methods: This systematic review and meta-analysis searched the PubMed, Embase, and Cochrane Library databases until December 2022. The included studies were randomized controlled trials (RCTs) comparing the use of e-health interventions and traditional offline smoking cessation care interventions. The primary outcome of the studies was the point smoking cessation rate (7-day and 30-day), and the secondary outcome was sustained smoking cessation rates. Studies were excluded if there was no clear e-health intervention described or if standard-compliant cessation outcomes were not clearly reported. Fixed-effects meta-analysis and meta-regression analyses were performed on the included study data to evaluate the effectiveness of the interventions. The meta-analysis outcome was the risk ratio (RR) and a 95% confidence interval. The study was registered with PROSPERO, CRD42023388667. Findings: We collectively screened 2408 articles, and ultimately included 39 articles with a total of 17,351 eligible participants, of which 44 studies were included in the meta-analysis. The meta-analysis revealed that compared to traditional smoking cessation interventions, e-health interventions can increase point quit rates (RR 1.86, 95% CI 1.69-2.04) as well as sustained quit rates in the long-term (RR 1.79, 95% CI 1.60-2.00) among smokers. Subgroup analysis showed that text and telephone interventions in e-health significantly improved short-term quit rates for up to 7 days (RR 2.10, 95% CI 1.77-2.48). Website and app interventions also had a positive impact on improving short-term quit rates for up to 7 days (RR 1.74, 95% CI 1.56-1.94). The heterogeneity of the study results was low, demonstrating the significant smoking cessation advantages of e-health interventions. Interpretation: We have found that personalized e-health interventions can effectively help smokers quit smoking. The diverse remote intervention methods of e-health can provide more convenient options for further customization. Additionally, further follow-up research is needed to evaluate the sustained effectiveness of interventions on smokers' continuous abstinence over a longer period (greater than one year). In the future, e-health can further optimize smoking cessation strategies. Funding: No funding.

Propranolol inhibits EMT and metastasis in breast cancer through miR-499-5p-mediated Sox6.

PURPOSE: This study will focus on 4T1 cells, a murine mammary adenocarcinoma cell line, as the primary research subject. We aim to investigate the inhibitory effects and mechanisms of propranolol on epithelial-mesenchymal transition (EMT) in breast cancer cells, aiming to elucidate this phenomenon at the miRNA level. METHODS: In this study, the EMT inhibitory effect of propranolol was observed through in vitro and animal experiments. For the screening of potential target miRNAs and downstream target genes, second-generation sequencing (SGS) and bioinformatics analysis were conducted. Following the screening process, the identified target miRNAs and their respective target genes were confirmed using various experimental methods. To confirm the target miRNAs and target genes, Western Blot (WB), reverse transcription polymerase chain reaction (RT-PCR), and immunofluorescence experiments were performed. RESULTS: In this study, we found that propranolol significantly reduced lung metastasis in 4T1 murine breast cancer cells (p < 0.05). In vitro and in vivo experiments demonstrated that propranolol inhibited the epithelial-mesenchymal transition (EMT) as evidenced by Western Blot analysis (p < 0.05). Through next-generation sequencing (SGS), subsequent bioinformatics analysis, and PCR validation, we identified a marked downregulation of miR-499-5p (p < 0.05), suggesting its potential involvement in mediating the suppressive effects of propranolol on EMT. Overexpression of miR-499-5p promoted EMT, migration, and invasion of 4T1 cells, and these effects were not reversed or attenuated by propranolol (Validated via Western Blot, wound healing assay, transwell migration, and invasion assays, p < 0.05). Sox6 was identified as a functional target of miR-499-5p, with its downregulation correlating with the observed EMT changes (p < 0.05). Silencing Sox6 or overexpressing miR-499-5p inhibited Sox6 expression, further promoting the processes of EMT, invasion, and migration in 4T1 cells. Notably, these effects were not alleviated by propranolol (validated via Western Blot, wound healing assay, transwell migration, and invasion assays, p < 0.05). The direct interaction between miR-499-5p and Sox6 mRNA was confirmed by dual-luciferase reporter gene assay. CONCLUSION: These results suggest that propranolol may have potential as a therapeutic agent for breast cancer treatment by targeting EMT and its regulatory mechanisms.

A gene signature predicting prognosis of patients with lower-grade gliomas receiving temozolomide therapy.

Temozolomide (TMZ) has been used as a first-line therapy against lower-grade gliomas (LGGs) combined with other chemotherapy drugs. However, there has been no reliable index predicting TMZ response of patients with LGGs. In this study, we aim to investigate the relationship between gene expressions and the prognosis of TMZ therapy in LGGs. We integrated transcriptome and clinical data of 171 LGGs from the Chinese Glioma Genome Atlas (CGGA). Consensus LASSO Cox regression was used to identify 14 key genes related to different clinical outcomes under TMZ chemotherapy. We constructed and evaluated a risk score based on the 14 genes. Patients with LGGs of lower risk scores (low-risk group) generally had better survival than those LGGs of higher risk scores (high-risk group), which is independent of clinicopathological factors. High-risk patients showed activation of innate and humoral-type immunity. The prognostic contribution of the risk score was validated in an independent validation cohort of 65 patients. Besides, combined with three independent predictors (grade, IDH1 mutation status, and chr1p19q co-deletion status), we further developed a nomogram to predict the benefit of TMZ treatment in LGGs. Our results indicate that a transcriptome-based index can optimize the treatment strategy for patients with LGGs under TMZ therapy.

LMP2-mRNA lipid nanoparticle sensitizes EBV-related tumors to anti-PD-1 therapy by reversing T cell exhaustion.

BACKGROUND: Targeting EBV-proteins with mRNA vaccines is a promising way to treat EBV-related tumors like nasopharyngeal carcinoma (NPC). We assume that it may sensitize tumors to immune checkpoint inhibitors. RESULTS: We developed an LMP2-mRNA lipid nanoparticle (C2@mLMP2) that can be delivered to tumor-draining lymph nodes. C2@mLMP2 exhibited high transfection efficiency and lysosomal escape ability and induced an increased proportion of CD8 + central memory T cells and CD8 + effective memory T cells in the spleen of the mice model. A strong synergistic anti-tumor effect of C2@mLMP2 in combination with αPD-1 was observed in tumor-bearing mice. The mechanism was identified to be associated with a reverse of CD8 + T cell exhaustion in the tumor microenvironment. The pathological analysis further proved the safety of the vaccine and the combined therapy. CONCLUSIONS: This is the first study proving the synergistic effect of the EBV-mRNA vaccine and PD-1 inhibitors for EBV-related tumors. This study provides theoretical evidence for further clinical trials that may expand the application scenario and efficacy of immunotherapy in NPC.

Protocol for identifying immune checkpoint on circulating tumor cells of human pancreatic ductal adenocarcinoma by single-cell RNA sequencing.

Circulating tumor cells (CTCs) are regarded as the "seeds" of tumor metastasis. Identifying immune checkpoints on CTCs is essential for establishing efficient immunotherapies to prevent tumor metastasis. Here, we present a protocol for isolating CTCs and obtaining single-cell suspensions from pancreatic ductal adenocarcinoma liver metastatic patients. We describe steps for biospecimen acquisition, CTC isolation, and tissue dissociation. We then detail procedures for performing single-cell RNA-seq, annotating cell types, and identifying immune checkpoints on CTCs. For complete details on the use and execution of this protocol, please refer to Liu et al. (2023).1.

Integrative models of histopathological images and multi-omics data predict prognosis in endometrial carcinoma.

Objective: This study aimed to predict the molecular features of endometrial carcinoma (EC) and the overall survival (OS) of EC patients using histopathological imaging. Methods: The patients from The Cancer Genome Atlas (TCGA) were separated into the training set (n = 215) and test set (n = 214) in proportion of 1:1. By analyzing quantitative histological image features and setting up random forest model verified by cross-validation, we constructed prognostic models for OS. The model performance is evaluated with the time-dependent receiver operating characteristics (AUC) over the test set. Results: Prognostic models based on histopathological imaging features (HIF) predicted OS in the test set (5-year AUC = 0.803). The performance of combining histopathology and omics transcends that of genomics, transcriptomics, or proteomics alone. Additionally, multi-dimensional omics data, including HIF, genomics, transcriptomics, and proteomics, attained the largest AUCs of 0.866, 0.869, and 0.856 at years 1, 3, and 5, respectively, showcasing the highest discrepancy in survival (HR = 18.347, 95% CI [11.09-25.65], p < 0.001). Conclusions: The results of this experiment indicated that the complementary features of HIF could improve the prognostic performance of EC patients. Moreover, the integration of HIF and multi-dimensional omics data might ameliorate survival prediction and risk stratification in clinical practice.

High-intensity interval training in breast cancer patients: A systematic review and meta-analysis.

BACKGROUND: Women with breast cancer and improved survival often experience treatment-related impairments. High-intensity interval training (HIIT) has emerged as a promising exercise therapy modality for adult cancer patients. However, the overall effects of HIIT in breast cancer patients remain scarce and controversial. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the impact of HIIT on health-related outcomes in breast cancer patients. METHODS: We searched the PubMed, Embase, and Web of Science from inception to November 7, 2022. Eligible studies included randomized controlled trials that compared HIIT interventions with usual care (UC) or MICT in breast cancer patients. The primary outcome assessed was physical fitness, and exploratory outcomes included body composition, blood-borne biomarkers, and patient-reported outcomes. Summary data were extracted, and standardized mean differences (SMD) were calculated for meta-analysis. For outcomes that could not be pooled, a systematic review was conducted. RESULTS: Our analysis included 19 articles from 10 studies, encompassing 532 participants who met the inclusion criteria. Pooled results demonstrated that HIIT was superior to UC in improving peak oxygen uptake (VO2peak ). The SMD for VO2peak (L/min) and VO2peak (mL/kg/min) was 0.79 (95% CI 0.13, 1.45) and 0.59 (95% CI 0.01, 1.16), respectively. No significant differences in VO2peak were found between the HIIT and MICT groups. Meta-analyses on body composition and blood-borne biomarkers showed no significant differences between HIIT and UC. Systematic review indicated favorable effects of HIIT on muscle strength, fatigue, and emotional well-being. CONCLUSIONS: HIIT is a time-efficient alternative to MICT for improving VO2peak and may also enhance muscle strength and alleviate fatigue and emotional symptoms in breast cancer patients. HIIT should be considered as an important component of exercise prescription in breast cancer care. Further studies with larger cohorts are needed to determine the clinical significance of HIIT-induced changes in terms of other outcomes in women with breast cancer.

The association of living alone and social isolation with sarcopenia: A systematic review and meta-analysis.

BACKGROUND: Living alone can cause social isolation and is correlated with multiple adverse health outcomes. Evidence about the association of living alone and social isolation with sarcopenia is limited. This meta-analysis aims to investigate the correlation between living alone, social isolation, and sarcopenia. METHODS: According to the PRISMA guidelines, we systematically searched Medline, Embase, Web of Science, and Scopus for literature published up to June 30, 2023. We conducted reference checking to supplement the references. Two investigators independently screened the references for eligibility and assessed the quality of the references. We included references involving data on living alone, social isolation, and sarcopenia. Two investigators recorded study data for meta-analysis and study characteristics. RESULTS: Data regarding living alone and sarcopenia were available from 13 studies. Meta-analysis demonstrated that living alone is correlated with sarcopenia (odds ratio, 1.51; 95 % CI, 1.31-1.75; p < 0.001). The gender-stratified analysis demonstrated that women living alone are more likely to have sarcopenia (odds ratio, 1.81; 95 % CI, 1.32-2.48; p < 0.001) but not men (odds ratio, 1.24; 95 % CI, 0.56-2.74; p = 0.60). Data regarding social isolation and sarcopenia were available from five studies. Social isolation is also associated with sarcopenia (odds ratio, 1.70; 95 % CI, 1.51-1.92; p < 0.001). And subgroup analysis demonstrated that social isolation is a risk factor for sarcopenia (odds ratio, 1.79; 95 % CI, 1.55-2.06; p < 0.001). CONCLUSIONS: This meta-analysis revealed the association of living alone and social isolation with sarcopenia. Gender differences can help to screen high-risk groups of sarcopenia and reduce healthcare expenditures. As a further development of living alone, social isolation may play a more important role in sarcopenia than living alone.

Targeting lymph node delivery with nanovaccines for cancer immunotherapy: recent advances and future directions.

Although cancer immunotherapy is a compelling approach against cancer, its effectiveness is hindered by the challenge of generating a robust and durable immune response against metastatic cancer cells. Nanovaccines, specifically engineered to transport cancer antigens and immune-stimulating agents to the lymph nodes, hold promise in overcoming these limitations and eliciting a potent and sustained immune response against metastatic cancer cells. This manuscript provides an in-depth exploration of the lymphatic system's background, emphasizing its role in immune surveillance and tumor metastasis. Furthermore, it delves into the design principles of nanovaccines and their unique capability to target lymph node metastasis. The primary objective of this review is to provide a comprehensive overview of the current advancements in nanovaccine design for targeting lymph node metastasis, while also discussing their potential to enhance cancer immunotherapy. By summarizing the state-of-the-art in nanovaccine development, this review aims to shed light on the promising prospects of harnessing nanotechnology to potentiate cancer immunotherapy and ultimately improve patient outcomes.

Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection.

The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants. In Chengdu, China, an infection wave was predominantly induced by the BA.5 subvariant. It is crucial to determine whether the hybrid anti-SARS-CoV-2 immunity following BA.5 infection, coupled with a variety of immune background, is sufficient to shape the immune responses against newly emerged Omicron subvariants, especially for XBB lineages. To investigate this, we collected serum and nasal swab samples from 108 participants who had been infected in this BA.5 infection wave, and evaluated the neutralization against pseudoviruses. Our results showed that convalescent sera from individuals, regardless of vaccination history, had remarkably compromised neutralization capacities against the newly emerged XBB and XBB.1.5 subvariants. Although post-vaccination with BA.5 breakthrough infection slightly elevated plasma neutralizing antibodies against a part of pseudoviruses, the neutralization activities were remarkably impaired by XBB lineages. Furthermore, we analyzed the impacts of the number of vaccinations, age, and sex on the humoral and cellular immune response after BA.5 infection. Our findings suggest that the neutralization against XBB lineages that elicited by current hybrid immunity after BA.5 infection, are remained at low levels, indicating an urgent need for the development of next-generation of COVID-19 vaccines that designed based on the XBB sub-lineages and other future variants.