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Abstract Introduction Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are critical components of the extracellular matrix (ECM) in colorectal cancer (CRC). We aimed to evaluate the prognostic value of MMP-2 and MMP-9 in patients with CRC. Methods We performed a meta-analysis of cohort studies with available data on the effect of MMP-2 and MMP-9 expression on both disease-free survival (DFS) and overall survival (OS) by the risk ratios (RRs) with their 95% confidence intervals (CIs). Studies were subgrouped based on the different tissue types, including cancer tissue and normal tissue, and the subgroup effect of MMP expression in different tissues was analyzed through meta-regression. To ensure the quality and reduce the risk of bias, the Newcastle‒Ottawa Scale (NOS) was used to assess the included studies. A sensitivity analysis was randomly performed to assess the potential impact of each study on our results. Results Eighteen trials were selected (Table 1) and included a total of 3944 patients. According to our primary meta-analysis, the expression of MMP-2 was significantly associated with a decrease in OS (RR = 1.75, 95% CI = 1.34 to 2.29, P

Abstract Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition of this condition is still not well understood. To fill this gap, we analyzed 75,641 cells from cardiac myxoma tissues based on single-cell sequencing. We defined a population of myxoma cells, which exhibited a resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, and adhesion. The clinical relevance of the cell populations indicated a higher proportion of myxoma cells and M2-like macrophage infiltration, along with their enhanced spatial interaction, were found to significantly contribute to the occurrence of embolism. The immune cells surrounding the myxoma exhibit inhibitory characteristics, with impaired function of T cells characterized by the expression of GZMK and TOX, along with a substantial infiltration of tumor-promoting macrophages expressed growth factors such as PDGFC. Furthermore, in vitro co-culture experiments showed that macrophages promoted the growth of myxoma cells significantly. In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.

Abstract Colorectal carcinoma (CRC) stands as a pressing global health issue, marked by the unbridled proliferation of immature cells influenced by multifaceted internal and external factors. Numerous studies have explored the intricate mechanisms of tumorigenesis in CRC, with a primary emphasis on signaling pathways, particularly those associated with growth factors and chemokines. However, the sheer diversity of molecular targets introduces complexity into the selection of targeted therapies, posing a significant challenge in achieving treatment precision. The quest for an effective CRC treatment is further complicated by the absence of pathological insights into the mutations or alterations occurring in tumor cells. This study reveals the transfer of signaling from the cell membrane to the nucleus, unveiling recent advancements in this crucial cellular process. By shedding light on this novel dimension, the research enhances our understanding of the molecular intricacies underlying CRC, providing a potential avenue for breakthroughs in targeted therapeutic strategies. In addition, the study comprehensively outlines the potential immune responses incited by the aberrant activation of signaling pathways, with a specific focus on immune cells, cytokines, and their collective impact on the dynamic landscape of drug development. This research not only contributes significantly to advancing CRC treatment and molecular medicine but also lays the groundwork for future breakthroughs and clinical trials, fostering optimism for improved outcomes and refined approaches in combating colorectal carcinoma.

Abstract 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.

Abstract The rising psychological issues among cancer patients call for timely treatment. Psychological issues such as anxiety, depression, and distress are particularly common among cancer patients and have a significant impact on their treatment and prognostic outcomes. Distraction has been proven to mitigate mental disorders as a strategy of intervention. Digital tools like social short video platforms offer cost‐effective mental healthcare potential, but there is a lack of longitudinal studies demonstrating their intervention effectiveness. This study aimed to assess the impact of social short video platforms on the psychological well‐being of cancer patients, focusing on anxiety, depression, and distress. We studied 455 digestive system cancer patients using mixed methods. The effect on psychological symptoms was evaluated via cross‐sectional analysis of 392 patients and pre‐post intervention analysis of 63 patients, employing the Hospital Anxiety and Depression Scale and Distress Thermometer. The findings showed lower anxiety, depression, and distress scores among regular users of social short video platforms. The intervention led to reduced anxiety and depression scores. As a prevalent app of social short video platforms, these platforms might be a safe and convenient nonpharmacological assisted tool for enhancing mental health care during cancer treatment.

Abstract The rapid progress in cancer treatment, along with the increase in cure and control rates, has led to the gradual acceptance of cancer as a chronic disease. Cancer treatment is comprehensive and long‐term. However, cancer symptoms and treatment side effects can hinder patients' quality of life and adherence to treatment, ultimately impacrefting their long‐term survival. Acupuncture (AC) and electro‐acupuncture (EA) have been widely used to treat various diseases. AC and EA have demonstrated their ability to relieve symptoms and side effects related to cancer treatment. The review provides a brief overview of the historical lineage and basic principles of AC treatment, as well as a detailed exploration of the mechanisms and clinical applications of AC and EA to relieve cancer symptoms and treatment side effects. AC and EA can play a therapeutic role by regulating systems of nervous, endocrine, immune and so on. Clinical studies have demonstrated that AC and EA can effectively relieve pain, postoperative ileus, and other symptoms. The safety of AC and EA has been tested worldwide. Furthermore, we discuss the challenges and future research directions for AC and EA in the field of cancer treatment.

BackgroundAlthough prognostic models based on pyroptosis-related genes (PRGs) have been constructed in bladder cancer (BLCA), the comprehensive impact of these genes on tumor microenvironment (TME) and immunotherapeutic response has yet to be investigated.MethodsBased on expression profiles of 52 PRGs, we utilized the unsupervised clustering algorithm to identify PRGs subtypes and ssGSEA to quantify immune cells and hallmark pathways. Moreover, we screened feature genes of distinct PRGs subtypes and validated the associations with immune infiltrations in tissue using the multiplex immunofluorescence. Univariate, LASSO, and multivariate Cox regression analyses were employed to construct the scoring scheme.ResultsFour PRGs clusters were identified, samples in cluster C1 were infiltrated with more immune cells than those in others, implying a favorable response to immunotherapy. While the cluster C2, which shows an extremely low level of most immune cells, do not respond to immunotherapy. CXCL9/CXCL10 and SPINK1/DHSR2 were identified as feature genes of cluster C1 and C2, and the specimen with high CXCL9/CXCL10 was characterized by more CD8 + T cells, macrophages and less Tregs. Based on differentially expressed genes (DEGs) among PRGs subtypes, a predictive model (termed as PRGs score) including five genes (CACNA1D, PTK2B, APOL6, CDK6, ANXA2) was built. Survival probability of patients with low-PRGs score was significantly higher than those with high-PRGs score. Moreover, patients with low-PRGs score were more likely to benefit from anti-PD1/PD-L1 regimens.ConclusionPRGs are closely associated with TME and oncogenic pathways. PRGs score is a promising indicator for predicting clinical outcome and immunotherapy response.

Abstract 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

Abstract 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.

Abstract 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.

Abstract 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.

Abstract 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. Graphical Abstract

Abstract 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.

Abstract 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.

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 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.

Summary: 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.

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.

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as “eat me” signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

Field manual labor behavior recognition is an important task that applies deep learning algorithms to industrial equipment for capturing and analyzing people’s behavior during field labor. In this study, we propose a field manual labor behavior recognition network based on an enhanced SlowFast architecture. The main work includes the following aspects: first, we constructed a field manual labor behavior dataset containing 433,500 fast-track frames and 8670 key frames based on the captured video data, and labeled it in detail; this includes 9832 labeled frames. This dataset provides a solid foundation for subsequent studies. Second, we improved the slow branch of the SlowFast network by introducing the combined CA (Channel Attention) attention module. Third, we enhanced the fast branch of the SlowFast network by introducing the ACTION hybrid attention module. The experimental results show that the recognition accuracy of the improved SlowFast network model with the integration of the two attention modules increases by 7.08%. This implies that the improved network model can more accurately locate and identify manual labor behavior in the field, providing a more effective method for problem solving.

Summary: 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 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Head and neck cancer (HNC) is malignant, genetically complex and difficult to treat and is the sixth most frequent cancer, with tobacco, alcohol and human papillomavirus being major risk factors. Based on epigenetic data, HNC is remarkably heterogeneous, and treatment remains challenging. There is a lack of significant improvement in survival and quality of life in patients with HNC. Over half of HNC patients experience locoregional recurrence or distal metastasis despite the current multiple traditional therapeutic strategies and immunotherapy. In addition, resistance to chemotherapy, radiotherapy and some targeted therapies is common. Therefore, it is urgent to explore more effective and tolerable targeted therapies to improve the clinical outcomes of HNC patients. Recent targeted therapy studies have focused on identifying promising biomarkers and developing more effective targeted therapies. A well understanding of the pathogenesis of HNC contributes to learning more about its inner association, which provides novel insight into the development of small molecule inhibitors. In this review, we summarized the vital signaling pathways and discussed the current potential therapeutic targets against critical molecules in HNC, as well as presenting preclinical animal models and ongoing or completed clinical studies about targeted therapy, which may contribute to a more favorable prognosis of HNC. Targeted therapy in combination with other therapies and its limitations were also discussed.

Nanoprobes that offer both fluorescence imaging (FI) and magnetic resonance imaging (MRI) can provide supplementary information and hold synergistic advantages. However, synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups, high stability, great biocompatibility and desired dual-modality imaging results remains challenging. In this study, we used an amphiphilic block polymer from (ethylene glycol) methyl ether methacrylate (OEGMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) derivatives as a carrier to conjugate a MR contrast agent, Gd-DOTA, and a two-photon fluorophore with an aggregation-induced emission (AIE) effect, TPBP, to construct a MR/two-photon fluorescence dual-modality contrast agent, Gd-DOTA-TPBP. Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r1 value for Gd-DOTA-TPBP, revealing a great MR imaging resolution. The contrast agent specifically accumulated in the tumor region, allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging. Meanwhile, coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity, but also significantly enhanced its imaging performance in an aqueous phase. Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI. Since high-resolution, complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP, it has great potential in the early phase of disease diagnosis.

Abstract Notch and Hedgehog signaling are involved in cancer biology and pathology, including the maintenance of tumor cell proliferation, cancer stem-like cells, and the tumor microenvironment. Given the complexity of Notch signaling in tumors, its role as both a tumor promoter and suppressor, and the crosstalk between pathways, the goal of developing clinically safe, effective, tumor-specific Notch-targeted drugs has remained intractable. Drugs developed against the Hedgehog signaling pathway have affirmed definitive therapeutic effects in basal cell carcinoma; however, in some contexts, the challenges of tumor resistance and recurrence leap to the forefront. The efficacy is very limited for other tumor types. In recent years, we have witnessed an exponential increase in the investigation and recognition of the critical roles of the Notch and Hedgehog signaling pathways in cancers, and the crosstalk between these pathways has vast space and value to explore. A series of clinical trials targeting signaling have been launched continually. In this review, we introduce current advances in the understanding of Notch and Hedgehog signaling and the crosstalk between pathways in specific tumor cell populations and microenvironments. Moreover, we also discuss the potential of targeting Notch and Hedgehog for cancer therapy, intending to promote the leap from bench to bedside.

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.

Abstract Purpose This study aimed to explore the efficiency and safety of the new generation antibody-drug conjugate Trastuzumab deruxtecan (DS-8201a) in treating HER2-positive solid cancers. Method By searching PubMed, Medline and Ovid for all clinical trials related to the safety and efficacy of DS-8201a. Event rates were calculated for all adverse events (AEs) to evaluate the safety of DS-8201a. Objective response rate (ORR) and progression-free survival (PFS) were summarized to assess the potency of DS-8201a. Result The AEs with event rates greater than 30% regardless of grades were nausea, decreased appetite, vomiting, fatigue, anemia, decreased neutrophil count, alopecia and diarrhea. In the grade 3 or more, decreased neutrophil count, anemia and decreased white blood cell count were the only three AEs with event rates greater than 10% (20.3, 15.0 and 10.3%). The median PFS of patients with breast cancer, gastric cancer and other HER2-positive solid cancers were 9.0-22.1, 3.0-8.3 and 4.1-11.9 months. The median ORR was 37-79.9% in patients with breast and gastric cancer and 28.3-55% in patients with other HER2-positive cancers. Conclusion DS-8201a plays an active role in treating HER2-positive cancers, especially breast and gastric cancer, which have HER2 amplification. The most common AEs of DS-8201a were related to gastrointestinal and hematological system. Decreased white blood cell count and appetite were the AEs occurred with high grades.

Abstract Cancer cells characterized by uncontrolled growth and proliferation require altered metabolic processes to maintain this characteristic. Metabolic reprogramming is a process mediated by various factors, including oncogenes, tumor suppressor genes, changes in growth factors, and tumor–host cell interactions, which help to meet the needs of cancer cell anabolism and promote tumor development. Metabolic reprogramming in tumor cells is dynamically variable, depending on the tumor type and microenvironment, and reprogramming involves multiple metabolic pathways. These metabolic pathways have complex mechanisms and involve the coordination of various signaling molecules, proteins, and enzymes, which increases the resistance of tumor cells to traditional antitumor therapies. With the development of cancer therapies, metabolic reprogramming has been recognized as a new therapeutic target for metabolic changes in tumor cells. Therefore, understanding how multiple metabolic pathways in cancer cells change can provide a reference for the development of new therapies for tumor treatment. Here, we systemically reviewed the metabolic changes and their alteration factors, together with the current tumor regulation treatments and other possible treatments that are still under investigation. Continuous efforts are needed to further explore the mechanism of cancer metabolism reprogramming and corresponding metabolic treatments.

Abstract Background Deep learning methods have great potential to predict tumor characterization, such as histological diagnosis and genetic aberration. The objective of this study was to evaluate and validate the predictive performance of multimodality imaging-derived models using computer-aided diagnostic (CAD) methods for prediction of MDM2 gene amplification to identify well-differentiated liposarcoma (WDLPS) and lipoma. Materials and methods All 127 patients from two institutions were included with 89 patients in one institution for model training and 38 patients in the other institution for external validation between January 2012 and December 2018. For each modality, handcrafted radiomics analysis with manual segmentation was applied to extract 851 features for each modality, and six pretrained convolutional neural networks (CNNs) extracted 512–2048 deep learning features automatically. Extracted imaging-based features were selected via univariate filter selection methods and the recursive feature elimination algorithm, which were then classified by support vector machine for model construction. Integrated with two significant clinical variables, age and LDH level, a clinical-radiological model was constructed for identification WDLPS and lipoma. All differentiation models were evaluated using the area under the receiver operating characteristics curve (AUC) and their 95% confidence interval (CI). Results The multimodality model on deep learning features extracted from ResNet50 algorithm (RN-DL model) performed great differentiation performance with an AUC of 0.995 (95% CI 0.987–1.000) for the training cohort, and an AUC of 0.950 (95% CI 0.886–1.000), accuracy of 92.11%, sensitivity of 95.00% (95% CI 73.06–99.74%), specificity of 88.89% (95% CI 63.93–98.05%) in external validation. The integrated clinical-radiological model represented an AUC of 0.996 (95% CI 0.989–1.000) for the training cohort, and an AUC of 0.942 (95% CI 0.867–1.000), accuracy of 86.84%, sensitivity of 95.00% (95% CI 73.06–99.74%), and specificity of 77.78% (95% CI 51.92–92.63%) in external validation. Conclusions Imaging-based multimodality models represent effective discrimination abilities between WDLPS and lipoma via CAD methods, and might be a practicable approach in assistance of treatment decision.

Abstract Triple negative breast cancer (TNBC) is a subtype of breast cancer, with estrogen receptor, human epidermal growth factor receptor 2 and progesterone receptor negative. TNBC is characterized by high heterogeneity, high rates of metastasis, poor prognosis, and lack of therapeutic targets. Now the treatment of TNBC is still based on surgery and chemotherapy, which is effective only in initial stage but almost useless in advanced stage. And due to the lack of hormone target, hormonal therapies have little beneficial effects. In recent years, signaling pathways and receptor-specific targets have been reported to be effective in TNBC patients under specific clinical conditions. Now targeted therapies have been approved for many other cancers and even other subtypes of breast cancer, but treatment options for TNBC are still limited. Most of TNBC patients showed no response, which may be related to the heterogeneity of TNBC, therefore more effective treatments and predictive biomarkers are needed. In the present review, we summarize potential treatment opinions for TNBC based on the dysregulated receptors and signaling pathways, which play a significant role in multiple stages of TNBC development. We also focus on the application of immunotherapy in TNBC, and summarize the preclinical and clinical trials of therapy for patients with TNBC. We hope to accelerate the research and development of new drugs for TNBC by understanding the relevant mechanisms, and to improve survival.

Abstract The adenoma-carcinoma sequence is a well-accepted roadmap for the development of sporadic colorectal cancer. However, cellular heterogeneity in aberrant epithelial cells limits our understanding of carcinogenesis in colorectal tissues. Here, we performed a single-cell RNA sequencing survey of 54,788 cells from patient-matched tissue samples, including blood, normal tissue, para-cancer, polyp, and colorectal cancer. At each stage of carcinogenesis, we characterized cell types, transcriptional signatures, and differentially expressed genes of distinct cell populations. The molecular signatures of epithelial cells at normal, benign, and malignant stages were defined at the single-cell scale. Adenoma and carcinoma precursor cell populations were identified and characterized followed by validation with large cohort biopsies. Protein tyrosine kinases (PTKs) BMX and HCK were identified as potential drivers of adenoma initiation. Specific BMX and HCK upregulations were observed in adenoma precursor cell populations from normal and adenoma biopsies. Overexpression of BMX and HCK significantly promoted colorectal epithelial cell proliferation. Importantly, in the organoid culture system, BMX and HCK upregulations resulted in the formation of multilayered polyp-like buds protruding towards the organoid lumen, mimicking the pathological polyp morphology often observed in colorectal cancer. Molecular mechanism analysis revealed that upregulation of BMX or HCK activated the JAK-STAT pathway. In conclusion, our work improved the current knowledge regarding colorectal epithelial evolution during carcinogenesis at the single-cell resolution. These findings may lead to improvements in colorectal cancer diagnosis and treatment.

ObjectiveThis review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors.MethodsPubMed, Embase, and ClinicalTrials.gov were searched until 10 February 2022. The safety outcome as adverse events and efficacy outcomes, including objective response rate, stable disease rates, and progressive disease rates, were selected and analyzed by comprehensive meta-analysis version 3.0 and STATA 15.0.ResultsThe most common all-grade adverse events were hyperphosphatemia, dry mouth, stomatitis, diarrhea, and dysgeusia. The occurrence of ≥3 adverse events was relatively low, and stomatitis and hyponatremia were the most common. Moreover, eye disorders could not be ignored. Efficacy in urothelial carcinoma patients was obviously better than in other solid tumor patients, with a higher objective response rate (0.38 versus 0.10) and lower progressive disease rate (0.26 versus 0.68). All responses occurred in patients with fibroblast growth factor receptor (FGFR) alteration. In those patients, a specific FGFR alteration (FGFR3-TACC3) was observed to have a maximum response.ConclusionErdafitinib has satisfactory clinical activity for metastatic urothelial carcinoma and other solid tumors, while the toxicity is acceptable. With more RCTs and combination therapy trials published, erdafitinib will be applied widely.

Abstract Background There is no unified treatment standard for patients with extranodal NK/T-cell lymphoma (ENKTL). Cancer neoantigens are the result of somatic mutations and cancer-specific. Increased number of somatic mutations are associated with anti-cancer effects. Screening out ENKTL-specific neoantigens on the surface of cancer cells relies on the understanding of ENKTL mutation patterns. Hence, it is imperative to identify ENKTL-specific genes for ENKTL diagnosis, the discovery of tumor-specific neoantigens and the development of novel therapeutic strategies. We investigated the gene signatures of ENKTL patients. Methods We collected the peripheral blood of a pair of twins for sequencing to identify unique variant genes. One of the twins is diagnosed with ENKTL. Seventy samples were analyzed by Robust Multi-array Analysis (RMA). Two methods (elastic net and Support Vector Machine-Recursive Feature Elimination) were used to select unique genes. Next, we performed functional enrichment analysis and pathway enrichment analysis. Then, we conducted single-sample gene set enrichment analysis of immune infiltration and validated the expression of the screened markers with limma packages. Results We screened out 126 unique variant genes. Among them, 11 unique genes were selected by the combination of elastic net and Support Vector Machine-Recursive Feature Elimination. Subsequently, GO and KEGG analysis indicated the biological function of identified unique genes. GSEA indicated five immunity-related pathways with high signature scores. In patients with ENKTL and the group with high signature scores, a proportion of functional immune cells are all of great infiltration. We finally found that CDC27, ZNF141, FCGR2C and NES were four significantly differential genes in ENKTL patients. ZNF141, FCGR2C and NES were upregulated in patients with ENKTL, while CDC27 was significantly downregulated. Conclusion We identified four ENKTL markers (ZNF141, FCGR2C, NES and CDC27) in patients with extranodal NK/T-cell lymphoma.

Fermented food has been demonstrated to increase immunity, protect against pathogens, and improve cancer survival. However, the relationship between fermented vegetables and immunotherapy has not been tested. We conducted a randomized controlled trial. The experimental group (n = 36) was supplemented with fermented vegetable enzyme every day for 2 cycles of immunotherapy, while the control group (n = 36) received a normal diet. The treatment response, nutritional and immunological indexes were collected at baseline and after 2 cycles of therapy. After comparing the baseline and the follow-up CT, no significant difference was found between the two groups. The hemoglobin, FT4, AST, albumin, LDL-C, and IgG indexes were better in the experimental group, meaning the side effects of immunotherapy in esophageal cancer patients. Fermented foods can alleviate the side effects of esophageal cancer immunotherapy combined with chemotherapy to a certain extent, such as anemia, malnutrition, and elevated AST.

Human papillomaviruses (HPVs) have been recognized as the etiologic agents of various cancers and are called HPV-driven cancers. Concerning HPV-mediated carcinogenic action, gene therapy can cure cancer at the molecular level by means of the correction of specific genes or sites. CRISPR-Cas9, as a novel genetic editing technique, can correct errors in the genome and change the gene expression and function in cells efficiently, quickly, and with relative ease. Herein, we overviewed studies of CRISPR-mediated gene remedies for HPV-driven cancers and summarized the potential applications of CRISPR-Cas9 in gene therapy for cancer.

Abstract Background Emerging evidence provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), and rare anti‐PF therapeutic method has promising effect in its treatment. Rho‐associated coiled‐coil kinases (ROCK) inhibition significantly ameliorates bleomycin‐induced PF and decreases macrophage infiltration, but the mechanism remains unclear. We established bleomycin and radiation‐induced PF to identify the activity of WXWH0265, a newly designed unselective ROCK inhibitor in regulating macrophages. Methods Bleomycin‐induced PF was induced by intratracheal instillation and radiation‐induced PF was induced by bilateral thoracic irradiation. Histopathological techniques (haematoxylin and eosin, Masson's trichrome and immunohistochemistry) and hydroxyproline were used to evaluate PF severity. Western blot, quantitative real‐time reverse transcription‐polymerase chain reaction and flow cytometry were performed to explore the underlying mechanisms. Bone marrow‐derived macrophages (BMDMs) were used to verify their therapeutic effect. Clodronate liposomes were applied to deplete macrophages and to identify the therapeutic effect of WXWH0265. Results Therapeutic administration of ROCK inhibitor ameliorates bleomycin‐induced PF by inhibiting M2 macrophages polarisation. ROCK inhibitor showed no significant anti‐fibrotic effect in macrophages‐depleted mice. Treatment with WXWH0265 demonstrated superior protection effect in bleomycin‐induced PF compared with positive drugs. In radiation‐induced PF, ROCK inhibitor effectively ameliorated PF. Fibroblasts co‐cultured with supernatant from various M2 macrophages phenotypes revealed that M2 macrophages stimulated by interleukin‐4 promoted extracellular matrix production. Polarisation of M2 macrophages was inhibited by ROCK inhibitor treatment in vitro. The p‐signal transducer and activator of transcription 3 (STAT3) in lung tissue and BMDMs was significantly decreased in PF in vivo and vitro after treated with ROCK inhibitors. Conclusion Inhibiting ROCK could significantly attenuate bleomycin‐ and radiation‐induced PF by regulating the macrophages polarisation via phosphorylation of STAT3. WXWH0265 is a kind of efficient unselective ROCK inhibitor in ameliorating PF. Furthermore, the results provide empirical evidence that ROCK inhibitor, WXWH0265 is a potential drug to prevent the development of PF.

Epithelial ovarian cancer (EOC) ranks as the second most common cause of gynecologic cancer death. The conventional treatment for patients with EOC is postoperative therapy along with platinum chemotherapy. However, a more efficient treatment regimen is of great need for these patients diagnosed with advanced disease (FIGO stages III–IV), whose survival is approximately 29%. Immunotherapy seems to be an encouraging therapeutic strategy for EOC. Given the crucial role in the complicated interactions between tumor cells and other cells, the tumor microenvironment (TME) influences the response to immunotherapy. In this review, we discuss feasible strategies for EOC immunotherapy by exploiting the reciprocity of cancer cells and the constituents of the TME.

Metastasis is responsible for 90% of deaths in cancer patients. Most patients diagnosed with metastatic cancer will die within 5 years. PA is good for health and has become an emerging adjuvant therapy for cancer survivors. Regular moderate exercise substantially lowers the incidence and recurrence of several cancers, alleviates cancer-related adverse events, enhances the efficacy of anti-cancer treatments, and improves the quality of life of cancer patients. Revealing the mechanisms of PA inhibiting tumor metastasis could upgrade our understanding of cancer biology and help researchers explore new therapeutic strategies to improve survival in cancer patients. However, it remains poorly understood how physical activity prevents metastasis by modulating tumor behavior. The immune system is involved in each step of tumor metastasis. From invasion to colonization, immune cells interact with tumor cells to secret cytokines and proteases to remodel the tumor microenvironment. Substantial studies demonstrated the ability of physical activity to induce antitumor effects of immune cells. This provides the possibility that physical activity can modulate immune cells behavior to attenuate tumor metastasis. The purpose of this review is to discuss and summarize the critical link between immune function and exercise in metastasis prevention.

Ovarian cancer is currently one of the most common malignant tumors in females with poor survival rates around the world, killing about 200,000 women each year. Although great progress has been made in treatment, most patients receiving first-line therapy experience tumor recurrence. The tumor microenvironment plays an important role in regulating the progression and prognosis of ovarian cancer. Cancer-associated mesothelial cells are the main cell population in the tumor microenvironment, which affect the progression, prognosis and chemical resistance of ovarian cancer. Cancer-associated mesothelial cells can also interact with other microenvironmental components, such as exosomes, macrophages, and adipocytes. Some studies have developed drugs targeting cancer-associated mesothelial cells in ovarian cancer to evaluate the therapeutic efficiency. In this review we highlighted the key role of cancer-associated mesothelial cells in the progression and prognosis of ovarian cancer. We also described the progress of cancer-associated mesothelial cells targeted therapy for ovarian cancer. Continued insight into the role of cancer-associated mesothelial cells in ovarian cancer will potentially contribute to the development of new and effective therapeutic regiments.

Abstract The 2019 coronavirus disease (COVID‐19) pandemic has become a global crisis. In the immunopathogenesis of COVID‐19, SARS‐CoV‐2 infection induces an excessive inflammatory response in patients, causing an inflammatory cytokine storm in severe cases. Cytokine storm leads to acute respiratory distress syndrome, pulmonary and other multiorgan failure, which is an important cause of COVID‐19 progression and even death. Among them, activation of inflammatory pathways is a major factor in generating cytokine storms and causing dysregulated immune responses, which is closely related to the severity of viral infection. Therefore, elucidation of the inflammatory signaling pathway of SARS‐CoV‐2 is important in providing otential therapeutic targets and treatment strategies against COVID‐19. Here, we discuss the major inflammatory pathways in the pathogenesis of COVID‐19, including induction, function, and downstream signaling, as well as existing and potential interventions targeting these cytokines or related signaling pathways. We believe that a comprehensive understanding of the regulatory pathways of COVID‐19 immune dysregulation and inflammation will help develop better clinical therapy strategies to effectively control inflammatory diseases, such as COVID‐19.

Abstract Background Intrahepatic cholangiocarcinoma is an aggressive liver carcinoma with increasing incidence and mortality. A good auxiliary prognostic prediction tool is desperately needed for the development of treatment strategies. The purpose of this study was to explore the prognostic value of the radiomics nomogram based on enhanced CT in intrahepatic cholangiocarcinoma. Methods In this retrospective study, 101 patients with pathological confirmation of intrahepatic cholangiocarcinoma were recruited. A radiomics nomogram was developed by radiomics score and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by a nomogram. Model performance and clinical usefulness were assessed by calibration curve, ROC curve, and survival curve. Results A total of 101patients (mean age, 58.2 years old; range 36–79 years old) were included in the study. The 1-year, 3-year, and 5-year overall survival rates were 49.5%, 26.6%, and 14.4%, respectively, with a median survival time of 12.2 months in the whole set. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found three independent prognostic factors. The radiomics nomogram showed a significant prognosis value with overall survival. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole set (30.4% vs. 56.4% and 13.0% vs. 30.6%, respectively, p = 0.018). Conclusions This radiomics nomogram has potential application value in the preoperative prognostic prediction of intrahepatic cholangiocarcinoma and may facilitate in clinical decision-making.

Abstract Background Histopathological image features offer a quantitative measurement of cellular morphology, and probably help for better diagnosis and prognosis in head and neck squamous cell carcinoma (HNSCC). Methods We first used histopathological image features and machine‐learning algorithms to predict molecular features of 212 HNSCC patients from The Cancer Genome Atlas (TCGA). Next, we divided TCGA‐HNSCC cohort into training set (n = 149) and test set (n = 63), and obtained tissue microarrays as an external validation set (n = 126). We identified the gene expression profile correlated to image features by bioinformatics analysis. Results Histopathological image features combined with random forest may predict five somatic mutations, transcriptional subtypes, and methylation subtypes, with area under curve (AUC) ranging from 0.828 to 0.968. The prediction model based on image features could predict overall survival, with 5‐year AUC of 0.831, 0.782, and 0.751 in training, test, and validation sets. We next established an integrative prognostic model of image features and gene expressions, which obtained better performance in training set (5‐year AUC = 0.860) and test set (5‐year AUC = 0.826). According to histopathological transcriptomics risk score (HTRS) generated by the model, high‐risk and low‐risk patients had different survival in training set (HR = 4.09, p

BackgroundRaman spectroscopy (RS) has shown great potential in the diagnosis of oral squamous cell carcinoma (OSCC). Although many single-central original studies have been carried out, it is difficult to use RS in real clinical settings based on the current limited evidence. Herein, we conducted this meta-analysis of diagnostic studies to evaluate the overall performance of RS in OSCC diagnosis.MethodsWe systematically searched databases including Medline, Embase, and Web of Science for studies from January 2000 to March 2022. Data of true positives, true negatives, false positives, and false negatives were extracted from the included studies to calculate the pooled sensitivity, specificity, accuracy, positive and negative likelihood ratios (LRs), and diagnostic odds ratio (DOR) with 95% confidence intervals, then we plotted the summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) to evaluate the overall performance of RS. Quality assessments and publication bias were evaluated by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) checklist in Review Manager 5.3. The statistical parameters were calculated with StataSE version 12 and MetaDiSc 1.4.ResultsIn total, 13 studies were included in our meta-analysis. The pooled diagnostic sensitivity and specificity of RS in OSCC were 0.89 (95% CI, 0.85–0.92) and 0.84 (95% CI, 0.78–0.89). The AUC of SROC curve was 0.93 (95% CI, 0.91–0.95).ConclusionsRS is a non-invasive diagnostic technology with high specificity and sensitivity for detecting OSCC and has the potential to be applied clinically.

Abstract Metabolic reprogramming manifested as glycolysis is considered a character of metabolic activity in tumor cells. Glucose used in glycolysis is the major energy source to support the growth and development of tumor cells, contributing to the high glycolytic flux production for the accumulation of cell mass. Of note, beside high consumption of glucose, the glutamine of nonessential amino acids (NEAAs) could be used as a carbon and nitrogen source. However, glucose and glutamine alone are still not enough to serve as the nutritional source for tumors. Other NEAAs are also important, such as serine, asparagine, and arginine. Related studies have confirmed in cells and animal models that either increase or decrease of NEAAs can limit the growth of tumor cells. Therefore, NEAAs deprivation diet has attracted more attention in recent years and it has been gradually applied in clinical practice for further research. In this review, the possible mechanism and potential applications of NEAAs in diet deprivation therapy are summarized, which may provide a direction for the future application in cancer treatment.