Identification of formation mechanism and key elements of quality geriatric care behavior of nursing assistants in nursing homes: a grounded theory study.

Objectives: This study aimed to identify the key elements and develop a formation mechanism model of quality geriatric care behavior for nursing assistants. Methods: This qualitative research employed the strategy of grounded theory proposed by Strauss and Corbin. Furthermore, the data was collected by participatory observation and semi-structured interviews. A total of 12 nursing managers, 63 nursing assistants, and 36 older people from 9 nursing homes in 6 cities were interviewed, whereas for the observatory survey, participants were recruited from 2 nursing homes. Results: The comparative and analysis process revealed 5 key elements of quality geriatric care behavior, including holistic care, personalized care, respect, positive interaction, and empowerment. Based on the Capability-Opportunity-Motivation-Behavior (COM-B) model, key elements and the 3 stages of quality geriatric care behavior (negative behavior cognition stage, practice exchange run-in stage, and positive behavior reinforcement stage), the theoretical framework of the formation mechanism was established. Conclusion: The results indicated that nursing assistants' capabilities, motivation, and organizational and environmental support are vital for quality care behaviors. The theoretical framework established in this study provides theoretical support and practical reference to policymakers, institutional administrators, and healthcare professionals for improving nursing assistant's care behaviors.

Association between neutrophil-to-lymphocyte ratio and outcomes in hospitalized patients with left ventricular thrombus.

BACKGROUND: Left ventricular thrombus (LVT) is a severe cardiovascular complication occurring in approximately 10% of patients with acute anterior ST-segment elevation myocardial infarction. This study aimed to evaluate the association between neutrophil-to-lymphocyte ratio (NLR) and in-hospital major adverse cardiovascular and cerebrovascular events (MACCE) in patients with LVT. MATERIAL AND METHODS: This multicenter retrospective study was conducted between January 2000 and June 2022 in hospitalized patients with LVT. The outcome included in-hospital MACCE. The association between NLR and in-hospital MACCE was measured by odds ratios (ORs). The restricted cubic spline model was used for dose-response analysis. RESULTS: A total of 197 LVT patients from four centers were included for analysis in this study. MACCE occurred in 13.7% (27/197) of the patients. After adjusting for estimated glomerular filtration rate (eGFR), D-dimer, and age, the OR for MACCE comparing first to the third tertile of NLR was 13.93 [95% confidence interval: 2.37-81.77, P  = 0.004, P -trend = 0.008]. When further adjusting for etiology and heart failure with reduced ejection fraction (HFrEF), the association remained statistically significant. Spline regression models showed an increasing trend in the incidence of MACCEs with NLR both in crude and adjusted models. Subgroup analyses showed that a high NLR may be correlated with poorer outcomes for LVT patients older than 65 years, or with hypertension, dyslipidemia, low ejection fraction, liver, and renal dysfunctions. CONCLUSION: In conclusion, these findings suggested that higher NLR may be associated with an increased risk of in-hospital MACCE in patients with LVT.

Hepatic arterial infusion chemotherapy, lenvatinib plus programmed cell death protein-1 inhibitors: A promising treatment approach for high-burden hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients. METHODS: We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths. CONCLUSION: The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.

A Critical Review of the Effectiveness of Biochar Coupled with Arbuscular Mycorrhizal Fungi in Soil Cadmium Immobilization.

Cadmium-contaminated soil significantly threatens global food security and human health. This scenario gives rise to significant worries regarding widespread environmental pollution. Biochar and arbuscular mycorrhizal fungi (AMF) can effectively immobilize cadmium in the soil in an environmentally friendly way. Existing studies have separately focused on the feasibility of each in remediating polluted soil. However, their association during the remediation of cadmium-polluted soils remains unclear. This review paper aims to elucidate the potential of biochar, in conjunction with AMF, as a strategy to remediate soil contaminated with cadmium. This paper comprehensively analyzes the current understanding of the processes in cadmium immobilization in the soil environment by examining the synergistic interactions between biochar and AMF. Key factors influencing the efficacy of this approach, such as biochar properties, AMF species, and soil conditions, are discussed. The influences of biochar-AMF interactions on plant growth, nutrient uptake, and overall ecosystem health in cadmium-contaminated environments are highlighted. This review indicates that combining biochar and AMF can improve cadmium immobilization. The presence of AMF in the soil can create numerous binding sites on biochar for cadmium ions, effectively immobilizing them in the soil. Insights from this review contribute to a deeper understanding of sustainable and eco-friendly approaches to remediate cadmium-contaminated soils, offering potential applications in agriculture and environmental management.

Tracking Ion Transport in Nanochannels via Transient Single-Particle Imaging.

The transport behavior of ions in the nanopores has an important impact on the performance of the electrochemical devices. Although the classical Transmission-Line (TL) model has long been used to describe ion transport in pores, the boundary conditions for the applicability of the TL model remain controversial. Here, we investigated the transport kinetics of different ions, within nanochannels of different lengths, by using transient single-particle imaging with temporal resolution up to microseconds. We found that the ion transport kinetics within short nanochannels may deviate significantly from the TL model. The reason is that the ion transport under nanoconfinement is composed of multi basic stages, and the kinetics differ much under different stage domination. With the shortening of nanochannels, the electrical double layer (EDL) formation would become the "rate-determining step" and dominate the apparent ion kinetics. Our results imply that using the TL model directly and treating the in-pore mobility as an unchanged parameter to estimate the ion transport kinetics in short nanopores/nanochannels may lead to orders of magnitude bias. These findings may advance the understanding of the nanoconfined ion transport and promote the related applications.

CKLF as a Prognostic Biomarker and Its Association with Immune Infiltration in Hepatocellular Carcinoma.

The Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family, comprising nine members, is involved in the tumorigenesis and progression of various cancers. However, the expression profiles and clinical significance of CMTM family members in hepatocellular carcinoma (HCC) are not fully clarified. In this study, the RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas (TCGA) databases. The Kaplan-Meier method and the Cox proportional hazards regression analysis were used to evaluate the prognostic significance of CMTM family members. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were employed to explore the relationship between CMTM family genes and the tumor microenvironment in HCC. Finally, the prognostic CMTM family gene expression was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining in clinical HCC tissue specimens. The results indicated that, compared with normal tissues, the expression of CKLF, CMTM1, CMTM3, CMTM4, CMTM7, and CMTM8 were significantly upregulated in HCC, while the expression of CMTM2, CMTM5, and CMTM6 were significantly downregulated in HCC. Univariate and multivariate Cox regression analysis demonstrated that CKLF was an independent prognostic biomarker for the overall survival (OS) of HCC patients. In HCC, the expression of CKLF was found to be correlated with immune cell infiltration, immune-related functions, and immune checkpoint genes. The qRT-PCR and IHC confirmed that CKLF was highly expressed in HCC. Overall, this research suggested that CKLF is involved in immune cell infiltration and may serve as a critical prognostic biomarker, which provides new light on the therapeutics for HCC.

A comprehensive analysis of PANoptosome to prognosis and immunotherapy response in pan-cancer.

PANoptosis, a programmed cell death, shares key characteristics of apoptosis, pyroptosis, and necroptosis. Accumulating evidence suggests that PANoptosis plays a crucial role in tumorigenesis. However, the respective regulation mechanisms in cancer are so far unclear. Using various bioinformatic approaches, we comprehensively analyzed the expression patterns, genetic alterations, prognostic value, and immunological role of PANoptosis genes in pan-cancer. Expression of the PANoptosis gene, PYCARD, was validated based on the Human Protein Atlas database and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). We found that PANoptosis genes were aberrantly expressed in most cancer types, which was consistent with the validation of PYCARD expression. Concurrently, PANoptosis genes and PANoptosis scores were significantly associated with patient survival in 21 and 14 cancer types, respectively. Pathway analysis showed that PANoptosis score was positively correlated with pathways linked to immune and inflammatory responses in pan-cancer, such as IL6-JAK-STAT3 signaling, the interferon-gamma response, and IL2-STAT5 signaling. In addition, the PANoptosis score was significantly correlated with the tumor microenvironment, the infiltration levels of most immune cells (i.e.NK cells, CD8+ T cells, CD4+ T cells, DC cells), and immune-related genes. Furthermore, it was a predictive indicator of immunotherapy response in patients with tumors. These insights substantially improve our understanding of PANoptosis components in cancers and may inspire the discovery of novel prognostic and immunotherapy response biomarkers.

Corrigendum: A comprehensively prognostic and immunological analysis of actin-related protein 2/3 complex subunit 5 in pan-cancer and identification in hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fimmu.2022.944898.].

DLGAP4 acts as an effective prognostic predictor for hepatocellular carcinoma and is closely related to tumour progression.

Disc large associated protein 4 (DLGAP4) plays an important role in neurological diseases, but the role and mechanism of DLGAP4 in hepatocellular carcinoma (HCC) remain unclear. In this study, the prognostic effect of DLGAP4 on HCC patients was investigated by means of bioinformatics. The correlation of DLGAP4 expression with the prognosis of HCC patients was evaluated by TCGA data analysis, and the correlation between DLGAP4 expression and the clinical characteristics of HCC patients was evaluated by the Wilcoxon signed rank test and logistic regression analysis. Kaplan‒Meier and Cox regression methods were used to assess the effect of DLGAP4 expression level on overall survival, and nomograms were used to illustrate the correlation between DLGAP4 gene expression and HCC risk. The genes related to DLGAP4 in HCC were screened, and GO/KEGG enrichment analysis was performed. Furthermore, in vitro and in vivo experiments were conducted to detect the effect of DLGAP4 expression on the proliferation, migration and metastasis of HCC cells. We also examined the effect of DLGAP4 expression on enriched pathway proteins to explore the possible mechanism. The expression levels of DLGAP4 were significantly higher in HCC cell lines and tissue samples than in normal liver cell lines and tissues. The expression of DLGAP4 was significantly associated with clinical characteristics. Survival analysis showed that high expression of DLGAP4 was associated with a poor prognosis in HCC. Multivariate analysis showed that high expression of DLGAP4 was an independent risk factor affecting the overall survival rate in HCC patients. By means of ROC curve analysis and nomograms, we determined the value of DLGAP4 expression in the diagnosis and prognosis evaluation of HCC. GO/KEGG enrichment analysis showed that the PPAR signalling pathway was differentially enriched in patients with high expression of DLGAP4. According to in vitro and in vivo experiments, DLGAP4 knockdown inhibited the proliferation and metastasis of HCC cells and decreased the expression of PPARß/δ protein. In contrast, overexpression of DLGAP4 promoted the proliferation and metastasis of HCC cell, and increased the expression of PPARß/δ protein.In contrast, overexpression of DLGAP4 promoted the proliferation and metastasis of HCC cells and increased the expression of PPARß/δ protein. The results show a close correlation between DLGAP4 expression and clinicopathological features of HCC, and DLGAP4 can be used as a prediction biomarker of HCC.

Risk factors for in-hospital systemic thromboembolism in myocardial infarction patients with left-ventricular thrombus: A multicenter retrospective study.

Left-ventricular thrombus (LVT) is a potentially life-threatening disease. However, few studies have explored the risk factors of in-hospital systemic thromboembolism (ST) in LVT patients. In this multicenter retrospective study, we enrolled myocardial infarction patients with LVT from January 2008 to September 2021. Multivariable logistic regression analysis was applied to identify the independent risk factors for ST in LVT patients. A total number of 160 hospitalized LVT patients [median follow-up period 50 months (18.3-82.5 months)] were subjected to analysis. Of them, 54 (33.8%) patients developed acute myocardial infarction, 16 (10%) had ST, and 33 (20.6%) died. Comparable baseline characteristics were established between the ST and non-ST groups, except for the heart failure classification (P = .014). We obtained the following results from our multivariable analysis, based on the use of HFrEF as a reference: HFpEF [odd ratio (OR), 6.2; 95% confidence interval (CI), 1.4-26.3; P = .014] and HFmrEF (OR, 5.0; 95%CI, 1.1-22.2; P = .033). In conclusion, HFpEF, and HFmrEF may be independent risk factors for in-hospital ST development.

Optimal exogenous calcium alleviates the damage of Snow-melting agent to Salix matsudana seedlings.

As the main component of snowmelt agents, NaCl is widely used in northern winters and significantly impacts the expected growth of garden plants in north China. Salix matsudana is also faced with salt stress caused by snowmelt, which seriously affects its development as the main tree species in the northern landscape. However, how exogenous calcium alleviates salt stress in Salix matsudana is not yet clear. In this study, the indicators of growth indices, photosynthetic characteristics and stress resistance were measured by hydroponic assays in combination with three NaCl conditions (0, 50 and 200 mmol·L-1) and five calcium concentrations (0, 2.5, 5, 10 and 20 mmol·L-1). The study's results indicated that the application of exogenous calcium remarkably promoted the growth of Salix matsudana seedlings under NaCl stress. When the exogenous calcium concentration was 10 mmol·L-1, the plant height and basal diameter of Salix matsudana seedlings increased significantly, and the biomass of all parts reached the maximum (P< 0.05). Exogenous calcium can substantially improve the photosynthesis of Salix matsudana seedlings under salt stress. The photosynthetic parameters, photosynthetic pigment content and photosynthetic product synthesis of Salix matsudana seedlings were significantly increased at an exogenous calcium concentration of 10 mmol·L-1, and the photosynthetic level of Salix matsudana seedlings reached the highest value. The chlorophyll fluorescence parameters (F v /F m, F v /F 0) of Salix matsudana seedlings were significantly decreased under different concentrations of NaCl stress. The maximum photochemical efficiency (F v /F m) and potential photochemical efficiency (F v /F 0) of Salix matsudana seedlings peaked when the exogenous calcium concentration was 10 mmol·L-1, which was significantly higher than that of the other treatments (P< 0.05). The water use efficiency of Salix matsudana was affected considerably by NaCl stress. The WUE and iWUE peak values of Salix matsudana were significantly higher than those of other calcium concentrations at 10 mmol·L-1 (P< 0.05). Exogenous calcium can increase the activities of CAT, SOD and POD enzymes in Salix matsudana seedlings under different NaCl concentrations. Under NaCl stress, adding exogenous calcium promoted the survival rate and growth of Salix matsudana seedlings. In conclusion, the optimum exogenous calcium concentration for Salix matsudana seedlings was 10 mmol·L-1. High or low concentrations of exogenous calcium did not achieve the best results in alleviating salt stress in Salix matsudana.

A comprehensive prognostic and immunological analysis of ephrin family genes in hepatocellular carcinoma.

Background: Ephrins, a series of Eph-associated receptor tyrosine kinase ligands, play an important role in the tumorigenesis and progression of various cancers. However, their contributions to hepatocellular carcinoma (HCC) remain unclear. Thus, we aimed to explore their prognostic value and immune implications in HCC. Methods: Multiple public databases, such as TCGA, GTEx, and UCSC XENA, were used to analyze the expression of ephrin genes across cancers. Kaplan-Meier analysis and Cox regression were used to explore the prognostic role of ephrin genes in HCC. A logistic regression model was utilized to evaluate the association between ephrin gene expression and clinical characteristics. Gene set enrichment analysis (GSEA) was conducted to elucidate their potential biological mechanisms. Various immune algorithms were utilized to investigate the correlation between ephrin genes and tumor immunity. We also analyzed their association with drug sensitivity, and gene mutations. Finally, RT-qPCR was performed to validate the expression of ephrin family genes in HCC cells and clinical tissues. Results: The expression of EFNA1, EFNA2, EFNA3, EFNA4, EFNB1, and EFNB2 was upregulated in most cancer types, while EFNA5 and EFNB3 was downregulated in most cancers. In HCC, the expression levels of EFNA1, EFNA3, EFNA4, EFNB1, and EFNB2 were significantly higher in tumor tissues than in normal tissues. High expression of EFNA3, EFNA4, and EFNB1 was associated with tumor progression and worse prognosis in HCC patients. The expression of EFNA3 and EFNA4 was negatively associated with the stromal/ESTIMATE scores, while EFNB1 was positively correlated with the immune/stromal/ESTIMATE scores. Moreover, these ephrin genes were closely relevant to the infiltration of immune cells, such as B cells, CD4+ T cells, CD8+ T cells, neutrophil cells, macrophage cells, and dendritic cells. EFNB1 expression was positively associated with most immune-related genes, while EFNA3/EFNA4 was positively related to TMB and MSI. In addition, EFNA3, EFNA4, and EFNB1 were related to drug sensitivity and affected the mutation frequency of some genes in HCC. Conclusion: EFNA3, EFNA4, and EFNB1 are independent prognostic factors for HCC patients and are closely correlated with tumor immunity, which may provide a new direction for exploring novel therapeutic targets and biomarkers for immunotherapy.

A comprehensively prognostic and immunological analysis of actin-related protein 2/3 complex subunit 5 in pan-cancer and identification in hepatocellular carcinoma.

Background: Actin-related protein 2/3 complex subunit 5 (ARPC5) is one of the members of actin-related protein 2/3 complex and plays an important role in cell migration and invasion. However, little is known about the expression pattern, prognosis value, and biological function of ARPC5 in pan-cancer. Thus, we focus on ARPC5 as cut point to explore a novel prognostic and immunological biomarker for cancers. Methods: The public databases, including TCGA, GTEx, and UCEC, were used to analyze ARPC5 expression in pan-cancer. The Human Protein Atlas website was applied to obtain the expression of ARPC5 in different tissues, cell lines, and single-cell types. Univariate Cox regression analysis and Kaplan-Meier analysis were used to explore the prognosis value of ARPC5 in various cancers. Spearman's correlation analysis was performed to investigate the association between ARPC5 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, RNA modification genes, DNA methyltransferases, and tumor stemness. Moreover, qPCR, Western blot, and immunohistochemistry were carried out to examine the differential expression of ARPC5 in HCC tissues and cell lines. CCK8, EdU, flow cytometry, wound-healing assays, and transwell assays were conducted to explore its role in tumor proliferation, apoptosis, migration, and invasion among HCC cells. Results: ARPC5 expression was upregulated in most cancer types and significantly associated with worse prognosis in KIRC, KIRP, LGG, and LIHC. mRNA expression of ARPC5 showed low tissue and cell specificity in normal tissues, cell lines, and single-cell types. ARPC5 expression was positively correlated with the tumor microenvironment scores, immune infiltrating cells, immune checkpoint-related genes in most cancers. ARPC5 in STAD and BRCA was positively associated with TMB, MSI, and neoantigens. We also discovered that ARPC5 was correlated with the expression of m1A-related genes, m5C-related genes, m6A-related genes, and DNA methyltransferases. In experiment analyses, we found that ARPC5 was significantly highly expressed in HCC tissues and HCC cells. Functionally, silencing ARPC5 dramatically decreased proliferation, migration, and invasion ability of HCC cells. Conclusions: ARPC5 expression affects the prognosis of multiple tumors and is closely correlated to tumor immune infiltration and immunotherapy. Furthermore, ARPC5 may function as an oncogene and promote tumor progression in HCC.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with programmed cell death protein-1 antibody and lenvatinib for advanced hepatocellular carcinoma.

Background: The purpose of the study was to assess the efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) who are undergoing hepatic arterial infusion chemotherapy (HAIC) combined with programmed cell death protein-1 (PD-1) antibody and lenvatinib. Methods: We retrospectively evaluated 61 patients treated with HAIC combined with PD-1 antibody and lenvatinib at the Second Affiliated Hospital of Nanchang University between September 2020 and January 2022 for advanced HCC. We analyzed tumor response, progression free survival (PFS), and treatment-related adverse events (TRAEs). Results: The objective response rate (ORR) was 36.1% (RECIST 1.1)/57.4% (mRECIST) and the disease control rate (DCR) was 82.0%. The overall median PFS was 6.0 months, 6.7 months for first-line treatment, and 4.3 months for second-line treatment. The most common TRAEs were neutropenia (50.8%), abdominal pain (45.9%), and aspartate aminotransferase increase (39.3%). Conclusion: Hepatic arterial infusion chemotherapy combined with PD-1 antibody and lenvatinib is effective in the treatment of advanced HCC, and the TRAEs are generally controllable.

Identification of an Epithelial-Mesenchymal Transition-Related Long Non-coding RNA Prognostic Signature to Determine the Prognosis and Drug Treatment of Hepatocellular Carcinoma Patients.

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. Epithelial-mesenchymal transition (EMT) is crucial for cancer progression and metastasis. Thus, we aimed to construct an EMT-related lncRNA signature for predicting the prognosis of HCC patients. Methods: Cox regression analysis and LASSO regression method were used to build an EMT-related lncRNAs risk signature based on TCGA database. Kaplan-Meier survival analysis was conducted to compare the overall survival (OS) in different risk groups. ROC curves and Cox proportional-hazards analysis were performed to evaluate the performance of the risk signature. RT-qPCR was conducted in HCC cell lines and tissue samples to detect the expression of some lncRNAs in this risk model. Furthermore, a nomogram involving the risk score and clinicopathological features was built and validated with calibration curves and ROC curves. In addition, we explored the association between risk signature and tumor immunity, somatic mutations status, and drugs sensitivity. Results: Twelve EMT-related lncRNAs were obtained to construct the prognostic risk signature for patients with HCC. The Kaplan-Meier curve analysis revealed that patients in the high-risk group had worse overall survival (OS) than those in low-risk group. ROC curves and Cox regression analysis suggested the risk signature could predict HCC survival exactly and independently. The prognostic value of the risk model was confirmed in the testing and entire groups. We also found AC099850.3 and AC092171.2 were highly expressed in HCC cells and HCC tissues. The nomogram could accurately predict survival probability of HCC patients. Gene set enrichment analysis (GSEA) and gene ontology (GO) analysis showed that cancer-related pathways and cell division activity were enriched in high-risk group. The SNPs showed that the prevalence of TP53 mutations was significantly different between high- and low-risk groups; the TP53 mutations and the high TMB were both associated with a worse prognosis in patients with HCC. We also observed widely associations between risk signature and drugs sensitivity in HCC. Conclusion: A novel EMT-related lncRNAs risk signature, including 12 lncRNAs, was established and identified in patients with HCC, which can accurately predict the prognosis of HCC patients and may be used to guide individualized treatment in the clinical practice.

ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion.

Background: Actin-related protein 2/3 complex subunit 2 (ARPC2) plays a fundamental role in actin filament nucleation and is critical for tumor cell migration and invasion. However, its abnormal expression, clinical significance, and biological function in human pan-cancer have been poorly explored. Thus, we focused on ARPC2 as an entry point for identifying novel pan-cancer prognostic biomarkers. Methods: The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were used to assess the differential expression of ARPC2 in pan-cancer. The Human Protein Atlas was used for the tissue/cell-specific expression analysis of ARPC2. The genetic alteration information of ARPC2 was obtained from the cBioPortal database and the GSCALite platform. The prognostic value of ARPC2 was explored in pan-cancer using Cox regression and Kaplan-Meier analyses. Spearman correlation analysis was performed to investigate the relationship between ARPC2 expression and tumor mutational burden (TMB), DNA methyltransferases, microsatellite instability (MSI), immune-related genes, and mismatch repairs (MMRs). The ESTIMATE and CIBERSORT algorithms were used to evaluate the association between ARPC2 expression and the tumor microenvironment (TME) and immune infiltrating cells. We also conducted differential expression analysis of ARPC2 in hepatocellular carcinoma (HCC) tissues and cell lines using qPCR, western blotting, and immunohistochemistry and explored its role in tumor proliferation, migration, and invasion of HCC cells. Results: ARPC2 expression was significantly upregulated in multiple tumor types and significantly correlated with worse prognosis and higher clinicopathological stage. Genetic alterations and DNA methylation in tumor tissues may contribute to the aberrant expression of ARPC2. ARPC2 expression was significantly correlated with the tumor microenvironment (TME), infiltrating immune cells, TMB, microsatellite instability (MSI), and immune checkpoint-related genes in certain cancer types. In this experimental study, we found that the expression of ARPC2 was dramatically upregulated in HCC tissues and cell lines compared to adjacent liver tissues and normal liver cell lines. Functionally, ARPC2 silencing in HCC cells significantly inhibited cell proliferation, migration, and invasion, while the overexpression of ARPC2 promotes tumor proliferation, migration, and invasion. Conclusion: ARPC2 is a promising prognostic and immunological biomarker for multiple tumor types and is likely to play an important role in HCC progression and metastasis.

The Prognostic Value of Lysine Acetylation Regulators in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a tumor with high morbidity and mortality worldwide. lysine acetylation regulators (LARs) dynamically regulate Lysine acetylation modification which plays an important regulatory role in cancer. Therefore, we aimed to explore the potential clinical prognostic value of LARs in HCC. Methods: Differentially expressed LARs in normal liver and HCC tissues were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. To identify genes with prognostic value and establish the risk characteristics of LARs, consensus clustering was employed. We used univariate Cox regression survival analysis and LASSO Cox regression based on LARs to determine the independent prognostic signature of HCC. CIBERSORT and Gene Set Enrichment Analysis (GSEA) were used to estimate immune infiltration and functional enrichment analysis respectively. The expression of LAR was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). statistical analyses were conducted using SPSS and R software. Results: In this study, the 33 LARs expression data and corresponding clinical information of HCC were obtained using TCGA and ICGC datasets. We found majority of the LARs were differentially expressed. Consensus cluster analysis was carried out based on the TCGA cohort, and three HCC subtypes (cluster 1, 2, and 3) were obtained. The LA3 subgroup had the worst clinical outcomes. Nine key LARs were identified to affect prognosis. The results showed that LARs signature has a strong independent prognostic value in HCC patients, whether in the training datasets or in the testing datasets. GSEA results showed that various tumor-related processes and pathways were abundant in the high-risk groups. RT-qPCR results showed that HAT1, HDAC1, HDAC2, HDAC4, and HDAC11 were highly expressed in HCC cells. Conclusion: Our results suggest that LARs play critical roles in HCC and are helpful for individual prognosis monitoring and clinical decision-making of HCC.

Diagnostic Accuracy of Artificial Intelligence Based on Imaging Data for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: The presence of microvascular invasion (MVI) is considered an independent prognostic factor associated with early recurrence and poor survival in hepatocellular carcinoma (HCC) patients after resection. Artificial intelligence (AI), mainly consisting of non-deep learning algorithms (NDLAs) and deep learning algorithms (DLAs), has been widely used for MVI prediction in medical imaging. Aim: To assess the diagnostic accuracy of AI algorithms for non-invasive, preoperative prediction of MVI based on imaging data. Methods: Original studies reporting AI algorithms for non-invasive, preoperative prediction of MVI based on quantitative imaging data were identified in the databases PubMed, Embase, and Web of Science. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) scale. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model with 95% CIs. A summary receiver operating characteristic curve and the area under the curve (AUC) were generated to assess the diagnostic accuracy of the deep learning and non-deep learning models. In the non-deep learning group, we further performed meta-regression and subgroup analyses to identify the source of heterogeneity. Results: Data from 16 included studies with 4,759 cases were available for meta-analysis. Four studies on deep learning models, 12 studies on non-deep learning models, and two studies compared the efficiency of the two types. For predictive performance of deep learning models, the pooled sensitivity, specificity, PLR, NLR, and AUC values were 0.84 [0.75-0.90], 0.84 [0.77-0.89], 5.14 [3.53-7.48], 0.2 [0.12-0.31], and 0.90 [0.87-0.93]; and for non-deep learning models, they were 0.77 [0.71-0.82], 0.77 [0.73-0.80], 3.30 [2.83-3.84], 0.30 [0.24-0.38], and 0.82 [0.79-0.85], respectively. Subgroup analyses showed a significant difference between the single tumor subgroup and the multiple tumor subgroup in the pooled sensitivity, NLR, and AUC. Conclusion: This meta-analysis demonstrates the high diagnostic accuracy of non-deep learning and deep learning methods for MVI status prediction and their promising potential for clinical decision-making. Deep learning models perform better than non-deep learning models in terms of the accuracy of MVI prediction, methodology, and cost-effectiveness. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID=260891, ID:CRD42021260891.

Efficacy and Safety of Fruquintinib Plus PD-1 Inhibitors Versus Regorafenib Plus PD-1 Inhibitors in Refractory Microsatellite Stable Metastatic Colorectal Cancer.

BACKGROUND: Microsatellite stability (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. Studies have shown that antiangiogenic drugs combined with programmed death receptor-1 (PD-1) inhibitors can improve immunosuppression. The purpose of this study was to compare the efficacy of fruquintinib combined with PD-1 inhibitor (FP) and regorafenib combined with PD-1 inhibitor (RP) in the treatment of advanced mCRC with MSS or pMMR. MATERIALS AND METHODS: We retrospectively collected advanced MSS or pMMR mCRC patient data from The Second Affiliated Hospital of Nanchang, China, from June 2019 to March 2021. Then, we analyzed and compared the efficacy and safety of FP and RP. RESULTS: A total of 51 patients who met the criteria were divided into FP (n = 28) and RP groups (n = 23). The overall response rate of the FP and RP groups was 7.1% and 8.7% and the disease control rate was 89.3% and 56.5%, respectively. The median progression-free survival (PFS) time was higher in the FP group than in the RP group (6.4 vs. 3.9 months, respectively; P = 0.0209). Patients with no liver metastasis, KRAS wild type, and left colon tumor may benefit from FP. Eight patients (15.7%) had grade 3 toxicity related to treatment. Cox multivariate regression analysis showed that the treatment method was an independent risk factor for median PFS time. CONCLUSION: Our study indicates that FP could improve PFS time of patients with advanced mCRC compared with RP.

Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma.

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the "limma" package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.