Knockdown of hsa_circ_0102231 Impedes the Progression of Liver Cancer through the miR-873-SOX4 Axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. AIM: The objective of this study was to investigate the role of circular RNA 0102231 (hsa_circ_ 0102231) in the progression of liver cancer. METHODS: In this study, quantitative polymerase chain reaction experiments were performed to quantify the hsa_circ_0102231 level in different liver cancer cell lines. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pull-down assay, were used to identify putative hsa_circ_ 0102231 downstream targets. Colony formation and CCK8 assays were utilized to examine cell proliferation, whereas Transwell assays were employed to monitor cell migration. Lastly, the role of hsa_circ_0102231 in liver cancer was assessed in a subcutaneous xenograft model. RESULTS: The expression of hsa_circ_0102231 increased significantly in HepG2 and Huh-7 cells compared with controls, and hsa_circ_0102231 knockdown inhibited cell proliferation and migration in vitro and in vivo. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pulldown assay, revealed that miR-873 and SOX4 were hsa_circ_0102231 downstream targets. miR-873 inhibition or SOX4 overexpression rescued the proliferation and migration of HepG2 and Huh-7 cells after hsa_circ_0102231 knockdown. Furthermore, SOX4 overexpression reversed the miR-873-induced inhibition of cell migration and proliferation in vitro. CONCLUSION: These results show that hsa_circ_0102231 knockdown impedes the progression of liver cancer by regulating the miR-873/SOX4 axis. However, further studies are needed to determine whether hsa_circ_0102231 may be a therapeutic target in liver cancer.

LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

Purpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC). Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators. Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators. Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.

Why does mobile payment promote purchases? Revisiting the pain of paying, and understanding the implicit pleasure via selective attention.

The past years have witnessed a phenomenal growth of the mobile payment market, but how mobile payment affects purchase behavior receives less attention from academics. Recent studies suggested that lower pain of paying may not fully clarify the relationship between mobile payment and increased purchases (i.e., mobile payment effect). The current research first introduced price level in Study 1 and demonstrated that the pain of paying served as an underlying mechanism only in the high-price condition rather than the low-price condition. As such, Study 2 was conducted in a low-price context to address the uncovered mechanisms. We propose a new concept of "pleasure of payment" that is defined as an implicit and consumption-related hedonic response based on the cue theory of consumption. By tracking spontaneous attention to positive attributes (i.e., benefits) of products, Study 2 demonstrated this implicit pleasure as a psychological mechanism for the mobile payment effect when the pain of paying was not at play. These findings have important implications for mobile payment in research and practice by identifying price level as a boundary condition for the role of pain of paying and understanding the positive downstream consequences of mobile payment usage on consumer psychology.

Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal system. ZNF710 is a transcription factor (TF), and zinc finger protein 710 (ZNF710)-AS1-201 is an immune-related long noncoding RNA (lncRNA) that is upregulated in GC cells. AIM: To assess the correlation between ZNF710-AS1-201 and immune microenvironment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells. METHODS: We obtained data from The Cancer Genome Atlas and Wujin Hospital. We assessed cell growth, migration, invasion, and programmed cell death using cell counting kit-8, EdU, scratch, Transwell, and flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify the potential downstream targets of ZNF710-AS1-201. RESULTS: In GC tissues with low ZNF710-AS1-201 expression, immunoassays detected significant infiltration of various antitumor immune cells, such as memory CD8 T cells and activated CD4 T cells. In the low-expression group, the half-maximal inhibitory concentrations (IC50s) of 5-fluorouracil, cisplatin, gemcitabine, and trametinib were lower, whereas the IC50s of dasatinib and vorinostat were higher. The malignant degree of GC was higher and the stage was later in the high-expression group. Additionally, patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates. In vitro, the overexpression of ZNF710-AS1-201 greatly enhanced growth, metastasis, and infiltration while suppressing cell death in HGC-27 cells. In contrast, the reduced expression of ZNF710-AS1-201 greatly hindered cell growth, enhanced apoptosis, and suppressed the metastasis and invasion of MKN-45 cells. The expression changes in ZNF710 were significant, but the corresponding changes in isocitrate dehydrogenase-2, Semaphorin 4B, ARHGAP10, RGMB, hsa-miR-93-5p, and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201, as determined by qRT-PCR. CONCLUSION: Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells. It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC. Nevertheless, it is still necessary to determine the specific targets of the ZNF710 TF.

Prognostic Evaluation for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Patients Treated with Transarterial Chemoembolization Plus Molecular Targeted Therapies-Development and Validation of the ABPS Score.

RATIONALE AND OBJECTIVES: Transarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: A retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score. Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study. RESULTS: The ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1: 0 score; grade 2: 1 score), PVTT(I-II type: 0 score; III-IV type: 1 score), and systemic-immune inflammation index (SII,<550 × 1012: 0 score; ≥550 × 1012: 1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1-2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6-12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P < 0.05). These research findings were further validated in the external validation cohorts. CONCLUSION: The ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients.

A multi-institutional study to predict the benefits of DEB-TACE and molecular targeted agent sequential therapy in unresectable hepatocellular carcinoma using a radiological-clinical nomogram.

OBJECTIVE: Exploring the efficacy of a Radiological-Clinical (Rad-Clinical) model in predicting prognosis of unresectable hepatocellular carcinoma (HCC) patients after drug eluting beads transcatheter arterial chemoembolization (DEB-TACE) to optimize the targeted sequential treatment. METHODS: In this retrospective analysis, we included 202 patients with unresectable HCC who received DEB-TACE treatment in 17 institutions from June 2018 to December 2022. Progression-free survival (PFS)-related radiomics features were computationally extracted from HCC patients to build a radiological signature (Rad-signature) model with least absolute shrinkage and selection operator regression. A Rad-Clinical model for postoperative PFS was further constructed according to the Rad-signature and clinical variables by Cox regression analysis. It was presented as a nomogram and evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis. And further evaluate the application value of Rad-Clinical model in clinical stages and targeted sequential therapy of HCC. RESULTS: Tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and radiomics score (Rad-score) were found to be independent risk factors for PFS after DEB-TACE treatment for unresectable HCC, with the Rad-Clinical model being the greatest predictor of PFS in these patients (hazard ratio: 2.08; 95% confidence interval: 1.56-2.78; P < 0.001) along with high 6 months, 12 months, 18 months, and 24 months area under the curves of 0.857, 0.810, 0.843, and 0.838, respectively. In addition, compared to the radiomics and clinical nomograms, the Radiological-Clinical nomogram also significantly improved the classification accuracy for PFS outcomes, based on the net reclassification improvement (45.2%, 95% CI 0.260-0.632, p < 0.05) and integrated discrimination improvement (14.9%, 95% CI 0.064-0.281, p < 0.05). Based on this model, low-risk patients had higher PFS than high-risk patients in BCLC-B and C stages (P = 0.021). Targeted sequential therapy for patients with high and low-risk HCC in BCLC-B stage exhibited significant benefits (P = 0.018, P = 0.012), but patients with high-risk HCC in BCLC-C stage did not benefit much (P = 0.052). CONCLUSION: The Rad-Clinical model may be favorable for predicting PFS in patients with unresectable HCC treated with DEB-TACE and for identifying patients who may benefit from targeted sequential therapy.

Comparing the effectiveness and safety of Sorafenib plus TACE with Apatinib plus TACE for treating patients with unresectable hepatocellular carcinoma: a multicentre propensity score matching study.

OBJECTIVE: Local combined systemic therapy has been an important method for the treatment of unresectable hepatocellular carcinoma (HCC).The purpose of this study was to compare the effectiveness and safety of transarterial chemoembolization (TACE) plus Sorafenib versus TACE plus Apatinib for treating patients with unresectable HCC. METHODS: The clinical data of patients with unresectable HCC who were treated with TACE plus Sorafenib or TACE plus Apatinib at 5 Chinese medical centers between January 2016 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) was applied to reduce the bias from confounding factors. RESULTS: A total of 380 patients were enrolled, of whom 129 cases were treated with TACE plus Sorafenib and 251 cases with TACE plus Apatinib. After the 1:1 PSM, 116 pairs of patients were involved in this study. The results showed that the PFS and OS in the TACE-Sorafenib group were significantly longer than those in the TACE-Apatinib group (PFS: 16.79 ± 6.45 vs. 14.76 ± 6.98 months, P = 0.049; OS: 20.66 ± 6.98 vs. 17.69 ± 6.72 months, P = 0.013). However, the ORR in the TACE-Apatinib group was markedly higher than that in the TACE-Sorafenib group (70.69% vs. 56.03%, P = 0.021). There were more patients with adverse events (AEs) in the TACE-Apatinib group than those in the TACE-Sorafenib group before dose adjustment (87 vs. 63, P = 0.001); however, the number of patients who suffered from AEs was not significantly different between the two groups after the dose adjustment (62 vs. 55, P = 0.148). No treatment-related death was found in the two groups. Subgroup analysis revealed that patients with unresectable HCC could better benefit from regular doses than reduced doses (Sorafenib, 22.59 vs. 18.02, P < 0.001; Apatinib, 19.75 vs. 16.86, P = 0.005). CONCLUSION: TACE plus either Sorafenib or Apatinib could effectively treat patients with unresectable HCC, the safety of TACE plus Sorafenib was better. and the ORR of TACE plus Apatinib was higher.

Over-expression of RRM2 predicts adverse prognosis correlated with immune infiltrates: A potential biomarker for hepatocellular carcinoma.

Background: Ribonucleotide reductase regulatory subunit M2 (RRM2) has been reported to be an oncogene in some malignant tumors, such as lung adenocarcinoma, oral squamous cell carcinoma, glioblastoma, and breast cancer. However, the clinical significance of RRM2 in hepatocellular carcinoma has been less studied. The aim of this study was to assess the importance of RRM2 in hepatocellular carcinoma (HCC) based on the Cancer Genome Atlas (TCGA) database. Methods: The RRM2 expression levels and clinical features were downloaded from the TCGA database. Immunohistochemistry results between tumor tissues and normal tissues were downloaded from the Proteinatlas database. Meanwhile, the expression levels of RRM2 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Western Blotting. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein-interactions (PPI) network were constructed to analyze RRM2-related downstream molecules. In addition, RRM2 expression-related pathways performed by gene set enrichment analysis (GSEA). Association analysis of RRM2 gene expression and immune infiltration was performed by single-sample GSEA (ssGSEA). Results: The RRM2 expression level in tumor tissues was higher than normal tissues (P <0.001). The elevated expression of RRM2 in HCC was significantly correlated with T stage (P <0.05), pathologic stage (P <0.05), tumor status (P <0.05), histologic grade (P<0.001), and AFP (P <0.001). HCC with higher RRM2 expression was positively associated with worse OS (overall survival), PFS (progression-free survival), and DSS (disease-specific survival). In the univariate analysis, the expression of RRM2, T stage, M stage, pathologic stage, and tumor status were negatively correlated with OS (P <0.05). Further analysis using multivariate Cox regression showed that tumor status (P<0.01) and RRM2 expression (P<0.05) were independent prognostic factors of OS in HCC. GO/KEGG analysis showed that the critical biological process (chromosome condensation and p53 signaling pathway) might be the possible function mechanism in promoting HCC. Moreover, GSEA showed that several pathways were enriched in RRM2 high-expression samples, including PD-1 signaling, cell cycle, P27 pathway, and T cell receptor signaling pathway. RRM2 was significantly correlated with the infiltration level of CD8 T cells, Cytotoxic cells, DCs, Neutrophils, NK cells, and T helper cells (P <0.05). Conclusion: Over-expression of RRM2 predict adverse prognosis and is correlated with immune infiltrates in HCC. RRM2 may be a significant molecular biomarker for HCC diagnosis and prognosis.

Identification and Analysis of Crucial Genes in H. pylori-Associated Gastric Cancer Using an Integrated Bioinformatics Approach.

Background: The relationship between H. pylori infection and gastric cancer (GC) has been widely studied, and H. pylori is considered as the main factor. Utilizing bioinformatics analysis, this study examined gene signatures related to progressing H. pylori-associated GC. Materials and Methods: The dataset GSE13195 was chosen to search for abnormally expressed genes in H. pylori-associated GC and normal tissues. The TCGA-STAD database was chosen to verify the expression of key genes in GC and normal tissues. Results: In GSE13195, a total of 332 differential expression genes (DEGs) were screened. The results of weighted gene co-expression network analysis showed that the light cyan, plum2, black, and magenta4 modules were associated with stages (T3, T2, and T4), while the orangered4, salmon2, pink, and navajowhite2 modules were correlated with lymph node metastasis (N3, N2, and N0). Based on the results of DEGs and hub genes, a total of 7 key genes (ADAM28, FCER1G, MRPL14, SOSTDC1, TYROBP, C1QC, and C3) were screened out. These gene mRNA levels were able to distinguish between normal and H. pylori-associated GC tissue using receiver operating characteristic curves. After transcriptional level verification and survival analysis, ADAM28 and C1QC were excluded. An immune infiltration study revealed that key genes were involved in regulating the infiltration levels of cells associated with innate immune response, antigen presentation process, humoral immune response, or Tcell-mediated immune response. In addition, drugs targeting FCER1G and TYROBP have been approved and are under investigation. Conclusion: Our study identified five key genes involved in H. pylori-associated GC tumorigenesis. Patients with higher levels of C3 expression had a poorer prognosis than those with lower levels. In addition, these key genes may serve as biomarkers and therapeutic targets for H. pylori-associated GC diagnosis, targeted therapy, and immunotherapy in the future.

Pleasure of paying when using mobile payment: Evidence from EEG studies.

Mobile payment has emerged as a popular payment method in many countries. While much research has focused on the antecedents of mobile payment adoption, limited research has investigated the consequences of mobile payment usage relating to how it would influence consumer behaviors (e.g., purchase intention or willingness to pay). Here, we propose that mobile payment not just reduces the "pain of paying," a traditional view explaining why cashless payment stimulates spending, but it also evokes the "pleasure of paying," raising from the enhanced processing fluency in completing transactions. We tested this new conceptualization of "pleasure of paying" using EEG, complementing other behavioral measures. In two studies, we found that mobile payment effectively enhanced purchase likelihood (study 1, N = 66) and such an enhancement is generalizable to both hedonic and utilitarian products (study 2, N = 29). By employing EEG measures, we provided the first neural evidence of "pleasure of paying" in addition to the signal of "pain of paying." Critically, we demonstrated that the "pleasure of paying" is a distinctive psychological mechanism that is induced by mobile payment usage and that the "pleasure of paying" joins the "pain of paying" to mediate the increased purchase intention. We discuss the contributions and implications of these results to the ongoing evolution of cashless payment societies.

A new acidic microenvironment related lncRNA signature predicts the prognosis of liver cancer patients.

Background: The acidic microenvironment (AME), like hypoxia, inflammation, or immunoreaction, is a hallmark of the tumor microenvironment (TME). This work aimed to develop a prediction signature dependent on AME-associated lncRNAs in order to predict the prognosis of LC individuals. Methods: We downloaded RNA-seq information and the corresponding clinical and predictive data from The Cancer Genome Atlas (TCGA) dataset and conducted univariate and multivariate Cox regression analyses to identify AME-associated lncRNAs for the construction of a prediction signature The Kaplan-Meier technique was utilized to determine the overall survival (OS) rate of the high (H)-risk and low (L)-risk groups. Using gene set enrichment analysis (GSEA) the functional variations between the H- and L-risk groups were investigated. The association between the prediction signature and immunological state was investigated using single-sample GSEA (ssGSEA). Additionally, the association between the predicted signature and the therapeutic response of LC individuals was evaluated. Lastly, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to verify the risk model. Results: We generated a signature comprised of seven AME-associated lncRNAs (LINC01116, AC002511.2, LINC00426, ARHGAP31-AS1, LINC01060, TMCC1-AS1, AC012065.1). The H-risk group had a worse prognosis than the L- risk group. The AME-associated lncRNA signature might determine the prognosis of individuals with LC independently. The AME-related lncRNA signature shows a greater predictive effectiveness than clinic-pathological factors, with an area under the receiver operating characteristic (ROC) curve of 0.806%. When participants were categorized based on several clinico-pathological characteristics, the OS of high-risk individuals was shorter compared to low-risk patients. GSEA demonstrated that the metabolism of different acids and the PPAR signaling pathway are closely associated with low-risk individuals. The prognostic signature was substantially associated with the immunological status of LC individuals, as determined by ssGSEA. High risk individuals were more sensitive to some immunotherapies (including anti-TNFSF4 anti-SIRPA, anti-CD276 and anti-TNFSF15) and some conventional chemotherapy drugs (including lapatinib and paclitaxel). Finally, the expression levels of the seven lncRNAs comprising the signature were tested by qRT-PCR. Conclusions: A basis for the mechanism of AME-associated lncRNAs in LC is provided by the prediction signature, which also offers clinical therapeutic recommendations for LC individuals.

A novel difficulty scoring system of laparoscopic liver resection for liver tumor.

Objectives: To develop a novel difficulty scoring system (NDSS) to predict the surgical difficulty of laparoscopic hepatectomy. Patients and methods: A total of 138 patients with liver tumors performed liver resection (LLR) between March 2017 to June 2022 were selected from Affiliated Hospital of Jiangnan University and Wujin Hospital Affiliated with Jiangsu University.Patient demographics, laboratory tests, intraoperative variables, pathological characteristics were assessed. We also assessed the Child Pugh score and the DSS-B score. Results: Patients were divided into training and testing cohort according to their hospital. Patients in training cohort were divided into high and low difficult groups based on operation time, blood loss and conversion. Higher percentage of patients with malignant liver tumor (87.0% vs. 58.1%; P = 0.003) or history of hepatobiliary surgery (24.1% vs. 7.0%; P = 0.043) in high difficult group than in low difficult group. To improve the difficulty scoring system, we incorporated the history of hepatobiliary surgery and nature of the tumor. A novel difficulty scoring system was established. The results showed that the operation time (P < 0.001), blood loss (P < 0.001), ALT (P < 0.001) and AST (P = 0.001) were associated with the novel difficulty score significantly. Compared with DSS-B, the NDSS has a higher area under the receiver operating characteristic (AUROC) (0.838 vs. 0.814). The nomogram was established according to the NDSS. The AUROCs of the nomogram in training and testing cohort were 0.833 and 0.767. The calibration curves for the probability of adverse event showed optimal agreement between the probability as predicted by the nomogram and the actual probability. Conclusions: We developed a nomogram with the NDSS that can predict the difficulty of LLR. This system could more accurately reflect the difficulty of surgery and help liver surgeons to make the surgical plan and ensure the safety of the operation.

Identification of Key Genes in the HBV-Related HCC Immune Microenvironment Using Integrated Bioinformatics Analysis.

Purpose: Hepatocellular carcinoma (HCC) has poor prognosis and high mortality among gastrointestinal tumors because of its insidious onset and strong invasiveness. However, there was little understanding of their pathogenesis. The purpose of this study was to use bioinformatics analysis to identify genes associated with the immune microenvironment in HBV-related HCC and to develop new therapeutic targets to prevent and treat cancer. Methods: RNA-seq data of HBV-related HCC cases were downloaded from TCGA-LIHC database. ESTIMATE and Deseq2 algorithms were used to screen out differentially expressed genes (DEGs). WGCNA was used to construct gene coexpression networks. In key modules, functional enrichment analysis was performed. Protein-protein interaction (PPI) was used to screen hub genes, and survival analysis was conducted to assess their prognostic significance. Following, we search for key genes differentially expressed between cancerous and paracancerous tissues in GSE136247 and GSE121248 datasets. Reveal the potential links between key genes in immune infiltration by using TIMER. Finally, in TCGA-LIHC database, integration of key genes with clinical data were used to further validate their correlation with prognosis. Results: In the cohort of HBV-related HCC patients, immune/stromal/ESTIMATE scores were not significantly associated with patient prognosis. After bioinformatics analysis, screening out five key genes was significantly related to the prognosis of HBV-related HCC. Downregulation of SLAMF1 and TRAF3IP3 suggested poor prognosis and was related to a variety of immune cell infiltration. Furthermore, compared with adjacent nontumor tissues, TRAF3IP3 and SLAMF1 were highly expressed in tumor tissues and were linked to tumor recurrences. Conclusion: In conclusion, SLAMF1 and TRAF3IP3 were identified with higher expression in tumor tissues and associated with tumor recurrence. It will be a new research direction of tumor progress and treatment.

Construction of a Prognostic Immune-Related LncRNA Risk Model for Gastric Cancer.

Gastric cancer (GC) is one of the most common malignancies, and novel prognostic biomarkers for it are urgently required. This study is aimed at screening a group of immune-related lncRNAs (IRLs) in predicting the prognosis of GC patients. Genetic and clinical information from the 360 GC patients was included in this study. Eight IRLs in lncRNA-miRNA-mRNA network were screened out according to differential expression analysis. A novel risk score model with three IRLs (MIR4435-1HG, UCA1, and RP11-617F23.1) were identified, and patients were assigned to a high-risk group and a low-risk group. Patients in the low-risk group had a better prognosis. In addition, two nomograms were developed to predict the prognosis of GC. We evaluated the correlation between IRLs and the immune infiltration level of GC using TIMER. Furthermore, we verified that RP11-617F23.1 was significantly upregulated in human GC tissues compared with their adjacent tissues. And, patients with high RP11-617F23.1 expression in tumor tissues had poorer survival. In conclusion, we established a novel risk model based on IRLs for predicting the prognosis of GC. Meanwhile, a novel IRL, RP11-617F23.1, could serve as a predictor of prognosis for patients with GC.

Single medium-sized hepatocellular carcinoma treated with sequential conventional transarterial chemoembolization (cTACE) and microwave ablation at 4 weeks versus cTACE alone: a propensity score.

BACKGROUND: Microwave ablation (MWA) is a potentially curative treatment for unresectable patients with hepatocellular carcinoma (HCC) ≤ 3 cm, while its therapeutic efficacy decreases significantly for HCC > 3cm. Previous studies have demonstrated that conventional transarterial chemoembolization (cTACE) combined with MWA (cTACE-MWA) may improve local tumor control rate and reduce the recurrence rate for HCC > 3cm. However, there have been few study designs to analyze the clinical efficacy of cTACE-MWA for medium-sized HCC (3-5cm). Therefore, this study aims to compare the clinical efficacy and safety of cTACE-MWA with cTACE alone for a single medium-sized HCC of 3-5 cm in diameter. METHODS: We retrospectively investigate the data of 90 patients with a single medium-sized HCC who were referred to our hospital and underwent cTACE-MWA or cTACE alone from December 2017 to March 2020. Then, patients were identified with propensity score-matched (1:1). The local tumor response to treatment and time to progression (TTP) were compared using mRECIST criteria between the cTACE-MWA group and the cTACE group. RESULTS: A total of 42 patients were included after matching (cTACE-MWA: 21; cTACE: 21). Comparing with cTACE, cTACE-MWA demonstrate significantly better local tumor control (ORR: 95.2% vs 61.9%, p = 0.02; DCR: 95.2% vs 66.7%, p = 0.045) and TTP (median 19.8 months vs 6.8 months, p < 0.001). The 1- and 2-year cumulative probabilities of OS were 100% and 95% in the cTACE-MWA group, which were significantly higher than those in the cTACE group (95% and 76%) (p = 0.032). Multivariate Cox regression analysis illustrates that cTACE-MWA was associated with better TTP (hazard ratio, 0.28; 95% CI: 0.1, 0.76; p = 0.012), but tumor size was associated with worse TTP (hazard ratio, 1.71; 95% CI: 1.01, 2.89; p = 0.045). CONCLUSIONS: cTACE followed by MWA improved TTP and OS in patients with a single medium-sized HCC, and no major complication was observed in this study.

Novel Hypoxia-Associated Gene Signature Depicts Tumor Immune Microenvironment and Predicts Prognosis of Colon Cancer Patients.

Hypoxia, a typical hallmark of numerous tumors, indicates poor infiltration of antitumor lymphocytes, as well as facilitates the development, progression, and drug resistance of malignant cells. Here, the present research was performed to identify novel hypoxia-related molecular markers and their correlation to the tumor immune microenvironment (TIME) in colon cancer. The expression of hypoxia-related gene signature was extracted from The Cancer Genome Atlas (TCGA) COAD cohort. Based on this signature, a risk score model was constructed using the Lasso regression model. Its discrimination ability and stability were validated in another independent cohort (GSE17536) from Gene Expression Omnibus (GEO) database. Moreover, molecular biology experiments (quantitative real-time PCR and multiple immunohistochemistry) were performed to validate the results of bioinformatics analyses. Three hub genes, including PPFIA4, SERPINE1, and STC2, were chosen to build the risk score model. All of these genes were increasingly expressed in the hypoxia subgroup (HS). Compared with the normoxia subgroup (NS), HS had worse pathological features (T, N, M, and stage) and overall survival (OS), more expression of immune checkpoint molecules, poorer infiltration of some pro-inflammation immune cells (CD4+ T cells and CD8+ T cells), and enriched infiltration of M0/M2 macrophages. After the risk model was proven to be valuable and stable, a nomogram was built based on this model and some clinicopathological factors. Moreover, it had been identified that three hub genes were all increasingly expressed in hypoxic conditions by quantitative real-time PCR (qPCR). The results of multiple immunohistochemistry (mIHC) also showed that higher expression of hub genes was associated with poorer infiltration of pro-inflammation immune cells (CD8+ T cells and M1 macrophages) and richer infiltration of anti-inflammation immune cells (Treg cells and M2 macrophages). In conclusion, the present study uncovered the relations among hypoxia, TIME, and clinicopathological features of colon cancer. It might provide new insight and a potential therapeutic target for immunotherapy.

Development of novel models for predicting mismatch repair protein deficiency and relevant disease-free survival in colorectal cancer patients.

PURPOSE: DNA mismatch repair (MMR) protein deficiency has attached more attention for its potential to be a biomarker of immunotherapy for colorectal cancer (CRC) patients. However, clinical models involving the expression status of MMR protein are rare. Herein, we sought to develop two clinical models (a diagnostic model for the prediction of MMR status and a prognostic model for the prediction of disease-free survival) for CRC patients. METHODS: A total of 582 CRC patients were finally included. There were 53 patients with deficient expression of MMR protein. The differences between the deficient MMR (dMMR) group and the proficient MMR (pMMR) group were analyzed. RESULTS: Compared to pMMR patients, those with dMMR status were younger and had better pathological features (depth of invasion, lymph node metastasis, distant metastasis, pathological stage, perineuronal invasion, and PLT level) and disease-free survival (DFS). The tumor location of the left colon, adenocarcinoma, and abnormal PLT level were identified as the independent predictors for pMMR. Based on these data, we developed the diagnostic model using Logistic regression analysis. It showed a satisfactory accuracy (AUC = 82.3% in the derivate set; AUC = 73.6% in the validation set). Furthermore, pMMR, poorer differentiation, perineuronal invasion, distant metastasis, lower hemoglobin level, and abnormal CEA level were established as the independent prognostic factors of poorer DFS. Based on them, a prognostic model with valuable performance (1-year AUC = 75.5%/3-year AUC = 76.9% in the derivate set; 1-year AUC = 72.3%/3-year AUC = 73.8% in the validation set) was developed. CONCLUSIONS: Our diagnostic and prognostic models could identify CRC patients at risk for pMMR protein expression and disease recurrence. It may contribute to improving the diagnosis and treatment of CRC patients at an individual level.

Meta-Analysis of Children's Acute Psychological Stress and Action Stress on Immune Function under Microscope Images.

The immune system is a complex system, mainly including immune cells and immune organs. When the human body is invaded by foreign substances, the immune system will play a role in resisting the attack of harmful substances and pure necrotic cells, which is the defense structure of the body. The purpose of this study was to analyze children's acute psychological stress and action stress, and judge the adverse effects on immune function. Through the stress experiment of rats, three experimental groups were set up, which were placebo control group, placebo stress group, and drug stress group. The experiments include material-level test, sugar preference test, body weight test, and lymphocyte test. The experimental data show that stress reaction not only causes negative emotions, but also reduces weight gain by about 5%, and sugar preference decreases by about 40% compared with the normal group. There was no significant difference in the number of granulocytes and intermediate cells in the blood, but the number of lymphocytes increased from 2.49 × 109/L to 5.03 × 109/L. It shows that acute psychological stress has an inhibitory effect on the immune function of the body; not only suitable load exercise can improve the immune function of the body but also the mechanism may be that moderate load exercise makes the rat axis has better adaptability, and improves hormones, cytokines, and cytokines. The secretion of neurotransmitters can maintain the stability of the body's immune function.

Spiro[cyclopentadithiophene-dioxolane]-Based D-A-D Type Organic Molecule for Both Crystallization Improvement and Band Adjustment of Perovskites.

To improve the crystallization and meanwhile adjust the band levels of perovskites, we design and synthesize a novel organic molecule, 4,4'-(spiro[cyclopenta[1,2-b:5,4-b']dithiophene-4,2'-[1,3]dioxolane]-2,6-diyl)bis(N,N-bis(4-methoxyphenyl)aniline) (TM1), to dissolve in an antisolvent for the antisolvent engineering of perovskite solar cells (PSCs). The coordination interactions between TM1 and Pb2+ ions in perovskites and the hydrogen bonds between the O atoms in the methoxy of TM1 and the MA+ in perovskites are characterized with X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Owing to these interactions, TM1 can improve the perovskite crystallization, which reduces the trap density, enhances the interfacial hole extraction, and retards charge recombination as well, boosting short-circuit photocurrent notably. TM1 also shifts the valence band of perovskites upward by 0.17 eV, which aligns better with the highest occupied molecular orbital of hole transport materials and thus increases the open-circuit photovoltage significantly. As a result, the power conversion efficiency is enhanced from 17.22 to 20.21% by TM1. Moreover, TM1 can also improve device stability significantly. These findings demonstrate that TM1 is a kind of functional material as an additive in an antisolvent for both crystallization improvement and energy level adjustment of perovskites toward highly efficient and stable PSCs.

Black Phase of Inorganic Perovskite Stabilized with Carboxyimidazolium Iodide for Stable and Efficient Inverted Perovskite Solar Cells.

As all-inorganic perovskite (CsPbI3-xBrx) is prone to phase transition from the α phase (black phase) to the δ phase (yellow phase) in a humid environment or under heating, improving the phase stability of all-inorganic perovskite of the black phase is one of the urgent problems to solve. Herein, 1,2-dimethyl-3-acetylimidazolium iodide (DMAII) is spin-coated onto the surface of CsPbI3-xBrx perovskite for use in p-i-n perovskite solar cells (PSCs). We find that the DMAII coating has two effects on the CsPbI3-xBrx perovskite film: surface passivation and phase stabilization of perovskite. Traps in the CsPbI3-xBrx perovskite film can be reduced significantly by DMAII passivation, resulting in enhanced hole extraction and suppressed charge recombination. Consequently, the power conversion efficiency (PCE) is improved from 10.81 to 13.14%. Moreover, the DMAII coating can significantly inhibit the phase transition from the α phase to the δ phase in a humid environment or under heating, as characterized by the X-ray diffraction pattern, UV-vis absorption spectrum, and film color. After exposing the CsPbI3-xBrx perovskite films to a humid atmosphere (relative humidity = 40-60%) for 6 h, the PCE decreases dramatically to only 0.12% of the initial PCE for the PSC without the DMAII coating, while the PCE maintains 80% of the initial PCE for the PSC with the DMAII coating. In addition, when the PSC devices are heated at 120 °C for 4 h, the control PSC shows a 96% decrease in PCE, while the PCE decay is only 9% for the DMAII-coated PSC. These findings indicate that carboxyl-substituted imidazolium iodide is a kind of promising material to not only passivate traps but also stabilize the black phase of all-inorganic perovskite.