Accurate and fast implementation of soybean pod counting and localization from high-resolution image.

Introduction: Soybean pod count is one of the crucial indicators of soybean yield. Nevertheless, due to the challenges associated with counting pods, such as crowded and uneven pod distribution, existing pod counting models prioritize accuracy over efficiency, which does not meet the requirements for lightweight and real-time tasks. Methods: To address this goal, we have designed a deep convolutional network called PodNet. It employs a lightweight encoder and an efficient decoder that effectively decodes both shallow and deep information, alleviating the indirect interactions caused by information loss and degradation between non-adjacent levels. Results: We utilized a high-resolution dataset of soybean pods from field harvesting to evaluate the model's generalization ability. Through experimental comparisons between manual counting and model yield estimation, we confirmed the effectiveness of the PodNet model. The experimental results indicate that PodNet achieves an R2 of 0.95 for the prediction of soybean pod quantities compared to ground truth, with only 2.48M parameters, which is an order of magnitude lower than the current SOTA model YOLO POD, and the FPS is much higher than YOLO POD. Discussion: Compared to advanced computer vision methods, PodNet significantly enhances efficiency with almost no sacrifice in accuracy. Its lightweight architecture and high FPS make it suitable for real-time applications, providing a new solution for counting and locating dense objects.

Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy.

Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built a neural network incorporating factors associated with neoantigen production, presentation, and recognition, which exhibited potential for differentiating cancer patients likely to benefit from ICIs. Our findings highlight the clinical utility of evaluating HLA-I tumor antigen presentation capacity and describe how ICI response may depend on HLA-mediated immunity.

Risk Perception Scale of Disease Aggravation for older patients with non-communicable diseases: Instrument development and cross-sectional validation study.

AIM: The present study aimed to develop the Risk Perception Scale of Disease Aggravation for older patients with non-communicable diseases and evaluate its psychometric properties. DESIGN: Instrument development and cross-sectional validation study were conducted. METHODS: This study contained four phases. In phase I, a systematic literature review was conducted to identify the conception of disease aggravation and risk perception. In phase II, a draft scale was formulated from face-to-face semi-structured in-depth interviews by Colaizzi's seven-step qualitative analysis method and group discussions among the researchers. In phase III, domains and items of the scale were revised in accordance with the suggestions from Delphi consultation and patient feedback. In phase IV, psychometric properties were evaluated. FINDINGS: Exploratory and confirmatory factor analyses determined four structural factors. Convergent and discriminant validities were acceptable because the average variance extracted coefficients ranged from .622 to .725, and the square roots of the average variance extracted coefficients for the four domains were larger than those of bivariate correlations between domains. The scale also exhibited excellent internal consistency and test-retest reliability (Cronbach's alpha coefficient = .973, intraclass correlation coefficient = .840). CONCLUSIONS: Risk Perception Scale of Disease Aggravation is a new instrument that measures the risk perception of disease aggravation for older patients with non-communicable diseases, including possible reason, serious outcome, behaviour control and affection experience. The scale contains 40 items that are scored on a 5-point Likert scale, and it has acceptable validity and reliability. IMPACT: The scale is applied to identify different levels of risk perception of disease aggravation for older patients with non-communicable diseases. Clinical nurses can provide targeted interventions to improve older patients' risk perception of disease aggravation based on levels of risk perception during hospitalization and the period before discharge. PATIENT OR PUBLIC CONTRIBUTION: Experts provided suggestions for revising the scale dimensions and items. Older patients participated in the scale revision process to improve the wording of the scale.

Comparison of anesthetic effects of different doses of alfentanil combined with ciprofol in elderly patients undergoing ERCP: a randomized controlled trial.

BACKGROUND AND OBJECTS: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are often old and poor in physical fitness. The purpose of this study was to investigate the anesthetic effect of different doses of alfentanil combined with ciprofol in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). METHODS: In this clinical trial, 137 patients, who were candidates for ERCP were randomly divided into three groups. Group A were given 0.15 µg/kg/min of alfentanil in maintenance stage, Group B were given 0.25 µg/kg/min and Group C were given 0.35 µg/kg/min. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2) of the patients at each time point including the entry into the operation room (T0), at the beginning of surgery(T1), 10 min after surgery(T2), 20 min after surgery(T3), 30 min after surgery(T4),endoscopy withdrawal (T5) were recorded. Adverse events(including respiratory depression, body movement and hypoxemia),the dosage of ciprofol, the time of operation time and awakening were recorded. RESULTS: Compared with Group A, MAP and HR in Group B and Group C was decreased during T1-T5 (P < 0.05). Compared with group B, MAP and HR in group C was decreased during T1-T5 (P < 0.05). Compared with Group A and Group C,the number of adverse reactions of Group B was decreased(P < 0.05). There was no statistical difference in surgical time among the three groups(P > 0.05),but a statistically significant difference in recovery time (P < 0.05). CONCLUSION: The adverse events of alfentanil 0.25µg/kg/min combined with ciprofol were low, and the anesthetic effect was the best.

[Expression and significance of jumonji domain-containing protein 2B and hypoxia inducible factor-1α in non-Hodgkin lymphoma tissues in children]. / 含jumonji结构域的蛋白2Bå’Œç¼ºæ°§è¯±å¯¼å› å­1α在儿童非霍奇金淋巴瘤组织中的表达及意义.

OBJECTIVES: To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children. METHODS: Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed. RESULTS: The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024). CONCLUSIONS: JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.

Nurses' Colleague Solidarity and Job Performance: Mediating Effect of Positive Emotion and Turnover Intention.

Background: Job performance is known as an essential reflection of nursing quality. Colleague solidarity, positive emotion, and turnover intention play effective roles in a clinical working environment, but their impacts on job performance are unclear. Investigating the association between nurses' colleague solidarity and job performance may be valuable, both directly and through the mediating roles of positive emotion and turnover intention. Methods: In this cross-sectional study, a total of 324 Chinese nurses were recruited by convenience sampling method from July 2016 to January 2017. Descriptive analysis, Spearman's correlation analysis, and the structural equation model were applied for analysis by SPSS 26.0 and AMOS 24.0. Results: A total of 49.69% of participants were under 30 years old, and 90.12% of participants were female. Colleague solidarity and positive emotion were positively connected with job performance. The results indicated the mediating effects of positive emotion and turnover intention in this relationship, respectively, as well as the chain mediating effect of positive emotion and turnover intention. Conclusions: In conclusion, dynamic and multiple supportive strategies are needed for nurse managers to ameliorate nursing job performance by improving colleague solidarity and positive emotion and decreasing turnover intention based on the job demand-resource model.

A Comprehensive Benchmark of Transcriptomic Biomarkers for Immune Checkpoint Blockades.

Immune checkpoint blockades (ICBs) have revolutionized cancer therapy by inducing durable clinical responses, but only a small percentage of patients can benefit from ICB treatments. Many studies have established various biomarkers to predict ICB responses. However, different biomarkers were found with diverse performances in practice, and a timely and unbiased assessment has yet to be conducted due to the complexity of ICB-related studies and trials. In this study, we manually curated 29 published datasets with matched transcriptome and clinical data from more than 1400 patients, and uniformly preprocessed these datasets for further analyses. In addition, we collected 39 sets of transcriptomic biomarkers, and based on the nature of the corresponding computational methods, we categorized them into the gene-set-like group (with the self-contained design and the competitive design, respectively) and the deconvolution-like group. Next, we investigated the correlations and patterns of these biomarkers and utilized a standardized workflow to systematically evaluate their performance in predicting ICB responses and survival statuses across different datasets, cancer types, antibodies, biopsy times, and combinatory treatments. In our benchmark, most biomarkers showed poor performance in terms of stability and robustness across different datasets. Two scores (TIDE and CYT) had a competitive performance for ICB response prediction, and two others (PASS-ON and EIGS_ssGSEA) showed the best association with clinical outcome. Finally, we developed ICB-Portal to host the datasets, biomarkers, and benchmark results and to implement the computational methods for researchers to test their custom biomarkers. Our work provided valuable resources and a one-stop solution to facilitate ICB-related research.

Causality between heart failure and epigenetic age: a bidirectional Mendelian randomization study.

AIMS: Heart failure (HF) is a prevalent age-related cardiovascular disease with poor prognosis in the elderly population. This study aimed to establish the causal relationship between ageing and HF by conducting a bidirectional Mendelian randomization (MR) analysis on epigenetic age (a marker of ageing) and HF. METHODS AND RESULTS: Genome-wide association study data for epigenetic age (GrimAge, HorvathAge, HannumAge, and PhenoAge) and HF were collected and assessed for significant genetic variables. A bidirectional MR analysis was carried out using the random-effects inverse-variance weighted (IVW) method as the primary approach, while other methods (MR-Egger, weighted median, simple mode, and weighted mode) and multiple sensitivity analyses (heterogeneity analysis, leave-one-out sensitivity analysis, and horizontal pleiotropy analysis) were employed to evaluate the impact of epigenetic age on HF and vice versa. Bidirectional MR analysis of two samples revealed that the epigenetic PhenoAge clock increased the risk of HF [IVW odds ratio (OR) 1.015, 95% confidence interval (CI) 1.002-1.028, P = 0.028 and weighted median OR 1.020, 95% CI 1.001-1.038, P = 0.039]. Other results were not statistically significant. CONCLUSIONS: The bidirectional MR analysis demonstrated a causal link between genetically predicted epigenetic age and HF in individuals of European descent. Further research into epigenetic age in other populations and additional genetic information related to HF is warranted.

OsMADS5 interacts with OsSPL14/17 to inhibit rice root elongation by restricting cell proliferation of root meristem under ammonium supply.

Nitrogen (N) is a vital major nutrient for rice (Oryza sativa). Rice responds to different applications of N by altering its root morphology, including root elongation. Although ammonium ( NH 4 + ) is the primary source of N for rice, NH 4 + is toxic to rice roots and inhibits root elongation. However, the precise molecular mechanism that NH 4 + -inhibited root elongation of rice is not well understood. Here, we identified a rice T-DNA insert mutant of OsMADS5 with a longer seminal root (SR) under sufficient N conditions. Reverse-transcription quantitative PCR analysis revealed that the expression level of OsMADS5 was increased under NH 4 + compared with NO 3 - supply. Under NH 4 + conditions, knocking out OsMADS5 (cas9) produced a longer SR, phenocopying osmads5, while there was no significant difference in SR length between wild-type and cas9 under NO 3 - supply. Moreover, OsMADS5-overexpression plants displayed the opposite SR phenotype. Further study demonstrated that enhancement of OsMADS5 by NH 4 + supply inhibited rice SR elongation, likely by reducing root meristem activity of root tip, with the involvement of OsCYCB1;1. We also found that OsMADS5 interacted with OsSPL14 and OsSPL17 (OsSPL14/17) to repress their transcriptional activation by attenuating DNA binding ability. Moreover, loss of OsSPL14/17 function in osmads5 eliminated its stimulative effect on SR elongation under NH 4 + conditions, implying OsSPL14/17 may function downstream of OsMADS5 to mediate rice SR elongation under NH 4 + supply. Overall, our results indicate the existence of a novel modulatory pathway in which enhancement of OsMADS5 by NH 4 + supply represses the transcriptional activities of OsSPL14/17 to restrict SR elongation of rice.

A multicenter phase II trial of primary prophylactic PEG-rhG-CSF in pediatric patients with solid tumors and non-Hodgkin lymphoma after chemotherapy: An interim analysis.

BACKGROUND: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) can be used in pediatric patients. This study assessed the safety and efficacy of PEG-rhG-CSF as a primary prophylactic drug against neutropenia after chemotherapy in pediatric patients with solid tumors or non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: This phase II study (between October 2020 and March 2022) enrolled pediatric patients with solid tumors or NHL treated with high-intensity chemotherapy and with grade ≥3 myelosuppression for at least 14 days during chemotherapy. Prophylactic PEG-rhG-CSF was given at 100 µg/kg body weight (maximum total dosage of 6 mg) once 24-48 h following chemotherapy for two cycles. The primary endpoint was the incidence of PEG-rhG-CSF-related adverse events (AEs). The key secondary endpoints were the rates of grade 3/4 neutropenia and febrile neutropenia (FN). RESULTS: This study included 160 pediatric patients with a median age of 6.22 (0.29, 18.00) years. Fifty-eight patients (36.25%) were diagnosed with sarcoma. AEs potentially related to PEG-rhG-CSF included bone pain (n = 32), fatigue (n = 21), pain at the injection site (n = 21), and myalgia (n = 20). The rates of grade 3/4 neutropenia and FN during treatment were 57.28% and 29.45%, respectively. CONCLUSION: PEG-rhG-CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04547829.

A bioinformatics approach to identifying the biomarkers and pathogenesis of major depressive disorder combined with acute myocardial infarction.

This study investigated the pathogenesis of major depressive disorder (MDD) and acute myocardial infarction (AMI) using bioinformatics. We analyzed MDD and AMI (MDD-AMI) datasets provided by the Gene Expression Omnibus (GEO) database for genes common to MDD and AMI using GEO2R and weighted gene co-expression network analysis (WGCNA). We also performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and we used Disease Ontology (DO) analysis to identify a) the pathways through which genes function and b) comorbidities. We also created a protein-protein interaction (PPI) network using the STRING database to identify the hub genes and biomarkers. NetworkAnalyst 3.0 was used to construct a transcription factor (TF) gene regulatory network. We also identified relevant complications and potential drug candidates. The 27 genes common to MDD and AMI were enriched in the pathways regulating TFs and mediating immunity and inflammation. The hub genes in the PPI network included TLR2, HP, ICAM1, LCN2, LTF, VCAN, S100A9 and NFKBIA. Key TFs were KLF9, KLF11, ZNF24, and ZNF580. Cardiovascular, pancreatic, and skeletal diseases were common complications. Hydrocortisone, simvastatin, and estradiol were candidate treatment drugs. Identification of these genes and their pathways may provide new targets for further research on the pathogenesis, biomarkers, and treatment of MDD-AMI. Together our results suggested that TLR2 and VCAN might be the key genes associated with MDD complicated by AMI.

Strigolactone and gibberellin signaling coordinately regulate metabolic adaptations to changes in nitrogen availability in rice.

Modern semi-dwarf rice varieties of the "Green Revolution" require a high supply of nitrogen (N) fertilizer to produce high yields. A better understanding of the interplay between N metabolism and plant developmental processes is required for improved N-use efficiency and agricultural sustainability. Here, we show that strigolactones (SLs) modulate root metabolic and developmental adaptations to low N availability for ensuring efficient uptake and translocation of available N. The key repressor DWARF 53 (D53) of the SL signaling pathway interacts with the transcription factor GROWTH-REGULATING FACTOR 4 (GRF4) and prevents GRF4 from binding to its target gene promoters. N limitation induces the accumulation of SLs, which in turn promotes SL-mediated degradation of D53, leading to the release of GRF4 and thus promoting the expression of genes associated with N metabolism. N limitation also induces degradation of the DELLA protein SLENDER RICE 1 (SLR1) in an D14- and D53-dependent manner, effectively releasing GRF4 from competitive inhibition caused by SLR1. Collectively, our findings reveal a previously unrecognized mechanism underlying SL and gibberellin crosstalk in response to N availability, advancing our understanding of plant growth-metabolic coordination and facilitating the design of the strategies for improving N-use efficiency in high-yield crops.

Utility of cell-free DNA from bronchial washing fluid in diagnosis and genomic determination for radiology-suspected pulmonary nodules.

BACKGROUND: Bronchial washing fluid (BWF) is a less-invasive specimen. Due to the limited sensitivity of BWF cellular component diagnosis, the aim of this study was to explore the potential role of BWF supernatant as a source of liquid biopsy of lung cancer. METHODS: This prospective study enrolled 76 suspected and 5 progressed lung cancer patients. Transbronchial biopsy tissues, BWF supernatant (BWF_Sup) and BWF precipitant (BWF_Pre) were tested by a targeted panel of 1021 genes. RESULTS: BWF_Sup cell-free DNA (cfDNA) was superior to tissue biopsy and BWF_Pre in determining mutational allele frequency, tumour mutational burden, and chromosomal instability. Moreover, BWF_Sup and BWF_Pre achieved comparable efficacy to tissue samples in differentiating malignant and benign patients, but only BWF_Sup persisted differentiated performance after excluding 55 malignancies pathologically diagnosed by bronchoscopic biopsy. Among 67 malignant patients, 82.1% and 71.6% of tumour-derived mutations (TDMs) were detected in BWF_Sup and BWF_Pre, respectively, and the detectability of TDMs in BWF_Sup was independent of the cytological examination of BWF. BWF_Sup outperformed BWF_Pre in providing more subclonal information and thus might yield advantage in tracking drug-resistant markers. CONCLUSIONS: BWF_Sup cfDNA is a reliable medium for lung cancer diagnosis and genomic profiles and may provide important information for subsequent therapeutic regimens.

Comprehensive characterization of genomic and radiologic features reveals distinct driver patterns of RTK/RAS pathway in ground-glass opacity pulmonary nodules.

Ground-glass opacity (GGO)-associated pulmonary nodules have been known as a radiologic feature of early-stage lung cancers and exhibit an indolent biological behavior. However, the correlation between driver genes and radiologic features as well as the immune microenvironment remains poorly understood. We performed a custom 1021-gene panel sequencing of 334 resected pulmonary nodules presenting as GGO from 262 Chinese patients. A total of 130 multiple pulmonary nodules were sampled from 58 patients. Clinical-pathologic and radiologic parameters of these pulmonary nodules were collected. Immunohistochemistry (IHC) and multiplex immunofluorescent staining (mIF) were applied to analyze proliferation and immune cell markers of GGO-associated pulmonary nodules. Compared with pure GGO nodules, mixed GGO nodules were enriched for invasive adenocarcinoma (IAC) (182/216 vs 73/118, P < .001). Eighty-eight percent (294/334) of GGO-associated nodules carried at least one mutation in EGFR/ERBB2/BRAF/KRAS/MAP2K1 of the RTK/RAS signaling pathway, and the alterations in these driver genes were mutually exclusive. The analysis of multifocal pulmonary nodules from the same patient revealed evidence of functional convergence on RTK/RAS pathways. Nodules with ERBB2/BRAF/MAP2K1 mutations tended to be more indolent than those with EGFR and KRAS mutations. IHC and mIF staining showed that KRAS-mutant GGO nodules displayed higher infiltration of CD4+ T cell and CD8+ T cell as well as stronger proliferation and immune inhibitory signals. Our study demonstrates a driver landscape of radiologically detectable GGO-associated pulmonary nodules in Chinese patients and supports that different driver patterns in RTK/RAS pathway are corresponding to different radiologic features.

Dysregulated Immune and Metabolic Microenvironment Is Associated with the Post-Operative Relapse in Stage I Non-Small Cell Lung Cancer.

The underlying mechanism of post-operative relapse of non-small cell lung cancer (NSCLC) remains poorly understood. We enrolled 57 stage I NSCLC patients with or without relapse and performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on available primary and recurrent tumors, as well as on matched tumor-adjacent tissues (TATs). The WES analysis revealed that primary tumors from patients with relapse were enriched with USH2A mutation and 2q31.1 amplification. RNA-seq data showed that the relapse risk was associated with aberrant immune response and metabolism in the microenvironment of primary lesions. TATs from the patients with relapse showed an immunosuppression state. Moreover, recurrent lesions exhibited downregulated immune response compared with their paired primary tumors. Genomic and transcriptomic features were further subjected to build a prediction model classifying patients into groups with different relapse risks. We show that the recurrence risk of stage I NSCLC could be ascribed to the altered immune and metabolic microenvironment. TATs might be affected by cancer cells and facilitate the invasion of tumors. The immune microenvironment in the recurrent lesions is suppressed. Patients with a high risk of relapse need active post-operative intervention.

Influencing factors of lung cancer patients' participation in shared decision-making: a cross-sectional study.

PURPOSE: The purpose of this study was to investigate and analyze the level of actual participation and perceived importance of shared decision-making on treatment and care of lung cancer patients, to compare their differences and to explore their influencing factors. METHODS: A total of 290 lung cancer patients were collected from oncology and thoracic surgery departments of a comprehensive medical center in Qingdao from October 2018 to December 2019. Participants completed a cross-sectional questionnaire to assess their actual participation and perceived importance in shared decision-making on treatment and care. Descriptive analysis and non-parametric tests were carried out to assess the status quo of patients' shared decision-making on treatment and care. Binary logistic regression analysis with a stepwise back-wards was applied to predict factors that affected patients' participation in shared decision-making. RESULTS: The results showed that patients with lung cancer had a low degree of participation in shared decision-making. There were significant differences between actual participation and perceived importance of shared decision-making on treatment and care. Education level, age, gender, income, marital status, personality, the course of the disease (> 6 months), and the pathological TNM staging (III) affected patient's level of participation in shared decision-making. CONCLUSION: Actual participation in shared decision-making on the treatment and care of lung cancer patients was low and considered unimportant. We could train oncology nurses to use patient decision aids to help patients and families participate in shared decision-making on patients' value, preferences and needs.

Identification of gastric cancer with convolutional neural networks: a systematic review.

The identification of diseases is inseparable from artificial intelligence. As an important branch of artificial intelligence, convolutional neural networks play an important role in the identification of gastric cancer. We conducted a systematic review to summarize the current applications of convolutional neural networks in the gastric cancer identification. The original articles published in Embase, Cochrane Library, PubMed and Web of Science database were systematically retrieved according to relevant keywords. Data were extracted from published papers. A total of 27 articles were retrieved for the identification of gastric cancer using medical images. Among them, 19 articles were applied in endoscopic images and 8 articles were applied in pathological images. 16 studies explored the performance of gastric cancer detection, 7 studies explored the performance of gastric cancer classification, 2 studies reported the performance of gastric cancer segmentation and 2 studies analyzed the performance of gastric cancer delineating margins. The convolutional neural network structures involved in the research included AlexNet, ResNet, VGG, Inception, DenseNet and Deeplab, etc. The accuracy of studies was 77.3 - 98.7%. Good performances of the systems based on convolutional neural networks have been showed in the identification of gastric cancer. Artificial intelligence is expected to provide more accurate information and efficient judgments for doctors to diagnose diseases in clinical work.

Acute-Phase Serum Amyloid A May Predict Microvascular Invasion and Early Tumor Recurrence in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma Undergoing Liver Resection.

OBJECTIVE: To elucidate the impact of acute-phase protein serum amyloid A (aSAA) on microvascular invasion (MVI) and early recurrence in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: HBV-related HCC patients (n = 192) undergoing liver resection were included in the study. The protein levels of aSAA were analyzed by immunohistochemical staining in 172 tumor specimens, and further detected via western blotting in HCC and their corresponding portal vein tumor thrombus (PVTT) (n = 20). Cox and logit regression analysis was performed. Exploratory subgroup analysis was used to balance the potential confounders. RESULTS: HBV-related HCC patients with high aSAA levels tended to have high HBV-DNA loads. Logit and Cox regression analyses revealed high expression of aSAA is an independent risk factor not only for MVI (OR 5.384, 95% CI 2.286-13.301, P < 0.001) but also for early recurrence (HR 6.040, 95% CI 1.970-18.540, P = 0.002), overall recurrence (HR 3.720, 95% CI 2.140-6.450, P < 0.001), and overall survival (HR 4.15, 95% CI 2.380-7.230, P < 0.001). Subgroup analysis showed that the effects of aSAA were consistent across all subgroups examined. Additionally, the aSAA protein level was significantly higher in PVTT than that in its corresponding tumor specimen. A high HBV-DNA level and large tumor size were the independent risk factors for early HCC recurrence in patients with high levels of aSAA. CONCLUSIONS: High expression of aSAA was an independent risk factor for MVI and early tumor recurrence in HBV-related HCC patients after liver resection. The aSAA protein level could thus be a promising biomarker for predicting MVI and early recurrence in these patients.

LncRNA NORAD Mediates the Proliferation and Apoptosis of Diffuse Large-B-Cell Lymphoma via Regulation of miR-345-3p/TRAF6 Axis.

BACKGROUND: Diffuse large-B-cell lymphoma (DLBCL), as the most common subtype of B Cell Non-Hodgkin lymphoma (B-NHL), is one of the lymphoid malignancies with poor prognosis worldwide. Non-coding RNA activated by the DNA damage (NORAD), a novel identified lncRNA involved in the DNA repairment process, is reportedly to participate in carcinogenesis, and it is predicted to sponge miR-345-3p. However, LncRNA NORAD has never been investigated in DLBCL. AIM OF THE STUDY: To investigate the role of LncRNA NORAD and miR-345-3p in DLBCL cells and explore the underlying mechanisms. METHODS: LncRNA NORAD and miR-345-3p levels were determined in the blood samples from patients with B-NHL. Human DLBCL cell lines DB and SU-DHL-4 were transfected with LncRNA NORAD small interfering RNA, miRNA-345-3p mimics, or miRNA-345-3p inhibitor using Lipofectamine RNAiMAX Reagent. Cell cycle, proliferation, and apoptosis were assessed in the transfected cells. RESULTS: Silencing of lncRNA NORAD and overexpression of miR-345-3p both inhibited cell proliferation, induced cell cycle arrest, and triggered apoptosis in DLBCL cells. Inhibition of miR-345-3p counteracted the suppression effects of LncRNA NORAD silencing on DLBCL progression. In addition, LncRNA NORAD shared the regulatory binding sites of miR-345-3p with TNF receptor associated factor 6 (TRAF6). Knockdown of LncRNA NORAD decreased the levels of TRAF6, simultaneously, resulted in deactivation of PI3K/Akt pathway in DLBCL cells. CONCLUSION: LncRNA NORAD regulated DLBCL cell growth and apoptosis via miR-345-3p/TRAF6/PI3K/Akt axis.

MiR-363 suppresses the tumor growth of natural killer/T-cell lymphoma via the SIRT6/PI3K/AKT axis.

Background: Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive tumor of non-Hodgkin's lymphoma. The role of micro ribonucleic acid (RNA) (miR)-363 in NKTCL has not yet been elucidated. The present study aimed to investigate the potential role of miR-363 in NKTCL. Methods: The expression of the top five differentially expressed microRNAs (miRNAs) as well as sirtuin 6 (SIRT6) in NK normal cells and its tumor cell lines were explored. The clinical tissues of NKTCL patients were collected and analyzed for expression of miR-363 and SIRT6. In addition, human NK/T-cell lymphoma cells (SNK-6) were transfected into different groups to detect cell proliferation and apoptosis abilities through cell counting kit 8 (CCK-8) experiment and flow cytometry analysis. Western blot assay was employed to examine protein expression. NKTCL nude mice models were constructed by subcutaneous injection of stably transfected SNK-6 cells to validate the mechanism of miR-363 in NKTCL via SIRT6 in vivo. Results: MiR-363 was down-regulated in NKTCL tissues and cell lines. Overexpression of miR-363 inhibited cell proliferation and promoted cell apoptosis. In contrast, SIRT6 was up-regulated in NKTCL and proved to be a downstream target of miR-363. SIRT6 could activate the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Also, miR-363 mimic could suppress the proliferation and induce the apoptosis of NKTCL via the SIRT6/PI3K/AKT axis both in vitro and in vivo. Conclusions: MiR-363 suppresses the SIRT6/PI3K/AKT pathway to restrain cell proliferation and accelerate cell apoptosis during NKTCL progression.