Long non-coding RNA ENST00000503625 is a potential prognostic biomarker and metastasis suppressor gene in prostate cancer.

BACKGROUND: Dysregulation of Long Non-coding RNAs (lncRNAs) emerges to be a hallmark of cancers. Metastatic prostate cancer and localized disease that recurs after treatment are clinical challenges, it remains unclear how lncRNA plays a role in those processes. METHODS: From previous RNA-Seq data on 65 prostate cancer and adjacent normal tissues. We identified a novel lncRNA ENST00000503625 down-regulated in prostate cancer and correlated with tumor progression characteristics. Public datasets were examined for associations between ENST00000503625 expression and clinical parameters and prognoses. Subsequently, we constructed and externally validated a nomogram for predicting biochemical recurrence (BCR). Finally, in vitro experiments were carried out to determine how ENST00000503625 functions biologically in prostate cancer. RESULTS: Low ENST00000503625 in tumor was associated with poor clinical features and prognoses. TCGA pan-cancer analysis found that ENST00000503625 was deregulated in a variety of tumors and correlated with overall survival, disease-specific survival, and progression-free survival. The nomogram for predicting BCR was constructed using TCGA data, which exhibited excellent accuracy in external validation with Chinese Prostate Cancer Genome and Epigenome Atlas data. Gene Ontology and KEGG pathway analysis found that genes related to ENST00000503625 were enriched in multiple tumor progression related pathways. When ENST00000503625 was knocked down in vitro, the epithelial-mesenchymal transition was induced, by which cancer cells migrated and invaded more readily. CONCLUSION: Our data suggested that ENST00000503625 may serve as a potential prognostic marker or a therapeutic target for prostate cancer metastases.

Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Is a Promising Signature to Predict Prognosis and Therapies for Hepatocellular Carcinoma (HCC).

BACKGROUND: The roles of mitochondria and the endoplasmic reticulum (ER) in the progression of hepatocellular carcinoma (HCC) are well established. However, a special domain that regulates the close contact between the ER and mitochondria, known as the mitochondria-associated endoplasmic reticulum membrane (MAM), has not yet been investigated in detail in HCC. METHODS: The TCGA-LIHC dataset was only used as a training set. In addition, the ICGC and several GEO datasets were used for validation. Consensus clustering was applied to test the prognostic value of the MAM-associated genes. Then, the MAM score was constructed using the lasso algorithm. In addition, uncertainty of clustering in single-cell RNA-seq data using a gene co-expression network (AUCell) was used for the detection of the MAM scores in various cell types. Then, CellChat analysis was applied for comparing the interaction strength between the different MAM score groups. Further, the tumor microenvironment score (TME score) was calculated to compare the prognostic values, the correlation with the other HCC subtypes, tumor immune infiltration landscape, genomic mutations, and copy number variations (CNV) of different subgroups. Finally, the response to immune therapy and sensitivity to chemotherapy were also determined. RESULTS: First, it was observed that the MAM-associated genes could differentiate the survival rates of HCC. Then, the MAM score was constructed and validated using the TCGA and ICGC datasets, respectively. The AUCell analysis indicated that the MAM score was higher in the malignant cells. In addition, enrichment analysis demonstrated that malignant cells with a high MAM score were positively correlated with energy metabolism pathways. Furthermore, the CellChat analysis indicated that the interaction strength was reinforced between the high-MAM-score malignant cells and T cells. Finally, the TME score was constructed, which demonstrated that the HCC patients with high MAM scores/low TME scores tend to have a worse prognosis and high frequency of genomic mutations, while those with low MAM scores/high TME scores were more likely to have a better response to immune therapy. CONCLUSIONS: MAM score is a promising index for determining the need for chemotherapy, which reflects the energy metabolic pathways. A combination of the MAM score and TME score could be a better indicator to predict prognosis and response to immune therapy.

Elevated serum HbA1c level, rather than previous history of diabetes, predicts the disease severity and clinical outcomes of acute pancreatitis.

INTRODUCTION: The aim of our study is to explore the value of serum glycosylated hemoglobin A1c (HbA1c) in disease severity and clinical outcomes of acute pancreatitis (AP). RESEARCH DESIGN AND METHODS: Patients with AP were included from January 2013 to December 2020, retrospectively, dividing into normal serum HbA1c level (N-HbA1c) group and high serum HbA1c level (H-HbA1c) group according to the criteria HbA1c <6.5%. We compared patient characteristics, biochemical parameters, disease severity, and clinical outcomes of patients with AP in two groups. Besides, we evaluated the efficacy of serum HbA1c to predict organ failure (OF) in AP patients by receiver operating curve (ROC). RESULTS: We included 441 patients with AP, including 247 patients in N-HbA1c group and 194 patients in H-HbA1c group. Serum HbA1c level was positively correlated with Atlanta classification, systemic inflammatory response syndrome, local complication, and OF (all p<0.05). Ranson, BISAP (bedside index of severity in acute pancreatitis), and CT severity index scores in patients with H-HbA1c were markedly higher than those in patients with N-HbA1c (all p<0.01). ROC showed that the best critical point for predicting the development of OF in AP with serum HbA1c is 7.05% (area under the ROC curve=0.79). Logistic regression analysis showed H-HbA1c was the independent risk factor for the development of OF in AP. Interestingly, in patients with presence history of diabetes and HbA1c <6.5%, the severity of AP was significantly lower than that in H-HbA1c group. Besides, there was no significant difference between with and without history of diabetes in N-HbA1c group. CONCLUSIONS: Generally known, diabetes is closely related to the development of AP, and strict control of blood glucose can improve the related complications. Thus, the level of glycemic control before the onset of AP (HbA1c as an indicator) is the key to poor prognosis of AP, rather than basic history of diabetes. Elevated serum HbA1c level can become the potential indicator for predicting the disease severity of AP.

Nanozyme-like single-atom catalyst combined with artesunate achieves photothermal-enhanced nanocatalytic therapy in the near-infrared biowindow.

Selectively generating active free radical (AFR) in tumor microenvironment (TME) can promote irreversible oxidation of biomolecules and damage tumor cells, resulting in effective tumor inhibition. However, therapeutic efficacy of AFR-based tumor suppression approaches is often limited by insufficient amount of H2O2 or O2 within TME. To overcome this obstacle, we design a pH/photothermal dual responsive nanosystem (PFeSA@AS) for combined photothermal and nanocatalytic therapy in the near-infrared biowindow. Here the Fe single-atom dispersed N, S-doped carbon nanosheets (FeSA) nanozyme is dispersed by phospholipid-polyethylene glycol-amine (DSPE-PEG-NH2), and further loads artesunate (AS) via an amide reaction. Upon 808-nm laser irradiation in TME, the AS is released and further be catalyzed by the FeSA nanozyme to produce cytotoxic C-centered AFRs, and further be accelerated due to the photothermal conversion performance of FeSA (23.35%). The nanocatalytic process of FeSA nanozyme is realized by density functional theory (DFT). The tumor inhibition rates of a CT26 xenograft model is 92% through a photothermal-enhanced nanocatalytic synergistic therapy, and negligible systematic toxicity is observed. This work offers a potential paradigm of multifunctional single atomic catalysts (SACs) for enhancing tumor nanocatalytic therapy. STATEMENT OF SIGNIFICANCE: We designed a pH/photothermal dual responsive nanosystem (PFeSA@AS) for nanocatalytic therapy: (1) the nanosystem responsively releases AS under 808-nm laser irradiation in TME; (2) FeSA in the nanosystem can act as heme mimetic to convert AS into high cytotoxic C-centered free radicals for nanocatalytic therapy; (3) the photothermal conversion performance of FeSA further enhances the catalytic process to yield abundant AFR. Both in vitro and in vivo results demonstrate that this nanosystem can efficiently inhibit tumor growth through a photothermal-enhanced nanocatalytic synergistic therapy.

C-Type Lectin Receptors-Triggered Antifungal Immunity May Synergize with and Optimize the Effects of Immunotherapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system worldwide, and there is a lack of effective treatment for late-stage HCC. Recent experimental studies have demonstrated that dysfunction of the intestinal flora has a significant impact on hepatocarcinogenesis. The pathophysiological link between the intestine, its microbiota, and the liver has been described as the "gut-liver axis". Dysbiosis of the intestinal flora and increased permeability of the intestinal wall are closely associated with liver pathology through the immune response. The "gut-liver axis" theory has been applied to the clinical study of the pathogenesis and treatment of HCC. The intestinal fungal community, as part of the gut microbiome, has a significant impact on human health and disease, while relatively little research has been done in HCC. In this study, we performed a comprehensive analysis of the expression and potential biological functions of the fungal recognition receptors C-type lectin receptors (CLRs) (Dectin-1, Dectin-2, Dectin-3, and Mincle) in HCC. We found that CLRs were downregulated in HCC, and their expressions were correlated with the clinical prognosis of HCC patients. Further studies suggested that the expression of CLRs were significantly correlated with immune infiltration and immunotherapy efficacy in HCC. Based on previous studies and our findings, we hypothesize that intestinal fungal communities and CLRs-triggered antifungal immunity have a key role in the pathogenesis of HCC, and these findings may provide new perspectives and targets for HCC immunotherapy.

Human endoderm stem cells reverse inflammation-related acute liver failure through cystatin SN-mediated inhibition of interferon signaling.

Acute liver failure (ALF) is a life-threatening disease that occurs secondary to drug toxicity, infection or a devastating immune response. Orthotopic liver transplantation is an effective treatment but limited by the shortage of donor organs, the requirement for life-long immune suppression and surgical challenges. Stem cell transplantation is a promising alternative therapy for fulminant liver failure owing to the immunomodulatory abilities of stem cells. Here, we report that when transplanted into the liver, human endoderm stem cells (hEnSCs) that are germ layer-specific and nontumorigenic cells derived from pluripotent stem cells are able to effectively ameliorate hepatic injury in multiple rodent and swine drug-induced ALF models. We demonstrate that hEnSCs tune the local immune microenvironment by skewing macrophages/Kupffer cells towards an anti-inflammatory state and by reducing the infiltrating monocytes/macrophages and inflammatory T helper cells. Single-cell transcriptomic analyses of infiltrating and resident monocytes/macrophages isolated from animal livers revealed dramatic changes, including changes in gene expression that correlated with the change of activation states, and dynamic population heterogeneity among these cells after hEnSC transplantation. We further demonstrate that hEnSCs modulate the activation state of macrophages/Kupffer cells via cystatin SN (CST1)-mediated inhibition of interferon signaling and therefore highlight CST1 as a candidate therapeutic agent for diseases that involve over-activation of interferons. We propose that hEnSC transplantation represents a novel and powerful cell therapeutic treatment for ALF.

Genetic variation and marker-trait association affect the genomic selection prediction accuracy of soybean protein and oil content.

Introduction: Genomic selection (GS) is a potential breeding approach for soybean improvement. Methods: In this study, GS was performed on soybean protein and oil content using the Ridge Regression Best Linear Unbiased Predictor (RR-BLUP) based on 1,007 soybean accessions. The SoySNP50K SNP dataset of the accessions was obtained from the USDA-ARS, Beltsville, MD lab, and the protein and oil content of the accessions were obtained from GRIN. Results: Our results showed that the prediction accuracy of oil content was higher than that of protein content. When the training population size was 100, the prediction accuracies for protein content and oil content were 0.60 and 0.79, respectively. The prediction accuracy increased with the size of the training population. Training populations with similar phenotype or with close genetic relationships to the prediction population exhibited better prediction accuracy. A greatest prediction accuracy for both protein and oil content was observed when approximately 3,000 markers with -log10(P) greater than 1 were included. Discussion: This information will help improve GS efficiency and facilitate the application of GS.

Enzyme-Assisted Extraction of Narirutin from Citri Reticulatae Pericarpium and Anti-allergic Asthma Activity.

BACKGROUND: Asthma is a heterogeneous disorder of the airways related to inflammation; it affects millions of people worldwide. Due to the side effects of inhaled corticosteroids, researchers focused on the therapeutic effects of compounds derived from natural products. OBJECTIVE: To investigate the therapeutic benefits of Narirutin a valuable flavonoid in Citri Reticulatae Pericarpium for asthma. METHODS: Narirutin was extracted using the enzyme-assisted method with the L9 (34) orthogonal array to optimize the temperatures, pH, and reaction time. The mechanism of action of Narirutin was investigated via ELISA, flow cytometry, and Western blot analysis in vivo. RESULTS: Narirutin suppressed inflammatory cell infiltration in the lung tissue and decreased IgE and IgG1 levels in serum in vivo. It can also alleviate interleukin (IL)-4, IL-5, and interferon-γ concentrations in bronchoalveolar lavage fluid in mice. Moreover, it increased the ratio of CD4+/CD8+ T cells. Additionally, Narirutin significantly suppressed p-ERK1/2 and p-JNK expression in the MAPK signaling pathway. CONCLUSION: Narirutin affects the Th1/Th2 imbalance through the p-ERK and p-JNK suppression in the MAPK signaling pathway.

Integrative molecular analyses define correlates of high B7-H3 expression in metastatic castrate-resistant prostate cancer.

B7-H3 (CD276) is an immune checkpoint overexpressed in prostate cancer with minimal expression in normal tissues and associated with poor prognosis, making it an excellent therapy target. We interrogated B7-H3 expression and its regulation in metastatic castration-resistant prostate cancer (mCRPC). We found greater expression of B7-H3 transcript relative to other immunotherapy targets (CTLA-4, PD-L1/2), including in tumors that lacked expression of prostate-specific membrane antigen (PSMA). Enzalutamide-resistant mCRPC cells demonstrated increased amounts of B7-H3, and this was associated with resistance signaling pathways. Using a machine-learning algorithm, the gene network of B7-H3 was strongly correlated with androgen receptor (AR) and AR co-factor (HOXB13, FOXA1) networks. In mCRPC samples, the B7-H3 promoter and distal enhancer regions exhibited enhanced transcriptional activity and were directly bound by AR and its co-factors. Altogether, our study characterizes molecular profiles and epigenetic regulation of B7-H3-expressing mCRPC tumors, which informs optimal precision-oncology approaches for mCRPC patients.

The association between cerebrospinal ferritin and soluble triggering receptor expressed on myeloid cells 2 along Alzheimer's continuum.

Brain iron accumulation, which is indicated in the cerebrospinal fluid (CSF) ferritin, is associated with the development of Alzheimer's Disease (AD). Studies have indicated that iron deposition might participate in Alzheimer's pathology through the induction of microglial activation. A soluble triggering receptor expressed on myeloid cells 2 (sTrem2) in CSF is increasingly recognized as a reliable indicator for microglia activity in the brain and participates in the development of neuroinflammation. However, the association between CSF ferritin and sTrem2 under the AD continuum has not been well-established. We enrolled individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants were classified into healthy controls (HC, n = 46) and AD continuum (n = 105) in the combined strata of Amyloid/Tau/Neurodegeneration (ATN) mode and Clinical Dementia Rating (CDR) criteria. The associations between CSF ferritin (indicating iron burden) and sTrem2, as well as AD pathology, which is reflected by Aß42, t-tau, and p-tau in CSF, were explored. CSF ferritin was significantly associated with sTrem2 among all participants (ß = 0.517, P < 0.001, FDR < 0.001), HC (ß = 0.749, P = 0.006, FDR = 0.010), and AD continuum (ß = 0.488, P < 0.001, FDR < 0.001), respectively. However, ferritin predicted the accelerated sTrem2 level in those with high ferritin (ß = 0.549, P = 0.036, FDR = 0.045). In conclusion, CSF ferritin serves as a potential biomarker of Trem2-indicated microglia function.

Advances in Versatile GeTe Thermoelectrics from Materials to Devices.

Driven by the intensive efforts in the development of high-performance GeTe thermoelectrics for mass-market application in power generation and refrigeration, GeTe-based materials display a high figure of merit of >2.0 and an energy conversion efficiency beyond 10%. However, a comprehensive review on GeTe, from fundamentals to devices, is still needed. In this regard, the latest progress on the state-of-the-art GeTe is timely reviewed. The phase transition, intrinsic high carrier concentration, and multiple band edges of GeTe are fundamentally analyzed from the perspectives of the native atomic orbital, chemical bonding, and lattice defects. Then, the fabrication methods are summarized with a focus on large-scale production. Afterward, the strategies for enhancing electronic transports of GeTe by energy filtering effect, resonance doping, band convergence, and Rashba band splitting, and the methods for strengthening phonon scatterings via nanoprecipitates, planar vacancies, and superlattices, are comprehensively reviewed. Besides, the device assembly and performance are highlighted. In the end, future research directions are concluded and proposed, which enlighten the development of broader thermoelectric materials.

Perivascular Space Predicts Brain Hypometabolism of Individuals with Underlying Amyloid Pathology.

BACKGROUND: Reduced signal on fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valid proxy for neurodegeneration in Alzheimer's disease (AD). Perivascular space (PVS) is believed to be associated with AD pathology and cognitive decline. OBJECTIVE: This study aimed to investigate the associations of PVS with FDG-PET and cognitive performance based on the burden of amyloid pathology. METHODS: We used magnetic resonance imaging (MRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). MRI-visible PVS in basal ganglia (BG) and centrum semi-oval (CSO) were visually classified as: none/mild, moderate or frequent/severe. The association of PVS with brain FDG-PET was explored based on the burden of amyloid pathology, where a cerebrospinal fluid (CSF) t-tau/Aß42 with the ratio≥0.27 was defined as high amyloid pathology. Moreover, the relationships between PVS and cognitive performance variables (ADNI-MEM and ADNI-EF) were studied. RESULTS: For participants with higher tau/Aß42 ratio, CSO-PVS severity was independently associated with lower FDG-PET. There were significant interaction effects between moderate or frequent/severe CSO-PVS and time on FDG decline in people with high amyloid pathology. The interaction between CSO-PVS and time (follow-up) was consistently associated with ADNI-MEM and ADNI-EF decline in individuals with high amyloid pathology. CONCLUSION: The study established the differential utility of PVS in BG and CSO for predicting brain metabolism. These findings suggest that CSO-PVS serves as a contributing factor to brain metabolism and cognitive decline associated with amyloid pathology.

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations.

Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.

Oral Intervention of Narirutin Ameliorates the Allergic Response of Ovalbumin Allergy.

A new intervention was investigated for the induction of oral tolerance (OT) of OVA using narirutin by in vivo and in vitro experiments combined with network pharmacology and structural analysis of molecular docking. Narirutin (and its metabolism naringenin) has effects on OT by affecting B cell function, DCs, and T cell response by prediction. It was verified that narirutin could affect B cell function of secreting antibodies, thereby reducing the ability of DCs to absorb antigens by affecting GATA3, CCR7, STAT5, and MHCII expression and regulating T cell response by suppressing Th2 and improving Treg cells in vivo. Molecular docking showed that steric hindrance effects may be the reason for weaker binding energy with targets of narirutin. However, this does not mean that it has no bioactivity, for it can inhibit mast cell degranulation. This finding is interesting because it offers the possibility of using natural compounds to promote oral tolerance.

Transplantation of Mesenchymal Stem Cells Attenuates Acute Liver Failure in Mice via an Interleukin-4-dependent Switch to the M2 Macrophage Anti-inflammatory Phenotype.

Background and Aims: Transplantation of mesenchymal stem cells (MSCs) derived from bone marrow (BM) is an alternative treatment of acute liver failure (ALF) mainly because of the resulting anti-inflammatory activity. It is not known how MSCs regulate local immune responses and liver regeneration. This study explored the effects of MSCs on hepatic macrophages and the Wnt signaling pathway in ALF. Methods: MSCs were isolated from BM aspirates of C57BL/6J mice, and transplanted in mice with ALF induced by D-galactosamine (D-Gal). The proliferation of hepatocytes was assayed by immunohistochemical (IHC) staining of Ki-67 and proliferating cell nuclear antigen (PCNA). The levels of key proteins in the Wnt signaling pathway were assayed by western blotting and cytokines were determined enzyme-linked immunosorbent assays (ELISAs). A macrophage polarization assay characterized the M1/M2 ratio. The potential role of interleukin-4 (IL-4) in the biological activity of MSCs was determined by silencing of IL-4. Results: Transplantation of allogeneic MSCs significantly attenuated D-Gal-induced hepatic inflammation and promoted liver regeneration. MSC transplantation significantly promoted a phenotypic switch from proinflamatory M1 macrophages to anti-inflammatory M2 macrophages, leading to significant Wnt-3a induction and activation of the Wnt signaling pathway in mice with D-Gal-induced ALF. Of the paracrine factors secreted by MSCs (G-CSF, IL-6, IL-1 beta, IL-4, and IL-17A), IL-4 was specifically induced following transplantation in the ALF model mice. The silencing of IL-4 significantly abrogated the phenotypic switch to M2 macrophages and the protective effects of MSCs in both the ALF model mice and a co-culture model in an IL-4 dependent manner. Conclusions: In vivo and in vitro studies showed that MSCs ameliorated ALF through an IL-4-dependent macrophage switch toward the M2 anti-inflammatory phenotype. The findings may have clinical implications in that overexpression of IL-4 may enhance the therapeutic effects of allogeneic MSC transplantation in the treatment of ALF.

QTL and candidate genes for heterophylly in soybean based on two populations of recombinant inbred lines.

Heterophylly, the existence of different leaf shapes and sizes on the same plant, has been observed in many flowering plant species. Yet, the genetic characteristics and genetic basis of heterophylly in soybean remain unknown. Here, two populations of recombinant inbred lines (RILs) with distinctly different leaf shapes were used to identify loci controlling heterophylly in two environments. The ratio of apical leaf shape (LSUP) to basal leaf shape (LSDOWN) at the reproductive growth stage (RLS) was used as a parameter for classifying heterophylly. A total of eight QTL were detected for RLS between the two populations and four of them were stably identified in both environments. Among them, qRLS20 had the largest effect in the JS population, with a maximum LOD value of 46.9 explaining up to 47.2% of phenotypic variance. This locus was located in the same genomic region as the basal leaf shape QTL qLSDOWN20 on chromosome 20. The locus qRLS19 had the largest effect in the JJ population, with a maximum LOD value of 15.2 explaining up to 27.0% of phenotypic variance. This locus was located in the same genomic region as the apical leaf shape QTL qLSUP19 on chromosome 19. Four candidate genes for heterophylly were identified based on sequence differences among the three parents of the two mapping populations, RT-qPCR analysis, and gene functional annotation analysis. The QTL and candidate genes detected in this study lay a foundation for further understanding the genetic mechanism of heterophylly and are invaluable in marker-assisted breeding.

Propensity-matched pair analysis of safety and efficacy between laparoscopic and open radical nephrectomy for the treatment of large renal masses (>10 cm): a retrospective cohort study.

Background: Open radical nephrectomy (ORN) is a practical procedure for treating patients with large renal carcinomas >10 cm in size, and few studies have focused on feasibility and safety of laparoscopic radical nephrectomy (LRN). The current study was to assess the safety and effectiveness of LRN and ORN in large renal carcinoma patients by propensity matched pair analysis. Methods: In this cohort study, a retrospective review of radical nephrectomy data from October 2010 to October 2018 at Changhai Hospital was conducted. Patients with renal carcinomas >10 cm in size by pre-operative images were included. Patients' demographics including age, gender, body mass index (BMI), tumor size, operation time, hospitalization days, etc. were collected. Renal tumor patients undergoing LRN or ORN were match-paired by gender, BMI, age, and tumor size. Peri-operative outcomes including estimated blood loss and complications were compared. The follow-up contents included survival time, disease progression, and cause of death, and cancer-specific and progression-free survival were estimated via Kaplan-Meier curve analysis. Results: Among 92 patients with clinical T2b renal masses, 37 pairs were matched. The average tumor sizes of the LRN and ORN groups were 11.37±0.30 and 11.67±0.33 cm (P=0.375), respectively. The average operating time for LRN was slightly longer (204.32±11.17 vs. 192.78±8.50 min, P=0.414). Estimated blood loss (EBL) (336.49±63.58 mL for LRN vs. 545.95±74.52 mL for ORN, P=0.036), the length of postoperative stay [6.0 (5.0-9.0) for LRN vs. 9.0 (6.0-11.5) days for ORN, P=0.015], and removal time of the drainage tube [4.0 (3.0-5.0) days for LRN vs. 5.0 (4.0-6.0) for ORN, P<0.001] were less than in the LRN group. The pathological subtype and Fuhrman grade were comparable. Both groups were followed up for a similar period, and no difference was observed in 5-year survival rates. Conclusions: Considering the conversion rates and overall complication rates, it seems that LRN for large renal carcinomas demonstrated equivalent peri-operative safety and effectiveness compared with ORN, with no adverse effects on midterm oncological outcomes.

Roles and regulation of histone acetylation in hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is the most frequent malignant tumor of the liver, but its prognosis is poor. Histone acetylation is an important epigenetic regulatory mode that modulates chromatin structure and transcriptional status to control gene expression in eukaryotic cells. Generally, histone acetylation and deacetylation processes are controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Dysregulation of histone modification is reported to drive aberrant transcriptional programmes that facilitate liver cancer onset and progression. Emerging studies have demonstrated that several HDAC inhibitors exert tumor-suppressive properties via activation of various cell death molecular pathways in HCC. However, the complexity involved in the epigenetic transcription modifications and non-epigenetic cellular signaling processes limit their potential clinical applications. This review brings an in-depth view of the oncogenic mechanisms reported to be related to aberrant HCC-associated histone acetylation, which might provide new insights into the effective therapeutic strategies to prevent and treat HCC.

Lymph node ratio is a superior predictor in surgically treated early-onset pancreatic cancer.

Background: The prognostic performance of four lymph node classifications, the 8th American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) N stage, lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), and examined lymph nodes (ELN) in early-onset pancreatic cancer (EOPC) remains unclear. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched for patients with EOPC from 2004 to 2016. 1048 patients were randomly divided into training (n = 733) and validation sets (n = 315). The predictive abilities of the four lymph node staging systems were compared using the Akaike information criteria (AIC), receiver operating characteristic area under the curve (AUC), and C-index. Multivariate Cox analysis was performed to identify independent risk factors. A nomogram based on lymph node classification with the strongest predictive ability was established. The nomogram's precision was verified by the C-index, calibration curves, and AUC. Kaplan-Meier analysis and log-rank tests were used to compare differences in survival at each stage of the nomogram. Results: Compared with the 8th N stage, LODDS, and ELN, LNR had the highest C-index and AUC and the lowest AIC. Multivariate analysis showed that N stage, LODDS, LNR were independent risk factors associated with cancer specific survival (CSS), but not ELN. In the training set, the AUC values for the 1-, 3-, and 5-year CSS of the nomogram were 0.663, 0.728, and 0.760, respectively and similar results were observed in the validation set. In addition, Kaplan-Meier survival analysis showed that the nomogram was also an important factor in the risk stratification of EOPC. Conclusion: We analyzed the predictive power of the four lymph node staging systems and found that LNR had the strongest predictive ability. Furthermore, the novel nomogram prognostic staging mode based on LNR was also an important factor in the risk stratification of EOPC.