Epigenetic Regulatory Axis MIR22-TET3-MTRNR2L2 Represses Fibroblast-Like Synoviocyte-Mediated Inflammation in Rheumatoid Arthritis.

OBJECTIVE: The specific role of fibroblast-like synoviocytes (FLSs) in the pathogenesis of rheumatoid arthritis (RA) is still not fully elucidated. This study aimed to explore the molecular mechanisms of epigenetic pathways, including three epigenetic factors, microRNA (miRNA)-22 (MIR22), ten-eleven translocation methylcytosine dioxygenase 3 (TET3), and MT-RNR2 like 2 (MTRNR2L2), in RA-FLSs. METHODS: The expression of MIR22, TET3, and MTRNR2L2 in the synovium of patients with RA and arthritic mice were determined by fluorescence in situ hybridization, quantitative polymerase chain reaction (qPCR), immunohistochemistry, and Western blot. Mir22-/- and Tet3+/- mice were used to establish a collagen antibody-induced arthritis (CAIA) model. Mir22 angomir and Tet3 small interfering RNA (siRNA) were used to illustrate the therapeutic effects on arthritis using a collagen-induced (CIA) model. Bioinformatics, luciferase reporter assay, 5-hydroxymethylcytosine (5hmC) dot blotting, chromatin immunoprecipitation-qPCR, and hydroxymethylated DNA immunoprecipitation were conducted to show the direct repression of MIR22 on the TET3 and transcriptional activation of TET3 on MTRNR2L2. RESULTS: The Mir22-/- CAIA model and RA-FLS-related in vitro experiments demonstrated the inhibitory effect of MIR22 on inflammation. MIR22 can directly inhibit the translation of TET3 in RA-FLSs by binding to its 3' untranslated region in TET3. The Tet3+/- mice-established CAIA model showed less severe symptoms of arthritis in vivo. In vitro experiments further confirmed the proinflammatory effect of TET3 in RA. In addition, the CIA model was used to validate the therapeutic effects of Mir22 angomir and Tet3 siRNA. Finally, TET3 exerts its proinflammatory effect by promoting 5hmC production in the promoter of its target MTRNR2L2 in RA-FLSs. CONCLUSION: The key role of the MIR22-TET3-MTRNR2L2 pathway in RA-FLSs provided an experimental basis for further studies into the pathogenesis and related targets of RA from the perspective of FLSs.

The network characteristics in schizophrenia with prominent negative symptoms: a multimodal fusion study.

Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.

The application of HER2 and CD47 CAR-macrophage in ovarian cancer.

BACKGROUND: The chimeric antigen receptor (CAR)-T therapy has a limited therapeutic effect on solid tumors owing to the limited CAR-T cell infiltration into solid tumors and the inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Macrophage is an important component of the innate and adaptive immunity, and its unique phagocytic function has been explored to construct CAR macrophages (CAR-Ms) against solid tumors. This study aimed to investigate the therapeutic application of CAR-Ms in ovarian cancer. METHODS: In this study, we constructed novel CAR structures, which consisted of humanized anti-HER2 or CD47 scFv, CD8 hinge region and transmembrane domains, as well as the 4-1BB and CD3ζ intracellular domains. We examined the phagocytosis of HER2 CAR-M and CD47 CAR-M on ovarian cancer cells and the promotion of adaptive immunity. Two syngeneic tumor models were used to estimate the in vivo antitumor activity of HER2 CAR-M and CD47 CAR-M. RESULTS: We constructed CAR-Ms targeting HER2 and CD47 and verified their phagocytic ability to ovarian cancer cells in vivo and in vitro. The constructed CAR-Ms showed antigen-specific phagocytosis of ovarian cancer cells in vitro and could activate CD8+ cytotoxic T lymphocyte (CTL) to secrete various anti-tumor factors. For the in vivo model, mice with human-like immune systems were used. We found that CAR-Ms enhanced CD8+ T cell activation, affected tumor-associated macrophage (TAM) phenotype, and led to tumor regression. CONCLUSIONS: We demonstrated the inhibition effect of our constructed novel HER2 CAR-M and CD47 CAR-M on target antigen-positive ovarian cancer in vitro and in vivo, and preliminarily verified that this inhibitory effect is due to phagocytosis, promotion of adaptive immunity and effect on tumor microenvironment.

Association of Attenuated Niacin Response With Inflammatory Imbalance and Prediction of Conversion to Psychosis From Clinical High-risk Stage.

Objective: Attenuated niacin responses and changes in cytokine levels have been reported in schizophrenia. However, prior studies have typically focused on schizophrenia, and little is known about the association between niacin response and inflammatory imbalance in clinically high-risk psychosis (CHR). This study aimed to assess the niacin response to inflammatory imbalance for association with conversion to psychosis within 2 years.Methods: A prospective case-control study was performed to assess the niacin response and interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels in 60 CHR individuals and 60 age- and sex-matched healthy controls (HC) from May 2019 to December 2021. Participants with CHR were identified using the Structured Interview for Prodromal Syndromes. The niacin-induced responses were measured using laser Doppler flowmetry. From the dose-response curves, the log-transferred concentration of methylnicotinate required to elicit a half-maximal blood flow response (LogEC50) and maximal minus minimal blood flow response (Span) values were calculated for each subject. Serum cytokine levels were measured using enzyme-linked immunosorbent assay. Individuals with CHR were then divided into converters (CHR-C, n = 15) and non-converters (CHR-NC, n = 45) to psychosis based on their 2-year follow-up clinical status.Results: The CHR group exhibited significantly higher LogEC50 (t = 3.650, P < .001) and Span (t = 2.657, P = .009) values than the HC group. The CHR-C group exhibited a significantly shorter Span (t = 4.027, P < .001) than the CHR-NC group. The LogEC50 showed a trend toward significance (t = 1.875, P = .066). None of the cytokine levels were significant. The conversion outcome can therefore be predicted by applying LogEC50 (P = .049) and Span (P < .001). The regression model with variables of LogEC50, Span, family history, and scores of positive symptoms showed good discrimination of subsequent conversion to psychosis and achieved a classification accuracy of 91.7%. The decreased LogEC50 in the CHR-C group was significantly correlated with the increased IL-1ß/IL-10 ratio (Spearman ρ = -0.600, P = .018), but this correlation was nonsignificant in the CHR-NC group.Conclusions: Our findings indicate a significant association between niacin response and psychosis conversion outcomes in individuals with CHR. Compared with peripheral inflammatory cytokines, the niacin response can better predict conversion, although there may be an intersection between the two in biological mechanisms.

CCR2 antagonist represses fibroblast-like synoviocyte-mediated inflammation in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease with a global incidence of approximately 1%. Its complex pathogenesis makes the development of RA-related therapeutics very difficult. Existing drugs for RA have many side effects and are prone to drug resistance. One potential target for RA drugs includes C-Cchemokinereceptortype2 (CCR2), which belongs to the G protein-coupled receptor family. A series of RA drugs targeting CCR2 have been developed; however, the pre-clinical and clinical research results for CCR2 antagonists are inconsistent. We found that CCR2 was also expressed in primary Fibroblast-like synoviocyte (FLS) from patients with RA. CCR2 antagonists can inhibit inflammatory cytokines and matrix metalloproteinases released by RA-FLS but do not affect the proliferation and migration ability of RA-FLS. In addition, CCR2 antagonist-treated RA-FLS indirectly repressed macrophage-mediated inflammation and rescued the viability of chondrocytes. Finally, a CCR2 antagonist ameliorated the collagen-induced arthritic (CIA). CCR2 antagonists may exert anti-inflammatory effects on RA-FLS by inhibiting the JAK-STAT pathway. In summary, a CCR2 antagonist can exert anti-inflammatory effects by acting on RA-FLS. This study provides a new experimental basis for the use of CCR2 antagonists in the development of RA drugs.

The effect of initial antipsychotic treatment on hippocampal and amygdalar volume in first-episode schizophrenia is influenced by age.

BACKGROUND: Antipsychotic treatment has been shown to yield hippocampal and amygdalar volumetric changes in first-episode schizophrenia (FES). However, whether antipsychotic induced volumetric changes interact with age remains unclear. METHODS: The current study includes data from 120 medication naïve FES patients and 110 matched healthy controls (HC). Patients underwent MRI scans before (T1) and after (T2) antipsychotic treatment. HCs underwent MRI scans at baseline only. The hippocampus and amygdala were segmented via Freesurfer 7. General linear models were conducted to investigate the effect of age by diagnosis interaction on baseline volume. Linear mixed models (LMM) were used to detect the effect of age on volumetric changes from pre to post treatment in FES. RESULTS: GLM revealed a trending effect (F = 3.758, p = 0.054) of age by diagnosis interaction on the baseline volume of the left (whole) hippocampus, with older FES patients showing smaller hippocampal volumes, relative to HC, when controlled sex, education years, and ICV. LMM showed a significant age by time-point interaction effect (F = 4.194, estimate effect = -1.964, p = 0.043) on left hippocampal volume in all FES and significant time effect(F = 6.608,T1-T2(estimate effect) = 62.486, p = 0.011), whereby younger patients showed greater hippocampal volumetric decreases following treatment. At the subfield level, a significant time effect emerged in left molecular_layer_HP (F = 4.509,T1-T2(estimate effect) = 12.424, p = 0.032, FDR corrected) and left cornu ammonis(CA)4 (F = 4.800,T1-T2(estimate effect) = 7.527, p = 0.046, FDR corrected), implying volumetric reduction after treatment in these subfields. CONCLUSIONS: Our findings suggest that age plays an important role in the neuroplastic mechanisms of initial antipsychotics on the hippocampus and amygdala of schizophrenia.

Increased anxiety and stress-related visits to the Shanghai psychiatric emergency department during the COVID-19 pandemic in 2020 compared to 2018-2019.

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a significant and far-reaching impact on mental health. The psychiatric emergency department (PED) is pivotal in the management of acute and severe mental illnesses, especially anxiety-and stress-related disorders. Aims: This study aimed to evaluate whether changes in the frequency or patients' demographics of visiting the PED occurred during the COVID-19 pandemic among individuals with anxiety and stress-related disorders. Methods: This cross-sectional study used data on PED visit counts from the largest psychiatric hospital in China between 2018 and 2020 (before and during the COVID-19 pandemic). Data from 2020, representing the COVID-19 pandemic period, were extracted from electronic medical records and compared using descriptive statistics for the same periods in 2018 and 2019. Results: The number of PED visits related to anxiety and stress disorders per year increased from 83 in 2018 to 136 (63.9% increase) in 2019 and 239 (188.0% increase) in 2020. Compared to that in 2018 and 2019, the proportion of PED visits in 2020 among patients with anxiety and stress disorders increased significantly. Patients with anxiety-and stress-related disorders during PED visits in 2020 were younger than those in 2018 and 2019 (three-year groups: F = 9.124, df = 2, p < 0.001). Conclusion: Despite the epidemic-policy barriers against PED visits, PED care seeking has increased, thereby underscoring the need for crisis prevention services for patients with stress and anxiety disorders.

Role of chemokine receptor 2 in rheumatoid arthritis: A research update.

Rheumatoid arthritis (RA) is a multisystemic and inflammatory autoimmune disease characterized by joint destruction. The C-C motif chemokine receptor 2 (CCR2) is mainly expressed in monocytes and T cells, initiating their migration to sites of inflammation, ultimately leading to cartilage damage and bone destruction. CCR2 has long been considered a prospective target for treating autoimmune diseases. However, clinical studies on inhibitors or neutralizing antibodies against CCR2 in RA have exhibited limited efficacy. Recent evidence indicates that CCR2 may play different roles in RA. Hence, a comprehensive understanding regarding the role of CCR2 may facilitate the development of targeted drugs and provide novel insights for improving CCL2-mediated inflammatory diseases. This review summarizes the biological characteristics of CCR2, the related signaling pathways, and recent developments in CCR2-targeting therapeutics.

Perylene-based molecular device: multifunctional spintronic and spin caloritronic applications.

Carbon-based magnetic molecular junctions are promising candidates for nanoscale spintronic applications because they are atomically thin and possess high stability and peculiar magnetism. Herein, based on first-principles and non-equilibrium Green's function, we designed a carbon-based molecular spintronic device composed of carbon atomic chains, zigzag-edged graphene nanoribbon (ZGNR), and a perylene molecule. Our results show that the device exhibits integrated spintronic and spin caloritronic functionalities, such as the bias-voltage driven spin filtering effect, negative differential resistance effect and giant magnetoresistance, temperature-gradient driven spin Seebeck effect, thermal spin filtering effect, high thermal magnetoresistance, and thermal colossal giant magnetoresistance. Furthermore, considering the phonon vibration effect, the spin and charge thermoelectric figure of merits (ZTsp and ZTch) can be enhanced and the peak of ZTsp is much larger than that of ZTch, indicating the excellent thermospin performance. The asymmetrical contact configuration between the carbon atomic chain and perylene/ZGNR inhibits the phonon thermal conductivity significantly, leading to the optimal ZTsp and ZTch of 2.4 and 0.5 at 300 K, respectively. These results suggest multifunctional spintronic and spin caloritronic applications for the perylene-based molecular device.

Structural, electronic phase transitions and thermal spin transport properties in 2D NbSe2 and NbS2: a first-principles study.

How to effectively tune 2D electronic and magnetic properties is key to developing novel spintronic materials and devices. Although the strain induced metal-to-half-metal electronic phase transition (EPT) has been studied in 2H NbSe2 and NbS2 monolayers, the 1T phase, the Coulomb interaction and the transport properties have not been explored. Here, using first-principles calculations in junction with nonequilibrium Green's function, we present a comprehensive and comparative study on the strain tuned structural, electronic, magnetic and thermal spin transport properties for NbSe2 and NbS2 monolayers with and without Coulomb interaction. It is found that the Coulomb interaction makes the strain induced 2H-to-1T structural phase transition easier. Similar to the 2H phase, there is also a strain induced metal-to-half-metal EPT for the 1T phase without Coulomb interaction, and the Coulomb interaction makes the ETP easier. Remarkably, the 2H-NbSe2 monolayer with Coulomb interaction is a bipolar spin gapless semiconductor (SGS), and novel Dirac half-metal and usually SGS can be obtained by the tensile strain. In addition, we predict the excellent spin Seebeck effect and thermal spin diode effect in the bipolar SGS of the 2H-NbSe2 monolayer with Coulomb interaction, and expect the spin filtering effect and high magnetoresistance in the half-metals driven by the strain. We also discuss the strength of Coulomb interaction by comparing the theoretical and available experimental electronic states, indicating the indispensability of Coulomb interactions. These results suggest that 2D NbSe2 and NbS2 are promising candidates for phase-change spintronic materials and devices, and will stimulate extensive studies on this class of 2D systems.

PU.1 promotes development of rheumatoid arthritis via repressing FLT3 in macrophages and fibroblast-like synoviocytes.

OBJECTIVES: To uncover the function and underlying mechanism of an essential transcriptional factor, PU.1, in the development of rheumatoid arthritis (RA). METHODS: The expression and localisation of PU.1 and its potential target, FMS-like tyrosine kinase 3 (FLT3), in the synovium of patients with RA were determined by western blot and immunohistochemical (IHC) staining. UREΔ (with PU.1 knockdown) and FLT3-ITD (with FLT3 activation) mice were used to establish collagen antibody-induced arthritis (CAIA). For the in vitro study, the effects of PU.1 and FLT3 on primary macrophages and fibroblast-like synoviocytes (FLS) were investigated using siRNAs. Mechanistically, luciferase reporter assays, western blotting, FACS and IHC were conducted to show the direct regulation of PU.1 on the transcription of FLT3 in macrophages and FLS. Finally, a small molecular inhibitor of PU.1, DB2313, was used to further illustrate the therapeutic effects of DB2313 on arthritis using two in vivo models, CAIA and collagen-induced arthritis (CIA). RESULTS: The expression of PU.1 was induced in the synovium of patients with RA when compared with that in osteoarthritis patients and normal controls. FLT3 and p-FLT3 showed opposite expression patterns compared with PU.1 in RA. The CAIA model showed that PU.1 was an activator, whereas FLT3 was a repressor, of the development of arthritis in vivo. Moreover, results from in vitro assays were consistent with the in vivo results: PU.1 promoted hyperactivation and inflammatory status of macrophages and FLS, whereas FLT3 had the opposite effects. In addition, PU.1 inhibited the transcription of FLT3 by directly binding to its promoter region. The PU.1 inhibitor DB2313 clearly alleviated the effects on arthritis development in the CAIA and CIA models. CONCLUSIONS: These results support the role of PU.1 in RA and may have therapeutic implications by directly repressing FLT3. Therefore, targeting PU.1 might be a potential therapeutic approach for RA.

The role of a key transcription factor PU.1 in autoimmune diseases.

PU.1, a transcription factor member of the E26 transformation-specific family, affects the function of a variety of immune cells in several physiological and pathological conditions. Previous studies studying the role of PU.1 in pathological conditions have mainly focused on immune system-related cancers, and a series of articles have confirmed that PU.1 mutation can induce a variety of immune cell-related malignancies. The underlying mechanism has also been extensively validated. However, the role of PU.1 in other major immune system-related diseases, namely, systemic autoimmune diseases, is still unclear. It was only in recent years that researchers began to gradually realize that PU.1 also played an important role in a variety of autoimmune diseases, such as rheumatoid arthritis (RA), experimental autoimmune encephalomyelitis (EAE) and systemic lupus erythematosus (SLE). This review article summarizes the findings of recent studies that investigated the role of PU.1 in various autoimmune diseases and the related underlying mechanisms. Furthermore, it presents new ideas and provides insight into the role of PU.1 as a potential treatment target for autoimmune diseases and highlights existing research problems and future research directions in related fields.

Screening of the Key Genes for the Progression of Liver Cirrhosis to Hepatocellular Carcinoma Based on Bioinformatics.

Hepatocellular carcinoma (HCC), which is among the most globally prevalent cancers, is strongly associated with liver cirrhosis. Using a bioinformatics approach, we have identified and investigated the hub genes responsible for the progression of cirrhosis into HCC. We analyzed the Gene Expression Omnibus (GEO) microarray datasets, GSE25097 and GSE17549, to identify differentially expressed genes (DEGs) in these two conditions and also performed protein-protein interaction (PPI) network analysis. STRING database and Cytoscape software were used to analyze the modules and locate hub genes following which the connections between hub genes and the transition from cirrhosis to HCC, progression of HCC, and prognosis of HCC were investigated. We used the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to detect the molecular mechanisms underlying the action of the primary hub genes. In all, 239 DEGs were obtained, with 94 of them showing evidence of upregulation and 145 showing evidence of downregulation in HCC tissues as compared to cirrhotic liver tissues. We identified six hub genes, namely, BUB1B, NUSAP1, TTK, HMMR, CCNA2, and KIF2C, which were upregulated and had a high diagnostic value for HCC. Besides, these six hub genes were positively related to immune cell infiltration. Since these genes may play a direct role in the progression of cirrhosis to HCC, they can be considered as potential novel molecular indicators for the onset and development of HCC.

A pan-cancer analysis of the oncogenic role of dual-specificity tyrosine (Y)-phosphorylation- regulated kinase 2 (DYRK2) in human tumors.

Although there have been studies correlating DYRK2 with a number of human cancers, there has been no pan-cancer analysis. Therefore, through the TCGA database, we conducted a related study on the expression of DYRK2 in cancers.The expression of DYRK2 is obviously increased in some cancers, while the opposite is true in others, and there is a clear association between its expression and the prognosis of cancer patients.The mutation of DYRK2 is also significantly correlated with patients' prognosis in certain human tumors. In addition, phosphorylation and methylation levels of DYRK2 are different between tumor tissues and adjacent normal tissues in various tumors. In the tumour microenvironment, the expression of DYRK2 correlates with cancer-associated fibroblast infiltration, such as BLCA or HNSC. In order to fully understand the role of DYRK2 in different tumors, we conducted a pan-cancer analysis.

Development and Validation of a Novel Circadian Rhythm-Related Signature to Predict the Prognosis of the Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most important causes of cancer-related deaths and remains a major public health challenge worldwide. Considering the extensive heterogeneity of HCC, more accurate prognostic models are imperative. The circadian genes regulate the daily oscillations of key biological processes, such as nutrient metabolism in the liver. Circadian rhythm disruption has recently been recognized as an independent risk factor for cancer. In this study, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were compared and 248 differentially expressed genes (DEGs) of the circadian rhythm were identified. HCC was classified into two subtypes based on these DEGs. The prognostic value of each circadian rhythm-associated gene (CRG) for survival was assessed by constructing a multigene signature from TCGA cohort. A 6-gene signature was created by applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all patients in TCGA cohort were divided into high- and low-risk groups according to their risk scores. The survival rate of patients with HCC in the low-risk group was significantly higher than that in the high-risk group (p < 0.001). The patients with HCC in the Gene Expression Omnibus (GEO) cohort were also divided into two risk subgroups using the risk score of TCGA cohort, and the overall survival time (OS) was prolonged in the low-risk group (p = 0.012). Based on the clinical characteristics, the risk score was an independent predictor of OS in the patients with HCC. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that multiple metabolic pathways, cell cycle, etc., were enhanced in the high-risk group. Using the metabolic pathway single-sample gene set enrichment analysis (ssGSEA), it was found that the metabolic pathways in the high- and low-risk groups between TCGA and GEO cohorts were altered essentially in the same way. In conclusion, the circadian genes play an important role in HCC metabolic rearrangements and can be further used to predict the prognosis the patients with HCC.

Ultrasensitive detection of multiple Alzheimer's disease biomarkers by SERS-LFA.

Alzheimer's disease (AD) is one of the top public health crises in the 21st century, especially in an aging society. Early diagnosis, prevention, and intervention can significantly reduce the risk of AD. Detection of multiple AD biomarkers in blood is an effective strategy and has drawn more and more attention in recent years. However, the concentration of AD biomarkers is very low, therefore, point-of-care testing (POCT) techniques are needed for sensitive detection. Herein, a lateral flow assay, based on Surface-enhanced Raman scattering nanotags (SERS-LFA), is proposed for the simultaneous quantification of multiple AD biomarkers including Amyloid-beta 42, Amyloid-beta 40, tau proteins, and neurofilament light chain. The limit of detection for four AD biomarkers is 138.1, 191.2, 257.1, and 309.1 fg mL-1, respectively, which are two orders of magnitude lower than their concentrations in blood. Compared with the existing detection technology, SERS-LFA has the advantages of high specificity, high sensitivity, low cost, multiple detection, and rapid detection. Therefore, SERS-LFA has a broad application prospect in the early diagnosis and monitoring of AD in the future.

Pan-Cancer Analysis Predicts the Immunological and Prognostic Role of ZC3H12C in KIRC.

ZC3H12C is an important member of the CCCH-zinc finger protein family and is mainly involved in host immune and inflammatory diseases. However, its abnormal expression and prognostic value in cancer have not yet been established. Through comparative analysis of the Cancer Genome Atlas (TCGA) database, we found that ZC3H12C is the most relevant to the prognosis, grade, and stage of renal clear cell carcinoma (ccRCC) across 33 cancers. With the help of patient transcription and clinical data from the TCGA and GEO (GSE53757, GSE36895) databases, we determined that in the immune environment of patients with ccRCC, ZC3H12C was clearly negatively correlated with Tregs and was significantly positively correlated with monocytes. In addition, protein phosphorylation and DNA methylation analysis also showed that ZC3H12C negatively regulates the role of cancer in ccRCC. Our research may provide new insights into ccRCC immunotherapy and bring forth novel biomarkers and therapeutic targets.

Prognostic Significance of Preoperative Integrated Liver Inflammatory Score in Patients with Hepatocellular Carcinoma.

BACKGROUND The Integrated Liver Inflammatory Score (ILIS), which includes 5 serum indicators (albumin, bilirubin, neutrophil count, alpha-fetoprotein [AFP], and alkaline phosphatase [ALP]), is a novel inflammation-based predictive model associated with poor survival in hepatocellular carcinoma (HCC) patients. Our study aimed to assess the prognostic value of ILIS in HCC patients undergoing radical hepatectomy and establish a nomogram and artificial neural network based on their ILIS scores. MATERIAL AND METHODS This multicenter retrospective study included patients from 2 institutions from 2007 to 2017. Independent risk factors associated with Recurrence-free survival (RFS) and overall survival (OS) were identified through univariate and multifactor analysis in the training and validation groups, respectively. Afterward, column line graphs and artificial neural networks (ANN) were constructed and validated using the validation group. RESULTS A total of 432 patients were included in this study (275 in the training group and 157 in the validation group). In both cohorts, ILIS was correlated with pathological features such as tumor size, degree of differentiation, Child-Pugh class classification, and BCLC staging. Moreover, ILIS was identified as an independent risk factor for OS. ILIS-based nomograms and artificial neural networks also showed the prognostic value of ILIS. CONCLUSIONS Preoperative ILIS is an independent and effective predictor of prognosis in HCC patients treated with radical hepatectomy, as shown by the fact that higher ILIS are associated with worse patient prognosis. We have also established nomograms and ANNs that predict HCC prognosis with high accuracy.