Association of interleukin-6, ferritin, and lactate dehydrogenase with venous thromboembolism in COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is frequntly accompanied by venous thromboembolism (VTE), and its mechanism may be related to the abnormal inflammation and immune status of COVID-19 patients. It has been proved that interleukin-6 (IL-6), ferritin and lactate dehydrogenase (LDH) may play an important role in the occurrence of VTE in COVID-19 infection. But whether they can server as predictors for VTE in COVID-19 is still unclear. In this study, we performed a systematic review and meta-analysis to compare IL-6, ferritin and LDH in VTE and non-VTE COVID-19 patients in order to shed light on the prevention and treatment of VTE. METHODS: Related literatures were searched in PubMed, Embase, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), WANGFANG. COVID-19 patients were divided into VTE group and non-VTE group. Meta-analysis was then conducted to compare levels of IL-6, ferritin and LDH between the two groups. RESULTS: We finally included and analyzed 17 literatures from January 2019 to October 2022. There was a total of 7,035 COVID-19 patients, with a weighted mean age of 60.01 years. Males accounted for 62.64% and 61.34% patients were in intensive care unit (ICU). Weighted mean difference (WMD) of IL-6, ferritin and LDH was 31.15 (95% CI: 9.82, 52.49), 257.02 (95% CI: 51.70, 462.33) and 41.79 (95% CI: -19.38, 102.96), respectively. The above results indicated that than compared with non-VTE group, VTE group had significantly higher levels of IL-6 and ferritin but similar LDH. CONCLUSION: This systematic review and meta-analysis pointed out that elevated levels of IL-6 and ferritin were significantly possitive associated with VTE, thus could be used as biological predictive indicators of VTE among COVID-19 patients. However, no association was found between level of LDH and VTE. Therefore, close monitoring of changes in IL-6 and ferritin concentrations is of great value in assisting clinicans to rapidly identify thrombotic complications among COVID-19 patients, hence facilitating the timely effective managment. Further studies are required in terms of the clinical role of cytokines in the occurrence of VTE among COVID-19 infection, with more reliable systematic controls and interventional trials.

Effects of Cu ratios on the C1-C6 growth mechanism on copper-nickel bimetallic surfaces.

The adsorption and growth mechanisms of Cn (n = 1-6) on different Cu-Ni surfaces are calculated by density functional theory (DFT). The results demonstrate that Cu doping affects the growth mechanism of the deposited carbon on the catalyst surface. Firstly, the addition of Cu weakens the interaction between Cn and the adsorbed surface, which is proved by the results of density of states (DOS) and partial density of states (PDOS). The weakening of the interaction allows Cn to perform at higher proportions of Cu-doped surfaces with a behavior consistent with that in the gas phase. A comparison of the growth energies of the different pathways of Cn in the gas phase shows that the main pathway for the Cn growth is chain-to-chain (CC). The CC reaction is also the main pathway for the growth of Cn on the surfaces, which is enhanced by the doping of Cu. In addition, analysis of the growth energy revealed that C2-C3 is the rate-determining step in the growth process of Cn. The doping of Cu enhances the growth energy of this step, contributing to the suppression of the growth of the deposited carbon on the adsorbed surface. Moreover, an average carbon binding energy shows that the doping of Cu on the Ni surface could weaken the structural stability of Cn, favoring the elimination of carbon deposited on the catalyst surface.

Comprehensive analysis: Necroptosis-related lncRNAs can effectively predict the prognosis of glioma patients.

Glioma is the most common and fatal primary brain tumor in humans. A significant role for long non-coding RNA (lncRNA) in glioma is the regulation of gene expression and chromatin recombination, and immunotherapy is a promising cancer treatment. Therefore, it is necessary to identify necroptosis-related lncRNAs in glioma. In this study, we collected and evaluated the RNA-sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA, https://www.ncbi.nlm.nih.gov/, Data Release 32.0, March 29, 2022) glioma patients, and necroptosis-related lncRNAs were screened. Cox regression and least absolute shrinkage and selection operator (LASSO) analysis were performed to construct a risk score formula to explore the different overall survival between high- and low-risk groups in TCGA. Gene Ontology (GO) and pathway enrichment analysis (Kyoto Encyclopedia of Genes and Genomes (KEGG)) were performed to identify the function of screened genes. The immune correlation analysis showed that various immune cells and pathways positively associated with a patient's risk score. Furthermore, the analysis of the tumor microenvironment indicated many immune cells and stromal cells in the tumor microenvironment of glioma patients. Six necroptosis-related lncRNAs were concerned to be involved in survival and adopted to construct the risk score formula. The results showed that patients with high-risk scores held poor survival in TCGA. Compared with current clinical data, the area under the curve (AUC) of different years suggested that the formula had better predictive power. We verified that necroptosis-related lncRNAs play a significant role in the occurrence and development of glioma, and the constructed risk model can reasonably predict the prognosis of glioma. The results of these studies added some valuable guidance to understanding glioma pathogenesis and treatment, and these necroptosis-related lncRNAs may be used as biomarkers and therapeutic targets for glioma prevention.

New biomarker: the gene HLA-DRA associated with low-grade glioma prognosis.

BACKGROUND: Low-grade gliomas (LGG) are WHO grade II tumors presenting as the most common primary malignant brain tumors in adults. Currently, LGG treatment involves either or a combination of surgery, radiation therapy, and chemotherapy. Despite the knowledge of constitutive genetic risk factors contributing to gliomas, the role of single genes as diagnostic and prognostic biomarkers is limited. The aim of the current study is to discover the predictive and prognostic genetic markers for LGG. METHODS: Transcriptome data and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We first performed the tumor microenvironment (TME) survival analysis using the Kaplan-Meier method. An analysis was undertaken to screen for differentially expressed genes. The function of these genes was studied by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Following which a protein-protein interaction network (PPI) was constructed and visualized. Univariate and multivariate COX analyses were performed to obtain the probable prognostic genes. The key genes were selected by an intersection of core and prognostic genes. A clinical correlation analysis of single-gene expression was undertaken. GSEA enrichment analysis was performed to identify the function of key genes. Finally, a single gene-related correlation analysis was performed to identify the core immune cells involved in the development of LGG. RESULTS: A total of 529 transcriptome data and 515 clinical samples were obtained from the TCGA. Immune cells and stromal cells were found to be significantly increased in the LGG microenvironment. The top five core genes intersected with the top 38 prognostically relevant genes and two key genes were identified. Our analysis revealed that a high expression of HLA-DRA was associated with a poor prognosis of LGG. Correlation analysis of immune cells showed that HLA-DRA expression level was related to immune infiltration, positively related to macrophage M1 phenotype, and negatively related to activation of NK cells. CONCLUSIONS: HLA-DRA may be an independent prognostic indicator and an important biomarker for diagnosing and predicting survival in LGG patients. It may also be associated with the immune infiltration phenotype in LGG.

Lanthanide Coordination Polymer-Based Composite Films for Selective and Highly Sensitive Detection of Cr2O72- in Aqueous Media.

Due to the high carcinogenicity and bioaccumulation effects of dichromate ions in the human body, sensitive and rapid detection of Cr2O72- ions is necessary. Herein, two lanthanide coordination polymers based on a linear dicarboxylic acid ligand, named {Ln(cpon)(Hcpon)(H2O)3}n [Ln = Tb, Tbcpon; Eu, Eucpon; H2 cpon = 5-(4-carboxy-phenoxy)-nicotinic acid], have been successfully synthesized. These two isostructural compounds contain one-dimensional zigzag chains that consist of uncoordinated carboxyl groups and pyridine groups in the framework, and the one-dimensional chains can further form a three-dimensional supramolecular stacking structure by intermolecular interaction. Both Tbcpon and Eucpon show good luminescence performance and high stability. Tbcpon exhibits a good ability to sense Cr2O72- ions in aqueous solution. Moreover, the composite film material composed of Tbcpon and poly(methyl methacrylate) (PMMA) exhibits superior luminescence properties compared to those of pure Tbcpon. The Tbcpon-PMMA film exhibits an excellent ability to recognize Cr2O72- ions with high selectivity and a low detection limit of 5.6 ppb, which is much lower than the maximum contamination standard of 100 ppb in drinking water specified by the U.S. Environmental Protection Agency. Furthermore, the Tbcpon-PMMA film shows good recyclability for more than five cycles and anti-interference ability. After the introduction of the slightly soluble polymer poly(vinyl alcohol) (PVA), the Tbcpon-PVA composite film can effectively detect Cr2O72- ions in as little as 1 min. These composite films could be potentially used as test strips for trace detection and rapid detection of Cr2O72- ions in aqueous solution.

STMN1 as a candidate gene associated with atypical meningioma progression.

OBJECTIVES: Meningiomas are the most common type of primary intracranial tumor. Atypical meningiomas are especially difficult to manage due to frequent disease recurrence. This study aimed to examine the role of stathmin (coded by the gene STMN1) as a factor in atypical meningioma recurrence. PATIENTS AND METHODS: A total of 59 sporadic atypical meningioma formalin-fixed paraffin-embedded (FFPE) samples were collected. The mRNA levels of the biomarker gene STMN1 were tested using quantitative RT-PCR. RESULTS: We observed significant up-regulation of STMN1 mRNA expression in recurrent tumors in comparison with primary tumors (p<0.05). Moreover, mRNA expression levels of STMN1 significantly correlated with Ki-67 score (r=0.93, p<0.01). Multivariate survival analyses indicated that high expression of STMN1, high Ki-67 score, and more advanced patient age at diagnosis (>60yrs) each act as independence prognostic factors for recurrence. Kaplan-Meier analysis revealed that STMN1 expression pattern could effectively predict prognosis of atypical meningioma in patients (p<0.01). CONCLUSIONS: Our study indicates for the first time that an increased risk of sporadic atypical meningioma recurrence can be found in cases with elevated expression of STMN1. These results suggest that STMN1 expression might serve as a biomarker for determining patient atypical meningioma prognosis.

MicroRNA-10b mediates TGF-ß1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition.

Although it is well known that exaggerated proliferation, metastasis and the mesenchymal subtype is related with worst prognoses in glioblastoma (GBM) and that transforming growth factor-ß1 (TGF-ß1) is a potent factor in regulating the proliferation, migration and epithelial-mesenchymal transition (EMT) phenotype of GBM, the detailed mechanisms are still far from elucidated. MicroRNAs (miRNAs) are small non-coding RNAs which play critical roles in various diseases by regulating target gene expression. We report that miR-10b, a molecule downstream of TGF-ß1, is involved in TGF-ß1-regulated GBM cell proliferation, migration and EMT. We found that exposure of GBM cells to TGF-ß1 significantly upregulated miR-10b expression. Overexpression of miR-10b promotes GBM cell proliferation, migration and EMT, whereas depletion of miR-10b obtained reverse effects. Further studies uncovered that some tumor-associated genes including epithelial cadherin (E-cadherin), apoptotic protease activating factor 1 (Apaf-1) and phosphatase and tensin homolog (PTEN) are target genes of miR-10b. In human GBM xenografts, antagomiR directed against miR-10b markedly suppressed tumor growth, and the tumor volume shrunk from 1252.5±285 to 873.4±205 mm3 after antagomiR­10b treatment for 3 weeks compared with the control group (P<0.01). Taken together, our data collectively demonstrate that the proliferation, migration and EMT features of GBM cells can be regulated by TGF-ß1 stimulation through controlling miR-10b. Thus, our findings provide a rationale for targeting TGF-ß1 or miR-10b for the treatment of GBM.

Microembolic signals detected with transcranial doppler sonography differ between symptomatic and asymptomatic middle cerebral artery stenoses in Northeast China.

Although microembolus monitoring has been widely used for ischemic cerebrovascular disease, the clinical significance of microembolic signal (MES) in asymptomatic middle cerebral artery (MCA) stenosis remains unclear. We aim to investigate the frequency of MES and the value of MES in predicting ischemic stroke secondary to asymptomatic MCA stenosis. From June 2011 to December 2012, microembolus monitoring was performed in 83 asymptomatic and 126 symptomatic subjects. By comparing the demographics and risk factors between the symptomatic and asymptomatic subjects, we found that the ratio of male sexuality and smoking history differed (101/126 vs 43/83, and 88/126 vs 38/83, respectively, p<0.01). The frequency of MES was significantly higher in the symptomatic group than in the asymptomatic group (49/126 vs 2/108, p<0.01). Specifically, the frequency of MES in the symptomatic and asymptomatic groups with mild stenosis, moderate stenosis, severe stenosis and occlusion groups was 4/18 (22.22%) vs 0/30 (0), 13/31 (41.94%) vs 1/28 (3.57%), 30/62 (48.39%) vs 1/39 (2.56%), 2/15 (13.33%) vs 0/11 (0), respectively. Except for the occlusive group, the frequency of MES is correlated with stenosis degree and symptom. Two patients in the asymptomatic group were found positive for MES, and the MES number was 1 for both. During the one-year follow-up, neither of them developed ischemic stroke. In conclusion, MES detected with TCD differs between symptomatic and asymptomatic MCA stenoses. Due to the low frequency, the value of MES as a predictor of subsequent ischemic stroke in patients with asymptomatic MCA stenosis might be limited.

[Effect of pathogenic dampness on changes of cytokines of rats with different gradients of evil-cold invading Fei].

OBJECTIVE: To research the influence of pathogenic dampness on changes of cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interluekin-4 (IL-4), interferon-gamma (IFN-gamma), etc. in the lung of rats with different gradients of evil-cold invading Fei. Methods One hundred and four Wistar rats of SPF grade were randomized depending on the digital table into 13 groups, 8 in each group: the normal temperature group, the 6 evil-cold invasive groups (ECG1-6) and the 6 cold-dampness invasive groups (CDG1-6). Rats in the ECG and CDG groups were exposed to cold or cold-dampness to different gradients, for subgroups 1 to 6, -10 degrees C, 0 degrees C, 10 degrees C, 20-10 degrees C, 20-0 degrees C and 20 - -10 degrees C was applied respectively for 2 h, then fed at room temperature to observe their general condition. Rats were sacrificed 4 days later and their lung tissue was taken out for determination of the contents of TNF-alpha, IL-6, IFN-gamma and IL-4 in lung tissue homogenate. Results Compared with the corresponding ECG groups, the contents of TNF-alpha, IL-6 and IL-4 were higher (P < 0.05 or P < 0.01), content of IFN-gamma and IFN-gamma/IL-4 ratio were significantly lower in the CDG groups (P < 0.01). CONCLUSION: Pathogenic dampness could aggravate the injury of Fei caused by the pathogenic cold to induce the change of inflammation related cytokines to a certain extent, and the unbalance of Th1/Th2 immune response in organism could be worsened as well.

[Effects of pathogenic wind-dampness on lung tissue cytokines in rats with syndrome due to pathogenic cold invading lung].

OBJECTIVE: To explore the effects of wind and dampness pathogens on cytokines in the lung tissue of rats with cold syndrome due to different gradient cold pathogens. METHODS: One hundred and four Wistar rats of SPF grade were randomly divided into 13 groups: normal temperature group, six cold pathogen groups and six cold plus wind-dampness pathogen (wind of grade 5 and 90%-100% relative humidity) groups. The cold pathogens were constant low temperature (including 10 degrees C, 0 degree C, -10 degrees C) and temperature change (including 20 to 10 degrees C, 20 to 0 degrees C, and 20 to -10 degrees C). The rats in different groups were kept in a temperature-controlled box under the corresponding condition for 2 hours on the first day of experiment. Then, the rats were all raised in normal temperature for 4 days and the rats' behaviors were observed. The contents of tumor necrosis factor alpha (TNF-alpha), interleukin-6(IL-6) and interleukin-4 (IL-4) in lung homogenate were measured by radioimmunoassay and the content of interferon-gamma (IFN-gamma) was detected by enzyme-linked immunosorbent assay. RESULTS: In comparison with cold pathogen groups, contents of TNF-alpha, IL-6 and IL-4 were obviously increased in lung homogenate of rats in cold plus wind-dampness pathogen groups (P<0.01), and the content of IFN-gamma and IFN-gamma/IL-4 ratio were obviously decreased (P<0.01). CONCLUSION: Wind-dampness pathogen can seriously aggravate the injury to lung tissue caused by cold pathogen, and the unbalance of Th(1)/Th(2) in lung homogenate of rats.

[Variabilities of the impacts of cold pathogen and cold-dampness pathogen on fractalkine mRNA expression in lung tissues of rats].

OBJECTIVE: To study the variabilities of the effects of cold pathogen and cold-dampness pathogen on the fractalkine (FKN) mRNA expression in lung tissues of rats. METHODS: Twenty-four Wistar rats of SPF grade were randomly divided into 3 groups: normal temperature group, cold pathogen group and cold-dampness pathogen group. There were 8 rats in each group. Rats in normal temperature group were bred at (20+/-2)degrees centigrade and under normal humidity (50%-55%) for 2 h. Rats in cold pathogen group were bred at -10 degrees centigrade and under normal humidity (50%-55%) for 2 h, and the rats in cold-dampness pathogen group were bred at -10 degrees centigrade and under high humidity (90%-100%) for 2 h. Rats in the three groups were bred in thermostats under the corresponding conditions on the first day of experiment, and then the rats in different groups were all bred at normal temperature. Lung specimens in 3 groups were gathered four days later. The behavior and the pathological changes in the lung tissues of rats in different groups were observed. The content of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in lung homogenate was detected by radioimmunoassay (RIA) method. Expression of FKN mRNA in lung homogenate was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The lung tissues of rats in both cold pathogen group and cold-dampness pathogen group had various degrees of pathological changes. Compared with normal temperature group, the content of IL-6 and TNF-alpha was increased obviously in lung homogenate of rats in both cold pathogen group and cold-dampness pathogen group (P<0.01). The content of IL-6 and TNF-alpha in lung homogenate of rats in cold-dampness pathogen group was obviously higher than that in cold pathogen group (P<0.01). The RT-PCR results showed a low expression of FKN mRNA in lung tissues of rats in normal temperature group. If the injured lung tissues were aggravated, the expression of FKN mRNA in the lung tissues was elevated. Compared with normal temperature group, FKN mRNA expressions in both cold pathogen group and cold-dampness pathogen group were increased obviously (P<0.01). FKN mRNA expression in lung homogenate of rats in cold-dampness pathogen group was also obviously higher than that in cold pathogen group (P<0.01). CONCLUSION: Cold pathogen can induce lung injury and up-regulate the FKN mRNA expression in lung tissue. Dampness pathogen can up-regulate the FKN mRNA expression through aggravating the injury of lung tissues caused by cold pathogen. FKN has a close relationship with the lung injury.