Establishment of a cell senescence related prognostic model for predicting prognosis in glioblastoma

Background: Glioblastoma (GBM) is highly malignant and has a worse prognosis with age, and next-generation sequencing (NGS) provides us with a huge amount of information about GBM.Materials and Methods: Through the enrichment scores of cell senescence-related pathways, we constructed a consensus matrix and mined molecular subtypes and explored the differences in pathological, immune/pathway and prognostic. Also we identified key genes related to cell senescence characteristics using least absolute shrinkage and selection operator (Lasso) regression and univariate COX regression analysis models. The use of risk factor formats to construct clinical prognostic models also explored the differences in immunotherapy/chemotherapy within the senescence-related signatures score (SRS.score) subgroups. Decision trees built with machine learning to identify the main factors affecting prognosis have further improved the prognosis model and survival prediction.Results: We obtained seven prognostic-related pathways related to cell senescence. We constructed four different molecular subtypes and found patients with subtype C1 had the worst prognosis. C4 had the highest proportion of patients with IDH mutations. 1005 differentially expressed genes (DEGs) were analyzed, and finally 194 Risk genes and 38 Protective genes were obtained. Eight key genes responsible for cell senescence were finally identified. The clinical prognosis model was established based on SRS.score, and the prognosis of patients with high SRS.score was worse. SRS.score and age were the vital risk factors for GBM patients through decision tree model mining.Conclusion: We constructed a clinical prognosis model that could provide high prediction accuracy and survival prediction ability for adjuvant treatment of patients with GBM

Construction and validation of a glioblastoma prognostic model based on immune-related genes

BackgroundGlioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued.PurposeHere, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM.MethodsGlioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandem mass spectrometry and western blotting (WB).ResultsSix IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB.ConclusionHerein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research

Plasma microRNA Profiles as a Potential Biomarker in Differentiating Adult-Onset Still's Disease From Sepsis

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by cytokine storm. However, a diagnostic test for AOSD in clinical use is yet to be validated. The aim of our study was to identify non-invasive biomarkers with high specificity and sensitivity to diagnosis of AOSD. MicroRNA (miRNA) profiles in PBMC from new-onset AOSD patients without any treatment and healthy controls (HCs) were analyzed by miRNA deep sequencing. Plasma samples from 100 AOSD patients and 60 HCs were used to validated the expression levels of miRNA by qRT-PCR. The correlations between expression levels of miRNAs and clinical manifestations were analyzed using advanced statistical models. We found that plasma samples from AOSD patients showed a distinct miRNA expression profile. Five miRNAs (miR-142-5p, miR-101-3p, miR-29a-3p, miR-29c-3p, and miR-141-3p) were significantly upregulated in plasma of AOSD patients compared with HCs both in training and validation sets. We discovered a panel including 3 miRNAs (miR-142-5p, miR-101-3p, and miR-29a-3p) that can predict the probability of AOSD with an area under the receiver operating characteristic (ROC) curve of 0.8250 in training and validation sets. Moreover, the expression levels of 5 miRNAs were significantly higher in active AOSD patients compared with those in inactive patients. In addition, elevated level of miR-101-3p was found in AOSD patients with fever, sore throat and arthralgia symptoms; the miR-101-3p was also positively correlated with the levels of IL-6 and TNF-α in serum. Furthermore, five miRNAs (miR-142-5p, miR-101-3p, miR-29c-3p, miR-29a-3p, and miR-141-3p) expressed in plasma were significantly higher in AOSD patients than in sepsis patients (P < 0.05). The AUC value of 4-miRNA panel (miR-142-5p, miR-101-3p, miR-29c-3p, and miR-141-3p) for AOSD diagnosis from sepsis was 0.8448, revealing the potentially diagnostic value to distinguish AOSD patients from sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as a potential non-invasive biomarker for diagnosis of AOSD and monitoring disease activity

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Four new species of Closterocerus Westwood (Hymenoptera, Eulophidae) from China, with a key to Chinese species

Four new species of Closterocerus Westwood, C. rectisulcus sp. nov., C. shaanxiensis sp. nov., C. separatus sp. nov. and C. unifasciatus sp. nov. are described from China, each with a distinct pattern on the fore wings, and belonging to subgenus Closterocerus. A key to all species of the genus Closterocerus in China is provided

Three new species of Quadrastichus Girault (Hymenoptera, Eulophidae) from China with a key to Chinese species

Six species of Quadrastichus Girault (Eulophidae: Tetrastichinae) from China are reviewed, including three new species: Q. longiseta sp. nov., Q. flavomaculatus sp. nov., Q. longiscapus sp. nov. and one new country record, Q. vacuna (Walker, 1839). New distributional data for Q. anysis (Walker, 1839) and Q. sajoi (Szelényi, 1941), and a key to the Chinese species of Quadrastichus based on females, are included

A new species of Asecodes Förster (Hymenoptera, Eulophidae) and first record of A. reticulatum (Kamijo) from China, with a key to Chinese species

A new species of Asecodes Förster, A. medogense sp. nov. is described from Tibet, China and A. reticulatum (Kamijo) is reported from China for the first time. A key to all known species of genus Asecodes in China is provided

A new species of Asecodes Förster (Hymenoptera, Eulophidae) and first record of A. reticulatum (Kamijo) from China, with a key to Chinese species

A new species of Asecodes Förster, A. medogense sp. nov. is described from Tibet, China and A. reticulatum (Kamijo) is reported from China for the first time. A key to all known species of genus Asecodes in China is provided