Adult epithelioid glioblastoma exhibits an extremely poor prognosis and high frequency of SWI/SNF complex mutation: Insights from a retrospective study.

Epithelioid glioblastoma (eGBM) is a rare subtype of GBM. Given the update of the definition of GBM, the understanding of the molecular characteristics and prognosis of "true" adult eGBM remains limited. Herein, we retrospectively analyzed the clinicopathological data of 39 adult eGBM cases. Adult eGBM primarily affected females, with a male-to-female ratio of 1:2.3. The average age of diagnosis was 53 years, and the tumor affected the temporal lobe in 41% of cases (16/39, 41%). Microscopically, the tumors consisted mainly or entirely of epithelioid cells. Perivascular infiltration (10/39, 25.6%) and leptomeningeal dissemination (7/39, 17.9%) were not uncommon. BRAF V600E mutation was detected in 40.9% of cases (n = 9/22). Next-generation sequencing revealed that CDKN2A/B homogeneous deletion was the most frequently mutated gene (8/10, 80%), followed by TERT promoter mutation (7/10, 70%), Cyclin-dependent kinases 4 or 6 (CDK4/6) amplification (5/10, 50%) and BRAF V600E mutation (50%, 5/10). Notably, the incidence of ARID1B mutation in eGBM was 50% (5/10), representing the first report of such a mutation in this subtype of GBM. ARID1B was known to be a subunit of the SWI/SNF chromatin remodeler. Chromosome analysis showed a 7+/10- signature in 90% (9/10) cases. Adult eGBM carried a dismal prognosis compared to GBM with IDH and H3 wild-type (typical GBM) (OS: 13.89 vs 24.30 months; P = .003) and even typical GBM without MGMT promoter methylation (OS: 13.89 vs 22.08 months; P = .036). Based on these findings, it can be concluded that adult eGBM harbors a high frequency of the 7+/10- signature and alterations in the MAPK pathway, SWI/SNF complex and cyclin-related genes and portends an extremely poor prognosis.

Accuracy assessment of robot-assisted implant surgery in dentistry: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: The systematic assessment of accuracy of robot-assisted implant surgery is lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the accuracy of robot-assisted implant surgery and compare it with computer-aided implant surgery in partially and completely edentulous patients and human phantoms. MATERIAL AND METHODS: The studies were selected from ScienceDirect, Web of science, Cochrane Library, PubMed, and CNKI databases. The risk of bias of the included studies was evaluated with the risk of bias in nonrandomized studies of interventions tool. The mean and standard deviation of global coronal, apical, and angular deviations of implants were the primary outcome. Meta-analysis was conducted to evaluate the accuracy of the robot-assisted implant surgery and compare it with computer-aided implant surgery in dental implantation (α=.05). RESULTS: Eleven in vitro studies with 809 implants and 10 clinical studies with 257 implants were included. For the in vitro studies, the mean global coronal, apical, and angular deviations of robot-assisted implant surgery were 0.7 mm (95% CI: 0.6 to 0.8), 0.8 mm (95% CI: 0.6 to 1.0), and 1.8 degrees (95%CI: 1.2 to 2.5), respectively. For the clinical studies, the average global coronal, apical, and angular deviations of robot-assisted implant surgery were 0.6 mm (95% CI: 0.5 to 0.8), 0.7 mm (95% CI: 0.6 to 0.8), and 1.6 degrees (95%CI: 1.1 to 2.0), respectively. For the in vitro studies, the robot-assisted implant surgery group showed significantly more decrease in global coronal deviation than the computer-assisted implant surgery group (P=.012). The robot-assisted implant surgery group offered smaller global apical deviation (P=.001) and angular deviation (P<.001) than the computer-assisted implant surgery group. CONCLUSIONS: Robot navigation is a clinically reliable method of implant placement. Significantly lower global coronal, apical, and angular deviations were observed for robot-assisted implant surgery compared with computer-assisted implant surgery in human phantoms.

The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress.

Animal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, blood glucose and lipid profiles were measured. The high-fat (HF) diet damaged insulin sensitivity and increased triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and liver lipid deposition. STZ increased blood glucose and liver fibrosis with less effects on blood lipids or liver lipid deposition. The combination of DIO and STZ treatments led to significant liver lipid deposition and fibrosis. Female mice showed delayed body weight gain on HF diet and resisted STZ-induced hyperglycemia. However, once they developed DIO, which occurs around 26 weeks of HF diet, the female mice were prone to STZ-induced hyperglycemia. In hindlimb ischemia, male mice in the DIO-STZ group showed significantly worse neovascularization compared with DIO or STZ groups. The DIO-STZ females showed significantly worse recovery than the DIO-STZ males. Our observations suggest that DIO-STZ is a plausible model for studying metabolic and cardiovascular disorders in obesity and diabetes. Moreover, the findings in female animals stress the need to assess sexual dimorphism and investigate the underlying mechanisms that contribute to the worse vasculopathy manifestations in females in metabolic models.

Stroke as initial manifestation of non-small cell lung cancer with Trousseau syndrome.

OBJECTIVE: Stroke is a rare but fatal complication of advanced cancer with Trousseau syndrome, especially as initial symptoms. Here, we report the clinical characteristics, treatment, and prognosis of patients with non-small cell lung cancer (NSCLC) who initially presenting with acute multiple cerebral infarction. METHODS: The clinical characteristics, imaging, treatment, and oncological outcomes of 10 patients diagnosed with Trousseau syndrome and NSCLC between 2015 and 2021 at Guangdong Sanjiu Brain Hospital were retrospectively collected and analyzed. The clinical course of two typical cases were presented. RESULTS: All 10 patients with pathologically confirmed lung adenocarcinoma initially presented with neurological symptoms, including hemiplegic paralysis (7 patients, 70%), dizziness (5 patients, 50%), and unclear speech (3 patients, 30%). The median age was 63.5 years. Eight and two cases were stage III and IV, respectively, at the initial diagnosis. Five patients underwent driver gene testing, revealing three patients with EGFR-sensitive mutations, one patient with ALK fusion, and one patient with wild-type EGFR. All 10 patients received antiplatelet therapy, and six patients subsequently received anti-cancer treatment. The median overall survival of the patients was 8.5 months (95% confidence interval) and 1-year survival rate was 57.1%. Patients who received antitumor treatment, especially those harboring driver gene mutations and received tyrosine kinase inhibitors, had better neurological symptom recovery and superior oncological prognosis (median overall survival, not reached versus 7.4 months, p = 0.038). CONCLUSION: Trousseau syndrome, presenting as multiple cerebral infarctions, is a rare complication of lung adenocarcinoma. Both antiplatelet and antitumor treatment are recommended to achieve better neurological recovery and oncological prognosis in these patients.

Process-based dynamic identification indicators of soybean chilling damage and analysis of the corresponding spatiotemporal characteristics in Northeast China.

Northeast China (NEC) is one of the main soybean-producing areas among the northern-latitude regions. Climate warming leads to frequent extreme disasters, and the threat of chilling damage to soybean production in NEC cannot be ignored. The study aimed to construct a dynamic disaster identification index based on the static evaluation of soybean after the disaster, taking into account the process of soybean chilling damage and using the historical disaster records to realize the dynamic prediction and analysis before the disaster. Taking soybean in NEC as the research object, chilling damage indicators of soybeans in NEC were constructed by dividing the mature regions, using daily temperature anomaly and negative temperature anomaly day data with the comprehensive consideration of the chilling damage intensity, duration, and temperature recovery. The results showed that the comprehensive indicators determined by the cumulative value of temperature anomaly-the cumulative days of negative temperature anomaly had better applicability in NEC than the single factor indicator. The indicator results were basically consistent with the historical disaster records, and the accuracy rate of the indicator verification reached 90.9%. Based on the analysis of the constructed indicators, the frequency of delayed chilling damage in NEC showed a fluctuating downward trend from 1961 to 2020. The station ratio of delayed chilling damage in NEC showed a fluctuating downward trend, with the most obvious downward trend occurring for severe damage, followed by moderate damage, and the least obvious trend observed for light damage. The scope of chilling damage gradually narrowed, with the frequency increasing from southeast to northwest. The high-risk areas of chilling damage were concentrated mainly in the northern part of Heilongjiang Province and the East Four Leagues. The risk of chilling damage in most areas of Jilin Province and Liaoning Province was relatively low. The study results provide basic support for the risk research of soybean chilling damage and for ensuring disaster monitoring and early warnings, and the risk assessment based on the chilling damage process has positive significance for adjusting agricultural structure and improving the distribution of soybean varieties.

Quantitative Proteomics Reveals Transforming Growth Factor ß Receptor Targeted by Resveratrol and Hesperetin Coformulation in Endothelial Cells.

The endothelium is the frontline target of multiple metabolic stressors and pharmacological agents. As a consequence, endothelial cells (ECs) display highly dynamic and diverse proteome profiles. We describe here the culture of human aortic ECs from healthy and type 2 diabetic donors, the treatment with a small molecular coformulation of trans-resveratrol and hesperetin (tRES+HESP), followed by proteomic analysis of whole-cell lysate. A number of 3666 proteins were presented in all of the samples and thus further analyzed. We found that 179 proteins had a significant difference between diabetic ECs vs. healthy ECs, while 81 proteins had a significant change upon the treatment of tRES+HESP in diabetic ECs. Among them, 16 proteins showed a difference between diabetic ECs and healthy ECs and the difference was reversed by the tRES+HESP treatment. Follow-up functional assays identified activin A receptor-like type 1 and transforming growth factor ß receptor 2 as the most pronounced targets suppressed by tRES+HESP in protecting angiogenesis in vitro. Our study has revealed the global differences in proteins and biological pathways in ECs from diabetic donors, which are potentially reversible by the tRES+HESP formula. Furthermore, we have identified the TGFß receptor as a responding mechanism in ECs treated with this formula, shedding light on future studies for deeper molecular characterization.

Lorlatinib for ALK-fused, infant-type hemispheric glioma with lung metastasis: a case report.

Infant-type hemispheric glioma, a new subtype of pediatric high-grade glioma, arises in the cerebral hemispheres. Despite better survival outcomes, the treatment of infant-type hemispheric glioma is still facing challenges. Here, we reported a case of QKI-ALK fusion, infant-type hemispheric glioma with lung metastasis who achieved a complete clinical response after lorlatinib treatment. This typical case demonstrated the importance of appropriate molecularly targeted treatments in ALK-fused tumors, and lorlatinib may serve as an effective complement to conventional chemotherapy and radiotherapy in primary glioma harboring ALK fusions and its metastasis.

Boosting UPR transcriptional activator XBP1 accelerates acute wound healing.

Patients' suffering from large or deep wounds caused by traumatic and/or thermal injuries have significantly lower chances of recapitulating lost skin function through natural healing. We tested whether enhanced unfolded protein response (UPR) by expression of a UPR transcriptional activator, X-box-binding protein 1 (XBP1) can significantly promote wound repair through stimulating growth factor production and promoting angiogenesis. In mouse models of a second-degree thermal wound, a full-thickness traumatic wound, and a full-thickness diabetic wound, the topical gene transfer of the activated form of XBP1 (spliced XBP1, XBP1s) can significantly enhance re-epithelialization and increase angiogenesis, leading to rapid, nearly complete wound closure with intact regenerated epidermis and dermis. Overexpression of XBP1s stimulated the transcription of growth factors in fibroblasts critical to proliferation and remodeling during wound repair, including platelet-derived growth factor BB, basic fibroblast growth factor, and transforming growth factor beta 3. Meanwhile, the overexpression of XBP1s boosted the migration and tube formation of dermal microvascular endothelial cells in vitro. Our functional and mechanistic investigations of XBP1-mediated regulation of wound healing processes provide novel insights into the previously undermined physiological role of the UPR in skin injuries. The finding opens an avenue to developing potential XBP1-based therapeutic strategies in clinical wound care protocols.

The PTEN-associated immune prognostic signature reveals the landscape of the tumor microenvironment in glioblastoma.

Glioblastoma (GBM) is a common brain tumor with a complex and diverse tumor microenvironment (TME). As PTEN mutation is the most common mutation in GBM, we aimed to investigate how PTEN mutation regulates the immune response in GBM TME and thus affects the prognosis of GBM patients. In this study, we conducted a comprehensive analysis of multiple levels of data, including whole-exome sequencing (WES), transcriptome RNA sequencing, patient survival and immune signatures, to study the relationship between PTEN mutation and TME in GBM. We developed an immune-related prognostic signature (IPS) based on the PTEN-associated immune-related genes (IRGs), and the IPS exhibited a powerful prognosis prediction capacity in different GBM cohorts. A scoring nomogram based on the IPS was also established for clinical application. In addition, the correlations of the IPS with tumor immune cell infiltration and immune checkpoints were systematically analyzed. This study illustrates the influence of PTEN mutation on the immune microenvironment of GBM. Our IPS, which is sensitive to PTEN mutation status, can enhance the prognosis prediction ability for GBM patients and provides potential targets for immunotherapy.

Inhibition of GPR39 restores defects in endothelial cell-mediated neovascularization under the duress of chronic hyperglycemia: Evidence for regulatory roles of the sonic hedgehog signaling axis.

Impaired endothelial cell (EC)-mediated angiogenesis contributes to critical limb ischemia in diabetic patients. The sonic hedgehog (SHH) pathway participates in angiogenesis but is repressed in hyperglycemia by obscure mechanisms. We investigated the orphan G protein-coupled receptor GPR39 on SHH pathway activation in ECs and ischemia-induced angiogenesis in animals with chronic hyperglycemia. Human aortic ECs from healthy and type 2 diabetic (T2D) donors were cultured in vitro. GPR39 mRNA expression was significantly elevated in T2D. The EC proliferation, migration, and tube formation were attenuated by adenovirus-mediated GPR39 overexpression (Ad-GPR39) or GPR39 agonist TC-G-1008 in vitro. The production of proangiogenic factors was reduced by Ad-GPR39. Conversely, human ECs transfected with GPR39 siRNA or the mouse aortic ECs isolated from GPR39 global knockout (GPR39KO) mice displayed enhanced migration and proliferation compared with their respective controls. GPR39 suppressed the basal and ligand-dependent activation of the SHH effector GLI1, leading to attenuated EC migration. Coimmunoprecipitation revealed that the GPR39 direct binding of the suppressor of fused (SUFU), the SHH pathway endogenous inhibitor, may achieve this. Furthermore, in ECs with GPR39 knockdown, the robust GLI1 activation and EC migration were abolished by SUFU overexpression. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, the GPR39KO mice demonstrated a faster pace of revascularization from hind limb ischemia and lower incidence of tissue necrosis than GPR39 wild-type (GPR39WT) counterparts. These findings have provided a conceptual framework for developing therapeutic tools that ablate or inhibit GPR39 for ischemic tissue repair under metabolic stress.

Transcriptome analysis reveals key drought-stress-responsive genes in soybean.

Drought is the most common environmental stress and has had dramatic impacts on soybean (Glycine max L.) growth and yield worldwide. Therefore, to investigate the response mechanism underlying soybean resistance to drought stress, the drought-sensitive cultivar "Liaodou 15" was exposed to 7 (mild drought stress, LD), 17 (moderate drought stress, MD) and 27 (severe drought stress, SD) days of drought stress at the flowering stage followed by rehydration until harvest. A total of 2214, 3684 and 2985 differentially expressed genes (DEGs) in LD/CK1, MD/CK2, and SD/CK3, respectively, were identified by RNA-seq. Weighted gene co-expression network analysis (WGCNA) revealed the drought-response TFs such as WRKY (Glyma.15G021900, Glyma.15G006800), MYB (Glyma.15G190100, Glyma.15G237900), and bZIP (Glyma.15G114800), which may be regulated soybean drought resistance. Second, Glyma.08G176300 (NCED1), Glyma.03G222600 (SDR), Glyma.02G048400 (F3H), Glyma.14G221200 (CAD), Glyma.14G205200 (C4H), Glyma.19G105100 (CHS), Glyma.07G266200 (VTC) and Glyma.15G251500 (GST), which are involved in ABA and flavonoid biosynthesis and ascorbic acid and glutathione metabolism, were identified, suggesting that these metabolic pathways play key roles in the soybean response to drought. Finally, the soybean yield after rehydration was reduced by 50% under severe drought stress. Collectively, our study deepens the understanding of soybean drought resistance mechanisms and provides a theoretical basis for the soybean drought resistance molecular breeding and effectively adjusts water-saving irrigation for soybean under field production.

Identification of key genes with prognostic value in gastric cancer by bioinformatics analysis.

Background: Gastric cancer (GC) is a digestive system tumor with high morbidity and mortality. It is urgently required to identify genes to elucidate the underlying molecular mechanisms. The aim of this study is to identify the key genes which may affect the prognosis of GC patients and be a therapeutic strategy for GC patients by bioinformatic analysis. Methods: The significant prognostic differentially expressed genes (DEGs) were screened out from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. The protein-protein interaction (PPI) network was established by STRING and screening key genes by MCODE and CytoNCA plug-ins in Cytoscape. Functional enrichment analysis, construction of a prognostic risk model, and nomograms verify key genes as potential therapeutic targets. Results: In total, 997 genes and 805 genes were related to the prognosis of GC in the GSE84437 and TCGA datasets, respectively. We define the 128 genes shared by the two datasets as prognostic DEGs (P-DEGs). Then, the first four genes (MYLK, MYL9, LUM, and CAV1) with great node importance in the PPI network of P-DEGs were identified as key genes. Independent prognostic risk analysis found that patients with high key gene expression had a poor prognosis, excluding their age, gender, and TNM stage. GO and KEGG enrichment analyses showed that key genes may exert influence through the PI3K-Akt pathway, in which extracellular matrix organization and focal adhesion may play important roles in key genes influencing the prognosis of GC patients. Conclusion: We found that MYLK, MYL9, LUM, and CAV1 are potential and reliable prognostic key genes that affect the invasion and migration of gastric cancer.

MicroRNA-466 and microRNA-200 increase endothelial permeability in hyperglycemia by targeting Claudin-5.

Endothelial cell (EC) permeability is essential to vascular homeostasis in diabetes. MicroRNAs are critical gene regulators whose roles in the EC permeability have yet to be characterized. This study aims to examine the change in cell permeability induced by miR-200 and miR-466 in ECs. Human aortic ECs and dermal microvascular ECs from healthy subjects and type 2 diabetic patients were used. Our in vitro experiments unveiled higher expressions of miR-200 family members and miR-466 in diabetic ECs and in healthy ECs when exposed to high glucose. Overexpression of both miR-200 and miR-466 significantly increased EC permeability through transcriptional suppression of Claudin-5, the cell tight junction protein, by directly binding to its 3' untranslated region. In a mouse model of chronic hyperglycemia mimicking type 2 diabetes in humans (db/db mice), the delayed closure rate of a full-thickness excisional wound was partly rescued by topical application of the miR-200 inhibitor. The topical application of both miR-200 and miR-466 inhibitors exhibited improved efficacy in accelerating wound closure compared with the topical application of miR-200 inhibitor alone. Our study demonstrated the potentially effective approach of miR-200/miR-466 cocktail inhibition to restore vascular integrity and tissue repair in hyperglycemia.

Accuracy of CAD-CAM milling versus conventional lost-wax casting for single metal copings: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Information comparing the marginal and internal adaptation of single metal copings fabricated via computer-aided design and computer-aided manufacturing (CAD-CAM) milling and lost-wax casting is insufficient. PURPOSE: The purpose of this systematic review and meta-analysis was to compare the adaptation of single metal copings fabricated via CAD-CAM milling to that of copings fabricated via lost-wax casting and to identify factors that influenced their accuracy. MATERIAL AND METHODS: Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, Elsevier ScienceDirect, PubMed, Cochrane Library, SpringerLink, and Wiley online databases were searched to select qualified articles, which were assessed by the methodological items for nonrandomized studies (MINORS) criteria. The data on the mean absolute marginal gap, marginal gap, axial gap, occlusal gap, and internal gap values of single metal copings fabricated via CAD-CAM milling and lost-wax casting were extracted, and meta-analysis and meta-regression were used with R software (α=.05) and random-effects models to estimate differences and homogeneity between the 2 methods. RESULTS: For the single metal copings, lost-wax casting and CAD-CAM milling led to similar marginal and internal accuracies, but lost-wax casting led to better absolute marginal gap values. For the cast copings, Ni-Cr alloy (92.8 µm) and noble alloy (51.5 µm) led to the largest and smallest marginal gaps, respectively, (P=.005). For milled copings, the noble alloy led to the smallest marginal gap (19.1 µm), and Co-Cr alloy to the largest (76.2 µm) (P=.012). Soft milling led to a more accurate marginal gap (41.4 µm) than hard milling (66.1 µm) (P=.04). CONCLUSIONS: When CAD-CAM milling was used to fabricate single metal copings, no advantage in precision was found compared with lost-wax casting, and single metal copings cast from handmade conventional wax patterns had better marginal adaptation than those fabricated via CAD-CAM milling. Noble metal copings had improved marginal accuracy than base metal copings for both the casting and milling methods. Single copings fabricated via soft milling from unsintered metal blocks had more accurate marginal adaption than copings fabricated via hard milling.

Identification of an Immune-Related Prognostic Risk Model in Glioblastoma.

Background: Glioblastoma (GBM) is the most common and malignant type of brain tumor. A large number of studies have shown that the immunotherapy of tumors is effective, but the immunotherapy effect of GBM is not poor. Thus, further research on the immune-related hub genes of GBM is extremely important. Methods: The GBM highly correlated gene clusters were screened out by differential expression, mutation analysis, and weighted gene co-expression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and proportional hazards model (COX) regressions were implemented to construct prognostic risk models. Survival, receiver operating characteristic (ROC) curve, and compound difference analyses of tumor mutation burden were used to further verify the prognostic risk model. Then, we predicted GBM patient responses to immunotherapy using the ESTIMATE algorithm, GSEA, and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Results: A total of 834 immune-related differentially expressed genes (DEGs) were identified. The five hub genes (STAT3, SEMA4F, GREM2, MDK, and SREBF1) were identified as the prognostic risk model (PRM) screened out by WGCNA and LASSO analysis of DEGs. In addition, the PRM has a significant positive correlation with immune cell infiltration of the tumor microenvironment (TME) and expression of critical immune checkpoints, indicating that the poor prognosis of patients is due to TIDE. Conclusion: We constructed the PRM composed of five hub genes, which provided a new strategy for developing tumor immunotherapy.

Survival outcomes, hematologic complications and growth impairment after sequential chemoradiotherapy in intracranial NGGCTs: a retrospective study.

PURPOSE: This study aimed to evaluate the clinical features, prognostic factors, and survival outcomes for patients with intracranial nongerminomatous germ cell tumors (NGGCTs), with a particular focus on treatment toxicity for long-term survivors. METHODS: Intracranial NGGCTs treated with platinum-based chemotherapy and craniospinal irradiation (CSI) in our institution were retrospectively analyzed. Hematological complications following sequential chemoradiotherapy as well as height and weight in childhood survivors were evaluated. Plasma growth hormone (GH) concentrations prior to and after radiotherapy were obtained for the comparisons. RESULTS: A total of 111 intracranial NGGCTs were included. The 3­year overall survival (OS) and event-free survival (EFS) rates were 83.5% ± 3.9% and 71.0% ± 4.8%, respectively. A combined treatment modality consisting of ≥ 4 cycles of platinum-based chemotherapy and CSI was associated with an improved OS (P = 0.003) and EFS (P < 0.001). Thrombocytopenia of any grade occurred in 35.4% (34/96) of patients, and the threshold age for an increased risk of thrombocytopenia was 14 years (area under the curve AUC = 0.752, P < 0.0001) as derived from receiver operating characteristic (ROC) analysis. Growth impediment was found in 8 of 56 (14%) patients. The age for receiving radiotherapy was found to inversely correlate with height development, revealing a cut-off age of 11.5 years for risking growth impairment (AUC = 0.806, P = 0.004). Consistently, a significant decline in plasma growth hormone after radiotherapy was observed in patients ≤ 11.5 years (P < 0.01) but not patients > 11.5 years. (P > 0.05). CONCLUSION: Our study suggested that a combined treatment modality with at least four cycles of chemotherapy and CSI was safe and effective for patients with intracranial NGGCTs. Radiotherapy should be used with caution for patients < 11.5 years due to growth impairment.

Histone H3.3 G34-mutant Diffuse Gliomas in Adults.

The characteristics of H3.3 G34-mutant gliomas in adults have yet to be specifically described. Thirty adults with H3.3 G34-mutant diffuse gliomas were retrospectively reviewed for clinical and pathologic information. Molecular profiling using next-generation sequencing was performed in 29 of the 30 H3.3 G34-mutant patients with 1 patient lacking available tumor samples, as well as 82 IDH/H3 wild-type adult diffuse glioma patients. The age at diagnosis of H3.3 G34-mutant diffuse gliomas was significantly younger than IDH/H3 wild-type gliomas (24 vs. 57 y, P<0.001). Overall, 19 of the 30 patients were diagnosed of glioblastoma with the primitive neuronal component, and 8 were glioblastoma. The molecular profiling analysis revealed higher frequencies of Olig-2 loss of expression, TP53 mutation, ATRX mutation, PDGFRA mutation, and MGMT promoter methylation (P<0.05) in H3.3 G34-mutant gliomas than IDH/H3 wild-type gliomas. No TERT promoter mutation and only 1 case of EGFR amplification were detected in the H3.3 G34-mutant cohort, the frequencies of which were significantly higher in the IDH/H3 wild-type cohort. A dismal prognosis was observed in H3.3 G34-mutant patients comparing to IDH/H3 wild-type cohort (overall survival: 14 vs. 22 mo; P=0.026). Univariate and multivariate analyses showed that the extent of resection and TP53 mutation were independently affecting prognosis. The distinct pathologic and molecular features of H3.3 G34-mutant diffuse gliomas in adult patients demonstrated the clinical importance of detecting H3.3 G34R/V mutations. The dismal prognosis of this rare high-grade glioma disease we reported here would further promote the investigation of dedicated therapeutic strategies.

Selective laser sintering versus conventional lost-wax casting for single metal copings: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Evidence comparing the marginal and internal fit of single metal copings fabricated via selective laser sintering and conventional lost-wax casting is inadequate. PURPOSE: The purpose of this systematic review was to compare the fit of single metal copings fabricated via selective laser sintering and lost-wax casting. Moreover, the effects of different variables on fit accuracy were determined. MATERIAL AND METHODS: Google Scholar, ScienceDirect, SpringerLink, and Wiley databases were searched electronically as well as manually. The mean absolute marginal gap, marginal gap, internal gap, axial gap, and occlusal gap values of single metal copings fabricated via selective laser sintering and lost-wax casting were statistically analyzed to determine and evaluate the factors affecting the fit accuracy (α=.05). RESULTS: Single metal copings fabricated via selective laser sintering had mean absolute marginal gaps and occlusal gaps similar to those of copings fabricated via lost-wax casting, based on a subgroup meta-analysis of gaps evaluated using stereomicroscopy (P>.05). The fit of single metal copings was not affected by the type of tooth (P>.05). The conventional impression, the indirect digital scan, and the direct digital scan led to similar values of mean axial gap, internal gap, and marginal gap for the copings fabricated via lost-wax casting (P>.05). The indirect and direct digital scans led to similar values of mean axial gap, internal gap, and marginal gap for the copings fabricated via selective laser sintering (P>.05). Printed wax patterns provided significantly smaller mean axial gap values than milled plastic or milled wax patterns for the copings fabricated via lost-wax casting (P<.05). Printed, milled, and conventional wax patterns had similar mean marginal gaps and internal gaps for the copings fabricated via lost-wax casting (P>.05). For single copings fabricated via lost-wax casting, Ni-Cr and Co-Cr had similar mean internal gaps (P>.05). CONCLUSIONS: No statistically significant differences were found between single metal copings fabricated via selective laser sintering and lost-wax casting. Selective laser sintering can satisfy the clinical requirement for single metal copings.

A preparation method for the organoid model of patient-derived glioblastoma / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨胶质母细胞瘤（GBM）患者肿瘤组织来源的GBM类器官（GBO）模型的制备方法。方法：选取2021年广东三九脑科医院新诊断经病理确诊的8例GBM患者的新鲜肿瘤组织标本，将其剪成0.5~1 mm大小的组织碎片并用特制的培养基进行培养，待其成球且直径达到1 mm时剪小传代，同时选取培养2周以上的GBO进行石蜡包埋、切片，后进行H-E染色和免疫组化染色检测，并与亲本GBM组织进行组织学与细胞学的比较。结果：成功培养2例可传代冻存的GBO，并建立GBO生物库。H-E染色结果显示，GBO保留了与亲本GBM组织相似的组织结构和细胞形态；免疫组化实验结果显示，GBO与GBM组织中GFAP、OLIG2、Ki67和ATRX分子的表达情况一致。结论：将患者来源的GBM组织在体外剪小并用特制培养基培养，可构建与GBM患者肿瘤组织在组织和细胞层面一致的GBO。