Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism betwee...Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.展开更多
Anaphylaxis is a serious systemic reaction that is part of the general pattern of potentially fatal hypersensitivity reactions requiring immediate management. We report the case of a patient presenting to emergency wi...Anaphylaxis is a serious systemic reaction that is part of the general pattern of potentially fatal hypersensitivity reactions requiring immediate management. We report the case of a patient presenting to emergency with signs of malaria and pneumonia who was diagnosed with grade 4 anaphylaxis following antibiotic injection in the emergency department. The patient was 30 years old, with no previous history of anaphylaxis, and presented to the emergency department with fever, dry cough, headache and dizziness associated with prostration. Physical examination showed stable hemodynamics (BP = 110/80 mmHg, HR = 95 p/min,) and respiratory function with SpO<sub>2</sub> = 98%, HR = 22 c/min and crepitus rales at the base of the lungs. The laboratory work-up carried out in the emergency department revealed a biological inflammatory syndrome associated with hyperleukocytosis of 11,260/mm<sup>3</sup>, a positive thick drop with GE(+) dp = 1183 T/microlitre;blood glucose = 0.83 g/l;Covid 19 RDT = (negative). A diagnosis of malaria and pneumonia was made and antibiotic therapy (ceftriaxone) and artesunate were indicated. During the injection of ceftriaxone 1 g, the patient became agitated, followed by cardiorespiratory arrest, confirming the diagnosis of stage 4 anaphylaxis. Treatment consisted of stopping the ceftriaxone injection, external cardiac massage and ventilation, intravenous adrenaline and vascular filling, which enabled the patient to recover and stabilize. The diagnosis of anaphylaxis is clinical. Early administration of adrenaline is the mainstay of treatment.展开更多
B4C, SiC and C, Cu functionally graded-materials (FGMs) have been developed by plasma spraying and hot pressing. Their high-heat flux properties have been investigated by high energy laser and electron beam for the si...B4C, SiC and C, Cu functionally graded-materials (FGMs) have been developed by plasma spraying and hot pressing. Their high-heat flux properties have been investigated by high energy laser and electron beam for the simulation of plasma disruption process of the future fusion reactors, And a study on eroded products of B4C/Cu FGM under transient thermal load of electron beam was performed. In the experiment, SEM and EDS analysis indicated that B4C and SiC were decomposed, carbon was preferentially evaporated under high thermal load, and a part of Si and Cu were melted, in addition, the splash of melted metal and the particle emission of brittle destruction were also found. Different erosive behaviors of carbon-based materials (CBMs) caused by laser and electron beam were also discussed.展开更多
文摘Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.
文摘Anaphylaxis is a serious systemic reaction that is part of the general pattern of potentially fatal hypersensitivity reactions requiring immediate management. We report the case of a patient presenting to emergency with signs of malaria and pneumonia who was diagnosed with grade 4 anaphylaxis following antibiotic injection in the emergency department. The patient was 30 years old, with no previous history of anaphylaxis, and presented to the emergency department with fever, dry cough, headache and dizziness associated with prostration. Physical examination showed stable hemodynamics (BP = 110/80 mmHg, HR = 95 p/min,) and respiratory function with SpO<sub>2</sub> = 98%, HR = 22 c/min and crepitus rales at the base of the lungs. The laboratory work-up carried out in the emergency department revealed a biological inflammatory syndrome associated with hyperleukocytosis of 11,260/mm<sup>3</sup>, a positive thick drop with GE(+) dp = 1183 T/microlitre;blood glucose = 0.83 g/l;Covid 19 RDT = (negative). A diagnosis of malaria and pneumonia was made and antibiotic therapy (ceftriaxone) and artesunate were indicated. During the injection of ceftriaxone 1 g, the patient became agitated, followed by cardiorespiratory arrest, confirming the diagnosis of stage 4 anaphylaxis. Treatment consisted of stopping the ceftriaxone injection, external cardiac massage and ventilation, intravenous adrenaline and vascular filling, which enabled the patient to recover and stabilize. The diagnosis of anaphylaxis is clinical. Early administration of adrenaline is the mainstay of treatment.
文摘B4C, SiC and C, Cu functionally graded-materials (FGMs) have been developed by plasma spraying and hot pressing. Their high-heat flux properties have been investigated by high energy laser and electron beam for the simulation of plasma disruption process of the future fusion reactors, And a study on eroded products of B4C/Cu FGM under transient thermal load of electron beam was performed. In the experiment, SEM and EDS analysis indicated that B4C and SiC were decomposed, carbon was preferentially evaporated under high thermal load, and a part of Si and Cu were melted, in addition, the splash of melted metal and the particle emission of brittle destruction were also found. Different erosive behaviors of carbon-based materials (CBMs) caused by laser and electron beam were also discussed.
