Objective To compare the adverse reactions to pegasparaginase(PEG-ASP)and Erwiniaasparaginase(ASP)in the treat-ment of pediatric acute lymphoblastic leukemia(ALL)and to provide clinical guidance for treatment.Methods A total of 13 patients who were switched from PEG-ASP to Erwinia ASP due to allergic reactions during the induction phase of ALL treatment at the Depart-ment of Hematology and Oncology,Children's Hospital Affiliated of Zhengzhou University between February 2022 and February 2023 were selected as the case group.A control group of 26 patients treated with PEG-ASP and matched for sex at a ratio of 1∶2 was also selected.Pre-and post-treatment coagulation function,blood biochemistry,blood ammonia level,and gastrointestinal reactions were compared between the groups.Results There were no significant differences in AST,TB,UB,TC,TG,AMY,UN,Cr,APTT,and Fbg levels between the two groups,pre-and post-treatment.However,ALT,GGT,BB,and Glu levels were higher in the control group,whereas albumin was lower than in the case group(P<0.05).Both groups had an increased post-treatment blood ammonia level(P<0.05),with significantly a higher level observed in the case group than in the control group(P<0.001).No significant differences in adverse gastro-intestinal reactions were observed between the two groups.Conclusion Erwinia ASP and PEG-ASP affected liver function in pediatric ALL re-induction therapy with minimal effects on coagulation and weaker gastrointestinal reaction.Erwinia ASP significantly affected the blood ammonia level,and both treatments caused mild gastrointestinal reactions.Regular blood ammonia monitoring,post Erwinia ASP treatment,is recommended.

Objective To compare the adverse reactions to pegasparaginase(PEG-ASP)and Erwiniaasparaginase(ASP)in the treat-ment of pediatric acute lymphoblastic leukemia(ALL)and to provide clinical guidance for treatment.Methods A total of 13 patients who were switched from PEG-ASP to Erwinia ASP due to allergic reactions during the induction phase of ALL treatment at the Depart-ment of Hematology and Oncology,Children's Hospital Affiliated of Zhengzhou University between February 2022 and February 2023 were selected as the case group.A control group of 26 patients treated with PEG-ASP and matched for sex at a ratio of 1∶2 was also selected.Pre-and post-treatment coagulation function,blood biochemistry,blood ammonia level,and gastrointestinal reactions were compared between the groups.Results There were no significant differences in AST,TB,UB,TC,TG,AMY,UN,Cr,APTT,and Fbg levels between the two groups,pre-and post-treatment.However,ALT,GGT,BB,and Glu levels were higher in the control group,whereas albumin was lower than in the case group(P<0.05).Both groups had an increased post-treatment blood ammonia level(P<0.05),with significantly a higher level observed in the case group than in the control group(P<0.001).No significant differences in adverse gastro-intestinal reactions were observed between the two groups.Conclusion Erwinia ASP and PEG-ASP affected liver function in pediatric ALL re-induction therapy with minimal effects on coagulation and weaker gastrointestinal reaction.Erwinia ASP significantly affected the blood ammonia level,and both treatments caused mild gastrointestinal reactions.Regular blood ammonia monitoring,post Erwinia ASP treatment,is recommended.

Lipotoxicity,caused by intracellular lipid accumulation,accelerates the degenerative process of cellular senescence,which has implications in cancer development and therapy.Previously,camitine palmi-toyltransferase 1C (CPT1C),a mitochondrial enzyme that catalyzes carnitinylation of fatty acids,was found to be a critical regulator of cancer cell senescence.However,whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown.An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231,HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C.Cellular lipotoxicity was further confirmed by lipotoxicity assays.Significant changes were found in the lipidome of CPT1 C-depleted cells,including major alterations in fatty acid,diacylglycerol,triacylglycerol,oxidative lipids,cardiolipin,phosphatidylglycerol,phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin.This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialde-hyde and reactive oxygen species,signatures of lipid peroxidation and oxidative stress.Reduction of ATP synthesis,loss of mitochondrial transmembrane potential and down-regulation of expression of mito-chondriogenesis gene mRNAs indicated mitochondrial dysfunction induced by lipotoxicity,which could further result in cellular senescence.Taken together,this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence,suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.