Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

Mutations in the mitochondrial DNA have been certified to be one of the most important causes of maternally inherited sensorineural hearing loss. Among these, mitochondrial 12S rRNA1555A>G, 1494C>T and other mutations are associated with both nonsyndromic and drug induced hearing loss caused by aminoglycosides. Individuals carrying 1555A>G or 1494C>T mutation have a variety of clinical manifestations, which implies that the 1555A>G or 1494C>T mutation is a chief factor underlying the development of deafness but insufficient to produce the clinical phenotype. Therefore other modifier factors, such as aminoglycosides, mitochondrial haplotypes, secondary mutation or nuclear modifier genes, may play an important role in the phenotypic expression of the deafness-associated mitochondrial 12S rRNA1555A>G or 1494C>T mutation. In this review, the modifier factors for the phenotypic expression of deafness-associated mitochondrial 12S rRNA1555A>G or 1494C>T mutations were summarized and proposed the pathogenesis of maternally inherited deafness.

OBJECTIVE To investigate the bacterial distribution and sensitivity to antibiotics isolated from infected patients in emergency department. METHODS The antimicrobial susceptibility tests to commonly used antibiotics were performed to the specimen send by the emergency and respiratory departments in our hospital in 2007.The data were analyzed respectively. RESULTS Totally 340 strains were isolated in emergency department and 366 strains were isolated in respiratory department.The main bacteria isolated were similar in the two departments such as Acinetobacter baumannii,Pseudomonas aeruginosa,Staphylococcus aureus and Escherichia coli,but their sensitivities to antibiotics were different. CONCLUSIONS Bacterial distribution of the infected patients in emergency department is similar to respiratory departments,but their sensitivities to antibiotics are different.

To study the effect of Spirulina Com pound Tablet(FST) on the level of serum lipids in hyperlipidemic mice.METH ODS:The experimental hyperlipidemic mice were divided into four groups.Amo ng them,two groups were treated with FST 1.5g/kg,3g/kg respectively by ig admini stration,and one group was given lipanthyl 0.05g/kg by ig administration as the positive drug control,another group was received physiological saline by ig admi nistration as the hyperlipidemic control.The treatment were consecutively carrie d out for 14 days.Then the serum lipids of each group were determined with autom atic biochemistry analysor.RESULTS:Compared with the hyperlipidemic control group,it was found that FST could significantly decrease the level of to tal serum cholesterol(TC),triglyceride(TG),and low density lipoprotein-choleste rol(LDL-C),as well as remarkably increase the content of serum high density lip oprotein-cholesterol(HDL-C) and the value of HDL-C/TC in the hyperlipidemic m ice.Furthermore,the results also showed that FST could obviously raise the conce ntration of the serum apolipoproteinAI(apoAI) and reduce the concentration of ap olipoproteinB(apoB)(Whereas FST 1.5g/kg had no significant effect on apoB).CONCLUSION:FST could remarkably decrease the content of serum lipids and regulate the apolipoprotein in the hyperlipidemic mice.

With the doses of Spirulina compound tablet (FST) 1.5g?kg 1 ,3g?kg 1 by ig administration to normal rats,alloxan (ALX) induced diabetic rats and hyperlipidemic model rats respectively for 14 days ,then the fast blood glucose(FBG) and the serum lipids were detected.The results showed that FST could decrease the FBG and the serum TC,TG,LDL C,increase HDL C in normal and in diabetic rats.(But FST 1.5g?kg 1 had no significant effect on TG,HDL C in normal rats).In addition,it was found that FST could remarkably decrease the level of serum TC,TG, and LDL C,as well as increase HDL C in hyperlipidemic model rats.It is suggested that FST not only significantly decrease the FBG and the lipids contents both in normal and in diabetic rats,but also remarkably decrease the serum lipids level in hyperlipidemic model rats. [WT5HZ]