Objective: To investigate the effect of adiponectin levels with its related mechanism in diabetic myocardial ischemia-reperfusion injury and ischemia post-conditioning in experimental rats. Methods: A total of 80 male SD rats were randomly divided into 6 groups: Normal sham (NS) group,n=8, Normal ischemia-reperfusion injury (NIRI) group,n=16, Normal ischemia post-conditioning (NIPO) group,n=16 and Diabetic mellitus sham (DMS) group,n=8, Diabetic mellitus ischemia-reperfusion injury (DMIRI) group,n=16, Diabetic mellitus ischemic post-conditioning (DMIPO) group,n=16. DM rats model was established by intraperitoneal injection of streptozotocin; IR model was established by occlusion of left anterior descending (LAD) coronary artery for 30 min followed by reperfusion for 120min; IPO model was established by 3 cycles of ischemia for 10s and reperfusion for10s; the rats in Sham group received silk line wrapping of LAD without occlusion. The myocardial infarction (MI) area was measured by TTC staining, plasma adiponectin level was examined by ELISA, the protein expressions of p-Akt and total-Akt were detected by Western blot analysis. Results: Compared with NIRI group, NIPO group had decreased MI area,P<0.05, while DMIRI group and DMIPO group had increased MI area,P<0.01; compared with NS group, NIRI group and NIPO group showed up-regulated expression of adiponectin and p-Akt,P<0.05 and DMS group showed down-regulated p-Akt,P<0.05. Compared with NIPO group, three DM groups presented down-regulated adiponectin and p-Akt,P<0.05. Linear correlation analysis indicated that plasma adiponectin expression level was negatively related to MI area and positively related to myocardial tissue p-Akt expression with the correlation coefifcient at 0.63 and 0.65 respectively, P<0.01. Conclusion: Down-regulated plasma adiponectin expression may cause the inactivation of PI3K/Akt signal pathway and therefore aggravate DM ischemia-reperfusion injury which cannot be protected by ischemic post-conditioning in experimental rats.

Objective To summarize the efficacy and adverse reactions of incremental corticotrophin (ACTH) therapy in the treatment of infantile spasms (IS),and to provide new clinical treatment options.Methods The clinical data of 40 children with IS who were hospitalized in the Department of Neurology,Shanghai Children's Medical Center,Shanghai Jiaotong University School of Medicine,treated with ACTH from January 2016 to January 2018 were collected and retrospectively analyzed.All the children were treated with intravenous infusion of ACTH with an initial dose 12.5 U/d for 3 days.If the spasms did not disappear,dosage of ACTH increased to 25.0 U/d for another 3 days.If the spasms could not yet be fully controlled,the dosage increased to 40.0 U/d,and the total course of treatment did not exceed 2 weeks.If the spasms disappeared at each dose stage or the course of treatment reached to 2 weeks,ACTH would be changed to Prednisone 2 mg/(kg · d) orally,which gradually decreased in 2 months.All children underwent electroencephalogram examination before and after treatment.Results Forty patients with IS were treated with ACTH increasing therapy.The disappearance rate of spasms was 40.0％ (16/40 cases) totally,with 7.5％ (3/40 cases) at the dosage phase of 12.5 U/d,16.2％ (6/37 cases) at the dosage stage of 25.0 U/d,and 22.6％ (7/31 cases) at the dosage of 40.0 U/d.The disappearance rate of hypsarrhythmia on electroencephalogram was 60.0％ (24/40 cases) generally,and 5.0％ (2/40 cases),10.8％ (4/37 cases),58.1％ (18/31 cases),respectively at above different dosage phases,while 37.5％ (15/40 cases) of the children had mild adverse reactions,mostly respiratory infections.Conclusions The short-term efficacy of the ACTH incremental therapy in the treatment of IS is positive,and the incidence of adverse reactions is low.

OBJECTIVE: To explore the genetic basis for 7 patients with Alström syndrome. METHODS: DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4). CONCLUSION ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.
Alstrom Syndrome/genetics* ; Cell Cycle Proteins/genetics* ; Humans ; Mutation ; Pedigree ; Whole Exome Sequencing