The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Objective:To conduct clinical and genetic analysis in two cases of cholestatic liver disease to determine the specific etiology of cholestasis.Methods:Clinical data and the medical histories in family members of two cases were collected. The gene variation was detected by whole-exome sequencing technology. Sanger sequencing validation and bioinformatics analysis were performed on patients and their parents with suspected pathogenic mutations.Results:Whole-exome sequencing showed that the ABCB4 gene of case 1 (a male, 16 years old) had compound heterozygous mutations of c.646C > T from the father and c.927T > A from the mother, while the ABCB4 gene of case 2 (a female, 17 years old) had a compound heterozygous mutation of c.2784-1G > A from the father and c.646C > T from the mother. New mutation sites that had not been previously reported were c.646C > T, c.927T > A, and c.2784-1G > A.Conclusion:In this study, both cases had progressive familial intrahepatic cholestasis type 3 (PFIC-3) caused by ABCB4 gene mutations, and it also enriched the ABCB4 pathogenic variant spectrum. Whole-exome sequencing technology provides a reliable diagnostic tool for etiological analysis.

Objective:To measure the predictive value of miR-424 on the risk of sepsis complicated with acute respiratory distress syndrome(ARDS), and to explore its correlation with the prognosis of ARDS children.Methods:A prospective study was conducted.The data of children with sepsis (some complicated with ARDS), who were treated in Henan Provincial People′s Hospital (People′s Hospital, Zhengzhou University) were collected from February 2020 to February 2021.The incidence of ARDS and the fatality rate of ARDS children were recorded.Children were divided into survival group and death group according to whether death or not.The expression of miR-424 in peripheral blood mononuclear cells was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Pearson correlation analysis was made to investigate the relationship between the expression level of miR-424 and Pediatric Critical Illness Score(PCIS), Sequential Organ Failure Assessment(SOFA) score, oxygenation index(P/F ratio), C-reactive protein(CRP), procalcitonin (PCT), interleukin 6 (IL-6) and interleukin 8 (IL-8). The factors affecting the prognosis of ARDS children were analyzed by multivariate Logistic regression.Receiver operating characteristic curve(ROC)was used to assess the accuracy of miR-424 in early diagnosis of sepsis complicated with ARDS, and to measure the predicative value of miR-424 on the risk of death in sepsis patients with ARDS. Results:A total of 121 sepsis patients were included in this study, and 36 cases of them were complicated with ARDS.The expression level of miR-424(0.56±0.17)in the blood of sepsis patients complicated with ARDS was significantly lower than that of sepsis patients without ARDS (0.98±0.26)( t=8.776, P<0.001). The expression of miR-424 was negatively co-rrelated with IL-6( r=-0.627, P<0.01), IL-8 ( r=-0.651, P<0.01) and CRP( r=-0.472, P<0.05)in sepsis patients with ARDS.The expression of miR-424 was positively correlated with PCIS score( r=0.330, P<0.05), P/F ratio ( r=0.592, P<0.001) and albumin ( r=0.496, P<0.05) in sepsis patients with ARDS.The ROC showed that miR-424 [area under curve(AUC)=0.908, 95% CI: 0.856-0.960] could differentiate sepsis patients with ARDS from those without ARDS.Compared with that of the survival group(0.63±0.15), miR-424 of the death group decreased significantly(0.42±0.14)( t=3.890, P<0.05). The decreased miR-424 (AUC=0.845, 95% CI: 0.696-0.995)indicated an increased risk of death in children with ARDS.Multivariate Logistic regression analysis showed that miR-424( OR=0.001, P=0.033)and albumin ( OR=0.553, P=0.040) were independent risk factors for death in ARDS children. Conclusions:miR-424 can help with early diagnosis of sepsis complicated with ARDS, and can be used as a predictor of the prognosis of sepsis children complicated with ARDS.

Objective:To study effects of Orff rhythm-beat-tap training on positive emotions in elderly patients with mild dementia.Methods:Using the convenient sampling method, a total of 72 elderly patients with mild dementia who were treated in the Third People's Hospital of Huzhou from August 2018 to August 2019 were selected as the research objects and they were divided into two groups using the simple random sampling method. After the start of the study, 2 cases dropped out because of failure to persist in training, 1 case dropped out because of transfer during hospitalization and 1 case dropped out because of aggravation of the disease and changing drugs. A total of 68 cases were included in the study, including 33 cases in the intervention group and 35 cases in the control group. The control group received routine nursing, while the intervention group received 12-week Orff rhythm-beat-tap training on this basis. The scores of Positive and Negative Affect Schedule (PANAS) , Apathy Evaluation Scale (AES) and Dementia Mood Assessment Scale (DMAS) were evaluated before and after the intervention.Results:The score of positive emotion after intervention in the intervention group was (31.58±1.87) , higher than (26.66±2.93) in the control group, and the difference was statistically significant ( t=8.297, P<0.01) . After intervention, the score of negative emotion of the intervention group was (21.97±2.30) , the score of apathy was (44.88±5.22) , and the score of dementia mood was (23.18±4.33) , which were lower than (23.80±3.94) , (51.91±7.49) and (26.09±6.20) of the control group, and there were statistically significant differences in scores between the two groups ( t=-2.356, -4.514, -2.225; P<0.05) . Conclusions:Orff rhythm-beat-tap training is suitable for elderly patients with mild dementia, which can effectively enhance positive emotional experience of patients, improve apathy and optimize mood.