Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Analysis of the changes and characteristics of pediatric outpatient visits in a general hospital in Beijing before and after the COVID-19 pandemic / 北京大学学报(医学版)

OBJECTIVE@#To analyze the changes and characteristics of pediatric outpatient visits in a general hospital before and after the coronavirus disease (COVID-19) epidemic.@*METHODS@#Based on the registration data of pediatric outpatient visits in the information system (HIS)of Beijing Tsinghua Changgung Hospital, from January 1 2018 to December 31 2020, aged 0 to 16 years, we analyzed the changes of outpatient visits before and after the epidemic, focusing on respiratory infection including influenza. The relationship between the outpatient visits and age and quarterly distribution were also studied.@*RESULTS@#(1) Respiratory infection accounted for the majority of outpatient visits in 2018 and 2019 (60.6% and 60.5%, respectively). Non-respiratory infection accounted for the main proportion of outpatient visits in 2020, while respiratory infection accounted for only 47.4%. Annual respiratory infection visits, respiratory infectious diseases visits especially influenza visits all decreased significantly in 2020 compared with that in 2018 and 2019 (P < 0.05). (2)Respiratory infection visits were highest in the infant group, lowest in the school age group (P < 0.05) and highest in the fourth quarter each year. It decreased significantly in the second quarter of 2020 with statistical significance when compared with the other quarters of 2020(P < 0.05). (3)Influenza accounted for the highest proportion of respiratory infectious diseases visits in each year. It was highest in first quarter, which was significantly different from the other quarters of the year (P < 0.05). There were different distributions of influenza visits throughout 2018 and 2019, while it was only distributed in the first quarter and 99% in January in 2020.@*CONCLUSION@#The respiratory infection and influenza visits have decreased significantly in our pediatric outpatient department after the COVID-19 epidemic, which is considered closely related to the lifestyle and personal protection after the epidemic. It is recommended that health education on respiratory infection and influenza prevention should be strengthened, especially in winter and spring, to promote the development of good respiratory and hand hygiene habits.

Metabolic phenotype and cardiovascular risk factors in the first degree relatives of Chinese women with polycystic ovary syndrome / 中华内分泌代谢杂志

To test the hypothesis that the first degree relatives of Chinese women with polycystic ovarian syndrome (PCOS) have higher risk of cardiovascular disease than those without PCOS.The metabolic phenotype and risks of cardiovascular disease were evaluated in 110 family members of 35 women with PCOS and 85 unrelated healthy control subjects without family history of diabetes and PCOS ( four age- and weight-matched subgroups ).The prevalence of impaired glucose tolerance was 51.4％ in mothers and 57.5％ in fathers with their daughters suffering from PCOS.The first degree relatives of PCOS women had significantly higher serum fasting insulin level,homeostasis model assessment for insulin resistance,insulin area under the curve,and lower insulin sensitivity index in all subgroups than the control subjects( P＜0.05 ).The control subjects had significantly elevated high molecular weight-adiponectin levels and decreased high sensitive-C reactive protein levels compared to the first degree relatives of PCOS women in all subgroups.Parents and brothers,but not sisters,of women with PCOS had significantly higher total cholesterol and low density lipoprotein-cholesterol ( P＜ 0.05 ),as well as triglyceride levels ( P＜ 0.05 ),compared with control subjects.The first degree relatives of PCOS women had features of insulin resistance and increased risk of cardiovascular disease.

Relation between hypothalamic-pituitary-adrenal axis activity and insulin resistance in woman with polycystic ovary syndrome / 中华内分泌代谢杂志

Forty women with polycystic ovary syndrome( PCOS) were enrolled. Basal plasma and urine cortisol, pituitary hormones, homeostasis model assessment for insulin resistance, and plasma cortisol in 0. 25 mg dexamethasone inhibition test were determined. In over-weight or obese PCOS patients, cortisol levels before and after inhibition test were increased (P<0. 05 or P<0. 01 ). The results suggest that the feed-back regulation of glucocorticoids to hypothalamas-pituitary is impaired and the change in hypothalamic-pituitary-adrenal axis is associated with insulin resistance.

Expression and clinical significance of platelet-derived growth factor A in placenta of pre-eclampsia / 中华妇产科杂志

Objective To investigate the expression and clinical significance of platelet-derived growth factor A (PDGF-A) on placenta tissue from pre-eclampsia.Methods The expression of PDGF-A in the placenta of 38 pre-eclampsia patients and 22 normal pregnant women at third trimester was detected by immunohistochemistry method.Results (1)PDGF-A was mainly expressed in the cytomembrane and cytoplasm of cytotrophoblasts and the endothelial cell of capillary in placenta.(2) The rates of PDGF-A expression of cytotrophoblasts were 63% (24/38) in pre-eclampsia group and 32% (7/22) in normal pregnancy group,which exhibited significant difference (P ＜0.05).(3) The rates of PDGF-A expression of endothelial cell were 68% (26/38) in pre-eclampsia group and 27% (6/22) in normal pregnancy group,which also showed significant difference (P ＜0.01).(4)The rates of PDGF-A expression of cytotrophoblasts were 39% (7/18) in mild pre-eclampsia patients and 85% (17/20) in severe pre-eclampsia,which reached statistical difference (P ＜ 0.01).Conclusion The increasing expression of PDGF-A in cytotrophoblast and endothelial cell in placenta might confer the occurrence and progression of preeclampsia.

Effects of ganglioside on cell apoptosis of rats with acute cerebral ischemia-reperfusion injury / 中国组织工程研究

BACKGROUND: Cell apoptosis and expression of related apoptotic gene are found in rats with acute cerebral ischemia-reperfusion injury.OBJECTIVE: To study the effects of ganglioside on cell apoptosis in rats with acute cerebral ischemia-reperfusion injury.DESIGN: Randomized control animal experiment.SETTING: Department of Neurology, China-Japan Friendship Hospital of Jilin University.MATERIALS: The experiment was conducted in the Animal Laboratory of China-Japan Friendship Hospital of Jilin University at April 2002.Forty-eight healthy male Wistar rats aged 3-4 months with the body mass of (220±50) g were selected and randomly divided into ischemia-reperfusion group and ischemia-reperfusion + administration group (intraperitoneal injection of ganglioside GM-1 at 30 minutes before ischemia) with 24 rats in each group, and each group was subdivided into three groups according to the reperfusion time: 3-hour, 6-hour and 24-hour with 8 rats in each time-point.METHODS: ①Rat models of cerebral ischemia-reperfusion were established. ②Diphenylamine method was adopted to detect changes of DNA splitting rate in brain tissues at 3 hours,6 hours and 24 hours after cerebral ischemia.100 mg of cerebral cortex was made into 10% homogenate by adding into 0.9 mL of splitting fluid,which was then put in the centrifuge tube for repeated freezing and melting. The supernatant and deposit were collected.DNA splitting rate = supernatant absorption/(supernatant absorption + deposit absorption). ③Immunohistochemical method was used to study the expression of protein kinase Cδ (PKCδ) as well as changes of ganglioside after administration. MAIN OUTCOME MEASURES: Changes of DNA splitting rate in cerebral cortex of rats as well as intensity of PKCδ expression.RESULTS: One rat in the normal saline control group died for exceeding anesthetization at the 6th hour of reperfusion, and 2 rats died at the 24th hour of reperfusion, which were supplemented respectively. With the time of reperfusion increasing, changes of DNA splitting rate significantly increased, which peaked at the 24th hour. The expression of PKCδ peaked at the 6th hour of reperfusion and gradually decreased. The DNA splitting rate and PKCδ expression were remarkably decreased at corresponding time-points in the ganglioside group.CONCLUSION: Ganglioside can inhibit cell apoptosis and reduce PKCδ expression after cerebral ischemia-reperfusion to protect cerebral ischemia-reperfusion injury.