The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.
Musa/genetics* ; Phylogeny ; Fungal Proteins ; Cell Nucleus ; Histones ; Stress, Physiological/genetics*

Objective To observe the value of quantitative CT(QCT)abdominal body fat parameters combined with clinical-imaging model for predicting recurrent acute pancreatitis(RAP).Methods Data of 468 patients with acute pancreatitis(AP),including 207 cases of RAP(RAP group)and 261 cases of non-RAP(non-RAP group)were retrospectively analyzed.Clinical information,conventional CT manifestations and QCT parameters such as abdominal subcutaneous fat area(SFA),visceral fat area(VFA),total abdominal fat area(TFA),hepatic fat content and pancreatic fat content at the first visit were recorded or measured.Clinical characteristics,CT manifestations and QCT parameter values were compared between groups,and the independent factors for predicting RAP were selected with multivariate logistic regression analysis.Then a clinical-imaging model and a comprehensive model combining with QCT parameters were constructed,and their efficacies for predicting RAP were evaluated with receiver operating characteristic(ROC)curves,and the area under the curves(AUC)were calculated.Results Compared with non-RAP group,patients in RAP group were younger,had higher percentage of alcohol consumption,biliary stones and hyperlipidemia,as well as of distinct pancreatic margins on CT images,also higher VFA,TFA,liver fat content and pancreatic fat content(all P＜0.05).Alcohol consumption,hyperlipidemia,biliary stones,pancreatic margins and pancreatic fat content were all independent predictors of RAP,and the comprehensive model constructed based on these five had higher AUC(0.860)than clinical-imaging model constructed based on the previous 4 factors(0.701)and pancreatic fat content alone(0.770)(both P＜0.001).Conclusion QCT abdominal body fat parameters combined with clinical-imaging comprehensive model was effective for predicting the risk of RAP.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Peroral endoscopic myotomy (POEM) has emerged as a rescue treatment for recurrent or persistent achalasia after failed initial management. Therefore, we aimed to investigate the efficacy and safety of POEM in achalasia patients with failed previous intervention. We searched the MEDLINE, Embase, Cochrane, and PubMed databases using the queries “achalasia,” “peroral endoscopic myotomy,” and related terms in March 2019. Data on technical and clinical success, adverse events, Eckardt score and lower esophageal sphincter (LES) pressure were collected.The pooled event rates, mean differences (MDs) and risk ratios (RR) were calculated. A total of 15 studies with 2,276 achalasia patients were included. Overall, the pooled technical success, clinical success and adverse events rate of rescue POEM were 98.0% (95% confidence interval [CI], 96.6% to 98.8%), 90.8% (95% CI, 88.8% to 92.4%) and 10.3% (95% CI, 6.6% to 15.8%), respectively. Seven studies compared the clinical outcomes of POEM between previous failed treatment and the treatment naïve patients. The RR for technical success, clinical success, and adverse events were 1.00 (95% CI, 0.98 to 1.01), 0.98 (95% CI, 0.92 to 1.04), and 1.17 (95% CI, 0.78 to 1.76), respectively. Overall, there was significant reduction in the pre- and post-Eckardt score (MD, 5.77; p<0.001) and LES pressure (MD, 18.3 mm Hg; p<0.001) for achalasia patients with failed previous intervention after POEM. POEM appears to be a safe, effective and feasible treatment for individuals who have undergone previous failed intervention. It has similar outcomes in previously treated and treatment-naïve achalasia patients.

Objective:To understand the current situation of effective teaching behavior of clinical nursing teachers and analyze it.Methods:A convenient sampling method was used to conduct a questionnaire survey on nursing students and teaching teachers in Tai′an City central hospital and the Second Affiliated Hospital of Shandong First Medical University, using Cui Shasha Chinese version of Nursing Clinical Teacher Effectiveness Inventory as the research tool.Results:The score of the teachers in the "interpersonal relationship" dimension was the highest (6.32±0.89), while the score in the "nursing ability" dimension was the lowest (5.95±0.99). There was no statistically significant difference between college students and undergraduate students in the evaluation of effective teaching behaviors of teachers, while there was statistically significant difference between nursing students (including college students and undergraduate students) and teachers in all dimensions and total scores of the scale ( t values were -4.616--2.250, P<0.05 or 0.01). Teachers and students were more consistent with the 10 items with low scores than the 10 items with high scores (the total number of items was 2 and 5, respectively). Conclusions:The teaching teacher should be able to correctly identify and judge the learning needs of the internship nursing students, so that the teaching effect meets the expectations of the internship nursing students, and should be targeted when teaching internship nursing students of different educational levels as well as focusing on nursing research.

Objective:To systematically evaluate the effects of different umbilical cord time on maternal and fetal outcomes.Methods:Meta analysis was used, CNKI, Wanfang, VIP, PubMed, The Cochrane Library, EBSCO, Web of Science database, etc. were searched. The literatures were screened according to the inclusion and exclusion criteria, and the literature quality was evaluated. Revman 5.2 software was used for data processing and analysis.Results:A total of 9 randomized controlled trials were included. Meta-analysis showed that delayed umbilical cord did not increase postpartum 2,24 h hemorrhage[mean difference ( MD)=-40.69, 95%confidence interval (CI) (-83.05-1.67), P>0.05 and MD=-10.33, 95% CI (-22.47-1.81), P>0.05] and did not prolong the third stage of labor [ MD= 0.32, 95% CI (-0.71-1.35), P>0.05] compared with conventional umbilical cord (early umbilical cord) method. 1,5 min Apgar scores for different neonatal umbilical cord time was not statistically significant[ MD=0.05, 95% CI (-0.02-0.12), P>0.05 and MD=-0.01, 95% CI (-0.04-0.03), P>0.05]. There was no significant difference in neonatal weight [ MD=72.91, 95% CI (-53.98-199.80), P>0.05]. Delayed umbilical cord could improve the newborn's 24 h capillary hemoglobin [ MD=17.69, 95% CI (13.55-21.83), P<0.01] and bilirubin peak [ MD=17.50, 95% CI (11.88-23.12), P<0.01]. Conclusions:Delayed umbilical cord and early umbilical cord did not increase postpartum hemorrhage and prolong the third stage of labor, and had no adverse effects on maternal. The peak levels of capillary hemoglobin and bilirubin in newborns were increased 24 h, but there was no significant difference in neonatal 1 min and 5 min Apgar scores and neonatal weight.

Macrolide antibiotics are a class of broad-spectrum antibiotics with the macrolide as core nucleus. Recently, antibiotic pollution has become an important environmental problem due to the irregular production and abuse of macrolide antibiotics. Microbial degradation is one of the most effective methods to deal with antibiotic pollution. This review summarizes the current status of environmental pollution caused by macrolide antibiotics, the degradation strains, the degradation enzymes, the degradation pathways and the microbial processes for degrading macrolide antibiotics. Moreover, the critical challenges on the biodegradation of macrolide antibiotics were also discussed.
Anti-Bacterial Agents ; Biodegradation, Environmental ; Macrolides

Objective:To discuss the necessity and feasibility of constructing the baccalaureate midwifery education standard in China by the comparative study of WHO and ICM education standards, combined with China's medical nursing education standards.Methods:We searched the scientific literature using the databases of CNKI, Wanfang, VIP and the official websites of WHO and ICM. Comparative study was conducted combined with the literature study, analyze the specific fields and indicators required for baccalaureate midwifery education standards in China.Results:ICM standard is more accord with the actual needs of the construction of baccalaureate midwifery education standard in China.Conclusion:It is feasible and necessary to construct the baccalaureate midwifery education standard according to ICM standards, this study further provides reference and basis for constructing the baccalaureate midwifery education standard in China.