Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

A study on intervention strategies for patients′ stereotyping of nurses / 中国实用护理杂志

Objective:To explore strategies of improving patients' stereotyping of nurses, by analyzing patients′ stereotypes of nurses.Methods:The phenomenological analysis method in qualitative research was used to conduct semi-structured interviews with 12 inpatients by objective sampling method.Results:The patients′ stereotype of nurses could be summarized into three topics, it mainly consisted of three aspects: patients′ cognition of the role of nurses, patients′ stereotype of nurse-patient relationship and factors affecting nurse-patient relationship from patients′ perspective, among which factors affecting nurse-patient relationship included doctors′ attitude towards nurses, public opinion effect of media reports and patients′ negative psychological experience.Conclusions:The prejudice of patients to the relationship between nurses and patients is not optimistic, it is suggested to improve patients′ stereotyping of nurses by reconstructing the ideal role of nurses, building harmonious trusting relationships and providing friendly support from the "others".

Countermeasure research on cultivation of humanistic care ability of nursing interns / 中国实用护理杂志

Objective:Through analyzing the influencing factors of nursing humanistic care ability, this paper discusses the countermeasures of cultivating the humanistic care ability of nursing interns.Methods:Nursing interns between September 2018 and April 2019 in Dalian Maternal and Child Health Hospital, the First Affiliated Hospital of Dalian Medical University and the Second Affiliated Hospital of Dalian Medical University were chosen, two questionnaires were conducted at the beginning of the internship and at the end of the internship after the cultivation of humanistic care ability, 344 of them participated in the initial survey, 331 people took part in the end of the survey.Results:The overall average score of nursing interns at early stage of nursing interns was 181.31±22.81, while the score at the final stage was 187.73±18.23, the difference was statistically significant ( t value was 4.03, P<0.05); the score of each dimension which included understanding, courage and patience was 71.66±8.83, 59.49±9.59, 56.59±5.33 respectively, lower than the standard of foreign countries which were respectively 80.22±7.56, 65.25±11.57, 63.11±4.19. The abilities of humanistic care of Chinese nursing interns were lower than those at abroad. Gender (X 1) , relationship with mother (X 3) and relationship with classmates (X 4) are influential factors of humanistic care abilities for nursing interns ( t value was 2.448, 2.784, 3.189, P<0.05). Conclusions:The implementation of cultivating humanistic care abilities for nursing interns can be based on creating medical humanities atmosphere in hospital, improving teachers′ humanistic are abilities and strengthening nurse′ professional identity and sense of responsibility.

Secondary metabolites from Corynespora cassiicola J9, an endophytic fungus associated with Blumea balsamifera (L.) DC / 药学学报

Chemical investigation on the rice culture of Corynespora cassiicola J9, an endophyte inhabiting in Blumea balsamifera (L.) DC. resulted in isolation of eight compounds, including a new depsidone derivative, corynether C (1), and seven analogues, corynether B (2), corynetherlactone A (3), corynether A (4), diaryl ether (5), corynesidone C (6), corynesidone D (7), and corynesidone A (8). Their structures were deduced based on 1D and 2D NMR spectroscopy, and HR-ESI-MS data. All of the isolated compounds were evaluated for inhibitory activities against Lissorhoptrus oryzophilus Kuschel by the leaf spray assay. Unfortunately, none of them showed inhibitory effects.

A special issue to mark the 90th Anniversary of College of Life Sciences, Zhejiang University / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The College of Life Sciences (CLS) remains one of the most prestigious-and the oldest-colleges in Zhejiang University. This special issue, which includes 16 reviews contributed by our alumni and faculties, is dedicated to mark the 90th Anniversary of CLS. The reviews provide a glimpse of current progresses in the areas of life sciences such as biochemical processes and their association with diseases (Ding et al., 2019; Hu et al., 2019; Jin et al., 2019; Nie and Yi, 2019), cancer biology (Feng, 2019; Huang et al., 2019; Leonard and Zhang, 2019; Zhu F et al., 2019), plant and environmental microbiology (Li et al., 2019; Yang et al., 2019; Zhu XR et al., 2019), cell cycle (Gao and Liu, 2019; Zhang et al., 2019), RNA biology (Gudenas et al., 2019; Luo et al., 2019), and protein structural biology (Yang and Tang, 2019).

Discussion on the role of blood bank in the work of blood donation / 中国输血杂志

The work of blood donation has its own characteristics,including high demand of the blood quality and safety,the limited period of blood validity,blood donation is not a necessary behavior of the people、the particularity of blood donation publicity and so on.We are now facing the downward trend of blood donation,the employees'quality is not high enough,the fragility of blood donation and so on.In facing of the difficulties,we should start from our own,clear our thinking,assume the responsibilities and with the rigorous attitude,at the same time we should steadfastly promote the blood donation publicity.

Analysis of metabolic pathway of terpenoids in Blumea balsamifera / 中国中药杂志

In order to provide a theoretical basis for the regulation of active ingredient, the terpenoids metabolic pathway and specific enzymes in Blumea balsamifera are investigated. Basing on transcriptome information, B. balsamifera terpenoids metabolic pathway was analyzed in KEGG data base. Four metabolic pathway of terpenoids were found in KEGG data base. They were terpenoid backbone biosynthesis, monoterpenoid biosynthesis, diterpenoid biosynthesis, sesquiterpenoid and triterpenoid biosynthesis, contained 103, 10, 29,59 genes, respectively. Through the analysis of the enzyme and product in the pathway, the result showed that there were 8 kinds of monoterpenes, 3 kinds of diterpenes, 3 kinds of triterpenes and sesquiterpenes. The mainly key enzymes were deoxyxylulose 5-phosphate synthase, HMG-CoA reductase and allyl transferase system. In B. balsamifera, there were relatively few monoterpenes synthetic enzymes, while the type of products was much more than other terpenes. This may be relate to the non-specific catalytic characteristic of monoterpene synthase. It is expected to improve the yield of terpenoids in B. balsamifera by analysis the pathways and regulation the key enzymes.

Metabolic pathway of flavonoids in Blumea balsamifera / 中国中药杂志

To better understand the biosynthetic pathway of flavonoids in Blumea balsamifera, and to increase the biosynthesis of flavone and flavonol amount, we carried out this research. Basing on transcriptome information, B. balsamifera flavonoids metabolic pathway was analyzed in KEGG data base. The result demonstrated that two metabolic pathways of flavonoids were found in KEGG data base. They were flavonoid biosynthesis pathway (No.ko00941) that contained 32 genes and flavone and flavonol biosynthesis pathway (No.ko00944) that contained 12 genes. Metabolic pathway of flavonoids in B. balsamifera was similar to that in other plants. Chalcone synthase (CHS) and Chalconeisomerase were much likely to be key enzymes on metabolic pathway of flavonoids in B. balsamifera. HCT was much relevant to biosynthesis of favones.

The interaction between ononin and human intestinal bacteria / 药学学报

The study aims to screen the ability of the bacteria to metabolize ononin and assess the effect of ononin on the intestinal bacteria. Fresh human fecal sample was obtained from a healthy volunteer, diluted serially in sterile water and sixty-nine different bacterial colonies were picked out ultimately. UPLC-Q-TOF/MS with automated data analysis software (MetaboLynx) was applied to fast analysis of ononin metabolites. Furthermore, an E(max) precision microplate reader was employed to determine the growth situation of Enterococcous sp., Enterobacter sp., Lactobacilli sp., and Bifidobacteria sp. Results indicated that hydrogenation, demethylation, hydroxylation and deglycosylation were the major metabolic pathways of ononin by human intestinal bacteria in vitro. Ononin can inhibit the growth of pathogen such as Enterococcus sp., Enterobacter sp. and can promote the growth of probiotics such as Bifidobacteria sp. and Lactobacilli sp. This study suggested that intestinal bacteria have the metabolic effects of ononin and the biotransformation was completed by different bacteria. And ononin can affect the balance of intestinal flora and the degree of influence varies depending on the bacterial species and the concentration of ononin.

Metabolism of naringin produced by intestinal bacteria / 药学学报

Naringin has been reported to possess a wild range of biological activities. However, the route and metabolites of naringin produced by intestinal bacteria are not well understood. In this paper, different bacteria were isolated from human feces and their abilities to convert naringin to different metabolites were studied. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) with automated data analysis software (MetaboLynx) was applied to fast analysis of naringin metabolites. Using MSE and mass defect filter techniques, three metabolites were detected and tentatively identified. The results indicated that acetylation, hydrolyzation and hydrolyzation with hydrogenation were the major metabolic pathways of naringin in vitro. Then, we studied the gene sequence of the 16S rRNA of the bacteria by extraction of genomic DNA of the strain, PCR amplification and clone of the 16S rRNA. The consequence proved that Enterococcus sp.30, Bacillus sp.46, Escherichia sp.54 and Escherichia sp.63 have the peculiar metabolism characteristic of naringin.

Effect of low glomerular filtration rate on evaluating the cardiac function by N-terminal pro-brain natriuretic peptide in patients with hypertension / 中华核医学与分子影像杂志

Objective To assess the diagnostic accuracy of NT-proBNP in hypertension patients by observing the effect of decreased GFR on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with different cardiac function.Methods Eighty-nine hypertension patients were divided into two groups based on the results of UCG.Forty-three patients had normal left ventricular function and 46 patients had dysfunction.GFR,NT-proBNP and other biochemical markers of cardiac and renal function were measured.The factors affecting the NT-proBNP concentration under normal left ventricular function were analyzed,and the diagnostic value of NT-proBNP affected by normal or decreased GFR(＞ 80 ml/min or ≤80 ml/min) under different left ventricular functions were further assessed.The two-sample t test,rank sum test and multiple regression analysis were used to analyze their statistical difference and relationship.Results In patients with normal left ventricular function,GFR (β =-0.361,P ＜ 0.05) and left ventricular end-diastolic diameter (LVEDD,β =0.385,P ＜ 0.05) were significant factors to NT-proBNP level.They were both meaningful compared with LVEF (β =0.189,P ＞0.05) and septal thickness (β =0.003,P ＞ 0.05).The median concentration of NT-proBNP was 13.18 and 24.14 μg/L in patients with normal left ventricular function and dysfunction,respectively (Z =-3.19,P ＜ 0.01).While in patients with decreased GFR,6 cases with normal left ventricular function and 19 cases with dysfunction had a median concentration of NT-proBNP of 38.45 and 44.20 μg/L,respectively (Z =-0.45,P ＞ 0.05).In patients with normal GFR,37 cases with normal left ventricular function and 27 cases with dysfunction had a median concentration of NT-proBNP of 12.51 and 20.31 μg/L,which was lower than that of patients with decreased GFR (Z =-2.76,both P ＜ 0.05).The NT-proBNP concentration had no significant difference between patients of normal left ventricular function with decreased GFR and patients of dysfunction with normal GFR (38.45 and20.31 μg/L,Z=-2.18,P＞0.05).Conclusion In hypertension patients,the effect of decreased GFR on assessing the diagnostic accuracy of NT-proBNP for left ventricular dysfunction should be considered.

Study on optimization of drying method and its mechanism in Ginkgo biloba leaves / 中国中药杂志

To provide a scientific evidence for the initial primary processing method, an ultra-high performance liquid chromatography combined with a triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) was used to analyze the contents variation of catechins, flavonoids, flavonoid glycosides, biflavones, terpene lactones and phenolic acids during the process of drying in the sun, in the shade, and baked with 35, 45, 60, 80 degrees C, respectively. The results show that drying in the 80 degrees C is conducive to the accumulation of catechins, flavonoid glycosides, terpene lactones, better than the effects of other procedures. Therefore, the fast drying at 80 degrees C is beneficial for the retention of various types of active ingredient of Ginkgo biloba, and this method could be applied as a preferably dry processing.

Evaluation of mouse acute liver damage by breath test with domestically synthesized ~(13)C-methacetin / 上海交通大学学报（医学版）

Objective To establish a convenient ~(13)C-breath test system in live mice,and investigate the value of ~(13)C-methacetin breath test(~(13)C-MBT) in the diagnosis of acute liver damage of mice with domestically synthesized ~(13)C-methacetin. Methods Domestically synthesized ~(13)C.methacetin was prepared from aeamol by methylation. Abdominal injection of CCl_4 was adopted to duplicate acute liver damage of mice,then the mice were housed under normal laboratory condition for a whole month to gain recovery,which were indentified by hepatic pathological examinations and biochemical teats of liver function.After fasting, the mice were orally administered ~(13)C-methacetin,and the expired air was collected at various time points. Infrared spectrometer was employed, and delm over baseline(DOB) curves of ~(13)C-exhalation were drawn. Results Six to eight min after administration of ~(13)C-methacetin,the rate of ~(13)C-exhalation peaked in control group(51.9±2.04), and decreased thereafter. Sixteen min after administration of ~(13)C-methacetin,the rate of ~(13)JC-exhalation peaked in model group(26.37±5.74), and decreased thereafter.There were significant differences between these two groups(P<0.05).There was no significant difference in peak value and time to reach the peak on DOB curves of ~(13)C-methacetin breath test after the two groups of mice were housed under the same condition for a month(P>0.05).Conclution ~(13)C-MBT facilitates the collection and evaluation of ~(13)CO_2 in the expired air of live mice,and yields precise reflection of alterations of liver function in acute liver injury and functional recovery.

Influence of nutritional status at birth on development of metabolic syndrome in adulthood: An advance / 第二军医大学学报

Aging as a global problem is intensifying with the development of economy; reducing the chronic diseases in the elderly and improving the life quality of the whole population are a study focus of medical researchers of today. The changes of cells, tissues, and organs in adults are not reversible to different extents. Fetal origin hypothesis believes malnutrition early in life is closely associated with the metabolic syndrome in adults, and if measures is taken at early stage of life, it may reduce or avoid a series of disease in adults. This paper reviews the association of malnutrition at early stage of life with metabolic syndrome (obesity, hyperglycemia, hypertension, and hyperlipemia) in adults.

Surgical treatment of the tumors of posterior part of third ventricle and pineal region / 军事医学科学院院刊

Objective:To summarize the experiences of the surgical treatment of tumors in the posterior part of the third ventricle and pineal region. Methods: Twenty-seven patients with tumors in this region treated microsurgically from 1990 to 2000 were analyzed. The surgical indications, approaches, and operative key points were discussed. The prognostic factors were also analyzed. Results:Tumors were removed totally in 11 patients, removed subtotally in 7 and removed partially in 5. Biopsy and ventriculo-peritoneal shunt was performed in 4 patients. Of 17 patients in follow-up, 13 patients survived longer than 5 years. Conclusions: Most tumors in the posterior part of the third ventricle and pineal region can be surgically removed.Sufficient specimen obtained in the operation can confirm pathologic property of the tumor,guiding next chemotherapy and radiotherapy.

Clinical analysis of pregnancy and postpartum cardiovascular complications in Marfan syndrome / 中华妇产科杂志

Objective To investigate the management of pregnancy and cardiovascular complications in women with Marian syndrome(MFS).Methods From October 1994 to September 2006, 30 patients with MFS undergoing cardiovascular surgery were studied retrospectively.Results In the labor of 46 offsprings given birth by 30 women,5 cases(11%)were performed elective cesarean section because of the existence of aortic complication,and 12(26%)were diagnosed as MFS.The gestation in two patients was terminated due to deterioration of aortic abnormalities during their third trimester,and they received surgical treatment with Bcntall procedure.Two developed acute aortic dissection during labor and post delivery respectively.With the manipulation of anticoagulation peripartum,one who had the implantation with mechanical prosthesis went through pregnancy and delivery uneventfully.The average duration between delivery and cardiovascular surgery was(15?9)years.Conclusions Vaginal delivery can be done safely in patients with the MFS who do not have or have mild cardiovascular system abnormalities,aortic dissection,or other important cardiac abnormalities,cesarean section should be the preferred method of delivery.Women with MFS are at increased risk for dissection and congestive heart failure during pregnancy and should be counseled before pregnancy about these risks,as well as the inheritance of the condition.