Objective To observe the manifestations of isolated bicuspid aortic valve(i-BAV)in children using echocardiography.Methods Echocardiographic data of 79 children with i-BAV were retrospectively analyzed,and classification of i-BAV was performed.The patients were divided into complication group(n=50)and non-complication group(n=29)according to the existence of valve and/or aortic involvement or not,and echocardiographic parameters were compared between groups.Results After adjusting body surface area(BSA),in complication group,left ventricular end-systolic diameter/BSA was lower,while left ventricular myocardial mass index group was higher than those in non-complication group(both P＜0.05).Type 0 i-BAV was found in 22 cases,with lat subtype as the most common ones(18/22,81.82％),while Type Ⅰ was observed in 57 cases with L-R subtype as the most common ones(39/57,68.42％).The most common subtype in complication group was also Type Ⅰ L-R(31/50,62.00％),with incidence of valve involvement of 90.00％(45/50),mainly including mild aortic stenosis and/or incompetence(37/45,82.22％),and incidence of aorta involvement of 24.00％(12/50),all with type Ⅰ or Ⅱ aortic widening.Conclusion The most common subtype of i-BAV in children was type Ⅰ L-R,with mild valve damage as the main complication and possibility of left ventricular myocardial remodeling.

Objective To analyze the literature of leech in medicine using CiteSpace knowledge map,comprehensively understand the research status,hotspots and development trends of component analysis and pharmacological effects of leech,and provide reference for researchers in the field of leech.Methods CiteSpace 6.1 R3 software was used to analyze the relevant literature of leech in the field of medical research in CNKI and Web of Science databases from 1996 to 2022.The bibliometric and visual analysis of the number of articles,authors,research institutions,keyword co-occurrence,clustering and emergence were carried out.Results A total of 1 115 Chinese articles in CNKI database and 237 English articles in Web of Science database were included.The analysis of Chinese and English literature showed that the author Shi Hongzhuan had the largest number of Chinese articles,and the German author Hildebrandt had the largest number of English articles.Shandong University of Traditional Chinese Medicine and Chinese Academy of Sciences were the institutions with the largest number of articles in Chinese and English respectively.The country with the most published English literature is the United States.Chinese and English keyword co-occurrence and cluster analysis showed that Chinese literature focused on the study of its active ingredient hirudin,including molecular structure,pharmacological efficacy,mechanism of treating thrombosis,coronary heart disease,kidney disease and other diseases,and paid attention to the differences in the active ingredients of different types of leeches.In addition,English literature focused on the clinical external use of living leeches.The emergence of keywords suggested that the mechanism of action,the search and synthesis of hirudin analogues,and the pharmacodynamic mechanism of compatibility application were not only the current research hotspots,but also the future hot spots.Conclusion The analysis of leech components,the pharmacological mechanism of leech in the treatment of cardiovascular diseases,chronic kidney diseases and other diseases have always been the research hotspots.Hirudin analogues,the pharmacodynamic mechanism of compatibility application,network pharmacology,molecular docking and so on may be the future research hotspots and trends of leeches.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

To evaluate the relationship between atherosclerosis and hemodynamic of coronary artery in mice detecting by ultrasound bio‐microscopy flow imaging . Methods Double 14 20‐week‐old LDL‐R‐/‐and C57BL/6 male mice were selected ,and randomly divided into two groups in each genotype according to weight . Each two groups were fed to 28 weeks or 36 weeks age respectively with west diet . Coronary artery hemodynamics in these mice were assessed in vivo by Vevo ?2100 ultrasound imaging system ,then the intima‐media thickness( IM T ) of aorta in histopathology were analyzed . T he differences of coronary artery hemodynamic parameters such as maximum velocity ( Vmax ) ,mean velocity ( Vmean) and velocity time integral ( V T I) were compared between mice of different genotypes of the same week and mice of different weeks of the same genotype . And the relationship between coronary artery hemodynamic in ultrasound and aortic IM T in histopathology were analyzed . Results ① All coronary hemodynamic parameters in LDL‐R‐/‐ mice were significantly lower than those of wild‐type mice except the Vmax between two 28‐week‐old genotypes group at the same weeks of age of different genotypes ( all P ＜0 .05) . But there was no significant difference in coronary artery hemodynamic parameters between mice of the same genotype at different weeks of age( P ＞0 .05) . ②T he histopathological measurements of aortic IM T in LDL‐R‐/‐mice were significantly higher than those of wild type mice ( all P ＜ 0 .05 ) ,and those of 36‐week‐old mice were significantly higher than those of 28‐week‐old mice ( all P ＜ 0 .05 ) . ③ All coronary hemodynamic parameters such as Vmax ,Vmean and V TI were negatively correlated with pathological measurements of aortic IM T ( r ＝ －0 .532 , －0 .423 , －0 .524 ; all P ＜ 0 .05 ) . Conclusions The parameters of coronary artery hemodynamics obtained by ultrasound bio‐microscopy are well correlated with the pathological results of atherosclerosis . Ultrasound bio‐microscopic flow imaging can be used as a new method to evaluate the degree of atherosclerosis in mice by detecting the hemodynamic parameters of coronary artery .

Objective To evaluate the different change in atherosclerosis between apolipoprotein E knockout ( ApoE-/-) mice and low density lipoprotein receptor knockout ( LDL-R-/-) mice in different diet by vivo ultrasound biomicroscopy(UBM) . Methods Thirty-two 8 weeks age ApoE-/- mice and twenty-eight 20 weeks age LDL-R-/- mice were selected ,and each mouse model were divided into four groups randomly according to weight . Two groups of each model were fed with normal diet for 8 weeks and 16 weeks respectively as general groups ,and two other groups were fed with west diet as high-fat groups . Intima-media thickness ( IM T ) in the aortic root of all groups were assessed by Vevo 770 UBM , and all measurementsofUBMwerecomparedwithhistopathologyandblood-fat.Results ①Thickenwallor plaque in aortic root showed by UBM and histopathology could be found in ApoE-/- mice in all diet conditions ,but the changes in LDL-R-/- mice only could be found in high-fat diet conditions;② IM T of ApoE-/- mice measured in histopathology were significantly higher than LDL-R-/- mice in all diet condition ( P<0 .05) ,but in UBM ,the IMT of ApoE-/- mice showed significantly higher than that of LDL-R-/- mice only in general diet groups and 8 weeks high-fat diet group ( P <0 .05) ;③In blood-fat ,the total cholesterol ( TC) in ApoE-/- mice were significantly higher than that of LDL-R-/- mice in all diet conditions ( P <0 .05) . But triglyceride ( TG) was higher only in general diet when it was compared between ApoE-/- mice and LDL-R-/- mice . Conclusions It is recommend to select ApoE-/- mice as animal model in atherosclerosis study rather than LDL-R-/- mice ,because the higher serum TC and higher susceptible of atherosclerosis in ApoE-/- mice . The west diet is necessary if LDL-R-/- mice was used to atherosclerosis study .

Objective: To determine the distribution characteristics of waist circumference (WC), waist height ratio (WHtR) of 6–18 years olds in Guangzhou, and to put forward the WC and WHtR appropriate boundary values for 6–18 years olds on the basis of cardiovascular disease (CVD) risk factor assessment. Methods: We analyzed the height, weight, WC and its metabolic indication data (blood pressure, fasting blood glucose, and blood lipids) of 15 000 children in Guangzhou, aged 6–18, with the receiver-operating characteristic curve (ROC), and explored the best value point of WC and WHtRfor the prediction of cardiovascular diseases. Results: When the WC percent reached P85, and WHtR reached 0.48, the cardiovascular risk factors of fasting blood-glucose, blood pressure, and blood fat were signiifcantly higher. Conclusion: The 85th percentile value of WC and 0.48 of WHtR are the appropriate boundary values in increasing the cardiovascular disease risk factors in Chinese children and teenagers. WC and WHtR as a relatively simple inspection method, can well predict cardiovascular diseases, and be used in the conventional measuring items among students.

Objective To investigate the ultrasound diagnostic value for nipple discharge disease by comparison with fiberoptic ductoscopy. Methods Fiberoptic ductoscopy and ultrasonic inspection were performed on fifty-seven patients with spontaneous nipple discharge,and the results were analysed. Results In all patients, 55 cases (96. 49 % ) were abnormal in high-frequency ultrasound inspection:27 mammary duct expansion(47.36%),19 occupying lesion with mammary duct expansion or cyst (33.33%),6 cystic echo ( 10. 52% ) ,3 only solid echopattern (5.26%) ,and 2 nothing found (3.51% ). In ultrasonic inspection,color and pulse Doppler signal were found in 7 cases. On the other hand, 26 galactophoritis (45.61%), 12mammary duct ectasia (21.05 %), 17 intraductal papilloma (29.82%), 2 breast carcinoma (3.50%) were diagnosed by fiberoptic ductoscopy. In all 19 cases with occupying lesion,ultrasonography's sensitivity was 52. 63% ,specificity was 89. 47%, misdiagnosis rate was 10. 50%, rate of missed diagnosis was 47.36%.Conclusions To nipple discharge disease, high-frequency ultrasound has high sensitivity, easy to find abnormal indication,but is not accurate enough in the diagnosis of smaller occupying lesion.

Objective To construct pcDNA3-HIF-1? eukaryotic expression vector and to investigate its function in breast cancer MCF-7 cells.Methods RT-PCR was applied to amplify human HIF-1? cDNA from MCF-7 cells with a pair of sequence specific primers carrying a restriction enzyme site XbaⅠ or HindⅢ on each 5′end.HIF-1?(cDNA) was inserted into pMD18-T after sequencing,and then inserted into pcDNA3 vector.The recombinant vector was transfected into MCF-7 cells to observe its expression and function by Western blot and dual-luciferase reporter gene assay.Realtime-PCR was performed to detect the inducible expression of C-MET mRNA by HIF-1?,the anti-apoptotic effect of HIF-1 under hypoxia was analysed by detecting the Caspase3/7 activity.Results The sequence of pcDNA3-HIF-1? is identical with the gene bank.It enhances the expression of HRE reporter gene and C-MET mRNA,but decreases the Caspase3/7 activity in MCF-7 cells under hypoxia.Conclusion The pcDNA3-HIF-1? eukaryotic expression vector was successfully constructed,it not only has strong DNA binding and inducing activity,but also has anti-apoptotic effect in hypoxia MCF-7 cells.

Objective To construct pGL3-EPO-HRE reporter gene vector and to detect its function.Methods To synthesize two single-strand DNA fragments which had overlap sequence at the 3'end,then mixed them to construct the double-strand DNA fragment which include three copies of(57 bp) human erythropoietin(EPO) HRE.There was MluⅠor BglⅡ digestive site at the end of this DNA fragment.After inserting the(87 bp) fragment into pMD18-T for sequencing,the correct sequence was inserted into pGL3-promoter to construct pGL3-EPO-HRE.The recombinant vector was co-transfected into MCF-7 cells with pcDNA3-HIF-1?or pcDNA3 respectively,(12 h) later cells were treated with(100 ?mol/L) cobalt chloride(CoCl_(2)) for(24 h), then the expression of pGL3-EPO-HRE was observed by dual-luciferase reporter gene assay method.Results The sequence of pGL3-EPO-HRE was identical with human EPO HRE sequence.pGL3-EPO-HRE luciferase activity increased about 10 fold(P