Resolution revolution:advances and prospects of cryo-EM in structural biology / 复旦学报（医学版）

Cryo electron microscopy (cryo-EM) is one of the most important methods in structural biology.In the past five years,cryo-EM has milestone breakthrough due to revolutionary advances in hardware and methodology.The resolution has been pushed to as high as 1.8 （A),which significantly extended the research scope of this method.Single particle reconstruction method has become one of the most exciting fields of structural biology and related subjects.Here we will briefly introduce the history of cryo-EM,recent revolutionary breakthrough,and the facility at Fudan University.

Effect of Xinjikang on left ventricular hypertrophy remodeling in hypertensive rats

OBJECTIVE@#To investigate the effects of Xinjikang on the left ventricular hypertrophy remodeling and myocardial activity in hypertension.@*METHODS@#Sixty Wistar rats were randomly divided into four groups. The pressure-loaded left ventricular hypertrophy model was established with abdominal aorta ligation method. Rats in A and B groups were intragastrically administered with physiological saline, while C and D groups were administered with Xinjikang and metoprolol, respectively. The changes in blood pressure, E/A ratio, myocardial pathological morphology, myocardial lipoperoxides and superoxide dismustase activity in four groups were observed and compared before and after treatment.@*RESULTS@#There were statistically significant differences in E/A ratio between C group after treatment and model group (P0.05); after treatment the myocardial lipoperoxides and superoxide dismustase contents in C and D groups were improved significantly compared with model group (P<0.05).@*CONCLUSIONS@#Xinjikang can improve myocardial injury, restore myocardial parenchyma and myocardial interstitial remodeling functions in hypertensive rats with the left ventricular hypertrophy.

Spatiotemporal expression patterns of histone acetyltransferase steroid receptor coactivator-1 in developing mouse heart / 第二军医大学学报

Objective: To study the spatiotemporal expression pattern of histone acetyltransferase steroid receptor coactivator-1 (SRC1) in developing mouse heart, so as to explore the relationship of SRC1 with heart development. Methods: The normal mouse hearts were collected at E7.5-E18 and 1 day and 3 months after birth; 9 specimens were chosen for each time point to observe the spatial expression of SRC1 by immunohistochemistry technique, and 6 specimens of each time point were used to examine the temporal expression of SRC1 protein by Western blotting technique and to plot the time-dose curve. Results Immunohistochemistry showed no expression of SRC1 in the heart primordium at E7.5; only very weak SRC1 expression was found in the cardiac tube at E8. 5-E9.5. Weak SRC1 expression was found in the trabeculae after E10.5 and relatively strong and widespread expression was found in other heart regions. Western blotting results demonstrated that SRC1 protein expression at E10.5 was significantly lower than those at E11.5 and E12.5 (P0.05). SRC1 expression reached the peak at E11. 5-E12.5, and there was no significant difference between the two time points (P>0.05). SRC1 expression gradually decreased after Ell. 5-E12.5 till the adulthood, and there were no significant differences in the expression after E13.5 (P>0.05). Conclusion: Widespread distribution of SRCl is present in the developing mouse heart after ES. 5, and the expression is in a dynamical spatiotemporal pattern, suggesting that SRC1 may take part in the overall regulation of the heart development, and it might has a closer relationship with the early induction of the heart septa.

Methodological study on real-time three-dimensional echo-cardiography and its application in the diagnosis of complex congenital heart disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Real-time three-dimensional echocardiography (RT-3DE) has made revolutionized improvements of cardiac imaging during the past few years. However, there is no standard examination method for RT-3DE so far. This study aimed to establish the diagnostic method of RT-3DE and evaluate its application in the diagnosis of complex congenital heart diseases (CHD).</p><p><b>METHODS</b>Fifty patients with complex CHD were examined by RT-3DE with modes of Live 3DE and Full Volume. A series of novel volumetric views combined with Van Praagh sequential segmental approach were introduced to reveal the pathological morphology of the hearts, which were compared with the findings of two-dimensional echocardiography (2DE), angiography and cardiac surgery.</p><p><b>RESULTS</b>In 50 patients, 190 image acquisitions of Full Volume were performed at several acoustic windows including subcostal, apical and parasternal regions. Among them, 94.2% (179/190) of image acquisitions were successful. Most sectional volumetric views could be clearly displayed in 92.6% of the successful image acquisitions. However, sectional volumetric views could not be clearly displayed in 7.4%, which was mainly due to poor perspective conditions of examination location, improper instrument multi-parameter setting and insufficient information of whole heart captured in Full Volume acquisitions. As compared with surgical findings and angiography, RT-3DE made correction to the diagnoses in 2 cases including 1 with corrected transposition of the great arteries and the other with single atrium and mitral cleft. The diagnoses initially made by 2DE for these 2 patients were double outlet right ventricle with transposition of the great arteries and complete atrio-ventricular septal defect.</p><p><b>CONCLUSIONS</b>RT-3DE can clearly display the pathological morphology of complex CHD by a series of novel volumetric views combined with sequential segmental approach through providing more spatial informative cardiovascular structures, which provides a practical method for RT-3DE diagnosis.</p>

Pathological diagnosis of conotruncal defects by transthoracic three-dimensional echocardiography / 中华儿科杂志

<p><b>OBJECTIVE</b>Recently, it has been demonstrated in several studies that three-dimensional echocardiography (3DE) with any cut view interpretation of the cardiac morphological structures and its dynamic three-dimensional display can conform to the need of accurate anatomical diagnosis of complex congenital heart diseases including conotruncal defects (CTD). 3DE can not only provide functional and morphological information of CTD to decide on surgical repair but also simulate the intra operative visualization of complex anatomical cardiac structures to improve the understanding of the anatomy of CTD, but there have been scarce studies to assess systematically the potential noninvasive diagnostic value of transthoracic 3DE for CTD in children. Thus, this study attempted to evaluate the diagnostic value of transthoracic 3DE for the pathological diagnosis of CTD in children.</p><p><b>METHODS</b>HP Sonos 5500 echocardiographic system interfaced with Tomtec 3DE imaging system (echo-view 4.2 software) was used to diagnose 210 patients (132 male, 78 female, aged 0-15 years, mean 3.2 +/- 3.2 years) with CTD in Shanghai Children's Medical Center from May 2000 to November 2003, including 62 patients with double outlet right ventricle, 48 patients with transposition of great arteries, 48 patients with tetralogy of Fallot, 38 patients with pulmonary atresia with interventricular septal defect and 14 patients with persistent truncus arteriosus. Diagnostic method consisting of ten designed 3DE sectional views and Van Praagh's sequential segmental approach in congenital heart diseases was used in this study. And the results were compared with those diagnosed by two-dimensional echocardiography (2DE) and angiocardiography. Surgical findings were considered as the "gold standard".</p><p><b>RESULTS</b>There were 526 image acquisitions of transthoracic 3DE in the 210 patients with CTD including 200 through subcostal window, 254 through parasternal window and 72 through apical window, among which 477 image acquisitions (93.2%) could demonstrate good spatial cardiovascular structures. Meanwhile, six 3DE sectional views of the diagnostic method of the ten designed 3DE sectional views were identified for the diagnosis of CTD as follows: en-face view of atrial and ventricular septa from left ventricle (L1a); en-face view of atrial and ventricular septa from right ventricle (L2a); four-chamber view of whole-heart oblique frontal plane (Ha and Hb); en-face view of atrial-ventricular valve from atria (S1a) and en-face view of atrial-ventricular valve from ventricles (S2a). The 3DE sectional diagnosis showed that 3DE could provide more information of inner cardiac structure than 2DE, such as ventricular configuration identification, atrial-ventricular and ventricular-arterial continuity, location and shape of ventricular septal defect (VSD), and appreciation of the defects related with aorta and pulmonary arteries, etc. In 147 cases of surgical repair, both 3DE and 2DE were in accordance with the surgical findings, but 3DE had new findings in 18 (12.2%) cases and corrected the diagnoses in 10 (6.8%) cases as compared with 2DE.</p><p><b>CONCLUSION</b>The 3DE sectional diagnostic method could make a successfully sectional diagnosis of pathological morphology in CTD by demonstrating more spatial information of inner cardiac structure than 2DE and angiocardiography.</p>