Objective:To analyze the relationship between genotype and clinical phenotype of the MYH7-R453C mutation in five Chinese hypertrophic cardiomyopathy (HCM) families.Methods:A retrospective cohort study was conducted on 527 unrelated HCM probands who were first diagnosed at the First Affiliated Hospital of Air Force Medical University (Xijing Hospital) from February 2014 to July 2018, and the high-throughput whole exome targeted sequencing of 96 genes related to hereditary cardiovascular disease was performed on the probands. The probands carrying the MYH7-R453C mutation were screened out, and their family members carrying the mutation were verified using Sanger sequencing. Healthy individuals without family history of genetic diseases from the same period and ethnicity were recruited as controls. Clinical data such as echocardiography, 12-lead electrocardiogram, and cardiac magnetic resonance imaging of the probands and their family members were collected, and the correlation between patient genotype and clinical phenotype was analyzed. Endpoint or key events were recorded through hospital re-examination or telephone follow-up.Results:The MYH7-R453C mutation was detected in 5 HCM probands, and clinical data and genetic results of 20 family members, including probands, were collected. Among them, 13 carried the MYH7-R453C mutation, of which 12 were diagnosed with HCM, and one child (F1Ⅲ 5) experienced early changes of HCM. The seven family members who did not carry the MYH7-R453C mutation had normal echocardiograms and 12-lead electrocardiograms. Among the 12 patients diagnosed with HCM, 2 experienced (F2Ⅱ 7, F5Ⅰ 2) sudden cardiac death, 2 experienced (F1Ⅲ 1, F3Ⅲ 3) events of sudden cardiac death survival, 2(F1Ⅱ 2, F3Ⅱ 1) died from heart failure during the follow-up period. Combined with the initial visit and follow-up, 4 families (F1, F2, F3, F5) had a family history of sudden death, among which 3 families probands or multiple family members experiencing sudden death before the age of 30 and adverse outcomes such as implantation of implantable cardioverter-defibrillators after sudden death survival. Conclusions:In the five families with HCM carrying MYH7-R453C mutations, genotype is highly correlated with clinical phenotype, and patients have a high risk of sudden death and poor prognosis. Early diagnosis of individuals carrying the MYH7-R453C gene mutation, both within the patient′s family and in the patients themselves, is crucial for initiating early treatment, preventing sudden death, and assessing prognosis.

Circadian rhythm is a phenomenon of diurnal changes in life activities formed by a transcription-translation feedback loop of biological clock genes affected by external environmental conditions. The circadian rhythm system controls almost all physiological processes in the organism, and these processes will change as the external environment changes. Previous studies have shown that the hypothalamic-pituitary-thyroid axis in mammals is regulated by the central diurnal pacemaker of the suprachiasmatic nucleus of the hypothalamus, so part of the thyroid function is controlled by the biological clock, and the secretion of thyroid hormones in blood can present a circadian rhythm. However, the molecular mechanism of the biological clock's regulatory effect on thyroid is still unclear. Whether circadian rhythm interference is related to the disorder of thyroid function or the occurrence of thyroid diseases is worthy of attention. This paper focused on the research progress of biological clock, circadian rhythm, and thyroid function, specifically the characteristics of circadian rhythm of thyroid physiological function and the effects of sleep deprivation, light at night, and night shift work on thyroid function, elaborated the relationships of circadian rhythm disorder with thyroid function and thyroid diseases represented by thyroid malignant tumors. The review summarized that circadian rhythm disorder may disrupt the rhythmic secretion of thyroid hormones, but no clear conclusion is reached yet on any effect on thyroid diseases, especially thyroid malignant tumors, so it is necessary to further strengthen the relevant epidemiological and molecular mechanism research.

Objective:To evaluate the changes of left ventricular (LV) myocardial systolic strain and twist motion including global longitudinal strain(GLS), global circumferential strain(GCS), global radial strain(GRS), global area strain(GAS), LV basal segment rotation angle (Rotation-basal), LV apical segment rotation angle (Rotation-apical), LV twist angle (Twist), LV torsion(Torsion) by three-dimensional speckle tracking imaging(3D-STI) in adult patients with hypertrophic cardiomyopathy (HCM), and further to analyze the correlations between LV twist and its morphology and global systolic function.Methods:A total of 45 patients with HCM from the General Hospital of Ningxia Medical University from September 2017 to June 2019 were enrolled. In addition, 50 healthy subjects were recruited as a control group. Left atrial dimension(LAD), interventricular septal end-diastole dimension(IVSD), LV posterior wall end-diastole dimension (LVPWD), LV mass index(LVMI) and other parameters were respectively measured by conventional two-dimensional transthoracic echocardiography. LV end-diastole volume(EDV), LV end-systole volume(ESV), calculated stroke volume(SV) and LV ejection fraction (LVEF) were respectively measured by 3D transthoracic echocardiography. Full-volume 3D dynamic images were performed using matrix transducer X5-1. LV Rotation-basal, Rotation-apical, Twist and Torsion, GLS, GCS, GRS and GAS were respectively analyzed by off-line TomTec software. The differences of those parameters between the two groups were compared. The correlations between 3D-Torsion parameters and those parameters by two-dimensional echocardiography was further analyzed.Results:Compared with control group, LAD, IVSD, LVPWD and LVMI of HCM group were increased(all P<0.01), EDV, ESV, SV, LVEF and E/A were decreased(all P<0.01). Compared with control group, GLS, GCS and GRS of HCM group were decreased(all P<0.01). Rotation-basal, Rotation-apical, Twist and Torsion were increased(all P<0.01), and there was no significant difference of GAS between the two groups( P>0.05). In HCM group, IVSD was not correlated with Rotation-basal ( P>0.05), but negatively correlated with Rotation-apical, Twist and Torsion ( r=-0.327, -0.439, -0.374; all P<0.05); LVEF and LVMI were not correlated with Rotation-basal, Rotation-apical, Twist and Torsion (all P>0.05). Conclusions:①3D-STI can detect the earlier subtle changes of left ventricular three-dimensional systolic strain in HCM patients; ②LV three-dimensional Twist inereases considerably in HCM patients; ③LV Twist, Torsion and Rotation-apical are significantly decreased with the increase of IVSD in HCM patients; However, LVEF and LVMI are not significantly correlated with Rotation-basal, Rotation-apical, Twist and Torsion.

Objective:To investigate the feasibility of ultrasound-guided percutaneous endomyocardial septal cryoablation of in vitro porcine hearts and to compare its effect with the percutaneous endomyocardial radiofrequency ablation.Methods:Experiment 1: Six in vitro porcine hearts were divided into 1 min ( n=2), 3 min ( n=2) and 5 min ( n=2) groups according to the cryoablation time, and all were subjected to ultrasound-guided percutaneous intra-myocardial septal cryoablation at 100% power respectively. After cryoablation, ultrasound images, the size of the solid dissection of the ice ball, and the size of the necrotic area after melting of the frozen ice ball were measured. Experiment 2: The in vitro porcine hearts were divided into cryoablation group ( n=3) and radiofrequency ablation group ( n=3), and ultrasound-guided percutaneous endomyocardial septal cryoablation and radiofrequency ablation were performed with 100% cryo power and 40 W radiofrequency power, and the extent of complete necrotic area and incomplete necrotic area were compared between the two ablation methods after 1 min. Results:Experiment 1: In the 1 min cryoablation time group ( n=2), the short diameter of the puck measured by ultrasound was (8.00±0.84)mm, the short diameter of the puck measured by solid was (8.38±1.19)mm, and the short diameter of the necrotic zone measured by solid was (8.35±0.83)mm; in the 3 min group ( n=2), the short diameter of the puck measured by ultrasound was (19.4±0.28)mm, and the short diameter of the puck measured by solid was (19.03±0.33)mm, solid measurement of the short diameter of the necrotic zone was (19.16±0.25)mm; in the 5 min group ( n=2), the short diameter of the puck measured under ultrasound was (26.4±2.54)mm, solid measurement of the short diameter of the puck was (26.01±0.24)mm, and solid measurement of the short diameter of the necrotic zone was (24.82±0.25)mm. Randomized blocks analysis of variance was performed on this data and the difference of block Factor b (freezing time: 1 min, 3 min, 5 min) among the three groups was statistically significant( F=505.884, P<0.001). The SNK- q test showed that all three groups differed from each other(all P<0.05). The analysis results for the treatment factors K (measurement modality-ultrasound image measurements, solid anatomical measurements of the puck, and measurements of the necrotic area after melting of the frozen puck) was not statistically significant ( F=0.470, P=0.635). Experiment 2: In the RF ablation group ( n=3), the ratio of incomplete necrotic zone to the radius of the RF ablation area was 0.64±0.01; in the cryoablation group ( n=3), the ratio of incomplete necrotic zone to the radius of the ablation area was 0.26±0.02. The difference was statistically significant( P=0.002) and it can be considered that the incomplete necrotic zone of cryoablation was smaller than that of RF ablation. Conclusions:Percutameous intramyocardial septal cryoablation is controllable in scope, ultrasound image evaluation of ablation area is more accurate and incomplete necrosis area is small, which may have potential applications in cardiac ablation.

Objective:To quantitatively evaluate myocardial microcirculation perfusion changes after percutaneous intracardiac septal radiofrequency ablation (PIMSRA, Liwen procedure) in patients with obstructive hypertrophic cardiomyopathy (HOCM) using myocardial contrast echocardiography (MCE) and to further establish the effect of the procedure and predict the long-term prognosis of patients.Methods:A total of 45 patients with HOCM treated by the Liwen procedure in the First Affiliated Hospital of Air Force Medical University (Xijing Hospital) from July 2019 to June 2020 were included. MCE was performed before and 6 months after surgery, respectively. Time-intensity perfusion curve analysis was performed using QLab 10.8 offline software to obtain quantitative parameters of myocardial microcirculation perfusion including myocardial blood volume (A value), myocardial blood flow velocity (β value), and myocardial blood flow (A×β value), then the changes in parameters before and after the procedure were compared.Results:After the Liwen procedure, the mean septal thickness and mean left ventricular free wall thickness were significantly reduced, accompanied by a significant reduction in the left ventricular outflow tract pressure gradient (LVOT-PG) and mitral regurgitation length, and a significant improvement in mitral systolic antegrade motion (SAM) (all P<0.001). In addition, the left ventricular ejection fraction (LVEF) did not deteriorate significantly ( P=0.560) and the E/e′ ratio decreased after the procedure ( P=0.015). Besides, the A values of both the ventricular septum and the left ventricular free wall were not significantly changed compared to those before procedure ( P>0.05), whereas the β values and A×β values were obviously increased ( P<0.05). Conclusions:Myocardial blood velocity and myocardial blood flow in the septum and left ventricular free wall were significantly increased in patients with HOCM after the Liwen procedure, suggesting a significant improvement in myocardial microcirculation perfusion. MCE provides a non-invasive quantitative evaluation parameters of myocardial microcirculation perfusion for the Liwen procedure for the treatment of HOCM.

Objective:Biobank construction plays an irreplaceable role in the research of accurate prevention and treatment of diseases. Shared biobank network based on a large crowd queue is the way of the future. This subject is one of the key contents of national precision medicine "The Breast Cancer Cohort Study in Chinese Women: (BCCS-CW)" , aiming to solve the bottleneck of insufficient standardization and sharing.Methods:The establishment of "entity library-information library-extension library" , the widely Shared network of biobank of breast cancer specific disease cohort, and the establishment of strict standard setting and quality control standard to construct the standardized biobank.Results:This biobank provides a shared biobank resource for breast cancer risk assessment, prediction and early warning, early screening, classification, individualized treatment, efficacy and safety prediction and monitoring and other accurate prevention and treatment programs and clinical decision-making system research.Conclusion:The data of this biological sample bank is refined and complete, and the sample size of cases is sufficient, which can meet the research needs of medical big data, genomics, metabonomics, epigenetics and other fields.

Objective: The aim of this study was to evaluate the value for CBL and LBL teaching method in the training of refresher doctors in reproductive medicine. Methods: A questionnaire survey was conducted among 186 refresher doctors who had studied in the reproductive medicine center at Peking University Third Hospital from January 2016 and December 2017 one year after their graduation. We tested 33 refresher doctors in observe group and 33 refresher doctors in the CBL+LBL group who graduated at the same period. Results: Ninety-two refresher doctors responded to the investigation. The questionnaire survey showed that 84.78% of the refresher doctors thought that CBL and LBL teaching method could improve their learning abilities, clinical problem analysis and solving skills, and surgical techniques, which was conducive to promoting their assisted reproductive technology. Besides, 63.04% of refresher doctors believed this method improved their research abilities. In CBL+LBL group, examination scores of theoretical knowledge were significantly higher than the observe group (P<0.05). Conclusion The combination of CBL and LBL is effective and feasible in the training of refresher doctors in reproductive medicine.

Now the visiting physicians are usually trained without effective supervision and guidance mechanism.Since 2017,the Emergency Department of Peking University Third Hospital has adopted the training model under tutor system for visiting physicians.Tutors and visiting physicians are matched 1∶1.Personalized training program is made by tutors and visiting physicians depending on the level of the hospital where visiting physicians practice in,educational background,clinical experience,length and the goal of study.The training plan is refined according to the timeline in order to facilitate the tutor and training physician's own precise management.Since implementation of this training model,the visiting physicians say they are more efficient to complete the training program and learned more than before.The teaching ability of tutors has further been enhanced.

Objective:To investigate the clinical features of placental thrombosis complicated with fetal growth restriction(FGR),and to analyze its diagnosis and treatment methods. Methods:Combined with reviewing the relevant literatures, the clinical data of a case of placental thrombosis complicated with FGR was retrospectively analyzed. The patient with 32 1/7 weeks of gestation was hospitalized due to placental blood sinus found one month ago;at the same time FGR was found by ultrasound examination. The patient was intravenously given nutritional support treatment such as amino acid and glucose.At the same time, the patient was continuously given low-flow oxygen. Results:The patient received cesarean section at 35 2/7 weeks of gestation and a baby girl with 1 280 g weight and 32 cm length was gained;many blood sinus in the maternal surface of placenta were seen with the largest diameter of 3-4cm;the placenta was hypertrophic, weighted 540 g .After operation,the newborn was transferred to Department of Neonatology and followed up for 1 month.1 month later, the infant could eat by herself, other physical examinations were finished without any obvious abnormal findings and the newbron discharged from hospital after recovery. Conclusion:Placental thrombosis complicated with FGR is very common in clinic and this disease severely endangers the neonatal health. Early diagnosis and reasonable treatment can improve the pregnancy outcomes.

Objective To determine the pollution sources that influence the level of exposure to particulate matter 2.5 (PM2.5) in the elderly,and calculate the quantitative contributions of difference sources.Methods Personal exposure PM samples were collected in the summer and winter of 2011 from 101 elderly men in a Tianjin community.Chemical species (elements,water-soluble ions and carbonaceous species) were analyzed in PM samples to determine PM2.5 concentrations and chemical compositions.The Positive Matrix Factorization (PMF) model,which is recommended by the US Environmental Protection Agency,was employed to quantitatively analyze the contribution of each potential sources to personal levels of PM2.5 exposure.Results In both summer and winter,the model identified the same six sources of personal exposure to PM2.5 in the elderly:fugitive dust (marker species:Si,Al,Ca,Mg,Fe etc.),coal combustion emissions (marker species:organic carbon (OC) and SO42-),vehicle exhausts (marker species:inorganic carbon and NO3),secondary sulfates and nitrates (marker species:NO3-,SO42-and NH4 +),industrial emissions (marker species:Mn,Ni,Cu,Zn,Pb etc.),and indoor sources (marker species:OC,K,Si,Al etc.).Among these six potential sources,vehicle exhausts (summer:33.6％,winter:24.2％),secondary sulfates and nitrates (summer:27.4％,winter:29.1％),as well as coal combustion emissions (summer:19.9％,winter:24.1％) were the greatest contributors.Conclusions Coal combustion and vehicle exhaust emissions were the major sources of personal exposure to PM2.5 in the elderly,suggesting that these two sources were the key contributors to the precursor gases of secondary sulfate and nitrate.Key Project of Chinese National Programs for Fundamental Research and Development (2011CB503801)