[Impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity and pulse pressure on all-cause mortality].

Objective: To evaluate the impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity (baPWV) and pulse pressure (PP) on all-cause mortality. Methods: This study is a prospective cohort study. Individuals participated in the Kailuan Study and completed baPWV measurements between 2010 and 2016 were included in this study. After stratifying by sex, 75th percentile baPWV and PP values for different age group were calculated at five years interval. BaPWV and PP values below the 75th percentile were defined as normal, and those above or equal to the 75th percentile were defined as increased. The participants were allocated to four groups according to their PP and baPWV status: normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group. The primary outcome was all-cause mortality during the follow-up period. Cox proportional hazards models were used to explore the impact of individual and combined assessment of baPWV and PP on all-cause mortality events. Results: A total of 39 339 participants were enrolled in this study, aged (49.3±12.8) years, of which 28 731 (73.03%) were males. There were 23 268, 6 025, 6 210 and 3 836 cases in the normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group, respectively. The average follow-up duration was (4.98±2.53) years. During the follow-up period, all-cause mortality occurred in 998 individuals. Multivariate Cox regression analysis showed increased risk of all-cause mortality in the high baPWV/normal PP group (HR=1.27, 95%CI 1.07-1.50), and in the high baPWV/PP group (HR=1.33, 95%CI 1.08-1.65) compared to the normal baPWV/PP group. Increased pulse pressure alone had no impcat on all-cause death (HR=1.06, 95%CI 0.87-1.29). Conclusions: The risk of all-cause mortality significantly increases with increased age-and sex-specific baPWV and PP values. BaPWV may be a better predictor of all-cause mortality than PP in this cohort.

[Association between clinical phenotypes of hypertrophic cardiomyopathy and Ca2+ gene variation gene variation].

Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca2+ gene variation) and to compare clinical phenotypes of HCM patients with Ca2+ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca2+ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca2+ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca2+ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca2+ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca2+ gene variant group (only 1 Ca2+ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca2+ gene variation (Ca2+ gene variation group). Compared with gene negative group, patients in Ca2+ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death (P<0.05); echocardiographic results showed that patients in Ca2+ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with sarcomere gene variation group, patients in Ca2+ gene variation group had later onset age and higher blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca2+ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05); patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P<0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca2+ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca2+ gene variation.

[Myocardial biopsy of Liwen procedure: representability and etiological diagnostic value of cardiac samples obtained by a novel technique in patients with hypertrophic cardiomyopathy].

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)µm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.

[Dysregulated proportion of intrahepatic Treg cells and Th17 along with CD8+ T lymphocytes drives disease progression after kasai biliary atresia surgery].

Objective: To analyze the clinicopathological characteristics and intrahepatic immune cells infiltration condition after Kasai biliary atresia surgery. Methods: Data of 28 cases who underwent liver transplantation in the liver transplantation center of our hospital from June 2017 to March 2019 were enrolled. Of which, 20 cases were in the biliary atresia group (divided into two subgroups: 10 cases without Kasai surgery and 10 cases after Kasai surgery, and latter subsided cholestasis) and 8 cases in the control group. Clinical and pathological morphological characteristics of the groups were compared. Liver tissue sections were stained with immunohistochemistry and CD3, CD4, CD8, CD20, Foxp3, and interleukin-17A were quantitatively analyzed. Kruskal-Wallis test was used to measure the above indicators, and rank-sum test or Fisher's exact test was used to compare the count data. Results: The degree of clinical and pathological cholestasis in the biliary atresia group after Kasai surgery was significantly lower than that of the group without Kasai surgery, and the degree of liver fibrosis was also significantly reduced (P < 0.05), but there was no statistically significant difference in the degree of inflammation in the portal vein area between the two groups (P > 0.05). There was statistically significant difference in the types of immune cells infiltrated in the liver (P < 0.05). Compared with the group without Kasai surgery, the infiltration of CD3, CD8, IL-17A and Foxp3 positive cells in the portal vein area after Kasai surgery group (P < 0.05) was significantly reduced, but there was no statistically significant difference in the proportion of Foxp3/CD4 positive cells between the two groups (P > 0.05), which continued to be lower than that of the control group (P < 0.05). Compared with the non-Kasai surgery group, the proportion of Foxp3/IL-17A and Foxp3/CD8 positive cells in the portal vein area did not increase significantly after Kasai surgery group (P > 0.05), and remained lower than the control group. However, the proportion of Foxp3/IL-17A and Foxp3/CD8 positive cells was significantly reduced (P ​​< 0.05). Conclusion: Intrahepatic inflammatory cell infiltration and regulatory/effector T lymphocyte proportion dysregulation exist in patients with subsided cholestasis after Kasai biliary atresia surgery, which may be an important factor to promote the disease progression.

[Comparative study of clinicopathological features, and risk factors of advanced fibrosis between genders with non-alcoholic fatty liver disease].

Objective: To comparatively study the similarities and differences between the clinical, pathological, and risk factors of advanced fibrosis in men and women with non-alcoholic fatty liver disease (NAFLD). Methods: 267 patients with NAFLD diagnosed by liver biopsy were retrospectively included, and were divided into male and female groups. The difference of clinical and pathological indexes were compared between the two groups. The measurement data were in accordance with normal distribution. The comparison between the two groups was performed by independent sample t-test. The non-parametric test was used for non-normal distribution. The classification data were expressed as a percentage, and the chi-square test was used for comparison between groups. Logistic regression analysis was used to analyze the risk factors. Results: The age of onset of NAFLD was significantly lower in male than female patients (P < 0.01). There was no statistically significant difference between the male and female groups in terms of body mass index and the prevalence of type 2 diabetes (P > 0.05). Biochemical index: The levels of alanine aminotransferase, albumin, total bilirubin and uric acid were significantly higher in male than female patients (P < 0.01). Liver pathology: The proportion of ballooning degeneration was significantly lower in male than female patients (P < 0.01). There was not statistically significant difference between the two groups in the proportion of steatohepatitis score, non-alcoholic steatohepatitis (52.0% vs. 61.5%, P = 0.283) and advanced liver fibrosis (14.3% vs. 17.8%, P = 0.162). Thrombocytopenia was a common independent risk factor for advanced stage liver fibrosis (OR = 0.984, 0.978~0.989, P < 0.01). Type 2 diabetes was only an independent risk factor for advanced stage liver fibrosis in men (OR = 6.557, 1.667~25.782), P < 0.01). Elevated AST was only an independent risk factor for advanced stage liver fibrosis in women (OR = 1.016, 1.003~1.028, P = 0.012). Conclusion: In NAFLD patients, there are some clinical and pathological differences between genders. Platelets are a common predictor of advanced liver fibrosis in men and women. Type 2 diabetes in men and elevated aspartate aminotransferase in women can be regarded as independent risk factors for advanced liver fibrosis.

[Clinicopathological features of Caroli disease/Caroli syndrome: an analysis of 21 cases].

Objective: To summarize and compare clinicopathological features of Caroli disease and Caroli syndrome. Methods: A total of 21 patients diagnosed with Caroli disease or Caroli syndrome in Beijing Friendship Hospital, Capital Medical University, from January 2015 to December 2018 were included. Through the clinical manifestations and comparative analysis of the differences between different clinical types, the liver pathological features of these patients were described. Results: Of all patients included, 8 were male and 13 were female, and the medium age was 13.5 year old. The initial symptom was fever in 6 cases (28.6%), gastrointestinal bleeding in 6 cases (28.6%) and hepatosplenomegaly in 9 cases (42.8%). Caroli disease accounted for 6 cases (28.6%) and Caroli syndrome 15 cases (71.4%). The total bilirubin [6.7 (4.7, 15.0) vs 16.0(10.9, 33.0)µmol/L] and direct bilirubin [1.3(0.9,6.4)vs 3.5(2.7, 16.2)µmol/L] were significantly lower in Caroli disease group in comparison to those in Caroli syndrome group(both P<0.05). The hemoglobin [117.0 (106.0, 126.2) vs 85.0 (74.0, 103.0) g/L] and platelet count [286.0 (149.8, 467.5)×10(9)/L vs 76.1(55.0,123.0)×10(9)/L] in Caroli disease group were significantly higher than those in Caroli syndrome group (both P<0.05). There were 10 patients (47.6%) who underwent liver transplantation. Child-Pugh-Turcotte Score (liver function reserve) were significantly higher than that in the non-liver transplantation group[8.0(8.0, 10.2)vs 5.0 (5.0, 6.0), P<0.05]. Conclusions: Early symptoms of Caroli disease/Caroli syndrome are atypical and prone to misdiagnosis and misdiagnosis. The diagnosis is usually based on pathology and may be supplemented by laboratory examination and imaging analysis.

[The role of three-dimensional speckle tracking imaging derived parameters on predicting outcome of hypertrophic cardiomyopathy patients with MYH7 mutations].

Objective: To evaluate the cardiac functional changes in hypertrophic cardiomyopathy(HCM) patients with ß-myosin heavy chain gene (MYH7) mutations by three-dimensional (3D) speckle tracking imaging(3D-STI) and conventional echocardiography modalities, and then to explore the potential predictors of adverse cardiovascular events in these patients. Methods: A consecutive series of 192 HCM patients admitted in our center from October 2014 to October 2016 were genetically screened to identify MYH7 mutations in this retrospective study. A total of 43 HCM patients with MYH7 mutations were enrolled. The patients were divided into events group(n=13) and no event group(n=30) according to the presence or absence of adverse cardiovascular events(primary and secondary endpoints). All patients were followed up to January 2019 after comprehensive evaluation of 3D-STI, two-dimensional and Doppler echocardiography. The adverse cardiovascular events were recorded. Results: The median follow up time was 1 012 (812, 1 330) days. During follow-up, 13 patients (30.2%) reached endpoints: 6 cases of the primary endpoints(2 cases of sudden cardiac death(SCD), 3 cases of survival after defibrillation, and 1 case of appropriate implantable cardioverter-defibrillator(ICD) discharge); 7 cases of the second endpoints(5 cases of heart failure hospitalization, 1 case of syncope and cardioversion due to supraventricular tachycardia, and 1 case of end-stage HCM). Patients with adverse cardiovascular events had higher prevalence of syncope and risk of SCD, enlarged left atrial volume index(LAVI) and reduced 3D left ventricular global longitudinal train (3D-GLS), as compared to those without adverse events(all P<0.05). The multivariate Cox regression analysis showed that reduced 3D-GLS(HR=0.814, 95%CI 0.663-0.999, P=0.049) was an independent predictor for adverse cardiovascular events. The cutoff value of 3D-GLS≤13.67% was linked with significantly increased risk of adverse cardiovascular events in this patient cohort(AUC=0.753, 95%CI 0.558-0.948, sensitivity 86%, specificity 69%, P<0.05). The Kaplan-Meier analysis indicated that the patients with the 3D-GLS≤ 13.67% faced higher risk of death than those with 3D-GLS>13.67%. Conclusion: 3D-GLS is useful on predicting adverse cardiovascular events in HCM patients with MYH7 mutations.

[EASL clinical practice guidelines recommendations for drug-induced liver injury in 2019].

Idiosyncratic (unpredictable) drug-induced liver injury (iDILI) is one of the most challenging liver diseases encountered by hepatologists due to its diverse clinical and pathological manifestations and lack of specific diagnostic markers. An increasing awareness of iDILI diagnosis and carefully excluding liver damage induced by other causes is the key to a proper diagnosis of iDILI. However, delayed diagnosis, inappropriate monitor and care leads to serious clinical consequences, such as acute liver failure or even liver-related death. In addition, there is presently no effective treatment for iDILI. Herein, we presented the main recommendations of the recent EASL published first DILI guidelines into Chinese language to facilitate liver disease authors and health workers to understand the latest research progress of DILI.

[Operative method choice and strategy of laparoscopic surgery therapy for gallbladder stones and common bile duct stones].

Objective: To explore the selection method and technology of laparoscopic surgery for gallbladder stones and common bile duct stones(GCBDS). Methods: Data was collected from 318 in-patients of GCBDS at Department of General Surgery,Xuanwu Hospital of Capital Medical University from January 2013 to December 2017, and 298 in-patients acceptedlaparoscopic cholecystectomy(LC) and choledocholithotomy were recruited into final analysis.There were 138 males and 160 females,aged (60.4±18.6)years (range:25-89 years).Retrospective analysis was done on method distribution,effect and safety of laproscopic surgery.Comparisons of basic characters and therapeutic effects were performed betweenlaparoscopic common bile duct exploration (LCBDE) combined with primary closure and T tube drainage(TTD). Results: Among therecruited in-patients,LC combined with common bile duct exploration was performed in 7 cases(2.3%, 7/298), LC combined with LCBDE was performed in 291 cases(97.7%,291/298).There were 133 cases (45.7%,133/291) who treated by LCBDE combined with TTD and 158 cases(54.3%,158/291) who treated by LCBDE combined with primary closure.In LCBDE combined with primary closure group,18 cases (11.4%,18/158)had intraoperative biliary manometry.All patients were followed up for 6 months at least and there no death.Postoperative complications rate was 10.0% (29/291).There were no significant differences in sex ratio,age,American Society of Anesthesiologists score,concomitant diseases and previous abdominal surgery history between LCBDE combined with primary closure and LCBDE combined with TTD group.Patients in LCBDE combined with primary closure group were accompanied with less acute cholangitis than TTD group (43.3% vs.76.7%; χ(2)=9.061, P=0.002).There were no significant differences in the diameter of common bile duct, the number of stones, hospitalization expenses and the incidence of complications between the two groups(all P>0.05).LCBDE combined with primary closure had shorter operation time ((134.2±28.3)minutes vs.(148.3±19.6)minutes; t=-1.830, P=0.011)and post-operative hospitalization time ((5.6±2.6)days vs. (7.2±2.4)days; t=-1.847,P=0.014).Bile duct leakage rate was higher in primary closure group(6.3% vs.0.8%, χ(2)=3.934, P=0.047) and TTD group had higher residual stones rate(6.8% vs.1.3%; χ(2)=6.008, P=0.014). Conclusion: Strategy for treating GCBDS by laparoscopic surgery should be considered preoperative evaluation and intraoperative exploration to select appropriate minimally invasive surgical methods and techniques.

[Efficacy and safety of transthoracic echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation for the treatment of patients with obstructive hypertrophic cardiomyopathy].

Objective: To investigate the safety and efficacy of transthoracic echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Nine HOCM patients with interventricular septal thickness ≥15 mm and ≤25 mm who were treated with PIMSRA between October 2016 to March 2017 in the Hypertrophic Cardiomyopathy Center of Xijing Hospital of Air Force Military Medical University were enrolled,and the clinical data were retrospectively analyzed.Interventricular septum thickness, left ventricular outflow tract diameter and maximum gradient were measured by transthoracic echocardiography immediately after procedure, at 1 month, 3 months and 6 months after operation.Symptoms and New York Heart Association (NYHA) functional class were assessed, and provoked left ventricular outflow tract gradient and exercise time were measured after 6 months. Results: The anterior interventricular septum ((21.5±2.6) mm vs. (24.7±2.7) mm, P<0.05) and posterior interventricular septum (21.1±2.5) mm vs. (22.6±3.3) mm, P<0.05) were significantly increased,left ventricular outflow tract diameter was widened ((8.2±3.4) mm vs. (4.8±2.2) mm, P<0.05), left ventricular outflow tract gradient ((26.8±19.6) mmHg (1 mmHg=0.133 kPa) vs. (83.3±32.4) mmHg, P<0.05) and mitral regurgitation (2.0±1.9) ml vs. (3.2±3.0) ml, P<0.05) were significantly decreased immediately after ablation compared with pre-operation values. Anterior interventricular septum, posterior interventricular septum and left ventricular outflow tract gradient further decreased after 1 month ((17.5±2.0) mm vs. (24.7±2.7) mm, P<0.05; (16.9±2.1) mm vs. (22.6±3.3) mm, P<0.05; (11.6±4.0) mmHg vs. (26.8±19.6) mmHg, P<0.05, respectively) compared with values immediately after ablation. Anterior interventricular septum and posterior interventricular septum decreased after 3 and 6 months ((14.8±1.7) mm and (13.4±2.0) mm vs. (17.5±2.0) mm, all P<0.05; (12.9±1.9) mm and (12.3±2.4) mm vs. (16.9±2.1) mm, all P<0.05, respectively) compared with values at 1 month after ablation.There were no significantly difference in left ventricular outflow tract gradient at 3 and 6 months post procedure compared with 1 month after ablation (all P>0.05). Compared with pre-operation, provoked left ventricular outflow tract gradient decreased ((25.5±11.4) mmHg vs. (147.8±58.0) mmHg, P<0.01), and total exercise time increased ((9.3±1.6) minutes vs. (6.7±1.6) minutes, P=0.03) at 6 months after operation.The symptoms were disappeared in 5 patients. There were 2 cases with NYHA class Ⅱ and 7 cases with NYHA class Ⅲ before operation,while there were 6 patients with NYHA classⅠ and 3 patients with NYHA class Ⅱ at 6 months after operation (P<0.01). Conclusion: Transthoracic echocardiography-guided PIMSRA is a safe and effective new treatment approach for patients with obstructive hypertrophic cardiomyopathy.

[Predicting value of 2014 European guidelines risk prediction model for sudden cardiac death (HCM Risk-SCD) in Chinese patients with hypertrophic cardiomyopathy].

Objective: To evaluate the predicting value of the 2014 European Society of Cardiology (ESC) guidelines risk prediction model for sudden cardiac death (HCM Risk-SCD) in Chinese patients with hypertrophic cardiomyopathy (HCM), and to explore the predictors of adverse cardiovascular events in Chinese HCM patients. Methods: The study population consisted of a consecutive 207 HCM patients admitted in our center from October 2014 to October 2016. All patients were followed up to March 2017. The 5-year SCD probability of each patient was estimated using HCM Risk-SCD model based on electrocardiogram, echocardiography and cardiac magnetic resonance (CMR) examination results. The primary, second, and composite endpoints were recorded. The primary endpoint included SCD and appropriate ICD therapy, identical to the HCM Risk-SCD endpoint. The second endpoint included acute myocardial infarction, hospitalization for heart failure, thrombus embolism and end-stage HCM. The composite endpoint was either the primary or the second endpoint. Patients were divided into the 3 categories according to 5-year SCD probability assessed by HCM Risk-SCD model: low risk group<4%,intermediate risk group ≥4% to<6%, and high risk group≥6%. Results: (1) Prevalence of endpoints: All 207 HCM patients completed the follow-up (350 (230, 547) days). During follow-up, 8 (3.86%) patients reached the primary endpoints (3 cases of SCD, 3 cases of survival after defibrillation, and 2 cases of appropriate ICD discharge); 21 (10.14%) patients reached the second endpoints (1 case of acute myocardial infarction, 16 cases of heart failure hospitalization, 2 cases of thromboembolism, and 2 cases of end-stage HCM). (2) Predicting value of HCM Risk-SCD model: Patients with primary endpoints had higher prevalence of syncope and intermediate-high risk of 5-year SCD, as compared to those without primary endpoints (both P<0.05). (3) Predicting value of HCM Risk-SCD model: The low risk group included 122 patients (59%), the intermediate risk group 42 (20%), and the high risk group 43 (21%). There was a clear trend towards to higher heart rate, higher values of PTF(V1) and plane QRS-T angle, higher left ventricular mass index (LVMI), elevated maximal left ventricular outflow tract pressure gradient (LVOT-PGmax), enlarged left atrial dimension(LAD) and volume index (LAVI), reduced systolic mitral annular velocity (s'), and higher late gadolinium enhancement (LGE) volume and mass in patients with high risk of 5-year of SCD, as compared to those with low-intermediate risk (all P<0.05). Moreover, 5-year SCD probability was positively correlated with heart rate, plane QRS-T angle, LVMI, LAVI, LGE%, and negatively correlated with s'(r=0.161, P=0.019; r=0.669, P=0.001; r=0.206, P=0.004; r=0.284, P=0.000; r=0.351, P=0.000; r= -0.245, P=0.001; respectively). (4) LAD, LAVI, e' and s' were independent predictors for poor outcomes. HCM patients with LAD≥39 mm, LAVI≥49.6 ml/m(2), e'≤6.5 cm/s and s'≤6.6 cm/s were more likely to have adverse cardiovascular events (AUC 0.702, 95%CI 0.604-0.799, P=0.001; AUC 0.700, 95%CI 0.567-0.833, P=0.001; AUC 0.716, 95%CI 0.616-0.817, P=0.000; AUC 0.764, 95%CI 0.676-0.853, P=0.000,respectively). Conclusions: The HCM Risk-SCD model is of value in predicting SCD for Chinese HCM patients. The plane QRS-T angle and LGE% are the best predictors of 5-year SCD risk in Chinese HCM patients. Moreover, conventional echocardiographic parameters, including LAD, LAVI, e' and s', are useful to predict adverse cardiovascular events among Chinese HCM patients.

Characterization of RsMYB28 and RsMYB29 transcription factor genes in radish (Raphanus sativus L.).

Glucosinolates (GSLs) are important secondary metabolites in Brassicaceae plants. Previous studies have mainly focused on GSL contents, types, and biosynthesis-related genes, but the molecular characterization patterns of GSL biosynthesis-related transcription factors remain largely unexplored in radish (Raphanus sativus L.). To isolate transcription factor genes regulating the GSL biosynthesis, genomic DNA and cDNA sequences of RsMYB28 and RsMYB29 genes were isolated in radish. Two R2R3-MYB domains were identified in the deduced amino acid sequences. Subcellular localization and yeast-one hybrid assays indicated that both the RsMYB28 and RsMYB29 genes were located in the nucleus and possessed transactivation activity. Reverse transcription quantitative analysis showed that the RsMYB28 and RsMYB29 genes were expressed in seeds, leaves, stems, and roots at the seedling, taproot thickening, and mature stages. Both genes were highly expressed during the seedling and taproot thickening stages. The expression level of RsMYB28 was found to be up-regulated following wounding, glucose, and abscisic acid treatments, whereas RsMYB29 was up-regulated following wounding and methyl jasmonate treatments. These results provide insights into the biological function and characterization of the RsMYB28 and RsMYB29 genes, and facilitate further dissection of the molecular regulatory mechanism underlying the GSL biosynthesis in radish.

[P1208fs mutation in the cardiac myosin binding protein C is associated with hypertrophic cardiomyopathy in a Chinese pedigree].

OBJECTIVE: To identify the potential mutations in a Chinese pedigree with hypertrophic cardiomyopathy (HCM), and to analyze the genotype-phenotype relationship in this pedigree. METHODS: Clinical history and physical examinations, electrocardiography (ECG), echocardiography (UCG), cardiac magnetic resonance (CMR) data were obtained from 10 members of a three-generation Chinese family with HCM. A total of 96 genes related to hereditary cardiomyopathy were detected by exon and boarding intron analyses in the proband using second-generation sequencing. Mutations identified in the proband were confirmed by bi-directional Sanger sequencing in the rest 9 family members and 300 healthy controls. RESULTS: Three mutations, including MYBPC3-P1208fs, ANK2-H556R and ANK2-P1974H, were identified in this pedigree. MYBPC3-P1208fs gene mutation was detected in 3 family members (proband, his mother and son), while this mutation was not detected in the rest family members. HCM was diagnosed in the proband and his mother by ECG, UCG and CMR. Son of the proband demonstrated early phenotype of HCM: although UCG and CMR were normal, ECG showed sinus bradycardia and paroxysmal supraventricular arrhythmias as well as ST segment changes. The onset age of HCM diagnosis of the proband and his mother was 42 and 50 years old, presented with palpitation and chest pain, and myocardial fibrosis sign in CMR. Furthermore, we found that left ventricular myocardial fibrosis is related to ECG changes (increasing r wave, ST segment change) in the proband and his mother. No HCM phenotype was evidenced in the 7 family members carrying ANK2-H556R and ANK2-P1974H mutations. CONCLUSIONS: Our results show that MYBPC3-P1208fs gene mutation is associated HCM phenotype in this Chinses pedigree. This mutation is associated with myocardial fibrosis and ST changes in HCM phenotype in this pedigree while ANK2-H556R and ANK2-P1974H mutations are not related to HCM phenotype in this family.

[Transcription factor activator protein 2C contribute to molar development in mice].

Objective: Explore the expression pattern of transcription factor activator protein 2C (Tfap2c) and identify the roles of Tfap2c during tooth development. Methods: Real-time quantitative PCR (RT-qPCR) was used to analyze the relative expression level of Tfap2c in various organs of embryo day(E)14.5 mouse embryos and mouse molar germs at E12.5-E18.5 and postnatal day (P)0-P7. The expression position of Tfap2c in mouse molar germs was demonstrated by frozen section immunofluorescence staining. Cultured mandibular molar germs were transfected with control siRNA or Tfap2c siRNA to evaluate the effect of Tfap2c on tooth molar germs development, and RT-qPCR was used to detect the relative expression level of genes related to odontoblast expression. Dental mesenchymal cells were isolated from E14.5 molar germs and transfected with control siRNA or Tfap2c siRNA, cell counting kit 8 and scratch healing test were applied to detect dental mesenchymal cell viability and migration. Results: Tfap2c was highly expressed in the early development period of mouse molar germs. Tfap2c was expressed in the epithelial and mesenchymal tissues of E13.5 mouse molar germs and there was no significant difference of relative expression of Tfap2c between them (t=1.06, P=0.472). Tfap2c was expressed in mesenchymal tissues of E14.5 mouse molar germs and the relative expression of Tfap2c in mesenchymal tissues was significantly higher than epithelial tissues (t=37.29, P<0.0001). For molar germs transfected with Tfap2c siRNA, the relative height of cusps (0.708±0.171) and the ratio of cusp height and crown height (0.321±0.068) was significantly lower than control group (1.000±0.287 and 0.483±0.166) (t=2.79, P=0.012; t=2.85, P=0.015). But there was no significant difference in relative height (1.078±0.206, 0.993±0.254, t=0.83, P=0.419)and relative width (1.000±0.116, 0.999±0.122, t=0.01, P=0.992) of crowns between two groups. The relative expression level of genes related to odontoblast expression was decreased (Dspp: t=15.33, P<0.001; Dmp1: t=13.81, P<0.001). Tfap2c siRNA hinders cell migration in dental mesenchymal cells (t=29.86, P=0.001), but there was no significant difference in CCK8 absorbance value between two groups. The relative expression level of genes related to odontoblast expression was also decreased in dental mesenchymal cells transfected with Tfap2c siRNA (Dspp: t=3.86, P=0.031; Dmp1; t=4.36, P=0.022). Conclusions: Tfap2c highly expressed in the early morphogenesis period of mouse molar germs, mainly in mesenchymal tissues. Tfap2c affected the cusps formation of mouse molar germs and migration of dental mesenchymal cells.

[Discussion on the history of Pinelliae Rhizoma Praeparatum(Fa banxia) Processing].

Before the Song Dynasty, the main processing method of Pinelliae Rhizoma was soup washing. The "new method" in Taiping Huimin Heji JuFang is a processing method that concocted with Ginger,white alum and starter-making.The "Fa Banxia" in the Yuan Dynasty's Yuyuan Yaofang comes from the Taiping Huimin Heji JuFang, and the Fa Wen Banxia, Fa Bai Banxia, and Fa Hong Banxia are the processing methods of patent medicine with a variety of other herbs.Fa Banxia appeared in the Ming Dynasty, and its auxiliary materials were ginger and white alum, and medical formulary began to include formulas containing Fa Banxia. Bencao Gangmu abbreviates the Yuan Dynasty's Fabai Banxia as "Fa Banxia", and is elaborated under the item attached "prescription" item instead of the "treatment". In the literature of Materia Medica, it is recorded that the preparation of auxiliary materials in Fa Banxia increased, including lime, licorice, soap horn, and simple nitro.After Daoguang in the Qing Dynasty, the Fa Banxia in famous medical cases was more used, and at that time, Fa Banxia was Xian Banxia. There are two recipes for Xian Banxia: one is made with seven processes, and the other is soaked in alum licorice water. During the Republican period, Zhang Cigong also pointed out that Fa Banxia was sliced Xian Banxia after rinsing and boiling, while the preparation method of Xian Banxia was Banxia made of ginger and white alum.Ye Juquan pointed out that the so-called "fa" is neither an ancient method nor a new method, questioning the process of repeated immersion in Banxia. After 1949, the questioning of Fa Banxia continued unceasing.Influenced by this, the 1960 edition Beijing Traditional Chinese Medicine Slice Cutting Experience included the method of soaking alum, licorice ,lime water, and was included in the 1963 edition of the Pharmacopoeia of the People's Republic of China.The 1985 version reduced the soaking time and eliminated the soaking process of alum based on the 1963 version, and this method is still used today.

A preliminary clinical study on high-intensity focused ultrasound therapy for tubal pregnancy.

Our aim was to explore the clinical application value of high-intensity focused ultrasound (HIFU) therapy for tubal pregnancy. Forty hospitalized patients with tubal pregnancies (28 cases of non-ruptured tubal pregnancy and 12 cases of ruptured tubal pregnancy) were selected to receive HIFU therapy. Serum human chorionic gonadotropin (ß-HCG) concentrations were compared before and after treatment. Serum ß-HCG was measured weekly and patients received observation only if the concentration decreased by 15% or more, compared with the previous value. Patients were given supplement HIFU therapy if the decrease in the serum ß-HCG was <15% within two weeks. Ultrasound was used to detect the volume changes in the ectopic lesions before and after treatment, and changes in vital signs and complications were recorded. Contrast-enhanced ultrasonography was used to assess fallopian tube patency after treatment. HIFU treatment was successful in 33 of the 40 patients (82%). Seven patients failed HIFU treatment and received surgical therapy (18%). Before and after treatment, serum ß-HCG concentrations and lesion volume were significantly different (P < 0.05, P < 0.01, respectively). Post-treatment tubal contrast-enhanced ultrasonography showed tubal patency on the affected side in 21 cases (64%) at six months and in 27 cases (82%) at 12 months. In conclusion, HIFU is safe and effective, and can be a treatment option for tubal pregnancy.

[Implementing and evaluating the online course system of orthodontic education].

A new teaching mode with the combination of online teaching and flipped class was designed and implemented in the Stomatological College of Nanjing Medical University based on the National Online Open Courses, the Virtual Interactive Network Teaching Platform and the E-learning Network Teaching Platform. The new online course system of orthodontic education was constructed with several components including the process and outcome assessments, the professional literature and knowledge summary reports and the virtual interactive online training. With the informative and convenient online teaching resources and modes, students' comprehensive abilities of independent learning were improved.

[Identification of serum biomarkers and evaluation of metabolism disorders in patients with oral squamous cell carcinoma].

Objective: To explore the changes in serum metabolic profile in patients with oral squamous cell carcinoma (OSCC) and to identify the diagnostic biomarkers in order to provide new ideas for the early diagnosis of OSCC. Methods: In total, 76 OSCC patients who were diagnosed at the Department of Oral and Maxillofacial Surgery and 70 healthy individuals who at the Department of Medical Center of The First Affiliated Hospital of Zhengzhou University from August 2019 to January 2020 were recruited in The study. According to the random number table method, all subjects were divided into a test group (n=96) and a verification group (n=50). Subjects in the test group consisted of 51 OSCC patients and 45 healthy subjects and subjects in the verification group included 25 OSCC patients and 25 healthy individuals. Serum samples and clinical data of each of the subjects were collected. The serum samples were analyzed by ultra-high-performance liquid chromatography quadrupole-Orbitrap high resolution accurate mass spectrometry. Principal component analysis, orthogonal partial least square discrimination analysis and t-test were used to profile the differential metabolites in the test group. Pathway analysis of differential metabolites was performed. In addition, binary logistic regression analysis and receiver operating characteristic analysis were used in order to establish the potential diagnostic panel. Results: Twenty-one endogenous differential metabolites were identified showing significant association with OSCC. Results of pathway analysis suggested that OSCC associated with lipid metabolism and amino acid metabolism (P<0.05). A novel diagnostic panel consisting of lysophosphatidylcholine (LysoPC) (16∶0/0∶0), LysoPC[18∶1(9z)/0∶0], taurine and D-glutamic acid was defined. The panel performed a high area under the receiver operating characteristic curve (0.998, 95%CI: 0.994-0.999, P<0.05). Conclusions: There were obvious lipid and amino acid metabolism disorders in OSCC patients. It was an effective method to establish a diagnostic model by metabolomics.

Ultrastructural evidence for communication between intramuscular vagal mechanoreceptors and interstitial cells of Cajal in the rat fundus.

To assess whether afferent vagal intramuscular arrays (IMAs), putative gastrointestinal mechanoreceptors, form contacts with interstitial cells of Cajal of the intramuscular type (ICC-IM) and to describe any such contacts, electron microscopic analyses were performed on the external muscle layers of the fundus containing dextran-labelled diaminobenzidin (DAB)-stained IMAs. Special staining and embedding techniques were developed to preserve ultrastructural features. Within the muscle layers, IMA varicosities were observed in nerve bundles traversing major septa without contact with ICC-IM, contacting unlabelled neurites and glial cells. IMA varicosities were encountered in minor septa in contact with ICC-IM which were not necessarily in close contact with muscle cells. In addition, IMA varicosities were observed within muscle bundles in close contact with ICC-IM which were in gap junction contact with muscle cells. IMAs formed varicosities containing predominantly small agranular vesicles, occasionally large granular vesicles and prejunctional thickenings in apposition to ICC-IM processes, indicating communication between ICC and IMA via synapse-like contacts. Taken together, these different morphological features are consistent with a hypothesized mechanoreceptor role for IMA-ICC complexes. Intraganglionic laminar ending varicosities contacted neuronal somata and dendrites in the myenteric plexus of the fundus, but no contacts with ICC associated with Auerbach's plexus were encountered.