The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Objective:Melanoma is highly malignant and heterogeneous.It is essential to develop a specific prognostic model for improving the patients'survival and treatment strategies.Recent studies have shown that ferroptosis results from the overproduction of lipid peroxidation and is an iron-dependent form of programmed cell death.Despite this,ferroptosis-related genes(FRGs)and their clinical significances remain unknown in malignant melanoma.This study aims to assess the role of FRGs in melanoma,with the goal of developing a novel prognostic model that provides new insights into personalized treatment and improvement of therapeutic outcomes for melanoma. Methods:We systematically characterized the genetic alterations and mRNA expression of 73 FRGs in The Cancer Genome Atlas(TCGA)-skin cutaneous melanoma(SKCM)dataset in this study.The results were validated with real-time RT-PCR and Western blotting.Subsequently,a multi-gene feature model was constructed using the TCGA-SKCM cohort.Melanoma patients were classified into a high-risk group and a low-risk group based on the feature model.As a final step,correlations between ferroptosis-related signatures and immune features,immunotherapy efficacy,or drug response were analyzed. Results:By analyzing melanoma samples from TCGA-SKCM dataset,FRGs exhibited a high frequency of genetic mutations and copy number variations(CNVs),significantly impacting gene expression.Additionally,compared with normal skin tissue,30 genes with significantly differential expression were identified in melanoma tissues.A prognostic model related to FRGs,constructed using the LASSO Cox regression method,identified 13 FRGs associated with overall survival prognosis in patients and was validated with external datasets.Finally,functional enrichment and immune response analysis further indicated significant differences in immune cell infiltration,mutation burden,and hypoxia status between the high-risk group and the low-risk group,and the model was effective in predicting responses to immunotherapy and drug sensitivity. Conclusion:This study develops a strong ferroptosis-related prognostic signature model which could put forward new insights into target therapy and immunotherapy for patients with melanoma.

Objective: To analyze the clinical characteristics and imaging features of occupational pulmonary thesaurosis induced by dust of iron and its compounds (OPTIDIC). Methods: A total of 230 cases of occupational welder's pneumoconiosis (OWP) patients or observation subjects were selected as the research subjects using the retrospective analysis method. They were diagnosed in four occupational disease diagnosis institutions in Shandong Province from 2010 to 2017. The high kV X-ray chest radiography or chest digital radiograph (hereinafter referred to as X-ray) were re-read to screen OPTIDIC patients. The clinical data of OPTIDIC patients were collected and analyzed. Results: Among the 230 cases, 56 cases were diagnosed as OPTIDIC, accounting for 24.3%. The clinical symptoms of the 56 patients with OPTIDIC were cough, sputum, chest tightness, shortness of breath, and difficulty breathing, while their physical signs were low or coarse breath sounds in lungs and others. Most of the X-ray results showed p shadows or q shadows, accounted for 98.2%, of which p/p shadow and q/q shadow accounted for 62.5%. The result of chest computed tomography (CT) showed diffuse point/round shadow and diffuse glass shadow in OPTIDIC patients. The result of fibro-bronchoscopy showed that a large amount of iron lutein particles was accumulated in macrophages and biopsy of lung showed idiopathic pulmonary hemosiderosis in OPTIDIC patients. Conclusion: The clinical characteristics of OPTIDIC patients showed no different from OWP. However, the result of X-ray of OPTIDIC patients mainly showed small circular shadows, and their CT images mainly showed diffuse point/round shadows or grinding glass shadow, which could be used to the differential diagnosis of OPTIDIC and OWP.

Objective:To investigate the clinical efficacy and prognostic influencing factors of radical surgery for duodenal gastrointestinal stromal tumor (GIST).Methods:The retrospective cohort study was conducted. The clinicopathological data of 741 duodenal GIST patients who under-went radical surgery in 17 medical centers, including 121 cases in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 121 cases in Chinese PLA General Hospital, 116 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 77 cases in Fudan University Shanghai Cancer Center, 77 cases in West China Hospital, Sichuan University, 31 cases in Guangdong Provincial People′s Hospital, 24 cases in Fujian Cancer Hospital, 22 cases in Fujian Medical University Union Hospital, 25 cases in Shengjing Hospital of China Medical University, 19 cases in Xiangya Hospital, Central South University, 23 cases in Zhejiang Cancer Hospital, 17 cases in Liaoning Cancer Hospital＆Institute, 17 cases in the First Affiliated Hospital of Xiamen University, 15 cases in Sun Yat-sen University Cancer Center, 14 cases in the First Affiliated Hospital of Nanjing Medical University, 14 cases in Zhongshan Hospital Affiliated to Xiamen University and 8 cases in General Hospital of Chinese People′s Liberation Army Air Force, from January 2010 to April 2020 were collected. There were 346 males and 395 females, aged 55(range, 17?86)years. Observation indicators: (1) neoadjuvant treatment; (2) surgical and postoperative situations; (3) follow-up; (4) stratified analysis. Follow-up was conducted using outpatient examination or telephone interview. Patients were followed up once every 3?6 months during neoadjuvant therapy and once every 6?12 months after radical surgery to detect tumor recurrence and survival of patient up to April 2022. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, and the matching tolerance was 0.02. Results:(1) Neoadjuvant therapy. Of the 741 patients, 34 cases received neoadjuvant therapy for 8(range, 3?44)months. Cases assessed as partial response, stable disease and progressive disease before the radical surgery of the 34 cases were 21, 9, 4, respectively. The tumor diameter of the 34 patients before the neoadjuvant therapy and before the radical surgery were 8.0(range, 3.0?26.0)cm and 5.3(range, 3.0?18.0)cm, with the regression rate as 31.9%(range, ?166.7% to 58.3%). (2) Surgical and postoperative situations. Of the 741 patients, 34 cases underwent radical surgery after receiving neoadjuvant therapy, and 707 cases underwent radical surgery directly. All the 741 patients underwent radical surgery successfully, in which 633, 102 and 6 cases received open surgery, laparoscopic surgery and endoscopic treatment, respectively. Of the 633 cases receiving open surgery and the 102 cases receiving laparoscopic surgery, cases with surgical resection range as pancreatoduodenectomy (PD) was 238, and cases with surgical resection range as duodenal limited resection, including duodenal wedge resection, distal gastrectomy, segmental duodenal resection, local resection of duodenal tumor or segmental duodenum combined with subtotal gastrectomy, was 497, 226, 55, 204, 12. Of the 741 patients, 131 cases had post-operative complications including 113 cases with grade Ⅰ?Ⅱ complications and 18 cases with ≥ grade Ⅲ complications of the Clavien-Dindo classification. The duration of postoperative hospital stay of the 741 patients was 13(range, 4?120)days. Of the 707 patients receiving direct radical surgery, 371 cases were evaluated as extremely low risk, low risk, medium risk of the modified National Institutes of Health (NIH) risk classification after surgery, and 336 cases were evaluated as high risk in which 205 cases receive postoperative adjuvant imatinib therapy with the treatment time as 24(range, 6?110)months. (3) Follow-up. All the 741 patients were followed up for 58(range, 7?150)months. During the follow-up, 110 patients had tumor recurrence and metastasis. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 741 patients were 100.0%, 98.6%, 94.5% and 98.4%, 90.9%, 84.9%, respectively. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 707 patients receiving direct radical surgery were 100.0%, 98.5%, 94.3% and 98.4%, 91.1%, 85.4%, respectively. (4) Stratified analysis. ① Analysis of prognostic factors in patients undergoing radical surgery directly. Results of univariate analysis showed that primary tumor location, tumor diameter, mitotic count, modified NIH risk classification and tumor gene information were related factors affecting the overall survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.43, 0.18, 0.22, 0.06, 0.29, 95% confidence intervals as 0.20?0.93, 0.09?0.35, 0.10?0.50, 0.03?0.12, 0.09?0.95, P<0.05). The primary tumor location, tumor diameter, mitotic count, modified NIH risk classification were related factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.65, 0.25, 0.25, 0.10, 95% confidence intervals as 0.41?1.03, 0.17?0.37, 0.15?0.42, 0.07?0.15, P<0.05). Results of multivariate analysis showed that primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation were independent risk factors affecting the overall survival of 365 patients with primary duodenal GIST after removing 342 patients without tumor gene information who underwent direct radical surgery ( hazard ratio=2.85, 2.73, 3.13, 95% confidence intervals as 1.12?7.20, 1.07?6.94, 1.23?7.93, P<0.05). Tumor diameter >5 cm and mitotic count >5/50 high power field were independent risk factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=3.19, 2.98, 95% confidence intervals as 2.05?4.97, 1.99?4.45, P<0.05). ② Effect of postoperative adjuvant therapy on prognosis of high-risk patients of modified NIH risk classification. Of the 336 patients evaluated as high risk of the modified NIH risk classification, the 5-year overall survival rate and 5-year disease-free survival rate were 94.6% and 77.3% in the 205 cases with postoperative adjuvant therapy, versus 83.2% and 64.4% in the 131 cases without postoperative adjuvant therapy, showing significant differences between them ( χ2=8.39, 4.44, P<0.05). Of the 205 patients evaluated as high risk of the modified NIH risk classification who received postoperative adjuvant therapy, there were 106 cases receiving postoperative adjuvant therapy <36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 87.1% and 58.7%, and there were 99 cases receiving post-operative adjuvant therapy ≥36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 100.0% and 91.5%. There were significant differences in the 5-year overall survival rate and 5-year disease-free survival rate between the 106 patients and the 99 patients ( χ2=13.92, 29.61, P<0.05). ③ Comparison of clinical efficacy of patients with different surgical methods. Before propensity score matching, cases with primary tumor located at bulb, descending, horizontal, ascending segment of duodenum, cases with tumor diameter ≤5 cm and >5 cm were 95, 307, 147, 34, 331, 252, in the 583 patients receiving open surgery with complete clinical data, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery with complete clinical data, showing no significant difference in the primary tumor location ( χ2=0.94, P>0.05), and a significant difference in the tumor diameter ( χ2=17.33, P<0.05) between them. After propensity score matching, the above indicator were 16, 39, 20, 8, 67, 16 in the 83 patients receiving open surgery, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery, showing no significant difference between them ( χ2=1.54, 0.00, P>0.05). Cases with postoperative complications, cases with grade Ⅰ?Ⅱ complica-tions and ≥grade Ⅲ complications of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 17, 12, 5, 11(range, 5?120)days, 92.0%, 100.0% in the 83 patients receiving open surgery, versus 9, 7, 2, 11(range, 5?41)days, 91.6%, 97.3% in the 83 patients receiving laparoscopic surgery, showing no signi-ficant difference in postoperative complications, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=2.91, Z=3 365.50, χ2=3.02, 1.49, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification between them ( P>0.05). ④ Comparison of clinical efficacy of patients with primary tumor located at the descending segment of duodenum who underwent surgery with different surgical resection scopes. Before propensity score matching, cases with tumor diameter ≤5 cm and >5 cm, cases with tumor located at opposite side of mesangium and mesangium were 71, 85, 28, 128 in the 156 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 92, 41, 120, 13 in the 133 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing significant differences between them ( χ2=16.34, 150.10, P<0.05). After propensity score matching, the above indicator were 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference between them ( χ2=0.00, 0.00, P>0.05). Cases with postopera-tive complications, cases with grade Ⅰ?Ⅱ complications and ≥grade Ⅲ compli-cations of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 13, 11, 2, 15(range, 9?62)days, 94.2%, 64.3% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 9, 8, 0, 15(range, 7?40)days, 100.0%, 78.8% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference in post-operative complica-tions, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=0.99, 0.34, 1.86, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification ( P>0.05) and there was a significant difference in duration of postopera-tive hospital stay ( Z=614.50, P<0.05) between them. Conclusions:The clinical efficacy of radical surgery for duodenal GIST are ideal. Primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation are independent risk factors affec-ting the overall survival of patients undergoing direct radical surgery and tumor diameter >5 cm and mitotic count >5/50 high power field are independent risk factors affecting the disease-free survival of patients. There is no significant difference in the short-term efficacy and long-term prognosis between patients undergoing open surgery and laparoscopic surgery. For patients with primary tumor located at the descending segment of duodenum, the duration of postoperative hospital stay is longer in patients undergoing PD compared with patients undergoing duodenal limited resection. For patients evaluated as high risk of the modified NIH risk classification, posto-perative adjuvant therapy and treatment time ≥36 months are conducive to improving the prognosis of patients.

Objective:To investigate the effect of L-carnitine on myocardial ischemia-reperfusion injury in patients undergoing coronary artery bypass grafting (CABG) operation.Methods:The clinical data of 60 patients who had underwent CABG under extracorporeal circulation in Department of Cardiovascular Surgery, the First Affiliated Hospital of Medical College of Xi′an Jiaotong University from January 2015 to December 2017 was retrospectively analyzed. L-carnitine was infused into the patients in the observation group while the equal amount of normal saline was given to the patients in the control group during perioperative period. Venous blood was collected from each patient 1 hour before the surgery and at 2, 6, 24 and 72 hours after unclamping the aorta, then serum levels of aspartate aminotransferase (AST), lactic acid dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB isozyme (CK-MB) were detected. Additionally, cardiac function indices including stroke volume (SV), left ventricular diastolic diameter (LVDD), cardiac output (CO), Left ventricular ejection fraction (lVEF) were compared between the two group patients before the surgery and 6 days after operation.Results:Compared with before the operation, the levels of serum enzymes were all significantly increased after unclamping the aorta. The levels of serum AST, LDH and CK reached their peak at 24 hours after unclamping the aorta. Notably, the levels of serum AST, LDH and CK in the experimental group were lower than that in the control group at each time point after unclamping the aorta ( P<0.05). For serum CK-MB, the level in the experimental group reached its peak at 6 hours after unclamping the aorta, while the peak value was observed at 24 hours after unclamping the aorta in the control group. The level of CK-MB in the experimental group was significantly decreased compared with the control group at each time point after unclamping the aorta ( P<0.05). Moreover, there were no significant differences in cardiac function indices between the 2 groups before the operation ( P>0.05). The levels of SV, CO and LVEF in the experimental group were significantly increased while the level of LVDD was obviously decreased compared to that in the control group after the operation ( P<0.05). Conclusions:L-carnitine has protective effects on myocardial ischemia-reperfusion injury in patients undergoing CABG operation under cardiopulmonary bypass, with reducing serum levels of myocardial enzyme in these patients.

Objective To investigate the difference of curative effects and prognosis between coronary artery bypass grafting with and without cardiopulmonary bypass.Methods 152 patients who were operated using off-pump coronary artery bypass grafting (OPCABG) and 107 patients who were performed with on-pump coronary artery bypass grafting (CABG) in the authors'department during the period from October 2013 to October 2017 were included in the study.The differences of postoperative recovery and major complications between the two groups were analyzed.Results Compared with CABG group,patients in OPCABG group had shorter intensive care unit (ICU) monitoring time,electrocardio-monitoring time,duration of antibiotic treatment,time of drainage tube intubation,mechanical ventilation time,arterial piezometer tube monitoring time and length of hospital stay (P ＜ 0.05).And postoperative draining fluid volume in patients of OPCABG group was also less than that in CABG group (P ＜ 0.05).Additionally,there was no difference between the two groups in postoperative parameters including renal insufficiency,using intra-aortic balloon pump (IABP) machine,perioperative myocardial infarction,second operation for hemorrhage,the occurrence of postoperative arrhythmias and cerebrovascular accident (P ＞ 0.05).However,the incidence of postoperative pulmonary infection was significantly higher in patients of CABG group than that in OPCABG group (P ＜ 0.05).Conclusions The incidence of postoperative pulmonary infection was significantly decreased in OPCABG group compared with that in CABG group.And the postoperative recovery of patients undergoing off-pump coronary artery bypass grafting was superior to that of patients undergoing onpump coronary artery bypass grafting.

Objective To investigate the effect of intravenous drip of levocarnitine during perioperative period on serum cytokines and cardiac troponin (cTn) I in patients undergoing coronary artery bypass grafting (CABG) under extracorporeal circulation. Methods The clinical data of 70 patients who had underwent CABG under extracorporeal circulation in Department of Cardiovascular Surgery, the First Affiliated Hospital of Medical College of Xi′an Jiaotong University from January 2015 to December 2017 were retrospectively analyzed. Among them, 35 cases were treated with intravenous infusion of levocarnitine (experiment group), and 35 cases were not treated with intravenous infusion of levocarnitine (control group). The serum levels of cTnI, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and IL-10 1 h before operation and 2, 6, 24, 72 h after aorta open were detected; the postoperative recovery and complication were recorded. Results There were no statistical differences in TNF-α, IL-6, IL-8, IL-10 and cTnI before operation between 2 groups (P＞0.05); the indexes 2, 6, 24 and 72 h after aorta open were significantly higher than those before operation, and there were statistical differences (P＜0.05). The TNF-α, IL-6 and cTnI 2, 6, 24 and 72 h after aorta open in experiment group were significantly lower than those in control group, and the IL-10 was significantly higher than that in control group; the IL-8 2, 6 and 24 h after aorta open in experiment group were significantly lower than that in control group, and there were statistical differences (P＜0.05). The ICU monitoring time, electrocardio-monitoring time, duration of antibiotic treatment, duration of drainage tube, mechanical ventilation time and length of hospital stay in experiment group were significantly shorter than those in control group: (2.9 ± 0.5) d vs. (3.5 ± 0.8) d, (5.7 ± 1.8) d vs. (7.6 ± 3.2) d, (6.7 ± 1.5) d vs. (9.8 ± 2.2) d, (3.1 ± 0.8) d vs. (3.9 ± 1.4) d, (3.3 ± 2.1) d vs. (5.1 ± 2.3) d and (8.1 ± 2.2) d vs. (12.8 ± 2.6) d, and there were statistical differences (P＜0.01). Moreover, there were no severe perioperative complications such as myocardial infarction and pulmonary infection in 2 groups. Conclusions Intravenous drip of levocarnitine during perioperative period could effectively control postoperative inflammatory response and myocardial injury in patients undergoing CABG under extracorporeal circulation. The effect of levocarnitine may be related to its ability to balance the levels between proinflammatory cytokines and anti-inflammatory cytokines.

Objective: To investigate the effect of Calcium dibutyryladenosine cyclophosphate on myocardial ischemia-reperfusion injury in patients undergoing coronary artery bypass grafting (CABG) operation. Methods: The clinical data of 62cases were retrospectively analyzed. These patients were performed coronary artery bypass graft (CABG) operation under cardiopulmonary bypass (CPB) in the First Affiliated Hospital of Medical College of Xi′an Jiaotong University from January 2013 to January 2016. According to the use calcium dibutyryladenosine cyclophosphate, 62 patients were divided into the control group and the experimental group. Thirty-one cases in the experimental group were given an intravenous drip of calcium dibutyryladenosine cyclophosphate, while other 31 cases in the control group were not given to calcium dibutyryladenosine cyclophosphate during perioperative period. Venous blood was collected from each patient 1 h before the surgery and 2, 6, 24 and 72 h after unclamping the aorta, then serum levels of aspartate aminotransferase (AST), lactic acid dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB isozyme (CK-MB) were detected. Additionally, cardiac function indices including SV, LVDD, CO, LVEF in these patients were recorded before the operation and 6 days after operation. Results: Compared with those before the operation, the levels of serum enzymes were all significantly increased after unclamping the aorta. The levels of serum AST, LDH and CK reached their peak 24 h after unclamping the aorta. Notably, the levels of serum AST, LDH and CK in the experimental group were lower than those in the control group at each time point after unclamping the aorta (P < 0.05). For serum CK-MB, the level in both the two groups reached its peak 6 h after unclamping the aorta. The level of CK-MB in the experimental group was significantly decreased compared with that in the control group 6, 24 and 72 h after unclamping the aorta (P < 0.05). Moreover, there were no significant differences in cardiac function indices between the 2 groups before the operation (P > 0.05). The levels of SV, CO and LVEF in the experimental group were significantly increased while the level of LVDD was obviously decreased compared to that in the control group after the operation, SV: (70.93 ± 9.72) ml vs. (65.07 ± 6.81) ml, CO: (5.32 ± 0.98) L vs. (4.29 ± 0.91) L, LVEF: (57.87 ± 8.92)% vs. (52.68 ± 7.31)% and LVDD: (55.67 ± 4.12) mm vs. (62.85 ± 5.71) mm, and there were statistical differences (P < 0.05). Conclusions Calcium dibutyryladenosine cyclophosphate has protective effects on myocardial ischemia-reperfusion injury and cardiac function in patients undergoing CABG operation under CPB, by reducing serum levels of myocardial enzymes in these patients.

Objective: To investigate the impact of aortic root morphology on the implantation depth of aortic valve prosthesis during trans-catheter aortic valve replacement (TAVR) in bicuspid aortic valve patients. Methods: Clinical data of 40 patients with native bicuspid aortic valve stenosis who underwent TAVR using the self-expandable prosthesis (the Venus A-valve) from 2014 to 2017 in Fuwai Hospital was retrospectively analyzed. The patients were divided into non-deep implantation group (implant depth ≤10 mm by instant angiogram after implantation,29 cases) and deep implantation group (implant depth> 10 mm by instant angiogram after implantation,11 cases).Pre-procedural aortic root characteristics (e.g. calcification, angle and dimensions) were assessed by CT. The impact of aortic root morphology on the implantation depth and clinical outcomes were also evaluated. Results: The age was (75.1±5.9) years with equal representation from the raphe-type and non-raphe type (52.5%(21/40) and 47.5%(19/40)).The bigger aorta angle ((56.5±4.5)° vs. (47.4±9.4)°, P=0.004),more frequent mild-calcification (HU850, <200 mm³) or severe-calcification(HU850, >1 000 mm³) of aortic leaflets (7/11 vs. 4/29, P=0.006), as well as higher ratio of left ventricular outflow tract perimeter to annulus perimeter ((109.2±7.5)% vs. (101.5±6.5)%, P=0.004) were found in the deep implantation group compared to the non-deep implantation group. The new in-hospital onset of bundle-branchheart-block or atrioventricular block conduction disturbance rate was higher in the deep implantation group than in the non-deep implantation group (6/11 vs. 2/29, P=0.030).Left ventricular ejection fraction was similar between deep implantation group and non-deep implantation group at baseline((49.9±8.9)% vs. (55.8±10.4)%, P=0.117), and was significantly lower in the deep implantation group than in the non-deep implantation group at 30 days after implantation ((51.6±12.8)% vs. (60.9±8.1)%, P=0.020). Conclusion Aortic root morphology of bicuspid aortic valve patients is associated with implantation depth of the prosthesis during TAVR, which affects the conduction system and left ventricular function during and post TAVR.

Nourishing kidney-yin (NKY) granules and warming kidney-yang (WKY) granules represent one of the prescriptions that prescribed in treating primary osteoporosis (POP) in light of tonifying kidney and nourishing essence principle as well as the theory of "treating both the disease and traditional Chinese medicine (TCM) syndrome".Both granules were created through the systematic analysis of clinic prescriptions by Professor Shi Qi.Consequently clinical investigations have well established that NKY granules significant improved bone mineral density (BMD) as well as relieved the kidney-yin deficiency syndromes in POP patients.Meanwhile,WKY granules relieve kidney-yang deficiency syndrome and the quality of life (QOL).What is more,pharmacological study established the application of common cnidium fruit,and fructus ligustri lucidi alleviated bone loss in OVX-induced mice.In addition,investigation with effective components identified that both NKY and WKY granules play systematic pharmacological effects on bone remodeling by regulating the expression of BMP/Smad,Wnt/β-catenin,RANKL/RANK/OPG axis,and Notch.The drug discovery was performed by the lead of traditional Chinese medicine (TCM) theory.It is one successful transformation investigation based on pharmacological effects,clinical intervention,animal model,cell culture and molecular investigation.