Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

OBJECTIVE: To study the trend of surgical type, surgical procedure and etiological distribution of upper urinary tract repair in recent 10 years. METHODS: The preoperative and perioperative variables and follow-up data of upper urinary tract reconstruction surgery in RECUTTER (Reconstruction of Urinary Tract: Technology, Epidemiology and Result) database from 2010 to 2021 were searched, collected and analyzed. The surgical type, surgical procedure, duration of hospitalization, time of operation, incidence of short-term complications, and proportion of the patients undergoing reoperations were compared between the two groups of 2010-2017 period and 2018-2021 period. RESULTS: A total of 1 072 patients were included in the RECUTTER database. Congenital factors and iatrogenic injuries were the main causes of upper urinary tract repair. Among them, 129 (12.0%) patients had open operation, 403 (37.6%) patients had laparoscopic surgery, 322 (30.0%) patients had robot-assisted laparoscopic surgery and 218 (20.3%) patients had endourological procedure. In the last decade, the total number of surgeries showed a noticeable increasing annual trend and the proportion of robot-assisted laparoscopic surgery in 2018-2021 was significantly higher than that in 2010-2017 (P < 0.001). The 1 072 patients included 124 (11.6%) cases of ileal ureter replacements, 440 (41.1%) cases of pyeloplasty, 229 (21.4%) cases of balloon dilation, 109 (10.2%) cases of ureteral reimplantation, 49 (4.6%) cases of boari flap-Psoas hitch surgery, 60 (5.6%) cases of uretero-ureteral anastomosis, 61 (5.7%) cases of lingual mucosal onlay graft ureteroplasty or appendiceal onlay flap ureteroplasty. Pyeloplasty and balloon dilatation had been the main types of surgery, while the proportion of lingual mucosal onlay graft ureteroplasty plus appendiceal onlay flap ureteroplasty had increased significantly in recent years (P < 0.05). In addition, the time of operation was significantly increased (P < 0.05) after 2018, which was considered to be related to the sharp increase in the proportion of robot-assisted laparoscopic surgery. We found that minimally invasive surgery (endourological procedure and robot-assisted laparoscopic surgery) as an independent risk factor (P=0.050, OR=0.472) could reduce the incidence of short-term post-operative complications. CONCLUSION We have justified the value of the RECUTTER database, created by the Institute of Urology, Peking University in data support for clinical research work, and provided valuable experience for the construction of other multi-center databases at home and abroad. In recent 10 years, we have observed that, in upper urinary tract reconstruction surgery, the surgery type tends to be minimally invasive and the surgery procedure tends to be complicated, suggesting the superiority of robot-assisted laparoscopic surgery.
Humans ; Laparoscopy/methods* ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome ; Ureter/surgery* ; Ureteral Obstruction/surgery* ; Urologic Surgical Procedures/methods*

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*

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.

OBJECTIVETo observe the biomechanical effects of the lateral wall of the femur in treating femoral intertrochanteric fractures with intramedullary or extramedullary fixation to guide the choice of clinical fixed methods.

METHODSTwelve adults femur specimens of intertrochanteric fractures were belong to the type A1 of the AO fracture classification and randomly divided into the lateral wall complete PFNA group, the lateral wall complete PF-LCP group, the lateral wall breakage PFNA group, lateral wall breakage PF-LCP group, every group had 3 specimens. The four groups of specimens were subjected to compressive loading experiment with Universal Material Testing Machine. The maximum loading force was observed. The distance between fracture ends, the distance of fracture dislocation and the sliding distance of the fracture fragments along the intertrochanteric were measured with Calipers.

RESULTSThe maximum loading force of lateral wall complete PFNA group were larger than that of lateral wall complete PF-LCP group, and the maximum loading force of lateral wall breakage PFNA group were larger than that of lateral wall breakage PF-LCP group, there were significant differences (<0.05). The distance between fracture ends of the four groups before compression were not significant differences(>0.05). The distance between fracture ends, the distance of fracture dislocation and the sliding distance of the fracture fragments were not significant differences between lateral wall complete PFNA group and lateral wall complete PF-LCP group after compression (>0.05). But the distance between fracture ends, the distance of fracture dislocation and the sliding distance of the fracture fragments of lateral wall breakage PFNA group were less than that of lateral wall breakage PF-LCP group(<0.05).

CONCLUSIONSIntramedullary fixation of intertrochanteric fractures have stronger loading force. Both intramedullary and extramedullary fixation of intertrochanteric fractures have strong stability when the lateral wall of the femur is complete, but intramedullary fixation of intertrochanteric fractures is stronger stability than extramedullary fixation when the lateral wall of the femur is broken. So the intramedullary fixation is the first choice for the treatment of intertrochanteric fracture.

OBJECTIVETo establish double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of human soluble VE-cadherin in human plasma and to investigate its value in clinical use.

METHODSThe monoclonal antibodies against human VE-cadherin were prepared from BALB/c mice immunized with prokaryotic expression recombinant proteins, and the best combination of double antibodies was selected by checkerboard titration method. Double antibody sandwich ELISA for the determination of human VE-cadherin was established by using HRP-labeled McAb as a detection antibody and a capture antibody. The methodology performance was evaluated. The plasma concentrations of VE-cadherin in 28 healthy subjects and 60 patients with cancer were determined.

RESULTSThe double antibody sandwich ELISA for the determination of human VE-cadherin was established by selecting the combination of double antibodies. The detection limit was 24.7 pg/ml, the coefficients of variation for inner-batch and inter-batch were 4.1%-7.7% and 8.7%-10.8% respectively. The average recovery was 96.7%. The plasma level of soluble VE-cadherin in normal controls was 262.1±11.75 pg/ml. The plasma level of soluble VE-cadherin was 173.9±17.98 pg/ml in 24 patients with leukemia, 311.7±25.24 pg/ml in 14 patients with stomach cancer, 206.8±25.01 pg/ml in 11 patients with lung cancer, and 310.7±11.82 pg/ml in others patients(9 patients with breast cancer, 1 patients with gliomas, 1 patients with liver cancer).

CONCLUSIONThe developed ELISA kit has better sensitivity and specificity, and can be used in detection of human soluble VE-cadherin in human plasma, therefore, it can provide a new mathod for diagnosis of cancer patients.

Retinalvein occlusion (RVO) is the most common retinal vascular disease.The main causes of visual impairment and blindness are macular edema and retinal neovascularization.Drug therapies are the effective and safe method in the treatment of RVO currently.The main drugs conclude corticosteroid drugs,anti-vascular endothelial growth factor drugs,thrombolytic drugs and traditional drugs.This article reviews the recent progress in RVO in order to provide some valuable references for clinical treatment.

Objective To investigate the value of arterial spin labeling (ASL) MRI in evaluation of renal cortex perfusion in patients with type 2 diabetes.Methods Fifty patients with type 2 diabetes were enrolled and divided into simple diabetes (SD) group (n=25) and diabetes kidney disease (DKD) group (n=25) according to suffering from DKD or not.Based on estimated glomerular filtration rate (eGFR),DKD group were further divided into mild disease subgroup (n=11,eGFR≥ 60 ml/[min · 1.73m2]) and moderate-severe disease subgroup (n=14,eGFR＜60 ml/[min · 1.73m2]).Twenty-five healthy volunteers were recruited as control group at the same time.ASL MRI were performed on all participants.The cortical renal blood flow (RBF) of bilateral kidneys were measured by 2 radiologists.The consistency between 2 radiologists was analyzed.Statistical analysis were conducted to analysis the differences in cortical RBF among different groups.Correlation analysis were performed to evaluate the relationship between RBF and eGFR in type 2 diabetes patients.Results Cortical RBF values measured by two radiologists showed high consistency (all ICC＞0.90).There was significant difference in cortical RBF among control group ([269.71±33.28]ml/[100 g · min]),SD group ([258.52±42.30]ml/[100 g · min]),mild disease group ([242.86±56.86]ml/[100 g · min]) and moderate-severe disease group ([173.39±27.16]ml/ [100 g· min];F=20.66,P＜0.01).Moreover,the RBF in moderate-severe disease group was significantly lower than those in other groups (all P＜0.01).And no significant differences of RBF was found among the remainder groups (P=0.064,0.320).RBF in type 2 diabetes patients was positively correlated to eGFR (r=0.646,P＜0.001).Conclusion ASL MRI is a valuable tool to quantitatively assess the renal perfusion in patients with type 2 diabetes mellitus,which can provide potential imaging indicator as RBF for the functional evaluation of kidney.

OBJECTIVETo investigate the expression level of WT1 gene in bone marrow of patients with acute myeloid leukemia (AML) and its relationship with prognosis.

METHODSThe copy numbers of WT1 and internal reference gene in bone marrow samples from 75 newly diagnosed AML patients were detected by using real-time quantitative PCR. The gene WT1 expression level was determined by the ratio of the copy numbers of WT1 to reference gene. And the clinical characteristics, the complete remission (CR) rate after induction chemotherapy, 2-year overall survival (OS) rate and event-free survival (EFS) rate were calculated and analysed.

RESULTSThe expression level of WT1 did not significantly correlate with common clinical parameters such as age, sex, molecular abnormality, FAB classification and risk stratification. The CR rate in the high WT1 expression group before treatment was 65.4%, which was lower than that of 93.9% in the low expression group (χ2=8.25, P<0.01). The 2-year overall survival rate and event-free survival rate of the two groups were statistically significantly different (P<0.05), and the OS and EFS rates in high WT1 expression group were lower than those in low expression group. After the induction chamotheropy for about 1, 3 month and 6 months, the 2-year OS rate significantly increased in patients with decrease of WT1 gene expression level by one log or more (P<0.05).

CONCLUSIONThe expression level of WT1 gene in bone marrow may be an effective marker to evaluate therapy efficacy and prognosis for AML patients (non APL).

Bone Marrow ; metabolism ; Disease-Free Survival ; Genes, Wilms Tumor ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Prognosis ; Real-Time Polymerase Chain Reaction ; Remission Induction ; Survival Rate ; WT1 Proteins ; genetics ; metabolism