Development of an In Vitro Model to Characterize the Effects of Transcatheter Aortic Valve on Coronary Artery Flow

Impairment of coronary artery flow, in either acute or chronic conditions, is a severe complication of transcatheter aortic valve (TAV) implantation, which can arise due to improper TAV positioning. However, little work has been done to quantify the effects of the TAV positioning on the coronary flow. In this study, a realistic in vitro model of coronary artery flow was developed and used to investigate the impact of TAV deployed orientations on coronary flow. The coronary hemodynamics was first replicated mathematically using a lumped parameter model with time‐varying myocardial resistance. Based on the analytical model, two stepper motor controlled stopcock valves were integrated in a left heart simulator to represent the variable myocardial resistance in the experimental setup. The coronary flow and pressure waveforms obtained from the in vitro system were consistent with published data. With a TAV deployed in different orientations, the measured results demonstrated that TAV orientation does not have a significant impact on the coronary flow. The developed in vitro model can be further utilized to simulate coronary flow under various pathological conditions.     

神经节苷脂联合Bobath技术对脑卒中弛缓性瘫痪患者三维步态时空和表面肌电参数的影响

目的：观察神经节苷脂联合 Bobath技术对脑卒中弛缓性瘫痪患者三维步态时空和表面肌电参数的影响。方法将63例脑卒中弛缓性瘫痪患者分为A组31例、B组32例,A组采用Bobath技术、电针和中频治疗,B组在A组治疗基础上加用神经节苷脂治疗。治疗前后检测两组的三维步态时空参数（步速、支撑相、摆动相、双支撑相、步长）和患侧腓肠肌和胫前肌在踝关节屈伸最大等长收缩状态下表面肌电参数[均方根值（RMS）、肌电积分值（iEMG）、协同拮抗率（CR）]。结果治疗前,两组所有参数比较,差异均无统计学意义（P＞0．05）。治疗后两组的步速、支撑相、摆动相、双支撑相、RMS、iEMG、CR和B组的步长均较前改善（P＜0．05）;与A组比较,治疗后B组上述指标的改善更为明显（P＜0．05）。结论在常规治疗基础上,神经节苷脂联合Bobath技术能更好地改善脑卒中弛缓性瘫痪患者三维步态时空和表面肌电各项指标,疗效显著。     

Establishment and assessment of a novel in vitro bio-PK/PD system in predicting the in vivo pharmacokinetics and pharmacodynamics of cyclophosphamide

1.?A novel bio-pharmacokinetic/pharmacodynamic (PK/PD) system was established and assessed in predicting the PK parameters and PD effects of the model drug cyclophosphamide (CP) considering the interrelationships between drug metabolism, pharmacological effects and dynamic blood circulation processes in vitro.

2.?The system contains a peristaltic pump, a reaction chamber with rat liver microsomes (RLMs) encapsulated in pluronic F127–acrylamide–bisacrylamide (FAB) hydrogels, an effector cell chamber and a recirculating pipeline. The metabolism and pharmacological effects of CP (5, 10 and 20?mM) were measured by HPLC and MTT assay. A mathematical model based on mass balance was used to predict the in vitro clearance of CP. In vivo clearance of CP was estimated by in vitro to in vivo extrapolations (IVIVE) and simulations using Simcyp® software.

3.?The predicted in vivo clearance of CP at concentrations of 5, 10 and 20?mM was 11.36, 10.12 and 10.68?mL/min/kg, respectively, within two-fold differences compared with the reported 11.1?mL/min/kg. The survival ratio of effector cells during the metabolism and circulation of CP was significantly enhanced.

4.?This system may serve as an alternative approach to predict in vivo metabolism, pharmacological effects and toxicity of drugs, ensuring an efficient drug screening process.     

Being overweight or obese as a risk factor for acute liver injury secondary to acute acetaminophen overdose

Purpose

Increased incidences of hepatotoxicity have been observed in obese patients with acute acetaminophen overdose. We evaluate whether the status of being overweight or obese is associated with increase in the development of hepatotoxicity and acute liver injury (ALI) in patients with acute acetaminophen overdose.

Methods

This was a retrospective cohort study comparing the risk of hepatotoxicity and ALI between overweight or obese patients (body mass index [BMI] ≥ 25) and normal BMI patients (BMI ≤ 24.9) presenting with acute acetaminophen overdose at Siriraj Hospital during January 2004 to June 2012. All patients were treated with intravenous N‐acetylcysteine. Psi parameters were calculated. High psi was defined as psi of ≥5.0 mM‐hour. Data were analyzed using multinomial logistic regressions, odds ratio (OR), stratified OR, and 95% confidence interval (CI).

Results

There were 197 patients who fulfilled the criteria for analysis, 35 (17.8%) were obese, 24 (12.2%) were overweight, and 138 (70%) were normal BMI cases. Hepatotoxicity and ALI developed in 25 (12.7%) and 40 (20.3%) cases, respectively. Multinomial logistic regression revealed that the overweight‐obesity status and log₁₀(psi value) were significant risk factors of ALI, with OR (95% CI) of 2.68 (1.21‐5.95) and 1.74 (1.27‐2.38), respectively, while only log₁₀(psi) was a significant risk factor of hepatotoxicity with OR (95% CI) 378.51 (39.49‐3627.99). From stratification, overweight‐obesity had significant odds ratios for ALI in strata with low acetaminophen concentration, early initiation of N‐acetylcysteine and low psi.

Conclusion

We conclude that being overweight or obese is an independent risk factor of ALI in acute acetaminophen overdoses.     

精液参数对宫腔内人工授精妊娠结局的影响

目的探讨精液参数对宫腔内人工授精妊娠结局的影响,为需要IUI患者提供参考。方法回顾性分析2010年7月-2016年10月在吉林大学第一医院接受IUI治疗的511对不孕症夫妇,共完成1090个周期。比较分析男女双方年龄、不孕年限、原发性或继发性不孕、处理前精子的活力、浓度、总数、前向精子运动总数(TMS)及处理后前向运动精子活动总数(PTMS)与IUI临床妊娠率间的关系。结果1090个IUI周期共获得130个妊娠周期,周期妊娠率为11.93%,女方年龄、不孕年限在妊娠组与非妊娠组中比较差异有统计学意义(P<0.05)。处理前精子的活力、浓度、总数、TMS、PTMS等参数比较差异无统计学意义(P>0.05),多因素Logistic回归分析结果显示精液常规各项参数与临床妊娠率均无明显相关性(P>0.05)。结论在IUI中女方年龄、不孕年限可影响IUI临床妊娠率;各项精液参数与IUI临床妊娠率无明显相关性,不能有效预测此类型患者IUI的临床妊娠结局。     

一种简易可行的血液流变学参数处理方法

本文通过理论分析及冠心病患者的流变学数据观察说明只要测得全血在观粘度、血浆粘度及血细胞压积，即可通过简单的计算得到较全面、较理想地反映血液流变特性变化的指标。     

丹参提取过程动力学研究:模型建立及关键工艺参数考察

该研究以Fick第一扩散定律、分配平衡来表示丹参药材宏观层面内、外传质过程,建立传质模型,并将药材比表面积融合在传质阻力中,从而有效避免了药材形状不规则问题,扩大了模型适用范围。同时进一步将传质模型与酚酸降解动力学模型结合,建立丹酚酸B、紫草酸和丹参素的提取动力学模型。将模型应用于丹参提取过程研究,敏感性分析结果表明,在最大提取率(320 min)附近,模型预测相对误差在5%以内,模型预测性能较好。不同工艺参数考察结果表明,搅拌会显著加快丹酚酸B传质速率;溶剂倍量对丹酚酸B传质和降解无明显影响;温度的倒数与传质阻力对数值线性关系良好,决定系数为0.996,温度与传质阻力符合阿伦尼乌斯公式。研究结果表明,在较高提取温度(358 K以上)下,紫草酸和丹参素浓度变化受传质影响较弱,只需考虑降解对其浓度变化的影响。该研究为中药提取的工艺优化和质量控制提供了基础。     

高度发育不良性腰椎滑脱复位程度与脊柱-骨盆矢状位参数变化的关系

目的 :分析高度发育不良性腰椎滑脱(high dysplastic developmental spondylolisthesis,HDDS)的手术复位程度与脊柱-骨盆矢状位参数变化的关系,以了解复位至何种程度能够显著改善术后脊柱-骨盆矢状位序列。方法:回顾性分析2007年3月～2019年4月在我院骨科接受手术治疗的35例HDDS患者,滑脱节段均为L5,年龄14.9±5.9岁(9～35岁)。均行减压、部分复位或完全复位、椎弓根螺钉内固定融合术。随访42.5±33.1个月(3～120个月)。依据术后末次随访时的Dubousset腰骶角(Dubousset lumbosacral angle,Dub-LSA)将患者分为70°(7例)、70°～79.9°(8例)、80°～89.9°(4例)及≥90°(16例)四组,依据末次随访时滑脱的Meyerding分度将患者分为Ⅲ度及以上(5例)、Ⅱ度(6例)、Ⅰ度以内(24例)三组,分别对比各组的术前、末次随访时脊柱-骨盆参数的变化。结果:滑脱率术前为(66.7±22.5)%(35%～100%),末次随访时为(18.9±20.9)%(0%～72%);DubLSA术前为61.9°±14.7°,末次随访时82.1°±17.3°。末次随访时Dub-LSA越大、滑脱程度越低,脊柱-骨盆矢状位参数较术前改善越明显;直至Dub-LSA≥90°和滑移程度在Ⅰ度以内时,骨盆倾斜角(pelvic tilt,PT)和骶骨倾斜角(sacral slope,SS)均有显著性改善,由后倾型骨盆转变为平衡型骨盆的比例显著增加。Dub-LSA≥90°组术前与末次随访时PT分别为36.4°±6.5°与27.2°±4.9°(P0.001)、SS分别为33.5°±9.1°与42.1°±9.3°(P0.001)、平衡型骨盆比例分别为0%(0/16)与43.8%(7/16)(P=0.007),末次随访时与术前比较均有统计学差异。末次随访时滑脱程度在Ⅰ度以内组,术前与末次随访时PT分别为38.9°±8.6°与30.6°±7.4°(P0.001)、SS分别为31.4°±11.5°与41.2°±8.7°(P0.001)、平衡型骨盆比例分别为0%(0/24)与29.2%(7/24)(P=0.009),末次随访时与术前比较均有统计学差异。结论:将HDDS患者的Dub-LSA复位至≥90°和将滑移复位至Ⅰ度以内能够显著改善脊柱-骨盆矢状位参数,并且能够将部分(43.8%)后倾型骨盆改善为平衡型骨盆。     

The relationship between spinopelvic parameters and clinical symptoms of severe isthmic spondylolisthesis: a prospective study of 64 patients

Purpose

To investigate the relationship between spinopelvic parameters and clinical symptoms for patients with severe isthmic spondylolisthesis.

Methods

A series of spinopelvic parameters were measured in 64 patients with L5 severe isthmic spondylolisthesis. The patients were divided into two groups according to Oswestry score obtained preoperatively, i.e. mild or severe low back pain group. T test was used to compare parameters between two groups, and multiple linear regression analysis was employed to investigate the association between parameters and Oswestry score.

Results

Compared with two group patients, parameters of spondylolisthesis grade, pelvic tilt (PT), lumbar lordosis (LL), T9 tilting angle (T9TA), sacro-femoral horizontal distance (SFHD), distance between perpendicular line through C7 and sacrum (SC7D), pelvic tilt/sacral slope (PT/SS), sacro-femoral horizontal distance/vertical distance (SFHD/SFVD), and lumbar lordosis/thoracic kyphosis (LL/TK) were significantly increased in severe low back pain group, while SS and SFVD were significantly decreased, and no significant difference was found for pelvic incidence (PI) and TK. The statistical analysis showed that spondylolisthesis grade, PT, SC7D, LL, SFHD, PT/SS, SFHD/SFVD, and LL/TK had a significant positive correlation with Oswestry score, with an order of spondylolisthesis grade > PT/SS > SC7D > PT > SFHD/SFVD > SFHD > LL/TK > LL. No significant correlation was found for PI, TK, T9TA with Oswestry score, while SS and SFVD had a significant negative correlation with Oswestry score, with an order of SS > SFVD.

Conclusions

The spinopelvic parameters (spondylolisthesis grade, SS, PT, SC7D, LL, SFVD, SFHD, PT/SS, SFHD/SFVD, LL/TK) are significantly correlated with clinical symptoms of severe isthmic spondylolisthesis in patients. The association of the exacerbation of low back pain with SS (correlation coefficient −0.981, strong) and SFVD (correlation coefficient −0.802, strong) is the most significant correlation.