不同吸痰方法对机械通气患者气道影响及临床效应研究

目的:探讨密闭式和开放式吸痰方法对机械通气患者的影响及临床效应.方法:选择我院机械通气患者83例,随机分为密闭组和开放组,密闭组采用密闭式吸痰方法时机械通气患者进行吸痰,开放组采用开放式吸痰方法对机械通气患者进行吸痰.观察两组患者吸痰前后血氧饱和度(SpO2)的变化、呼吸道粘膜的损伤发生率及肺部感染发生率.结果:吸痰后密闭组呼吸道粘膜损伤发生率显著低于开放组(P＜0.01),肺部感染率显著低于开放组(P＜0.01).结论:密闭式吸痰在机械通气患者气道护理效果方面显著优于开放式吸痰,在机械通气气道护理工作中值得借鉴.     

不同治疗方式对冠心病合并心脏瓣膜炎患者血清炎性反应的影响

目的:比较不同治疗方式对冠心病合并心脏瓣膜炎的临床指标、生活质量及血清炎性反应的影响。方法:选取2014年2月~2016年6月期间于本院进行治疗的64例冠心病合并心脏瓣膜炎患者为研究对象,将其随机分为对照组和观察组每组各32例,对照组进行常规的药物治疗,观察组则进行外科手术治疗,然后将两组患者治疗前后的心脏功能指标、生活质量及血清炎性指标进行比较。结果:治疗前两组患者的心脏功能指标、生活质量及血清炎性指标比较,P均0.05,而治疗后观察组的心脏功能指标、生活质量及血清炎性指标均显著地好于对照组,P均0.05,均有显著性差异。结论:外科手术对冠心病合并心脏瓣膜炎患者血清炎症因子水平及生活质量具有积极的改善作用,适于临床进一步推广应用。     

Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing

Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes.     

Second Harmonic Generation Microscopy Probes Different States of Motor Protein Interaction in Myofibrils

The second harmonic generation (SHG) signal intensity sourced from skeletal muscle myosin II strongly depends on the polarization of the incident laser beam relative to the muscle fiber axis. This dependence is related to the second-order susceptibility χ⁽²⁾, which can be described by a single component ratio γ under generally assumed symmetries. We precisely extracted γ from SHG polarization dependence curves with an extended focal field model. In murine myofibrillar preparations, we have found two distinct polarization dependencies: With the actomyosin system in the rigor state, γ_rig has a mean value of γ_rig = 0.52 (SD = 0.04, n = 55); in a relaxed state where myosin is not bound to actin, γ_rel has a mean value of γ_rel = 0.24 (SD = 0.07, n = 70). We observed a similar value in an activated state where the myosin power stroke was pharmacologically inhibited using N-benzyl-p-toluene sulfonamide. In summary, different actomyosin states can be visualized noninvasively with SHG microscopy. Specifically, SHG even allows us to distinguish different actin-bound states of myosin II using γ as a parameter.     

氨甲环酸不同给药方式对心脏瓣膜置换术患者的效果差异和安全性分析

目的:探讨氨甲环酸不同给药方式对心脏瓣膜置换术患者的效果差异和安全性。方法:选择2016年7月至2019年11月我院接诊的112例接受体外循环下心脏瓣膜置换术的患者,通过随机数表法分为三组,A组38例,B组38例,C组36例。A组在切皮前给予氨甲环酸注射液10 mg/kg单次静脉推注,B组在切皮前给予氨甲环酸注射液10 mg/kg的单次静脉推注后,之后再以5mg/kg/h的速度持续静脉泵注,直至手术结束;C组不使用氨甲环酸。比较三组围术期情况、不同时间点凝血功能及引流量的变化,并评价安全性。结果:通过对三组患者的术后24 h出血量、输液量、异体红细胞输血例数和输血量进行对比,结果显示,A组和B组上述情况均比对照组少(P<0.05),但A组和B组患者上述情况经过比较显示,差异无统计学意义(P>0.05);在手术结束时(T1)、术后6 h(T2)、术后12 h(T3)、术后24 h(T4)时点时,A组和B组患者的血小板计数(PLT)、血红蛋白(Hb)、纤维蛋白原(FIB)水平的结果均比C组高,活化部分凝血活酶时间(APTT)、国际标准化比值(INR)、D-二聚体(D-D)水平的结果均明显比C组低(P<0.05),但A组和B组患者在上述时间点各指标进行比较,差异无统计学意义(P>0.05);A组和B组患者在T2、T3、T4时点时引流量均比对照组低(P<0.05),但是A组和B组术后各时间点引流量的比较结果显示,差异无统计学意义(P>0.05);A组和B组术后肾功能损伤发生率比较差异有统计学意义(P<0.05)。结论:氨甲环酸对心脏瓣膜置换术患者具有血液保护作用,但和单次静脉推注氨甲环酸相比,术中持续泵注氨甲环酸并没有进一步改善患者术后凝血功能、出血量及引流量,且有增加肾损伤的风险,在临床应用上应注意药物使用方式,为患者提供更安全的用药方式。     

体外循环预充还原型谷胱甘肽对心脏瓣膜置换术患者的临床研究

摘要 目的：观察体外循环（CPB）预充还原型谷胱甘肽（GSH）对心脏瓣膜置换术患者心肌损伤指标和炎症因子指标的影响。方法：选择2020年10月到2021年10月期间于我院行心脏瓣膜置换术治疗的180例患者。以随机数字表法分为对照组和研究组,均为90例。研究组患者CPB预充GSH 1200 mg,对照组患者预充等量氯化钠注射液。观察两组患者围术期指标、心肌损伤指标[肌酸激酶（CK）、乳酸脱氢酶（LDH）、肌钙蛋白Ⅰ（cTnⅠ）、肌红蛋白（Mb）]、炎症因子指标[肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）]变化,并记录两组并发症发生情况。结果：研究组术中转流时间、呼吸机使用时间、ICU留置时间、术后多巴胺使用天数短于对照组,术后多巴胺使用总量少于对照组（P<0.05）。主动脉开放后2 h、12 h、24 h,两组CK、LDH、cTnⅠ、Mb水平均升高后下降（P<0.05）,且研究组CK、LDH、cTnⅠ、Mb水平低于对照组（P<0.05）。主动脉开放后2 h、12 h、24 h,两组IL-6、TNF-α水平均升高后下降（P<0.05）,且研究组IL-6、TNF-α水平低于对照组（P<0.05）。研究组的并发症发生率低于对照组（P<0.05）。结论：CPB预充GSH可减轻心脏瓣膜置换术患者心肌损伤,有效控制炎症反应,同时还可降低并发症发生率,缩短呼吸机使用时间、术中转流时间、ICU留置时间、术后多巴胺使用天数,减少术后多巴胺使用总量,效果显著。     

Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement

Objective

To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement.

Methods

We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms.

Results

A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88–4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges.

Conclusions

All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement.     

Using Adaptive Methods to Select Variables in Case‐Control Studies

A variables selection method for case‐control studies is proposed that uses an adaptive weighting scheme along with a permutation method to determine if a variable is useful in differentiating the cases from the controls. This adaptive method is used to select exposure variables for the analysis of data from a bladder cancer case‐control study. An extensive simulation study shows that the adaptive method is nearly as effective at finding those variables that are related to case‐control status when normally distributed variables are used. The simulation also shows that the proposed variable selection procedure is much more effective than the stepwise discriminant analysis method when the variables are not normally distributed. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

不同超滤方式对体外循环瓣膜置换术后患者心肺功能、补体和炎性介质的影响

摘要 目的：探讨不同超滤方式对体外循环（CPB）瓣膜置换术后患者心肺功能、补体和炎性介质的影响。方法：选择2018年1月~2022年6月于广西中医药大学附属瑞康医院接受CPB瓣膜置换术治疗的患者130例,应用随机数字表法将其分为常规超滤组（n=31）、改良超滤组（n=34）、零平衡超滤组（n=32）和联合组（改良超滤联合零平衡超滤）（n=33）。观察各组患者超滤前（T1）、超滤即刻（T2）、超滤后2 h（T3）、超滤后6 h（T4）心脏输出量（CO）、心脏指数（CI）、氧合指数（OI）、呼吸指数（RI）及肺静态顺应性（Cstat）,并比较不同时间点各组患者血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、补体3a（C3a）、补体5a（C5a）水平。结果：T2、T3、T4时间点联合组CO和CI水平高于其他三组（P<0.05）。T2、T3、T4时间点联合组RI水平低于其他三组,OI和Cstat水平高于其他三组（P<0.05）。T2、T3、T4时间点联合组IL-6、C3a、C5a水平均低于其他三组,且TNF-α水平低于常规超滤组及改良超滤组（P<0.05）。结论：相对常规超滤、改良超滤、零平衡超滤,改良超滤联合零平衡超滤对CPB瓣膜置换术后患者心肺功能影响较小,术后炎症介质、补体水平升高程度较低,滤过效果明显,更适于CPB瓣膜置换术。     

Predicting 7-Day Survival Using Heart Rate Variability in Hospice Patients with Non-Lung Cancers

Background

A simple and accurate survival prediction tool can facilitate decision making processes for hospice patients with advanced cancers. The objectives of this study were to explore the association of cardiac autonomic functions and survival in patients with advanced cancer and to evaluate the prognostic value of heart rate variability (HRV) in 7-day survival prediction.

Methods

A prospective study was conducted on 138 patients with advanced cancer recruited from the hospice ward of a regional hospital in southern Taiwan. Information on functional status and symptom burden of the patients was recorded. Frequency-domain HRV was obtained for the evaluation of cardiac autonomic functions at admission. The end point of the study was defined as the survival status at day 7 after admission to the hospice ward. Multivariate logistic regression analyses were performed to evaluate the independent associations between HRV indices and survival of 7 days or less.

Results

The median survival time of the patients was 20 days (95% CI, 17–28 days). Results from the multivariate logistic regression analysis indicated that the natural logarithm-transformed high-frequency power (lnHFP) of a value less than 2 (OR = 3.8, p = 0.008) and ECOG performance status of 3 or 4 (OR = 3.4, p = 0.023) were significantly associated with a higher risk of survival of 7 days or less. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve was 0.71 (95% CI, 0.61–0.81).

Conclusions

In hospice patients with non-lung cancers, an lnHPF value below 2 at hospice admission was significantly associated with survival of 7 days or less. HRV might be used as a non-invasive and objective tool to facilitate medical decision making by improving the accuracy in survival prediction.     

Serum Lipoprotein Abnormalities in Patients with Ischaemic Heart Disease: Comparisons with a Control Population

The frequency and nature of abnormalities of serum lipoproteins have been studied, using quantitative techniques, in 143 patients with ischaemic heart disease (I.H.D.). Rigorous selection criteria were used. The findings were related to the distribution of lipoprotein concentrations in a carefully screened control population. Hyperlipoproteinaemia occurred in 55% of patients and in 11 out of 15 patients aged less than 40 years. Raised triglyceride and cholesterol concentrations in very low density lipoprotein were the most frequent abnormalities followed by raised cholesterol content of low density lipoprotein. In young patients high density lipoprotein levels were subnormal. Hyperlipoproteinaemia of W.H.O. types IIa, IIb, III, IV, and V all seemed to be over-represented in I.H.D. I.H.D. patients with type IIa, IIb, and IV abnormalities were all significantly younger than I.H.D. patients with normal lipoprotein levels.     

Development of Methods and Techniques to Visualize Mechanical Tension in Embryos Using Genetically Encoded Fluorescent Mechanosensors

Russian Journal of Developmental Biology - Lately, the growing body of quantitative data has provided evidence of the importance of mechanical forces in embryogenesis. The study of spatial and...     

Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8⁺ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 10⁶). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1_126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1_950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.     

不同剂量氟伐他汀对冠心病伴血脂增高患者的临床作用研究

目的:观察不同剂量氟伐他汀对冠心病伴血脂增高患者的临床效果及安全性,为临床治疗提供依据。方法:选择我院2010年5月~2013年2月收治的96例冠心病伴高脂血症患者并将其进行随机分组,即20 mg及40 mg氟伐他汀治疗组各48例,观察和比较两组的临床疗效及不良反应的发生情况。结果:经4周、8周治疗后,两组患者的总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)的水平均较同组治疗前显著降低,差异均具有统计学意义(P0.05);高密度脂蛋白胆固醇(HDL-C)均较同组治疗前明显升高,差异有统计学意义(P0.05);40 mg组hs-CRP含量下降,较20mg组显著,差异明显具有统计学意义(P0.05)。结论:对于冠心病伴血脂增高患者,采用高剂量氟伐他汀进行降脂治疗临床疗效较好,且安全性高,建议推广应用。     

房水平单向活瓣式补片对老年先天性心脏病合并重度肺动脉高压 的临床效果分析

目的:探究房水平单向活瓣式补片对老年先天性心脏病伴重度肺动脉高压患者的作用疗效。方法:选取我院心血管科收治的先天性心脏病伴重度肺动脉高压患者80例,随机分为对照组和实验组。对照组40例,予以常规基础药物治疗(波生坦);实验组,在基础药物治疗两个疗程后,采用房水平单向活瓣式补片进行手术治疗。比较两组患者治疗前后的肺动脉压(PAP)、体动脉压(SAP)、肺动脉压/体动脉压(PAP/SAP)、动脉血氧分压(Pa O2)、二氧化碳分压(Pa CO2)及吸氧浓度、右室收缩末期内径变化情况。结果:治疗后,与对照组比较,实验组肺动脉压下降幅度较大(P0.05);与治疗前比较,实验组肺动脉压与体动脉压的比值显著下降,且优于对照组(P0.05);治疗后,实验组动脉血氧分压、二氧化碳分压以及吸氧浓度显著优于对照组(P0.05);治疗后,实验组患者右室收缩末期内径显著小于对照组(P0.05);随访结果:实验组死亡1例、术后活瓣坏死2例、其余37例病情均转好且无复发情况;对照组死亡4例、出现各项并发症16例、剩余20例病情转好。结论:房水平单向活瓣式补片法可有效改善患者的肺动脉压、体动脉压、动脉血氧分压、二氧化碳分压及吸氧浓度、右室收缩末期内径及6 min步行距离,对老年先天性心脏病伴重度肺动脉高压患者疗效显著。     

Fast Simulation of Mechanical Heterogeneity in the Electrically Asynchronous Heart Using the MultiPatch Module

Cardiac electrical asynchrony occurs as a result of cardiac pacing or conduction disorders such as left bundle-branch block (LBBB). Electrically asynchronous activation causes myocardial contraction heterogeneity that can be detrimental for cardiac function. Computational models provide a tool for understanding pathological consequences of dyssynchronous contraction. Simulations of mechanical dyssynchrony within the heart are typically performed using the finite element method, whose computational intensity may present an obstacle to clinical deployment of patient-specific models. We present an alternative based on the CircAdapt lumped-parameter model of the heart and circulatory system, called the MultiPatch module. Cardiac walls are subdivided into an arbitrary number of patches of homogeneous tissue. Tissue properties and activation time can differ between patches. All patches within a wall share a common wall tension and curvature. Consequently, spatial location within the wall is not required to calculate deformation in a patch. We test the hypothesis that activation time is more important than tissue location for determining mechanical deformation in asynchronous hearts. We perform simulations representing an experimental study of myocardial deformation induced by ventricular pacing, and a patient with LBBB and heart failure using endocardial recordings of electrical activation, wall volumes, and end-diastolic volumes. Direct comparison between simulated and experimental strain patterns shows both qualitative and quantitative agreement between model fibre strain and experimental circumferential strain in terms of shortening and rebound stretch during ejection. Local myofibre strain in the patient simulation shows qualitative agreement with circumferential strain patterns observed in the patient using tagged MRI. We conclude that the MultiPatch module produces realistic regional deformation patterns in the asynchronous heart and that activation time is more important than tissue location within a wall for determining myocardial deformation. The CircAdapt model is therefore capable of fast and realistic simulations of dyssynchronous myocardial deformation embedded within the closed-loop cardiovascular system.     

不同剂量阿托伐他汀钙短期应用对冠状动脉粥样硬化性心脏病患者血清 胆红素水平的影响

目的:探讨不同剂量阿托伐他汀钙短期应用对冠状动脉粥样硬化性心脏病患者血清胆红素水平的影响。方法:按照详细的纳入及排除标准的筛选共计264例冠状动脉粥样硬化性心脏病患者入选,分为20 mg和40 mg治疗剂量组,观察患者用药前后胆红素水平的变化水平的改变。结果:与服药前的相比,服用阿托伐他汀钙40 mg和20 mg的患者血清总胆红素、直接胆红素水平均呈显著性上升(P0.05),而间接胆红素水平差异无显著性。服药1个月后,40 mg组患者血清总胆红素、直接胆红素水平升高较20 mg组更显著(P0.05),但两组间接胆红素水平差异没有显著性。总胆红素变化率与患者胆固醇水平呈显著相关性,其20mg组为0.419,40 mg组为0.634(P0.001)。结论:阿托伐他汀钙治疗冠状动脉粥样硬化性心脏病患者可导致其血清总胆红素和直接胆红素水平升高,且高剂量较低剂量对总胆红素和直接胆红素的影响更明显。