肺部小肿瘤射波刀与γ刀计划的剂量学比较

目的 比较肺部小肿瘤的射波刀与γ刀照射计划的剂量学特点。方法 选择20例肺部小肿瘤患者,分别做射波刀计划1及γ刀计划2,分析各计划PTV的适形指数（CI）、均匀指数（HI）,肺接受5~30 Gy照射体积占全肺体积的百分比（V5、V10、V20、V30）,以及食管、脊髓最大受照剂量。结果 射波刀计划和γ刀计划的CI分别为0.67、0.58（t=1.58,P=0.100）;HI值分别为1.35、1.66（t=6.5,P=0.100）;双肺V5、V10、V20、V30在1计划中较2计划较大（t=5.12、4.67、5.73、6.12,P=0.000）;1、2计划的食管最大受量分别为（8.51±0.6）、（5.26±0.7）（t=-2.76,P=0.009）;脊髓最大受量分别为（9.1±1.2）、（3.4±1.4）（t=2.41、P=0.027）;每个计划食管、脊髓的剂量均不超过其限量。结论 射波刀照射计划在肺、食管、脊髓的受量大于γ刀计划,但靶区适形性、均匀性要高于γ刀计划。     

蒙特卡罗算法与筒串卷积算法在宫颈癌术后调强放疗中剂量学的研究

目的:探讨蒙特卡罗算法与筒串卷积算法在宫颈癌术后调强放疗中的剂量学差异。方法:选取2017年1月~2019年9月收治的90例宫颈癌术后调强放疗患者,予以同一治疗计划,分别以蒙特卡罗算法与筒串卷积算法进行剂量计算,比较两种算法计划靶区与危及器官剂量学差异。结果:蒙特卡罗算法靶区D2、D98、D50及HI指标低于筒串卷积算法(P<0.05);蒙特卡罗算法靶区CI值高于筒串卷积算法(P<0.05);蒙特卡罗算法脊髓D2、D50,直肠V40、D50,膀胱V30、V40,双侧股骨头V30、V40、D50指标均低于筒串卷积算法(P<0.05)。脊髓D2、D50,直肠V40、D50,膀胱V30、V40,双侧股骨头V30、V40、D50指标蒙特卡罗算法值均较低,差异均有统计学意义(P<0.05);直肠V30、膀胱D50指标对比无明显差异(P>0.05)。结论:宫颈癌术后调强放疗患者应尽量选取蒙特卡罗算法进行治疗计划设计,可显著提高靶区均匀性与适形度,还可降低正常组织受照剂量;若只可选用筒串卷积算法,则应适量减少子野数量,扩大最小子野面积。     

免疫球蛋白G4与恶性肿瘤

外周血免疫球蛋白G4(immunoglobulin G4, IgG4)异常升高以及病变组织中大量IgG4阳性浆细胞浸润是IgG4相关性疾病(IgG4 related disease, IgG4-RD)最显著的临床病理特征。IgG4-RD临床表现多样,病变几乎可以累及任何组织/器官,已引起学者们的广泛关注。随着研究的深入,发现IgG4表达异常不仅可引起IgG4-RD,作为一种免疫反应负向调控因子,IgG4与恶性肿瘤的发生与预后、肿瘤免疫均有一定相关性。本文回顾了IgG4与恶性肿瘤的关系及其在肿瘤免疫中的作用进展。     

基于蒙特卡罗算法的肿瘤放射治疗计划系统的研究进展

蒙特卡罗剂量计算法一直被公认为是最精确的辐射输运计算工具,因此很早就成为模拟辐射治疗粒子输运的重要方法之一。但真正能应用于肿瘤放射治疗临床工作的基于蒙特卡罗算法的放射治疗计划系统的推出却经历了一个漫长的时间过程。目前仍在进一步开发和优化中。现就通用蒙特卡罗应用程序的发展历史,介绍基于蒙特卡罗算法的放射治疗计划系统的研究基础;描述放射治疗过程中完整的辐射输运的组成部分;总结此类系统的优势、研发难点和特有的限制条件;介绍能使蒙特卡罗算法应用于临床的主要途径;并指出仍需要努力研究从而充分发挥其潜力的领域。     

人附睾蛋白4化学发光定量测定法的建立与评价

目的建立人附睾蛋白4(HE4)的化学发光定量检测方法,并进行方法学评价。方法血清中HE4与包被抗HE4单克隆抗体的微磁珠和辣根过氧化物酶(HRP)标记的抗HE4单克隆抗体反应形成双抗体夹心结构,HRP可催化发光底物液(含鲁米诺-H2O2-增强剂)产生大量光信号,根据光信号的量计算血清中HE4的浓度。依据国家体外诊断试剂性能评价指南性文件和美国临床和实验室标准化协会(CLSI)指南性文件,对本方法进行系统评价。结果建立的方法空白限(LoB)为1.014pmol/L、检测限(LoD)为5.252 pmol/L、定量检测限(LoQ)为10.568 pmol/L;甲胎蛋白(α-fetoprotein,AFP)≤400 IU/mL、癌胚抗原(carcinoembryonic antigen,CEA)≤1 777μg/L、糖类抗原(carbohydrate antigen,CA)125≤3 500 U/mL、CA19-9≤3 500U/mL对本方法无明显交叉反应;线性范围为20~1 700 pmol/L;在100 000 pmol/L时未出现明显钩状(Hook)效应;批内变异系数(CV)为1.5%~3.6%;日间CV为3.8%~6.4%;回收率为98.36%~99.14%;血红蛋白≤4.8 g/L、胆红素≤1 077.5μmol/L、乳糜微粒≤6 000浊度、生物素≤50μg/L、类风湿因子≤1 000 U/L对测定结果无明显影响;37℃保存7 d后相对偏差为-6.63%~10.23%;建立的方法(Y)与Fujirebio公司的ELISA试剂(X)进行方法学比对,相关曲线为Y=1.023X-12.280,r=0.989 7(P0.01)。结论本研究建立的HE4磁微粒化学发光免疫测定法各项性能符合临床实验室需求,为卵巢癌的辅助诊断提供了有效工具。     

1型糖尿病患者血清髓源性免疫抑制细胞与免疫球蛋白G4的意义及关系

目的探讨1型糖尿病（T1D）患者血清髓源性免疫抑制细胞（MDSCs）与免疫球蛋白G4（IgG4）的关系。 方法选取汕头大学医学院第二附属医院于2015年1月至2017年1月期间收治的T1D患者30例,2型糖尿病（T2D）患者20例;另选取同一家医院2015年1月至2017年1月期间健康体检者20例作为对照组。采用酶联免疫吸附法测定血清IgG4浓度,流式细胞分析术检测外周血MDSCs表达频率。采用t检验以及Mann-Whitney U检验比较3组间血清IgG4浓度及MDSCs表达频率的差异,采用Spearman相关分析法分析血清IgG4与MDSCs的相关性。 结果T1D组血清IgG4为（0.92±0.79）g/L,T2D组血清IgG4为（0.54±0.33）g/L,对照组血清IgG4为（0.34±0.15）g/L,T1D血清IgG4浓度高于对照组,差异具有统计学意义（t=4.900,P<0.001）,T1D组高于T2D组,差异具有统计学意义（t=2.830,P=0.007）,T2D组高于对照组,差异具有统计学意义（t=2.466,P=0.010）。T1D组外周血MDSCs表达频率为（4.09±1.53）%,T2D组外周血MDSCs表达频率为（2.86±1.63）%,对照组外周血MDSCs的表达频率为（1.93±0.76）%。T1D组外周血MDSCs的表达频率明显高于对照组,差异有统计学意义（Z=-9.650,P<0.01）。T1D组MDSCs表达频率高于T2D组,差异有统计学意义（t=2.899,P=0.005）。血清IgG4与MDSCs呈正相关（r=0.482,P<0.05）。 结论T1D患者MDSCs与IgG4升高,且IgG4与MDSCs呈正相关,具有重要研究意义。     

三维重建法测射血分数评价左心室收缩功能的临床价值

目的　探讨三维重建法测量左心室射血分数 (L VEF)评价左心室收缩功能的准确性及临床应用价值。方法　分别运用三维重建法及左室造影容积差法测定 30例冠心病、心肌缺血患者的 L VEF,并以左室造影容积差法测定的L VEF为标准 ,将结果对比分析。结果　采用三维重建法所测量的 L VEF与左室造影容积差法所测值非常接近 ,有高度的敏感性及准确性 ,两者数值相关显著(r=0 .913,P<0 .0 1) ,两者所测值比较无显著性差异 (P>0 .0 5 )。结论　三维重建法测定 L VEF相对于左室造影容积差法来说 ,有其一定的优越性 ,是一种准确的评价左室收缩功能的无创性新方法 ,具有一定的临床应用价值     

腹压训练加间歇导尿法对脊髓源性非反射型膀胱的综合效果评价

目的探讨脊髓源性非反射型膀胱的最佳护理方案。方法将60例脊髓源性非反射型膀胱患者随机分A、B、C3组,每组各20例;A组采用腹压训练加间歇导尿法,B组采用腹压训练加留置导尿管法,C组采用间歇导尿法。于护理3周后评价3组患者疗效、尿路感染发生率及经济学指标。结果干预3周后,3组患者的疗效差异均有统计学意义(P<0.05),其中以A组最佳;B组患者尿路感染发生率高于A组和C组,差异有统计学意义(P<0.05和P<0.01);出院时医疗成本从低到高依次为A、B、C组。结论腹压训练加间歇导尿术可以让患者尽早形成平衡膀胱,减少泌尿系感染,降低医疗费用,是脊髓源性非反射型膀胱的最佳护理方案。     

免疫透射比浊法测定尿免疫球蛋白G的建立与评价

免疫球蛋白G（IgG）是血清中含量较多的一种大分子免疫球蛋白（分子量为16KD），主要由脾及周围淋巴浆细胞合成，通常不易通过肾小球滤过膜，尿中排量极少。一般在肾小球病变较重时免疫球蛋白G才排出显著增加。尿中免疫球蛋白G增多与肾小球病变严重程度有关．大都是非选择性蛋白尿。     

免疫透射比浊法测定尿免疫球蛋白G的建立与评价

免疫球蛋白G（IgG）是血清中含量较多的一种大分子免疫球蛋白（分子量为16KD），主要由脾及周围淋巴浆细胞合成，通常不易通过肾小球滤过膜，尿中排量极少。一般在肾小球病变较重时免疫球蛋白G才排出显著增加。尿中免疫球蛋白G增多与肾小球病变严重程度有关．大都是非选择性蛋白尿。     

基于蒙特卡罗模拟的小动物质子CT最优射束能量

目的 观察基于蒙特卡罗模拟的小动物质子CT(PCT)的最优射束能量。方法 采用蒙特卡罗模拟建立PCT系统,分别以不同能量质子束对体模1、2进行扫描,并以滤波反投影法重建图像,观察其中不同材料质子的相对阻止本领(RSP)值、重建误差、空间分辨率、信号噪声比(SNR)及对比噪声比(CNR),评估图像质量,筛选最优质子射束能量。结果 重建图像中,特氟龙、聚丙烯及骨骼等效材料的RSP的相对误差均随质子能量增高而先降后升,于质子能量为130 MeV时最小,分别为0.76%、0.08%及0.05%。体模1内4种插件的SNR和CNR均随质子能量增高而降低。重建图基本无法分辨体模2内直径0.2 mm铝插件,质子能量较低时可分辨直径0.4 mm铝插件;不同质子能量下均可分辨直径0.8 mm铝插件,且空间分辨率随质子能量增高而提升,质子能量大于130 MeV后变化趋缓。结论 以蒙特卡罗模拟的小动物PCT平台的最优成像质子射束能量为130 MeV。     

Pharmacodynamic assessment of doripenem in peritoneal fluid against Gram-negative organisms: use of population pharmacokinetic modeling and Monte Carlo simulation

This study aimed to assess the peritoneal pharmacodynamics of intravenous doripenem using population pharmacokinetic modeling and Monte Carlo simulation. Drug concentrations in peritoneal fluid (PF) and serum from 11 laparotomy patients and MIC distributions against clinical isolates in Japan for 4 Gram-negative organisms were used. The probabilities of attaining the pharmacodynamic target (40% T > MIC) were greater in PF than in serum. To achieve a > or =90% probability of target attainment in PF, 0.25 g tid and 0.5 g tid (0.5-h infusions) had to be sufficient against Escherichia coli, Klebsiella spp., and Enterobacter cloacae; however, 1 g tid (0.5-h infusion) was required against Pseudomonas aeruginosa. Prolonged (4-h) infusion regimens resulted in increase of the target attainment probabilities in PF for P. aeruginosa. These results should help to achieve a better understanding of the peritoneal pharmacodynamics of doripenem while also helping to rationalize and optimize the dosing regimen for intra-abdominal infections.     

Evaluation of dosing designs of carbapenems for severe respiratory infection using Monte Carlo simulation

Using the Monte Carlo simulation method, the influence of various doses and dosing frequencies of carbapenems on the antimicrobial activities against Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa, which are the main causative organisms of respiratory infections, was studied with the aim of identifying optimized effectiveness. Based on pharmacokinetic (PK) parameters of individual carbapenems in healthy adults, data on changes in the respective blood concentrations in 2000 cases were simulated by applying a lognormal distribution to probability distributions of their volume of distributions and half-life periods. Based on minimum inhibitory concentration (MIC) distribution data of the individual carbapenems against these strains, MICs in the 2000 cases were also simulated. Using these data in blood concentrations and MICs, the probabilities of attaining various percentages of the dosing interval during which drug concentrations remain above MIC (T > MIC) were calculated at several dosing regimens. Considering the probabilities of attaining the bactericidal effect (50% T>MIC) and daily drug costs, imipenem (IPM) at 500 mg i.v. BID, panipenem (PAPM) at 500 mg i.v. BID, and biapenem (BIPM) at 300 mg i.v. BID against Streptococcus pneumoniae; meropenem (MEPM) at 500 mg i.v. BID or TID against Haemophilus influenzae infections; and MEPM at 500 or 1000 mg i.v. TID against Pseudomonas aeruginosa, each over 30 min, were determined as appropriate empirical treatments. Selecting carbapenems with superior antimicrobial activities and optimizing their dose regimens are important to improve the efficacy. Application of Monte Carlo simulation to MIC distributions allows determination of appropriate empiric therapy even if drug susceptibility of a causative organism in individual patients is unknown.     

基于蒙特卡洛的光伏多峰最大功率跟踪控制

针对局部阴影情况下,光伏输出曲线非线性和多峰值的特性,从概率论的角度出发,提出基于蒙特卡洛的光伏多峰值最大功率跟踪控制算法。对光伏输出曲线及均匀分布进行分析并构建概率模型。然后根据蒙特卡洛算法的基本原理,对模型特定区域内的随机变量进行统计以确定近似最大功率点。最后用常规最大功率算法提高收敛精度。与传统算法不同,新方法从概率论的角度,为解决局部阴影问题提供了一种新的思路,其收敛速度及准确性不受光伏曲线形状的影响,试验和仿真表明该算法能够有效的跟踪全局最大功率点,避免其收敛于局部最优解。     

Sequential Monte Carlo tracking of the marginal artery by multiple cue fusion and random forest regression

Given the potential importance of marginal artery localization in automated registration in computed tomography colonography (CTC), we have devised a semi-automated method of marginal vessel detection employing sequential Monte Carlo tracking (also known as particle filtering tracking) by multiple cue fusion based on intensity, vesselness, organ detection, and minimum spanning tree information for poorly enhanced vessel segments. We then employed a random forest algorithm for intelligent cue fusion and decision making which achieved high sensitivity and robustness. After applying a vessel pruning procedure to the tracking results, we achieved statistically significantly improved precision compared to a baseline Hessian detection method (2.7% versus 75.2%, p < 0.001). This method also showed statistically significantly improved recall rate compared to a 2-cue baseline method using fewer vessel cues (30.7% versus 67.7%, p < 0.001). These results demonstrate that marginal artery localization on CTC is feasible by combining a discriminative classifier (i.e., random forest) with a sequential Monte Carlo tracking mechanism. In so doing, we present the effective application of an anatomical probability map to vessel pruning as well as a supplementary spatial coordinate system for colonic segmentation and registration when this task has been confounded by colon lumen collapse.     

Monte Carlo simulation for evaluation of the efficacy of carbapenems and new quinolones against ESBL-producing Escherichia coli

Extended-spectrum β-lactamase (ESBL)-producing bacteria are known to be resistant to penicillins, cephalosporins, and monobactams because of their substrate specificity, and these bacteria are sensitive only to a narrow range of antimicrobial agents. The present study was undertaken to evaluate the efficacy of carbapenems and the new quinolones against ESBL-producing Escherichia coli, using a Monte Carlo simulation based on the pharmacokinetic/pharmacodynamic (PK/PD) theory. The time above MIC (TAM, %) served as the PK/PD parameter for carbapenems, with the target level set at 40%. The AUC/MIC served as the PK/PD parameter for the new quinolones, with the target level set at more than 125. In the analysis of drug sensitivity, the MIC50 of all carbapenems other than imipenem was low (0.03 μg/ml), while the MIC50 of the new quinolones was higher (1–2 μg/ml). The probability of achieving the PK/PD target with carba penems after two doses at the usual dose level, as determined by the Monte Carlo simulation, was high for each of the carbapenems tested (99.0% for biapenem, 99.60% for meropenem, and 95.03% for doripenem), except for imipenem. Among the new quinolones, the highest probability of achieving the PK/PD target was obtained with pazufloxacin (42.90%). Thus, the results of the present study have revealed that carbapenems are effective at the regular dose and can be used as the first-choice antibiotics for ESBL-producing E. coli because the resistance ratios for carbapenems are low compared to those of the new quinolones.     

Experimental verification of the efficacy of optimized two-step infusion therapy with meropenem using an in vitro pharmacodynamic model and Monte Carlo simulation

In this study we compared the efficacy of a theoretically optimized two-step infusion therapy (OTIT; rapid first-step infusion and slow second-step infusion) to the efficacies of prolonged infusion therapy (PIT) and traditional 0.5 h infusion therapy (TIT) with meropenem against Pseudomonas aeruginosa using an in vitro pharmacodynamic model and a Monte Carlo simulation. In the in vitro pharmacodynamic model, the bactericidal effect against P. aeruginosa was evaluated for 8 h, which is the usual dosing interval of meropenem. It was confirmed that the durability of the bactericidal effect of OTIT (0.25–1 g/0.5 h + 0.25–1 g/4 h t.i.d.) was almost equal to that of PIT and superior to that of TIT (0.5–2 g/0.5–4 h t.i.d.). In addition, the initial bactericidal effects of OTIT were superior to those of the prolonged 4 h infusion. In the Monte Carlo simulation study, the probability of target attainments (PTAs) of all dosing regimens of OTIT at MICs of 2–8 μg/ml were apparently superior to those of TIT and 4- and 6 h-PIT, when the target therapeutic condition for serious life-threatening infections was the achievement of both the percentage of the dosing interval at which the drug concentration exceeds the MIC (%T _>MIC) ≥ 50% and the peak level divided by the MIC (C _max/MIC) ≥ 4. Especially, the PTAs of the dosing regimens of 0.25–1 g/0.5 h + 0.25–1 g/4–6 h were excellent at MICs of 2–8 μg/ml. Against recent clinical isolates of P. aeruginosa in Japan, the dosing regimens of OTIT provided higher PTAs compared with those of TIT and 4- and 6 h-PIT. These results suggested that OTIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of meropenem against serious life-threatening infections.     

Evaluation by Monte Carlo simulation of levofloxacin dosing for complicated urinary tract infections caused by Escherichia coli or Pseudomonas aeruginosa

We evaluated, by Monte Carlo simulation, 500-mg once-daily, 100-mg thrice-daily, 200-mg twice-daily, and 200-mg thrice-daily dose regimens of levofloxacin (LVFX), for the ratio of area under the concentration–time curve for 24 h (AUC_0–24) to minimum inhibitory concentration (MIC) (AUC_0–24/MIC) and the ratio of maximum plasma concentration (C _max) to MIC (C _max/MIC), which predict microbiological outcomes, and the C _max/MIC, which inhibits fluoroquinolone resistance selection, in complicated urinary tract infections (UTIs) with Escherichia coli or Pseudomonas aeruginosa. Monte Carlo simulation was performed for 10000 cases using the pharmacokinetic data of patients with complicated UTIs and the LVFX MIC distributions for E. coli or P. aeruginosa clinical strains. The probabilities of achieving the AUC_0–24/MIC target (66.2–67.9%) and the C _max/MIC target (64.5–67.5%) to eradicate E. coli were similar among the 4 regimens. In eradication of P. aeruginosa, the 200-mg thrice-daily and the once-daily dose regimens produced higher probabilities of achieving the AUC_0–24/MIC target (57.5%) and C _max/MIC target (55.1%), respectively. For the probabilities of achieving the C _max/MIC targets that prevent the emergence of fluoroquinolone resistance, the once-daily dose regimen (66.8%) did not differ from the other multiple-dose regimens (62.3–66.2%) in E. coli, whereas the former regimen (44.2%) was superior to the latter regimens (10.8–31.7%) in P. aeruginosa. The 500-mg once-daily dose regimen of LVFX, which produced the larger AUC_0–24 and higher C _max, could ensure the efficacy of eradication of uropathogens and reduce the risk of fluoroquinolone resistance selection in complicated UTIs.     

纤溶酶原激活物抑制剂-1(4G/5G)基因多态性与深静脉血栓事件的风险概率

目的分析我国西北地区纤溶酶原激活物抑制剂-1(PAI-1)(4G/5G)基因在不同人群中的分布情况,以及不同基因型患者血栓事件的发生率,为携带PAI-1(4G/5G)基因4G型的手术患者提供数据支持和用药指导。方法收集1 494例行基因位点检测人群血液样本,使用荧光探针原位杂交技术检测PAI-1(4G/5G)基因位点,分析我国西北地区PAI-1(4G/5G)基因在体检健康者、剖腹产患者、烧伤患者、心脑血管疾病患者之间4G基因型的差异性。结果 336例体检健康者中5G5G(野生型)78例(23.21%),4G5G(杂合突变型)152例(45.24%),4G4G(纯合突变型)106例(31.55%)。401例剖腹产患者中5G5G(野生型)60例(14.96%),4G5G(杂合突变型)195例(48.63%),4G4G(纯合突变型)146例(36.41%)。603例烧伤患者中5G5G(野生型)100例(16.58%),4G5G(杂合突变型)295例(48.93%),4G4G(纯合突变型)208例(34.49%)。154例心脑血管疾病患者中5G5G(野生型)21例(13.64%),4G5G(杂合突变型)81例(52.59%),4G4G(纯合突变型)52例(33.77%)。剖腹产患者、烧伤患者、心脑血管疾病患者PAI-1(4G/5G)基因4G型携带率与体检健康人群间的差异均有统计学意义(P0.05)。追踪观察200例烧伤手术患者,患病后2个月内有139例(69.5%)发生深静脉血栓事件,4G4G基因型血栓事件为86.49%(64/74),4G5G基因型血栓事件为65.00%(52/82),5G5G基因型血栓事件为50.00%(23/46),不同基因型深静脉血栓事件发生率的差异有统计学意义(P0.01)。结论通过分析PAI-1(4G/5G)基因在不同人群中的分布以及发生血栓事件的发生率,可预防或降低手术患者发生静脉血栓、脑卒中等的风险。