一个肿瘤化疗模型的几种求解方法

分别利用Bernoulli方程,Riccati方程求解方法和Mathematica软件,讨论一个肿瘤化疗模型的通解。

几种致吐药物比较优选顺铂剂量造家鸽化疗呕吐模型

目的:优选顺铂造家鸽化疗呕吐模型的最佳剂量,确保造模后家鸽能正常存活,为化疗呕吐实验研究提供一种稳定可靠的造模方法。方法:仿文献采用家鸽腹腔注射顺铂的方法,与传统的致吐剂硫酸铜和另一种化疗常用药环磷酰胺比较,优选顺铂剂量进行重复试验,连续观察30天。结果:一次性给予4.5mg·kg-1是顺铂致家鸽化疗呕吐模型的最佳剂量。结论:优选的顺铂剂量4.5mg·kg-1造家鸽化疗呕吐模型能够确保化疗后适宜呕吐,也能使化疗后家鸽正常存活,符合临床上化疗引起呕吐的致病特点。优选剂量致家鸽化疗呕吐模型重复性好、稳定、可靠,这对于化疗呕吐的实验研究有意义。

小半夏汤治疗化疗后呕吐模型的药效最佳配比研究

目的:研究小半夏汤治疗化疗后呕吐模型的药效最佳配比。方法:应用均匀设计的方法,将半夏与生姜的不同配比设计为5个水平,观察5组小半夏汤作用于化疗后家鸽呕吐模型后模型组和各用药组8h内潜伏期和呕吐次数。并寻求使8h内呕吐次数最小的配比。结果:小半夏汤有延长化疗后家鸽呕吐模型潜伏期的趋势或能延长潜伏期(P<0.05),能明显降低呕吐次数(P<0.01),其中按1:2配比效果最佳。结论:小半夏汤治疗化疗后呕吐模型的药效最佳配比为1:2。

化疗并发症预警模型在鼻咽癌患者化疗护理中的应用效果

目的探讨化疗并发症预警模型在鼻咽癌患者化疗护理中的应用效果。方法将我院2019年1月—2020年12月接收的102例鼻咽癌化疗患者根据随机数字表法分为对照组(给予常规化疗护理)与干预组(给予常规化疗护理+化疗并发症预警模型下护理),各51例,观察比较两组的化疗并发症发生率及化疗后生活质量变化。结果化疗并发症预警模型下护理干预后,干预组化疗期间的营养不良、便秘、恶心呕吐及骨髓抑制发生率分别为3.92%、3.92%、5.88%、1.96%,均显著低于对照组的17.65%、19.61%、21.57%、17.65%,P<0.05;干预组的QOL-NPC13量表各个领域评分均显著高于对照组,P<0.05。结论将化疗并发症预警模型应用于鼻咽癌患者化疗护理,能够有效降低化疗并发症发生率,提高患者化疗后生活质量。

RI与TACE联合栓塞Walker-256肝移植模型肿瘤组织中Bcl-2、P53的表达

目的研究核糖核酸酶抑制因子(RI)与TACE联合栓塞Walker-256肝移植模型对肿瘤组织Bcl-2、P53表达的影响。材料与方法将60只Walker-256荷瘤大鼠于移植后第14天随机分成肝动脉灌注化疗栓塞组(TACE组)、RI与TACE联合栓塞组和对照组,每组20只。各组分别经肝动脉注入:超液态碘油0.5 ml加5-Fu 20 mg/kg;RI 200单位加5-Fu 20 mg/kg加超液态碘油0.5 ml;生理盐水0.5 ml。于术后第7天用免疫组化的方法检测各组肿瘤组织中Bcl-2、P53的表达。结果Bcl-2阳性率TACE组为35%(7/20);联合栓塞组为30%(6/20);对照组为25%(5/20),各组无显著性差异(P>0.05)。P53阳性率TACE组为50%(10/20),联合栓塞组为45%(9/20),对照组为60%(12/20),各组无显著性差异(P>0.05)。结论RI与TACE联合栓塞与TACE相比,肿瘤组织中Bcl-2,P53的蛋白表达无明显差异。

多指标正交试验分析黄芪补血有效部位的交互关系

目的:分析黄芪补血有效部位(黄芪黄酮、黄芪多糖、黄芪皂苷)干预化疗性贫血模型小鼠的效应机制及其交互关系。方法:采用多指标正交试验将108只小鼠随机分为9组,每组12只。除正常组外,其余各组按100 mg·kg-1剂量腹腔注射环磷酰胺造模后,按L8(27)正交表开展实验,并运用多项指标计算综合评分方法对外周血红蛋白(Hb)浓度、红细胞(RBC)计数、红细胞压积(Hct)、白细胞(WBC)计数、骨髓集落刺激因子等指标进行直观分析和方差分析。结果:模型组与正常组比较,各单项指标差异均有统计学意义(P<0.05)。多糖对外周血象(红细胞),黄酮、皂苷对白细胞,黄酮、多糖对集落刺激因子作用显著(P<0.05),联合用药效果均不如单一用药。黄酮、多糖、皂苷对白细胞介素均有作用(P<0.05),黄酮与多糖合用效果优于单一用药。结论:黄芪多糖是促进化疗贫血小鼠红细胞增殖、粒系造血的最佳有效部位,黄酮、皂苷增加白细胞作用较佳。

化疗并发症预警模型在非小细胞肺癌化疗患者中的应用

目的探讨化疗并发症预警模型在非小细胞肺癌患者化疗期护理中的应用效果。方法采用便利抽样法,选取2016年1月—2019年2月郑州大学第一附属医院胸外科收治的非小细胞肺癌化疗患者106例为研究对象,按照入院时间分为对照组(n=52)和观察组(n=54)。对照组给予常规护理,观察组通过化疗并发症预警模型进行护理。采用汉密顿焦虑量表(HAMA)、汉密顿抑郁量表(HAMD)和癌症患者生命质量测定量表(EORTC QLQ-C30)比较两组干预效果,统计两组化疗期间并发症发生情况。结果观察组化疗期间并发症总发生率26.92%(14/52),对照组为46.15%(24/52),差异有统计学意义(χ2=4.147,P<0.05)。干预后3个月,观察组患者HAMA(9.87±4.25)分、HAMD(15.54±3.58)分,均低于对照组,差异均有统计学意义(t值分别为4.738、8.296;P<0.05)。观察组干预后功能评分、症状评分、整体生活质量评分、单项测量项目评分高于对照组,差异有统计学意义(P<0.05)。结论在非小细胞肺癌化疗期间通过化疗并发症预警模型进行护理能够降低患者化疗并发症发生率,缓解患者负性情绪,提高生活质量,值得临床推广应用。

Synthesis of platelet-activating factor and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis

AIM:To determine the platelet-activating factor (PAF) synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis. METHODS:Kupffer cells, isolated from the livers of control and CCl4-induced cirrhotic rats, were placed in serum-free medium overnight. PAF saturation binding, ET-1 saturation and competition binding were assayed. ET-1 induced PAF synthesis, mRNA expression of PAF, preproendothelin-1, endothelin A (ETA) and endothelin B (ETB) receptors were also determined. RESULTS:A two-fold increase of PAF synthesis (1.42 ± 0.14 vs 0.66 ± 0.04 pg/μg DNA) and a 1.48-fold increase of membrane-bound PAF (1.02 ± 0.06 vs 0.69 ± 0.07 pg/μg DNA) were observed in activated Kupffer cells of cirrhotic rats. The application of ET-1 to Kupffer cells induced PAF synthesis in a concentration-dependent manner in both cirrhotic and normal rats via ETB receptor, but PAF synthesis in the activated Kupffer cells was more effective than that in the normal Kupffer cells. In activated Kupffer cells, PAF receptor expression and PAF binding capacity were markedly enhanced. Activated Kupffer cells raised the [125I]-ET-1 binding capacity, but changed neither the affinity of the receptors, nor the expression of ETA receptor. CONCLUSION:Kupffer cells in the course of CCl4-induced cirrhosis are the main source of increased PAF. ET-1 is involved endogenously in stimulating the PAF synthesis in activated Kupffer cells via ETB receptor by paracrine. ETA receptor did not appear in activated Kupffer cells, which may exacerbate the hepatic and extrahepatic complications of cirrhosis.

Trans-arterial gene therapy for hepatocellular carcinoma in a rabbit model

AIM： To study the effect of adenovirus （Ad）-p53 gene therapy on hepatocellular carcinoma （HCC） in a rabbit model.METHODS： VX2 tumor was grown in the liver of 24rabbits. Animals were divided into four groups： group A receiving trans-arterial gene therapy （Ad-p53） only,group B receiving combined Ad-p53 therapy and transarterial embolization （lipiodol）, group C receiving transarterial chemoembolization （lipiodol ＋ mitomycin C）,control group （D） receiving sodium chloride. Tumor volume （V1） was measured by using MRI （d 13）.Interventional procedure was applied （d 14）.Tumor volume （V2） was assessed by MRT （d 21） and the mean ratio （V2/V1） was calculated. After the second MRI,specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 antibody.The positive expression was scored.RESULTS： Compared with control group （（^-x） = 3.14± 0.64）, therapeutic groups all showed a significant decrease in the tumor growth ratio （P 〈 0.05）. A slight difference was found between group A （（^-x） =2.35 ±0.59） and group B （（^-x） = 1.75 ± 0.28） （P = 0.048）. Nostatistically significant difference was observed between group B and group C （（^-x） = 2.00 ± 0.44）. The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C （P 〈 0.05）.Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them.CONCLUSION： Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.

Changing the paradigm：the potential for targeted therapy in laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.

Clinical outcome and predictors of survival after TIPS insertion in patients with liver cirrhosis

AIM： To determine the clinical outcome and predictors of survival after transjugular intrahepatic portosystemic stent shunt （TIPS） implantation in cirrhotic patients. METHODS： Eighty-one patients with liver cirrhosis and consequential portal hypertension had TIPS implanta- tion （bare metal） for either refractory ascites （RA） （n = 27） or variceal bleeding （VB） （n = 54）. Endpoints for the study were： technical success, stent occlusion and stent stenosis, rebleeding, RA and mortality. Clini- cal records of patients were collected and analysed. Baseline characteristics [e.g., age, sex, CHILD score and the model for end-stage liver disease score （MELD score）, underlying disease] were retrieved. The Kaplan- Meier method was employed to calculate survival from the time of TIPS implantation and comparisons were made by log rank test. A multivariate analysis of factors influencing survival was carried out using the Cox pro- portional hazards regression model. Results were ex- pressed as medians and ranges. Comparisons between groups were performed by using the Mann-Whitney U-test and the4,2 test as appropriate. RESULTS： No difference could be seen in terms of age, sex, underlying disease or degree of portal pressure gradient （PPG） reduction between the ascites and the bleeding group. The PPG significantly decreased from 23.4 ± 5.3 mmHg （VB） vs 22.1± 5.5 mmHg （RA） be- fore TIPS to 11.8 ±4.0 vs 11.7 ± 4.2 after TIPS im- plantation （P = 0.001 within each group）. There was a tendency towards more patients with stage CHILD A in the bleeding group compared to the ascites group （24 vs 6, P = 0.052）. The median survival for the ascites group was 29 mo compared to 〉 60 mo for the bleed- ing group （P = 0.009）. The number of radiological con- trols for stent patency was 6.3 for bleeders and 3.8 for ascites patients （P = 0.029）. Kaplan-Meier calculation indicated that stent occlusion at first control （P = 0.027）, ascites prior to TIPS implantation （P = 0.009）, CHILD stage （P = 0.013）, MELD score （P = 0.001） and those patients not having undergone liver transplantation （P = 0.024） were significant predictors of survival. In the Cox regression model, stent occlusion （P = 0.022）, RA （P = 0.043）, CHILD stage （P = 0.015） and MELD score （P = 0.004） turned out to be independent prognostic factors of survival. The anticoagulation management （P = 0.097）, the porto-systemic pressure gradient （P= 0.460） and rebleeding episodes （P = 0.765） had no significant effect on the overall survival. CONCLUSION： RA, stent occlusion, initial CHILD stage and MELD score are independent predictors of survival in patients with TIPS, speaking for a close follow-up in these circumstances.

OPTIMIZATION OF TETRANDRINE TREATMENT IN RAT HEPATIC FIBROSIS MODEL

Objective To optimize the therapeutic dosage of tetrandrine （Tet） in rat hepatic fibrosis roodel. Methods 50 Wistar rats were divided into 5 groups at random including normal control, model control, Tettreated model groups of 10mg· kg^ - 1· d^ - 1, 5mg· kg^ - 1· d^ - 1 and 2.5mg· kg^ - 1· d^ - 1（ n = 10 in each group ）. All rats, except for the normal controls, were injected with axenic porcine serum （0. 5ml each time, twice a week） intraperitoneally for 8 weeks to establish hepatic fibrosis. After the 8th week, rats of Tet-treated model groups were given by gavage once a day with different doses of Tet for another 8 weeks. Then the liver function, serum levels of hyaluronic acid （ HA ）, laminin （ LM）, and procollagen type Ⅲ （PCⅢ） were tested. Collagen type 1 and Ⅲ, pathological changes in liver tissue were also assessed. Results Most indices of liver function including alanine minotransferase （ALT）, aspartate aminotransferase （AST）, albumin （ ALB）, albumin/globulin ratio （ A/G） and alkaline phosphatase （ALP） improved significantly in Tet-treated groups with the exception of γ-glutamyl transpeptidase （γ- GT） and total bilirubin （TBIL）. Secondly, markedly lowered levels of HA, LM and collagen type I, III were also detected by radioimmunology and immunohistochemistry in the 5 mg· kg^ - 1· d^ - 1 Tet-treated model group. Moreover, pathologi- cal findings confirmed the statistically significant improvement in hepatofibrotic degree resulted from the treatment of 5mg· kg^ - 1· d^ - 1 rather than other doses of Tet. Conclusion For experimental Wistar rats, Tet exhibited an anti-hepatofibrotic action in doses within the range of 2.5mg· kg^ - 1· d^ - 1 to 10mg· kg^ - 1· d^ - 1 and 5mg· kg^ - 1· d^ - 1 may be the optimum one among all doses.

Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer:A meta-analysis

AIM:To investigate the effectiveness of 5-flurouracilbased neoadjuvant chemotherapy(NAC) for gastroesophageal and gastric cancer by meta-analysis.METHODS:MEDLINE and manual searches were performed to identify all published randomized controlled trials(RCTs) investigating the efficacy of the flurouracilbased NAC for gastroesophageal and gastric cancer,and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery.Studies that included patients with metastases at enrollment were excluded.Primary endpoint was the odds ratio(OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer.Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gas-troesophageal and gastric cancer.Safety analyses were also performed.The OR was the principal measurement of effect,which was calculated as the treatment group(NAC plus surgery) vs control group(surgery alone) and was presented as a point estimate with 95% confidence intervals(CI).All calculations and statistical tests were performed using RevMan 5.1 software.RESULTS:Seven RCTs were included for the analysis.A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group(n = 620) and control group(n = 629).The quality scores of the RCTs were assessed according to the method of Jadad.The RCT quality scores ranged from 2 to 7(5-point scale),with a mean of 3.75.The median follow-up time in these studies was over 3 years.The meta-analysis showed that NAC improved the overall survival rate(OR 1.40,95%CI 1.11-1.76;P = 0.005),which was statistically significant.The 3-year progression-free survival rate was significantly higher in treatment group than in control group(37.7% vs 27.3%)(OR 1.62,95%CI 1.21-2.15;P = 0.001).The tumor down-stage rate was higher in treatment group than in control group(55.76% vs 41.38%)(OR 1.77,95%CI 1.27-2.49;P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group(75.11% vs 68.56%)(OR 1.38,95%CI 1.03-1.85;P = 0.03),with significant differences.No obvious safety concerns about mortality and complications were raised in these trials.There were no statistically significant differences in perioperative mortality(5.08% vs 4.86%)(OR 1.05,95%CI 0.57-1.94;P = 0.87 fixed-effect model) and in the complication rate between the two groups(13.25% vs 9.66%)(OR 1.40,95%CI 0.91-2.14;P = 0.12 fixed-effect model).Trials showed that patients from Western countries favored NAC compared with those from Asian countries(OR 1.40,95%CI 1.07-1.83).Monotherapy was inferior tomultiple chemotherapy(OR 1.40,95%CI 1.07-1.83).Intravenous administration of NAC was more advantageous than oral route(OR 1.41,95%CI 1.09-1.81).CONCLUSION:Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer.Additionally,NAC can down the tumor stage and improve R0 resection.

Mathematical Simulation of Blood Purification for Leukemia by Immobilized L-asparaginase

Plasma was purified in an immobilized L-asparaginase column. The predicted results are in good agreement with experimental data. It is indicated that the mathematical model is suitable for the mass transfer and reaction of blood purification.

早发性卵巢功能不全动物模型评价思路

早发性卵巢功能不全(POI)是一种由高促性腺激素低雌激素症定义的综合征。文章基于POI的各项中、西医临床病症(证)特点及诊断标准,对现有POI动物模型进行吻合度评价。此外分析了现有POI模型优缺点及问题,针对POI病证结合模型提出建议,以期在现有成功构建的动物模型基础上,建立更完善的POI病证结合动物模型,有利于将来POI的生理病理机制研究,使基础实验与临床疗效相互验证。

16S rDNA克隆文库法分析两种鱿鱼墨多糖对小鼠肠道菌群多样性的影响

探讨北太平洋鱿鱼墨多糖与秘鲁鱿鱼墨多糖对化疗模型小鼠肠道菌群的影响。将40只Balb/c小鼠随机分为4组:正常组、模型组、北太平洋鱿鱼墨多糖组、秘鲁鱿鱼墨多糖组。采用环磷酰胺化疗模型,无菌收集小鼠粪便并提取细菌基因组DNA,通过构建各组小鼠肠道细菌的16S rDNA克隆文库,单酶切分型,观察鱿鱼墨多糖对肠道菌群的作用。试验结果表明:两种鱿鱼墨多糖对化疗模型小鼠肠道菌群种类有一定调节作用,且两种鱿鱼墨多糖效果不尽相同。

Optimization model research on efficacy in treatment of chronic urticaria by Chinese and Western Medicine based on a genetic algorithm

OBJECTIVE： To investigate the potential rules and knowledge of Traditional Chinese Medicine （TCM） and Western Medicine （WM） treatment on chronic urticaria （CU） based on data-mining methods. METHODS： Sixty patients with chronic urticaria, treated with TCM and WM, were selected. Gray correlation analyses were adopted to determine therapeutic efficacy. Association algorithms were utilized to ascertain the correlation between the disease course and treatment results. A genetic algorithm was applied to discover the optimization model in theTCM and WM treatment on CU. RESULTS： The total symptom scores after 4 weeks and 8 weeks of treatment in the TCM spleen-strengthening group correlated highly with the pretreatment total symptom score. The duration of treatment showed the greatest impact on the total symptom score. A quartic equation was established （y= - 1.6403x 10 - 6x4＋0.00025576x3＋0.0012819 x2 - 1.024x＋79.5879, and x=106.9518, y=83.0036） using the genetic algorithm. CONCLUSION： TCM treatment had a better effect in the later stage, whereas WM was better in the early stage. The duration of disease course had an impact on the effects of treatment. If the average total symptom score before treatment was 〈 83.0036, TCM or WM treatment could achieve better efficacy.

Dual-stimuli-sensitive poly(ortho ester disulfide urethanes)-based nanospheres with rapid intracellular drug release for enhanced chemotherapy

Herein, new poly（ortho ester disulfide urethanes） （POEDU） and poly（ortho ester urethanes） （POEU） were successfully syn- thesized via polycondensation between active esters of 1,6-hexandiol （HD） and dual-stimuli-sensitive ortho ester disulfide diamine or pH-senstive ortho ester diamine. The corresponding POEDU and POEU nanospheres were easily fabricated using an oil-in-water emulsion technique. In vitro degradation experiments indicated that POEDU nanospheres degraded faster than POEU nanospheres in mildly acidic and reductive environments. Doxorubicin （DOX） as a model antitumor drug was suc- cessfully incorporated into these nanospheres to give DOX-loaded nanoparticles （POEDU-DOX and POEU-DOX）. In vitro drug release studies showed that release of DOX from dual-stimuli-sensitive POEDU-DOX was accelerated compared with release from the pH-sensitive POEU-DOX under DL-dithiothreitol （DTT） and mildly acidic conditions. In addition, in vitro uptake and cytotoxicity assays revealed that POEDU-DOX exhibited more efficient antitnmor effect than POEU-DOX did against both two- dimensional （2D） cells and three-dimensional （3D） multicellular tumor spheroids （MCTS）. Finally, in a mice H22 tumor model, POEDU-DOX exhibited preferable antitumor capability. In conclusion, the pH and redox dual-stimuli-sensitive POEDU na- nospheres can be superior drug carriers for cancer treatment.

Chemo-damage modeling and cracking analysis of AAR-affected concrete dams

A chemo-damage model for cracking analysis of concrete dams affected by alkali-aggregate reaction (AAR) is proposed, which combines the plastic-damage model for concrete with the AAR kinetics law. The chemo-damage model is first verified by a stress-free AAR expansion test. The expansion deformation obtained from the simulation is in good agreement with the measurement, demonstrating that the proposed model has a sufficient accuracy to predict the expansion of AAR-affected concrete. Subsequently, the expansion deformation and cracking process of the AAR-affected Fontana gravity dam is analyzed. It shows that permanent displacements in the upstream direction and the vertical direction are gradually increased during the long-term operation period, and that their maximal values reach 1.6 and 3.6 cm, respectively. A crack is observed on the wall in the foundation drainage gallery, and extends towards the downstream face of the dam. With the further development of AAR, another crack forms on the downstream face, and then intersects with the gallery crack to penetrate the downstream side profile of the dam. The third crack occurs in the upstream side wall of the gallery and propagates a short distance towards the upstream face of the dam. The simulated cracking pattern in the dam due to AAR is similar to the in situ observation.