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目的探讨大剂量盐酸氨溴索对大鼠肺缺血再灌注损伤后肺的保护作用以及可能的作用机制。方法将健康雄性SD大鼠60只随机分成4组：对照组、氨溴索组、肺缺血再灌注（I/R）组、I/R＋氨溴索组,每组15只。造模前分别给予大剂量氨溴索组和I/R＋氨溴索组静脉注射盐酸氨溴索0.75g/L,分别给予对照组和I/R组注射与上述氨溴索治疗量等容量的生理盐水。观察肺组织病理学改变并评分,检测湿干重比值（W/D）、白介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）、细胞凋亡数目、核转录因子-κB（NF-κB）,Western blot方法观察大鼠肺组织Toll样蛋白4（Toll-like receptor 4,TLR4）信号通路的蛋白表达水平。结果与对照组相比,I/R组肺泡壁增宽,肺泡腔内可见出血等炎症表现,W/D、炎症因子显著升高,肺组织W/D、IL-1β、TNF-α、凋亡细胞、NF-κB活性和TLR4信号通路相关蛋白表达水平明显升高;与（I/R）组相比,I/R＋氨溴索组肺泡腔内出血、水肿等炎症表现减轻,W/D、炎症因子、凋亡细胞显著降低,肺组织NF-κB转录活性及TLR4信号通路表达水平明显降低。结论大剂量盐酸氨溴索通过下调TLR4信号通路发挥对缺血再灌注损伤大鼠的肺保护作用。

一、目的 回顾性分析1例恶性嗜铬细胞瘤术后全身多发转移患者先后4次接受大剂量^131I-MIBG治疗的经过,探讨^131I-MIBG用于治疗手术难以切除或术后复发的嗜铬细胞瘤的价值.

目的：探讨顺铂（DDP）化疗中肾毒性的监测方法。方法：动态观察61例肺癌患者接受含大剂量DDP（80－120mg/m^2)联合化疗114个周期的血清尿素氮（BUN）、肌酐（Cr)，以及尿β2－微球蛋白（β2－MG）、尿α1－微球蛋白（α1－MG）、尿白蛋白（Alb)、尿转铁蛋白（TRF）和尿维生素A1结合蛋白（RBP）等指标，筛选出能早期监测顺铂肾毒性的指标。结果：（1）化疗早期（第1－5天）尿β2－MG和α1－MG异常率明显高于其它指标（P＜0．001）；（2）血清BUN和Cr异常率于化疗后期（第10天）增高明显；（3）化疗后期血清BUN和Cr异常者在化疗早期均有尿β2－MG和／或α1－MG异常。结论：在含DDP的肺癌联合化疗中，尿β2－MG和α1－MG具有肾毒性的早期诊断价值。

目的 论证螺内酯的抗肝纤维化作用，动态观察其对大鼠肝纤维化进展中血管紧张素Ⅱ(AngⅡ)水平的影响。方法 90只SD大鼠随机分为3组：①正常对照组(8只)：正常饮水饮食，皮下注射纯花生油；②模型组(42只)：皮下注射40％(体积分数)四氯化碳花生油溶液，辅以高脂、高胆固醇、低蛋白饮食；③螺内酯组(40只)：造模方法同模型组，并以100mg·g^-1·d^-1剂量的螺内酯灌胃。于2、4、6、8周末，后两组分别处死一批动物，放免法测定其血清及肝匀浆中AngⅡ水平，取肝脏标本做HE和VG染色观察。结果 ①螺内酯组的一般状况较好，病理改变较模型组轻，胶原面积比减少，两者有显著差异(P<0．05)；②螺内酯组和模型组大鼠血清及肝匀浆中AngⅡ水平均从第2周开始较正常对照组显著升高；从第4周开始，螺内酯组血清中AngⅡ水平较同期模型组显著升高，而肝匀浆中AngⅡ水平较同期模型组显著降低。结论 大剂量螺内酯可以部分抑制肝纤维化的进展，其作用机制可能与肝纤维化进展过程中肝匀浆中AngⅡ水平降低有关。

Vitamin C was first suggested to have cancer-fighting properties in the 1930s and has been the subject of controversy ever since. Despite re- peated reports of selective cancer cell toxicity induced by high-dose vitamin C treatment in vitro and in mouse models, the mechanism of action has remained elusive.

Background: High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma. The plasma concentration of MTX is closely related to efficacy and toxicity. There are large individual differences. Many authors have described the pharmacokinetic (PK) profile of MTX regarding osteosarcoma under a variety of circumstances. However, no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed effects models (NONMEM) have been previously reported. The goals of this study were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in Chinese osteosarcoma patients, and to explore the influence of patient covariates and between-occasion variability on drug disposition. Methods: An intravenous HD-MTX solution (10 g/m 2 ) was given 274 times to 148 osteosarcoma patients. MTX plasma concentrations were measured at 0, 6, 12, 24, 48 and 72 h after commencement of the infusion, and the fluorescence polarization immunoassay was used to determine MTX plasma concentrations. The PPK model and parameters were estimated using NONMEM software. The effects of fixed-effect factors were evaluated, and the final regression model was obtained. Results: The following population parameters were obtained using a two-compartment model: CL1 (clearance of central compartment): (CL1 ) = CL1TV × [1 - θ CL 1- MTXNUM × MTXNUM] × [1 - θ CL 1- CrCl1 × (CrCl1 - 1.89)] × e ηCL 1i (L/h). V1 (central volume): (V1 )i = V1TV × e ηV 1i (L). CL2 (clearance of peripheral compartment): (CL2 )i = CL2TV × [1 - θCL 2 - BODY AREA × (body area - 1.62)] × e ηCL 2i (L/h). V2 (peripheral compartment): (V2 )i = V2TV × [1 - θ V 2-bodyarea × (bodyarea-1.62)] × e ηV 2i (L). The PPK parameters (RSD%) were CL1, V1, CL2 and V2 with values of 6.20 L/h (8.48%), 19.6 L (extremely small), 0.0172 L/h (50.9%) and 0.515 L (39.1%), respectively. Creatinine clearance and the number of methotrexate chemotherapy cycles before MTX infusion had a significant effect on the CL1, and body surface area had a significant effect on the CL2 and the V2 (P < 0. 01). Conclusions: A good fit was derived for the PPK. The model could be used to provide guidance for MTX treatment and reduce adverse effects.

Aim： To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection （DHI）. Methods： Adult male rats underwent middle cerebral artery occlusion （MCAO）, and were injected with DHI （DH-1： 1 mL/kg; DH-2： 2.5 mL/kg; DH-3：5 mL/kg, and DH-4：10 mL/kg, iv） daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum levels of 20 free amino acids were determined using HPLC, and the values were transformed through the quantitative analysis of the amino acids in the serum metabolic spectrum. Multivariate statistical analysis methods （PCA and PLS-DA） and web-based metabolomics tools （MetPa and MetaboAnalyst） were used to analyze the biological data sets for the amino acids. Results： Administration of DHI dose-dependently decreased cerebral infarct volume, and ameliorated neurological deficits. A total of 5, 6, 7 and 7 non-overlapping metabolites were identified in the DH-1, DH-2, DH-3, and DH-4 groups, respectively. Eight metabolites were shared between the DHI groups and the vehicle group. In addition, the serum levels of glutamic acid, aspartic acid and serine increased with increasing DHI dose. A total of 3, 2, 2 and 5 non-overlapping metabolic pathways were identified in the DH-1, DH-2, DH-3 and DH-4 groups, respectively, and glycine, serine, threonine and histidine metabolism were identified as overlapping pathways among the 4 dose groups. Conclusion： Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.

Introduction It is important to decrease the radiation exposure of normal tissue in intensity‐modulated radiation therapy (IMRT). Minimizing planning target volume (PTV) margins with more precise target localization techniques can achieve this goal. This study aimed to quantify the extent to which organs at risk (OARs) are spared when using reduced margins in the treatment of nasopharyngeal carcinoma (NPC). Methods Two IMRT plans were regenerated for 40 patients with NPC based on two PTV margins, which were reduced or unchanged following cone beam computed tomography online correction. The reduced‐margin plan was optimized based on maximal dose reduction to OARs without compromising target coverage. Dosimetric comparisons were evaluated in terms of target coverage and OAR sparing. Results Improvements in target coverage occurred with margin reduction, and significant improvements in dosimetric parameters were observed for all OARs (P < 0.05) except for the right optic nerve, chiasm, and lens. Doses to OARs decreased at a rate of 1.5% to 7.7%. Sparing of the left parotid and right parotid, where the mean dose (Dmean) decreased at a rate of 7.1% and 7.7%, respectively, was greater than the sparing of other OARs. Conclusions Significant improvements in OAR sparing were observed with margin reduction, in addition to improvement in target coverage. The parotids benefited most from the online imaging‐guided approach.

Shenqi Wuweizi tablet is a Chinese medicine preparation mainly composed of Codonopsis pilosula, Astragalus membranaceus, Kadsura longipedunculata and Ziziphus jujube with many curative effects. The maximum tolerance dose of Shenqi Wuweizi tablet in mice was studied, and its acute toxicity in mice was ex- plored. The results showed that Shenqi Wuweizi tablet did not cause the death of mice at the maximum dosage and mice did not show toxic reaction, so it could be used in livestock production and clinical veterinary treatment. The study provided a theoretical basis for application of Shenqi Wuweizi tablet in livestock production and clinical veterinary medication safety.

OBJECTIVE To investigate an initial approach of radiotherapy, which produces cellular radiation injury by high dose in one fraction. METHODS Human pancreatic carcinoma cell line MIA PaCa-2, was cultivated and divided into 5 groups: 0, 2, 5, 10, 17 Gy. Cultivated cells were irradiated by 6MV-X ray in one fraction. Analysis were done as follows: comet assay, which assessed the level of DNA damage in the treated cells right a er the cell was irradiated, fl ow cytometry, which was performed at 0, 6, 12, 24, 36 h a er the cell line treated to asses changes of its cell cycle, DNA ladder, which quantitatively assessed the degree of DNA injury after 6 and 12 h, and histological examination, which analyzed cellular morphology a er 24 h. RESULTS (1) A er X-ray irradiated, the morphological change of human pancreatic carcinoma cell line (MIA PaCa-2) was mainly swelling. (2) When the dose of radiation was lower than 10 Gy, increasing the dose could greatly improve cell necrosis, apoptosis and blockage of cell cycle in G2/M phase, which was consistent with the theory of radiation biology. (3) When radiation dose was more than the 10 Gy, the peak of apoptotic necrosis appeared strong and early. (4) The degree of DNA injury was also related to the dose of radiation therapy and most obvious in the 10 Gy group and not so obvious in the 17 Gy group. (5) When dose was less than 10 Gy, DNA ladder was a single electrophoretic band; in the 10 Gy group, the electrophoresis showed a multiple ladder band; when dose was more than 10 Gy, a vague and irregular band appeared on the electrophoresis. CONCLUSION Oncotic necrosis may be the main cell death style when dose per fraction is high, which differs from conventional dose fraction radiation therapy.