吉林192Ir放射事故患者局部急性放射损伤病理改变

目的观察一例大剂量全身极不均匀照射急性放射损伤患者数处局部病理改变。方法病理常规切片染色，光镜检查。结果吸收剂量右下肢为３７３８Ｇｙ，左手掌为８３０Ｇｙ，于照射后第８天行右下肢、左前臂截肢术。右手、左膝照射剂量相对较小但难以准确估计，红斑、水肿、水疱、溃疡出现相对较晚，于第５５天行右手指、左膝清创植皮术。镜下：右小腿局部皮肤和皮肤附属器官、皮下组织和骨胳肌广泛地坏死和弥漫性出血，但真皮中的立毛肌尚存；左手指、手掌皮肤表皮细胞空泡变性、坏死，并形成大小不一的囊泡，致使表皮与真皮分离，真皮弥漫性出血、中性粒细胞浸润，汗腺上皮细胞变性、坏死，皮下组织内弥漫性出血，少数脂肪细胞坏死。胫骨、腓骨上端和股骨、桡骨、尺骨下端处骨髓腔内造血组织各系细胞均消失。左膝、右手拇指、食指、中指皮肤示急性放射性溃疡。结论大剂量照射导致的急性放射损伤造成大面积、深达肌肉的软组织坏死及骨髓造血细胞消失。     

丙氧锗二酸对顺铂毒性的保护作用及其对抗癌效果的影响

 本文研究了丙氧锗二酸（Ge－132）对顺铂毒性及抗癌效果的影响，并对其保护作用与金属硫蛋白（metallothionein，MT）的关系进行了探讨。结果表明Ge－132对顺铂引起的肾脏、血液和致死的毒性具有明显的保护作用。其效果优于次硝酸秘、亚硒醚钠以及氧化锗；Ge－132无诱导MT的作用，经体内抑瘤实验及体外细胞毒性实验表明，Ge－132对顺铂的抑瘤作用无统计学意义的影响。     

Long-circulating and liver-targeted nanoassemblies of cyclic phosphoryl N-dodecanoyl gemcitabine for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a serious cancer with high mortality worldwide. Gemcitabine (GEM) is easily degraded in the circulation and has no tumor-targeted effect. In our previous research, an amphiphilic GEM derivative, cyclic phosphoryl N-dodecanoyl gemcitabine (CPDG) was prepared based on the techniques of HepDirect prodrug and self-assembled drug delivery systems (SADDS), which self-assembled into the stable nanoassemblies in water. In this study, the long-circulating nanoassemblies of CPDG/CHS-PEG1500 (9:1, mol/mol) were prepared for HCC treatment. In vitro and in vivo studies of the long-circulating CPDG nanoassemblies were explored. The degradation rates of CPDG depended on the media. CPDG showed much faster degradation in the acidic environment (pH 2.0) than the weak acidic and neutral media (pH 5.0, pH 7.4). However, the degradation half-life (t_1/2) of CPDG was about 43 h in the mouse plasma, longer than the t_1/2 at pH 2.0. Therefore, the long-circulating CPDG nanoassemblies could keep stable before reaching the targets in vivo. In the biodistribution study, the long-circulating CPDG nanoassemblies were bolus intravenously (i.v.) injected into the hepatocellular tumor-bearing mice. The distribution of CPDG in the tumors was much higher than that in the blood, indicating the tumor targeting of the long-circulating nanoassemblies. In the pharmacodynamic study, the long-circulating CPDG nanoassemblies were i.v. injected into the tumor-bearing mice with doses of (37.5, 75 μmol/kg) compared with GEM (150 μmol/kg). The mice were injected once every 3 days for totally 3 times. The long-circulating nanoassemblies nearly always showed the higher anti-cancer effects than GEM. The tumor inhibitory rates of GEM, the long circulating CPDG nanoassemblies (37.5, 75 μmol/kg) were 49.54, 42.97, 65.10%, respectively. Therefore, the long-circulating CPDG nanoassemblies had the much higher anti-cancer effect than GEM. The long-circulating CPDG nanoassemblies are promising nanomedicines to treat HCC. The combination design of tumor-targeted nanoassemblies based on HepDirect prodrug technique and SADDS theory is an effective method to modify the pharmacologically active nucleosides to treat some liver diseases.     

Ion Torrent ™ Genexus ™ Integrated Sequencer and ForeNGS Analysis Software—An automatic NGS-STR workflow from DNA to profile for forensic science

The Ion Torrent ™ Genexus ™ Sequencer (Genexus) is a highly integrated instrument that can automate library construction, templating, and sequencing in a single-instrument run. By programing the ForeNGS Analysis Software (FNAS), we bridged the gap between sequencing and genotyping without manual intervention. FNAS can automatically transfer sequencing output files from Genexus, analyze the repeat and flanking regions aligned to the GRCh38 assembly, name the alleles according to the ISFG guidelines, and generate user-friendly interactive profiles. Genexus and FNAS can accomplish the fully automatic DNA-to-Profile workflow in forensics. Based on our experiences, the optimal assay parameters on Genexus were validated as follows: 24 cycles of target amplification for library construction; 40 μL of library and 400 bp of template size for templating; 852 flows of dNTPs by order of Ion samba HID2 for sequencing; and 750,000 reads per sample at minimum for 16 samples multiplexed on a lane. By developmental validations of the Precision ID Globalfiler ™ NGS STR Panel v2, Genexus presented competitive performance at the optimal assay parameters qualified to detect commonly used forensic STR markers. It could produce repeatable and reproducible results, and human profiles could be easily separated from nonhuman profiles. Additionally, Genexus was sensitive enough to detect samples with 100 pg of input DNA, and it was suitable for various types of case samples, especially for low copy number samples and degraded samples. Moreover, minor contributors could be detected between the 4:1 and 1:4 mixtures with an analysis threshold of 50 × . The Genexus workflow is a robust and labor-effective solution enabling forensic scientists to obtain NGS-STR profiles within a single day and with only the need to prepare DNA extracts, then set up Genexus, and finally interpret profiles on FNAS.     

Antidepressant-like effects of 071031B,a novel serotonin and norepinephrine reuptake inhibitor

SNRIs (serotonin and norepinephrine reuptake inhibitors) have been proposed to exert increased therapeutic efficacy or be faster acting compared to commonly used antidepressants. In this study, we performed in vitro binding and uptake assays and in vivo behavioral tests to assess the pharmacological properties and antidepressant-like efficacy of the compound 071031B; we also performed cytotoxicity tests using HepG2 cells and SH-SY5Y cells to predict the toxicity of 071031B. In vitro, 071031B had high affinity for both serotonin transporters and norepinephrine transporters prepared from rat cortex tissue (K_i=2.68 and 1.09 nM, respectively) and recombinant cells (K_i=1.57 and 0.36 nM, respectively). Moreover, 071031B also potently inhibited the uptake of serotonin (5-HT) and norepinephrine (NE) into rat cortical synaptosomes (K_i=1.99 and 1.09 nM, respectively) and recombinant cells (K_i=3.23 and 0.79 nM, respectively). In vivo, acute administration of 071031B dose-dependently reduced the immobility time in the tail suspension test in mice and the forced swimming test in mice and rats with higher efficacy than duloxetine and showed no stimulatory effect on the locomotor activity. Chronic 071031B treatment (5 or 10 mg/kg) significantly reversed depressive-like behaviors in chronically stressed rats, including reduced sucrose preference, decreased locomotor activity, and prolonged latency to begin eating. Furthermore, 071031B also exhibited lower cytotoxicity in HepG2 cells and SH-SY5Y cells in vitro than duloxetine. These findings suggest that 071031B is a novel, balanced serotonin and norepinephrine reuptake inhibitor, with more potent antidepressant effects and lower hepatotoxicity and neurotoxicity in vitro than duloxetine.     

强烈化疗结合外周血造血干细胞移植（PBSCT）治疗小细胞肺癌——探索性临床研究

近年来自身外周血造血干细胞移植(PBSCT)治疗实体瘤的临床报道较多，发展迅速。本报告307医院肿瘤科于1994年3月至1995年9月期间采用强烈化疗结合PBSCT治疗小细胞肺癌10例，男性9例，女性1例，平均年龄44．9岁，均为经过常规治疗失败后进行强烈化疗的。外周血造血干细胞动员采用化疗1例，G—CSF1例，G—CSF 化疗3例，硫酸葡聚糖 G-CSF2例，单纯硫酸葡聚糖3例。干细胞采集2次3例，1次7例。2例患采集干细胞数较多，单个核细胞数分别为1×10^8／kg和0．6×10^8/kg，CFU—GM分别为0．4×10^6／kg和0．15×10^6／kg。经卡铂1500mg，VP—161000mg，阿霉素120mg化疗后患1例PR，1例至今无复发，这2例患白细胞下降最低点分别为0．2×10^9／kg和0．4×10^9／kg。血小板下降最低点均为4×10^9／L，达到移植水平，目前均存活。另8例患中，肿瘤PR4例，无变化4例，这8例患骨髓抑制也十分明显，6例白细胞下降Ⅳ度，6例血小板下降Ⅳ度。其他尚有消化道反应、脱发等反应，由于精心护理，无治疗引起死亡发生。作认为,小细胞肺癌对化疗、放疗均十分敏感，是PBSCT的适应症，但要考虑病期，身体状况，治疗方案等因素，而且这一治疗方法要求层流无菌病房，治疗费用也相当昂贵，固此强烈化疗结合PBSCT目前仍处于临床研究探索阶段。作对PBSCT的优点和今后研究方向进行了讨论。     

The effect of gefitinib (Iressa,ZD1839) in combination with oxaliplatin is schedule-dependent in colon cancer cell lines

Background Clinical trials of gefitinib (Iressa, ZD1839) in combination with cytotoxic agents have been carried out or are ongoing in several varieties of tumor. To provide a rationale for future clinical trials, the effects of combining gefitinib with oxaliplatin in different sequences of administration and different dose ratios in two colon cancer cell lines were evaluated.Materials and methods The colon cancer cell lines HT-29 and LoVo were used. The methods consisted of median effect and combination index analysis, Western blot, mass spectrometry, and a cell death ELISA.Results In vitro analysis demonstrated that the combination effects of the two agents were sequence-dependent. Changing the sequence of administration from gefitinib first to gefitinib last changed the combination effect from antagonism to synergy. The dose ratio between the two agents affected the combination effects. When equiactive doses of the two agents were used with the sequence gefitinib following oxaliplatin, the greatest level of synergism was obtained (CI=0.6±0.2, P=0.032). Further evaluation revealed that gefitinib significantly inhibited removal of Pt-DNA adducts (P<0.05), providing a potential explanation for the sequence-dependent synergy observed with gefitinib following oxaliplatin. However, this effect was not dose-dependent. Additional studies demonstrated that gefitinib enhanced the effects of oxaliplatin by maintaining oxaliplatin-induced apoptosis, and equiactive dose of gefitinib following oxaliplatin induced prominent enhancement of apoptosis.Conclusions Oxaliplatin followed by an equiactive relative dose of gefitinib is an appropriate combination for evaluation in colon cancer.     

6MVX射线超高剂量照射人离体血淋巴细胞微核的剂量效应研究

本文用CB微核法研究了超高剂量6MVX射线照射人离体血后微核(MN)的剂量效应关系, 见到剂量高至25Gy仍可见双核cB细胞, 在0～10Gy范围内, MN率与照射剂量呈正相关 关系, 并得到拟合较好的回归方程, 有可能打破近30正来生物剂量估算为5 Gy的上限, 使能直接的估算大于5Gy受照者的生物剂量, 摄高了以MN检测作为生物学剂量计的应用价值。10Gy以上, MN串的上升呈平缓的坪趋势, 在10～25Gy范围内虽不能精确的估算剂量, 但片中双核CB细胞的多少, 对判断剂量有—定参考价值。     

一例192Ir极不均匀外照射局部极重度放射损伤的临床观察

目的 对１例＾１９２Ｉｒ极不均匀外照射局部极重度放射损伤病人进行临床观察。方法 系统观察了病变的临床过程和应用红外线热成像技术测定了损伤部位的温度变化。结果 照射后２小时出现肢体麻木、抽搐，最早照后４小时出现红斑、肿胀，５４小时出现水疱，第５天出现坏死和剧痛，最晚出现红斑、肿胀是照射后４１天，４７天出现水疱和糜烂创面。红外线热成像显示：损伤早期温度升高，水疱、坏死区和损伤后期温度降低，温度升高越早     

MTT体外药敏试验指导下的乳癌预见性化疗

探讨３－（４,５）－双甲基－２－噻唑－（２,５）－二苯基溴化四氮唑蓝（ＭＴＴ）体外药敏试验指导临床乳癌化疗的价值。方法１５６例晚期乳癌病人中,８３例在化疗前接受了ＭＴＴ体外药敏试验。其中ＭＴＴ敏感组７３例,根据药敏结果指导化疗;ＭＴＴ耐药组１０例、对照组７３例则凭经验化疗。结果ＭＴＴ敏感组有效率为７６．７％（５６／７３）,ＭＴＴ耐药组和对照组分别为０（０／１０）及４３．８％（３２／７３）,差异有显著意义。敏感组与对照组在不同的治疗阶段、大部分病灶及化疗方案的小组比较中,差异也均有显著意义。敏感组病人再次复发转移率、死亡率显著减少,但再度复发病人的中位缓解期及中位生存期尚无显著变化。本研究体外药敏和体内疗效的总符合率为７９．５％［（５６＋１０）／８３］。结论ＭＴＴ体外药敏试验指导乳癌化疗是可行的,疗效也是满意的