脑转移瘤局部推量的临床观察

目的：观察脑转移瘤放射治疗局部推量的疗效。方法：回顾性分析63例进行放射治疗脑转移瘤病人,采用6MeV-X线,两侧平行相对野作全脑照射,临床靶体积（CTV）包括肿瘤靶体积（GTV）及周围水肿区,处方剂量为30-40Gy,分割次数为10-20次。其中27例缩野后局部推量20Gy。分析常规处方剂量后进行局部推量与未进行局部推量的两个组别局部区域复发率（LRR）、总生存率（OS）和KPS评分改变的差别。结果：中位随访6个月。局部推量组和未局部推量组的LRR分别为18.5%（5/27）和27.8%（10/36）;局部推量组和未局部推量组的OS分别为85.2%（23/27）和77.8%（28/36）;局部推量组和未局部推量组的KPS〉=70分别为18和19。结论：脑转移瘤常规处方剂量放疗后进行局部推量对脑转移瘤的局部控制率及KPS评分有益。     

脑转移瘤局部推量的临床观察

目的:观察脑转移瘤放射治疗局部推量的疗效。方法:回顾性分析63例进行放射治疗脑转移瘤病人,采用6MeV-X线,两侧平行相对野作全脑照射,临床靶体积(CTV)包括肿瘤靶体积(GTV)及周围水肿区,处方剂量为30~40Gy,分割次数为10~20次。其中27例缩野后局部推量20Gy。分析常规处方剂量后进行局部推量与未进行局部推量的两个组别局部区域复发率(LRR)、总生存率(OS)和KPS评分改变的差别。结果:中位随访6个月。局部推量组和未局部推量组的LRR分别为18.5%(5/27)和27.8%(10/36);局部推量组和未局部推量组的OS分别为85.2%(23/27)和77.8%(28/36);局部推量组和未局部推量组的KPS>=70分别为18和19。结论:脑转移瘤常规处方剂量放疗后进行局部推量对脑转移瘤的局部控制率及KPS评分有益。     

Characterization of a novel mutant KCNQ1 channel subunit lacking a large part of the C-terminal domain

A mutation of KCNQ1 gene encoding the alpha subunit of the channel mediating the slow delayed rectifier K⁺ current in cardiomyocytes may cause severe arrhythmic disorders. We identified KCNQ1(Y461X), a novel mutant gene encoding KCNQ1 subunit whose C-terminal domain is truncated at tyrosine 461 from a man with a mild QT interval prolongation. We made whole-cell voltage-clamp recordings from HEK-293T cells transfected with either of wild-type KCNQ1 [KCNQ1(WT)], KCNQ1(Y461X), or their mixture plus KCNE1 auxiliary subunit gene. The KCNQ1(Y461X)-transfected cells showed no delayed rectifying current. The cells transfected with both KCNQ1(WT) and KCNQ1(Y461X) showed the delayed rectifying current that is thought to be mediated largely by homomeric channel consisting of KCNQ1(WT) subunit because its voltage-dependence of activation, activation rate, and deactivation rate were similar to the current in the KCNQ1(WT)-transfected cells. The immunoblots of HEK-293T cell-derived lysates showed that KCNQ1(Y461X) subunit cannot form channel tetramers by itself or with KCNQ1(WT) subunit. Moreover, immunocytochemical analysis in HEK-293T cells showed that the surface expression level of KCNQ1(Y461X) subunit was very low with or without KCNQ1(WT) subunit. These findings suggest that the massive loss of the C-terminal domain of KCNQ1 subunit impairs the assembly, trafficking, and function of the mutant subunit-containing channels, whereas the mutant subunit does not interfere with the functional expression of the homomeric wild-type channel. Therefore, the homozygous but not heterozygous inheritance of KCNQ1(Y461X) might cause major arrhythmic disorders. This study provides a new insight into the structure–function relation of KCNQ1 channel and treatments of cardiac channelopathies.     

白头翁汤合芍药汤加减联合左氧氟沙星对细菌性痢疾患者细菌清除率及CRP和TNF\|α水平的影响

目的探究白头翁汤合芍药汤加减联合左氧氟沙星对细菌性痢疾患者细菌清除率及血清CRP、TNF-α水平的影响。方法选择我院2016年1月至2017年1月收治的60例细菌性痢疾患者为研究对象,采取随机数字表法将患者分为观察组和对照组各30例,对照组患者采用左氧氟沙星治疗,观察组患者采用白头翁汤合芍药汤加减联合左氧氟沙星治疗,对比两组患者疗效、细菌清除率、治疗前后血清C反应蛋白(CRP)及肿瘤坏死因子α(TNF-α)水平变化、患者发热消失时间、腹痛腹泻消失时间、不良反应情况。结果观察组患者有效率(100.00%)高于对照组(83.33%),观察组患者病原菌清除率(100.00%)高于对照组(80.00%),差异均有统计学意义(均P0.05)。治疗前两组患者CRP、TNF-α水平差异无统计学意义(P0.05),治疗后两组患者CRP、TNF-α水平均显著降低,且观察组低于对照组,差异均有统计学意义(均P0.05)。治疗后观察组患者发热消失时间、腹痛腹泻消失时间均短于对照组(均P0.05),同时两组患者不良反应发生率均为3.33%。结论白头翁汤合芍药汤加减联合左氧氟沙星可有效清除细菌性痢疾患者体内病原菌,提升临床疗效,促进患者快速康复,且患者不良反应发生率低,安全可靠,值得推广应用。     

Early life stress effects on adult stress-induced corticosterone secretion and anxiety-like behavior in the C57BL/6 mouse are not as robust as initially thought

Understanding environmental effects on mouse brain development would allow us to take advantage of powerful genetic tools to determine the interaction between genetic and epigenetic factors governing brain development in C57BL/6 mice. Experiment 1 examined whether time of day for neonatal manipulations affects adult stress-induced hormone secretion. Three rearing groups were examined: early handled (EH; dam removed 10 min/day); maternal separated (MS; dam removed 180 min/day); and an animal facility raised (AFR) control. Separations occurred during either the first or last 3 h of the light phase. Corticosterone (CORT) secretion in response to 100 dB white noise was assessed in adulthood. Both EH and MS males separated during the last 3 h of the light phase exhibited blunted stress-induced CORT compared to all other groups. Experiment 2 varied time of behavior testing. A fourth group was also added: maternal isolated (MI; separated from dam and littermates 180 min/day). Adult male behavior was assessed in three different tests. EH males tested in the elevated zero maze (EZM) during the light phase and MS males tested in the EZM during the dark phase exhibited diminished anxiety-like behavior compared to the other groups. We conclude that the EH protocol is marginally effective in blunting stress-induced CORT secretion and anxiety-like behavior in C57BL/6 mice, and these early handling effects are influenced by time of day. We also conclude that the 3 h MS or MI protocol is not effective in exacerbating future adult stress-induced CORT secretion or anxiety-like behavior in C57BL/6 mice.     

Temperature-dependent biotransformation of 2,4'-dichlorobiphenyl by psychrotolerant Hydrogenophaga strain IA3-A: higher temperatures prevent excess accumulation of problematic meta-cleavage products

AIMS: The present work investigates the possibility that temperature could regulate the pattern of transformation of 2,4'-chlorobiphenyl (2,4'-CB) by psychrotolerant Hydrogenophaga sp. IA3-A. Methods AND RESULTS: Transformation of 2,4'-chlorobiphenyl to 2- and 4-chlorobenzoic acid (2- and 4-CBA), and meta-cleavage products by cells of strain IA3-A incubated at 10 degrees C, 25 degrees C, 37 degrees C or 45 degrees C were monitored by UV spectrometry, HPLC and GC-MS analyses. Cultures incubated at 10 degrees C, 25 degrees C or 37 degrees C produced low amounts of CBAs and excess levels of meta-cleavage products from 2,4'-CB. Cultures incubated at 45 degrees C transformed most of the degraded 2,4'-CB to CBAs and low level of meta-cleavage product. Culture extracts contained unusual varieties of isomeric hydroxylated metabolic products. CONCLUSIONS: Efficient transformation of 2,4'-CB to CBAs was possible in cultures incubated at 45 degrees C. Evidence for the involvement of multiple pathways in the transformation of 2,4'-CB in strain IA3-A suggests that differential regulation of the pathways at different temperatures was likely responsible for the change in the pattern of transformation of 2,4'-CB in cultures incubated at 45 degrees C. Significance AND IMPACT OF THE STUDY: It may be possible to condition cells to transform chlorinated biphenyls more efficiently without accumulating excess level of toxic intermediates.     

二不同年龄组脉搏波特征参数的研究

选取20名年轻的（21-29岁）和20名年老的（70—80岁）血压正常的健康受试者为研究对象,以12位、250Hz采集每位受试者的指端脉搏波数据、为了研究脉搏波波形特征与生理因素的关系,提出了脉搏波导数最大值这一新的特征参数,该参数具有灵敏度高、计算简单的优点．我们用MATLAB编程自动检测出波形特征点的位置,并计算出每位受试者的各项特征参数值、结果如下：脉搏波导数最大值是年轻组明显大于年老组（P〈0．01）,波图面积的K值是年轻组小于年老组（P〈0．1）．结果预示了这些指标可作为评价心血管系统功能的重要依据。     

Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor.     

Modification of extracorporeal photopheresis technology with porphyrin precursors. Comparison between 8-methoxypsoralen and hexaminolevulinate in killing human T-cell lymphoma cell lines in vitro

Background

Extracorporeal photopheresis that exposes isolated white blood cells to 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light is used for the management of cutaneous T-cell lymphoma and graft-versus-host disease. 8-MOP binds to DNA of both tumor and normal cells, thus increasing the risk of carcinogenesis of normal cells; and also kills both tumor and normal cells with no selectivity after UV-A irradiation. Hexaminolevulinate (HAL)-induced protoporphyrin-IX is a potent photosensitizer that localizes at membranous structures outside of the nucleus of a cell. HAL-mediated photodynamic therapy selectively destroys activated/transformed lymphocytes and induces systemic anti-tumor immunity. The aim of the present study was to explore the possibility of using HAL instead of 8-MOP to kill cells after UV-A exposure.

Methods

Human T-cell lymphoma Jurkat and Karpas 299 cell lines were used to evaluate cell photoinactivation after 8-MOP and/or HAL plus UV-A light with cell proliferation and long term survival assays. The mode of cell death was also analyzed by fluorescence microscopy.

Results

Cell proliferation was decreased by HAL/UV-A, 8-MOP/UV-A or HAL/8-MOP/UV-A. At sufficient doses, the cells were killed by all the regimens; however, the mode of cell death was dependent on the treatment conditions. 8-MOP/UV-A produced apoptotic death exclusively; whereas both apoptosis and necrosis were induced by HAL/UV-A.

Conclusion

8-MOP can be replaced by HAL to inactivate the Jurkat and Karpas 299 T-cell lymphoma cells after UV-A irradiation via apoptosis and necrosis. This finding may have an impact on improved efficacy of photopheresis.