原位移植人耐药肺癌的p53基因与药物的联合治疗

人耐药肺癌细胞GLK的p53基因在codom245发生G→T突变,利用GLK细胞的裸鼠原位移植模型,将逆转病毒载体介导的野生型P53基因(PDOR53W)通过气管注入,以增加GLK细胞的药物敏感性,然后结合腹腔注射阿霉素进行实验治疗.结果发现肺内接种2×10⁷GLK细胞后30d,75%的对照组裸鼠形成肉眼可见的肿瘤结节;单独气管注入pDOR53W培养上清液的裸鼠有约37%成瘤,而且肿瘤体积比对照组明显减小;气管注入pDOR53W结合阿霉素治疗的则只有11.1%成瘤,肿瘤体积也明显减小;单独阿霉素治疗而没有气管注入pDOR53W的裸鼠有66.7%成瘤, 用PCR和Southern杂交方法证实在注入pDOR53W的移植瘤中均可检测出外源病毒p53 DNA的存在.这表明逆转病毒载体介导的野生型p53基因局部注射结合药物治疗可能是人耐药肺癌治疗的有效方法.     

小型黑光灯治疗斑块型银屑病疗效观察

目的:观察小型黑光灯治疗斑块型银屑病疗效。方法:采用小型黑光灯(电压220V,电流0.34A,功率25.4W,主波峰长365nm,辐照度为1070μW/cm2)治疗76例斑块型银屑病患者,20次为一疗程。结果:小型黑光灯第一疗程和第二疗程临床显效率分别达72.37%和84.21%,未发现明显不良反应。结论:小型黑光灯治疗斑块型银屑病具有治疗方便、疗效好,不良反应小等优点。     

藏北高山嵩草草甸群落特征及生产力对模拟增温幅度的响应

青藏高原气候严酷,陆地表层生态系统脆弱,其高寒植物群落特征及生态系统生产力对气候变化的响应极其敏感。利用开顶箱(OTCs,Open Top Chambers)式装置在藏北高山嵩草(Kobresia pygmaea)草甸设置不同增温梯度实验(W1、W2、W3、W4),探究增温对高寒草甸植物群落特征及地上生产力的影响。研究结果表明:1)与对照样地相比,增温减少了植物群落总盖度(2015年,W1、W2、W3、W4分别显著减少了28%、23%、59%、60%; 2016年,W4显著减少了83%)和高山嵩草盖度(2015年,W1、W2、W3、W4分别显著减少了26%、33%、681%、64%; 2016年,W4显著减少了85%),而低幅度增温(W1、W2)对委陵菜属植物盖度无显著影响,高幅度增温(W3、W4)显著减少了委陵菜属植物盖度(2015年,W3、W4分别显著减少了58%和60%;2016年,W4显著减少了71%); 2)对整个植物群落而言,增温幅度较低时,增温对群落的生长和生物量的积累有促进作用,当温度升高超过一定程度,这种促进作用会逐渐减弱甚至变成抑制作用(2015年,W4显著减少了地上生物量69%; 2016年,W4显著减少了地上生物量82%); 3)高山嵩草盖度和其他物种总盖度存在显著的年际差异,而委陵菜属植物盖度无明显的年际变化。研究结果预示着,一定程度的升温会促进高寒草甸植物群落的生长,但温度升高超过一定幅度时,会导致草地生产力下降,草地退化加剧,同时当地群落中委陵菜属植物在全球变化背景下相对稳定,这类物种在未来气候变暖的背景下可能具有更强的竞争力。     

藏北高山嵩草草甸群落特征及生产力对模拟增温幅度的响应

青藏高原气候严酷,陆地表层生态系统脆弱,其高寒植物群落特征及生态系统生产力对气候变化的响应极其敏感。利用开顶箱(OTCs,Open Top Chambers)式装置在藏北高山嵩草(Kobresia pygmaea)草甸设置不同增温梯度实验(W1、W2、W3、W4),探究增温对高寒草甸植物群落特征及地上生产力的影响。研究结果表明:1)与对照样地相比,增温减少了植物群落总盖度(2015年,W1、W2、W3、W4分别显著减少了28%、23%、59%、60%;2016年,W4显著减少了83%)和高山嵩草盖度(2015年,W1、W2、W3、W4分别显著减少了26%、33%、61%、64%;2016年,W4显著减少了85%),而低幅度增温(W1、W2)对委陵菜属植物盖度无显著影响,高幅度增温(W3、W4)显著减少了委陵菜属植物盖度(2015年,W3、W4分别显著减少了58%和60%;2016年,W4显著减少了71%);2)对整个植物群落而言,增温幅度较低时,增温对群落的生长和生物量的积累有促进作用,当温度升高超过一定程度,这种促进作用会逐渐减弱甚至变成抑制作用(2015年,W4显著减少了地上生物量69%;2016年,W4显著减少了地上生物量82%);3)高山嵩草盖度和其他物种总盖度存在显著的年际差异,而委陵菜属植物盖度无明显的年际变化。研究结果预示着,一定程度的升温会促进高寒草甸植物群落的生长,但温度升高超过一定幅度时,会导致草地生产力下降,草地退化加剧,同时当地群落中委陵菜属植物在全球变化背景下相对稳定,这类物种在未来气候变暖的背景下可能具有更强的竞争力。     

测墒补灌对冬小麦氮素积累与转运及籽粒产量的影响

2007-2009年,在田间条件下,以冬小麦品种济麦22为材料,以0-140 cm土层平均土壤相对含水量为指标设计4个测墒补灌试验处理:W0(土壤相对含水量为播种期80%+拔节期65%+开花期65%)、W1(土壤相对含水量为播种期80%+拔节期70%+开花期70%)、W2(土壤相对含水量为播种期80%+拔节期80%+开花期80%)和W3(土壤相对含水量为播种期90%+拔节期80%+开花期80%),研究不同水分处理对冬小麦氮素积累与转运、籽粒产量、水分利用效率及土壤硝态氮含量的影响。结果表明:(1)成熟期小麦植株氮素积累量为W1处理最高,W3处理次之,W0和W2处理最低,W0和W2处理间无显著差异;氮素向籽粒的分配比例为W2处理显著低于W1处理,W0、W1、W3处理间无显著差异。开花期和成熟期营养器官氮素积累量、营养器官氮素向籽粒中的转移量、成熟期籽粒氮素积累量均为W1>W3>W2>W0,各处理间差异显著。(2)随着小麦生育进程的推进,0-200 cm土层土壤硝态氮含量先降低后回升再降低,在拔节期最低。成熟期W0和W1处理0-200 cm土层土壤硝态氮含量较低,W2和W3处理120-200 cm土层土壤硝态氮含量较高。(3)W0处理小麦氮素吸收效率、利用效率和氮肥偏生产力最低;随灌水量的增加,氮素利用效率呈先升高后降低趋势;W1处理小麦对氮素的吸收效率和利用效率较高,氮肥偏生产力最高。W0处理水分利用效率较高,但籽粒产量最低;灌水处理籽粒产量、灌溉水利用效率和灌溉效益两年度均随测墒补灌量的增加而显著降低。在本试验条件下,综合氮素利用、籽粒产量、灌溉水利用效率及土壤中硝态氮的淋溶,W1是高产节水的最佳灌溉处理,在2007-2008年和2008-2009年度补灌量分别为43.83 mm和13.77 mm。     

水分胁迫对银水牛果生长及光合气体交换参数的影响

实验以盆栽3年生银水牛果幼苗为材料,设置正常供水(W1)和轻度(W2)、中度(W3)、重度(W4)土壤水分胁迫共4个处理进行人工模拟实验,以探讨银水牛果的抗旱特征.结果显示,(1)随着水分胁迫的加剧,W2～W4银水牛果植株生长量较W1分别显著降低58.85%、72.06%、87.31%,地径生长量较W1分别显著降低38.46%、61.92%、84.62%;(2)随着水分胁迫的加剧,Pn日变化曲线由"单峰型"转为"双峰型",且Pn、Gs、Tr逐渐降低,Ls值升高;(3)W3处理下Ci值最小,Ls值最大,而水分利用效率WUE最高;(4)随着水分胁迫的加剧,Gs与Pn的相关性迅速下降,W2～W4的相关系数较W1分别下降5.06%、8.47%、24.38%;W4处理下Ci与Pn呈负相关.研究表明,银水牛果在土壤含水量为7.2%～14.35%干旱条件下水分利用效率最高,证明银水牛果具有较强的抗旱性.     

增施钾肥对大棚蟠桃品质及营养生长的影响

该研究以蟠桃品种‘金霞蟠桃’和‘玉霞蟠桃’为试材,分别在2个品种成熟前3周(3W)、2周(2W)和1周(1W)每树环施钾肥(K2O)1 000g,比较不同时期施肥处理蟠桃果实外观品质、内在品质以及营养生长的变化。结果表明:(1)在蟠桃果实成熟前2W和3W尤其是2W施用钾肥,蟠桃果实单果重和体积总体较大,‘金霞蟠桃’2W处理果实单果重、横径和侧径分别显著高于1W处理11.48%、3.51%和3.03%,‘玉霞蟠桃’2W处理则分别显著高于1W处理56.86%、14.97%和3.67%;(2)不同时期增施钾肥对‘玉霞蟠桃’果实颜色的变化影响总体较小,‘金霞蟠桃’2W和3W处理果实的a*值分别显著高于1W处理55.02%和44.49%,但2W和3W处理之间差异不显著;(3)增施钾肥后,2个蟠桃品种果实可溶性固形物含量、蔗糖含量从高到低依次为2W3W1W,可溶性糖总量大小也依次为2W3W1W,但2W和3W处理间差异不显著;不同时期增施钾肥对2个蟠桃品种果实有机酸总量和枝叶营养生长总体影响不大。研究认为,在蟠桃果实成熟前2周左右施用钾肥,成熟时果实体积、单果重增大,果肉可溶性固形物、蔗糖、可溶性总糖含量以及糖酸比高,果实综合品质得到有效改善,但增施钾肥过早或过晚都无法达到最佳效果。     

人工模拟降水格局变化对醉马草种子萌发和幼苗生长的影响

降水格局的变化会影响到植物种子萌发出苗过程及幼苗的更新。本研究以呈扩张趋势的草原毒害草醉马草(Achnatherum inebrians)种子为材料,利用环境控制培养箱进行降水量(W-60%,W-30%,W,W+30%,W+60%)和降水间隔(T5,T10)的双因素控制实验,探讨醉马草种子萌发和幼苗生长对降水格局变化的响应规律,以期为探索醉马草的发生规律及预测其潜在分布范围提供科学依据。结果表明:(1)在相同降水间隔条件下,醉马草的出苗速度和出苗率随着总降水量的增加而提高;延长降水间隔促进W和W+30%条件下醉马草出苗,加快出苗进程。(2)无论降水间隔是否变化,总降水量增加60%(W+60%)使出苗势和出苗指数显著提高(P<0.05);在W和W+30%条件下,延长降水间隔使出苗率、出苗势和出苗指数显著提高(P<0.05)。(3)无论降水间隔是否变化,总降水量减少30%(W-30%)显著抑制幼根和幼苗的生长,总降水量增加60%(W+60%)显著促进幼苗的生长(P<0.05);但总降水量增加30%(W+30%)和60%(W+60%)均显著降低根苗比(P<0.05)。...     

水氮耦合对小桐子生长和灌溉水利用效率的影响

为了研究水氮耦合对于小桐子生长和灌溉水利用效率的影响,采用3个供水水平(W1,15.3mm;W2,25.5mm;W3,40.7mm)和3个施氮水平(N1,0g·kg-1;N2,0.3g·kg-1;N3,0.6g·kg-1)进行盆栽实验。结果表明:与W3相比,W1和W2处理的株高、茎粗、叶面积和总干物质量分别降低了61%和34%、57%和35%、46%和32%、49%和35%,根冠比在W2处理时达到最大值;对不同氮素处理,株高和叶面积最大值均出现在N2处理,而茎粗和根冠比则随着施氮量的增加而减小;与W3N3相比,W2N2处理节省灌溉用水38%,节约氮肥施用量50%,其株高、茎粗和总干物质量分别减少了12%、21%和12%,根冠比和叶面积分别显著增加了48%和16%,灌水后第2天、第3天和第4天的蒸腾量分别显著降低21%、15%和12%,从而使灌溉水利用效率提高了40%。     

人工模拟降水格局变化对醉马草种子萌发和幼苗生长的影响

降水格局的变化会影响到植物种子萌发出苗过程及幼苗的更新。本研究以呈扩张趋势的草原毒害草醉马草(Achnatherum inebrians)种子为材料,利用环境控制培养箱进行降水量(W-60%,W-30%,W,W+30%,W+60%)和降水间隔(T5,T10)的双因素控制实验,探讨醉马草种子萌发和幼苗生长对降水格局变化的响应规律,以期为探索醉马草的发生规律及预测其潜在分布范围提供科学依据。结果表明:(1)在相同降水间隔条件下,醉马草的出苗速度和出苗率随着总降水量的增加而提高;延长降水间隔促进W和W+30%条件下醉马草出苗,加快出苗进程。(2)无论降水间隔是否变化,总降水量增加60%(W+60%)使出苗势和出苗指数显著提高(P0.05);在W和W+30%条件下,延长降水间隔使出苗率、出苗势和出苗指数显著提高(P0.05)。(3)无论降水间隔是否变化,总降水量减少30%(W-30%)显著抑制幼根和幼苗的生长,总降水量增加60%(W+60%)显著促进幼苗的生长(P0.05);但总降水量增加30%(W+30%)和60%(W+60%)均显著降低根苗比(P0.05)。降水量增加或减少不同程度地影响醉马草的出苗和生长,但在一定降水范围内,延长降水间隔则促进醉马草的出苗和幼苗生长。     

激光治疗急性膝关节膑下脂肪垫损伤 60例临床疗效观察

采用激光照射治疗急性膝关节膑下脂肪垫损伤60例。一次性治疗,治愈率85%,有效率15%,无效率0,未发现明显毒副作用。结果显示激光在软组织疼痛早期有很好的疗效。     

激光治疗急性踝关损伤40例临床疗效观察

采用SUNDOM-300I型半导体激光（波长810nm,终端输出功率0mW-500mW,连续可调,光速直径5mm）,治疗急性踝关节损伤40例,平均治疗次数为4次,治愈率72.5％,有效率27.5％,示发现明显毒副作用。结果显示激光在治疗软组织疼痛的早期有较好的疗效。     

光化学疗法治疗手角化过度性湿疹60例临床疗效观察

采用光化化学疗法,外涂0．2％8-MOP半小时后以光化肤康灯(主峰波长365nm,终端输出功率25．4W连续可词,幅照度：930UW／cm^2)照射,治疗手角化过度性湿疹60例,平均治疗间期1月,治愈率48．33％,显效率18．33％,有效率28．33％,无效率5％。未发现明显毒副作用。结果显示光化学疗法对手角化过度性湿疹有很好的疗效。     

Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation

Fifty consecutive new cardiology clinic patients who were on statin drug therapy (for an average of 28 months) on their initial visit were evaluated for possible adverse statin effects (myalgia, fatigue, dyspnea, memory loss, and peripheral neuropathy). All patients discontinued statin therapy due to side effects and began supplemental CoQ(10) at an average of 240 mg/day upon initial visit. Patients have been followed for an average of 22 months with 84% of the patients followed now for more than 12 months. The prevalence of patient symptoms on initial visit and on most recent follow-up demonstrated a decrease in fatigue from 84% to 16%, myalgia from 64% to 6%, dyspnea from 58% to 12%, memory loss from 8% to 4% and peripheral neuropathy from 10% to 2%. There were two deaths from lung cancer and one death from aortic stenosis with no strokes or myocardial infarctions. Measurements of heart function either improved or remained stable in the majority of patients. We conclude that statin-related side effects, including statin cardiomyopathy, are far more common than previously published and are reversible with the combination of statin discontinuation and supplemental CoQ(10). We saw no adverse consequences from statin discontinuation.     

微等离子体射频技术治疗成熟瘢痕50例临床观察

目的:研究新型微等离子体射频技术治疗瘢痕的效果。方法:50例成熟瘢痕患者,包括31例痤疮疤痕,19例外伤或手术疤痕。均采用微等离子体射频技术进行功率为70～90Watt的滑动式或定点式治疗,每4周治疗一次,共治疗2～5次,通过治疗前及治疗后3个月统一衡量标准对比来进行疗效评估。结果:成熟瘢痕表现为身体各部位分布形状不规则形状皮肤组织凹陷或轻度增生。通过临床指标评分,50例患者总有效率为82%。疗效显著18例(36%),有效22例(44%),轻微改善11例(22%),无效9例(18%)。结论:微等离子体射频技术能显著改善成熟瘢痕的色泽、质地和凸凹程度,不良反应少,是治疗成熟瘢痕的有效方法。     

Epimutations in Prader-Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurogenetic disorders that are caused by the loss of function of imprinted genes in 15q11-q13. In a small group of patients, the disease is due to aberrant imprinting and gene silencing. Here, we describe the molecular analysis of 51 patients with PWS and 85 patients with AS who have such a defect. Seven patients with PWS (14%) and eight patients with AS (9%) were found to have an imprinting center (IC) deletion. Sequence analysis of 32 patients with PWS and no IC deletion and 66 patients with AS and no IC deletion did not reveal any point mutation in the critical IC elements. The presence of a faint methylated band in 27% of patients with AS and no IC deletion suggests that these patients are mosaic for an imprinting defect that occurred after fertilization. In patients with AS, the imprinting defect occurred on the chromosome that was inherited from either the maternal grandfather or grandmother; however, in all informative patients with PWS and no IC deletion, the imprinting defect occurred on the chromosome inherited from the paternal grandmother. These data suggest that this imprinting defect results from a failure to erase the maternal imprint during spermatogenesis.     

4-Hydroxyandrostenedione treatment for postmenopausal patients with advanced breast cancer

We have treated 128 postmenopausal women with advanced breast cancer with 4-hydroxyandrostenedione. Of these, 118 were assessable for toxicity and 100 for response to treatment. Response to therapy was seen in 34% of patients and stabilization of disease in 12 patients. Three dose regimens were used (500 mg intramuscularly weekly; 250 mg intramuscularly every 2 weeks; and 500 mg orally daily). There was no difference in response in these three groups. Side effects were minimal and local reaction to injected drug was seen in 13% of patients. The sole severe side effect observed was neutropenia which was transient and reversible on discontinuing therapy. 4-Hydroxyandrostenedione is an effective nontoxic agent in the treatment of breast cancer.     

Increased radiation toxicity with germline ATM variant of uncertain clinical significance

BackgroundWhile patients with ataxia telangiectasia are known to have increased radiation sensitivity, patients with germline heterozygous ataxia telangiectasia mutated (ATM) mutations can have widely varying functional and clinical effects, which can make management decisions difficult. With an increased prevalence of gene panel-based testing for breast cancer patients, radiation oncologists are increasingly confronted with patients who carry germline ATM variants of uncertain clinical significance. This study describes the clinical courses and outcomes of 5 breast cancer patients with varying germline heterozygous ATM mutations undergoing radiation therapy at our institution in order to provide additional knowledge of the varying clinical effects to aid future decision making.Case SeriesWe identified 5 patients with breast cancer and varying germline heterozygous ATM mutations treated at the University of North Carolina Hospitals between 2015 and 2017. The median age at breast cancer diagnosis for the patient series was 46. Clinical effects of radiation treatment varied amongst the 5 patients. The one patient with a pathogenic ATM mutation had no increased radiation related toxicity. Of the 4 patients with ATM variants of uncertain significance, one patient had increased radiation sensitivity with Grade 3 dermatitis. All patients have remained recurrence free with a median duration of 18 months.ConclusionOur data illustrates that patients with germline heterozygous ATM mutations can have widely varying clinical effects with radiation therapy. Given the possibility of unpredictable deleterious effects, our study highlights the importance of caution and careful consideration when devising the multi-modality management strategy in these patients.     

Oxidative stress impairs glutamate uptake in fibroblasts from patients with Alzheimer's disease

Oxidative stress has been demonstrated in Alzheimer's disease (AD) brain and may affect glutamate transport (GT), thereby leading to excitotoxic neuronal death. Since oxidative stress markers have been shown also in peripheral tissues, we investigated possible GT alterations in fibroblast cultures obtained from 18 patients with AD and 15 control patients and analyzed the effects of the lipoperoxidation product 4-hydroxynonenal (4-HNE) and antioxidants. Basal GT was decreased by 60% in fibroblasts from patients with AD versus control patients. Exposure to HNE did not affect GT in control patients, but it reduced GT by 50% in patients with AD, without any concomitant change in cell viability; conversely, HNE exposure induced a larger increase in ROS intracellular levels in AD than in control fibroblasts. Glutathione and N-acetylcysteine completely blocked 4-HNE effects and also increased basal uptake in AD cells. Moreover, inhibition of glutathione synthesis in control fibroblasts by pretreatment with buthionine sulfoximine resulted in GT reduction (40%) and an increase in ROS levels after exposure to 4-HNE. Nevertheless, since there are no differences between GSH basal level in controls and patients with AD, the alteration of other antioxidant systems cannot be excluded. Our study supports the hypothesis of a systemic impairment of GT in AD, possibly linked to oxidative stress and to reduced antioxidant defenses, which may be partially reversed by antioxidant treatment. Therefore, we suggest fibroblast cultures as a tool for exploring pathogenetic mechanisms and possible therapeutic strategies in patients with AD.     

Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis

BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes. Further explanation of the adverse effects and their relation to discontinuation of medication will require better studies involving prospective collection of quality-of-life data.