BACKGROUND & AIMS: AIMS:To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction. METHODS:Eighteen patients inhaled methacholine (MCh) until FEV(1) decreased by 35% of control. Following administration of placebo, 200 microg salbutamol or 400 microg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV(1) and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method. RESULTS:For all functional variables, recovery times were significantly (P < 0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be delivered by the Diskus to achieve recovery times for FVC, FEV(1) and volume-adjusted mid-expiratory flow similar to those obtained with 200 microg salbutamol administered via the pMDI + Volumatic were 558 (95% CI 537, 579) microg, 395 (95% CI 388, 404) microg and 404 (95% CI 393, 415) microg, respectively, and corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI 1.94, 2.02), and 2.02 (95% CI 1.96, 2.07). CONCLUSIONS:Administration of salbutamol via the pMDI + Volumatic provides faster reversal of induced bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs with the pMDI + Volumatic is approximately twice that with the Diskus.

背景与目标： 目的：评估沙丁胺醇通过带间隔垫片的定量吸入器（pMDI Volumatic）和干粉吸入器（Diskus）给药后支气管扩张的发生速度，以及这些装置在哮喘患者中使用乙酰甲胆碱的相对效力引起的支气管收缩。
方法：十八例患者吸入乙酰甲胆碱（MCh），直到FEV（1）降低至对照组的35％。通过pMDI Volumatic或Diskus给予安慰剂，200μg沙丁胺醇或400μg沙丁胺醇后，我们计算了药物给药所花费的时间以及MCh后强制肺活量（FVC），FEV（90）出现90％的增加）和经过体积调整的呼气中气流量（恢复时间）。通过使用2乘2 Finney平行回归方法计算两个吸入装置要达到相似的恢复时间所要输送的沙丁胺醇剂量，以及该装置的相对效能。
结果：对于所有功能变量，pMDI Volumatic的恢复时间比Diskus试验明显缩短（P <0.01）。与通过pMDI Volumatic施用200微克沙丁胺醇获得的FVC，FEV（1）和经体积调节的呼气中流的恢复时间相比，由Diskus输送的沙丁胺醇的剂量为558（95％CI 537，579） ）微克，395（95％CI 388、404）微克和404（95％CI 393、415）微克，分别对应于2.79（95％CI 2.68、2.90），1.98（95％CI 1.94， 2.02）和2.02（95％CI 1.96，2.07）。
结论：通过pMDI Volumatic给予沙丁胺醇比通过Diskus可以更快地逆转诱导的支气管收缩。使用pMDI Volumatic靶向肺的沙丁胺醇剂量约为使用Diskus的两倍。

BACKGROUND & AIMS: :We studied 45 patients aged 14-66 years who had undergone stem cell transplantation for a variety of malignant conditions at least 12 months previously. Compared to normal controls, they had significantly reduced absolute numbers of CD4+, CD4+ CD45RA+ and CD4+ CD45RO+ T cells and a reduced CD4+ CD45RA+:CD4+ CD45RO+ ratio. In all subsets T-cell numbers were significantly greater 24 months, compared to 12-24 months, after transplantation and there was a nonsignificant trend towards lower T-cell numbers with increasing age. We conclude that the thymus, or putative thymic-equivalent tissue, remains functional in older adults.

背景与目标： ：我们研究了45位14-66岁的患者，这些患者至少在12个月前经历了各种恶性疾病的干细胞移植。与正常对照相比，他们的CD4，CD4 CD45RA和CD4 CD45RO T细胞绝对数显着降低，并且CD4 CD45RA：CD4 CD45RO比值降低。与移植后的12-24个月相比，所有亚组中的T细胞数量在24个月中均显着增加，并且随着年龄的增长，T细胞数量降低的趋势不明显。我们得出的结论是，在老年人中，胸腺或假定的胸腺等效组织仍保持功能。

BACKGROUND & AIMS: BACKGROUND:Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. METHODS:Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. RESULTS:Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. CONCLUSIONS:ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance.

背景与目标： 背景：认识到对当前标准顺铂和紫杉醇治疗的耐药性或易感性可以改善转移性或复发性宫颈癌的治疗效果。
方法：从参与顺铂和异环磷酰胺II期试验（有或没有紫杉醇）的患者中收集45份组织样本进行逆行分析。进行免疫组织化学和基因分型以测试ERCC1，IIIβ-微管蛋白，COX-2，CD4，CD8和ERCC1（C8092A和N118 N）和MDR1（C3435T和G2677T）基因多态性，作为可能的预测和预后标志物。对结果进行统计分析，并与患者特征和结局相关联。
结果：ERCC1表达水平较高的患者的PFS和OS短于ERCC1表达水平较低的患者（mPFS：5.1 vs 10.2个月，p = 0.027; mOS：10.5 vs. 21.4个月，p = 0.006）。 ERCC1 N118 N位点为TT的患者，MDR1 G2677 T位点为GT的患者的PFS明显更长（分别为p = 0.006和p = 0.027）。 ERCC1表达和ERCC1 N118 N多态性仍然是PFS的独立预测因子。有趣的是，与较低的IIIβ-微管蛋白表达[15/23（65.2％）]相比，较高的IIIβ-微管蛋白表达与化疗耐药性相关且反应较少[5/20（25％）]（p = 0.008）。最后，IIβ-微管蛋白水平和化疗方案是对治疗反应的独立预测因子。
结论：ERCC1表达被证明是我们基于顺铂化疗的转移性或复发性宫颈癌患者生存的重要预后因素。 ERCC1 N118 N和MDR1 G2677 T多态性也证明对疾病进展具有预后意义，而IIIβ-微管蛋白的过表达与化疗耐药性呈正相关。

BACKGROUND & AIMS: AIM:Anthracycline agents are undermined by their cardiotoxicity. As life expectancy following treatment is greatly improved, techniques that ensure early detection and timely management of cardiotoxicity are essential. The aim of the present study was to evaluate left ventricular (LV) systolic function with LV ejection fraction (LVEF) and two-dimensional myocardial strain up to 12 months after anthracycline chemotherapy, specifically in HER2/neu negative breast cancer patients. METHODS:Seventy-eight consecutive anthracycline naïve breast cancer patients were studied before and immediately after anthracycline chemotherapy. Fifty HER2/neu negative patients were studied over 12 months with serial echocardiograms at four time points. All patients were treated with standard regimens containing anthracyclines. RESULTS:Global systolic strain was significantly reduced immediately after, and 6 months after anthracyclines (-19.0 ± 2.3% to -17.5 ± 2.3% (P<0.001) and -18.2 ± 2.2% (P=0.01) respectively). A non-uniform reduction in strain was observed each time with relative sparing of the LV apex. LVEF remained largely unchanged at both time points. Global strain normalised by 12 months in the majority of patients. Persistently reduced strain was observed in 16% (n=8); these patients had a greater reduction in strain at 6 months (≤ -17.2%), and had received higher cumulative anthracycline doses. CONCLUSION:Myocardial strain imaging is more sensitive than LVEF for the early detection and intermediate term monitoring of LV systolic function following anthracycline chemotherapy in HER2/neu negative breast cancer patients, and may aid in the development of improved monitoring protocols.

背景与目标： 目的：蒽环类药物被其心脏毒性所破坏。随着治疗后预期寿命的大大提高，确保早期发现和及时处理心脏毒性的技术至关重要。本研究的目的是评估蒽环类药物化疗后长达12个月的左心室（LV）收缩功能，左室射血分数（LVEF）和二维心肌劳损，特别是在HER2 / neu阴性乳腺癌患者中。
方法：在蒽环类药物化疗之前和之后立即研究了88例连续使用蒽环类药物的初治乳腺癌患者。在12个月的时间里，通过四个系列的连续超声心动图研究了50例HER2 / neu阴性患者。所有患者均接受含蒽环类药物的标准治疗方案。
结果：蒽环类药物治疗后和治疗后6个月，整体收缩应变显着降低（分别为-19.0±2.3％至-17.5±2.3％（P <0.001）和-18.2±2.2％（P = 0.01））。每次观察到应变不均匀降低，但LV根尖相对较少。在两个时间点，LVEF基本上保持不变。大多数患者的总应变在12个月后恢复正常。观察到永久降低的应变为16％（n = 8）；这些患者在6个月时的应变降低更大（≤-17.2％），并且接受了更高的蒽环类药物累积剂量。
结论：对于HER2 / neu阴性乳腺癌患者，蒽环类药物化疗后，心肌应变成像对LV收缩功能的早期检测和中期监测比LVEF更为敏感，可能有助于开发改进的监测方案。

BACKGROUND & AIMS: :Chemotherapy-induced alopecia is a major problem in clinical oncology. Doxorubicin, a widely used cancer chemotherapy drug, induces disruption of the hair cycle and subsequent alopecia. We show in this report that doxorubicin causes disruption of the hair-follicle-associated blood vessel network resulting in a greatly reduced density of these blood vessels. Dystrophic hair follicles were also observed with abnormal melanogenesis in the mice treated with doxorubicin. Visualization of the effect of doxorubicin on hair-follicle angiogenesis was made possible by the use of transgenic mice in which green fluorescent protein was driven by regulatory elements of the nestin gene (ND-GFP). In these transgenic mice, the hair-follicle stem cells and the follicle structure as well as the blood vessels associated with the hair follicles express ND-GFP. The hair-follicle stem cells did not appear to be affected by doxorubicin, which may explain why hair regrows after chemotherapy. These results suggest that inhibition of hair-follicle-associated angiogenesis by doxorubicin may be an important factor in hair-follicle dystrophy associated with chemotherapy-induced alopecia. The ND-GFP mouse model is thus useful for the study of the role of angiogenesis in the hair-follicle cycle and the effect of drugs on processes associated with chemotherapy-induced alopecia.

背景与目标： 化学疗法引起的脱发是临床肿瘤学中的主要问题。阿霉素是一种广泛使用的癌症化学治疗药物，可引起毛发周期破坏和随后的脱发。我们在这份报告中表明，阿霉素会导致毛囊相关血管网络的破坏，从而导致这些血管的密度大大降低。在用阿霉素治疗的小鼠中还观察到营养不良的毛囊黑色素生成异常。通过使用其中巢蛋白基因（ND-GFP）调控元件驱动绿色荧光蛋白的转基因小鼠，可以看到阿霉素对毛囊血管生成的作用。在这些转基因小鼠中，毛囊干细胞，毛囊结构以及与毛囊相关的血管均表达ND-GFP。毛囊干细胞似乎没有受到阿霉素的影响，这可以解释为什么化疗后头发会长大。这些结果表明，阿霉素抑制与毛囊相关的血管生成可能是与化学疗法引起的脱发有关的毛囊营养不良的重要因素。因此，ND-GFP小鼠模型可用于研究血管生成在毛囊周期中的作用以及药物对与化学疗法引起的脱发相关的过程的作用。

BACKGROUND & AIMS: :Although many multiple myeloma (MM) patients initially respond to cytotoxic therapy, most eventually relapse. Novel therapeutic strategies employing a combination of chemotherapy with targeted biologics may significantly enhance the response of tumor cells to treatment. We tested a fully human anti-IGF-IR antibody (A12) against MM, and showed specific inhibition of IGF-I or serum-induced IGF-IR signaling in MM cells in vitro. The A12 as a single agent was demonstrated to exert modest to significant inhibition of tumor growth in vivo in various subcutaneous xenograft MM models. The A12 was also evaluated in a disseminated xenograft MM.1S NOD/SCID model as monotherapy or in combination with other drugs (bortezomib, melphalan) currently in clinical use. The tumor burden, as determined by luciferase bioimaging, was sharply decreased, and overall survival significantly prolonged when the therapies were combined. Immunohistochemical analysis demonstrated that the A12 treated tumors had significantly decreased vascularization compared to control tumors. Furthermore, most MM lines constitutively secreted significant quantities of VEGF, and this was enhanced following IGF-I treatment. Inhibition of IGF-IR by the A12 in vitro suppressed both constitutive and IGF-I-induced secretion of VEGF, indicating that a putative anti-angiogenic mechanism associated with the A12 treatment may contribute to its anti-tumor effect.

背景与目标： ：尽管许多多发性骨髓瘤（MM）患者最初对细胞毒性疗法有反应，但大多数最终会复发。采用化学疗法与靶向生物制剂相结合的新型治疗策略可以显着增强肿瘤细胞对治疗的反应。我们测试了针对MM的完全人源抗IGF-IR抗体（A12），并显示了MM细胞在体外对IGF-1或血清诱导的IGF-1R信号的特异性抑制。在各种皮下异种移植MM模型中，A12作为单一药剂被证明在体内对肿瘤生长具有中等至显着的抑制作用。还以单一疗法或与目前临床上使用的其他药物（硼替佐米，美法仑）联用的弥漫性异种移植MM.1S NOD / SCID模型评估了A12。通过萤光素酶生物显像确定的肿瘤负荷显着降低，并且当联合治疗时，总生存期显着延长。免疫组织化学分析表明，与对照肿瘤相比，A12治疗的肿瘤的血管形成明显减少。此外，大多数MM系组成型地分泌大量的VEGF，并且在IGF-I处理后其增强。在体外通过A12抑制IGF-IR抑制了组成型和IGF-I诱导的VEGF分泌，这表明与A12治疗相关的推定抗血管生成机制可能有助于其抗肿瘤作用。

BACKGROUND & AIMS: OBJECTIVE:To report the results of laparoscopic nephrectomy for unilateral Wilms' tumour in children treated with chemotherapy before surgery. PATIENTS AND METHODS:Eight children with unilateral nonmetastatic Wilms' tumour included in the International Society of Pediatric Oncology 2001 protocol were treated with vincristine/actinomycin D and then had laparoscopic nephrectomy and lymph-node sampling. A Veress needle puncture was made and a four-trocar transperitoneal approach was used in all cases. The tumour was extracted with no morcellation through a Pfannenstiel incision. RESULTS:All eight tumours were completely removed, with lymph node samples; intraoperative bleeding was minimal (50 mL). There were no complications after surgery and patients were discharged after 2-3 days. No recurrences of disease, port-site implantation or long-term complications were detected. CONCLUSIONS:Laparoscopic nephrectomy for unilateral Wilms' tumour is feasible in children after chemotherapy; it is safe and allows the complete surgical approach required for treating this tumour. Although the patients had a good long-term follow-up, more patients are needed to compare the results of laparoscopic techniques with open surgery.

背景与目标： 目的：报道腹腔镜肾切除术治疗儿童化疗前单侧Wilms肿瘤的结果。
患者与方法：将国际儿童肿瘤学会2001年方案中纳入的8例单侧非转移性Wilms肿瘤患儿用长春新碱/放线菌素D治疗，然后进行腹腔镜肾切除术和淋巴结取样。在所有情况下均进行了Veress穿刺，并使用了四针经腹膜入路。通过Pfannenstiel切口在没有粉碎的情况下提取肿瘤。
结果：8例肿瘤全部切除，淋巴结清扫。术中出血极少（50 mL）。手术后无并发症，2-3天后出院。没有发现疾病复发，港口植入或长期并发症。
结论：腹腔镜肾切除术治疗儿童单侧Wilms肿瘤是可行的。它是安全的，并允许治疗该肿瘤所需的完整手术方法。尽管患者长期随访良好，但仍需要更多患者将腹腔镜技术与开放手术的结果进行比较。

BACKGROUND & AIMS: OBJECTIVE:To evaluate clinical effects of shenqi fuzheng Injection ([Chinese characters: see text]) in the neoadjuvant chemotherapy for local advanced breast cancer and the effects on T-lymphocyte subsets. METHODS:During the period from 2000 to 2005, 126 patients with local advanced breast cancer were treated with the neoadjuvant chemotherapy. They were randomly divided into the following two groups: a control group of 61 cases treated by chemotherapy alone and a study group of 65 cases treated by chemotherapy plus shenqi fuzheng injection. All the cases of both groups were given the CEF (CTX 500 mg/m2, d1,8; EPI 40 mg/m2, d1, 8; and 5-Fu 500 mg/m2 d1,8) regimen. The clinical effects, the effects on T-lymphocyte subgroup and NK cells, and the toxic side effects were observed. RESULTS:All the patients completed two cycles of the chemotherapy, and the efficacy and the toxic side effects were evaluated. For the primary tumor in the breast, the total effective rate was 69.2% (45/65) in the study group and 49.2% (30/61) in the control group with a statistically significant difference in the intergroup comparison (chi2 = 5.251, P = 0.022, < 0.05). There was no progression of the disease in both the groups, and there were no grade IV toxic side effects in the two groups. The major toxic responses were myelosuppression and gastrointestinal reaction, which were milder in the study group than the control group, and with a shorter recovery course in the former than the latter. Besides, an obvious rise of the T-lymphocyte subgroup and NK cells was found in the study group after the neoadjuvant chemotherapy, with a very significant difference from the controls (P < 0.01). CONCLUSIONS:Shenqi fuzheng Injection can improve and regulate immune function of the patients with local advanced breast cancer given the neoadjuvant chemotherapy, and therefore it can enhance the curative effect and reduce the side effect as well.

背景与目标： 目的：评价参芪扶正注射液在局部晚期乳腺癌新辅助化疗中的临床疗效以及对T淋巴细胞亚群的影响。
方法：在2000年至2005年期间，对126例局部晚期乳腺癌患者进行了新辅助化疗。他们被随机分为以下两组：对照组61例单独接受化疗，研究组65例接受化学疗法加参芪扶正注射液治疗。两组的所有病例均接受CEF（CTX 500 mg / m2，d1,8; EPI 40 mg / m2，d1，8;和5-Fu 500 mg / m2 d1,8）方案。观察其临床效果，对T淋巴细胞亚群和NK细胞的影响以及毒性副作用。
结果：所有患者均完成了两个化疗周期，并评价了疗效和毒副作用。对于乳腺原发肿瘤，研究组的总有效率为69.2％（45/65），对照组为49.2％（30/61），组间比较的差异有统计学意义（chi2 = 5.251， P = 0.022，<0.05）。两组均无疾病进展，且两组均无IV级毒性副反应。主要的毒性反应是骨髓抑制和胃肠道反应，研究组的毒性反应轻于对照组，前者的恢复过程短于对照组。此外，在新辅助化疗后的研究组中，T淋巴细胞亚群和NK细胞明显升高，与对照组相比有非常显着的差异（P <0.01）。
结论：参芪扶正注射液可改善和调节新辅助化疗后局部晚期乳腺癌患者的免疫功能，因此可提高疗效，减少副作用。

BACKGROUND & AIMS: BACKGROUND:Chemotherapy and intensity-modulated radiotherapy (IMRT) have decreased treatment-related complications in adult patients with nasopharyngeal carcinoma (NPC). Our aim was to evaluate the toxicity profile of IMRT plus chemotherapy in pediatric NPC patients. OBSERVATIONS:Five patients were treated with chemotherapy and IMRT. All patients experienced grade 3-4 acute toxicities. With a median follow-up of 6.3 years, all patients experienced >or=3 long-term toxicities. The most common toxicities were hypothyroidism, xerostomia, hearing loss, and dental disease. CONCLUSIONS:We did not observe a significant decrease in long-term toxicities with IMRT plus chemotherapy in our small cohort of pediatric NPC patients.

背景与目标： 背景：化学疗法和调强放射疗法（IMRT）减少了成人鼻咽癌（NPC）患者的治疗相关并发症。我们的目的是评估IMRT联合化疗对小儿NPC患者的毒性。
观察：5例患者接受了化疗和IMRT治疗。所有患者均经历3-4级急性毒性。中位随访时间为6.3年，所有患者均经历了≥3的长期毒性。最常见的毒性是甲状腺功能减退，口干，听力下降和牙齿疾病。
结论：在我们的小儿NPC患者队列中，IMRT联合化疗未观察到长期毒性显着降低。

BACKGROUND & AIMS: :Gastrointestinal mucositis involves many changes at the gene level, affecting epithelial/subepithelial interactions and leading to overt damage. The regional specificity and time course of these changes, and how they relate to subsequent mucositis development however remain unknown. The aim of this study was to determine the early time course of gene expression changes along the gastrointestinal tract of the DA rat following chemotherapy. Female DA rats were treated with a single dose of 200 mg/kg irinotecan to induce mucositis, and were killed at short intervals following treatment. Small sections of stomach, jejunum and colon were harvested for analysis of genetic profiles. RNA was hybridised to high density Affymetrix oligonucleotide microarrays. Data analysis was carried out with software package, TimeCourse, freely available through Bioconductor. As early as 1 hr following chemotherapy, expression of hundreds of genes was altered, including those for transcription factors, stress response proteins and protein turnover. These genes are involved in cell proliferation, differentiation and apoptosis along with other cellular processes. At early time points, there was a significant response involving the mitogen-activated protein kinase pathway, cell cycle regulation and cytokine receptor signalling. At later time points, changes to the complement cascade became prominent. We have shown that changes in gene expression following chemotherapy occur by 1 hr, and persist for at least 72 hr after treatment. Many of these changes are highly likely to be specifically related to the subsequent development of gastrointestinal mucositis.

背景与目标： ：胃肠道粘膜炎在基因水平上涉及许多变化，影响上皮/耻骨上皮相互作用并导致明显的损害。这些变化的区域特异性和时程，以及它们与随后的粘膜炎发展之间的关系仍然未知。这项研究的目的是确定化学疗法后DA大鼠胃肠道基因表达变化的早期过程。用单剂量200 mg / kg伊立替康治疗雌性DA大鼠，以诱导粘膜炎，并在治疗后短时间处死。收集胃，空肠和结肠的小部分用于遗传特征分析。 RNA与高密度Affymetrix寡核苷酸微阵列杂交。数据分析是使用TimeCourse软件包进行的，该软件包可通过Bioconductor免费获得。化疗后1小时，数百种基因的表达发生了变化，包括转录因子，应激反应蛋白和蛋白更新的基因。这些基因与其他细胞过程一起参与细胞增殖，分化和凋亡。在早期时间点，有明显的反应，涉及丝裂原激活的蛋白激酶途径，细胞周期调节和细胞因子受体信号传导。在随后的时间点，补体级联的改变变得很明显。我们已经显示，化疗后基因表达的变化在1小时内发生，并在治疗后持续至少72小时。这些变化中的许多极有可能与胃肠道粘膜炎的后续发展特别相关。

BACKGROUND & AIMS: :Resistin is a circulating mediator of insulin resistance mainly expressed in human monocytes and responsive to inflammatory stimuli. Recent clinical studies have connected elevated resistin levels with the development and severity of heart failure. To further our understanding of the role of human resistin in heart failure, we studied a humanized mouse model lacking murine resistin but transgenic for the human Retn gene (Hum-Retn mice), which exhibits basal and inflammation-stimulated resistin levels similar to humans. Specifically, we explored whether resistin underlies acute anthracycline-induced cardiotoxicity. Remarkably, doxorubicin (25mg/kg ip) led to a 4-fold induction of serum resistin levels in Hum-Retn mice. Moreover, doxorubicin-induced cardiotoxicity was greater in the Hum-Retn mice than in littermate controls not expressing human resistin (Retn(-/-)). Hum-Retn mice showed increased cardiac mRNA levels of inflammatory and cell adhesion genes compared with Retn(-/-) mice. Macrophages, but not cardiomyocytes, from Hum-Retn mice treated with doxorubicin in vitro showed dramatic induction of hRetn (human resistin) mRNA and protein expression. We also examined resistin levels in anthracycline-treated breast cancer patients with and without cardiotoxicity. Intriguingly, serum resistin levels in women undergoing anthracycline-containing chemotherapy increased significantly at 3 months and remained elevated at 6 months in those with subsequent cardiotoxicity. Further, elevation in resistin correlated with decline in ejection fraction in these women. These results suggest that elevated resistin is a biomarker of anthracycline-induced cardiotoxicity and may contribute in the development of heart failure via its direct effects on macrophages. These results further implicate resistin as a link between inflammation, metabolism, and heart disease.

背景与目标： ：抵抗素是胰岛素抵抗的循环介质，主要在人单核细胞中表达，对炎症刺激有反应。最近的临床研究将抵抗素水平升高与心力衰竭的发展和严重程度联系在一起。为了进一步了解人类抵抗素在心力衰竭中的作用，我们研究了一种缺少鼠抵抗素但转为人类Retn基因（Hum-Retn小鼠）的人源化小鼠模型（Hum-Retn小鼠），其表现出与人类相似的基础和炎症刺激抵抗素水平。具体来说，我们探讨了抵抗素是否是急性蒽环类药物引起的心脏毒性的基础。值得注意的是，阿霉素（25mg / kg ip ip）导致Hum-Retn小鼠血清抵抗素水平提高了4倍。此外，在Hum-Retn小鼠中，阿霉素诱导的心脏毒性要比未表达人抵抗素（Retn（-/-））的同窝仔对照更大。与Retn（-/-）小鼠相比，Hum-Retn小鼠显示出炎症和细胞粘附基因的心脏mRNA水平升高。体外用阿霉素处理的Hum-Retn小鼠的巨噬细胞而非心肌细胞显示出hRetn（人类抵抗素）mRNA和蛋白表达的显着诱导。我们还检查了蒽环类药物治疗的有或没有心脏毒性的乳腺癌患者的抵抗素水平。有趣的是，接受含蒽环类药物化疗的妇女的血清抵抗素水平在3个月时显着增加，而在随后发生心脏毒性反应的妇女中，在6个月时仍然升高。此外，这些女性的抵抗素升高与射血分数下降相关。这些结果表明，升高的抵抗素是蒽环类药物诱导的心脏毒性的生物标志物，并可能通过其对巨噬细胞的直接作用而导致心力衰竭的发展。这些结果进一步暗示抵抗素是炎症，代谢和心脏病之间的联系。

BACKGROUND & AIMS: BACKGROUND:Several randomized controlled trials have examined, with conflicting results, the efficacy of the addition of anticholinergics to beta2 agonists in acute pediatric asthma. The pooling for a larger number of randomized controlled trials may provide not only greater power for detecting group differences and also provide better insight into the influence of patients' characteristics and treatment modalities on efficacy. OBJECTIVES:The aims of this study were to estimate the therapeutic and adverse effects attributable to the addition of inhaled anticholinergics to beta2 agonists in acute pediatric asthma. SEARCH STRATEGY:We searched Medline (1966 to April 2000), Embase (1980 to April 2000), Cinahl (1982 to April 2000) and reference lists of studies. We also contacted drug manufacturers and trialists. SELECTION CRITERIA:Randomised trials comparing the combination of inhaled anticholinergics and beta2 agonists with beta2 agonists alone in children aged 18 months to 17 years with acute asthma. DATA COLLECTION AND ANALYSIS:Assessments of trial quality and data extraction were done by two reviewers independently. MAIN RESULTS:Of the 40 identified trials, 13 were relevant and eight of these were of high quality. The addition of a single dose of anticholinergic to beta2 agonists did not reduce hospital admission [RR=0.93 (95% CI: 0.65, 1.32)]. However, significant group differences in lung function supporting the combination of anticholinergics and beta2-agonists were observed 60 minutes [SMD=0.57 (95% CI:0.21, 0.93)] and 120 minutes [SMD=0.53 (95% CI: 0.17, 0.90)] after the dose of anticholinergic. In contrast, the addition of multiple doses of anticholinergics to beta2 agonists reduced the risk of hospital admission by 25% [RR=0.75 (95% CI: 0.62,0.89)] in children with predominantly moderate and severe exacerbations. Twelve (95% CI: 8, 32) children would need to be treated to avoid one admission. When restricting this strategy to children with severe exacerbations, seven (95% CI: 5, 20) children need to be treated to avoid an admission. At 60 minutes after the last anticholinergic inhalation, a weighted mean group difference of 9.68 in change in % predicted FEV1 [95% CI:5.70, 13.68] favored anticholinergic use. In the two studies where anticholinergics were systematically added to every beta2 agonist inhalation, irrespective of asthma severity, no group differences were observed for the few available outcomes. There was no increase in the amount of nausea, vomiting or tremor in patients treated with anticholinergics. REVIEWER'S CONCLUSIONS:A single dose of an anticholinergic agent is not effective for the treatment of mild and moderate exacerbations and is insufficient for the treatment of severe exacerbations. Adding multiple doses of anticholinergics to beta2 agonists appears safe, improves lung function and would avoid hospital admission in 1 of 12 such treated patients. Although multiple doses should be preferred to single doses of anticholinergics, the available evidence only supports their use in school-aged children with severe asthma exacerbation. There is no conclusive evidence for using multiple doses of anticholinergics in children with mild or moderate exacerbations.

背景与目标： 摘要背景：几项随机对照试验已经检验了在急性小儿哮喘中向β2激动剂中添加抗胆碱能药的疗效，但结果相互矛盾。大量随机对照试验的汇集不仅可以提供更大的检测组差异的能力，还可以更好地了解患者的特征和治疗方式对疗效的影响。
目的：本研究的目的是评估在急性小儿哮喘中将吸入性抗胆碱能药添加到β2激动剂中所引起的治疗和不良反应。
搜索策略：我们检索了Medline（1966年至2000年4月），Embase（1980年至2000年4月），Cinahl（1982年至2000年4月）和参考研究清单。我们还联系了药品制造商和试验人员。
选择标准：随机对照试验比较了18个月至17岁急性哮喘儿童中吸入抗胆碱能药和β2激动剂与单独使用β2激动剂的组合。
数据收集与分析：两名审稿人分别对试验质量和数据提取进行评估。
主要结果：在40项确定的试验中，有13项是相关的，其中8项是高质量的。在β2激动剂中添加单剂量抗胆碱药并不能减少住院率[RR = 0.93（95％CI：0.65，1.32）]。然而，观察到60分钟[SMD = 0.57（95％CI：0.21，0.93）]和120分钟[SMD = 0.53（95％CI：0.17，0.90） ）]服用抗胆碱药后。相比之下，在以中度和重度急性发作为主的儿童中，向β2激动剂中添加多剂量的抗胆碱能药可使入院风险降低25％[RR = 0.75（95％CI：0.62,0.89）]。需要治疗十二名儿童（95％CI：8、32），以避免一次入院。当将这种策略限制为严重加重的儿童时，需要治疗七名（95％CI：5、20）儿童，避免入院。在最后一次抗胆碱能吸入后60分钟，加权平均组差异9.68的预测FEV1的变化百分比[95％CI：5.70，13.68]有利于抗胆碱能的使用。在两项研究中，每次吸入β2激动剂均系统地添加了抗胆碱药，而与哮喘的严重程度无关，在少数可获得的结果中未观察到组别差异。抗胆碱能药物治疗的患者的恶心，呕吐或震颤没有增加。
评论者的结论：单剂抗胆碱能药对轻度和中度加重无效，对重度加重也无效。在β2激动剂中添加多剂量的抗胆碱药似乎是安全的，可以改善肺功能，并且可以避免12名接受这种治疗的患者中的1名入院。尽管应该比单剂抗胆碱药更优选多剂，但现有证据仅支持将其用于严重哮喘加重的学龄儿童。没有确凿证据表明在轻度或中度加重的儿童中使用多剂量的抗胆碱能药。

BACKGROUND & AIMS: :Extranodal presentation in non-Hodgkin's lymphoma (NHL) is uncommon, and the mandible is very rarely involved. Primary NHL of the mandible, for the most part, has intermediate or high malignancy and has a much greater incidence of local recurrence compared with other sites of involvement. A 48-year-old Japanese man with NHL of the mandible received radiotherapy, followed by high-dose chemotherapy supported with peripheral blood stem cell transplantation (PBSCT). High-dose cyclophosphamide, Adriamycin, and vincristine were used for pretransplant conditioning. He achieved complete remission and has survived in continuous complete remission for more than 72 months to date. Marrow-ablative chemotherapy facilitated by PBSCT is thought to be useful as part of the primary therapy for patients with NHL who have poorer prognoses.

背景与目标： ：非霍奇金淋巴瘤（NHL）的外生表现很少见，下颌骨很少累及。与其他受累部位相比，下颌骨的原发性NHL在大多数情况下具有中度或高度恶性，并且局部复发的可能性要大得多。一名48岁的下颌骨NHL的日本男子接受了放疗，随后进行了大剂量化学疗法并辅以外周血干细胞移植（PBSCT）。大剂量的环磷酰胺，阿霉素和长春新碱用于移植前预处理。他实现了完全缓解，迄今为止，在连续完全缓解中存活了超过72个月。 PBSCT促进的骨髓消融化疗被认为是对预后较差的NHL患者的主要疗法的一部分。

BACKGROUND & AIMS: Background:We aimed to investigate the expression level of breast cancer susceptibility gene 2 (BRCA2) and its changes during chemotherapy in patients with different pathological types of mammary cancer (MC). Methods:Overall, 102 patients treated in Affiliated Tumor Hospital of Guangxi Medical University, China from April 2013 to August 2017 were enrolled as experimental group, including 58 patients with noninvasive MC (group A) and 44 with invasive MC (group B). Fifty healthy volunteers at the same time were enrolled as control group. The relative expression of BRCA2 in the blood of MC patients was detected by real-time fluorescence quantitative PCR (FQ-PCR). Results:In the experimental group, the expression level of BRCA2 in group A was higher than that in group B before chemotherapy (P<0.001); the expression level in group A and group B 1 month after chemotherapy was higher than that before chemotherapy (P<0.001); the expression level in the both groups 3 months after chemotherapy was higher than that 1 month after chemotherapy (P<0.001); the expression level of BRCA2 in blood of group A increased gradually before, 1 month and 3 months after chemotherapy (P<0.001). The expression level of BRCA2 in blood of group B increased gradually at the same time points (P<0.001). Conclusion:BRCA2 is over-expressed in noninvasive MC patient and under-expressed in invasive MC patient. And it can be used as an index for monitoring the condition of MC patients with different pathological types during chemotherapy.

背景与目标： 背景：我们的目的是研究乳腺癌的易感基因2（BRCA2）的表达水平及其在不同病理类型的乳腺癌（MC）患者化疗期间的变化。
方法：纳入2013年4月至2017年8月在广西医科大学附属肿瘤医院收治的102例患者作为实验组，其中58例为非侵入性MC（A组），44例为侵入性MC（B组）。同时纳入50名健康志愿者作为对照组。通过实时荧光定量PCR（FQ-PCR）检测MC患者血液中BRCA2的相对表达。
结果：实验组A组BRCA2表达高于化疗前B组（P <0.001）。 A组和B组化疗后1个月的表达水平高于化疗前（P <0.001）；两组化疗后3个月的表达水平均高于化疗后1个月（P <0.001）。 A组血液中BRCA2的表达在化疗前，化疗后1、3个月逐渐升高（P <0.001）。 B组血液中BRCA2的表达水平在同一时间点逐渐升高（P <0.001）。
结论：BRCA2在非侵袭性MC患者中过表达，而在侵袭性MC患者中过表达。可作为监测化疗过程中不同病理类型MC患者病情的指标。

BACKGROUND & AIMS: INTRODUCTION:Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on 'trial and error'. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking. METHODS AND ANALYSIS:In an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018-2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) <0.05 is considered significant in all analyses. ETHICS AND DISSEMINATION:Ethics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained. TRIAL REGISTRATION NUMBER:NTR6982; Pre-results.

背景与目标： 简介：先天性diaphragm肌疝（CDH）是the肌的发育缺陷，会损害正常的肺部发育，从而导致肺动脉高压（PH）。 CDH新生儿的PH是发病率和死亡率的主要决定因素。不同的疗法仍然主要基于“尝试和错误”。吸入一氧化氮（iNO）通常是首选药物。但是，iNO似乎并未提高死亡率。静脉西地那非可降低患有CDH的PH患儿的死亡率，但缺乏CDH患者的前瞻性数据。
方法和分析：在欧洲，加拿大和澳大利亚的一项开放标签，多中心，国际随机对照试验中，在4年期间（2018年至2022年）招募了330名CDH和PH新生儿。患者随机接受静脉注射西地那非或iNO治疗。西地那非在3分钟内的剂量为0.4µmg / kg；随后连续输注1.6μmg/ kg /天，iNO的剂量为20 ppm。主要结局是在没有肺血管扩张药治疗的第14天没有PH和/或在生命的前28天内没有死亡。次要结局指标包括生命第一年的PH临床和超声心动图标志。我们假设西地那非第14天的主要结局指标从68％降低到48％，减少了25％，这需要330名患者的样本量。将进行意向治疗分析。在所有分析中，p值（双面）<0.05被认为是显着的。
伦理与传播：荷兰的伦理委员会（MEC-2017-324）和涉及人类研究的中央委员会（NL60229.078.17）已获得伦理批准。将使用《赫尔辛基宣言》的原则，《涉及人类受试者的医学研究法》以及有关个人数据保护的国家法规。将获得父母的知情同意。
注册号：NTR6982;结果。