BACKGROUND & AIMS: :Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.

背景与目标： : 热休克蛋白90 (HSP90) 是各种蛋白质的结构折叠和构象完整性维持所必需的，包括与细胞信号传导相关的几种。利用HSP90抑制剂17-allylamino-17-demethoxygeldanamycin (17-AAG) 的最新研究表明，在实体瘤中具有抗肿瘤作用。为了测试HSP90是否可以靶向多发性骨髓瘤 (MM) 患者，我们首先通过免疫荧光和流式细胞仪分析研究了HSP90在骨髓瘤细胞系 (U266) 和原发性骨髓瘤细胞中的表达。在证明骨髓瘤细胞中HSP90表达后，通过免疫过氧化物酶染色分析了32 MM患者的档案样本。所有患者的骨髓瘤细胞在所有样品中均显示出HSP90的强细胞质表达，并且55% 还显示出同时的核免疫阳性。与未处理的对照细胞相比，用17AAG处理U266和原代MM细胞可显着增加细胞凋亡。对与17-aag孵育的MM细胞中抗凋亡BCL2家族蛋白和akt的分析表明，BCL-2，BCL-XL，MCL-1和akt下调。此外，尽管低浓度的硼替佐米不会导致细胞死亡，但17AAG和硼替佐米的组合治疗显示出对U266细胞系的协同凋亡作用。这些数据表明，靶向抑制HSP90可能被证明是开发MM患者未来治疗选择的有效且创新的策略。

BACKGROUND & AIMS: :Foxp3 has been shown to be both necessary and sufficient for the development and function of naturally arising CD4+ CD25+ regulatory T cells in mice. Mutation of Foxp3 in Scurfy mice and FOXP3 in humans with IPEX results in fatal, early onset autoimmune disease and demonstrates the critical role of FOXP3 in maintaining immune homeostasis. The FOXP3 protein encodes several functional domains, including a C2H2 zinc finger, a leucine zipper, and a winged-helix/forkhead (FKH) domain. We have shown previously that FOXP3 functions as a transcriptional repressor and inhibits activation-induced IL-2 gene transcription. To characterize the role of each predicted functional domain on the in vivo activity of FOXP3, we have evaluated the location of point mutations identified in a large cohort of patients with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) and found them to cluster primarily within the FKH domain and the leucine zipper, but also present within the poorly defined N-terminal portion of the protein. The molecular functions of each of the IPEX-targeted domains were investigated. We show that FOXP3 is constitutively localized to the nucleus and this localization requires sequences at both the amino and C-terminal ends of its FKH domain. Moreover, FOXP3 was found to homodimerize through its leucine zipper. We also identify a novel functional domain within the N-terminal half of FOXP3, which is required for FOXP3-mediated repression of transcription from both a constitutively active and a NF-AT-inducible promoter. Furthermore, we demonstrate that IPEX mutations in these domains correlate with deficiencies in FOXP3 repressor function, corroborating their in vivo relevance.

背景与目标： : Foxp3已被证明对于小鼠中自然产生的CD4 CD25调节性T细胞的发育和功能既必要又充分。在患有pex的Scurfy小鼠中Foxp3和人类中FOXP3的突变会导致致命的，早发性自身免疫性疾病，并证明了FOXP3在维持免疫稳态中的关键作用。FOXP3蛋白编码几个功能结构域，包括C2H2锌指，亮氨酸拉链和有翼螺旋/叉头 (FKH) 结构域。我们先前已经证明FOXP3作为转录阻遏物起作用并抑制激活诱导的IL-2基因转录。为了表征每个预测的功能域对FOXP3体内活性的作用，我们评估了在免疫失调，多内分泌病，肠病，X连锁综合征 (IPEX)，发现它们主要聚集在FKH结构域和亮氨酸拉链内，但也存在于蛋白质定义不明确的N端部分。研究了每个pex靶向域的分子功能。我们证明FOXP3组成性地定位于细胞核，并且这种定位需要在其FKH结构域的氨基和C末端都具有序列。此外，发现FOXP3通过其亮氨酸拉链同向二聚。我们还在FOXP3的N末端一半内鉴定了一个新的功能结构域，这是FOXP3-mediated抑制组成型活性和NF-AT诱导启动子转录所必需的。此外，我们证明了这些域中的IPEX突变与FOXP3阻遏物功能的缺陷相关，从而证实了它们在体内的相关性。

BACKGROUND & AIMS: PURPOSE OF REVIEW:Bortezomib-based combinations are being investigated in relapsed or refractory multiple myeloma with the aim of improving outcomes. This review presents recent data from clinical trials of these combinations and discusses their implications. RECENT FINDINGS:Preclinical findings indicating additive or synergistic activity of bortezomib plus conventional and novel agents for multiple myeloma appear to be supported by clinical studies of bortezomib-based combinations. Bortezomib combined with a broad set of active agents results in enhanced response rates, including high complete response rates. Encouraging responses to bortezomib and its combinations are also seen in elderly patients, patients with adverse prognostic factors such as refractory disease and increased beta2-microglobulin, patients with cytogenetic abnormalities such as chromosome 13 deletion, advanced bone disease, extramedullary involvement, and patients with renal impairment, including patients with renal failure requiring dialysis. Toxicities are predictable and manageable and comparable to those seen with bortezomib monotherapy. SUMMARY:Bortezomib-based combinations show promising activity in relapsed or refractory multiple myeloma, including reversal of chemoresistance to previously used agents. As high complete and overall response rates translate into longer survival, bortezomib-based combinations appear likely to have a significant impact on the multiple myeloma treatment algorithm and on the course of the disease itself.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Accumulating findings suggest that in acute myeloid leukemia (AML) patients, proinflammatory cytokines and growth factors play important roles in the proliferation and survival of AML cells in an autocrine and paracrine manner, leading to deterioration of AML. JTE-607 is a multiple cytokine inhibitor that potently suppresses production of proinflammatory cytokines. In the present study, we investigated the potency of JTE-607 as an antileukemic agent by exploiting a SCID mouse acute leukemia model. METHODS:SCID mice injected with anti-asialo-GM1 antibody were exposed to sublethal total-body irradiation at a dose of 3 Gy and then inoculated intravenously with AML cells. JTE-607 was administered using osmotic minipumps. The effects of JTE-607 on mouse survival time, human interleukin (IL)-8 levels in mouse plasma, and proportion of human CD45(+) cells in the bone marrow were studied. RESULTS:The survival time of the mice was strictly dependent on the number of U-937 cells proliferating in vivo. Administration of JTE-607 during the initial 7 days significantly prolonged survival of the mice, suggesting killing activity of JTE-607 against AML cells in vivo. Delayed administration of JTE-607 also prolonged the survival of mice bearing established leukemia with an effect comparable to the maximum tolerable dose of cytarabine. Flow cytometer analysis of bone marrow cells revealed decreased number of human CD45(+) cells. Human IL-8 level was also reduced by JTE-607. CONCLUSION:Our results indicate that JTE-607 has potential to be a new class of antileukemic drug that exerts inhibitory activities against both the proliferation and proinflammatory cytokine production of AML cells.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:In this article we focus on the role that chemokines and chemokine receptors play in the pathogenesis of multiple myeloma and the associated bone destructive process, and consider their utility as novel therapeutic targets for treating this devastating disease. METHODS:Current research on the role that chemokine and chemokine receptors play in the pathogenesis of myeloma is reviewed. RESULTS:The chemokines, MIP-1alpha, MCP-1, IL-8, and SDF-1, and their receptors play important roles in homing of MM cells, tumor growth, and bone destruction in myeloma. They are attractive therapeutic targets for treating myeloma patients. CONCLUSION:Addition of chemokine antagonists to current treatment regimens for myeloma should result in better therapeutic responses because of the loss of both the protective effect of the marrow microenvironment on the MM cells and the induction of osteoclast activity.

背景与目标：

BACKGROUND & AIMS: Environmental sensing in bacteria often involves the concerted action of sensor kinases and response regulators. Degenerate oligonucleotide primers were designed on the basis of amino acid similarity in the response regulators of these two-component systems. The primers were used in PCR to specifically amplify an internal DNA segment corresponding to the receiver module domain from genes encoding response regulators. Amplification products of the expected size were obtained from 12 different Gram-positive and Gram-negative bacteria. Sequence analysis revealed that 22 DNA fragments, which clearly originated from response regulator genes, were amplified from Escherichia coli, Agrobacterium tumefaciens, Bacillus subtilis and Lactobacillus bulgaricus. In each of these four species the receiver module of putative response regulator genes, which do not seem to be related to any of the already characterized genes, was identified. This simple and powerful method is therefore particularly useful for discovering new signal transduction systems which cannot be revealed by usual genetic studies.

背景与目标： 细菌中的环境传感通常涉及传感器激酶和响应调节剂的协同作用。简并寡核苷酸引物是根据这些两组分系统的响应调节剂中的氨基酸相似性设计的。引物用于PCR，以从编码反应调节剂的基因中特异性扩增与接收器模块结构域相对应的内部DNA片段。从12种不同的革兰氏阳性和革兰氏阴性细菌中获得了预期大小的扩增产物。序列分析表明，从大肠杆菌，根癌农杆菌，枯草芽孢杆菌和保加利亚乳杆菌中扩增出22个明显源自响应调节基因的DNA片段。在这四个物种中的每一个物种中，都鉴定了假定的反应调节基因的接收器模块，该模块似乎与任何已经表征的基因无关。因此，这种简单而强大的方法对于发现通常的遗传研究无法揭示的新信号转导系统特别有用。

BACKGROUND & AIMS: :Alkenylboronic acids have shown important biological activities that contribute to neuroprotection. We have determined their influence on the β-amyloid (βA) aggregation process, β-secretase and acethylcholinesterase activities on cell-free systems, on the redox and lipid peroxidation status, and on the vulnerability to apoptotic death in an APPswe neuroblastoma cell line, before and after hydrogen peroxide treatment. We have discovered that 2-arylvinylboronic acids and some of their esters possess a set of properties which makes them highly useful as neuroprotective agents affecting multiple biological targets involved in AD. These properties are not paralleled by the related 2-arylboronic acids.

背景与目标： : 烯基硼酸显示出重要的生物活性，有助于神经保护。我们已经确定了它们对 β-淀粉样蛋白 (β a) 聚集过程，β-分泌酶和乙胆碱酯酶在无细胞系统上的活性，对氧化还原和脂质过氧化状态以及对APPswe神经母细胞瘤细胞凋亡死亡的脆弱性的影响过氧化氢治疗之前和之后。我们发现2-芳基乙烯基硼酸及其某些酯具有一系列特性，这使它们作为影响AD中涉及的多个生物靶标的神经保护剂非常有用。这些性质与相关的2-芳基硼酸不平行。

BACKGROUND & AIMS: OBJECTIVES:Monochorionic (MC) twins are at increased risk of early fetal loss secondary to vascular complications such as twin-twin transfusion syndrome (TTTS). This study compared the early perinatal loss rates between MC and dichorionic (DC) twins in an era of invasive treatment for TTTS. METHODS:This was a retrospective study of all twin pregnancies of known chorionicity from a large regional cohort of nine hospitals over a 10-year period. Ultrasound data were matched to hospital delivery records and to a mandatory national register of pregnancy losses. Prospective risk of pregnancy loss from 14 to 24 weeks' gestation was calculated and the survival trend of MC and DC twins was analyzed using Kaplan-Meier survival analysis. RESULTS:The analysis included 3117 twin pregnancies (605 MC and 2512 DC). The total risk of early pregnancy loss (miscarriage and neonatal death) before 24 weeks was significantly higher in MC twins (60.3 per 1000 fetuses) than in DC twins (6.6 per 1000 fetuses), with a relative risk of 9.18 (95% CI, 6.0-13.9). Survival analysis showed a significant difference in overall and early mortality between MC and DC twins (log-rank test, P < 0.0001), while no difference was noted after 24 weeks' gestation (log-rank test, P = 0.08). CONCLUSIONS:Early pregnancy loss is significantly more common in MC than in DC twins, but no difference in the prospective risk of mortality between MC and DC twins is evident after 24 weeks' gestation. The observed early mortality rate has almost halved in comparison with previous studies in the published literature. Early detection and prompt treatment of complications in MC twins are likely to have contributed to this improvement in outcome.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Interleukin-17 (IL-17), which is secreted by Th17 cells, is a proinflammatory cytokine that is implicated in the pathogenesis of multiple sclerosis (MS) and plays a role in nonresponse of MS patients to interferon-β (IFN-β) therapy. OBJECTIVES:The purpose of this study was to establish a correlation between nonresponders (NR) and IL-17A serum titers and binding antibodies (BAbs) to IFN-β, as well as to find a correlation between IL-17A serum levels and other features of MS patients. METHODS:Our prospective study included 72 inactive relapsing-remitting multiple sclerosis (RRMS) patients that had been treated for at least 18 months with IFN-β and 15 healthy subjects. We determined the serum levels of IL-17A and of BAbs. IL-17A levels were considered elevated (IL-17A+) if the recorded value was greater than 1.6 pg/ml. RESULTS:Twenty-seven patients (37.5%) were NR and had a significantly higher serum IL-17A level compared to the responders group. Nineteen patients (26.4%) were IL-17A+ and had had a significantly higher number of relapses in the previous year and a higher Expanded Disability Status Score. The majority of IL-17A+ patients were NR and had a shorter MS duration. CONCLUSIONS:RRMS patients with high serum IL-17A levels do not respond well to IFN-β therapy and have shorter MS duration compared to patients with low IL-17A levels. This response is not influenced by the presence of BAbs.

背景与目标：

BACKGROUND & AIMS: :Molecular dynamics simulations in explicit water were carried out for two stacks, each composed of six 10-strand antiparallel β-sheets for two peptides corresponding to the diverging turn of two homologous Abl-SH3 domains. The first system, referred to as 10×6×MK contained the DLSFMKGE sequence from the Drosophila, while the second one, referred to as 10×6×KK, contained the human DLSFKKGE sequence. It was found that the 10×6×MK β-sheet stack is stable, but the 10×6×KK β-sheet stack is not. The stability of the 10×6×MK β-sheet stack results from the hydrophobic interactions of the methionine and phenylalanine residues and the leucine residues of the neighboring sheets. The Met, Phe, and Leu hydrophobic units make a hydrophobic core for the stack of β-sheets. During the MD run, the Met, Phe, and Leu residues of the neighboring β-sheets acted as a conformational switch moving the β-sheets so that the Phe residue interacted with the Met residue from the neighboring β-sheet. Replacement of Met by Lys destroys the hydrophobic core, which is the stability factor of the β-sheet stack. For the 10×6×KK system, individual β-sheets were preserved during simulations, but the interactions between the β-sheets were lost. The calculations of a six β-sheet stack confirm the conclusion drawn from our earlier studies of single β-sheet systems that the β-sheets must form stacks to be stabilized. These results suggest that the two conserved basic residues at the diverging turn of SH3 domains could act as gatekeepers to avoid aggregation.

背景与目标： : 在显式水中对两个堆栈进行了分子动力学模拟，每个堆栈由两个肽的六个10链反平行 β-折叠组成，对应于两个同源Abl-SH3域的发散转向。第一个系统 (称为10 × 6 × mk) 包含果蝇的DLSFMKGE序列，而第二个系统 (称为10 × 6 × kk) 包含人类DLSFKKGE序列。发现10 × 6 × mk β-折叠堆叠是稳定的，而10 × 6 × kk β-折叠堆叠则不稳定。10 × 6 × mk β-薄片堆叠的稳定性是由蛋氨酸和苯丙氨酸残基与相邻薄片的亮氨酸残基的疏水相互作用引起的。Met，Phe和Leu疏水单元为 β-折叠堆叠形成疏水核心。在MD运行期间，相邻 β-sheet的Met，Phe和Leu残基充当构象开关，移动 β-sheet，以使Phe残基与相邻 β-sheet的Met残基相互作用。用Lys代替Met会破坏疏水核，这是 β-折叠堆叠的稳定性因子。对于10 × 6 × kk系统，在模拟过程中保留了单个 β-折叠，但是 β-折叠之间的相互作用丢失了。六个 β-sheet堆栈的计算证实了我们先前对单个 β-sheet系统的研究得出的结论，即 β-sheet必须形成堆栈才能稳定。这些结果表明，在SH3结构域发散的转弯处的两个保守的碱性残基可以充当网守以避免聚集。

BACKGROUND & AIMS: :Over an 8 year period, 170 patients with multiple sclerosis (MS) and 134 healthy controls were assessed at monthly intervals in order to ascertain environmental factors which might be important in producing exacerbation or progression of the illness, and to compare the frequency of common viral infections in the two groups. During cumulative periods designated "at risk" (2 weeks before the onset of infection until 5 weeks afterwards) annual exacerbation rates were almost 3-fold greater than those during periods not at risk. Approximately 9% of infections were temporally related to exacerbations, whereas 27% of exacerbations were related to infections. Frequency of common infections was approximately 20-50% less in MS patients than controls; it was progressively less in those with greater disability. Even in minimally disabled patients with similar potential for infectious contacts, the infection rate was significantly less than in controls, suggesting that MS patients could have superior immune defences against common viruses.

背景与目标： : 在8年的时间里，每月对170名多发性硬化症 (MS) 患者和134名健康对照者进行评估，以确定可能对疾病恶化或进展很重要的环境因素，并比较两组中常见病毒感染的频率。在指定为 “处于危险中” 的累积期间 (感染发作前2周至之后5周)，年恶化率几乎是无危险期间的3倍。大约9% 的感染在时间上与恶化有关，而27% 的恶化与感染有关。MS患者的常见感染频率比对照组低约20-50%; 残疾程度较高的患者逐渐减少。即使在具有类似感染接触潜力的最小残疾患者中，感染率也明显低于对照组，这表明MS患者可以对普通病毒具有出色的免疫防御能力。

BACKGROUND & AIMS: Mees' lines, or transverse striate leukonychia, are classically associated with arsenic poisoning, but have been described in other cases of acute or chronic illness. Their pathogenesis is thought to be a disruption of nail plate keratinization secondary to systemic stress. Mees' lines are observed in a patient with helminthic and amebic infections and no history of arsenic exposure. This case demonstrates another clinical setting in which Mees' lines can appear, providing further evidence that Mees' lines may chronicle systemic disease.

背景与目标： Mees线或横纹白斑病通常与砷中毒有关，但在其他急性或慢性疾病病例中也有描述。它们的发病机理被认为是继发于全身压力的指甲板角质化的破坏。在患有蠕虫和阿米巴感染且没有砷暴露史的患者中观察到mees的行。该病例展示了另一种可能出现Mees' 线的临床环境，提供了进一步的证据表明Mees' 线可能会记录全身性疾病。

BACKGROUND & AIMS: :Stem cells have been widely assumed to be capable of replacing lost or damaged cells in a number of diseases, including Parkinson's disease (PD), in which neurons of the substantia nigra (SN) die and fail to provide the neurotransmitter, dopamine (DA), to the striatum. We report that undifferentiated human neural stem cells (hNSCs) implanted into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated Parkinsonian primates survived, migrated, and had a functional impact as assessed quantitatively by behavioral improvement in this DA-deficit model, in which Parkinsonian signs directly correlate to reduced DA levels. A small number of hNSC progeny differentiated into tyrosine hydroxylase (TH) and/or dopamine transporter (DAT) immunopositive cells, suggesting that the microenvironment within and around the lesioned adult host SN still permits development of a DA phenotype by responsive progenitor cells. A much larger number of hNSC-derived cells that did not express neuronal or DA markers was found arrayed along the persisting nigrostriatal path, juxtaposed with host cells. These hNSCs, which express DA-protective factors, were therefore well positioned to influence host TH+ cells and mediate other homeostatic adjustments, as reflected in a return to baseline endogenous neuronal number-to-size ratios, preservation of extant host nigrostriatal circuitry, and a normalizing effect on alpha-synuclein aggregation. We propose that multiple modes of reciprocal interaction between exogenous hNSCs and the pathological host milieu underlie the functional improvement observed in this model of PD.

背景与目标： : 人们普遍认为干细胞能够替代许多疾病中丢失或受损的细胞，包括帕金森氏病 (PD)，其中黑质 (SN) 的神经元死亡，无法向纹状体提供神经递质多巴胺 (DA)。我们报告了植入1-甲基-4-苯基-1,4，2,3-四氢吡啶处理的帕金森氏灵长类动物中的未分化人类神经干细胞 (hNSCs) 存活，迁移并通过行为改善定量评估具有功能影响在这个DA-缺陷模型中，其中帕金森氏征与DA水平降低直接相关。少数hNSC后代分化为酪氨酸羟化酶 (TH) 和/或多巴胺转运蛋白 (DAT) 免疫阳性细胞，这表明受损的成年宿主SN内部和周围的微环境仍允许通过反应性祖细胞发展DA表型。发现大量不表达神经元或DA标记的hNSC衍生细胞沿持续的黑质纹状体路径排列，与宿主细胞并列。因此，这些表达DA保护因子的hNSCs可以很好地影响宿主TH细胞并介导其他稳态调节，这反映在恢复到基线内源性神经元数量与大小之比，保留现存的宿主黑质纹状体回路以及对 α-突触核蛋白聚集的正常化作用。我们建议外源性hNSCs与病理性宿主环境之间相互作用的多种模式是该PD模型中观察到的功能改善的基础。

BACKGROUND & AIMS: :Multiple endocrine neoplasia type 1 is an autosomal dominant cancer syndrome characterized by pituitary, parathyroid and enteropancreatic endocrine tumors, which is caused by germline mutations of the tumor suppressor gene MEN1. In the case reported here, the patient had family with this disease whose germline MEN1 mutation was undetectable by conventional sequencing analysis. Further investigations involving polymorphism analyses, gene dose assay and nucleotide sequencing identified a large germline deletion of approximately 29 kilobase pairs spanning the whole MEN1 gene. The deletion was flanked by Alu repetitive sequences, suggesting unequal homologous recombination as the deletion mechanism. The polymorphism linkage data suggested that an asymptomatic son of the proband did not carry the family mutation. More direct evidence was obtained by gene dose assay and deletion-specific polymerase chain reaction, which demonstrated the normal MEN1 gene dosage and the absence of the deletion breakpoints in this asymptomatic subject and thus definitely excluded the possibility of disease predisposition.

背景与目标： : 多发性内分泌肿瘤1型是一种常染色体显性显性癌症综合征，其特征是垂体，甲状旁腺和肠胰腺内分泌肿瘤，由抑癌基因men1的种系突变引起。在此处报道的病例中，患者患有该疾病的家族，其生殖系MEN1突变无法通过常规测序分析检测到。涉及多态性分析，基因剂量测定和核苷酸测序的进一步研究确定了跨越整个MEN1基因的大约29千碱基对的大量种系缺失。缺失的两侧是Alu重复序列，表明不相等的同源重组是缺失机制。多态性连锁数据表明，先证者的无症状儿子没有携带家族突变。通过基因剂量测定和缺失特异性聚合酶链反应获得了更直接的证据，这表明该无症状受试者的正常MEN1基因剂量和缺失断点的缺失，因此明确排除了疾病易感性的可能性。

BACKGROUND & AIMS: :This paper reports the proceedings of a consensus meeting on the incidence and complications of multiple gestation in Canada. In addition to background presentations about current and possible future practice in Canada, the expert panel also developed a set of consensus points. The need for infertility to be understood, and funded, as a healthcare problem was emphasized, along with recognition of the emotional impact of infertility. It was agreed that the goal of assisted reproduction treatment is the delivery of a single healthy infant and that even though many positive outcomes have resulted from twin or even triplet pregnancies, the potential risks associated with multiple pregnancy require that every effort be made to achieve this goal. The evidence shows that treatments other than IVF (such as superovulation and clomiphene citrate) contribute significantly to the incidence of multiple pregnancy. There is an urgent need for studies to understand better the usage and application of these other fertility technologies within Canada, as well as the non-financial barriers to treatment. The final consensus of the expert panel was that with adequate funding and good access to treatment, it will be possible to achieve the goal of reducing IVF-related multiple pregnancy rates in Canada by 50%.

背景与目标： : 本文报告了关于加拿大多次妊娠的发生率和并发症的共识会议的会议记录。除了关于加拿大当前和可能的未来做法的背景介绍之外，专家小组还制定了一套共识点。强调了将不孕症理解为医疗保健问题并为其提供资金的必要性，并认识到不孕症的情感影响。与会者一致认为，辅助生殖治疗的目标是分娩一个健康的婴儿，尽管双胞胎甚至三胞胎怀孕产生了许多积极的结果，但与多胎妊娠相关的潜在风险需要尽一切努力实现这一目标。证据表明，除IVF以外的其他治疗方法 (例如超排卵和柠檬酸克罗米芬) 对多胎妊娠的发生率有显着贡献。迫切需要进行研究，以更好地了解加拿大境内这些其他生育技术的使用和应用，以及治疗的非金融障碍。专家小组的最后共识是，有足够的资金和良好的治疗机会，将有可能实现到50% 年将加拿大与IVF相关的多胎妊娠率降低的目标。