malformations

畸形
  • 文章类型: Journal Article
    酒精,或乙醇,是全球有害疾病和合并症的主要贡献者。怀孕期间使用酒精会干预发育中的胚胎,导致形态变化,神经认知缺陷,以及称为胎儿酒精谱系障碍(FASD)的行为变化。斑马鱼已被用作研究FASD的模型;然而,在斑马鱼FASD模型中,乙醇对氧化应激和炎症的作用机制和影响仍未被研究。因此,我们将斑马鱼胚胎暴露于不同浓度的乙醇(0%,0.5%,1.0%,1.25%,和1.5%乙醇(v/v))在受精后4-96小时(hpf)研究和表征FASD模型诱导氧化应激和炎症的乙醇浓度。这里,我们研究了不同时间点的存活率和发育毒性参数,并测量了氧化应激,活性氧(ROS)的产生,凋亡,斑马鱼幼虫的促炎基因表达。我们的发现表明,乙醇会导致各种发育异常,包括存活率下降,自发的尾部盘绕,孵化率,心率,和身体长度,与畸形增加有关。Further,乙醇暴露通过增加脂质过氧化和一氧化氮的产生以及降低谷胱甘肽水平来诱导氧化应激。随后,乙醇增加了ROS的产生,凋亡,乙醇暴露幼虫的促炎基因(TNF-α和IL-1β)表达。在所有研究参数中,1.25%和1.5%的乙醇对斑马鱼幼虫都有显着影响。然而,1.5%乙醇显示存活率降低和畸形增加。总的来说,1.25%乙醇是研究斑马鱼FASD模型氧化应激和炎症反应的理想浓度。
    Alcohol, or ethanol, is a major contributor to detrimental diseases and comorbidities worldwide. Alcohol use during pregnancy intervenes the developing embryos leading to morphological changes, neurocognitive defects, and behavioral changes known as fetal alcohol spectrum disorder (FASD). Zebrafish have been used as a model to study FASD; however, the mechanism and the impact of ethanol on oxidative stress and inflammation in the zebrafish FASD model remain unexplored. Hence, we exposed zebrafish embryos to different concentrations of ethanol (0 %, 0.5 %, 1.0 %, 1.25 %, and 1.5 % ethanol (v/v)) at 4-96 hours post-fertilization (hpf) to study and characterize the ethanol concentration for the FASD model to induce oxidative stress and inflammation. Here, we studied the survival rate and developmental toxicity parameters at different time points and measured oxidative stress, reactive oxygen species (ROS) generation, apoptosis, and pro-inflammatory gene expression in zebrafish larvae. Our findings indicate that ethanol causes various developmental abnormalities, including decreased survival rate, spontaneous tail coiling, hatching rate, heart rate, and body length, associated with increased malformation. Further, ethanol exposure induced oxidative stress by increasing lipid peroxidation and nitric oxide production and decreasing glutathione levels. Subsequently, ethanol increased ROS generation, apoptosis, and pro-inflammatory gene (TNF-α and IL-1β) expression in ethanol exposed larvae. 1.25 % and 1.5 % ethanol had significant impacts on zebrafish larvae in all studied parameters. However, 1.5 % ethanol showed decreased survival rate and increased malformations. Overall, 1.25 % ethanol is the ideal concentration to study the oxidative stress and inflammation in the zebrafish FASD model.
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  • 文章类型: Journal Article
    斑马鱼是最好的动物模型,已经尝试破译每种使用和感兴趣的杀菌剂的毒性机制。重要的是要了解毒物的多个目标,以估计其整体的毒性潜力。共有22种不同类别的杀菌剂,如抗菌药,唑霉素,多菌灵,羧基,百菌清,苯醚甲环唑,Etridiazole,氟西拉唑,fluxapyroxad,己唑醇,克雷辛磷甲基,代森锰锌,myclobutanil,丙草胺,丙环唑,propineb,吡唑酮酯,戊唑醇,甲基托布津,硫兰,对triploxystrobin和ziram在斑马鱼中的多个探索靶标进行了回顾和分析。当涉及到网络分析时,斑马鱼的毒性终点信息非常丰富。它们提供了进入受某种毒素影响的分子和细胞途径的窗口。然后,这可以用来深入了解潜在的毒性机制,并得出结论特定化合物诱导毒性的潜力。然后,这些知识可以用于指导有关药物开发的决策,环境法规,和其他研究领域。此外,使用斑马鱼的毒性终点也可用于更好地了解环境污染物对生态系统的影响。通过了解受给定毒素影响的途径,研究人员可以确定污染物如何与环境相互作用,以及如何导致健康或环境影响。
    Zebrafish being the best animal model to study, every attempt has been made to decipher the toxic mechanism of every fungicide of usage and interest. It is important to understand the multiple targets of a toxicant to estimate the toxic potential in its totality. A total of 22 fungicides of different classes like amisulbrom, azoxystrobin, carbendazim, carboxin, chlorothalonil, difenoconazole, etridiazole, flusilazole, fluxapyroxad, hexaconazole, kresoxim methyl, mancozeb, myclobutanil, prochloraz, propiconazole, propineb, pyraclostrobin, tebuconazole, thiophanate-methyl, thiram, trifloxystrobin and ziram were reviewed and analyzed for their multiple explored targets in zebrafish. Toxic end points in zebrafish are highly informative when it comes to network analysis. They provide a window into the molecular and cellular pathways that are affected by a certain toxin. This can then be used to gain insights into the underlying mechanisms of toxicity and to draw conclusions on the potential of a particular compound to induce toxicity. This knowledge can then be used to inform decisions about drug development, environmental regulation, and other areas of research. In addition, the use of zebrafish toxic end points can also be used to better understand the effects of environmental pollutants on ecosystems. By understanding the pathways affected by a given toxin, researchers can determine how pollutants may interact with the environment and how this could lead to health or environmental impacts.
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  • 文章类型: Case Reports
    我们报道了5例患者在壶腹和菌毛之间有单侧或双侧输卵管不连续,2017年至2023年,山东大学附属生殖医院偶尔通过腹腔镜联合宫腔镜检查发现。3例观察到左输卵管有这种畸形,右侧有1个箱子,双边1例。这些病例均未合并泌尿系畸形。手术后,有1例术后分娩,1正在怀孕,3尚未构思。输卵管的先天性壶腹和菌毛中断可能与生殖道或肾脏的其他明显畸形无关。然而,它可以导致输卵管积水和原发性或继发性不孕。手术管理选择,比如输卵管造口术,输卵管切除术,输卵管结扎,已经显示出改善妊娠结局的潜力。
    We reported 5 patients with unilateral or bilateral tubal discontinuity between the ampulla and fimbria, occasionally detected through laparoscopy combined with hysteroscopy at the Reproductive Hospital Affiliated with Shandong University from 2017 to 2023. Three cases were observed to have this malformation on the left fallopian tube, 1 case on the right side, and 1 case bilaterally. None of these cases were combined with urological malformations. After surgery, there was 1 instance of postoperative delivery, 1 ongoing pregnancy, and 3 not yet conceived. The congenital ampulla and fimbria interruption of the fallopian tube may be independent of other significant deformities of reproductive or renal tracts. However, it can lead to hydrosalpinx and primary or secondary infertility. Surgical management options, such as salpingostomy, salpingectomy, and tubal ligation, have shown the potential to improve pregnancy outcomes.
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  • 文章类型: Journal Article
    二苯甲酮(BP)家族,包括氧苯酮(BP-3),一种普遍的防晒成分和环境污染物,自2005年以来一直引起人们的关注。这项研究调查了斑马鱼(Daniorerio)eleutheroemes和盐水虾(Artemiasalina)无节幼体中的氧苯酮毒性,关注LC50和发展影响。采用超声辅助乳化液相微萃取法(UA-ELPME)检测斑马鱼胚胎(0.100-1.50mg/LBP-3,96h)和盐藻(0.100-5.00mg/LBP-3,48h)。HPLC-DAD测定BP-3浓度(最高:0.74±0.13mg/L)。虽然没有显著的斑马鱼胚胎死亡或孵化变化发生,发育效果明显。确定致死浓度(A.24h时的盐藻LC50=3.19±2.02mg/L;D.Rerio胚胎24h时的LC50=4.19±3.60mg/L),畸形表明潜在的致畸作用。A.salina表现出肠道改变,D.rerio胚胎表现出心包水肿和脊柱畸形。这些发现突出了氧苯酮的环境风险,对物种和生态系统健康构成威胁。
    The benzophenone (BP) family, including oxybenzone (BP-3), a prevalent sunscreen ingredient and environmental contaminant, has raised concerns since the year 2005. This study investigated oxybenzone toxicity in zebrafish (Danio rerio) eleutheroembryos and brine shrimp (Artemia salina) nauplii, focusing on the LC50 and developmental impacts. Zebrafish embryos (0.100-1.50 mg/L BP-3, 96 h) and A. salina (0.100-5.00 mg/L BP-3, 48 h) were tested with ultrasound-assisted emulsified liquid-phase microextraction (UA-ELPME) used for zebrafish tissue analysis. HPLC-DAD determined BP-3 concentrations (highest: 0.74 ± 0.13 mg/L). Although no significant zebrafish embryo mortality or hatching changes occurred, developmental effects were evident. Lethal concentrations were determined (A. salina LC50 at 24 h = 3.19 ± 2.02 mg/L; D. rerio embryos LC50 at 24 h = 4.19 ± 3.60 mg/L), with malformations indicating potential teratogenic effects. A. salina displayed intestinal tract alterations and D. rerio embryos exhibited pericardial edema and spinal deformities. These findings highlight oxybenzone\'s environmental risks, posing threats to species and ecosystem health.
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  • 文章类型: Journal Article
    植物中植物毒素的存在对草食动物构成了健康风险,特别是那些意外食用它们的反刍动物。这些产生的不利影响包括生殖改变,以堕胎为代表,不孕症,和新生儿的形态学改变,这通常归因于其他原因。虽然在某些情况下,含有这种代谢物的植物是已知的,其他时候他们不是,考虑到它们的毒性动力学未知,导致难以治疗的改变。这项文献研究的目的是提供有关植物雌激素等代谢物的信息,L-含羞草苷,labdane二萜-异芥酸,喹啉嗪生物碱和哌啶苦豆素,anabasine,coniine和相关生物碱,其中,在动物有机体及其产生的影响中发挥它们的作用。
    The presence of phytotoxins in plants constitutes a health risk for herbivores, particularly on ruminants who accidently consume them. Among the adverse effects produced by these are reproductive alterations, represented by abortion, infertility, and morphological alterations in neonates, which are frequently attributed to other causes. While in some cases the plants that contain such metabolites are known, other times they are not, leading to alterations that are difficult to treat considering that their toxicodynamics are unknown. The objective of this documentary research is to provide information on how metabolites such as phytoestrogens, L-mimosine, labdane diterpenoids - isocupressic acid, quinolizidine alkaloids and piperidine swainsonine, anabasine, coniine and associated alkaloids, among others, exert their action in the animal organism and the effects they produce.
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  • 文章类型: Journal Article
    对于怀孕时需要继续服用抗精神病药物的患者,存在很多争论,因为必须权衡与抗精神病药物本身相关的潜在致畸和畸形作用。为了解决这个问题,我们对PubMed进行了系统的审查,使用以下策略的PsycINFO和CINHAL数据库和ClinicalTrials.gov注册:(毒性或致畸性或畸形*或“出生缺陷*”或“先天性异常”或“先天性异常”或“大脑异常”或“行为异常”或“行为异常”)和抗精神病药物*(妊娠或妊娠或哺乳期或产前或产后)2023年9月27日。我们发现38项研究符合资格。最古老的文章发表于1976年,而大多数文章都是最近发表的。大多数研究得出结论,抗精神病药,尤其是第二代抗精神病药,缺乏致畸潜力,虽然很少有研究没有定论并推荐复制。大多数权威文章来自波士顿地区,在那里实施了大型数据库来研究精神药物的畸形潜力。其他可靠的数据库来自北欧登记册。总体结论是,抗精神病药物与畸形的关系并不比疾病本身更多;大多数研究认为,没有理由在怀孕期间停用抗精神病药物。
    There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR \"birth defect*\" OR \"congenital abnormality\" OR \"congenital abnormalities\" OR \"brain changes\" OR \"behavioral abnormalities\" OR \"behavioral abnormalities\") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics, especially the second-generation antipsychotics, were devoid of teratogenic potential, while few studies were inconclusive and recommended replication. Most authoritative articles were from the Boston area, where large databases were implemented to study the malformation potential of psychiatric drugs. Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics are no more related to malformations than the disorders themselves; most studies recommend that there are no reasons to discontinue antipsychotic medications in pregnancy.
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  • 文章类型: Journal Article
    散发性脑海绵状畸形(CCM)患者的(再)出血是CCM管理的主要目的。然而,提前准确识别散发性CCM患者的潜在(再)出血仍然是一个挑战。这项研究旨在开发机器学习模型,以检测散发性CCM患者的潜在(再)出血。本研究基于开放数据平台Dryad中731名零星CCM患者的数据集。2003年1月至2018年12月对散发性CCM患者进行5年随访。支持向量机(SVM)堆叠概括,和极端梯度提升(XGBoost)用于构建模型。通过受试者工作特征曲线下面积(AUROC)评估模型的性能,精确率-召回率曲线下面积(PR-AUC)和其他指标。共纳入517例散发性CCM患者(330例女性[63.8%],诊断时的平均[SD]年龄,42.1[15.5]年)。随访期间发生76例(再)出血(14.7%)。在3种机器学习模型中,XGBoost模型在交叉验证中产生最高平均值(SD)AUROC(0.87[0.06])。XGBoost模型的前4个特征以SHAP(Shapley添加剂扩张)排名。All-ElementsXGBoost模型在测试集中实现了0.84的AUROC和0.49的PR-AUC,灵敏度为0.86,特异性为0.76。重要的是,使用前4个特征开发的4元素XGBoost模型在测试集中获得0.83的AUROC和0.40的PR-AUC,0.79的灵敏度和0.72的特异性。两个基于机器学习的模型在识别散发性CCM患者5年内的潜在(再)出血方面实现了准确的性能。这些模型可以为临床决策提供见解。
    The (re)hemorrhage in patients with sporadic cerebral cavernous malformations (CCM) was the primary aim for CCM management. However, accurately identifying the potential (re)hemorrhage among sporadic CCM patients in advance remains a challenge. This study aims to develop machine learning models to detect potential (re)hemorrhage in sporadic CCM patients. This study was based on a dataset of 731 sporadic CCM patients in open data platform Dryad. Sporadic CCM patients were followed up 5 years from January 2003 to December 2018. Support vector machine (SVM), stacked generalization, and extreme gradient boosting (XGBoost) were used to construct models. The performance of models was evaluated by area under receiver operating characteristic curves (AUROC), area under the precision-recall curve (PR-AUC) and other metrics. A total of 517 patients with sporadic CCM were included (330 female [63.8%], mean [SD] age at diagnosis, 42.1 [15.5] years). 76 (re)hemorrhage (14.7%) occurred during follow-up. Among 3 machine learning models, XGBoost model yielded the highest mean (SD) AUROC (0.87 [0.06]) in cross-validation. The top 4 features of XGBoost model were ranked with SHAP (SHapley Additive exPlanations). All-Elements XGBoost model achieved an AUROCs of 0.84 and PR-AUC of 0.49 in testing set, with a sensitivity of 0.86 and a specificity of 0.76. Importantly, 4-Elements XGBoost model developed using top 4 features got a AUROCs of 0.83 and PR-AUC of 0.40, a sensitivity of 0.79, and a specificity of 0.72 in testing set. Two machine learning-based models achieved accurate performance in identifying potential (re)hemorrhages within 5 years in sporadic CCM patients. These models may provide insights for clinical decision-making.
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  • 文章类型: Journal Article
    在脊椎动物早期发育过程中应激的影响可能是特别有害的。避免鱼幼虫的应激源对于确保成年鱼的健康及其繁殖性能和整体生产至关重要。我们研究了在早期发育过程中直接暴露于连续急性应激源的后果,包括它们对miR-29a及其靶标的影响,生存,孵化率和畸形率,幼虫行为和软骨和眼睛发育。我们的目的是阐明这种脊椎动物模型物种中早期诱导应激的多效性作用。我们的结果表明,在早期发育过程中直接暴露于连续的急性应激源显着上调miR-29a和下调必需胶原转录本col2a1a,col6a2和col11a1a,存活率降低和畸形率增加(游泳膀胱,耳石,心脏水肿和眼部畸形),促进幼虫更高的不动率。我们的结果表明,早期阶段的压力可以诱导不同的眼组织结构和颅脑软骨发育改变。我们的研究有助于了解斑马鱼发育早期阶段压力条件的影响,作为脊椎动物研究的有价值的模型。这在发育生物学和水产养殖领域具有至关重要的意义,并且还强调了miR-29a作为评估硬骨鱼物种新型幼虫饲养计划的潜在分子标记。
    The effects of stress during early vertebrate development can be especially harmful. Avoiding stressors in fish larvae is essential to ensure the health of adult fish and their reproductive performance and overall production. We examined the consequences of direct exposure to successive acute stressors during early development, including their effects on miR-29a and its targets, survival, hatching and malformation rates, larval behaviour and cartilage and eye development. Our aim was to shed light on the pleiotropic effects of early-induced stress in this vertebrate model species. Our results showed that direct exposure to successive acute stressors during early development significantly upregulated miR-29a and downregulated essential collagen transcripts col2a1a, col6a2 and col11a1a, decreased survival and increased malformation rates (swim bladder, otoliths, cardiac oedema and ocular malformations), promoting higher rates of immobility in larvae. Our results revealed that stress in early stages can induce different eye tissular architecture and cranioencephalic cartilage development alterations. Our research contributes to the understanding of the impact of stressful conditions during the early stages of zebrafish development, serving as a valuable model for vertebrate research. This holds paramount significance in the fields of developmental biology and aquaculture and also highlights miR-29a as a potential molecular marker for assessing novel larval rearing programmes in teleost species.
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  • 文章类型: Journal Article
    内脏脉管系统与腹盆腔疾病分期密不可分,传播,以及常规和紧急病例的管理。综合评估需要用于异常检测和表征的专门成像技术。在非专用常规影像学检查中经常遇到血管病理学,这可能会模糊,模仿,或者混淆了许多血管诊断。这篇综述重点介绍了正常动脉,门静脉,和全身静脉解剖和临床相关变异;与图像采集技术和疾病模拟相关的诊断陷阱;以及常见和罕见血管疾病的特征,使放射科医生能够自信地解释血管发现并避免误诊。
    The visceral vasculature is inextricably intertwined with abdominopelvic disease staging, spread, and management in routine and emergent cases. Comprehensive evaluation requires specialized imaging techniques for abnormality detection and characterization. Vascular pathology is often encountered on nondedicated routine imaging examinations, which may obscure, mimic, or confound many vascular diagnoses. This review highlights normal arterial, portal venous, and systemic venous anatomy and clinically relevant variants; diagnostic pitfalls related to image-acquisition technique and disease mimics; and characteristics of common and rare vascular diseases to empower radiologists to confidently interpret the vascular findings and avoid misdiagnosis.
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  • 文章类型: Journal Article
    Previous studies on anuran anomalies predominantly examine isolated cases or focus on external and skeletal features. Our study analyzes a comprehensive sample collected from 1991 to 2017, examining the muscle-tendon system in 24 anuran species across adult, juvenile, and metamorphic stages. This extensive sample size allows us to investigate consistent anomaly patterns across different developmental stages and anuran families, exploring potential common developmental or genetic factors. Our detailed anatomical examination, encompassing musculature, tendons, and skeletal structures, revealed that 21% of the specimens displayed anomalies, a noteworthy finding considering the extensive sample size and duration of the studied sample. Of these anomalies, 17% affected the locomotor system, predominantly in the upper limbs. Key anomalies included, forelimbs and hindlimbs brachydactyly, rotation in forelimbs, partial kyphotic lordosis, and scoliosis. Notably, the digit 4 in the forelimbs and digits 4 and 5 in the hindlimbs were particularly susceptible to teratogenic effects, indicating possible prolonged exposure during development. Our study also uncovered combinations of anomalies and identified a phenotype similar to Poland syndrome. The findings validate the \"Logic of Monsters\" (LoMo theory) by Alberch, although the name itself may not be deemed appropriate, showing that developmental disruptions in tetrapods are not random but follow distinct sequences and patterns. The name, while unfortunate, accurately reflects the unusual nature of these developmental anomalies. This contributes to the evolving \"Evo-Devo-Path\" framework, highlighting the study\'s importance in understanding developmental disruptions in tetrapods.
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