Utility of the 3‐Vessel and 3‐Vessel and Trachea Views in Prenatal Diagnosis of a Pulmonary Artery Sling

A pulmonary artery (PA) sling is a very rare congenital cardiovascular anomaly, and only a few studies have reported PA slings in fetuses. The relationship of the PA, aorta, ductus arteriosus, and trachea can be evaluated in the 3‐vessel and 3‐vessel and trachea views during fetal echocardiography. A PA sling can be detected by abnormal positioning of the left PA in relation to the trachea when sweeping from the 3‐vessel view cranially to the 3‐vessel and trachea view. Here we report 3 cases of fetal PA slings and their follow‐ups. Two cases were confirmed by postnatal echocardiography, and the other case was confirmed by a cardiovascular cast after pregnancy termination. We emphasize that the 3‐vessel and 3‐vessel and trachea views are of crucial importance in the prenatal diagnosis of a PA sling.     

基于调控肠道菌群探讨中药防治脑卒中

肠道菌群是一个独特的生态系统,被称为人体"被遗忘的器官",被誉为人类的"第二基因组"。肠道菌群失调与许多中枢神经系统疾病相关,例如帕金森病、阿尔茨海默症、精神分裂症及多发性硬化等。脑卒中具有高的发病率、复发率、死亡率和致残率的特点。肠道菌群在脑卒中的发生、发展中起着关键的作用,可通过影响机体的吸收、代谢、血压、血糖、血脂及动脉粥样斑块等因素,进一步影响脑卒中的发病。中医认为脾胃气血流注失度、阴阳盛衰失衡,机体生理功能失调,化生"风、火、痰、虚、瘀"等病理产物,可致中风的发生。脾胃主腐熟运化水谷,肠道菌群影响饮食的消化吸收,现代研究的肠道菌群功能与中医之脾胃功能失调相关。因此,调整肠道菌群的稳态,可作为一个潜在的干预靶点预防和治疗缺血性脑卒中。中药干预脑卒中已经取得了很好的疗效,是否与调节肠道菌群有关,值得未来做进一步的研究。同时对中药有效成分(小檗碱、黄芩苷、白藜芦醇等),中药单方(丹参、红景天等)和中药组方(补阳还五汤、脑心通胶囊、补中益气汤等)防治脑缺血的研究进展进行综述,为缺血性脑卒中的预防和开发提供新的途径和思路。     

The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan

Introduction

For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM_2.5) levels on LC in Taiwan, in relation to contrasting PM_2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

Mechanisms of repigmentation induced by photobiomodulation therapy in vitiligo

Photobiomodulation (PBM) therapy is based on the exposure of biological tissues to low‐level laser light (coherent light) or light‐emitting diodes (LEDs; noncoherent light), leading to the modulation of cellular functions, such as proliferation and migration, which result in tissue regeneration. PBM therapy has important clinical applications in regenerative medicine. Vitiligo is an acquired depigmentary disorder resulting from disappearance of functional melanocytes in the involved skin. Vitiligo repigmentation depends on available melanocytes derived from (a) melanocyte stem cells located in the bulge area of hair follicles and (b) the epidermis at the lesional borders, which contains a pool of functional melanocytes. Since follicular melanoblasts (MBs) are derived from the melanocyte stem cells residing at the bulge area of hair follicle, the process of vitiligo repigmentation presents a research model for studying the regenerative effect of PBM therapy. Previous reports have shown favourable response for treatment of vitiligo with a low‐energy helium‐neon (He‐Ne) laser. This review focuses on the molecular events that took place during the repigmentation process of vitiligo triggered by He‐Ne laser (632.8 nm, red light). Monochromatic radiation in the visible and infrared A (IRA) range sustains matrix metalloproteinase (MMP), improves mitochondrial function, and increases adenosine triphosphate (ATP) synthesis and O₂ consumption, which lead to cellular regenerative pathways. Cytochrome c oxidase in the mitochondria was reported to be the photoacceptor upon which He‐Ne laser exerts its effects. Mitochondrial retrograde signalling is responsible for the cellular events by red light. This review shows that He‐Ne laser initiated mitochondrial retrograde signalling via a Ca²⁺‐dependent cascade. The impact on cytochrome c oxidase within the mitochondria, an event that results in activation of CREB (cyclic‐AMP response element binding protein)‐related cascade, is responsible for the He‐Ne laser promoting functional development at different stages of MBs and boosting functional melanocytes. He‐Ne laser irradiation induced (a) melanocyte stem cell differentiation; (b) immature outer root sheath MB migration; (c) differentiated outer root sheath MB melanogenesis and migration; and (d) perilesional melanocyte migration and proliferation. These photobiomodulation effects result in perifollocular and marginal repigmentation in vitiligo.     

磁敏感加权成像黑质“燕尾征”在帕金森病中的诊断价值

目的:探讨3.0 T磁敏感加权成像(susceptibility weighted imaging,SWI)中"燕尾征"缺失在帕金森病(Parkinson's dis-ease,PD)的诊断价值并分析黑质小体-1 (nigrosome-1)可视化与PD患者临床资料的相关性.方法:收集2017年9月至2019年11月于重庆医科大学附属第一医院神经内科住院的50例PD患者及年龄、性别与之匹配的57例非PD患者.所有受试者均接受3.0 T头颅SWI检查.在获得的SWI图像上,由2名临床医师采用盲法独立对双侧"燕尾征"进行评估.一侧"燕尾征"缺失即判定为PD.计算"燕尾征"缺失诊断PD的灵敏度、特异度、预测值和准确度,并分析nigrosome-1可视化与PD患者临床资料的相关性.结果:以临床诊断作为金标准,45例PD患者判断正确,评估者之间的一致性很高(k=0.963,P=0.000)."燕尾征"缺失诊断PD的灵敏度为90.0％,特异度为91.2％,阳性预测值为90.0％,阴性预测值为91.2％,准确度为90.7％.44例PD患者临床症状不对称,其中32例患者nigrosome-1可视化不对称.PD患者nigrosome-1可视化偏侧和临床症状偏侧比较差异无统计学意义(x2=5.756,P=0.056).11例PD患者双侧nigrosome-1全部缺失,纳入全部缺失组,其余PD患者为非全部缺失组.全部缺失组和非全部缺失组患者的汉密尔顿抑郁量表评分差异有统计学意义(U=126.500,P=-0.038),而病程、帕金森病统一评定量表第Ⅲ部分、改良Hoehn-Yahr(H-Y)分级、简易智能状态量表和蒙特利尔认知评估量表评分差异均无统计学意义(P=0.768、0.140、0.839、0.054、0.067).结论:"燕尾征"缺失诊断PD的准确率较高,缺失程度可能与PD患者的抑郁程度有关,对PD的诊断有一定参考价值.     

Putative protective neural mechanisms in prereaders with a family history of dyslexia who subsequently develop typical reading skills

Developmental dyslexia affects 40–60% of children with a familial risk (FHD+) compared to a general prevalence of 5–10%. Despite the increased risk, about half of FHD+ children develop typical reading abilities (FHD+Typical). Yet the underlying neural characteristics of favorable reading outcomes in at‐risk children remain unknown. Utilizing a retrospective, longitudinal approach, this study examined whether putative protective neural mechanisms can be observed in FHD+Typical at the prereading stage. Functional and structural brain characteristics were examined in 47 FHD+ prereaders who subsequently developed typical (n = 35) or impaired (n = 12) reading abilities and 34 controls (FHD?Typical). Searchlight‐based multivariate pattern analyses identified distinct activation patterns during phonological processing between FHD+Typical and FHD?Typical in right inferior frontal gyrus (RIFG) and left temporo‐parietal cortex (LTPC) regions. Follow‐up analyses on group‐specific classification patterns demonstrated LTPC hypoactivation in FHD+Typical compared to FHD?Typical, suggesting this neural characteristic as an FHD+ phenotype. In contrast, RIFG showed hyperactivation in FHD+Typical than FHD?Typical, and its activation pattern was positively correlated with subsequent reading abilities in FHD+ but not controls (FHD?Typical). RIFG hyperactivation in FHD+Typical was further associated with increased interhemispheric functional and structural connectivity. These results suggest that some protective neural mechanisms are already established in FHD+Typical prereaders supporting their typical reading development.     

GPER-induced signaling is essential for the survival of breast cancer stem cells

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER⁻/PR⁺ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.     

SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters

Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface.