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.     

重灸中脘穴对脾胃虚寒型糖尿病胃轻瘫患者胃肠激素、胃动力学的影响

目的观察重灸中脘穴对脾胃虚寒型2型糖尿病胃轻瘫患者胃肠激素、胃动力学的影响。方法选取符合纳入标准的88例脾胃虚寒型糖尿病胃轻瘫患者,按随机数字表法分为治疗组和对照组,每组44例。对照组采用常规药物治疗,治疗组采用重灸中脘穴治疗。疗程结束后记录并对比分析两组临床疗效、胃肠激素[胃泌素(GAS)、胃动素(MTL)]、胃动力学(胃收缩频率、胃排空时间、胃排空率)、主要临床症状评分等变化。结果治疗组临床疗效明显优于对照组,差异具有统计学意义(P<0.05);两组治疗后GAS、MTL均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05);两组治疗后胃收缩频率、胃排空时间、胃排空率均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05);两组治疗后主要临床症状评分均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05)。结论在常规药物治疗基础上重灸中脘穴治疗脾胃虚寒型2型糖尿病胃轻瘫,可调节胃肠激素,改善胃肠动力,促进胃肠功能恢复。     

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.     

小汤山地区0-3岁儿童喂养情况及母亲孕期贫血情况与贫血的关系

目的了解北京市小汤山地区儿童贫血分布情况,并指出合理化预防措施。方法采用日本产西斯美康xs-800i全血细胞分析仪,检测0-3岁儿童末梢血的血红蛋白含量。结果 2013年儿保门诊0~3岁儿童体检人数为1334人,其中贫血患儿为176名,贫血的发病率是13.19%。其中,本地儿童616人,贫血发病率是9.42%;流动儿童718人,贫血发病率是16.43%,二者间有统计学差异(P0.01);男性儿童贫血发病率为13.02%,女性贫血发病率13.46%,二者间无统计学差异(P0.01);6个月-1岁儿童贫血发病率为35.79%,1-2岁为4.48%,2-3岁为2.61%,三组间有统计学差异(P0.01),纯母乳喂养儿童贫血人数为47人,贫血的发病率是6.15%,混合喂养儿童贫血人数为29人,贫血的发病率是8.19%,人工喂养喂养儿童贫血人数为100人,贫血的发病率是46.30%,三者差异存在统计学意义(P0.01);母孕期贫血儿童贫血人数为97人,贫血的发病率是18.29%,母孕期无贫血儿童贫血人数为79人,贫血的发病率是10.75%,三者差异存在统计学意义(P0.01)。结论本地区0~3岁儿童贫血患病比6个月-1岁儿童显著增高,流动儿童比本市儿童贫血患病率显著增高,此外母孕期贫血及婴儿喂养方式的不同也是影响儿童贫血的原因,加强流动儿童管理,正确指导6个月后婴儿家长的喂养方法及加强预产妇孕期营养指导应成为今后工作的重点。     

医疗器械口咽通气道产品注册的常见问题及改进建议

近年来,医疗器械口咽通气道产品的注册数量日益增加,针对该产品的相关咨询也逐渐增多。但该产品暂无相关的注册技术审查指导原则,以致该产品的注册申报资料经常出现一些共性问题。现根据医疗器械口咽通气道产品相关法规和标准,对日常工作中遇到的常见问题进行归纳,分析该产品注册申报中的技术审评要求及共性问题,并给出对策或建议。