经皮对比增强超声在乳腺癌前哨淋巴结术前定位及转移风险评估中的临床应用价值

目的探讨经皮注射对比增强超声(CEUS)在乳腺癌前哨淋巴结(SLN)术前定位及转移风险评估中的临床应用价值。 方法根据纳入及排除标准，选择2019年5～9月在江苏大学附属人民医院乳腺外科行手术治疗的21例女性乳腺癌患者进行前瞻性研究。术前根据经皮CEUS示踪结果，在皮肤表面标记SLN位置及数目，根据其增强模式评估SLN转移风险，并在术中联合亚甲蓝共同确认SLN的位置及数目。以亚甲蓝染色的病理检查结果为金标准，计算经皮CEUS预测SLN状态的敏感度、特异度、阳性预测值、阴性预测值及准确率。用Kappa一致性检验分析CEUS与SLN常规病理检查结果的一致性及2名超声科医师对SLN增强模式判读的一致性。用Fisher精确概率法分析不同临床病理特征患者CEUS评估SLN结果的差异。 结果21例患者中，经皮CEUS共检出32枚SLN，亚甲蓝染色共检出71枚。经皮CEUS体表定位的SLN均为术中亚甲蓝染色的SLN,患者经皮CEUS检出(1.6±0.9)枚SLN,低于亚甲蓝染色检出的(3.4±1.4)枚(t＝5.017, P<0.001)。CEUS预测SLN转移风险：判定有SLN转移患者9例(病理证实SLN有转移7例，无转移2例)，判定无转移患者12例(病理证实SLN无转移11例，有转移1例)。CEUS评估SLN状态的敏感度7/8，特异度11/13，阳性预测值7/9，阴性预测值11/12，准确率85.7%(18/21)。CEUS与病理诊断结果具有较高一致性(Kappa ＝0.704，P＝0.001)。2名超声科医师对CEUS中32枚SLN增强模式的判读结果一致性较好(Kappa＝0.829，P<0.001)。不同组织学分级的患者，其CEUS预测结果比较，差异有统计学意义(P＝0.046)。 结论经皮CEUS是乳腺癌患者SLN术前定位及转移风险评估的一种有效方法。     

Investigating the association between eye colour and the Neurological Pupil index

IntroductionBrown or dark brown eyes make it difficult to distinguish the contrast between a black pupil and the surrounding iris, which may result in clinical assessment errors. The pupillometer can be used to derive an indexed value, the Neurological Pupil index™ (NPi) for pupillary light reflex. However, there are limited data associating the NPi and iris colour. We examine the NPi and eye colour association.MethodsData were pooled from the Establishing Normative Data for Pupillometer Assessments in Neuroscience Intensive Care (END-PANIC) Registry. The analysis includes 14,168 observations collected from 865 patients with neurological conditions who were admitted to the intensive care unit. Summary statistics and statistical models were developed to examine the association using Statistical Analysis Software (SAS) summary procedure.ResultsThe mean age of the cohort was 56 years (standard deviation = 17). Eye colour included dark brown (n = 339), blue (n = 234), brown (n = 173), green (n = 82), and other (n = 37). There was significant differences (p < 0.0001) between mean NPi values by eye colour [blue = 4.08 (0.92), brown = 3.34 (1.45), dark = 3.71 (1.33), green = 4.08 (0.67), other = 3.76 (1.25)]. However, a further random-effects mixed model after controlling for confounding variables revealed no significant difference in NPi values among different eye colour groups.ConclusionsThe pupillary light reflex, when assessed using the pupillometer, is not dependent on the eye colour. Practitioners are not required to consider eye colour as a confounder when they perform pupillary assessment for examining patients with neurological conditions.     

Comparison between a new platelet count drop method PL-11, light transmission aggregometry,VerifyNow aspirin system and thromboelastography for monitoring short-term aspirin effects in healthy individuals

Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11.     

Engraftable neural crest stem cells derived from cynomolgus monkey embryonic stem cells

Neural crest stem cells (NCSCs), a population of multipotent cells that migrate extensively and give rise to diverse derivatives, including peripheral and enteric neurons and glia, craniofacial cartilage and bone, melanocytes and smooth muscle, have great potential for regenerative medicine. Non-human primates provide optimal models for the development of stem cell therapies. Here, we describe the first derivation of NCSCs from cynomolgus monkey embryonic stem cells (CmESCs) at the neural rosette stage. CmESC-derived neurospheres replated on polyornithine/laminin-coated dishes migrated onto the substrate and showed characteristic expression of NCSC markers, including Sox10, AP2α, Slug, Nestin, p75, and HNK1. CmNCSCs were capable of propagating in an undifferentiated state in vitro as adherent or suspension cultures, and could be subsequently induced to differentiate towards peripheral nervous system lineages (peripheral sympathetic neurons, sensory neurons, and Schwann cells) and mesenchymal lineages (osteoblasts, adipocytes, chondrocytes, and smooth muscle cells). CmNCSCs transplanted into developing chick embryos or fetal brains of cynomolgus macaques survived, migrated, and differentiated into progeny consistent with a neural crest identity. Our studies demonstrate that CmNCSCs offer a new tool for investigating neural crest development and neural crest-associated human disease and suggest that this non-human primate model may facilitate tissue engineering and regenerative medicine efforts.     

A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

An interdisciplinary approach to investigate collective cell migration in neural crest

The neural crest serves as a powerful and tractable model paradigm for understanding collective cell migration. The neural crest cell populations are well-known for their long-distance collective migration and contribution to diverse cell lineages during vertebrate development. If neural crest cells fail to reach a target or populate an incorrect location, then improper cell differentiation or uncontrolled cell proliferation can result. A wide range of interdisciplinary studies has been carried out to understand the response of neural crest cells to different stimuli and their ability to migrate to distant targets. In this critical commentary, we illustrate how an interdisciplinary collaboration involving experimental and mathematical modeling has led to a deeper understanding of cranial neural crest cell migration. We identify open questions and propose possible ways to start answering some of the challenges arising.     

Chronic sleep loss disrupts blood–testis and blood–epididymis barriers,and reduces male fertility

Sleep loss increases blood–brain barrier permeability. As the blood–brain barrier and the blood–tissue barriers in the reproductive tract (blood–testis and blood–epididymis barriers) share common characteristics, we hypothesized that sleep restriction may also modify their barrier function. Previous reports showed that sleep loss decreased sperm viability and progressive fast mobility, which may be a consequence of altered blood–testis and blood–epididymis barrier. Therefore, we quantified changes in blood–testis and blood–epididymis barrier after sleep loss and related them to male fertility. Adult male Wistar rats were sleep restricted using the multiple‐platform technique in a protocol of 20 hr daily sleep deprivation plus 4 hr of sleep recovery in the home‐cage. At the 10th day, barrier permeability assays were performed with Na‐fluorescein, 10 kDa Cascade blue‐dextrans and Evans blue, and the expression of tight junction proteins, actin and androgen receptor was quantified. At the 10th day of sleep restriction and after sleep recovery days 1–7, males were placed with sexually receptive females, sexual behaviour was tested, and the percentage of pregnancies was calculated. Sleep restriction increased the barrier permeability to low‐ and high‐molecular‐weight tracers, and decreased the expression of tight junction proteins, actin and androgen receptor. Concomitantly, sleep restriction reduced the percentage of ejaculating males and the number of pregnancies. Sleep recovery for 2–3 days progressively re‐established fertility, as indicated by a higher percentage of ejaculating males and impregnated females. In conclusion, chronic sleep loss alters fertility concomitantly with the disruption of the blood–tissue barriers at the reproductive tract, the mechanism involves androgen signalling.     

The relationship between ANT1 and NFL with autophagy and mitophagy markers in patients with multiple sclerosis

Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease. Neurofilament light chain (NFL) is a novel adverting biomarker of axonal damage that suggested as a useful assistant in the monitoring of MS patients. It has been shown that the auto/mitophagy associated with MS pathogenesis. In this study, we aimed to study correlation between ATG5 and Parkin, as markers of autophagy and mitophagy respectively, with NFL and ANT1 in serum and cerebrospinal fluid (CSF) in MS subjects. ATG5, Parkin, NFL, and ANT1 levels were measured in a cross-sectional study of 40 MS patients compared with gender, age and BMI matching healthy volunteers. Based on our results, levels of ATG5, Parkin, and NFL significantly were elevated in both serum and CSF of MS patients comparing control individuals (p < 0.0001) but ANT1 levels significantly was decreased in both serum and CSF of MS patients comparing control individuals (p < 0.0001). The correlation indices between NFL, ANTI1, ATG5 and Parkin in both case and control groups showed a direct and moderate the correlation between ANTI1 and ATG5 in the CSF level of the control group (r = 0.554, P = 0.011). Our data support the feasibility of quantifying of NFL as a sensitive and clinically meaningful serum/CSF biomarker to follow-up nerve tissue injury in MS condition.