ZBTB16: A new biomarker for primitive neuroectodermal tumor element / Ewing sarcoma

Primitive neuroectodermal tumor (PNET) traditionally encompasses two different classes of tumors with similar morphology - PNET of the peripheral nervous system (pPNET) and PNET of the central nervous system (cPNET). The latter also includes germ cell tumor-derived PNET (gPNET). There are currently no specific markers for gPNET. This study seeks to investigate the expression of ZBTB16 in PNET and other small round blue cell tumors as well as its potential diagnostic utility. Immunohistochemical expression of the ZBTB16 was studied in a total of 27 PNETs (12 pPNETs, 8 cPNETs, 3 primary testicular gPNETs, and 4 metastatic gPNETs) and 38 small round blue cell tumors. Positive expression for ZBTB16 was seen diffusely in 9/12 (75%), moderately in 2/12 (17%) and focally in 1/12 (8%) of pPNETs, diffusely in 3/7 (43%) and moderately in 4/7 (57%) of gPNETs, and diffusely in 2/8 (25%), moderately in 2/8 (25%) and focally in 4/8 (50%) of cPNETs. Whereas, all of the 38 non-PNET small round blue cell tumors were nonreactive. The results suggest that ZBTB16 is a highly sensitive and specific biomarker for both pPNET and gPNET/cPNET. ZBTB16 effectively differentiates PNETs from other small round blue cell tumor mimics, including the two most common germ cell tumor-derived somatic malignancies - rhabdomyosarcoma and nephroblastoma. Of note, compared to the expression of ZBTB16 in pPNET/Ewing sarcoma and gPNET, the expression of ZBTB16 in cPNET was more variable, which appears consistent with the heterogeneity of cPNET. The close proximity of ZBTB16 and FLI-1 genes on chromosome 11q may explain the overexpression of ZBTB16 in PNET, especially in pPNET with t(1122) translocation.     

A diagnostically‐challenging case of melanoma ex blue nevus with comprehensive molecular analysis,including the 23‐gene expression signature (myPath melanoma)

Melanoma ex blue nevus (MEBN) is a rare, aggressive, and potentially lethal neoplasm. Distinguishing MEBN from an atypical cellular blue nevus can be very challenging. We report a diagnostically difficult case of MEBN with lymph node metastases, in which single nucleotide polymorphism array and fluorescence in situ hybridization were used to arrive at the correct diagnosis. It was also analyzed by the recently‐introduced proprietary 23‐gene expression signature test. To the best of our knowledge, this is the second reported case of MEBN analyzed by the 23‐gene expression signature, which provided a false‐negative result. More studies are needed to assess the sensitivity and specificity of this test in various melanocytic proliferations.     

彩色多普勒超声引导下亚甲蓝边界定位法在乳腺癌保乳手术中的应用价值

目的探讨术前彩色多普勒超声引导下应用亚甲蓝定位肿瘤边界在乳腺癌保乳手术中的效果。方法收集2015年5月至2017年12月拟行保乳手术的乳腺癌患者120例,随机分为观察组和对照组各60例。观察组术前在彩色多普勒超声引导下行亚甲蓝定位,对照组采用传统手术方法。所有标本切除后进行病理检查,统计两组切缘情况。从精准性及微创性两方面比较两种方法的手术效果。结果观察组中,3例(5.0%)最大切缘>2 cm,57例(95.0%)最大切缘≤2 cm;对照组中,31例(51.7%)最大切缘>2 cm,29例(48.3%)最大切缘≤2 cm。两组比较差异有统计学意义(P=0.000)。观察组6例(10.0%)患者的手术标本镜下切缘阳性,54例(90.0%)切缘阴性;对照组15例(25.0%)镜下切缘阳性,45例(75.0%)切缘阴性。两组比较差异有统计学意义(P=0.031)。观察组和对照组分别有2例和3例在行二次扩切后切缘仍为阳性,改行乳腺全切手术。结论采用术前彩色多普勒超声引导下亚甲蓝定位肿瘤边界指导乳腺癌保乳手术的方法较常规方法在手术精准性及微创性两方面均有优势。     

新生儿高胆红素血症的临床治疗分析

目的探讨布拉氏酵母菌散治疗对新生儿高胆红素血症的临床疗效。方法在2018年1月—2019年1月期间,将医院诊治的110例新生儿高胆红素血症患儿纳入研究对象,按照治疗方法的不同,将患儿分成两组,采用常规蓝光照射治疗的患儿定为对照组,55例,在蓝光治疗基础上增加布拉氏酵母菌散治疗的患儿定为观察组,55例,对比两组患儿治疗的临床效果。结果观察组和对照组治疗的有效率分别为98.18%和87.27%,有统计学意义(P<0.05);治疗后3 d和1周,两组患儿的胆红素水平明显下降,且观察组患儿下降更加明显,与对照组相比差异有统计学意义(P<0.05);观察组患儿黄疸消退时间为(5.12±1.21)d,对照组患儿黄疸消退时间为(7.21±1.22)d,有统计学意义(P<0.05);观察组不良反应发生率为5.45%,明显低于对照组的12.73%,有统计学意义(P<0.05)。结论对新生儿高胆红素血症患儿在常规蓝光治疗的基础上增加布拉氏酵母菌散进行治疗,可以显著提高临床治疗效果。     

分析蓝光照射、白蛋白治疗新生儿黄疸效果

目的探讨蓝光照射联合白蛋白治疗新生儿黄疸的临床效果。方法选取2018年1月—2018年12月医院收治的136例新生儿黄疸患儿,按随机数字表法分为A组(68例)和B组(68例),A组采取蓝光照射进行治疗,B组在此基础上联合白蛋白进行治疗,并比较不同组患儿治疗疗效。结果B组患儿治疗有效率较A组明显增加(P<0.05);B组患儿治疗前间接胆红素(IBIL)、总胆红素(TBIL)、γ-谷氨酰基转移酶(γ-GT)、游离脂肪酸(FFA)和超敏C反应蛋白(hsCRP)水平比较差异无统计学意义(P>0.05),治疗后B组患儿IBIL、TBIL、γ-GT、FFA和hs-CRP水平明显小于A组(P<0.05)。结论蓝光照射联合白蛋白静滴治疗新生儿黄疸临床疗效较好,有助于减轻胆红素水平以及改善临床症状。     

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。     

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.     

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.     

Antiviral photodynamic therapy: Inactivation and inhibition of SARS-CoV-2 in vitro using methylene blue and Radachlorin

IntroductionRecently, the COVID-19 pandemic has spread globally, necessitating the development of new methods for its prevention and treatment. The purpose of this study was to evaluate the antiviral activity of photodynamic therapy (PDT) against SARS-CoV-2 in vitro.MethodsVero E6 cells and SARS-CoV-2 isolated in Russia were used for PDT with methylene blue (MB) and Radachlorin. A continuous laser with wavelength λ = 662 nm in doses of 16 J/cm² and 40 J/cm² laser irradiation was used for PDT of a viral suspension and SARS-CoV-2-infected cells. The direct cytopathogenic effect of SARS-CoV-2 was evaluated via light microscopy to calculate the TCID₅₀ in the samples and perform statistical analysis.ResultsViral suspensions of SARS-CoV-2 that had a TCID₅₀ greater than 10³ were inactivated by PDT in the presence of MB and Radachlorin. Vero E6 cells were protected from 10⁴ TCID₅₀ of SARS-CoV-2 by PDT post infection. The range of protective concentrations was 1.0–10.0 μg/ml and 0.5–5.0 μg/ml for MB and Radachlorin, respectively. Additionally, it was found that MB and Radachlorin also possess significant antiviral activity even without PDT. The 50 % inhibitory concentration (IC₅₀) against 10² TCID₅₀ of SARS-CoV-2 was found to be 0.22 and 0.33 μg/mL with the addition of MB and Radachlorin, respectively, to cells concomitantly with virus, whereas in the case of applying the photosensitizers at 3.5 h post infection, the IC₅₀ was 0.6 and 2.0 μg/mL for MB and Radachlorin, respectively.ConclusionPDT shows high antiviral activity against SARS-CoV-2 when combined with MB and Radachlorin in vitro.