Global and Local Deformation Effects of Dry Vacuum-Consolidated Triaxial Compression Tests on Sand Specimens: Making a Database Available for the Calibration and Development of Forward Models

A comprehensive experimental database containing results of a series of dry vacuum-consolidated triaxial compression tests was populated. The tests were performed on sand specimens and conducted under similar experimental conditions, in which specimens’ boundary deformation was captured using a three-dimensional digital image correlation analysis (3D-DIC). The use of a standard triaxial device along with the 3D-DIC technology allowed the specimens’ global and local boundary displacement fields to be computed from start to end of the compression phase. By repeating each test under the same experimental conditions and building the specimens using the same type of sand, the boundary deformation patterns could be identified, and the statistics associated with both global and local displacement fields could be assessed. Making this experimental database available to others should serve to calibrate as well as develop new forward models to account for effects associated with the specimens’ local displacements and material heterogeneity and include statistics to represent a specimen’s random response. Moreover, this work will serve as a basis for the statistical characterization of spatio-temporal boundary localization effects used to develop stochastic models and machine-learning models, and simulate virtual triaxial tests.     

复发性阿弗他口炎致咽喉出血1例

本文报道1例发生于青年男性的复发性阿弗他口炎。患者男,34岁,因“咯血1 h”就诊于青岛大学附属医院耳鼻咽喉头颈外科急诊,在全身麻醉下行咽喉探查止血术,术中见：会厌畸形,呈分叶状,咽后壁大片白色溃疡,质地硬,范围自会厌上缘至梨状窝水平,会厌上缘附近可见凹陷创面,直径约1.2 cm,创面活动性渗血。溃疡区域组织活检,病理...     

Vaccine-induced myeloid cell population dampens protective immunity to SIV

Vaccines are largely evaluated for their ability to promote adaptive immunity, with little focus on the induction of negative immune regulators. Adjuvants facilitate and enhance vaccine-induced immune responses and have been explored for mediating protection against HIV. Using a regimen of peptide priming followed by a modified vaccinia Ankara (MVA) boost in a nonhuman primate model, we found that an SIV vaccine incorporating molecular adjuvants mediated partial protection against rectal SIVmac251 challenges. Animals treated with vaccine and multiple adjuvants exhibited a reduced viral load (VL) compared with those treated with vaccine only. Surprisingly, animals treated with adjuvant alone had reduced VLs that were comparable to or better than those of the vaccine-treated group. VL reduction was greatest in animals with the MHC class I allele Mamu-A*01 that were treated with adjuvant only and was largely dependent on CD8⁺ T cells. Early VLs correlated with Ki67⁺CCR5⁺CD4⁺ T cell frequency, while set-point VL was associated with expansion of a myeloid cell population that was phenotypically similar to myeloid-derived suppressor cells (MDSCs) and that suppressed T cell responses in vitro. MDSC expansion occurred in animals receiving vaccine and was not observed in the adjuvant-only group. Collectively, these results indicate that vaccine-induced MDSCs inhibit protective cellular immunity and suggest that preventing MDSC induction may be critical for effective AIDS vaccination.     

E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non–small cell lung cancer

Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non–small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations. Low MKRN3 expression levels correlate with poor patient survival. Reconstitution of MKRN3 in MKRN3-inactivated NSCLC cells directly abrogates in vitro and in vivo tumor growth and proliferation. MKRN3 knockout mice are susceptible to urethane-induced lung cancer, and lung cell–specific knockout of endogenous MKRN3 accelerates NSCLC tumorigenesis in vivo. A mass spectrometry–based proteomics screen identified PABPC1 as a major substrate for MKRN3. The tumor suppressor function of MKRN3 is dependent on its E3 ligase activity, and MKRN3 missense mutations identified in patients substantially compromise MKRN3-mediated PABPC1 ubiquitination. Furthermore, MKRN3 modulates cell proliferation through PABPC1 nonproteolytic ubiquitination and subsequently, PABPC1-mediated global protein synthesis. Our integrated approaches demonstrate that the CPP-associated gene MKRN3 is a tumor suppressor.     

牛黄熊脱氧胆酸抑制TNF-α刺激3T3-L1细胞脂肪分解

目的探讨牛黄熊脱氧胆酸(tauroursodeoxycholic acid,TUDCA)对TNF-α刺激3T3-L1细胞脂肪分解及其可能的机制。方法以3T3-L1前脂肪细胞经1-甲基-3-异丁基-黄嘌呤、地塞米松、胰岛素诱导分化成3T3-L1脂肪细胞,设:①对照组;②TNF-α(50 ng/ml)组;③TUDCA(1 mmol/L)+TNF-α(50 ng/ml)组;④TUDCA组(1 mmol/L)。通过油红O染色观察脂滴形态变化并测定培养基中甘油含量作为评价脂肪分解的指标,同时用Western blot检测脂滴包被蛋白perilipinA蛋白表达。结果 TNF-α可以显著刺激3T3-L1细胞脂肪分解,包括功能学显示甘油释放量显著增加[(2.784±0.104)mmol/L,P<0.01],形态学显示脂滴碎裂;TUDCA可以明显抑制TNF-α刺激的3T3-L1细胞脂肪分解,包括阻止脂滴形态的改变,逆转甘油的释放[(1.718±0.085)mmol/L,P<0.01]。通过Western blot检测结果显示TNF-α可以下调perilipin A蛋白表达[(0.227±0.004),P<0.01],而TUDCA可以阻断TNF-α对perilipin A蛋白表达的下调作用[(0.705±0.066),P<0.01]。结论 TUDCA可能通过阻止perilipin A蛋白下调而抑制TNF-α诱发脂肪分解,通过减少游离脂肪酸FFA,从而对胰岛素抵抗、糖尿病等具有一定的改善作用。     

精准肝切除与非规则性肝切除治疗肝内胆管结石的疗效对比

目的探讨精准肝切除与非规则肝切除治疗肝内胆管结石的临床疗效。 方法选取2015年1月至2016年9月收治的150例肝内胆管结石患者为观察对象,根据不同手术方式将患者分为PH组(73例,行精准肝切除)和IH组(77例,行非规则性肝切除),统计分析应用SPSS20.0软件,术中术后相关指标及肝功能指标等计量资料以( ±s)表示,采用独立t检验;结石残余率、复发率和术后并发症发生率等计数资料以例(%)表示,组间比较采用χ²检验,均以P<0.05为差异有统计学意义。 结果PH组手术时间长于IH组,而术中出血量、住院时间和肝功能恢复时间均低于IH组,差异有统计学意义(P<0.05);PH组的结石残余率为2.7%低于IH组的14.3%,结石复发率为0低于IH组的10.4%,术后并发症发生率为2.7%低于IH组的20.8%,差异均有统计学意义(P<0.05)。PH组术后ALP、ALT、TBA和GGT分别为(103.2±25.7) U/L、(40.2±11.2) U/L、(9.6±3.2) U/L、(82.4±15.3) μmol/L,明显低于IH组的(148.4±27.3) U/L、(49.3±10.7) U/L、(103.5±17.2) U/L、(17.7±5.6) μmol/L,差异有统计学意义(P<0.05)。 结论精准肝切除治疗肝内胆管结石可减轻手术创伤,降低术后并发症发生率,利于患者康复,优于非规则性肝切除。     

基于骰骨MRI的糖尿病足影像组学特征

目的 探究基于MRI影像组学特征辅助诊断糖尿病足（DF）的可行性。 方法 回顾性分析2018年8月至2020年8月于上海中医药大学附属上海市中西医结合医院行足部MRI检查的127例因足部疾患就诊患者的临床资料,其中男性83例、女性44例,年龄16~88（59.3±14.8）岁。根据患者临床诊断的不同分为DF组（85例）和非DF组（42例）;根据影像组学特点,采用简单随机抽样法,将患者以3∶2的比例随机分为训练组（76例）和测试组（51例）。在MRI的T1加权成像（WI）序列和质子密度加权成像（PDWI）压脂序列矢状面图像上勾画骰骨,提取影像组学特征参数,并构建T1WI序列模型、PDWI压脂序列模型及联合模型,联合模型包括性别、年龄、骨髓信号和影像组学特征参数。通过3组模型参数最大绝对值归一化的预处理,经过最优特征和模型选择筛选出最优特征维度。采用受试者工作特征（ROC）曲线,计算曲线下面积（AUC）,评估影像组学特征诊断DF的效能。2组间年龄的比较采用独立样本t检验,2组间性别和中足骨骨髓信号异常的比较采用χ2检验。 结果 DF组和非DF组患者在年龄、男女比例及中足骨骨髓信号异常间的差异均有统计学意义（t=29.2,χ2=17.15、6.53,均P<0.05）。T1WI序列模型、PDWI压脂序列模型和联合模型最终分别筛选出9、7和10个最优特征维度。支持向量机模型区别DF和非DF患者在T1WI序列模型上训练组和测试组的AUC分别为0.86和0.84,准确率分别为78%和69%; PDWI压脂序列模型上训练组和测试组的AUC分别为0.85和0.83,准确率分别为82%和78%;而联合模型上训练组和测试组的AUC分别为0.93和0.85,准确率分别为84%和76%。T1WI序列模型与PDWI压脂序列模型诊断效能相当,而联合模型优于二者单独应用。 结论 MRI影像组学特征能有效区分DF和非DF,有望为DF影像诊断提供一种新型、高效、无创的手段。     

TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4⁺ memory T cell loss in SIVmac251-challenged rhesus macaques

Adjuvant plays an important role in increasing and directing vaccine-induced immune responses. In a previous study, we found that a mucosal SIV vaccine using a combination of IL-15 and TLR agonists as adjuvant mediated partial protection against SIVmac251 rectal challenge, whereas neither IL-15 nor TLR agonists alone as an adjuvant impacted the plasma viral loads. In this study, dissociation of CD4⁺ T cell preservation with viral loads was observed in the animals vaccinated with adjuvants. Significantly higher levels of memory CD4⁺ T cell numbers were preserved after SIVmac251 infection in the colons of the animals vaccinated with vaccine containing any of these adjuvants compared to no adjuvant. When we measured the viral-specific CD8⁺ tetramer responses in the colon lamina propria, we found significantly higher levels of gag, tat, and pol epitope tetramer⁺ T cell responses in these animals compared to ones without adjuvant, even if some of the animals had similarly high viral loads. Furthermore, this CD4⁺ T preservation was positively correlated with increased levels of gag and Tat, but not pol tetramer⁺ T cell responses, and inversely correlated with beta-chemokine expression. The pre-challenged APOBEC3G expression level, which has previously been shown inversely associated with viral loads, was further found positively correlated with CD4⁺ T cell number preservation. Overall, these data highlight one unrecognized role of adjuvant in HIV vaccine development, and show that vaccines can produce a surprising discordance between CD4⁺ T cell levels and SIV viral load.