Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

基于代谢组学分析的18-三体妊娠羊水差异代谢物

摘要:目的通过 非靶向代谢组学方法分析18-三体( trisomy 18,T18) 妊娠母体羊水样本,探索其差异代谢物。方法采用病 例-对照研究,以8例18-三体妊娠母体羊水样本为病例组,40例正常胎儿母体羊水样本为对照组,采用气相色谱飞行时间质 谱技术( GC-T0F/MS)检测两组羊水样本。采用主成分分析(PCA)和正交偏最小二乘法判别分析(OPIS-DA)模型分析代谢谱 差异,通过单维统计分析寻找差异代谢物。结果PCA 和OPLS-DA模型分析均显示病例组与对照组之间无明显分离趋势。 通过单维分析在两组间共发现5种差异代谢物,分别为甘油醛、葡萄糖酸、硫酸吲哚酚.磷酸盐和泛酸(P<0.05)。结论羊水 代谢组学证实18-三体妊娠存在多种代谢物水平的差异,为疾病的发生机制的探索提供了更多研究思路。     

Temporal changes in extra-axial brain hematoma's signal intensity in magnetic resonance images of trauma patients: A preliminary,technical study

IntroductionDating the exact or estimated time of trauma is an important issue facing forensic medicine. Several clinical and radiological methods were used to achieve this purpose. In the recent study, we aimed to track the changes in the signal intensity of the extra-axial brain hematoma using magnetic resonance imaging (MRI) conventional sequences as well as diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC).Materials and methodsConsidering inclusion and exclusion criteria, all patients with blunt head trauma were involved. After proper management., stabilization, and resuscitation, the participants were assessed using conventional sequences of MRI and DWI twenty-four hours, forty-eight hours, and three weeks after the injury. Temporal changes of signal intensity were compared by Wilcoxon ranged test.ResultsSixteen patients sustaining blunt head trauma were included in this study. The study showed that during the time, diffusion restriction could be seen in an extraaxial hematoma. At the first 24 hours, the signal of hematoma was void in 87.5% of DWI and 100% of ADC. On the second day, they were hypo-signal in 75% of DWI and 100% 0f ADCs, and after three weeks, 100% of cases were hyper-signal in DWI and hypo-signal ADCs.ConclusionThis preliminary study has shown that the DWI can be used to detect and track the extra-axial hematoma. The signal intensity was void during the first twentyfour hours, although it became hypo-signal after 48 hours. Of note, the diffusion restriction is noted after three weeks.     

Retroperitoneal-first laparoscopic approach (Retlap)-assisted distal pancreatectomy with celiac axis resection (DP-CAR): A novel minimally invasive approach for achieving adequate dorsal surgical margin

BackgroundDistal pancreatectomy with celiac axis resection (DP-CAR) is a procedure to secure a surgical margin for a locally advanced pancreatic body cancer that invades the celiac axis. However, in patients with cancer close to the root of the celiac axis, obtaining adequate surgical margins can be difficult because the tumor obstructs the field of vision to the root of the celiac axis. Previously, we described the retroperitoneal-first laparoscopic approach (Retlap) to achieve both accurate evaluation of resectability for locally advanced pancreatic cancer requiring DP-CAR [1] and adequate surgical margin for laparoscopic distal pancreatectomy [2]. In this video, we introduce Retlap-assisted DP-CAR as a minimally invasive approach for performing an artery-first pancreatectomy [3, 4] and achieving sufficient dorsal surgical margin (Fig. 1).MethodsOur patient is a 67-year-old man with a 55 × 29-mm pancreatic body tumor after chemotherapy. Preoperative computed tomography revealed a tumor close to the root of the celiac axis. Because the area of tumor invasion on preoperative images was near the root of the celiac artery, Retlap-assisted DP-CAR was performed to determine whether the celiac axis can be secured and obtain an adequate dorsal surgical margin (Fig. 2).ResultsThe operative time and estimated blood loss was 715 min and 449 mL, respectively. In spite of the advanced tumor's location and size, R0 resection was achieved in a minimally invasive way.ConclusionRetlap-assisted DP-CAR is not only technically feasible and useful for achieving accurate evaluation of resectability but also facilitates obtaining an adequate surgical margin.     

温针灸阳陵泉穴治疗膝关节骨性关节炎临床疗效观察

目的:观察温针灸阳陵泉穴治疗膝关节骨性关节炎的临床疗效。方法:将2015年1月至2019年1月本院收治的膝关节骨性关节炎患者120例,根据随机数字表法分为对照组和观察组,每组60例。对照组给予等速肌力训练治疗,观察组在对照组的基础上加用温针灸阳陵泉穴治疗。观察两组患者膝关节屈曲度、伸直度,白细胞介素(interleukin,IL)-6及IL-18水平,VAS评分及膝关节症状和功能评分。结果:观察组治疗后屈曲度及伸直度均高于对照组,差异有统计学意义(P<0.05);观察组治疗后IL-6及IL-18水平均低于对照组,差异有统计学意义(P<0.05);观察组治疗后VAS评分低于对照组,差异有统计学意义(P<0.05);观察组治疗后症状和功能评分高于对照组,差异有统计学意义(P<0.05);观察组有效率95.0%,对照组有效率83.3%,观察组有效率高于对照组,差异有统计学意义(P<0.05)。结论:温针灸阳陵泉穴治疗膝关节骨性关节炎,可有效改善患者膝关节活动度,降低炎症因子,减轻疼痛,提高临床疗效。     

三七片DNA条形码分子鉴定及方法学考察

目的为研究DNA条形码技术在中成药鉴定中的应用,以三七片为研究对象,对方法的适用性、专属性与精密度进行考察。方法收集15批次市售三七片样品,考察三七片DNA提取条件,并对"中药材DNA条形码分子鉴定法指导原则"中PCR扩增、序列获得、结果判定等方法适用性进行确认;收集三七、人参、西洋参,制作三七片及其掺伪品,考察方法的专属性和重现性。结果三七片取样量100 mg,56℃水浴8 h所获得DNA的质量浓度平均值为60.7 ng/μL,PCR扩增、序列获得和结果判定均可获成功;三七、人参和西洋参的ITS2序列长度均为230bp,三七与人参、三七与西洋参的序列间均存在7个稳定的SNP位点,自制三七片和掺伪三七片均可成功获得ITS2序列,不同比例三七与人参、三七与西洋参的测序峰图在SNP位点处呈现相应峰高比的SNP套峰具备专属性;重复性、中间精密度和重现性考察符合《中国药典》2015年版(通则9101)相关要求。结论 ITS2序列作为DNA条形码能够稳定、准确鉴定三七片的原料药材,具备良好的专属性和精密度,三七片DNA条形码分子鉴定法将为保障三七片临床用药安全提供新的技术手段,并对《中国药典》其他收载单方制剂的鉴定提供参考。     

SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7

Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5’s interaction with SOX18 on MMP7‐mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR‐133a‐3p. Ectopic expression of SLC12A5 partly abolished miR‐133a‐3p‐mediated suppression of cell migration. SLC12A5‐SOX18 complex‐mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR‐133a‐3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma.     

Source imaging of seizure onset predicts surgical outcome in pediatric epilepsy

ObjectiveTo assess whether ictal electric source imaging (ESI) on low-density scalp EEG can approximate the seizure onset zone (SOZ) location and predict surgical outcome in children with refractory epilepsy undergoing surgery.MethodsWe examined 35 children with refractory epilepsy. We dichotomized surgical outcome into seizure- and non-seizure-free. We identified ictal onsets recorded with scalp and intracranial EEG and localized them using equivalent current dipoles and standardized low-resolution magnetic tomography (sLORETA). We estimated the localization accuracy of scalp EEG as distance of scalp dipoles from intracranial dipoles. We also calculated the distances of scalp dipoles from resection, as well as their resection percentage and compared between seizure-free and non-seizure-free patients. We built receiver operating characteristic curves to test whether resection percentage predicted outcome.ResultsResection distance was lower in seizure-free patients for both dipoles (p = 0.006) and sLORETA (p = 0.04). Resection percentage predicted outcome with a sensitivity of 57.1% (95% CI, 34–78.2%), a specificity of 85.7% (95% CI, 57.2–98.2%) and an accuracy of 68.6% (95% CI, 50.7–83.5%) (p = 0.01).ConclusionIctal ESI performed on low-density scalp EEG can delineate the SOZ and predict outcome.SignificanceSuch an application may increase the number of children who are referred for epilepsy surgery and improve their outcome.