Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

Constructing queer mother‐knowledge and negotiating medical authority in online lesbian pregnancy journals

Medical interactions around reproduction are increasingly extending beyond the physician's office and onto the Internet, where negotiation with medical authority occurs in complex and dynamic ways. Recently, scholars have noted the Internet's potential for creating spaces where women can dialogue with and reconstruct medical authority, yet this growing body of work is overwhelming heteronormative. This paper thus interrogates how lesbian women use the Internet to challenge, deploy, and rework medical authority around reproduction while navigating the transition to parenthood. I draw from 17 online journals authored by lesbian couples during the conception, pregnancy, and birth of their first child, each spanning between 18 months and 2 years, in order to understand how the transition process unfolds over time. I argue that lesbian couples engage with medical authority when seeking affirmation and normalisation yet discard and publicly reject the heteronormative assumptions that accompany reproductive medicine. Further, they chart a new process that I term ‘constructing queer mother‐knowledge’, in which they critique and balance knowledges from institutionalised medicine, their own bodies, and their queer communities. With this new concept, I complicate understandings of lesbian mothers‐to‐be and their interactions with medical authority as they build subversive families.     

肝细胞癌TACE术后病灶存活或复发18F-FDGPET/CT和增强CT诊断价值Meta分析

目的采用Meta分析方法评价¹⁸F-脱氧葡萄糖正电子发射计算机体层摄影(¹⁸F-FDG PET/CT)和增强CT(CECT)诊断经导管肝动脉化疗栓塞术(TACE)术后存活或复发病灶的临床价值。方法根据PRISMA报告规范开展Meta分析。检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方和维普数据库中¹⁸F-FDG PET/CT和CECT诊断TACE术后存活或复发病灶的临床研究,时间至2019-04。由2位研究人员独立筛选文献、提取资料,根据诊断准确性研究质量评价工具-2(QUADAS-2)评价纳入研究的偏倚风险后,采用Stata 12.0软件进行Meta分析,计算其汇总敏感度(Sen)和特异度(Spe),绘制受试者工作特征曲线(SROC)并计算曲线下面积(AUC)。结果共纳入10篇¹⁸F-FDG PET/CT及13篇CECT诊断TACE术后存活或复发病灶的原始研究,分别包括322例患者的467个病灶和748例患者的943个病灶。Meta分析显示,¹⁸F-FDG PET/CT诊断TACE术后存活或复发病灶的Sen=0.92(95%CI为0.87~0.94)、Spe=0.95(95%CI为0.82~0.99)、AUC=0.97(95%CI为0.93~0.99);CECT诊断TACE术后存活或复发病灶的Sen=0.72(95%CI为0.66~0.78)、Spe=0.99(95%CI为0.93~1.00)、AUC=0.87(95%CI为0.83~0.89)。此外,CECT诊断TACE术后存活或复发Sen(Z=2.34,P=0.02)和AUC(Z=2.21,P=0.03)值低于¹⁸F-FDG PET/CT,差异有统计学意义。结论相比于CECT,¹⁸F-FDG PET/CT对TACE术后存活或复发病灶具有较高诊断效能,可视为TACE术后存活或复发病灶有效的影像学诊断方法。     

Bone mineral density changes after parathyroidectomy are dependent on biochemical profile

Background

Bone mineral density (BMD) has been found to improve after parathyroidectomy (PTX) in patients with primary hyperparathyroidism. There are few data on the effect of PTX on BMD in normocalcemic and normohormonal primary hyperparathyroidism.

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.