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. 相似文献
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. 相似文献
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. 相似文献
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.
Methods
A retrospective analysis of 92 primary hyperparathyroidism patients who underwent PTX between 2004 and 2012 with pre- and post-PTX dual-energy x-ray absorptiometry was performed. Within-person changes in BMD pre- and post-PTX were analyzed using log linear mixed models, stratified by biochemical status.
Results
Bone mineral density increased post-PTX in the whole cohort at the lumbar spine (+2.5%), femoral neck (+2.1%), and total hip (+1.9%) and decreased at the one-third radius (–0.9%). On comparison of BMD changes by profile, BMD increased in those with the typical profile at the lumbar spine (3.2%), femoral neck (2.9%), and total hip (2.9%) but declined at the one-third radius (–1.5%). In contrast, BMD improved only at the femoral neck (4.3%) in the normohormonal group and did not change at any site in the normocalcemic group. The typical group had a greater increase in BMD over time at the femoral neck and total hip compared with normocalcemic patients.
Conclusion
Our results indicate that the skeletal benefit of PTX was attenuated in normocalcemic and normohormonal patients, suggesting that skeletal changes after PTX may depend on biochemical profile. 相似文献
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.
Methods
Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30?days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12?months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period.
Results
Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race.
Conclusions
No safety concerns arose, supporting the favorable benefit-risk profile of RZV. 相似文献