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.     

On the Relationship between Dynamic Contrast-Enhanced Ultrasound Parameters and the Underlying Vascular Architecture Extracted from Acoustic Angiography

Dynamic contrast-enhanced ultrasound (DCE-US) has been proposed as a powerful tool for cancer diagnosis by estimation of perfusion and dispersion parameters reflecting angiogenic vascular changes. This work was aimed at identifying which vascular features are reflected by the estimated perfusion and dispersion parameters through comparison with acoustic angiography (AA). AA is a high-resolution technique that allows quantification of vascular morphology. Three-dimensional AA and 2-D DCE-US bolus acquisitions were used to monitor the growth of fibrosarcoma tumors in nine rats. AA-derived vascular properties were analyzed along with DCE-US perfusion and dispersion to investigate the differences between tumor and control and their evolution in time. AA-derived microvascular density and DCE-US perfusion exhibited good agreement, confirmed by their spatial distributions. No vascular feature was correlated with dispersion. Yet, dispersion provided better cancer classification than perfusion. We therefore hypothesize that dispersion characterizes vessels that are smaller than those visible with AA.     

以专培学员为主导的CBL教学对心血管专培学员自身综合能力提升的影响

心血管专科医师规范化培训目标要求高于住院医师培训，完成心血管专培的医生应能在医疗、教学、科研能力上明显提高，达到心血管专科主治医师水平。如何提高心血管专培学员教学能力是专培中的难点。将专培学员随机分为两组,分别采用案例教学法（case-based learning, CBL）和传统教学法进行带教,课程结束后通过测验和调查问卷两种方式对教学效果进行考察。旨在探讨由心血管专培学员主导CBL教学法在实施过程中是否对其自身综合能力有所提升。结果显示，CBL教学法组学生临床理论及病例分析考试分数均高于对照组；心血管专培学员通过主导CBL教学，在教学能力、组织能力和学科协调均有提升；相较传统教学法,CBL教学法的教学效果更佳,有利于心血管专培学员自身综合能力提升。     

Accuracy of MRI-guided Versus Systematic Prostate Biopsy in Patients Under Active Surveillance: A Systematic Review and Meta-analysis

This meta-analysis focuses on the accuracy of upgrading to clinically significant prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsy (MRI-TB) versus systematic biopsy (SB). We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Literatura Latino Americana em Ciências da Saúde databases through January 2020 for comparative, retrospective/prospective, paired-cohort, and randomized clinical trials with paired comparisons. The population consisted of patients with low-risk PCa in active surveillance with at least 1 index lesion on imaging. We evaluated the quality of evidence by using the Quality Assessment of Diagnostic Accuracy Studies-2 score. Group comparisons considered the differences between the area under the curve summary receiver operating characteristic curve in a 2-tailed method. We also compared the positive predictive value of the best single method (MRI-TB or SB) and the referral study test (combined biopsy, a combination of MRI-TB and SB). The meta-analysis included 6 studies enrolling 741 patients. The pooled sensitivity for the 2 groups was 0.79 (95% confidence interval, 0.74-0.83; I² = 75%) and 0.67 (95% confidence interval, 0.63-0.74; I² = 55.4%), respectively. The area under the curve for the MRI-TB and SB groups were 0.99 and 0.92 (P < .001), respectively. The positive predictive value for the MRI-TB and combined biopsy groups were similar. The accumulated evidence suggests better results for MRI-TB compared with SB. Therefore, use of MRI-TB alone may be preferable in patients in active surveillance harboring low-risk PCa.     

Patients' expectations,experience and acceptability of postoperative analgesia: a nested qualitative study within a randomised controlled trial comparing rectus sheath catheter and thoracic epidural analgesia

Adequate postoperative analgesia is a key element of enhanced recovery programmes. Thoracic epidural analgesia is associated with superior postoperative analgesia but can lead to complications. Rectus sheath catheter analgesia may provide an alternative. In a nested qualitative study (within a two-year randomised controlled trial) focussing on the acceptability, expectations and experiences of receiving the interventions, participants (n = 20) were interviewed 4 weeks post-intervention using a grounded theory approach. Constant comparative analysis, with patient and public involvement, enabled emerging findings to be pursued through subsequent data collection. We found no notable differences regarding postoperative acceptability or the experience of pain management. Pre-operatively, however, thoracic epidural analgesia was a source of anticipatory fear and anxiety. Both interventions resulted in some experienced adverse events (proportionately more with thoracic epidural analgesia). Participants had negative experiences of the insertion of thoracic epidural analgesia; others receiving the rectus sheath catheter lacked confidence in staff members' ability to manage the local anaesthetic infusion pump. The anticipation of the technique of thoracic epidural analgesia, and concerns about its impact on mobility, represented an additional, unpleasant experience for patients already managing an illness experience, anticipating a life-changing operation and dealing with concerns about the future. The anticipation of rectus sheath catheter analgesia was not associated with such anxieties. Patients' experiences start far earlier than the experience of the intervention itself through anticipatory anxieties and fears about receiving a technique and its potential implications. Complex pain packages can take on greater meaning than their actual efficacy in relieving postoperative pain. Future research into patient acceptability and experience should not focus solely on efficacy of pain relief but should include anticipatory fears, anxieties and experiences.     

Factors associated with provision of depot medroxyprogesterone acetate to adolescents by US health care providers

ObjectiveIdentify factors associated with healthcare providers' frequency of depot medroxyprogesterone acetate (DMPA) provision to adolescents.Study designWe analyzed data from surveys mailed to a nationally representative sample of public-sector providers and office-based physicians (n=1984). We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with frequent DMPA provision to adolescents in the past year.ResultsAlthough most providers (>95%) considered DMPA safe for adolescents, fewer reported frequent provision (89% of public-sector providers; 64% of office-based physicians). Among public-sector providers, factors associated with lower odds of frequent provision included working in settings without Title X funding (aOR 0.44, 95% CI 0.30–0.64), reporting primary care as their primary clinical focus versus reproductive or adolescent health (aOR 0.42, 95% CI 0.28–0.61), and providing fewer patients with family planning services. Among office-based physicians, factors associated with lower odds of frequent provision included specializing in obstetrics/gynecology (aOR 0.50, 95% CI 0.27–0.91) and family medicine (aOR 0.21, 95% CI 0.09–0.47) versus adolescent medicine, completing training ≥15 versus <5 years ago (aOR 0.27, 95% CI 0.09–0.83), and reporting that 0–24% of patients pay with Medicaid or other government healthcare assistance versus ≥50% (aOR 0.23, 95% CI 0.09–0.61). The reason most commonly reported by providers for infrequent DMPA provision was patient preference for another method.ConclusionsWhile most providers reported frequently providing DMPA to adolescents, training on evidence-based recommendations for contraception, focused on subgroups of providers with lower odds of frequent DMPA provision, may increase adolescents' access to contraception.ImplicationsAlthough >95% of providers considered depot medroxyprogesterone (DMPA) a safe contraceptive for adolescents, only 89% of public-sector providers and 64% of office-based physicians reported frequently providing DMPA to adolescents. Provider training on evidence-based recommendations for contraception counseling and provision may increase adolescents' access to DMPA and all methods of contraception.