Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement

Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.     

Eulerian Algorithms for Computing the Forward Finite Time Lyapunov Exponent Without Finite Difference upon the Flow Map

In this paper, effective Eulerian algorithms are introduced for the computation of the forward finite time Lyapunov exponent (FTLE) of smooth flow fields. The advantages of the proposed algorithms mainly manifest in two aspects. First, previous Eulerian approaches for computing the FTLE field are improved so that the Jacobian of the flow map can be obtained by directly solving a corresponding system of partial differential equations, rather than by implementing certain finite difference upon the flow map, which can significantly improve the accuracy of the numerical solution especially near the FTLE ridges. Second, in the proposed algorithms, all computations are done on the fly, that is, all required partial differential equations are solved forward in time, which is practically more natural. The new algorithms still maintain the optimal computational complexity as well as the second order accuracy. Numerical examples demonstrate the effectiveness of the proposed algorithms.     

不同针灸疗法治疗寻常痤疮的网状Meta分析＊

目的 采用网状Meta分析方法，评价针刺、火针、艾灸等不同针灸疗法对寻常痤疮（acne vulgaris， AC）临床有效率及复发率的影响。方法 计算机检索PubMed、Embase、Cochrane、Web of Science、CINAHL、中国知网（China National Knowledge Infrastructure， CNKI）、万方数据库（WanFang Data）、中国生物医学文献数据库（China Biology Medicine disc， CBM）和维普中文期刊服务平台（VIP Database），搜集针灸疗法治疗寻常痤疮的随机对照试验（randomized controlled trail， RCT），检索时间均为建库至2021年3月，文献筛选、资料提取及偏倚风险评价均由两名研究者独立进行。数据分析使用Stata16.0软件。结果 纳入42项RCT，共3911例寻常痤疮患者。数据分析结果显示，临床总有效率：艾灸、放血、放血+穴位注射、放血+针刺、火针优于西药（P<0.05），放血、放血+穴位注射、放血+针刺、火针、穴位埋线优于针刺疗法（P<0.05），放血+针刺疗法优于自血疗法（P<0.05），累计排序概率曲线下面积（surface under the cumulative，SUCRA）显示放血+针刺治疗寻常痤疮总有效率最高；复发率：放血疗法+穴位注射优于电针（P<0.05），SUCRA结果显示针刺+自血疗法治疗寻常痤疮复发率最低。结论 放血联合针刺疗法在提高总有效率上具有最好的疗效，针刺联合自血疗法可有效降低复发率，受纳入研究所限，以上结论尚需更多大样本、高质量RCT进一步验证。     

Stereotactic body radiation therapy for primary liver tumors: An effective liver-directed therapy in the toolbox

The use of radiation for primary liver cancers has historically been limited because of the risk of radiation-induced liver disease. Treatment fields have become more conformal because of several technical advances, and this has allowed for dose escalation. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is now able to safely treat liver tumors to ablative doses while sparing functional liver parenchyma by using highly conformal therapy. Several retrospective and small prospective studies have examined the use of SBRT for liver cancers; however, there is a lack of well-powered randomized studies to definitively guide management in these settings. Recent advances in systemic therapy for primary liver cancers have improved outcomes; however, the optimal selection criteria for SBRT as a local therapy remain unclear among other liver-directed options such as radiofrequency ablation, transarterial chemoembolization, and radioembolization.     

Effects of Wenyang Zhenshuai Granules on the Expression of Key Mitochondrial Autophagy Proteins in the Doxorubicin-Induced Model of H9c2 Cardiomyocyte Injury

Bulletin of Experimental Biology and Medicine - This study aimed to explore the effects of Wenyang Zhenshuai granules (WZG) on the morphology of cardiomyocytes, cell viability, and the expression...     

Effect of pneumatic leg compression on post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy: a double-blind randomised controlled trial

Post-induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy. In this double-blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post-induction hypotension in these groups. Post-induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post-induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post-induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression-related complications. Pneumatic leg compression reduced post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post-induction hypotension among elderly patients undergoing general anaesthesia.     

Opposing patterns in self-reported and measured physical activity levels in middle-aged adults

Physical activity brings significant health benefits to middle-aged adults, although the research to date has been focused on late adulthood. This study aims to examine how ageing affects the self-reported and accelerometer-derived measures of physical activity levels in middle-aged adults. We employed the data recorded in the UK Biobank and analysed the physical activity levels of 2,998 participants (1381 men and 1617 women), based on self-completion questionnaire and accelerometry measurement of physical activity. We also assessed the musculoskeletal health of the participants using the dual-energy X-ray absorptiometry (DXA) measurements provided by the UK Biobank. Participants were categorised into three groups according to their age: group I younger middle-aged (40 to 49 years), group II older middle-aged (50 to 59 years), and group III oldest middle-aged (60 to 69 years). Self-reported physical activity level increased with age and was the highest in group III, followed by group II and I (P?<?0.05). On the contrary, physical activity measured by accelerometry decreased significantly with age from group I to III (P?<?0.05), and the same pertained to the measurements of musculoskeletal health (P?<?0.05). It was also shown that middle-aged adults mostly engaged in low and moderate intensity activities. The opposing trends of the self-reported and measured physical activity levels may suggest that middle-aged adults over-report their activity level as they age. They should be aware of the difference between their perceived and actual physical activity levels, and objective measures would be useful to prevent the decline in musculoskeletal health.

     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.