Qualitätsentwicklung im Gesundheitswesen: Sind wir schon so weit,wie wir wollten?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz -     

Nanotherapy: New Approach for Impeding Hepatic Cancer Microenvironment via Targeting Multiple Molecular Pathways

Objective: Hepatocellular carcinoma (HCC) microenvironment has been recognized as a key contributor for cancer progression, metastasis, and drug resistance. The crosstalk between tumor cells, the vascular endothelial growth factor (VEGF), and the chemokine (C-C motif) ligand 2 (CCL2) signaling networks mediates immunoinhibitory impact and facilitates tumor angiogenesis. The current investigation aimed at exploring the potent anti-cancer activity of the newly designed nano-based anti-cancer therapy comprising anti-VEGF drug, avastin (AV), and CCR2 antagonist (CR) to counteract HCC and tracking its mode of action in vivo. Methods: The prepared AV, CR, and AVCR nanoprototypes were characterized by nanoscale characterization techniques in our previous work. Here, they are applied for unearthing their anti-cancer properties / mechanisms in hepatic cancer-induced rats via analyzing protein levels and genetic expression of the elements incorporated in the angiogenesis, apoptosis, and metastasis signalling pathways. Results: The present results revealed a significant down-regulation in the angiogenesis, survival and metastasis indices along with up-regulation in the pro-apoptotic mediators upon treatment of hepatic cancer-bearing rats with the novel synthesized nanomaterials when compared with the untreated counterparts. We showed across HCC model that anti-VEGF in combination with CCR2 antagonism therapy leads to sensitization and enhanced tumor response over anti-VEGF or CCR2 antagonism monotherapy, particularly in its nanoscale formulation. Conclusion: The present approach provides new mechanistic insights into the powerful anti-hepatic cancer advantage of the novel nanoprototypes which is correlated with modulating critical signal transduction pathways implicated in tumor microenviroment such as angiogenesis, apoptosis and metastasis. This research work presents a substantial foundation for future studies focused on prohibiting cancer progression and recovery by targeting tumor microenviroment.     

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。     

Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Bioimpedance as a measure of fluids in patients with septic shock. A prospective observational study

Background

Septic shock is often treated with aggressive fluid resuscitation leading to profound fluid overload. The assessment of fluid status relies on suboptimal measures making treatment difficult. Bioelectrical impedance analysis is an alternative but the validity is unclear. The aim of this study was to determine the validity of bioelectrical impedance analysis for fluid measures in patients with septic shock.

Methods

Single-center, prospective observational cohort study. We included adult ICU patients with septic shock. We evaluated the agreement between measures on the left and right side of the patient and measures 1 h apart by two bioelectrical impedance devices. Results are presented as Bland Altman plots with 95% Limits of Agreements (LoA) and as correlations between bioelectrical impedance analysis results and clinical markers of fluids.

Results

Forty-nine patients were included. The agreement between measures on the left and the right side of the patient and after 1 h was overall without bias, but with wide LoA's. Fluid overload 1 h apart showed the most narrow 95% LoA (−2.4–2.9 L). The same wide limits of agreements were observed when comparing devices. For example, total body water with 95% LoA of −14.8 –16.7 L. Correlations between bioelectrical impedance analysis and clinical measures were low but statistically significant.

Conclusions

In patients with septic shock bioelectrical impedance analysis had no systematic errors or bias, but wide limits of agreement, indicating that the devices have a large and uncorrectable random error. Fluid status by bioelectrical impedance analysis is not sufficiently accurate to guide treatment in this group of patients.     

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...