Clinical Hemorheology and Microcirculation - Volume Pre-press, issue Pre-press

Authors: Krüger-Genge, A. | Steinbrecht, S. | Jung, C.G.H. | Westphal, Sophia | Klöpzig, Stefanie | Waldeck, P. | Küpper, J.-H. | Storsberg, J. | Jung, F.

Article Type: Research Article

Abstract: Within the last years a comprehensive number of scientific studies demonstrated beneficial effect of Arthropira platensis (AP ) as dietary supplement due to a high content of proteins, minerals and vitamins. Positive effects like promoting the immune system, reducing inflammation and an anti-oxidant capacity are reported. In this study, the effect of an aqueous AP extract on primary human venous endothelial cells (HUVEC) was investigated. In addition, the effect of AP on HUVEC treated with a bacterial toxin (lipopolysaccharide, LPA), inducing an activation of HUVEC and cellular detachment, was analyzed. Depending on the concentration of AP …extract a significantly accelerated formation of an endothelial cell monolayer was observed. Furthermore, the detachment of HUVEC after LPA addition was dramatically reduced by AP. In conclusion, the data are promising and indicatory for an application of Arthrospira platensis in the clinical field. Show more

Keywords: Arthrospira platensis – endothelial cells – xCELLigence system

DOI: 10.3233/CH-201096

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Chen, Ye | Wang, Shouhong | Huang, Jianrong | Fu, Yingyun | Wen, Juanmin | Zhou, Chengbin | Fu, Yang | Liu, Lei

Article Type: Research Article

Abstract: INTRODUCTION: Coronavirus disease-19 (COVID-19) is a new type of epidemic pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The population is generally susceptible to COVID-19, which mainly causes lung injury. Some cases may develop severe acute respiratory distress syndrome (ARDS). Currently, ARDS treatment is mainly mechanical ventilation, but mechanical ventilation often causes ventilator-induced lung injury (VILI) accompanied by hypercapnia in 14% of patients. Extracorporeal carbon dioxide removal (ECCO2R) can remove carbon dioxide from the blood of patients with ARDS, correct the respiratory acidosis, reduce the tidal volume and airway pressure, and reduce the incidence of VILI. …CASE REPORT: Two patients with critical COVID-19 combined with multiple organ failure undertook mechanical ventilation and suffered from hypercapnia. ECCO2R, combined with continuous renal replacement therapy (CRRT), was conducted concomitantly. In both cases (No. 1 and 2), the tidal volume and positive end-expiratory pressure (PEEP) were down-regulated before the treatment and at 1.5 hours, one day, three days, five days, eight days, and ten days after the treatment, together with a noticeable decrease in PCO2 and clear increase in PO2, while FiO2 decreased to approximately 40%. In case No 2, compared with the condition before treatment, the PCO2 decreased significantly with down-regulation in the tidal volume and PEEP and improvement in the pulmonary edema and ARDS after the treatment. CONCLUSION: ECCO2R combined with continuous blood purification therapy in patients with COVID-19 who are criti-cally ill and have ARDS and hypercapnia might gain both time and opportunity in the treatment, down-regulate the ventilator parameters, reduce the incidence of VILI and achieve favorable therapeutic outcomes. Show more

Keywords: Coronavirus disease-19, multiple organ failure, hypercapnia, continuous blood purification, extracorporeal carbon dioxide removal

DOI: 10.3233/CH-201080

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Yang, Wen-qi | Cui, Xiao-lan | Zhang, Ming | Yuan, Xiao-dong | Ying, Liang | Li, Feng-hua | Li, Hong-li

Article Type: Research Article

Abstract: OBJECTIVE: To assess iliac blood vessels using conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) before kidney transplantation (KT) and determine whether US findings related to post-transplant outcomes. METHODS: A total of 119 patients received US and CEUS before KT waiting-list acceptance. The preoperative iliac blood hemodynamics and vascular conditions were evaluated. The operative strategy and follow-up outcomes were recorded. Logistic regression and correlation analysis were used. The accuracy in determining the patency of iliac blood vessels was calculated before and after the injection of contrast materials. RESULTS: CEUS can help to significantly improve the visualization of …the internal iliac artery, but there was no significant correlation with post-transplant outcomes. In terms of accuracy, there were significant differences in determining the patency of internal iliac arteries between conventional US and CEUS (60.5% and 100%, p  <  0.001). The surgical strategy of one patient was regulated and two patients were excluded from KT according to US findings. CONCLUSIONS: Compared with conventional US, CEUS helps to improve the visualization of the internal iliac artery. Conventional US and CEUS have the potential to serve as effective methods to evaluate anatomy and hemodynamics of iliac vessels and have a potential value while defining clinical algorithms in surgery decision-making. Show more

Keywords: Contrast-enhanced ultrasonography, ultrasound, kidney transplantation, iliac artery

DOI: 10.3233/CH-201054

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Kexin, Song | Mingzi, Zhang | Hao, Liu | Yan, Hao | Zheng, Qi | Cheng, Feng | Youbin, Wang

Article Type: Research Article

Abstract: OBJECTIVE: Here we examined the influence of methane-rich saline treatment (MS) on the whole transcriptome of the skin flaps during the ischemia/reperfusion (I/R) injuryusing RNA-sequence (RNA-seq). METHODS: The rats were divided into three groups: the sham surgery group (SH),the I/R surgery group treated with physiological saline (I/R-P) or the I/R surgery group treated with the methane-rich saline (I/R-M) respectively. On the 72 hours after operation, the perfusion and the distribution of micro-circulatoryblood flow in skin flaps were observed by laser doppler flowmeters. The whole transcriptome alteration of the skin flaps was examined using RNA-seq. Moreover, the responses of …the skin flaps to MRS treatment were examined using bio-informatic and q-PCR approaches after I/R injury. RESULTS: The methane-rich saline (MS) treatment could expand survival area and improve the blood perfusion of the skin flaps after l/R injury. Compared to the I/R-P group, 474 genes significantly altered in the I/R-M group. These genes were mainly associated the development, the cell adhesion and migration. In addition, the PI3K-Akt signal pathway was meaningfully related to regulation of MS treatment. Q-PCR results confirmed that MS treatment positively regulated PI3K-Akt signal pathway relative genes and inhibited the cell adhesion relative genes. CONCLUSION: These results proved that methane-rich saline may alleviate I/R injury and improve flap survival rate by regulating cell adhesion and PI3K-Akt signal pathway. Show more

Keywords: Methane-rich saline, Ischemia/reperfusion injury, skin flaps, cell adhesion, PI3K-Akt signal pathway

DOI: 10.3233/CH-201046

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Troeltzsch, Daniel | Shnayien, Seyd | Gaudin, Robert | Bressem, Keno | Kreutzer, Kilian | Heiland, Max | Hamm, Bernd | Niehues, Stefan

Article Type: Research Article

Abstract: BACKGROUND: Post-therapeutic tissue is bradytrophic and thus has low perfusion values in PCT. In contrast, malignant tissue is expected to show higher perfusion values as cancer growth partially depends on angiogenesis. OBJECTIVES: This prospective study investigates perfusion computed tomography (PCT) for the post-therapeutic detection of cancer in the head and neck region. METHODS: 85 patients underwent PCT for 1) initial work-up of head and neck cancer (HNC; n =22) or 2) for follow-up (n =63). Regions of interest (ROIs) were placed in confirmed tumour, a corresponding location of benign tissue, and reference tissue. Perfusion was calculated …using a single input maximum slope algorithm. Statistical analysis was performed with the Mann-Whitney U-test. RESULTS: PCT allowed significant differentiation of malignant tissue from post-therapeutic tissue after treatment for HNC (p =0.018). Significance was even greater after normalization of perfusion values (p =0.007). PCT allowed highly significant differentiation of HNC from reference tissue (p <0.001). CONCLUSIONS: PCT provides significantly distinct perfusion values for malignant and benign as well as post-therapeutically altered tissue in the head and neck area, thus allowing differentiation of cancer from healthy tissue. Our results show that PCT in conjunction with a standard algorithm is a potentially powerful HNC diagnostic tool. Show more

DOI: 10.3233/CH-200919

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Werner, Jens Martin | Zidek, Martin | Kammerer, Sylvia | da Silva, Natascha Platz Batista | Jung, Friedrich | Schlitt, Hans Jürgen | Hornung, Matthias | Jung, Ernst-Michael

Article Type: Research Article

Abstract: OBJECTIVE: To assess the impact and procedural input of intraoperative ultrasound (IOUS) with contrast-enhanced ultrasound (CEUS) and ultrasound elastography on surgical decision making during the procedure and consequently the out-come after hepato-pancreatico-biliary (HPB) surgery. MATERIALS AND METHODS: Data of 50 consecutive patients, who underwent HPB surgery from 04/2018 to 07/2018 were prospectively collected for this study. During surgery, IOUS with a high-resolution ultrasound device using CEUS after bolus injection of 2.4–5 ml Sulphur hexafluoride microbubbles using a 6–9 MHz probe and a share wave and strain elastography was performed by an experienced examiner. Process and time analysis were carried out …using mobile phone timer. RESULTS: The IOUS with CEUS and elastography correctly identified 42 malignant tumors and 4 benign lesions. In 3 cases, the examination provided false positive result (identifying 3 benign lesions as malignant) and in 1 case a malignant lesion was incorrectly assessed as benign (sensitivity 97,7%, specificity 57,1%, PPV 93,3% and NPV 80%). The specific question by the surgeon could be answered successfully in 98% of the cases. In 76% of the cases, there was a modification (42%) or a fundamental change (34%) of the planned surgical approach due to the information provided by the IOUS. Within the last group, the IOUS had a major impact on therapy outcome. In 7 patients an additional tumor resection was required, in 5 patients the tumor was assessed as inoperable, and in total in 5 patients an intraoperative RFA (4/5) or postoperative RITA (1/5) was required. Regarding procedural input, there was only a slight, but significant difference between the transport and set-up times before the intraoperative use (mean: 14 min 22 s) and the return transport (mean 13 min 6 s), (p  = 0,038). The average examination time was 14 minutes, which makes only one third of the overall time demand. CONCLUSION: Combination of IOUS with CEUS and elastography in oncological HPB surgery provides valuable information that affects surgical decision-making. The procedural input of about 45 minutes seems to be a good investment considering the improvement of the surgical procedure and a significant modification of the therapy approach in the majority of the cases. Show more

Keywords: Surgical decision-making, hepato-pancreatico-biliary surgery, CEUS, elastography

DOI: 10.3233/CH-201031

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: Zhang, Zheng | Zhao, Shuangshuang | Wang, Keke | Shang, Mengyuan | Chen, Zheming | Yang, Haizhen | Chen, Yanwei | Chen, Baoding

Article Type: Research Article

Abstract: Integrated analysis of accumulated data is an effective way to obtain reliable potential diagnostic molecular of cervical lymph node metastases (LNM) in papillary thyroid carcinoma (PTC). The benefits of prophylactic lymph node dissection (PLND) for these clinically node-negative (cN0) patients remained considerable controversies. Hence, elucidation of the mechanisms of LNM and exploration of potential biomarkers and prognostic indicators are essential for accurate diagnosis of LNM in PTC patients. Up to date, advanced microarray and bioinformatics analysis have advanced an understanding of the molecular mechanisms of disease occurrence and development, which are necessary to explore genetic changes and identify potential diagnostic …biomarkers. In present study, we performed a comprehensive analysis of the differential expression, biological functions, and interactions of LNM-related genes. Two publicly available microarray datasets GSE60542 and GSE129562 were available from Gene Expression Omnibus (GEO) database. Differentially expressed genes between clinically node-positive (cN1) and cN0 PTC samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Our results identified 48 differentially expressed genes (DEGs) genetically associated with LNM in PTC patients. Gene ontology (GO) analyses revealed the changes in the modules were mostly enriched in the regulation of MHC class II receptor activity, the immune receptor activity, and the peptide antigen binding. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs displayed that the intestinal immune network for IgA production, staphylococcus aureus infection, and cell adhesion molecules (CAMs). To screen core genes related to LNM of PTC from the protein-protein interaction network, top 10 hub genes were identified with highest scores. Our results help us understand the exact mechanisms underlying the metastasis of cervical LNM in PTC tissues and pave an avenue for the progress of precise medicine for individual patients. Show more

Keywords: Lymph node metastasis (LNM), papillary thyroid carcinoma (PTC), hub genes, protein-protein interaction network (PPI)

DOI: 10.3233/CH-201074

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Kim, Kwan Wook | Kim, Sang Woo | Lim, Soyeon | Yoo, Kyung-Jong | Hwang, Ki-Chul | Lee, Seahyoung

Article Type: Research Article

Abstract: Hexokinase 2 (HK2) is a metabolic sensor that couples glycolysis and oxidative phosphorylation of mitochondria by binding to the outer mitochondrial membrane (OMM), and it also has been implicated in induction of apoptotic process by regulating the integrity of OMM. When HK2 detaches from the mitochondria, it triggers permeability increase of the OMM and subsequently facilitates the cytosolic release of cytochrome c, a major apoptosis-inducing factor. According to previous studies, a harsh microenvironment created by ischemic heart disease such as low tissue oxygen and nutrients, and increased reactive oxygen species (ROS) can cause cardiomyocyte apoptosis. Under these conditions, the expression …of HK2 in heart significantly decrease and such down-regulation of HK2 was correlated to the increased apoptosis of cardiomyocytes. Therefore, prevention of HK2 down-regulation may salvage cardiomyocytes from apoptosis. MicroRNAs are short, non-coding RNAs that either inhibit transcription of target mRNAs or degrade the targeted mRNAs via complementary binding to the 3’UTR (untranslated region) of the targeted mRNAs. Since miRNAs are known to be involved in virtually every biological processes, it is reasonable to assume that the expression of HK2 is also regulated by miRNAs. Currently, to my best knowledge, there is no previous study examined the miRNA-mediated regulation of HK2 in cardiomyocytes. Thus, in the present study, miRNA-mediated modulation of HK2 during ROS (H2 O2 )-induced cardiomyocyte apoptosis was investigated. First, the expression of HK2 in cardiomyocytes exposed to H2 O2 was evaluated. H2 O2 (500μM) induced cardiomyocyte apoptosis and it also decreased the mitochondrial expression of HK2. Based on miRNA-target prediction databases and empirical data, miR-181a was identified as a HK2-targeting miRNA. To further examine the effect of negative regulation of the selected HK2-targeting miRNA on cardiomyocyte apoptosis, anti-miR-181a, which neutralizes endogenous miR-181a, was utilized. Delivery of anti-miR-181a significantly abrogated the H2 O2 -induced suppression of HK2 expression and subsequent disruption of mitochondrial membrane potential, improving the survival of cardiomyocytes exposed to H2 O2 . These findings suggest that miR-181a-mediated down-regulation of HK2 contributes to the apoptosis of cardiomyocytes exposed to ROS. Neutralizing miR-181a can be a viable and effective means to prevent cardiomyocyte from apoptosis in ischemic heart disease. Show more

Keywords: Hexokinase 2, miR-181a, reactive oxygen species, ischemic heart disease, cardiomyocytes, apoptosis

DOI: 10.3233/CH-200924

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Wilma, Schierling | Kathrin, Bachleitner | Piotr, Kasprzak | Thomas, Betz | Alexander, Stehr | Karin, Pfister

Article Type: Research Article

Abstract: BACKGROUND: Acute lower limb ischemia (ALI) is associated with a high risk of limb loss and death. OBJECTIVE: The present study evaluates the safety of intraoperative, local urokinase lysis in patients with ALI and crural artery occlusion. METHODS: A total of 107 patients (115 legs) were treated surgically for ALI with additional intraoperative urokinase lysis to improve the outflow tract. Minor and major bleeding as well as efficacy of treatment and amputation-free survival were investigated. RESULTS: Complete restoration of at least one run-off vessel was achieved in 64%. Collateralization was improved in 34%. Lysis …failed in 2%. Major amputation rate was 27%overall (12%within 30 days) and depended on Rutherford class of ALI (overall/30 day: IIa 11%/6%; IIb 20%/17%; III 37%/15%). Amputation-free survival turned out to be 82%after 30 days, 58%after one, and 41%after five years. Minor bleeding occurred in 21%(24/115) and major bleeding in 3.5%(4/115). One of these patients died of haemorrhage. No patient experienced intracranial bleeding. CONCLUSION: Intraoperative urokinase lysis improves limb perfusion and causes low major and intracranial bleeding. It can be safely applied to patients with severe ischaemia when surgical restoration of the outflow tract fails. Show more

Keywords: Acute limb ischemia, bleeding, lysis, safety, thrombectomy, urokinase

DOI: 10.3233/CH-201049

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Lei, Weijuan | Lin, Juliar | Liu, Fang | Chen, Nina

Article Type: Research Article

Abstract: PURPOSE: Acute myeloid leukemia (AML) is a type of hematologic malignancy. This study was attempt to explore the effect of long noncoding RNA GAS6 antisense RNA1 (GAS6-AS1) on pediatric AML and the regulation mechanisms. METHODS: GAS6-AS1, microRNA-370-3p (miR-370-3p), and Tetraspanin3 (TSPAN3) expression in bone marrow (BM) tissues and cells was determined by qRT-PCR. The correlation between GAS6-AS1 and clinicopathological features of pediatric patients with AML was assessed. In vitro , viability and migration and invasion of AML cells were evaluated via MTT and transwell assays, respectively. Interactions among GAS6-AS1, miR-370-3p, and TSPAN3 were revealed by dual-luciferase reporter assays. …Western blot was applied to confirm the protein expression of TSPAN3. RESULTS: GAS6-AS1 and TSPAN3 expression was elevated in BM tissues of pediatric patients with AML and AML cells, but miR-370-3p expression was reduced. GAS6-AS1 expression was positively related to French-American-British (FAB) classification in pediatric patients with AML. In vitro , GAS6-AS1 deficiency restrained the viability, migration, and invasion of AML cells. Additionally, GAS6-AS1 mediated miR-370-3p expression indeed and TSPAN3 was identified as a target of miR-370-3p. Furthermore, miR-370-3p overexpression repressed the protein expression of TSPAN3. The feedback experiments demonstrated that miR-370-3p inhibition or TSPAN3 overexpression mitigated the suppressive effect of sh-GAS6-AS1 on the tumorigenesis of AML cells. CONCLUSION: GAS6-AS1 silencing restrained AML cell viability, migration, and invasion by targeting miR-370-3p/TSPAN3 axis, affording a novel therapeutic target for pediatric AML. Show more

Keywords: GAS6-AS1, acute myeloid leukemia, viability, miR-370-3p, TSPAN3

DOI: 10.3233/CH-201039

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2021