Clinical Hemorheology and Microcirculation - Volume 85, issue 4

Authors: Jung, Friedrich | Connes, Philippe | Lehmann, Christian

Article Type: Editorial

DOI: 10.3233/CH-239103

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 323-324, 2023

Authors: Wang, Yueru | Liu, Ping | Chen, Xiaoyan | Yang, Wuxiao

Article Type: Research Article

Abstract: BACKGROUND: Atherosclerosis (AS) was one of the main causes of death in the elderly, and lesions in human umbilical vein endothelial cells (HUVECs) could lead to AS. CircRNA-charged multivesicular body protein 5 (circ_CHMP5) was reported to participate in the progression of AS. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the levels of circ_CHMP5, miR-516b-5p, and transforming growth factor beta receptor 2 (TGFβR2) in AS patients or ox-LDL-induced HUVECs. 5-Ethynyl-2’-deoxyuridine and cell counting kit-8 assays were performed to detect cell proliferation. Proteins expression was assessed by western blot assay. Cell apoptosis was examined …by flow cytometry. Tube formation assay was utilized to measure the tube formation ability of HUVCEs. The targeting relationships between miR-516b-5p and circ_CHMP5 or TGFβR2 were confirmed by dual-luciferase reporter assay and RNA-pull down assay. RESULTS: Circ_CHMP5 was enhanced in the serum of AS patients and ox-LDL-exposure HUVECs. Ox-LDL blocked proliferation and tube formation of HUVECs and induced cell apoptosis, and circ_CHMP5 knockdown reversed these effects. In addition, circ_CHMP5 regulated the growth of ox-LDL-induced HUVECs through miR-516b-5p and TGFβR2. Moreover, the effects of circ_CHMP5 knockdown on ox-LDL-induced HUVECs were obviously recovered by downregulation of miR-516b-5p, and overexpression of TGFβR2 restored the effects of miR-516b-5p upregulation on ox-LDL-stimulated HUVECs. CONCLUSION: Silence of circ_CHMP5 overturned ox-LDL-treated inhibition of HUVECs proliferation and angiogenesis by miR-516b-5p and TGFβR2. These results provided new solutions for the treatment of AS. Show more

Keywords: Circ_CHMP5, miR-516b-5p, TGFβR2, HUVECs, AS

DOI: 10.3233/CH-231722

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 325-339, 2023

Authors: Li, Ning | Hu, Ziyue | Liu, Yang | Ding, Jianmin | Han, Pengcheng | Jing, Xiang | Kan, Yanmin

Article Type: Research Article

Abstract: BACKGROUND: VueBoxtrademark has been used for contrast analysis in DCE-US-based quantitative research. OBJECTIVE: Aim of this study was to use the enhancement-mode and VueBoxtrademark parameters to further evaluate the differential diagnostic value of DCE-US for renal tumors. METHODS: 24 patients with renal tumors, including 7 benign and 17 malignant, were retrospectively analyzed.The DCE-US enhancement-mode and VueBoxtrademark parameters correlated with the histological analyses of tumors were obtained and analyzed. RESULTS: The benign and malignant renal tumors showed significant differences in enhancement degree (P  = 0.017) and presence of a pseudocapsule (P  = 0.009) and in the VueBoxtrademark …parameters FT (P  = 0.045) and RT (P  = 0.039). Receiver operating characteristic analysis for differential diagnosis of benign and malignant renal tumors showed that AUC for a combination of enhancement degree and presence of a pseudocapsule was greater (AUC = 0.815) than the values for either parameter of enhancement mode alone. Similarly, the AUC for a combination of RT and FT was greater (AUC = 0.798) than the values for RT or FT alone. A comprehensive index obtaining by combining the enhancement-mode and VueBoxtrademark parameters showed the largest AUC (AUC = 0.916) with relatively high accuracy (87.50%), sensitivity (76.50%), and specificity (85.70%). CONCLUSIONS: DCE-US with enhancement mode and quantitative analysis can facilitate preoperative differential diagnosis of benign and malignant renal tumors. Show more

Keywords: Dynamic contrast-enhanced ultrasound, renal tumors, characteristics, enhancement mode, VueBoxtrademark parameters

DOI: 10.3233/CH-231750

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 341-354, 2023

Authors: Zhang, Yanbin | Yuan, Xiaodong | Xu, Jie | Gu, Huafen

Article Type: Research Article

Abstract: BACKGROUND: circRNAs (circRNAs) are involved in the process of cerebral ischemia-reperfusion injury (CI/RI). Our study aims to explore circRBM33 in the endothelial function of the blood-brain barrier (BBB). METHODS: The mouse middle cerebral artery occlusion model (MCAO) was established and restored to perfusion, and OGD/R-induced endothelial cells were used to simulate CI/RI. circRBM33, miR-6838-5p and PDCD4, as well as Occludin, ZO-1 and Claudin-5 TJs were evaluated by quantitative PCR and Western blot. The ring structure of circRBM33 was verified by RNAse R and actinomycin D experiments. MTT and LDH Cytotoxicity assay determined viability and toxicity, and flow cytometry …determined apoptosis rate. Inflammatory cytokines and the number of microglia in brain tissue were measured by ELISA and IHC. The interaction between genes was verified by RIP and dual luciferase reporter assay. RESULTS: circRBM33 was a circrRNA present in the cytoplasm and up-regulated in the brain tissue of MCAO mice and OGD/R-induced endothelial cells. Silenced circRBM33 promoted Occludin, ZO-1, and Claudin-5 expression and cell proliferation, and inhibited cytotoxicity, inflammatory response, and apoptosis. Functionally, circRBM33-absorbed miR-6838-5p was involved in regulating PDCD4, leading to endothelial cell dysfunction, and thus affecting the function of the BBB. CONCLUSIONS: circRBM33 by mediating miR-6838-5p/PDCD4 axis induces endothelial dysfunction, thereby affecting the BBB in mice with CI/RI. Show more

Keywords: CircRBM33, miR-6838-5p, PDCD4, blood-brain barrier

DOI: 10.3233/CH-231776

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 355-370, 2023

Authors: Wiewiora, Maciej | Jopek, Janusz | Świętochowska, Elżbieta | Sławomir, Gregorczyn | Piecuch Jr., Jerzy | Gąska, Mateusz | Piecuch, Jerzy

Article Type: Research Article

Abstract: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is highly malignant with a low 5-year survival rate. Blood biomarkers may be of value for the noninvasive diagnosis of pancreatic cancer. OBJECTIVE: This study assessed blood-based biomarkers and disturbances in red blood cell aggregation associated with pancreatic cancer. METHODS: We studied 61 patients who underwent pancreatic resection. Of these 61 patients, 46 patients had PDAC, and 15 patients had inflammatory tumours. Serum VEGF, hypoxia-inducible factor (HIF-1α), elastin-derived peptides (EDPs), total sialic acid (TSA) and resistin levels were measured. Red blood cell aggregation was assessed by a laser-assisted optical rotational cell …analyser. RESULTS: VEGF (p  < 0.000001), HIF-1α (p  = 0.000002), resistin (p  = 0.000349), EDP (p  = 0.000089) and TSA (p  = 0.000013) levels were significantly higher in the PDAC group than in the inflammatory tumour group. The aggregation index (AI), syllectogram amplitude (AMP) and threshold shear rate (γthr) were significantly higher in the PDAC group, whereas the aggregation half-time (t1/2 ) was lower than in the inflammatory tumour group. Multivariate analyses revealed that VEGF, TSA and EDP levels were variables that predicted PDAC. VEGF levels were the most powerful predictor of PDAC independent of CA 19-9 levels. The cut-off points for VEGF, TSA and EDP levels were 134.56 pg/ml, 109.11 mg/dl and 36.4 ng/ml, respectively, with sensitivities of 97.8%, 87% and 69.6%, respectively, and specificities of 86.7%, 86.7% and 93.3%, respectively. CONCLUSION: This study indicated that there are significant differences in blood-based biomarkers for differentiating between PDAC and inflammatory tumours of the pancreas. We also confirmed that PDAC is associated with the excessive aggregation of RBCs. Show more

Keywords: Pancreatic cancer, biomarker, diagnosis, red blood cell aggregation

DOI: 10.3233/CH-231814

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 371-383, 2023

Authors: Lyu, Shaojun | Chen, Zaihao | Cui, Meize | Wei, Qiuyang | Li, Yameng | Fang, Hui | Liu, Mingyu | Liu, Linli | Fu, Jiahao | Zhang, Jianwei

Article Type: Research Article

Abstract: OBJECTIVE: We explored the effectiveness of an online/offline mixed-mode Tai Chi cardiac rehabilitation program on the microcirculation of patients with coronary artery disease (CAD). DESIGN: Prospective, randomized controlled study. SETTING: It was conducted in a tertiary hospital. SUBJECTS: Twenty-six patients who met the diagnostic criteria for coronary artery disease were recruited. INTERVENTIONS: Patients were randomized divided into a 12-week Tai Chi cardiac rehabilitation program(TCCRP) or a conventional exercise rehabilitation program(CERP) in a 1:1 fashion, 4 weeks of in-hospital rehabilitation and 8 weeks of online rehabilitation at home (a total of 12 weeks …of intervention). MAIN OUTCOME MEASURES: Nailfold microcirculation (Morphological integrals, Blood flow integrals, Periphery capillary loop integrals, Overall integrals). MAIN OUTCOME MEASURES: Twenty patients completed the study. The Morphological integrals (baseline: 2.875±1.171 vs 12weeks: 1.863±0.414, t = 2.432, P  = 0.045 < 0.05) and Overall integrals (baseline: 5.563±2.001 vs 12weeks: 3.688±1.167, t = 3.358, P  = 0.012 < 0.05) decreased significantly in the TCCRP, The nailfold microcirculation integra decreased not significantly in the CERP (P  > 0.05). The nailfold microcirculation integra was not significantly different between the two groups after the intervention (P  > 0.05). CONCLUSIONS: The TCCRP improved the microcirculation of patients with CAD. Show more

Keywords: Online/offline mixed-mode, Tai Chi cardiac rehabilitation program, coronary artery disease, microcirculation

DOI: 10.3233/CH-231894

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 385-393, 2023

Authors: Li, Hua-Juan | Yang, Yu-Ping | Liang, Xin | Zhang, Zhi | Xu, Xiao-Hong

Article Type: Research Article

Abstract: OBJECTIVE: To explore the diagnostic performance of the currently used ultrasound-based thyroid nodule risk stratification systems (K-TIRADS, ACR -TIRADS, and C-TIRADS) in differentiating follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC). METHODS: Clinical data and preoperative ultrasonographic images of 269 follicular thyroid neoplasms were retrospectively analyzed. All of them were detected by Color Doppler ultrasound instruments equipped with high-frequency liner array probes (e.g. Toshiba Apoli500 with L5-14MHZ; Philips IU22 with L5-12MHZ; GE LOGIQ E9 with L9-12MHZ and MyLab Class C with L9-14MHZ). The diagnostic performance of three TIRADS classifications for differentiating FTA from FTC was evaluated by …drawing the receiver operating characteristic (ROC) curves and calculating the cut-off values. RESULTS: Of the 269 follicular neoplasms (mean size, 3.67±1.53 cm), 209 were FTAs (mean size, 3.56±1.38 cm) and 60 were FTCs (mean size, 4.07±1.93 cm). There were significant differences in ultrasound features such as margins, calcifications, and vascularity of thyroid nodules between the FTA and FTC groups (P  < 0.05). According to the ROC curve comparison analysis, the diagnostic cut-off values of K-TIRADS, ACR-TIRADS, and C-TIRADS for identifying FTA and FTC were K-TR4, ACR-TR4, and C-TR4B, respectively, and the areas under the curves were 0.676, 0.728, and 0.719, respectively. The difference between ACR-TIRADS and K-TIRADS classification was statistically significant (P  = 0.0241), whereas the differences between ACR-TIRADS and C-TIRADS classification and between K-TIRADS and C-TIRADS classification were not statistically significant (P  > 0.05). CONCLUSION: The three TIRADS classifications were not conducive to distinguishing FTA from FTC. It is necessary to develop a novel malignant risk stratification system specifically for the identification of follicular thyroid neoplasms. Show more

Keywords: TIRADS, follicular thyroid adenoma, follicular thyroid carcinoma

DOI: 10.3233/CH-231898

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 395-406, 2023

Authors: Li, Nana | Dong, Tiantian | Wang, Peihua | Li, Qi | Nie, Fang

Article Type: Research Article

Abstract: OBJECTIVE: Glypican-3 (GPC3) has emerged as a significant marker for the diagnosis and prognosis of hepatocellular carcinoma (HCC) and has garnered considerable attention as an immunotherapeutic target. In this study, we propose a combination of preoperative contrast-enhanced ultrasound (CEUS) imaging features and clinical factors to predict the positive expression of GPC3 in HCC patients. METHODS: We retrospectively included 30 cases of GPC3-negative HCC and 115 cases of GPC3-positive HCC patients who underwent conventional ultrasound and CEUS evaluation. We assessed and compared the clinical characteristics, conventional ultrasound features, and CEUS features between the two groups of HCC …patients. Based on the clinical and ultrasound features between the two groups, we developed a binary logistic regression model for predicting GPC3-positive HCC. RESULTS: A total of 145 HCC patients were included in this study. Binary logistic regression analysis showed that AFP > 20 ng/mL (OR = 4.047; 95% CI: 1.467-11.16; p  = 0.007), arterial phase hyperenhancement (APHE) (OR = 12.557; 95% CI: 3.608-43.706; p  < 0.001), and asynchronous perfusion (OR = 4.209; 95% CI: 1.206-14.691; p  = 0.024) were predictive factors for GPC3-positive HCC. Receiver operating characteristic (ROC) analysis was conducted to predict GPC3-positive expression. The model combining the three independent predictive factors showed good predictive performance (AUC 0.817, 95% CI: 0.731-0.902, sensitivity: 91.3%, specificity: 60.0%). This combined model demonstrated excellent discriminatory ability to predict GPC3-positive HCC. CONCLUSION: Preoperative integration of CEUS features and clinical factors can non-invasively and effectively identify GPC3-positive HCC patients, providing valuable assistance in making personalized treatment decisions. Show more

Keywords: Hepatocellular carcinoma, glypican-3, contrast-enhanced ultrasound

DOI: 10.3233/CH-231912

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 407-420, 2023

Authors: Zhang, Qi | Qiu, Yi-Jie | Yang, Dao-Hui | Lu, Xiu-Yun | Chen, Sheng | Dong, Yi | Wang, Wen-Ping

Article Type: Research Article

Abstract: PURPOSES: To evaluate the application of contrast enhanced ultrasound (CEUS) in preoperatively differential diagnosis between pancreatic solid pseudopapillary tumors (SPTs) and pancreatic neuroendocrine tumors (pNETs). PATIENTS AND METHODS: This retrospective study was approved by Institutional Review Board. Patients with surgical resection and histopathological diagnosis as SPTs and pNETs were included. All patients underwent B mode ultrasound (BMUS) and CEUS examinations within one week before surgical operation. On BMUS, the size, location, echogenicity, calcification, and margin of lesions were observed and recorded. On CEUS imaging, enhancement patterns, and enhancement degrees were recorded and analyzed. An independent t -test or …Mann-Whitney U test was used for comparison between continuous variables. Chi-square test was used to compare the CEUS patterns. RESULTS: From February 2017 to Dec 2022, patients diagnosed as SPTs (n  = 39) and pNETs (n  = 48) were retrospectively included. On BMUS, anechoic cystic changes (19/39, 48.72%) and hyperechoic calcification (14/39, 35.90%) are more commonly detected in SPTs (P  = 0.000). On CEUS imaging, the majority of SPTs (27/39, 69.23%) showed hypo-enhancement in the arterial phase, while most of the pNETs (36/48, 75.00%) showed hyper- or iso-enhancement in the arterial phase (P  = 0.000). In the venous phase, most of the SPTs (32/39, 82.05%) showed hypo-enhancement, while over half of pNETs (29/48, 60.42%) showed hyper- or iso-enhancement compared to pancreatic parenchyma (P  = 0.001). CONCLUSIONS: CEUS is a valuable and non-invasive imaging method to make preoperatively differential diagnoses between SPTs and pNETs. Show more

Keywords: Contrast enhanced ultrasound (CEUS), pancreatic neuroendocrine tumors (pNETs), solid pseudopapillary tumor (SPT), preoperative, diagnosis

DOI: 10.3233/CH-231932

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 421-431, 2023

Authors: Wang, Tong | Guo, Wenjuan | Zhang, Xuemei | Ma, Ji | Li, Fang | Zheng, Siqi | Zhu, Miao | Dong, Yi | Bai, Min

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the correlation between ultrasound performance and prognostic factors in malignant non-mass breast lesions (NMLs). MATERIALS AND METHODS: This study included 106 malignant NMLs in 104 patients. Different US features and contrast enhancement patterns were evaluated. Prognostic factors, including histological types and grades, axillary lymph node and peritumoral lymphovascular status, estrogen and progesterone receptor status and the expression of HER-2 and Ki-67 were determined. A chi-square test and logistic regression analysis were used to analyse possible associations. RESULTS: Lesion size (OR: 3.08, p  = 0.033) and posterior echo attenuation (OR: 8.38, p  < 0.001) were useful …in reflecting malignant NMLs containing an invasive carcinoma component. Posterior echo attenuation (OR: 7.51, p  = 0.003) and unclear enhancement margin (OR: 6.50, p  = 0.018) were often found in tumors with axillary lymph node metastases. Peritumoural lymphovascular invasion mostly exhibited posterior echo attenuation (OR: 3.84, p  = 0.049) and unclear enhancement margin (OR: 8.68, p  = 0.042) on ultrasound images. Perfusion defect was a comparatively accurate enhancement indicator for negative ER (OR: 2.57, p  = 0.041) and PR (OR: 3.04, p  = 0.008) expression. Calcifications (OR: 3.03, p  = 0.025) and enlarged enhancement area (OR: 5.36, p  = 0.033) imply an increased risk of positive HER-2 expression. Similarly, Calcifications (OR: 4.13, p  = 0.003) and enlarged enhancement area (OR: 11.05, p  < 0.001) were valid predictors of high Ki-67 proliferation index. CONCLUSION: Ultrasound performance is valuable for non-invasive prediction of prognostic factors in malignant NMLs. Show more

Keywords: Malignant non-mass breast lesions, contrast-enhanced ultrasound, prognosis factors

DOI: 10.3233/CH-231936

Citation: Clinical Hemorheology and Microcirculation, vol. 85, no. 4, pp. 433-445, 2023