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

Authors: Wei, Wenbo | Tang, Min | Wang, Qi | Li, Xiaoming

Article Type: Research Article

Abstract: BACKGROUND: Coronary artery disease (CAD) is a common coronary artery disease. The functional mechanism of circular RNA (circRNA) HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 (circ_HECW2, hsa_circ_0057583) in ox-LDL-treated human cardiac microvascular endothelial cells (hCMECs) is still unclear. METHODS: Expression levels of circ_HECW2, microRNA (miR)-942-5p, and toll-like receptor 4 (TLR4) were analyzed by quantitative real-time PCR (qRT-PCR) and western blot assays. Cell proliferation and apoptosis were analyzed by 5-ethynyl-2’-deoxyuridine (EdU) assay, cell counting kit-8 (CCK8) assay, and flow cytometry, respectively. Tube formation assay was performed to analyze the angiogenesis of cells. Luciferase reporter and …RNA pull-down assays were performed to analyze the target relationship among circ_HECW2, miR-942-5p and TLR4. RESULTS: Circ_HECW2 and TLR4 expression levels were up-regulated and miR-942-5p expression was decreased in the serum of CAD patients and oxidized low-density lipoprotein (ox-LDL)-induced hCMECs. Knockdown of circ_HECW2 enhanced cell proliferation and inhibited cell apoptosis in ox-LDL-treated hCMECs. MiR-942-5p was the target of circ_HECW2 and directly targeted TLR4. Moreover, the effect of circ_HECW2 knockdown could be weakened by anti-miR-942-5p, and TLR4 could restore the function of miR-942-5p on cell damage of ox-LDL-induced hCMECs. CONCLUSION: Circ_HECW2 could regulate ox-LDL-induced cardiovascular endothelial cell dysfunction through targeting miR-942-5p/TLR4 axis. Show more

Keywords: Circ_HECW2, miR-942-5p, TLR4, coronary artery disease

DOI: 10.3233/CH-221550

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2022

Authors: Li, Wei-Wei | Guo, Ze-Ming | Wang, Bing-Cai | Liu, Qing-Quan | Zhao, Wen-An | Wei, Xiao-Lan

Article Type: Research Article

Abstract: OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100μg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent …manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation. Show more

Keywords: PCSK9, atherosclerotic coronary, autophagy, endothelial cell, PI3K

DOI: 10.3233/CH-242172

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Ma, Lin | Song, Jun-Jie | Cui, Zhong-Ning | Niu, Zhi-Yong | Tian, Shao-Bin | Liu, Ming | Wang, Min | Zhang, Rong-Ping

Article Type: Research Article

Abstract: OBJECTIVE: This study was performed to explore the treatment of the injury caused by traumatic limb amputation. METHODS: From October 2002 to October 2021, 30 cases were enrolled in the present study. The reasons for injury were as follows: 8 cases with single hydraulic column crush injury, 12 cases with gear and wire rope stranding, 6 cases with belt avulsion injury, and 4 cases with carbon block smash injury. The present study application of a free or small saphenous vein bypass to reconstruct the injured artery and vein according to the concept of the angiosome model. The defective …vessels were bridged with the axial vessels of a flow-through flap, such as a medial calf flap or anterolateral femoral flap, to construct an additional blood supply and drainage vein for the severed limb. The clinical data of 30 cases with traumatic limb amputation of the lower leg and ankle were retrospectively analyzed. RESULTS: In all 30 cases of traumatic limb amputation, the replantation via the adoption of a flow-through flap was successful, and 85.6% of the patients remained in good postoperative condition. There were no symptoms of ischemia in the marginal segment after blood supply reconstruction of the transected limb by axial vascular bridging within the flap. CONCLUSION: Via the adoption of microsurgical techniques, the blood supply to the transected limb can be reconstructed by bridging the defective vessels with the adoption of the axial vessels of the flow-through flap is a feasible and advanced treatment option. Show more

Keywords: Angiosome concept, destructive amputation of limbs, replantation, flow-through flap

DOI: 10.3233/CH-242179

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Chen, Po-Yu | Huang, Hsing-Hao | Chan, Wing-Sum | Liu, Chih-Min | Wu, Tsung-Ta | Chen, Jyun-Han | Chao, Anne | Tien, Yu-Wen | Chiu, Ching-Tang | Yeh, Yu-Chang

Article Type: Research Article

Abstract: BACKGROUND: Recent studies have shown that dexmedetomidine may improve microcirculation and prevent organ failure. However, most evidence was obtained from experimental animals and patients receiving cardiac surgery with cardiopulmonary bypass. This study aimed to investigate the effect of dexmedetomidine on microcirculation and organ injuries in critically ill general surgical patients. METHODS: In this prospective randomized trial, patients admitted to the surgical intensive care unit after general surgery were enrolled and randomly allocated to the dexmedetomidine or propofol groups. Patients received continuous dexmedetomidine or propofol infusions to meet their requirement of sedation according to their grouping. At each time …point, sublingual microcirculation images were obtained using the incident dark field video microscope. RESULTS: Overall, 60 patients finished the trial and were analyzed. Microcirculation parameters did not differ significantly between two groups. Heart rate at 4 h after ICU admission and mean arterial pressures at 12 h and 24 h after ICU admission were lower in the dexmedetomidine group than in the propofol group. At 24 h, serum aspartate aminotransferase (41 (25–118) vs 86 (34–129) U/L, p  = 0.035) and alanine aminotransferase (50 (26–160) vs 68 (35–172) U/L, p  = 0.019) levels were significantly lower in the dexmedetomidine group than in the propofol group. CONCLUSION: Microcirculation parameters did not differ significantly between the dexmedetomidine and propofol groups. At 24 h after ICU admission, serum liver enzyme levels were lower in patients receiving dexmedetomidine as compared to propofol. Show more

Keywords: Microcirculation, dexmedetomidine, propofol, surgery, critical care

DOI: 10.3233/CH-232093

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2024

Authors: Wang, Fang | Guo, Zhangmei | Yang, Guiqi | Yang, Fan | Zhou, Qi | Lv, Hongbin

Article Type: Research Article

Abstract: PURPOSE: Diabetic retinopathy (DR) is a serious retinal vascular disease that affects many individuals in their prime working years. The present research aimed at whether and how LOC681216 (LNC-216) is involved in retinal vascular dysfunction under diabetic conditions. METHODS: Rat retinal microvascular endothelial cells (RRMECs) treated with high glucose (HG) were used for functional analysis. Gene expression analysis was conducted using the Clariom D Affymetrix platform. The wound healing, transwell, and vascular tube formation assays were used to identify the migration, invasion, and tube formation capability of RRMECs. The dual-luciferase reporter confirmed the binding interaction between miR-143-5p and …LNC-216 or matrix metallopeptidase 2 (MMP2). RESULTS: Lnc-216 was upregulated in RRMECs treated with HG. Lnc-216 knockdown markedly suppressed the tube formation, cell migration, and wound healing of cultured RRMECs under HG conditions. Mechanistically, Lnc-216 acted as a miR-143-5p sponge to affect the biological activity of miR-143-5p, which led to increased expression of matrix metallopeptidase 2 (MMP2). CONCLUSIONS: Lnc-216 attenuates diabetic retinal vascular dysfunction through the miR-143-5p/MMP2 axis, providing a potential therapeutic strategy for DR. Show more

Keywords: Lnc-216, miR-143-5p, microarray, diabetic retinopathy, MMP2

DOI: 10.3233/CH-242163

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Jin, Dong-Dong | Lin, Jin-Hua | Li, Shi-Hui | Zhuang, Bo-Wen | Xie, Xiao-Yan | Xie, Xiao-Hua | Wang, Yan

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to evaluate the clinical characteristics and features of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) in differentiating between renal urothelial carcinomas (RUC) and endophytic clear cell renal cell carcinomas (EccRCC). METHODS: A total of 72 RUCs and 120 EccRCCs confirmed by pathology were assessed retrospectively. Both CUS and CEUS were performed within 4 weeks before the surgery. Logistic regression analyses were used to select statistically significant variables of clinical, CUS, and CEUS features for the differentiation of RUC and EccRCC. Sensitivity (SEN), specificity (SPE), and the area under the receiver-operating characteristic curve (AUC) were …assessed for diagnostic performance. Inter- and intra-observer agreements of CUS and CEUS features were evaluated using the intra-class correlation coefficient(ICC). RESULTS: Multiple logistic regression analysis demonstrated that clinical (age >50 years old and hematuria), CUS (size <4.0 cm, hypo-echogenicity, irregular shape, hydronephrosis) and CEUS (absence of non-enhancement area, iso- /hypo-enhancement in cortical phase and absence of rim-like enhancement) features were independent factors for RUC diagnosis. When combining clinical characters with CUS and CEUS features into an integrated diagnostic criterion, the AUC reached 0.917 (95% CI 0.873–0.961), with a sensitivity of 95.8% and specificity of 87.5%. ICC ranged from 0.756 to 0.907 for inter-observer agreement and 0.791 to 0.934 for intra-observer agreement for CUS and CEUSfeatures. CONCLUSIONS: The combination of clinical features of age and hematuria with imaging features of CUS and CEUS can be useful for the differentiation between RUC and EccRCC. Show more

Keywords: Contrast-enhanced ultrasound, conventional ultrasound, urothelial carcinomas, endophytic clear cell renal cell carcinomas, differential diagnosis

DOI: 10.3233/CH-242119

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2024

Authors: Xue, Xiaolei | Wu, Liping | Zhang, Jinqing | Sun, Wei | Jiang, Shiqin | Chu, Xiaoling | Sun, Yingzi

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to summarize the clinical manifestations and ultrasound characteristics of primary thyroid lymphoma (PTL) and explore the key aspects in the process of diagnosing PTL. METHODS: We conducted a retrospective analysis of the clinical and ultrasound features of 11 patients with PTL who were admitted to Shandong Provincial Third Hospital, China, between May 2009 and August 2023. The pathology was confirmed in all cases through an ultrasound-guided core needle biopsy or surgical resection. RESULTS: The mean age of the 11 patients was 64.45±9.85 years. In six patients, the main clinical manifestation was a …palpable mass in the neck, five of whom had a significant increase in the size of the mass within 3 months to 2 years. Eleven patients had coexisting Hashimoto’s thyroiditis (HT). Three patients were diagnosed as having diffuse-type PTL, wherein the ultrasound showed enlargement of the affected thyroid gland with diffusely uneven hypoechoic parenchyma. In 7 patients with nodular type PTL and 1 case of mixed type PTL, the ultrasonographic features of the nodular lesions were of irregular morphology and yet had distinct borders, and only 1 case had gross calcification. There were 7 cases of hypoechoic lesions (7/11 cases, 63.6%), 9 cases where the lesions had linear echo chains (9/11 cases, 81.8%), and 10 cases (90.9%) where there was echogenic enhancement posterior to the lesion. CONCLUSION: In elderly patients with HT, the thyroid volume increases significantly in a short period of time and symptoms associated with compression in the neck region appear. The ultrasound characteristics were extremely hypoechoic lesions in the thyroid parenchyma, with more linear echo chains visible inside, accompanied by posterior echo enhancement. When encountering such presentations, physicians must consider the possibility of PTL. Performing a core needle biopsy in cases that raise suspicion can reduce the incidence of misdiagnosis. Show more

Keywords: Clinical features, core needle biopsy, diagnosis, primary thyroid lymphoma, ultrasound

DOI: 10.3233/CH-242258

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Gouia, H.-F. | Duraes, M. | Delpont, M. | Herlin, C. | Biron-Andreani, C. | Jeziorski, E. | Captier, G. | Theron, A.

Article Type: Research Article

Abstract: Idiopathic purpura fulminans (IPF) is a rare and severe form of purpura fulminans caused by acquired protein S deficiency. It can lead to severe thrombotic complications, such as large skin necrosis and amputation. The lesions almost exclusively affect the lower limbs, and their distribution is similar among patients with IPF, unlike classical purpura fulminans lesions. Our hypothesis is that vascular structures called perforasomes may be involved in IPF, possibly caused by protein S deficiency. We analyzed all case reports and case series published in the literature that provided sufficient data for an anatomical study of limb injuries. For precise …localization of areas of necrosis, we examined each case using descriptions and images to determine whether they overlapped with vascular territories that include perforasomes. We analyzed twelve cases from the literature and identified six vascular territories: the anterolateral, anteromedial, and posterior territories of the upper leg, as well as the anterolateral, anteromedial, and posterolateral territories of the lower leg. For each territory, we described the most probable vascular damage and the corresponding perforasome. IPF is a complex multifactorial disease in which a direct involvement of perforating arteries may be suspected and taken into account in the surgical of lesions. Show more

Keywords: Idiopathic purpura fulminans, protein S deficiency, perforasome, thrombosis, necrosis

DOI: 10.3233/CH-242162

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Kordi, Negin | Saydi, Ali | Azimi, Maliheh | Mazdarani, Farivar | Gadruni, Keivan | Jung, Friedrich | Karami, Sajad

Article Type: Research Article

Abstract: Copper is an essential element in the human body, involved in many physiological and metabolic functions, including coagulation, oxidative metabolism, and hormone production. The maintenance of copper homeostasis within cells is a complex procedure that is intrinsically controlled by a multitude of intricate mechanisms. Disorders of copper homeostasis encompass a wide range of pathological conditions, including degenerative neurological diseases, metabolic disorders, cardio-cerebrovascular diseases, and tumors. Cuproptosis, a recently identified non-apoptotic mode of cell death mode, is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis represents a novel form of cell death distinct from the previously described modes, …including apoptosis, necrosis, pyroptosis, and ferroptosis. Excess copper has been shown to induce cuproptosis by stimulating protein toxic stress responses via copper-dependent abnormal oligomerization of lipoylation proteins within the tricarboxylic acid cycle and the subsequent reduction of iron-sulfur cluster protein levels. Ferredoxin1 facilitates the lipoacylation of dihydrolipoyl transacetylase, which in turn degrades iron-sulfur cluster proteins by reducing Cu2+ to Cu+ , thereby inducing cell death. Furthermore, copper homeostasis is regulated by the copper transporter, and disturbances in this homeostasis result in cuproptosis. Current evidence suggests that cuproptosis plays an important role in the onset and development of several cardiovascular diseases. Copper-chelating agents, including ammonium tetrathiomolybdate (VI) and DL-penicillamine, have been shown to facilitate the alleviation of cardiovascular disease by inhibiting cuproptosis. It is hypothesized that oxidative phosphorylation inhibitors such as physical training may inhibit cuproptosis by inhibiting the protein stress response. In conclusion, the implementation of physical training may be a viable strategy to reducte the incidence of cuproptosis. Show more

Keywords: Copper, exercise, cell death, physical activity, cuproptosis

DOI: 10.3233/CH-242329

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Gogilashvili, Nino | Tsinamdzgvrishvili, Bezhan | Momtselidze, Nana | Jung, Friedrich | Plantl, Lukas | Urdulashvili, Tamar | Mantskava, Maia

Article Type: Research Article

Abstract: BACKGROUND: “Slow flow” is one very important concept in modern fundamental and clinical biomedicine. Slow coronary flow is indicative of delayed filling of the terminal coronary artery vessels, occurring in the absence of significant coronary stenosis. This group patient of patients exhibits a high incidence of disability and represents a significant financial and material burden for the state and the healthcare system in general. OBJECTIVE: The primary objective of our study was to examine patients with slow coronary flow. METHODS: We studied the standard parameters recommended by the international health care system (electrocardiography (by Medica QRS-12, …Germany), through the electrical activity of a patient’s heart by the electrical impulses (beating) of the heart; HC1(Germany); coagulogramma by Coatron M1 (Germany), troponin by AQT 90 (Germany); general blood test we used automatic human counting device HC1(Germany). Also, we investigate the original parameters (non-standard parameters, which we use in this pilot study) that we were first studied for this diagnosis and non-standard parameters. RESULTS: A general blood test showed that patients with slow flow had a higher blood leukocyte count than the control group, but the amount of hemoglobin was normal, the hematocrit was much higher than in the control group, and the platelet count was close to the lower limit of clinical standards. We obtained details of blood flow by coagulation situation, such as prothrombin time, prothrombin index, international normalized ratio, activated partial thromboplastin time, thrombin time, fibrinogen, and rheological properties such as index of erythrocyte aggregability, index of erythrocyte deformability, plasma viscosity, in silico blood rheological index. CONCLUSSION: Blood flow can be considered as a superposition of vortices with similar frequencies and wave vectors that change after bifurcations or other obstacles in the vascular network. These factors together determine the conditions for structuring the flow of moving blood. Disruption or alteration of these factors results in slow flow. It has been found that the speed of blood flow in the coronary arteries depends on changes in the number and function of red blood cells. Slow flow is directly influenced by the aggregation and deformation of red blood cells, their number, and plasma viscosity. Consequently, the rheological status plays a crucial role in determining blood flow and its velocity. Show more

Keywords: Slow flow, aggregation, deformation, coagulation/anticoagulation, in silico blood rheological index, plasma viscosity

DOI: 10.3233/CH-249104

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024