BACKGROUND: Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship.
METHODS: Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation.
RESULTS: The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation.
CONCLUSIONS: Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

Nail fold capillaroscopy is an important means of monitoring human health. Panoramic nail fold images improve the efficiency and accuracy of examinations. However, the acquisition of panoramic nail fold images is seldom studied and the problem manifests of few matching feature points when image stitching is used for such images. Therefore, this paper presents a method for panoramic nail fold image stitching based on vascular contour enhancement, which first solves the problem of few matching feature points by pre-processing the image with contrast-constrained adaptive histogram equalization (CLAHE), bilateral filtering (BF), and sharpening algorithms. The panoramic images of the nail fold blood vessels are then successfully stitched using the fast robust feature (SURF), fast library of approximate nearest neighbors (FLANN) and random sample agreement (RANSAC) algorithms. The experimental results show that the panoramic image stitched by this paper\'s algorithm has a field of view width of 7.43 mm, which improves the efficiency and accuracy of diagnosis.

The precise oxygen content thresholds of ischemic deep parenchymal (OCIDP) and that in cortical microcirculation (OCCM), which leads to ischemic penumbra converting into the infarcted core, remain uncertain. This study employed an invasive fiber-optic oxygen meter and a newly developed oxygen-responsive probe called RuA3-Cy5-rtPA (RC-rtPA) based on recombinant tissue-type plasminogen activator (rtPA) to examine the oxygen content thresholds. A mouse model of middle cerebral artery occlusion was generated and animals were randomly divided into a sham, 24-h reperfusion after 3-h ischemia (IR 3-h), and IR 6-h groups, all of which were sacrificed following reperfusion. Stroke severity was evaluated based on the infarction area, neurological symptoms, microcirculation perfusion, and microemboli in microcirculation. OCIDP was characterized based on its extent and distribution, whereas OCCM was measured using RC-rtPA. During ischemia, stroke severity escalation manifested as increasing infarction area, severe neurologic symptoms, and poorer microcirculation perfusion with more microthrombi depositions. OCIDP presented rapid decline following artery occlusion along with a gradual increase in the hypoxic area. Within 3 ​h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 ​h. Within 6 ​h, OCCM continued to decrease. A significant decrease in oxygen content in cortical venules and cortical parenchyma was observed. These findings assist in establishing the extent of the ischemic penumbra at the microcirculation level and offer a foundation for assessing the ischemic penumbra that could respond positively to reperfusion therapy beyond the typical time window.

The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of diffuse brain swelling or malignant brain herniation during decompressive craniectomy. The microcirculation and venous system are also involved in this process, but the precise mechanisms remain unclear. A physiological model of extremely high intracranial pressure was created in rats. This development triggered the TNF-α/NF-κB/iNOS axis in microglia, and released many inflammatory factors and reactive oxygen species/reactive nitrogen species, generating an excessive amount of peroxynitrite. Subsequently, the capillary wall cells especially pericytes exhibited severe degeneration and injury, the blood-brain barrier was disrupted, and a large number of blood cells were deposited within the microcirculation, resulting in a significant delay in the recovery of the microcirculation and venous blood flow compared to arterial flow, and this still persisted after decompressive craniectomy. Infliximab is a monoclonal antibody bound to TNF-α that effectively reduces the activity of TNF-α/NF-κB/iNOS axis. Treatment with Infliximab resulted in downregulation of inflammatory and oxidative-nitrative stress related factors, attenuation of capillary wall cells injury, and relative reduction of capillary hemostasis. These improved the delay in recovery of microcirculation and venous blood flow.

BACKGROUND: Capillary refill time (CRT) is defined as the time taken for color to return to an external capillary bed after pressure is applied to cause blanching. Recent studies demonstrated the benefits of CRT in guiding fluid therapy for sepsis. However, lack of consistency among physicians in how to perform and interpret CRT has led to a low interobserver agreement for this assessment tool, which prevents its availability in sepsis clinical settings.
OBJECTIVE: To give physicians a concise overview of CRT and explore recent evidence on its reliability and value in the management of sepsis.
METHODS: A narrative review.
RESULTS: This narrative review summarizes the factors affecting CRT values, for example, age, sex, temperature, light, observation techniques, work experience, training level and differences in CRT measurement methods. The methods of reducing the variability of CRT are synthesized. Based on studies with highly reproducible CRT measurements and an excellent inter-rater concordance, we recommend the standardized CRT assessment method. The threshold of normal CRT values is discussed. The application of CRT in different phases of sepsis management is summarized.
CONCLUSIONS: Recent data confirm the value of CRT in critically ill patients. CRT should be detected by trained physicians using standardized methods and reducing the effect of ambient-related factors. Its association with severe infection, microcirculation, tissue perfusion response, organ dysfunction and adverse outcomes makes this approach a very attractive tool in sepsis. Further studies should confirm its value in the management of sepsis.
CONCLUSIONS: As a simple assessment, CRT deserves more attention even though it has not been widely applied at the bedside. CRT could provide nursing staff with patient\'s microcirculatory status, which may help to develop individualized nursing plans and improve the patient\'s care quality and treatment outcomes.

The present study aimed to explore the clinical applicability of ultrasound super-resolution imaging (US SRI) for assessing renal microcirculation in patients with acute kidney injury (AKI). A total of 62 patients with sepsis were enrolled in the present study-38 with AKI and 24 control patients-from whom renal ultrasounds and clinical data were obtained. SonoVue contrast (1.5 mL) was administered through the elbow vein and contrast-enhanced ultrasound (CEUS) images were obtained on a Mindray Resona A20 ultrasound unit for 2 min. The renal perfusion time-intensity curve (TIC) was analyzed and, after 15 min, additional images were obtained to create a microscopic blood flow map. Microvascular density (MVD) was calculated and its correlation with serum creatinine (Scr) levels was analyzed. There were significant differences in heart rate, Scr, blood urea nitrogen, urine volume at 24 h, and glomerular filtration rate between the two groups (p < 0.01), whereas other characteristics, such as renal morphology, did not differ significantly between the AKI group and control group (p > 0.05). The time to peak and mean transit times of the renal cortex in the AKI group were prolonged compared to those in the control group (p < 0.01), while the peak intensity and area under the TIC were lower than those in the control group (p < 0.05). The MVD of the renal cortex in the AKI group was lower than that in the control group (18.46 ± 5.90% vs. 44.93 ± 11.65%; p < 0.01) and the MVD in the AKI group showed a negative correlation with Scr (R = -0.84; p < 0.01). Based on the aforementioned results, US SRI can effectively assess renal microcirculation in patients with AKI and is a noninvasive technique for the diagnosis of AKI and quantitative evaluation of renal microcirculation.

OBJECTIVE: Persistent microvascular obstruction (MVO) after successful percutaneous coronary intervention (PCI) in acute ST segment elevation myocardial infarction (STEMI) has been well-described. MVO predicts lack of recovery of left ventricular function and increased mortality. Sonothrombolysis utilizing diagnostic ultrasound induced cavitation of commercially available microbubble contrast has been effective at reducing infarct size and improving left ventricular ejection fraction (LVEF) when performed both pre- and post-PCI. However, the effectiveness of post-PCI sonothrombolysis alone after successful PCI has not been demonstrated.
METHODS: A prospective randomized controlled trial was performed in 50 consecutive consenting patients with anterior STEMI who underwent a continuous microbubble infusion immediately following successful PCI. Intermittent high mechanical index (MI) impulses were applied only in the sonthrombolysis group. Delayed enhancement magnetic resonance imaging (MRI) was performed at 48 h and again at 6-8 weeks to assess for differences in infarct size, LVEF, and MVO.
RESULTS: There were no differences between groups in age, gender, and cardiovascular risk factors. Significant (> 2 segments) MVO following successful PCI was observed in 66% of patients. Although sonothrombolysis reduced the extent of MVO acutely, there were no differences in infarct size, LVEF, or extent of MVO by MRI at 48 h. Twenty-eight patients returned for a follow up MRI at 6-8 weeks. LVEF improved only in the sonothrombolysis group (∆LVEF 7.81 ± 4.57% with sonothrombolysis vs. 1.77 ± 7.02% for low MI only, p = .011).
CONCLUSIONS: Post-PCI sonothrombolysis had minimal effect on reducing myocardial infarct size but improved left ventricular systolic function in patients with acute anterior wall STEMI.

OBJECTIVE: Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein-kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown.
METHODS: The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod-induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention.
RESULTS: Expression of Factor XII was markedly up-regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod-induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil-vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B2 receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation.
CONCLUSIONS: Activation of Factor XII promoted psoriasis via prekallikrein-dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis.

BACKGROUND: This study aims to explore whether Xuebijing (XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.
METHODS: A rat model of sepsis was established by cecal ligation and puncture (CLP). A total of 30 male SD rats were divided into four groups: sham group, CLP group, XBJ + axitinib group, and XBJ group. XBJ was intraperitoneally injected 2 h before CLP. Hemodynamic data (blood pressure and heart rate) were recorded. The intestinal microcirculation data of the rats were analyzed via microcirculation imaging. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in the rats. Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats. The expression of vascular endothelial growth factor A (VEGF-A), phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt), and phosphorylated Akt (p-Akt) in the small intestine was analyzed via Western blotting.
RESULTS: XBJ improved intestinal microcirculation dysfunction in septic rats, alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa, and reduced the systemic inflammatory response. Moreover, XBJ upregulated the expression of VEGF-A, p-PI3K/total PI3K, and p-Akt/total Akt in the rat small intestine.
CONCLUSIONS: XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

OBJECTIVE: To explore the changes in microcirculation and microvasculature of the bulbar conjunctiva during the short-term wearing of the scleral lenses (ScCL). And investigate the factors affecting the microcirculation and microvasculature of the bulbar conjunctiva.
METHODS: In this prospective cross-sectional study, functional slit lamp biomicroscopy (FSLB) was used to image the ocular surface microcirculation and microvascular images at two different sites (under the area of ScCL and outside of the area of ScCL) before (baseline) and during the wearing of ScCL at 0 h, 1 h, 2 h and 3 h. Anterior segment optical coherence tomography (AS-OCT) (RTVue, Optovue Inc, USA) was also used to image central post-lens tear film (PoLTF) and the morphology changes of the conjunctiva under the landing zone at the same time period. The semi-automatic quantification of microcirculation and microvasculature including vessel density (Dbox), vessel diameter (D), axial blood flow velocity (Va) and blood flow volume (Q). And the morphological changes of conjunctiva and PoLTF fogging grading were evaluated manually. The changes in the microcirculation and microvasculature of the ocular surface, PoLTF fogging grade and conjunctival morphology were compared before and during the ScCL wearing at different time periods, and the relationship between them was analyzed.
RESULTS: Nineteen eyes (11 right eyes, 8 left eyes) were analyzed in this study. Outside of the area of ScCL, the Dbox before wearing lenses was less than that at 0 h (P = 0.041). The Q at baseline was greater than that after 1 h ScCL wearing (P = 0.026). Under the area of the ScCL, the Q at 1 h was less than that at baseline and 3 h. During the ScCL wearing, statistically significant conjunctival morphology changes were found among different time stages (baseline (0 μm), 0 h (113.18 μm), 2 h (138.97 μm), 3 h (143.83 μm) (all P ＜0.05). Outside the area of the ScCL, the morphology changes of the conjunctiva were negatively correlated with the changes of Va (P＜0.001,r = -0.471) and Q (P = 0.003,r = -0.348),but positively correlated with the Dbox (P = 0.001,r = 0.386). Under the area of ScCL, the morphology changes of the conjunctiva were negatively correlated with the Q (P = 0.012, r = -0.291). The fogging grade was positively correlated with the Q under the area of the ScCL (P = 0.005, r = 0.331).
CONCLUSIONS: The microcirculation and microvasculature of the ocular surface and conjunctival morphology were changed after wearing ScCL in wearers, which indicated that the microvascular responses happened in the ScCL wearers and the severity of microvascular responses of the ocular surface related to the morphology changes of the conjunctiva. The quantification methods and findings in this study provide clues for the safety of ScCL wearing and may supervise the health of the wearer\'s ocular surface.