Microvascular Vessel Research Articles

BuZangTongLuo decoction improved hindlimb ischemia by activating angiogenesis and regulating gut microbiota in diabetic mice.

Seven traditional medicinal plants (including Astragalus membranaceus, Dioscorea hemsleyi, Salvia miltiorrhiza, Scrophularia ningpoensis, Ophiopogon japonicus, Panax ginseng and Fritillariae cirrhosae) and one insect leech (Whitmania pigra Whitman) were combined into BuZangTongLuo formula (BZTLF) under the guidance of traditional Chinese medicine. BZTLF is potentially effective against diabetic vascular complications. Previous studies failed to clarify the molecular mechanism through which BZTLF suppressed diabetic ischemia. In this study, we aimed to explore whether BZTLF treatment could prevent the occurrence of type 2 diabetic (T2D) hindlimb ischemia in mice. Further, we investigated the regulatory effect of BZTLF on angiogenesis-related VEGF signaling pathway and gut microbiota dysfunction in diabetic ischemia mice. C57BL/6J mice fed with high-fat diet (HFD) received STZ injection and femoral artery ligation to build T2D diabetic hindlimb ischemia model. Mice were gavaged with BZTLF (5 g [raw materials]/kg/d) or with metformin plus atorvastatin for three weeks. Laser doppler imaging system was utilized for the visualization of blood flow. Histochemistry analysis was performed for microvascular vessel staining. Western blot was applied to detect the protein changes of signaling molecules responsible for VEGF pathway. Finally, 16S rDNA gene sequencing was conducted for analysis of gut microbiota structure. BZTLF treatment remarkably restored blood flow and capillary density of diabetic hindlimb ischemia. And the protein changes of VEGF signaling molecules were reversed in BZTLF-treated diabetic ischemia mice, including the decreased VEGF and HIF-1α, and the increased NO, eNOS and p-ERK1/2. The gut microbiota analysis suggests that BZTLF treatment increased the abundances of several beneficial bacteria (Akkermansia, Bifidobacterium and Bacteroides), while decreased the populations of some harmful bacteria(Blautia, Weissella, Escherichia Shigella and Kurthia). By using Spearman's correlation analysis, these changed gut flora were positively/negatively correlated with VEGF signaling pathway or glycometabolic parameters. BZTLF displayed beneficial effects on diabetic hindlimb ischemia by reshaping the gut microbiota structure and stunning the VEGF/HIF-1α pathway.

Pedicle Corridors and Vessel Options for Free Flap Reconstruction following Endoscopic Endonasal Skull Base Surgery: A Systematic Review

Introduction Microvascular free flaps offer an alternative to local and regional flaps for coverage of complex or large skull base defects. Routes and approaches to these reconstructive options are complicated and require an understanding of complex head and neck anatomy. Methods A systematic review of the literature was performed using a set of search terms with the help of a qualified librarian. Articles were reviewed and selected for inclusion based on relevance. We were interested in reporting possible routes for free flap accessibility to the skull base as well as microvascular vessel options, as this choice may affect the geometry and accessibility to the defect. Results A total of 1,917 articles were obtained from a comprehensive search and 11 articles were ultimately found to be relevant to this review. Published options for vessel anastomosis and corridors to the skull base following endoscopic endonasal surgery are reviewed, including Caldwell-Luc/transbuccal space, prevertebral space, transpterygoid/parapharyngeal, and transmaxillary approaches. Conclusion The field of endoscopic surgery has continued to advance and provide options for tumors of the skull base. This has led to a need for creative routes to the skull base for free flap reconstruction.

Relationship of α2-Macroglobulin with Steroid-Induced Femoral Head Necrosis: A Chinese Population-Based Association Study in Southeast China.

ObjectiveThe present study aimed to identify the relationship of α‐2‐macroglobulin and microvascular vessel pathology with steroid‐induced femoral head necrosis in the Southeast Chinese population.MethodsThis study enrolled 40 patients diagnosed with steroid‐induced necrosis of the femoral head. Patients had various stages of femoral head necrosis. The differential expression of serum proteins and mRNA from patients with steroid‐induced necrosis of the femoral head (SINFH) and healthy volunteers was analyzed by western blot and quantitative polymerase chain reaction (QT‐PCR). The pathological change in osteocyte necrosis was indicated by hematoxylin and eosin stain and immunohistochemistry.ResultsHematoxylin and eosin stain showed histopathology changes in the necrotic area of patients with steroid‐induced INFH: bone trabeculae were fewer and thinner, became broken, fragmented and structurally disordered; intraosseous adipose cells became enlarged; the arrangement of the osteoblasts became irregular; and vacant bone lacunae increased. QT‐PCR showed significantly lower levels of α‐2‐macroglobulin in the serum of patients with SINFH than in controls (P < 0.05). Immunohistochemical staining and western blotting demonstrated that the expression of α‐2‐macroglobulin was significantly decreased in the necrotic area of SINFH patients (P < 0.05).ConclusionThe α‐2‐macroglobulin may be associated with the pathology of SINFH. The multiple pathological reactions occur in SINFH and α‐2‐macroglobulin may serve as a potential biomarker for the diagnosis of SINFH or a promising therapeutic target.

Discussion: Comparing Reconstructive Outcomes in Patients with Gustilo Type IIIB Fractures and Concomitant Arterial Injuries.

BACKGROUND The Gustilo classification serves as a proxy for injury severity, but recent data suggest rising complications with decreasing arterial runoff. This study aims to compare different microsurgical anastomosis options based on the number of patent vessels in the lower extremity. METHODS A single-center retrospective review of 806 lower extremity free flaps performed from 1976 to 2016 was performed. Patients with Gustilo type IIIB injuries were grouped based on the number of patent vessels in the leg (three, two, or one). Patients were compared based on the type of anastomosis performed, evaluating for perioperative complications and flap failures. RESULTS Perioperative complications occurred in 111 flaps (27 percent): 71 take-backs (17 percent), 45 partial losses (11 percent), and 37 complete losses (9 percent). Among patients with three-vessel runoff (61.8 percent), there was no difference in take-backs or flap loss between those with end-to-end versus end-to-side anastomoses. In 68 patients (18.7 percent) with two-vessel runoff, no difference between take-backs or flap loss was noted when comparing any anastomosis (i.e., end-to-end into an injured vessel, end-to-end into an uninjured vessel, or end-to-side into an uninjured vessel), although vein grafts were required more often in the end-to-side groups (p < 0.01). Finally, in 39 patients (10.7 percent) with single-vessel runoff, no difference was seen between end-to-end anastomosis into an injured vessel or end-to-side anastomosis into an uninjured vessel in terms of take-backs or flap loss. CONCLUSION Higher rates of flap failure correlated with decreasing numbers of patent vessels in the leg, but neither type of microvascular anastomosis nor vessel selection demonstrated any impact on reconstructive outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.

Robot-assisted microvascular anastomosis in head and neck free flap reconstruction: Preliminary experiences and results.

The da Vinci Surgical System has facilitated considerable advancements in surgery. The process and results of robot-assisted microvascular anastomosis in real clinical situations have rarely been reported. This study presents our experience of performing robot-assisted microvascular anastomosis in free flap reconstruction in patients with oropharyngeal cancer. This was a retrospective study of reconstructive operations using a free radial forearm flap for oropharyngeal defects after tumor extirpation in 15 consecutive adult patients (12 men and 3 women). In total, 17 robot-assisted microvascular vessel anastomoses (2 arteries and 15 veins) were performed; moreover, 13 arteries and 13 veins were anastomosed using the standard operating microscope and hand-sewing technique. The recipient and donor vessel diameters were 2.5 ± 0.7 and 2.1 ± 0.8 mm, respectively. The donor blood vessel diameter selected for anastomosis using da Vinci Surgical System was significantly smaller (2.1 ± 0.8 vs. 2.5 ± 0.6 mm) than that for a standard operating microscope and hand-sewing technique (p = .021), the operating time spent (38.4 ± 10.4 vs. 28.0 ± 7.7 min) was significantly longer (p < .001). The vascular patency rate was 100%, and all flaps survived without requiring additional operation for revision. Robotic surgical systems can facilitate vascular microanastomosis and provide a blood vessel patency rate comparable to that of a standard operating microscope and hand-sewing technique.

Plasma endothelin-1 and adrenomedullin are associated with coronary artery function and cardiovascular outcomes in humans

BackgroundEndothelin-1 (ET-1) is a vasoconstrictor associated with cardiovascular disease, whereas adrenomedullin (ADM) is a vasorelaxant with cardioprotective properties. We sought to determine the relationship between plasma ET-1 and ADM with coronary circulatory function and long-term major adverse cardiovascular events (MACE). MethodsThirty-two patients undergoing coronary angiography for chest pain were recruited. Baseline plasma ET-1 and ADM levels were measured. The index of microcirculatory resistance (IMR), coronary flow mediated dilatation (cFMD) and coronary flow reserve (CFR) were measured in a non-obstructed coronary artery. Patients were assessed for MACE over a median period of 8.8 years. ResultsPlasma ET-1 levels correlated with IMR (r = 0.57; p < 0.01) and ADM levels correlated with CFR (r = 0.50; p = 0.04) and cFMD (r = 0.62; p = 0.01). After adjustment for age, gender and cardiovascular risk factors, the association between ADM and cFMD (β = 0.79; p < 0.01) and between ET-1 and IMR (β = 5.7; p = 0.01) remained significant. IMR was higher, although not statistically significant, in patients with long-term MACE (17.9 ± 5.3 vs. 13.1 ± 6.0 units; p = 0.14). In patients free of MACE, cFMD (9.3 ± 7.6 vs. 2.8 ± 5.0%; p = 0.01) and plasma ADM levels (7.6 ± 5.3 vs. 4.0 ± 1.9 pmol/L; p = 0.07) were higher. ConclusionsPlasma ET-1 and ADM were associated with measures of coronary microvascular and coronary conduit vessel function, respectively. Increased cFMD and elevated plasma ADM were associated with a cardioprotective effect.

Talin-Dependent Integrin Activation Regulates VE-Cadherin Localization and Endothelial Cell Barrier Function.

Endothelial barrier function depends on the proper localization and function of the adherens junction protein VE (vascular endothelial)-cadherin. Previous studies have suggested a functional relationship between integrin-mediated adhesion complexes and VE-cadherin yet the underlying molecular links are unclear. Binding of the cytoskeletal adaptor protein talin to the β-integrin cytoplasmic domain is a key final step in regulating the affinity of integrins for extracellular ligands (activation) but the role of integrin activation in VE-cadherin mediated endothelial barrier function is unknown. To test the requirement of talin-dependent activation of β1 integrin in VE-cadherin organization and endothelial cell (EC) barrier function. EC-specific deletion of talin in adult mice resulted in impaired stability of intestinal microvascular blood vessels, hemorrhage, and death. Talin-deficient endothelium showed altered VE-cadherin organization at EC junctions in vivo. shRNA (short hairpin RNA)-mediated knockdown of talin1 expression in cultured ECs led to increased radial actin stress fibers, increased adherens junction width and increased endothelial monolayer permeability measured by electrical cell-substrate impedance sensing. Restoring β1-integrin activation in talin-deficient cells with a β1-integrin activating antibody normalized both VE-cadherin organization and EC barrier function. In addition, VE-cadherin organization was normalized by reexpression of talin or integrin activating talin head domain but not a talin head domain mutant that is selectively deficient in activating integrins. Talin-dependent activation of EC β1-integrin stabilizes VE-cadherin at endothelial junctions and promotes endothelial barrier function.

Plasma Endothelin-1 and Adrenomedullin are Associated with Coronary Artery Function and Cardiovascular Outcomes in Humans

Abstract Background Endothelin-1 (ET-1) is a vasoconstrictor associated with cardiovascular disease, whereas adrenomedullin (ADM) is a vasorelaxant with cardioprotective properties. We sought to determine the relationship between plasma ET-1 and ADM with coronary circulatory function and long-term major adverse cardiovascular events (MACE). Methods Thirty-two patients undergoing coronary angiography for chest pain were recruited. Baseline plasma ET-1 and ADM levels were measured. The index of microcirculatory resistance (IMR), coronary flow mediated dilatation (cFMD) and coronary flow reserve (CFR) were measured in a non-obstructed coronary artery. Patients were assessed for MACE over a median period of 8.8 years. Results Plasma ET-1 levels correlated with IMR (r = 0.57; p Conclusions Plasma ET-1 and ADM were associated with measures of coronary microvascular and coronary conduit vessel function, respectively. Increased cFMD and elevated plasma ADM were associated with a cardioprotective effect.

Numerical simulation on effect of red blood cell motion on flow behavior of liposome-encapsulated hemoglobin

We simulated flows in microvascular vessels containing deformable red blood cells (RBCs) and liposome-encapsulated hemoglobin (LEH) particles. Blood flow was computed by the lattice Boltzmann method (LBM), and fluid–membrane interaction between the flow field and RBCs was incorporated using the immersed boundary method (IBM). The simulation results indicated that the LEH dispersion in a direction perpendicular to the main flow was largely affected by the presence of RBCs. In particular, LEH dispersion was high in the presence of rigid RBCs with low deformability. These results could provide essential information for designing LEH-mediated efficient oxygen supply to tissues.

Quantification of kinetic rate constants for transcytosis of polymeric nanoparticle through blood-brain barrier

BackgroundPolymeric nanoparticles (PNP) have received significant amount of interests for targeted drug delivery across the blood-brain barrier (BBB). Experimental studies have revealed that PNP can transport drug molecules from microvascular blood vessels to brain parenchyma in an efficient and non-invasive way. Despite that, very little attention has been paid to theoretically quantify the transport of such nanoparticles across BBB. MethodsIn this study, for the first time, we developed a mathematical model for PNP transport through BBB endothelial cells. The mathematical model is developed based on mass-action laws, where kinetic rate parameters are determined by an artificial neural network (ANN) model using experimental data from in-vitro BBB experiments. ResultsThe presented ANN model provides a much simpler way to solve the parameter estimation problem by avoiding integration scheme for ordinary differential equations associated with the mass-action laws. Furthermore, this method can efficiently deal with both small and large data set and can approximate highly nonlinear functions. Our results show that the mass-action model, constructed with ANN based rate parameters, can successfully predict the characteristics of the polymeric nanoparticle transport across the BBB. ConclusionsOur model results indicate that exocytosis of nanoparticles is seven fold slower to endocytosis suggesting that future studies should focus on enhancing the exocytosis process. General significanceThis mathematical study will assist in designing new drug carriers to overcome the drug delivery problems in brain. Furthermore, we anticipate that this model will form the basis of future comprehensive models for drug transport across BBB.

Morphometric Reconstruction of Coronary Vasculature Incorporating Uniformity of Flow Dispersion.

Experimental limitations in measurements of coronary flow in the beating heart have led to the development of in silico models of reconstructed coronary trees. Previous coronary reconstructions relied primarily on anatomical data, including statistical morphometry (e.g., diameters, length, connectivity, longitudinal position). Such reconstructions are non-unique, however, often leading to unrealistic predicted flow features. Thus, it is necessary to impose physiological flow constraints to ensure realistic tree reconstruction. Since a vessel flow depends on its diameter to fourth power, diameters are the logical candidates to guide vascular reconstructions to achieve realistic flows. Here, a diameter assignment method was developed where each vessel diameter was determined depending on its downstream tree size, aimed to reduce flow dispersion to within measured range. Since the coronary micro-vessels are responsible for a major portion of the flow resistance, the auto regulated coronary flow was analyzed in a morphometry-based reconstructed 400 vessel arterial microvascular sub-tree spanning vessel orders 1–6. Diameters in this subtree were re-assigned based on the flow criteria. The results revealed that diameter re-assignment, while adhering to measured morphometry, significantly reduced the flow dispersion to realistic levels while adhering to measured morphometry. The resulting network flow has longitudinal pressure distribution, flow fractal nature, and near-neighboring flow autocorrelation, which agree with measured coronary flow characteristics. Collectively, these results suggest that a realistic coronary tree reconstruction should impose not only morphometric data but also flow considerations. The work is of broad significance in providing a novel computational framework in the field of coronary microcirculation. It is essential for the study of coronary circulation by model simulation, based on a realistic network structure.

Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma.

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to “interval cancers”. If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ‘‘mucus cap’’, and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions’ endoscopic characteristics, which include their (semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates.

Comparative analysis of tumor-associated vascular changes following TACE alone or in combination with sorafenib treatment in HCC: A retrospective study.

The objective of the present study was to investigate the tumor-associated vascular changes in hepatocellular carcinoma (HCC) following treatment with transarterial chemoembolization (TACE) combined with sorafenib. The data of 20 patients were retrospectively analyzed. Patients underwent treatment depending on their chosen regimens (orally administered sorafenib was recommended, however the cost prevented some study articipants from selecting this course). Based on this, the patients were divided into TACE combined with sorafenib (TS) (n=10) and TACE-only treatment groups (n=10). Digital subtraction angiography images of all patients were analyzed by 2 radiologists who were blind to the type of treatment administered. The diameters of the hepatic and proper hepatic arteries, and hepatic artery branches (tumor-associated arteries), the splenic, left gastric and gastroduodenal arteries or portal veins (non-tumor-associated arteries) and the number of microvascular vessels were compared prior to and following sorafenib treatment in the TS group, between the first and second sessions of TACE in the TACE-only group and between the TS and TACE-only groups. In the TS group, the diameters of the hepatic and proper hepatic arteries, their branches and the number of microvascular vessels were significantly decreased following sorafenib treatment (P<0.05), while the diameters of the splenic, gastroduodenal and left gastric arteries were not significantly altered (P>0.05). In the TACE-only group, the diameters of the hepatic, proper hepatic, splenic, left gastric and gastroduodenal arteries were not significantly different between the first and second TACE sessions (P>0.05), while the diameters of the hepatic artery branches and the number of microvascular vessels were significantly altered (P<0.05). TACE combined with sorafenib significantly decreased the diameters of the tumor-associated arteries and the number of tumor microvascular vessels when compared with TACE treatment alone (P<0.05). No significant difference in the diameters of the portal vein and its branches between the two groups was observed (P>0.05). Treatment with TACE combined with sorafenib may significantly affect the tumor-associated vasculature compared with treatment with TACE alone in HCC.

1462 Expression and function of laminin extracellular matrix in wound repair

Extracellular matrix plays critical roles in wound repair and tissue regeneration. Laminins are major non-collagenous extracellular components in the basement membrane (BM) of skin dermal-epidermal junction and microvascular blood vessels. In this study we used a porcine burn wound model to explore the expression and functions of laminins and some important dermal matrix proteins and regulators in wound repair. Swine were used for our animal model since their skin is morphologically similar to human skin. Fresh skin burn wound samples from 6 young female pigs were collected at days 0, 1, 4, 7, 10, 14 and 21 post wounding. mRNA expressions were analyzed using reverse transcription and polymerase chain reactions with gene specific primers. The results showed that: 1) marked induction of gene expression for epidermal BM reconstitution: the expressions of both major epidermal BM laminins, -332 and -511, were significantly increased shortly after wounding, with laminin511 the highest and lasted longer, with peak at day 7 and day 10 for laminin332 and laminin511, respectively; a marked increase of type IV collagen mRNA level peaked at day 1 and remained high over the course; 2) strong induction of gene expression for dermal restoration: the expression of blood vessel BM laminin411 increased shortly after wounding and reached peak at day 4; a significantly delayed induction of types I and III collagen expression was observed (from 10 days post wounding) compared with excisional wounds; the induction of elastin expression occurred at later stage of healing, 21 days post wounding; 3) increased expression of matrix metalloproteinases (MMP) for tissue remodeling: a striking increased expression of MMP1 and MMP9 was observed shortly after wounding and lasted through entire experiment; the marked induction of TIMP1, a tissue inhibitor of MMP, occurred shortly after wounding and lasted entire course while TIMP3 expression was significantly decreased; and 4) a strong correlation between increased dermal matrix expression and induction of regulatory growth factors of VEGF, TGFb, bFGF and CTGF.

Microvascular abnormalities in dry eye patients

This study was conducted to evaluate conjunctival blood flow velocities and microvascular network density in patients with dry eye disease (DED). Twenty-five patients with DED and 25 healthy controls were recruited. The microvasculature and microcirculation of the temporal bulbar conjunctiva of the right eyes were assessed using a functional slit-lamp biomicroscope. Vascular variables included blood flow velocity (BFV), blood flow rate (BFR), microvascular network density and vessel diameter. A fractal analysis was performed using the box counting method to measure the fractal dimension (Dbox) representing the vessel density. The bulbar BFV was 0.59 ± 0.09 mm/s in the DED group and 0.47 ± 0.12 in the control group (P < 0.001). BFR was 169.5 ± 1.8 in the DED group compared to the control group (107.2 ± 49.6) (P < 0.001). Dbox was higher in DED patients (1.65 ± 0.04) than controls (1.60 ± 0.07, P < 0.05). Moreover, the vessel diameter was larger in the DED group (21.8 ± 1.8 μm) compared with controls (17.9 ± 2.2 μm, P < 0.001). Dbox was positively related with ocular surface disease index (OSDI) in patients with DED (r = 0.54, P = 0.008). Microvascular alterations were found in the bulbar conjunctiva of DED patients, including increased blood flow velocity, higher vessel density and larger vessel diameter.

Ca2+ Signalling in Pericytes.

Microcirculation is the generic name for the finest level of the circulatory system and consists of arteriolar and venular networks located upstream and downstream of capillaries, respectively. Anatomically arterioles are surrounded by a monolayer of spindle-shaped smooth muscle cells (myocytes), while terminal branches of precapillary arterioles, capillaries and all sections of postcapillary venules are surrounded by a monolayer of morphologically different perivascular cells (pericytes). Pericytes are essential components of the microvascular vessel wall. Wrapped around endothelial cells, they occupy a strategic position at the interface between the circulating blood and the interstitial space. There are physiological differences in the responses of pericytes and myocytes to vasoactive molecules, which suggest that these two types of vascular cells could have different functional roles in the regulation of local blood flow within the same microvascular bed. Also, pericytes may play different roles in different microcirculatory beds to meet the characteristics of individual organs. Contractile activity of pericytes and myocytes is controlled by changes of cytosolic free Ca2+concentration. In this chapter, we attempt to summarize the results in the field of Ca2+ signalling in pericytes especially in light of their contractile roles in different tissues and organs. We investigate the literature and describe our results regarding sources of Ca2+, relative importance and mechanisms of Ca2+ release and Ca2+ entry in control of the spatio-temporal characteristics of the Ca2+ signals in pericytes, where possible Ca2+ signalling and contractile responses in pericytes are compared to those of myocytes.

Does the blood glucose control have an effect on the success of the painful diabetic neuropathy treatment?

Background/Aim. Diabetic neuropathy (DN) is the basic complication of diabetes, associated with impared glucoregulation, metabolic distrurbances, microvascular vessel damage and increased cardiovascular risk. We monitored the impact of glucoregulation on the efficacy of painful diabetic neuropathy (PDN) treatment, when all pharmaceutical treatment options were exhausted. Methods. Patients (n = 53, both gender, average age 68.3 ? 12.6) with PDN resistant to the pharmacotherapy were treated with the ultrasound- guided local anesthetic (0.5% procaine hydrochloride, 1% lidocaine, 0.25% levobupivacaine) blocks. Neuropathy was confirmed in accordance with the applicable European Federation of Neurological Societies (EFNS) criteria. Glycosylated hemoglobin (HbA1C) and blood glucose levels were monitored before and after therapy and one month after the treatment. Neuropathic pain was confirmed by Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) or Douleur neuropathique (DN4) or pain DETECT scales. The pain intensity was assessed by Visual analog scale, Neuropathic pain symptom and Neuropathic pain symptom inventory (VAS, NPS and NPSI, respectively) scales before and after therapy and one month after the treatment. The efficacy of the therapy was assessed as: excellent result (&gt; 50% of pain loss), good result (30%?49% of pain loss and the therapy does not work (&lt; 30% of pain loss). The correlation between glucoregulation and the outcome was examined. Results. Because the values of glycenia and HbA1c were not different among patients treated with different local anesthetics, they were presented together. All patients had elevated blood glucose and HbA1C levels before (8.23 ? 2.77 mmol/L and 8.53% ? 2.48% respectively), after (8.43 ? 2.461 mmol/L and 8.85% ? 2.87%, respectively) and one month after the treatment (8.49 ? 2.22 mmol/L and 8.51% ? 2.09%, respectively). The loss of the pain was not result of the decrease in blood glucose and HbA1C blood levels. VAS, NPS, NPSI values were the following before the therapy: 81.53 ? 11.62 mm; 62.00 ? 13.04; 53.40 ? 17.63, respectively; after the therapy: 29.00 ? 9.23 mm; 13.79 ? 6.65; 11.83 ? 7.93, respectively; and one month later: 26.15 ? 8.41 mm; 12.68 ? 6.03; 9.81 ? 7.64, respectively]. There was no correlation between glucoregulation and excellent outcome. Conclusion. Even though the disturbance of glucose control is the key factor for the progression of PDN, it is not significant for the outcome of the pain treatment. New investigations are required.

Role of pericytes in vascular immunosurveillance.

Pericytes build together with endothelial cells the microvascular vessel wall. They have been mainly implicated in angiogenesis and maintenance of the blood brain barrier, but there is accumulating evidence for an immunological function of pericytes. Occupying a strategic position between the blood stream and the interstitial space, pericytes are able to sense environmental cues from both sides in an organ-specific manner and serve as gatekeepers for innate immune cells. In addition, pericytes are able to interact with leukocytes mediated by adhesion molecules as well as chemokines and are involved from the development of leukocytes in the bone marrow to their migration to injured or infected areas in target tissues. During disease processes pericytes regulate blood flow, vascular permeability, and leukocyte recruitment, but also contribute to maladaptive tissue responses, such as fibrosis making pericytes an attractive therapeutic target.

Pathogenicity of streptococcus agalactiae in oreochromis niloticus

// Yang He 1, 6, * , Jin-Lu Huang 5, * , Kai-Yu Wang 1, 2 , De-Fang Chen 2 , Yi Geng 1 , Xiao-Li Huang 2 , Ping Ou-Yang 1 , Yi Zhou 3 , Jun Wang 6 , Jie Min 4 and Wei-Min Lai 1 1 Department of Basic Veterinary, College of Veterinary Medicine, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, Sichuan, 611130, P. R. China 2 Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Wenjiang, Sichuan, 611130, P. R. China 3 College of Life Science, Sichuan Agricultural University, Ya’an, Sichuan, 625000, P. R. China 4 College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Sichuan, 611130, P. R. China 5 Veterinary Research Institution of Haida, Guangdong, Guangzhou, 511490, P.R. China 6 College of Life Science, Neijiang Normal University, Neijiang, Sichuan, 641100, P. R. China * These authors contributed equally to this work Correspondence to: Kai-Yu Wang, email: kywang1955@126.com Keywords: oreochromis niloticus; group B streptococcus; histopathology; ultrapathology; ISH–PCR Received: April 25, 2017 Accepted: October 28, 2017 Published: January 02, 2018 ABSTRACT To extend our understanding of the pathogenesis of group B streptococcus (GBS), an infection model was established in the Nile tilapia, and the 50% lethal dose (LD50), the toxicity of the extracellular products, the histopathology, ultrapathology, and dynamic distribution of the bacterium were evaluated. After experimental intraperitoneal (i.p.) infection of the Nile tilapia, the LD50 of GBS resuspended in normal saline was 2.3 × 10 7 cfu/mL and that of GBS resuspended in bacterial culture medium was 7.7 × 10 6 cfu/mL. Enzymatic analysis of the extracellular products detected lipase and urease activities. The affected fish showed gross symptoms similar to those of naturally infected fish, including external signs (lethargy, abdominal distension, and abnormal swimming) and internal signs (hemorrhagic liver, enlarged and reddened spleen, hyperemic brain and kidney, empty stomach, and hemorrhagic enteritis). Histologically, hemorrhage, congestion, edema, and necrosis were apparent in the liver, kidney, spleen, heart, and brain. Bacterial colonization was first observed at 2 h postinfection (hpi) in the spleen, 4 hpi in the liver, and 12 hpi in the kidney, brain, and heart. Ultrastructurally, the cells showed nuclear shrinkage, hydropic mitochondrial damage, and increased secondary lysosomes. The bacteria were freely disseminated in the cytoplasm of phagocytes, brain microvascular endothelial cells, neurons, and blood vessels. These results indicate that GBS and their extracellular products are pathogenic to the Nile tilapia, damaging its splenic phagocytes, vascular and renal endothelial cells, liver hepatocytes, and brain neurocytes.

Diagnostic value of white light endoscopy and narrow band imaging for colorectal sessile serrated adenoma and hyperplastic polyp

Objective To differentiate colorectal sessile serrated adenoma (SSA) and large hyperplastic polyp (HP) with white light endoscopy and narrow band imaging. Methods Retrospective analysis was performed on the clinical data of 953 patients who underwent endoscopic screening for colorectal cancer at digestive endoscopy center of Peking Union Medical College Hospital from January 2015 to December 2015.Endoscopic features were compared with white light endoscopy and narrow band imaging between SSA and large HP in location, size, Paris classification, surface mucus, NICE classification and varicose microvascular vessel (VMV). Results A total of 28(2.9%) SSAs and 25(2.6%) HPs of diameter not less than 0.5 cm were detected in the total of 953 patients. Statistically significant difference was found in right hemi-colon, diameter not less than 1.0 cm and VMV in two groups(P<0.05). The sensitivities of the above three markers for SSA were 89.3%, 67.9% and 46.4% respectively. The specificities were 64.0%, 76.0% and 84.0% respectively. Diagnostic accuracies were 77.4%, 71.7% and 64.2% respectively. And the sensitivity, specificity and accuracy of three markers combined (at least two markers) were 75.0%, 88.0% and 81.1%, respectively. Conclusion SSA and large HP could be differentiated with a systemic consideration of lesion location, size, and surface of microvessels by using white light endoscopy and image-enhanced technique. Key words: Colonic polyps; Colonoscopy; Narrow band imaging; Sessile serrated adenoma; Hyperplastic polyp