Changes and significance of CD8 + CD28 - regulatory T cells in acute phase of Kawasaki disease / 中华微生物学和免疫学杂志

Objective:To investigate the changes of CD8 + CD28 - regulatory T cells (Treg) and its role in the pathogenesis of Kawasaki disease (KD). Methods:A total of 48 children with KD were enrolled in the present study from June 2019 to December 2021. Blood samples were collected from them during acute phage of KD and after intravenous immunoglobulin (IVIG) treatment. Another 32 age-matched healthy children were recruited as control group. The proportions of CD8 + CD28 -Treg cells and the expression of programmed cell death protein 1 (PD-1), factor associated suicide ligand (FasL), inducible T-cell co-stimulator ligand (ICOSL), CD80 and CD86 protein were evaluated by flow cytometry. The expression of Helios, perforin, granzyme B, immunoglobulin-like transcript 3 (ILT3) and ILT4 at the transcription level was measured by real-time PCR. Concentrations of IL-10 and TGF-β in the culture supernatants of CD8 + CD28 -Treg cells stimulated with activated CD4 + T cells were measured by ELISA. Results:⑴ The proportions of CD8 + CD28 -Treg cells and the expression of Helios in patients with acute KD were higher than those in the control group ( P<0.05), and reduced remarkably after IVIG therapy ( P<0.05). The two afore-mentioned indexes were lower in patients combined with coronary artery lesion (CAL) than in those without coronary artery lesion (NCAL) ( P<0.05). ⑵ Compared with the control group, the patients with acute KD showed increased expression of FasL, PD-1, ICOSL and perforin in CD8 + CD28 -Treg cells ( P<0.05). The concentrations of IL-10 and TGF-β1 in the culture supernatants of CD8 + CD28 -Treg cells from patients with acute KD were lower than those in the control group after stimulation with activated CD4 + T cells ( P<0.05), which restored to some extent after IVIG treatment ( P<0.05). All of the six above-mentioned indexes in the CAL group were found to be lower than those in the NCAL group ( P<0.05). There were slight differences in granzyme B expression between different groups ( P>0.05). (3) In comparison with the healthy controls, the patients with acute KD showed overexpressed co-stimulatory molecules such as CD80 and CD86 on CD14 + cells ( P<0.05) and up-regulated expression of inhibitory molecules ILT3 and ILT4 ( P<0.05), which were restored remarkably after IVIG treatment ( P<0.05). Furthermore, the expression of CD80 and CD86 at protein level increased in the CAL group than in the NCAL group ( P<0.05), while the expression of ILT3 and ILT4 at transcriptional level decreased in the CAL group ( P<0.05). Conclusions:Relative insufficiency and impaired function of CD8 + CD28 -Treg cells might be one of the important factors resulting in immune dysfunction and vascular damage in KD patients.

Changes and significance of granulocyte-like myeloid-derived suppressor cells during acute phase of Kawasaki disease / 中华微生物学和免疫学杂志

Objective:To investigate the changes and significance of granulocyte-like myeloid-derived suppressor cells (G-MDSC) in the acute phage of Kawasaki disease (KD).Methods:Forty-two children with acute KD were enrolled in the present study and 32 age-matched healthy children were selected as control group. The proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC, the concentration of reactive oxygen species (ROS) and the expression of arginase-1 (Arg-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte associated protein 4 (CTLA4), glycoprotein 130 (gp130) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) at protein level were detected by flow cytometry. Quantitative real-time PCR was used to measure the expression of inducible nitric oxide synthase (iNOS), interferon regulatory factor 8 (IRF-8), IL-6 receptor α subunit (IL-6Rα), granulocyte colony-stimulating factor receptor (G-CSFR), CCAAT/enhancer binding protein β (C/EBPβ), suppressor of cytokine signaling 1 (SOCS1) and SOCS3 at mRNA level in G-MDSC. Chromatin immunoprecipitation was performed to detect the acetylation of histone H3 at the promoters of SOCS1 and SOCS3 genes. Plasma concentrations of IL-6 and granulocyte colony-stimulating factor (G-CSF) and protein levels of IL-10, transforming growth factor-β (TGF-β) and nitric oxide (NO) in the culture supernatant of G-MDSC stimulated with LPS were measured by ELISA. Results:(1) Compared with the control group, the proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC as well as the concentration of ROS and the expression of inhibitory molecules (Arg-1, PD-L1 and CTLA4) in G-MDSC increased significantly in patients with acute KD ( P<0.05). Moreover, the concentrations of IL-10 and TGF-β in culture supernatant of G-MDSC were also higher than those of the control group after stimulation with lipopolysaccharide for 48 h ( P<0.05). All of the seven afore-mentioned indexes in KD patients with coronary artery lesion (CAL group ) were lower than those in patients without coronary artery lesion (NCAL group) ( P<0.05), and restored to some extent after IVIG therapy ( P<0.05). There were no statistical differences in iNOS expression or NO concentration in culture supernatant of G-MDSC among different groups ( P<0.05). (2) Plasma concentrations of IL-6 and G-CSF, and the expression of IL-6Rα, gp130, G-CSFR, pSTAT3 and C/EBPβ increased remarkably during acute phase of KD ( P<0.05). The expression of IRF-8 at transcription level in patients with acute KD was found to be lower than that of healthy controls ( P<0.05), and restored significantly after IVIG therapy ( P<0.05). Moreover, the plasma concentrations of IL-6 and G-CSF and the expression of IL-6Rα, gp130, G-CSFR and IRF-8 in the CAL group were higher than those in the NCAL group ( P<0.05), while the expression of pSTAT3 and C/EBPβ was lower in the CAL group ( P<0.05), which were restored by IVIG therapy ( P<0.05). (3) In patients with acute KD, the expression of SOCS1 and SOCS3 at mRNA level and histone acetylation at the promoters of SOCS1 and SOCS3 genes were reduced significantly in comparison with those in healthy controls ( P<0.05) , but were increased remarkably after IVIG treatment( P<0.05). The four indexes were higher in the CAL group than in the NCAL group ( P<0.05). Pearson correlation analysis showed the expression of SOCS1 and SOCS3 was negatively correlated with the protein level of pSTAT3 in G-MDSC of patients with acute KD ( r=-0.46 and -0.32, P<0.05). Conclusions:Changes in the number and function of G-MDSC caused by aberrant histone acetylation at SOCS1 and SOCS3 genes might contribute to the immune dysfunction and vascular damage in patients with KD.

No-Touch Saphenous Vein - Vascular Damage and the London Connection

ABSTRACT In this review, I summarise the circumstances leading to the collaboration between London and Örebro on the basic research performed to study potential mechanisms underlying the improved patency of saphenous veins harvested by the no-touch technique. Histological studies reveal various forms of vascular damage to saphenous vein grafts harvested in conventional coronary artery bypass grafting (CABG) whereas no-touch grafts retain a normal architecture. The perivascular fat that remains intact on no-touch saphenous vein grafts seems to play a particularly important role as the "protector" of all layers of the graft. In addition, the perivascular fat is a source of adipose cell-derived factors that may contribute to the success of the no-touch technique. While a number of trials have compared no-touch with conventional grafts following CABG, these have generally been limited to short follow-up periods, low patient numbers, and inadequate histological data. When handling no-touch saphenous vein at harvesting, there is no direct contact of the vein by surgical instruments, spasm does not occur, and high-pressure intraluminal distension is not required. While damage to both endothelial and vascular smooth muscle cells are evident at the microscopic and ultrastructural level in conventional saphenous vein grafts, their structure in no-touch grafts is preserved. Also, in no-touch veins, the vasa vasorum remains intact and transmural blood supply is maintained. This microvascular network is disrupted during conventional harvesting, a situation likely to stimulate processes involved in graft occlusion. The use of excess graft material for histology is to be encouraged for the assessment of vascular damage and even surgeon competence. If you don't look, you don't find.

Hematoma paroxístico de los dedos (Síndrome de Achenbach) / Paroxysmal finger haematoma (Achenbach syndrome)

RESUMEN El hematoma paroxístico de los dedos hace referencia a pacientes que padecen episodios súbitos de dolor y edema en uno o más dígitos con la subsecuente aparición de un hematoma, predominantemente en la región palmar de las falanges proximales. El hematoma paroxístico de los dígitos es una condición rara y benigna de etiología desconocida. Los síntomas prodrómicos como dolor, hormigueo y picazón pueden ocurrir desde minutos hasta horas antes de que aparezca el cambio de coloración. El sangrado subdérmico por lo general se detiene espontáneamente o minutos después de aplicar presión local y los cambios de coloración usualmente desaparecen. El diagnóstico se basa estrictamente en las características clínicas ya que todas las investigaciones de rutina suelen ser normales. El curso de esta condición es benigno y los síntomas se resuelven sin dejar secuelas permanentes. Los médicos deberían encontrarse alertas sobre esta condición para reconocerla y asesorar correctamente al paciente acerca de su pronóstico y evitar el pedido de estudios complementarios innecesarios.

SUMMARY Paroxysmal finger hematoma refers to patients suffering from episodic pain and swelling in one or more digits with subsequent appearance of a hematoma in the palmar aspect of the proximal phalanges. Paroxysmal finger hematoma is a rare and benign condition of unknown etiology. Prodromal symptoms such as pain, tingling and itching may occur from minutes to hours before the color change appears. Subdermal bleeding usually stops spontaneously or after local pressure is applied, and changes in coloration usually disappear. The diagnosis is strictly based on the clinical features since all routine investigations are usually normal. The course of this condition is benign and the symptoms resolve without permanent sequelae. Doctors should become aware of this condition to advise their patients about the prognosis and to avoid the request of unnecessary additional studies.

Reactividad vascular in vitro y estudio morfométrico de venas safenas utilizadas como bypass coronario: técnica "no-touch" versus convencional / In vitro vascular reactivity and morphometric study of saphenous veins graft used as coronary bypass: "no-touch" versus conventional technique

Resumen Introducción: Prolongar la permeabilidad de los injertos utilizados en bypass coronario es un desafío constante. Objetivo: Comparar anatomofuncionalmente venas safenas humanas (VSH) extraídas con técnica convencional (TC) vs técnica "no-touch" (NT). Material y Método: Estudio experimental. Se diseccionó VSH con TC y NT en el pabellón de cirugía cardiaca del Hospital Regional de Antofagasta. Las muestras de VSH fueron seccionadas en anillos de 3 mm y conservados en cámaras de órganos aislados con solución Ringer-Krebs. Para evaluar la vasomotilidad se administró norepinefrina (10-6M), papaverina (10-4M), acetilcolina (10-6M) y nitroprusiato de sodio (10-5M). Un segmento de las muestras fue fijado en formalina al 10%, procesado con técnica histológica y analizado bajo microscopía óptica. Las muestras fueron teñidas con hematoxilina-eosina, Verhoeff y orceína. El análisis estadístico fue realizado mediante el software Prism Graphad. Resultados: Reactividad vascular: La vasoconstricción inducida por noradrenalina fue significativamente superior en anillos del grupo NT vs TC (p < 0,0001). La vasodilatación producida por papaverina y acetilcolina fue superior en el grupo NT (p < 0,004) y (p < 0,0003), respectivamente. Estudio morfométrico: El grupo NT presentó túnica muscular (0,755 vs 0,680 mm), adventicia (0,5600 vs 0,4663 mm) y pared total (1,344 vs 0,962 mm) más gruesa que el grupo TC. No hubo diferencias significativas respecto el número de vasa vasorum. Conclusión: El grupo NT responde significativamente mejor a estímulos vasoconstrictores y vasodilatadores. Los resultados se asocian con las diferencias morfométricas.

Introduction: Prolonging of the grafts permeability used in coronary bypass is a constant challenge. Objective: To compare anatomical and functional human saphenous veins (VSH) extracted "No touch" (NT) technique vs conventional technique (TC). Materials and Methods: Experimental study. VSH dissected with CT and NT in the Regional Hospital of Antofagasta cardiac surgery ward. VSH samples were sectioned into 3 mm rings and preserved in isolated organs chambers with Krebs-Ringer solution. To evaluate the vasomotor activity, norepinephrine (10-6M), papaverine (10-4M), acetylcholine (10-6M) and sodium nitroprusside (10-5M) was administered. A segment of samples was fixed in 10% formalin, processed and histological analyzed under light microscopy technique with hematoxylin-eosin, Verhoeff and orceína. Statistical analysis was performed using the Prism software Graphad. Results: Vascular Reactivity: norepinephrine-induced vasoconstriction was significantly higher in the group rings NT vs TC (p < 0.0001). Vasodilation was higher with papaverine and acetylcholine in the NT group (p < 0.004) and (p < 0.0003), respectively. Morphometric study: The NT group presented muscularis (0.755 vs 0.680 mm), adventitious (0.5600 vs 0.4663 mm), and total wall (1.344 vs 0.962 mm) thicker than the TC group. No significant differences in vasa vasorum number identified. Conclusion: The NT group vasoconstrictor and vasodilator responds significantly better. Results correlate with morphometric differences.

Correlation study between four vessel regulate factors and white finger evaluating in workers exposed to hand-arm vibration / 中国职业医学

OBJECTIVE: To analyze the correlation between four vessel regulate factors and vibration-induced white finger( VWF) evaluating in workers exposed to hand-arm vibration,and discuss the value of regulate factors for VWF screening.METHODS: Using typical sampling method,77 male workers exposed to hand-arm vibration with more than 1 year of polish work from a metalwork factory were selected as the study subjects. Based on the workers' self-report,they were divided into VWF group( 43 workers) and non-VWF group( 34 workers). The venous blood from center elbow was collected and plasma was separated. The plasma level of endothelin( ET) was detected by radioimmunoassay. The plasma levels of transforming growth factor beta( TGF-β),soluble intercellular adhesion molecule-1( s ICAM-1) and 5-hydroxytryptamine( 5-HT) were detected by enzyme-linked immunosorbent assay. The regulate factors for evaluating VWF were screened and the new multivariable model index

Renal vascular damage and the expression of miR-145 in lupus nephritis / 临床儿科杂志

Objective To evaluate renal vascular damage (RVLs) and detect the expression of miR-145 in children with lupus nephritis (LN).Methods Clinical data of 41 cases of LN diagnosed by renal biopsy from the children with systemic lupus erythematosus (SLE) were collected. Glomerular damage score and RVLs were evaluated. The children were divided into groups according to RVLs score and pathological pattern. In situ hybridization was performed to detect the expression of miR-145 in kidney blood vessel. Differences in RVLs, miR-145 expression in the renal blood vessels and glomerular damage score were observed among the groups with different renal pathological pattern. Differences in clinical parameters, glomerular damage score and miR-145 expression in the renal blood vessels were investigated among groups with different RVLs. Results Among the groups with different pathological pattern, there was no difference in RVLs (P>?0.05) while signiifcant different were found in the expression of miR-145 and glomerular damage score (P??0.05) while a statistical different was found in the expression of miR-145 (P?

Micro-vascular Diseases of White Matter

White matter hyperintensity (WMH) is commonly observed on the brain MRI of elderly subjects. It has been considered as an important biomarker for the micro-vascular damages of white matter of the brain. Aging, hypertension, diabetes mellitus, and hyperhomocysteinemia have been associated with WMH development. WMH is an important risk factor for the vascular dementia (VD), however it also considered as one of risk factors for conversion of mild cognitive impairment to dementia and progression of Alzheimer's disease (AD). WMH has impact on gait, bladder control, and fine motor coordination. It also has negative effects on memory retrieval, mental flexibility, mental processing speed, and executive function by disconnecting nerve fibers that convey signals for normal cognition. Control of vascular risk factors can delay progression of WMH and this may be beneficial for VD as well as AD with ischemic changes, especially in the early state of diseases. In this paper, we will review clinical significance of WMH and three important diseases, subcortical vascular dementia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and cerebral amyloid angiopathy that associated with cerebral micro-vascular damages.