Postmastectomy syndrome (PMS) is a complex neurovascular set of symptoms that develops in most patients after breast cancer (BC) treatment and significantly reduces the quality of life. One of the potential mechanisms of its occurrence is considered to be an endothelial dysfunction. The possible method of reducing manifestation of endothelial dysfunction is systematic aerobic dynamic training.
OBJECTIVE: To evaluate the influence of 12-week aerobic dynamic training program of moderate intensity on the endothelial dysfunction laboratory markers and life quality in patients with PMS.
METHODS: Single-center prospective randomized trial included 40 patients with PMS divided into study (20 patients) and comparative (20 patients) groups, as well as 20 healthy female volunteers. The expression level of soluble intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) were evaluated in all participants at baseline by enzyme-linked immunosorbent assay method, and additionally psychological and physical component of health by SF-36 questionnaire were assessed in patients with PMS.
Patients of study group received a course of 12-week partially controlled aerobic dynamic training of moderate intensity lasting 45 minutes with frequency equal 5 times per week. Patients with PMS were re-evaluated for ICAM-1 and PECAM-1, as well as for life quality.
RESULTS: The group of patients with PMS after BC treatment had increased level of ICAM-1 in long-term period, that may indicate endothelial dysfunction. Statistically significant decrease of endothelial dysfunction laboratory markers was revealed in patients with PMS, who underwent the course of cardiorespiratory training. In the same time, the dynamics of changes in ICAM-1 was higher in the study group than in comparative group. Further, improvement of physical and psychological components of health by SF-36 questionnaire was found.
CONCLUSIONS: The program of cardiorespiratory trainings of moderate intensity in patients, who had BC treatment a year ago, decreases intercellular adhesion molecules level that may show an improvement of endothelial dysfunction.
Постмастэктомический синдром (ПМЭС) — сложный нейроваскулярный симптомокомплекс, развивающийся у большинства пациенток после лечения рака молочной железы (РМЖ) и существенно снижающий качество жизни. Одним из потенциальных механизмов его возникновения считается нарушение функции эндотелия. Возможным методом уменьшения выраженности дисфункции эндотелия являются систематические аэробные динамические тренировки.
UNASSIGNED: Оценить влияние 12-недельной программы аэробных динамических тренировок средней интенсивности на уровень лабораторных маркеров эндотелиальной дисфункции и качество жизни у пациенток с ПМЭС.
UNASSIGNED: В одноцентровое проспективное рандомизированное исследование было включено 40 пациенток с ПМЭС, разделенных на основную группу (20 пациенток) и группу сравнения (20 пациенток), а также 20 здоровых женщин-добровольцев. У всех участников исследования исходно методом иммуноферментного анализа (ИФА) был оценен уровень экспрессии растворимых молекул межклеточной адгезии 1-го типа (ICAM-1) и молекул адгезии эндотелия и тромбоцитов 1-го типа (PECAM-1), у пациенток с ПМЭС — также психологический и физический компонент здоровья по опроснику SF-36. Пациентки основной группы на протяжении 12 нед получали курс частично контролируемых аэробных динамических нагрузок средней интенсивности длительностью 45 мин с частотой 5 дней в неделю. Через 12 нед у пациенток с ПМЭС повторно оценивали уровень ICAM-1 и PECAM-1, а также качество жизни.
UNASSIGNED: В группе пациенток с ПМЭС в отдаленном периоде после лечения РМЖ повышен уровень ICAM-1, что может указывать на нарушение функции эндотелия. У пациенток с ПМЭС, прошедших курс кардиореспираторных тренировок, обнаружено статистически значимое снижение уровня лабораторных маркеров эндотелиальной дисфункции, при этом динамика изменений уровня ICAM-1 была значимо выше в основной группе по сравнению с группой сравнения. Также в основной группе выявлено улучшение физического и психологического компонентов здоровья по опроснику SF-36.
UNASSIGNED: Программа кардиореспираторных тренировок средней интенсивности у пациенток, перенесших лечение РМЖ более 1 года назад, снижает уровень молекул межклеточной адгезии, что может указывать на улучшение функции эндотелия.

Objective: To investigate the clinicopathological features and differential diagnosis of breast angiomatosis. Methods: Six cases of breast angiomatosis diagnosed at the Department of Pathology, the Seventh Medical Center, People\'s Liberation Army General Hospital and the Department of Pathology, Dongzhimen Hospital, Beijing University of Chinese Medicine from January 2011 to December 2023 were evaluated and reviewed. Results: All patients were female with an average age of 46 years at presentation, ranging from 25 to 62 years. The most common clinical presentation was a palpable unilateral breast mass with diameter ranging from 7 to 14 cm, and the average size was 11 cm. Histologically, all cases were composed of variably-sized ectatic, thin-walled blood vessels with minimal to no apparent smooth muscle, lined by flat normochromic endothelium without atypia, and diffusely infiltrating the breast stroma. Where present, the lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Immunohistochemical staining for CD31, CD34, Factor Ⅷ, Fli-1 and D2-40 revealed positive expression in vascular and/or lymphatic endothelial cells. Additionally, the Ki-67 proliferation index was found to be less than 1%. Conclusions: Angiomatosis of the breast is a rare benign vascular lesion. Distinguishing it from low-grade angiosarcoma requires careful consideration of the growth pattern, atypical features, and Ki-67 proliferation index.
目的： 探讨乳腺血管瘤病的临床病理特征及病理诊断。 方法： 收集解放军总医院第七医学中心病理科及北京中医药大学东直门医院病理科2011年1月至2023年12月诊断的共6例乳腺血管瘤病患者，分析其临床病理资料并复习相关文献。 结果： 6例患者均为女性，年龄范围25~62岁，平均年龄46岁。临床常表现为可触及的单侧乳腺肿块，肿瘤最大径7~14 cm，平均11 cm。组织学上，6例均表现为血管、淋巴管弥漫性增生，脉管腔扩张、大小不等、互相吻合、管壁薄，无/极少见平滑肌，内皮细胞扁平、无异型性，病变弥漫性浸润乳腺间质，但不破坏乳腺终末导管小叶单位。CD31、CD34、第Ⅷ因子相关抗原、Fli-1、D2-40等免疫组织化学染色结果显示血管和/或淋巴管内皮细胞阳性，Ki-67阳性指数均<1%。 结论： 乳腺血管瘤病是一种罕见的良性脉管性病变，与低级别血管肉瘤的鉴别需要关注病变生长模式、内皮细胞形态和Ki-67阳性指数。.

Inflammatory bowel disease (IBD) represents a group of recurrent chronic inflammatory disorders associated with autoimmune dysregulation, typically characterized by neutrophil infiltration and mucosal inflammatory lesions. Neutrophils, as the earliest immune cells to arrive at inflamed tissues, play a dual role in the onset and progression of mucosal inflammation in IBD. Most of these cells specifically express CD177, a molecule increasingly recognized for its critical role in the pathogenesis of IBD. Under IBD-related inflammatory stimuli, CD177 is highly expressed on neutrophils and promotes their migration. CD177 + neutrophils activate bactericidal and barrier-protective functions at IBD mucosal inflammation sites and regulate the release of inflammatory mediators highly correlated with the severity of inflammation in IBD patients, thus playing a dual role. However, mitigating the detrimental effects of neutrophils in inflammatory bowel disease remains a challenge. Based on these data, we have summarized recent articles on the role of neutrophils in intestinal inflammation, with a particular emphasis on CD177, which mediates the recruitment, transepithelial migration, and activation of neutrophils, as well as their functional consequences. A better understanding of CD177 + neutrophils may contribute to the development of novel therapeutic targets to selectively modulate the protective role of this class of cells in IBD.

Osteogenesis is tightly coupled with angiogenesis spatiotemporally. Previous studies have demonstrated that type H blood vessel formed by endothelial cells with high expression of CD31 and Emcn (CD31hi Emcnhi ECs) play a crucial role in bone regeneration. The mechanism of the molecular communication around CD31hi Emcnhi ECs and bone mesenchymal stem cells (BMSCs) in the osteogenic microenvironment is unclear. This study indicates that exosomes from bone mesenchymal stem cells with 7 days osteogenic differentiation (7D-BMSCs-exo) may promote CD31hi Emcnhi ECs angiogenesis, which was verified by tube formation assay, qRT-PCR, Western blot, immunofluorescence staining and µCT assays etc. in vitro and in vivo. Furthermore, by exosomal miRNA microarray and WGCNA assays, we identified downregulated miR-150-5p as the most relative hub gene coupling osteogenic differentiation and type H blood vessel angiogenesis. With bioinformatics assays, dual luciferase reporter experiments, qRT-PCR and Western blot assays, SOX2(SRY-Box Transcription Factor 2) was confirmed as a novel downstream target gene of miR-150-5p in exosomes, which might be a pivotal mechanism regulating CD31hi Emcnhi ECs formation. Additionally, JC-1 immunofluorescence staining, Western blot and seahorse assay results showed that the overexpression of SOX2 could shift metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis to enhance the CD31hi Emcnhi ECs formation. The PI3k/Akt signaling pathway might play a key role in this process. In summary, BMSCs in osteogenic differentiation might secrete exosomes with low miR-150-5p expression to induce type H blood vessel formation by mediating SOX2 overexpression in ECs. These findings might reveal a molecular mechanism of osteogenesis coupled with type H blood vessel angiogenesis in the osteogenic microenvironment and provide a new therapeutic target or cell-free remedy for osteogenesis impaired diseases.

Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End-MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632-driven End-MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End-MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End-MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients\' blood. Our findings definitively demonstrate that the End-MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

BACKGROUND: Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis.
METHODS: Male C57BL/6 mice were subjected to the high-fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full-thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions.
RESULTS: Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non-UVB-exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG-induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression.
CONCLUSIONS: UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB-induced ghrelin in therapeutic strategies targeting diabetic wound healing.

The effective treatment of acute lung injury (ALI) remains a significant challenge. Patients with ALI demonstrate an abundance of proinflammatory mediators in both bronchoalveolar lavage fluid (BALF) and circulating plasma. Bardoxolone methyl (BM) is a semi-synthetic triterpenoid derived from oleanolic acid, a natural product known for its ability to inhibit proinflammatory signaling. GSDMD is a signaling protein involved in pyroptosis, a form of programmed cell death. It has been reported that its upstream proteins play a role in the pathogenesis of ALI. However, there is currently no research examining whether the effect of BM on the occurrence and development of ALI is associated with changes in GSDMD protein. In this study, we prepared nanostructured lipid carriers loaded with BM and conjugated with anti-PECAM-1 antibody (PECAM@BM NLCs). PECAM@BM NLCs were designed to specifically bind to pulmonary vascular endothelial cells that highly express the PECAM-1 receptors. We also aimed to investigate the protective effects of PECAM@BM NLCs on ALI and elucidate the underlying molecular mechanisms. The results demonstrated that PECAM@BM NLCs accumulated in the lung tissues and significantly alleviated the inflammatory injury of ALI. This was evidenced by the changes in the lung wet/dry ratio, the total protein concentration, proinflammatory cytokines in BALF, and the histopathological progress. Additionally, we elucidated that PECAM@BM NLCs had the ability to inhibit the assembly of NLRP3 inflammasome and pro-caspase-1 complex, thereby suppressing the induction of pyroptosis. This mechanism resulted in the inhibition of N-terminal GSDMD expression and effectively prevented the progression of ALI.

BACKGROUND: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions.
OBJECTIVE: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets.
METHODS: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test.
RESULTS: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function.
CONCLUSIONS: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.

Differential diagnosis of atypical parathyroid tumors (APT) and parathyroid carcinomas (PC) is important in determining further management and prognosis. Morphologic diagnosis is sometimes difficult, in which case it is supplemented by immunohistochemical (IHC) examination.
OBJECTIVE: Studying the role of IHC analysis in the differential diagnosis of APT and PC.
METHODS: The study included 44 patients with morphologic diagnosis of the APT established after surgical treatment for primary hyperparathyroidism on the basis of Endocrinology Research Centre during 2018-2023. All cases underwent IHC examination with evaluation of CD31/CD34 and parathormone (PTH) expression for identification of vascular invasion, Ki-67, parafibromin.
RESULTS: According to the results of IHC analysis in 8/44 patients (18.2%) the diagnosis of APT was revised in favor of the PC: in 7 of them vascular invasion was detected; in 1 patient the additional series of slices in the surrounding fatty tissue revealed foci of tumor growth, confirmed by positive reaction with antibodies to PTH. According to IHC results, the material was divided into 2 groups: APT and PC. There were no differences in clinical and morphological characteristics, Ki-67% level and parafibromin expression between the groups.
CONCLUSIONS: Assessment of clinical and laboratory-instrumental data at the preoperative stage does not allow differentiating APT from PC. In case of APT diagnosis and detection of suspicious morphological features, it is necessary to perform IHC examination to exclude PC.
Дифференциальная диагностика атипических опухолей (АО) и карцином околощитовидных желез (ОЩЖ) имеет важное значение в определении дальнейшей тактики ведения и прогноза. Морфологическая диагностика в некоторых случаях вызывает сложности, в этом случае дополняется иммуногистохимическим (ИГХ) исследованием.
UNASSIGNED: Оценить вклад ИГХ-исследования в дифференциальную диагностику АО и карцином ОЩЖ.
UNASSIGNED: В исследование включено 44 пациента с морфологическим диагнозом АО ОЩЖ, установленным после хирургического лечения по поводу первичного гиперпаратиреоза на базе ФГБУ «НМИЦ эндокринологии» Минздрава России за 2018—2023 гг. Во всех случаях было проведено ИГХ-исследование с оценкой экспрессии CD31/CD34 и паратгормона (ПТГ) для идентификации сосудистой инвазии; Ki-67, парафибромина.
UNASSIGNED: По результатам ИГХ-анализа у 8 (18,2%) из 44 пациентов диагноз АО был пересмотрен в сторону карциномы ОЩЖ: у 7 из них выявлена сосудистая инвазия, у 1 пациента при проведении дополнительной серии срезов в окружающей жировой клетчатке диагностированы очаги опухолевого роста, подтвержденные положительной реакцией с антителами к ПТГ. В соответствии с результатами ИГХ-материал был разделен на 2 группы: АО и карцинома ОЩЖ. Различий по клинико-морфологическим характеристикам, уровню Ki-67% и экспрессии парафибромина между группами не выявлено.
UNASSIGNED: Оценка клинических и лабораторно-инструментальных данных на дооперационном этапе не позволяет дифференцировать АО и карциномы. В случае диагностики АО и выявления подозрительных морфологических признаков необходимо ИГХ-исследование для исключения карциномы ОЩЖ.