This study was performed to analyze fingertip capillary blood sampling in pediatric patients using microcapillary blood collection tubes and microhematocrit tubes and to compare the blood cell analysis results obtained via these two blood collection methods. Finger capillary blood was collected from 110 outpatients using microcapillary blood collection tubes and microhematocrit tubes and complete blood count analysis was performed with a Sysmex XS-900i hematology analyzer and manual microscopy for blood cell morphology. Paired data was evaluated for agreement and bias using the microhematocrit samples as the reference group and the samples from the microcapillary blood collection tubes as the observation group. The two blood collection methods demonstrated good agreement for measuring red blood cell (RBC) parameters (i.e., RBC, Hb, Hct, MCV, MCH and MCHC), wherein the relative bias was > allowable total error (TEa) in 0.91%, 1.82%, 11.82%, 1.82%, 0.91% and 8.18% of the parameter measures, respectively. According to industry requirements, the proportion of samples meeting the acceptable bias level should be > 80%. Additionally, the estimated biases at each medical decision level were within clinically acceptable levels for RBC, Hb, Hct, and MCV. However, the proportion of WBC and PLT counts with relative bias > TEa was 25.45% and 35.45%, respectively. Furthermore, the relative bias of the WBC count at the medical decision level of 0.5 × 109/L and that of the PLT counts at the medical decision levels of 10 × 109/L and 50 × 109/L were clinically significant. Bland-Altman analysis further showed a mean bias of 0.66 × 109/L (95% LoA, - 0.79 to 2.11) for the WBC count and 39 × 109/L (95% LoA, - 46 to 124) for the PLT count from the blood samples collected in the microcapillary blood collection tubes compared with the counts of those collected in the microhematocrit tubes. Neutrophil, monocyte, lymphocyte, eosinophil, and PLT counts increased significantly in the microcapillary blood collection tubes compared with those in the microhematocrit tubes, along with an elevated number of instrument false alarms (P < 0.05). The two capillary blood collection devices exhibit performance differences. Therefore, clinicians should pay attention to the variation in results caused by different blood collection methods.

Accurate reproduction of human intestinal structure and functionin vitrois of great significance for understanding the development and disease occurrence of the gut. However, mostin vitrostudies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization foundin vivo. Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with invivo-likering folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine.

目的： 探讨肝脏伴毛细血管增生的血管畸形临床病理特征。 方法： 收集海军军医大学东方肝胆外科医院和长海医院2014年6月至2022年9月手术治疗的4例肝脏伴毛细血管增生的血管畸形患者信息，并复习文献。 结果： 4例患者中男性1例，女性3例，平均年龄33岁。3例单发，1例多发，最大径0.7~7.5 cm。大体检查，病变灰白灰红色，病变中央可见坏死。镜下观察，病变由毛细血管样和海绵状血管样管腔构成，前者衬覆肥胖且钉状突起的内皮细胞，后者衬覆扁平状内皮细胞，细胞无异型，间质呈富于细胞的纤维样。病变中央区退变显著，周边区见扩张扭曲的血管，边界可伴舌状突起。免疫组织化学表达CD34和ERG，Glut-1阴性，Ki-67阳性指数<5%。患者术后恢复良好。 结论： 肝脏伴毛细血管增生的血管畸形是一种罕见的良性血管源性病变，毛细血管样和海绵状血管样管腔混合生长、毛细血管腔内钉状突起的内皮细胞、扩张扭曲的血管和Glut-1阴性是该病的重要提示。.

Liver fibrosis and cirrhosis, which are caused by chronic liver injury, represent common and intractable clinical challenges of global importance. However, effective therapeutics are lacking. Therefore, the study examines the effect of doxazosin on liver fibrosis. Carbon tetrachloride (CCl4) is injected into mice to establish a liver fibrosis model. Doxazosin (5 and 10 mg/kg) is administered daily by gavage. HE staining, Masson staining, Sirius Red staining, scanning electron microscopy, western blotting, real-time PCR, and immunofluorescence analysis are performed to estimate liver fibrosis and sinusoidal capillarization in mice. Cell Counting Kit-8 assays, western blotting, immunofluorescence analysis, tube formation, and transwell migration assays are performed on human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs) to elucidate the potential mechanism of doxazosin. Doxazosin alleviates liver fibrosis and sinusoidal capillarization in CCl4-induced mice. Angiogenesis is attenuated by doxazosin in HUVECs and HHSECs. This study demonstrates that doxazosin attenuated liver fibrosis by alleviating sinusoidal capillarization and liver angiogenesis.

Changes in the structure and function of nailfold capillaries may be indicators of numerous diseases. Noninvasive diagnostic tools are commonly used for the extraction of morphological information from segmented nailfold capillaries to study physiological and pathological changes therein. However, current segmentation methods for nailfold capillaries cannot accurately separate capillaries from the background, resulting in issues such as unclear segmentation boundaries. Therefore, improving the accuracy of nailfold capillary segmentation is necessary to facilitate more efficient clinical diagnosis and research. Herein, we propose a nailfold capillary image segmentation method based on a U2-Net backbone network combined with a Transformer structure. This method integrates the U2-Net and Transformer networks to establish a decoder-encoder network, which inserts Transformer layers into the nested two-layer U-shaped architecture of the U2-Net. This structure effectively extracts multiscale features within stages and aggregates multilevel features across stages to generate high-resolution feature maps. The experimental results demonstrate an overall accuracy of 98.23 %, a Dice coefficient of 88.56 %, and an IoU of 80.41 % compared to the ground truth. Furthermore, our proposed method improves the overall accuracy by approximately 2 %, 3 %, and 5 % compared to the original U2-Net, Res-Unet, and U-Net, respectively. These results indicate that the Transformer-U2Net network performs well in nailfold capillary image segmentation and provides more detailed and accurate information on the segmented nailfold capillary structure, which may aid clinicians in the more precise diagnosis and treatment of nailfold capillary-related diseases.

The capillarization of hepatic sinusoids resulting from the activation of hepatic stellate cells poses a significant challenge, impeding the effective delivery of therapeutic agents to the Disse space for liver fibrosis treatment. Therefore, overcoming these barriers and achieving efficient drug delivery to activated hepatic stellate cells (aHSCs) are pressing challenge. In this study, we developed a synergistic sequential drug delivery approach utilizing neutrophil membrane hybrid liposome@atorvastatin/amlisentan (NCM@AtAm) and vitamin A-neutrophil membrane hybrid liposome @albumin (VNCM@Bai) nanoparticles (NPs) to breach the capillary barrier for targeted HSC cell delivery. Initially, NCM@AtAm NPs were successfully directed to the site of hepatic fibrosis through neutrophil-mediated inflammatory targeting, resulting in the normalization of liver sinusoidal endothelial cells (LSECs) and restoration of fenestrations under the combined influence of At and Am. Elevated tissue levels of the p-Akt protein and endothelial nitric oxide synthase (eNOS) indicated the normalization of LSECs following treatment with At and Am. Subsequently, VNCM@Bai NPs traversed the restored LSEC fenestrations to access the Disse space, facilitating the delivery of Bai into aHSCs under vitamin A guidance. Lastly, both in vitro and in vivo results demonstrated the efficacy of Bai in inhibiting HSC cell activation by modulating the PPAR γ/TGF-β1 and STAT1/Smad7 signaling pathways, thereby effectively treating liver fibrosis. Overall, our designed synergistic sequential delivery system effectively overcomes the barrier imposed by LSECs, offering a promising therapeutic strategy for liver fibrosis treatment in clinical settings.

The etiology of primary pulmonary angiosarcoma is still unknown. Here we report a case of primary pulmonary angiosarcoma originated from a tuberculous scar and presented as aggressive deterioration with uncontrolled bleeding from capillaries with angiodysplasia.

Liver sinusoidal endothelial cells (LSECs) have an important role in hepatic ischemia‑reperfusion injury (I/R), but the specific molecular mechanism of action is unknown. LSEC proliferation is regulated and fenestration is maintained via the Sentrin/SUMO‑specific protease 1 (SENP1)/hypoxia‑inducible factor‑1α (HIF‑1α) signaling axis under hypoxic conditions. In the present study, a hypoxia‑reoxygenation (H‑R) injury model was established using mouse LSECs to explore the relationship between SENP1 and H‑R injury in vitro, and the specific underlying mechanism was identified, revealing new targets for the clinical attenuation of hepatic I/R injury. Following the culture of LSECs under H‑R conditions, it was demonstrated that the expression of SENP1 was upregulated by reverse transcription‑quantitative polymerase chain reaction and western blotting (WB). In addition, scanning electron microscopy indicated that fenestrae damage was increased, a Cell Counting Kit‑8 assay demonstrated that the proliferation of cells was impaired and flow cytometry showed that apoptosis was increased. After silencing SENP1 expression with short interfering RNA, the proliferation activity of LSECs decreased, the fenestrae damage increased, the apoptosis rate increased and the expression levels of SENP1, HIF‑1α, heme oxygenase and Bcl‑2 were downregulated (as demonstrated by WB), while the expression levels of apoptosis‑related proteins, cleaved‑caspase‑3 and Bax, were upregulated. Enzyme‑linked immunosorbent assay detection showed that the level of vascular endothelial growth factor in the supernatant decreased and the level of IL‑6 and TNF‑α increased. Following the administration of an HIF‑1α signaling pathway agonist, the situation was reversed. These results therefore suggested that SENP1 attenuated the reduction in proliferation, apoptosis and fenestration of LSECs observed following H‑R injury through the HIF‑1α signaling pathway. In conclusion, SENP1 may attenuate H‑R injury in LSECs in a HIF‑1α signaling pathway‑dependent manner.

暂无摘要。

Sepsis-induced acute lung injury (ALI) poses a significant threat to human health. Endothelial cells, especially pulmonary capillaries, are the primary barriers against sepsis in the lungs. Therefore, investigating endothelial cell function is essential to understand the pathophysiological processes of sepsis-induced ALI.
We downloaded single-cell RNA-seq expression data from GEO with accession number GSE207651. The mice underwent cecal ligation and puncture (CLP) surgery, and lung tissue samples were collected at 0, 24, and 48 h. The cells were annotated using the CellMarker database and FindAllMarkers functions. GO enrichment analyses were performed using the Metascape software. Gene set enrichment Analysis (GSEA) and variation Analysis (GSVA) were performed to identify differential signaling pathways. Differential expression genes were collected with the \"FindMarkers\" function. The R package AUCell was used to score individual cells for pathway activities. The Cellchat package was used to explore intracellular communication.
Granulocytes increased significantly as the duration of endotoxemia increased. However, the number of T cells, NK cells, and B cells declined. Pulmonary capillary cells were grouped into three sub-clusters. Capillary-3 cells were enriched in the sham group, but declined sharply in the CLP.24 group. Capillary-1 cells peaked in the CLP.24 group, while Capillary-2 cells were enriched in the CLP.48 group. Furthermore, we found that Cd74+ Capillary-3 cells mainly participated in immune interactions. Plat+ Capillary-1 and Clec1a+ Capillary-2 are involved in various physiological processes. Regarding cell-cell interactions, Plat+ Capillary-1 plays the most critical role in granulocyte adherence to capillaries during ALI. Cd74+ Capillary cells expressing high levels of major histocompatibility complex (MHC) and mainly interacted with Cd8a+ T cells in the sham group.
Plat+ capillaries are involved in the innate immune response through their interaction with neutrophils via ICAM-1 adhesion during endotoxemia, while Cd74+ capillaries epxressed high level of MHC proteins play a role in adaptive immune response through their interaction with T cells. However, it remains unclear whether the function of Cd74+ capillaries leans towards immunity or tolerance, and further studies are needed to confirm this.