Qiuju Li

Macrophages are the most abundant immune cells in endometriotic lesions, but the roles of specific macrophage subsets in local immune dysfunction remain poorly understood. Here, combining single‐cell RNA sequencing of 11 clinical samples with TREM2 knockout mouse models, co‐culture experiments, and pharmacological intervention, we identify TREM2 ⁺ macrophages as an immunoregulatory population enriched in endometriosis. CD8 ⁺ T and natural killer (NK) cells in endometriotic lesions exhibited exhaustion‐associated features and reduced cytotoxicity. Cell–cell communication analysis and functional experiments revealed that TREM2 ⁺ macrophages regulated CD8 ⁺ T cell activity through SPP1‐CD44‐associated communication and BAG3‐associated autophagy regulation. In a mouse model of endometriosis, TREM2 deficiency enhanced CD8 ⁺ T and NK cell cytotoxicity and reduced ectopic lesion growth. Pharmacological disruption of the BAG3–HSP70 interaction with YM‐1 impaired CD8 ⁺ T cell function and promoted lesion growth, and BAG3 silencing reduced autophagy‐related markers and effector function in CD8 ⁺ T cells, supporting the involvement of BAG3‐associated regulation in TREM2 ⁺ macrophage‐mediated immune dysfunction. Our data identify TREM2 ⁺ macrophages as important regulators of immune dysregulation in endometriosis and highlight TREM2 as a potential target for future non‐hormonal therapeutic strategies.

Accurate diagnosis of white blood cells from cytopathological images is a crucial step in evaluating leukaemia. In recent years, image classification methods based on fully convolutional networks have drawn extensive attention and achieved competitive performance in medical image classification. In this paper, we propose a white blood cell classification network called ResNeXt-CC for cytopathological images. First, we transform cytopathological images from the RGB color space to the HSV color space so as to precisely extract the texture features, color changes and other details of white blood cells. Second, since cell classification primarily relies on distinguishing local characteristics, we design a cross-layer deep-feature fusion module to enhance our ability to extract discriminative information. Third, the efficient attention mechanism based on the ECANet module is used to promote the feature extraction capability of cell details. Finally, we combine the modified softmax loss function and the central loss function to train the network, thereby effectively addressing the problem of class imbalance and improving the network performance. The experimental results on the C-NMC 2019 dataset show that our proposed method manifests obvious advantages over the existing classification methods, including ResNet-50, Inception-V3, Densenet121, VGG16, Cross ViT, Token-to-Token ViT, Deep ViT, and simple ViT about 5.5–20.43% accuracy, 3.6–23.56% F1-score, 3.5–25.71% AUROC and 8.1–36.98% specificity, respectively.

The absence of clinically objective methods to evaluate adenomyosis-associated pain and the poor understanding of its pathophysiology lead to treatment limitations. We conducted a resting-state functional magnetic resonance imaging study with 49 patients with pain-related adenomyosis and 30 pain-free controls to investigate brain morphological alterations and regional dysfunctions in patients with pain-related adenomyosis. These patients had significantly higher scores for anxiety and depression than the control group (p < 0.05). They also had a lower gray matter volume (GMV) in the bilateral insula, left angular gyrus, precuneus, left inferior temporal gyrus, and left postcentral gyrus (p < 0.05, AlphaSim corrected). Similarly, decreased voxel-mirrored homotopic connectivity was observed in the bilateral insula, posterior cingulate cortex, middle frontal gyrus, and postcentral gyrus in the adenomyosis patient group (p < 0.05, AlphaSim corrected). Regional homogeneity showed significant differences mainly in the bilateral cerebellum, left inferior frontal gyrus, medial prefrontal cortex, and posterior cingulate gyrus. Correlation analysis showed that the degree of depression in patients with adenomyosis was negatively correlated with the GMV of the left angular gyrus. The results show that these patients exhibited changes in multiple brain regions associated with pain as well as emotion perception and processing.

The main symptoms of adenomyosis may adversely affect physical and mental health and quality of life (QOL). However, studies are few on this topic. This study evaluated the effect of adenomyosis on anxiety, depression, and QOL. Participants with adenomyosis (n = 90) or leiomyoma (n = 59) completed questionnaires, including the visual analog scale (VAS) for pain, Hospital Anxiety and Depression Scale (HADS), and Short Form (SF)-36. HADS anxiety and depression positive rates, physical (PCS) and mental (MCS) component summary scores, and eight subscale scores of SF-36 were compared between the two groups. Among patients with adenomyosis, the incidence of anxiety symptoms was 28.9% (control group, 10.2%; OR = 3.589, 95% CI: 1.375–9.367), with 10% of patients showing moderate-to-severe symptoms. The incidence of depressive symptoms was 14.4% (control group, 3.4%; OR = 4.812, 95% CI: 1.044–22.168). The case group had significantly lower PCS and MCS scores than the control group. In patients with adenomyosis, being employed (OR = 6.393, 95% CI: 1.153–35.440) and perianal pain (OR = 25.419, 95% CI: 2.504–258.024) were risk factors for anxiety, and perianal pain (OR = 15.208, 95% CI: 3.050–75.836) was a risk factor for depression. Compared with leiomyoma, adenomyosis is associated with a higher risk of anxiety and depression, with a poorer QOL.

Background: Endometriosis is a common nonmalignant gynecological disorder that affects 10–15% women of reproductive age and causes several symptoms that result in decreased quality of life and a huge social burden. In recent decades, extracellular vesicles (EVs) have gained attention as a potential therapeutic tool; however, the therapeutic effects of EVs against endometriosis have not been reported. Accordingly, in this study, we investigated the feasibility of nanovesicles (NVs) derived from M1 macrophages (M1NVs) in treating endometriosis. Methods: M1NVs were prepared by serial extrusion. Co-culture assays were performed to investigate changes in tube formation and migration/invasion of eutopic endometrial stroma cells (ESCs) obtained from patients with endometriosis (EM-ESCs). A mouse model of endometriosis was established, and mice were treated with phosphate-buffered saline, M0NVs, or M1NVs to evaluate the efficacy and safety of M1NV for treating endometriosis. Results: M1NVs directly or indirectly inhibited the migration and invasion of EM-ESCs and reduced tube formation. In the mouse model, M1NVs suppressed the development of endometriosis through reprogramming of M2 macrophages, without causing damage to the organs. Conclusions: M1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.

Aims: To compare the efficacy of gonadotropin‐releasing hormone agonist (GnRH‐a) and GnRH‐a + levonorgestrel‐releasing intrauterine system (LNG‐IUS) after adenomyomectomy for improved adenomyosis‐associated symptoms.Methods: Overall, 193 patients with adenomyosis included in this study were categorized into three groups: adenomyomectomy (n = 57, group 1), adenomyomectomy + GnRH‐a (n = 83, group 2) and adenomyomectomy + GnRH‐a + LNG‐IUS (n = 53, group 3). Visual Analog Scale (VAS) scores and uterine volumes were determined to evaluate the severity of adenomyosis. Dysmenorrhea improvement and uterine volume were the main outcomes.Results: The VAS scores of all patients reduced from 7.3 (6.0, 8.5) to 0 (0, 0.6) at the 6 months after surgery, which were significantly higher in group 1 compared to other groups (P < 0.05). In groups 1, 2 and 3, there were 14, 7 and 4 patients, respectively, who suffered dysmenorrhea recurrence. The mean recurrent‐free‐survival (RFS) was 51.6 ± 2.4, 58.0 ± 1.2 and 58.3 ± 1.0 months, respectively, which was significantly shorter in group 1 (P < 0.05). The dysmenorrhea recurrences were 26.3%, 6.1%, 5.9% in groups 1, 2 and 3, respectively, at the 36 months, which was significantly higher in group 1 (P < 0.01). Significantly decreased uterine volumes were observed in all patients from 222.2 (147.6, 350.4) to 77.0 (65.9, 94.1) mL (P < 0.05) at the 6 month after surgery.Conclusion: Treatment GnRH‐a and LNG‐IUS after surgery could significantly reduce the recurrence and prolong the RFS. It seemed that the use of LNG‐IUS was beneficial for a lower recurrence in long‐term follow‐up.