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Tumour‐associated macrophages (TAMs) abundantly infiltrate high‐grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)‐differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte‐derived TAM (Mo‐TAM) and microglia‐derived TAM (Mg‐TAM) clusters across glioblastoma‐IDH‐wild type and astrocytoma‐IDH‐mutant‐grade 4 (Astro‐IDH‐mut‐G4). Single‐cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro‐IDH‐mut‐G4. Cell clustering, single‐cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM‐cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro‐IDH‐mut‐G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg‐TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg‐TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset‐specific markers identified spatial enrichment of distinct TAM clusters at peri‐vascular/necrotic areas in tumour parenchyma or at the tumour–brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo‐TAM‐inflammatory clusters, whereas Astro‐IDH‐mut‐G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH‐differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Objective: To determine whether electroacupuncture (EA) or moxibustion-like stimulation (MLS) can affect the cutaneous and/or systemic hypothalamic–pituitary–adrenal (HPA) axes. Methods: Rats were divided into Control, EA, 37°C MLS and 43.5°C MLS groups. EA and MLS were performed at bilateral ST36 or LI4. The expression of corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH) and the glucocorticoid receptor (GR) was detected in local cutaneous tissues at the site of ST36 and LI4 by immunohistochemical staining. In addition, levels of CRF, ACTH and corticosterone (CORT) in cutaneous tissue and plasma were determined. Results: Cutaneous expression of CRF, ACTH and GR significantly increased after EA at ST36, while only GR increased after 43.5°C MLS at ST36. The results of EA and MLS at LI4 were in parallel with those at ST36. In plasma, compared with the control group, the level of CORT increased after EA at ST36, while both ACTH and CORT were markedly increased after 43.5°C MLS. For LI4, plasma CRF and CORT increased after EA, while the levels of all three hormones increased following 43.5°C MLS. Notably, compared with the effect of EA, 43.5°C MLS at ST36 produced a more substantial increase in plasma CORT, and 43.5°C MLS at LI4 induced a more dramatic increase in plasma CRF and CORT. Conclusion: Both EA and 43.5°C MLS can activate the cutaneous and systemic HPA axes of the rat. EA tended to activate the local cutaneous HPA, while 43.5°C MLS was more likely to activate the systemic HPA axis. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of electroacupuncture (EA) on pain behavior, synovial inflammatory response and demyelination of saphenous nerve in the rats modeled with knee osteoarthritis (KOA) and explore the effect mechanism of EA for reliving allodynia., Methods: Eighty-four male SD rats were randomly divided into a control group, a model group and an EA group, 28 rats in each one. Intra-articular injection of sodium monoiodoacetate (MIA) was administered in right knee joint of each rat in the model group and the EA group to establish the KOA model. In the EA group, separately, on day 5, 7 and 9 after modeling, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave (2 Hz/15 Hz), 1 mA in current intensity, for 30 min in one intervention, once a day, and 3 interventions were required. On the 9th day after modeling, the weight-bearing rate was calculated for the affected limbs of the rats in each group, the synovial morphological changes were observed using HE and Masson staining, flow cytometry was adopted to detect the synovial immunocyte counts, and MSD multi-spot assay was used to detected the synovial inflammatory cytokine content. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was observed in each group and the ultrastructure of the saphenous nerve was observed under transmission electron microscopy., Results: On the 9th day after modeling, compared with the control group, the weight-bearing rate of the affected limb was reduced ( P <0.01), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis occurred in the affected limb; the counts of synovial CD11b + cells and M1 macrophages (CD11b + CD86 + ) were increased ( P <0.01), the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, IL-10 and IL-13 in the synovial tissue were elevated ( P <0.01, P <0.05) for the rats of the model group. Compared with the model group, the weight-bearing rate of the affected limb was increased ( P <0.05), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis were mitigated, the counts of CD11b + cells and M1 macrophages (CD11b + CD86 + ) in the synovial tissue, and the contents of TNF-α and IL-6 were reduced ( P <0.01, P <0.05) in the EA group. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was reduced in the model group when compared with the control group ( P <0.01), and it was increased in the EA group when compared with the model group ( P <0.05). Besides, in the model group, obviously, the myelin sheath structure was destroyed, the myelin layer was disintegrated and loosened, the axon was extruded or the layer thicken and cracked. Compared with the model group, the injury of saphenous nerve was alleviated remarkably in the EA group., Conclusion: The intervention with EA may attenuate the synovial inflammatory response and the injury of saphenous nerve in the affected limb of the rat with KOA, so that the spontaneous pain during the synovial inflammatory response stage and allodynia at the later stage are relieved.

Objective: To investigate the mechanism of electroacupuncture (EA) "Zusanli" (ST36) in delaying colon "inflammation-cancer transformation" in mice by anti-inflammatory., Methods: C57BL/6J mice were randomly divided into normal, model and EA groups, with 12 mice in each group. The mouse model of colorectal cancer (CRC) was established by intrape-ritoneal injection of azomethane (AOM) and feeding dextran sodium sulfate (DSS). At the beginning of the 2 nd cycle, EA was applied to bilateral ST36 for 30 min once every other day for 12 times. The number of colon tumors in each group was observed, and the weight and length of colon were recorded. The contents of interleukin (IL)-1β, IL-6, IL-17A, IL-23, tumor necrosis factor (TNF)-α and CXC chemokine ligand 1 (CXCL1) of serum and colon tissue were detected by MSD multifactorial assay.The apoptosis of local cells in colon tumor was observed by TUNEL staining. Cell proliferation in colon tumor was observed by immunohistochemistry., Results: Compared with the normal group, the colon length was significantly shortened ( P <0.05) and the colon mass was significantly increased ( P <0.001) in the model group, the contents of IL-1β, IL-6, TNF-α, IL-17A and CXCL1 of serum and colon tissue were significantly increased ( P <0.05, P <0.01, P <0.001), and the content of IL-23 was increased in colon tissue ( P <0.05) in the model group. Compared with the model group, the colon mass was decreased ( P <0.05) and the contents of IL-1β, IL-6, TNF-α and IL-17A in serum were decreased ( P <0.05), while the contents of IL-17A, CXCL1 and IL-23 in colon tissue were decreased ( P <0.05) in the EA group, the percentage of local apoptotic cells in the EA group was increased ( P <0.001), the percentage of PCNA positive cells was decreased ( P <0.001), the number of tumors and the tumor volume were significantly decreased ( P <0.01, P <0.05). The contents of IL-6, TNF-α, IL-17A and IL-23 in serum of CRC mice were positively correlated with tumor burden ( P <0.05).The contents of IL-1β, TNF-α, CXCL1 and IL-23 in colon tissue of CRC mice were positively correlated with tumor burden ( P <0.05)., Conclusion: Electroacupuncture at ST36 can inhibit the inflammatory response of AOM/DSS inflammatory associated CRC mice and delay the "inflammation-cancer transformation" of colon.