Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

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OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Objective To investigate the prognosis of patients with triple-negative invasive lobular carcinoma (TN-ILC) undergoing breast-conserving surgery combined with radiotherapy (BCS+RT) versus total mastectomy. Methods A retrospective analysis was performed for 2 386 female patients with TN-ILC who underwent surgery in the SEER database from 2006 to 2018, and the baseline characteristics (age, histological grade, AJCC stage, etc.) were balanced by propensity score matching (PSM, 1∶1, caliper value 0.02), and breast cancer-specific survival (BCSS) and overall survival (OS) were compared by Kaplan-Meier method and COX regression analysis. Results A total of 1 056 pairs of patients were obtained after PSM, and the BCS+RT group had significantly better BCSS and OS than the total mastectomy group (both P<0.001). Stratified analyses showed that BCS+RT had a survival advantage in all subgroups except histologic grade Ⅰ and tumor stage Ⅰ. Multivariate analysis confirmed that BCS+RT was an independent protective factor (BCSS: HR=0.682, OS: HR=0.607, both P<0.001). Conclusions BCS+RT significantly improves survival compared with total mastectomy in patients with TN-ILC, supporting BCS+RT as the preferred treatment strategy for eligible patients.

Objective To investigate the perioperative outcomes and postoperative pregnancy outcomes of patients with intrauterine adhesions(IUA)treated by see-and-treat hysteroscopy and traditional hysteroscopy in transcervical resection of adhesions(TCRA).Methods A retrospective cohort study was performed on 485 patients with moderate-to-severe IUA who met the inclusion criteria and admitted in our hospital from January 2019 to December 2021.According to surgical approaches,the patients were assigned into a see-and-treat mode group and a traditional mode group.After clinical diagnosis(ultrasound and symptoms)of IUA,the patients from the former group received direct hysteroscopic adhesion separation surgery,and those of the latter group were diagnosed by outpatient hysteroscopy first and then hysteroscopic adhesion separation surgery.The perioperative indicators,postoperative three-dimensional transvaginal ultrasound(3D-TVUS)examination related characteristics,postoperative menstrual recovery,postoperative pregnancy outcomes,obstetric related complications,and neonatal outcomes were collected and compared between the 2 groups.Results Among the enrolled 485 patients,there were 277 in the see-and-treat group and 208 in the traditional group.The success rate of surgical treatment was 89.89%in the see-and-treat group and 92.79%in the traditional group,but no statistical difference was seen between them(Chi-square=1.234,P=0.267).3D-TVUS examination displayed that the see-and-treat mode group obtained better improvement of endometrial morphology,uterine morphology and menstruation after operation than the traditional group(P<0.001).The postoperative pregnancy rate was slightly higher in the see-and-treat group than the traditional mode group(58.84%vs 58.17%,P=0.882).However,the see-and-treat mode showed obvious advantage in the postoperative natural pregnancy rate,with a rate of 90.80%,obviously higher than that in the traditional mode group(81.82%,P=0.026).The live birth rate was 70.55%in the see-and-treat mode group,excluding 1 case with ongoing pregnancy in the second trimester and 1 case with ongoing pregnancy in the third trimester,and the rate was 74.38%in the traditional group,excluding 3 cases with ongoing pregnancy in the third trimester,but there was no statistical difference between the 2 groups(P=0.303).In terms of obstetric-related complications,there were 0 cases of blood transfusion during delivery hospitalization in the see-and-treat group,while there were 7 cases in the traditional group(P=0.003).In neonatal outcomes,the rate of transfer to the pediatric department was 10.43%in the see-and-treat mode group and 22.22%in the traditional mode group(P=0.021).For health economics,the see-and-treat hysteroscopy group demonstrated a significant advantage over the traditional hysteroscopy group(P<0.001).There was no significant difference in pain scores between the 2 groups.Conclusion The see-and-treat approach is a safe,feasible,and highly efficient strategy for integrating the diagnosis and treatment of IUA,enabling maximal minimization of surgical trauma while optimizing time and cost efficiency.

Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38～2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.

Objective To explore the symptom clusters in renal transplant recipients and con-struct a concurrent symptom network to identify core symptoms.Methods A total of 343 patients with followed up after renal transplantation were selected as the study subjects.A general information questionnaire and the Chinese version of the Modified Transplant Symptom Occurrence and Symptom Distress Scale were employed to analyze the occurrence of symptoms in patients.In this study,only symptoms with an incidence rate greater than 20％and Spearman correlation coefficient greater than 0.40 between symptom severity and total score were retained.Exploratory factor analysis was used to extract symptom clusters with a factor loading of ≥0.45 as the criterion.The R language was utilized to construct symptom network,based on which core symptoms and bridge symptoms were identified.Results A total of 5 symptom clusters were extracted in this study:the neuro-gastrointestinal symp-tom cluster,the mood-related symptom cluster,the hormone-related symptom cluster,the energy de-ficiency symptom cluster and the vision-related symptom cluster.The core symptoms were anxiety(rs=1.75),mood swings(rs=1.50)and muscle weakness(rs=1.27).The top three symptoms in terms of bridge strength were muscle weakness(rb=0.87),lack of vitality(rb=0.66)and fa-tigue(rb=0.65).Conclusion Multiple symptoms are presented in patients after renal transplanta-tion.Based on the results of symptom network analysis,clinicians can strengthen the assessment of core symptoms and bridge symptoms to develop precise intervention strategies and improve the effectiveness of symptom management.

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Objective To observe the correlation between growth impairment induced by long-term oral glucocorticoids(GC)therapy and the ratio of FGF23/Klotho in children with primary nephrotic syndrome(PNS).Methods A prospective study was conducted on 56 children with GC-sensitive PNS who had discontinued GC therapy for more than 3 months and revisited the Department of Pediatrics of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine between June 2022 and December 2022.After monitoring qualitative and quantitative urine protein levels upon admission,the children with proteinuria relapse were treated with GC(GC group;n=29),while those without relapse did not receive GC treatment(non-GC group;n=27).In addition,29 healthy children aged 3 to prepuberty were selected as the control group.Height,bone age,growth rate,and the FGF23/Klotho ratio were compared among the groups.The correlations of the FGF23/Klotho ratio with height,bone age,and growth rate were analyzed.Results The FGF23/Klotho ratio in the GC group was significantly higher than that in the non-GC group after 1 month of GC therapy(P＜0.05),and the height and bone age growth rates within 6 months were lower than those in the non-GC group(P＜0.05).Correlation analysis showed significant negative correlations between the FGF23/Klotho ratio after 1 month of treatment and the growth rates of height and bone age within 6 months in children with PNS(r=-0.356 and-0.436,respectively;P＜0.05).Conclusions The disturbance in FGF23/Klotho homeostasis is one of the mechanisms underlying the growth impairment caused by long-term oral GC therapy.[Chinese Journal of Contemporary Pediatrics,2024,26(3):269-2741