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

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Objective This study compared the effects of intraoperative intercostal nerve block(ICNB)and preoperative ultrasound-guided paravertebral block(US-PVB)on postoperative complications in patients undergoing thoracoscopic lung surgery.Methods Data from 240 patients who underwent video-assisted thoracoscopic lung surgery under general anesthesia between January 2019 and December 2020 was retrospectively collected.These patients either received intraoperative intercostal nerve block(ICNB)(202 cases)or pre-operative ultrasound-guided paravertebral block(US-PVB)(38 cases).The incidence rates of overall postoperative complications,postoperative pulmonary complications,postoperative cardiac complications,postoperative cerebral complications,other postoperative complications,remedial analgesia requirement in the PACU,intraoperative fentanyl consumption,postoperative oral morphine equivalent(OME),perioperative OME,duration of postoperative drainage tube,postoperative ICU stay,and postoperative hospital stay were compared between the ICNB group and the US-PVB group.Univariate and multivariate regression were used to analyze the effects of different analgesia methods on postoperative complicationsResults There was no statistically significant difference in postoperative overall complications between the ICNB group and the US-PVB group(P＞0.05).In the univariate analysis,no significant difference was found in the overall postoperative complications between the ICNB group(16.3％)and the US-PVB group(13.2％)(OR=0.642,95％CI 0.239-1.786;P=0.404.Multivariate analysis also did not reveal any differences between the two groups(OR=0.843,95％CI 0.299-2.377;P=0746).For the analysis of secondary outcomes,according to multivariate analysis,there was no significant difference between the two groups in postoperative pulmonary complications,postoperative cardiac complications,other postoperative complications,remedial analgesia requirement in the PACU,intraoperative fentanyl consumption,postoperative OME,perioperative OME,duration of postoperative drainage tube,postoperative ICU stay or postoperative hospital stay(P＞0.05).Conclusion In this study,we found no difference in postoperative complications between intraoperative ICNB and preoperative US-PVB.

Objective:To investigate the effects of 0.1% prednisolone acetate eye drops on the intraoperative pain and expression levels of inflammatory factors in hepatitis B virus (HBV) carriers undergoing cataract surgery.Methods:A randomized single-blind controlled study was adopted.Thirty-six cataract patients diagnosed as HBV carriers in Beijing Tongren Hospital Affiliated to Capital Medical University from November 2021 to August 2023 were enrolled.All patients were scheduled to underwent phacoemulsification combined with intraocular lens implantation.The patients were randomly divided into prednisolone acetate group and control group using the random number table method, with 18 cases in each group.The two groups used 0.1% prednisolone acetate eye drops combined with 0.5% levofloxacin eye drops and 0.3% sodium hyaluronate eye drops combined with 0.5% levofloxacin eye drops for 3 days before the operation according to grouping, respectively.During cataract surgery, aqueous humor samples were collected, and cytokines in the samples were detected using the human cytokine antibody array detection technology.The degree of intraoperative pain of patients was evaluated using the Wong-Baker Scale and the intraoperative pain manifestation record form.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TREXKY2017-018).Written informed consent was obtained from each subject.Results:In the aqueous humor samples of patients in the prednisolone acetate group, the expressions of inflammatory factors such as tumor necrosis factor-β, monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-1 receptor antagonist were lower than those in the control group, and the differences were statistically significant ( t=-2.385, -2.286, -2.208, -2.134; all at P<0.05).The proportion of patients with obvious pain in the prednisolone acetate group was 16.7%(1/18), which was significantly lower than 61.1%(11/18) in the control group ( χ2=-2.697, P<0.05).The intraoperative pain score of patients in the prednisolone acetate group was 1(1, 2) points, which was lower than 2(1, 2) points in the control group, and the difference was statistically significant ( Z=-2.902, P<0.05). Conclusions:Preoperative use of prednisolone acetate eye drops for anti-inflammatory intervention can reduce the expression of inflammatory factors in patients' aqueous humor and mitigate the intraoperative pain during cataract surgery in HBV carriers.

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

In recent years,fluorescent probes have been widely valued due to the advantages of simple preparation,low cost,high sensitivity and real-time detection,and have shown important application value in the medical field.Meanwhile,the application of fluorescent probes in oral biofilms is becoming more and more widespread.This paper reviews the progress of the application of flu-orescent probe in oral biofilms on biostructures and abiostructures,as well as the prospect of their future.