Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

AIM:We investigated the survival,migration and differentiation abilities of human oligodendro-cyte precursor cells(hOPC)in the brains of mice with vascular dementia(VaD),the effects of hOPC on cerebral white matter,and the underlying mechanisms.METHODS:Mouse VaD model was constructed using the bilateral common ca-rotid artery stenosis method,and the mice were randomly divided into sham,VaD and hOPC groups.Eight weeks after model establishment,the mice in VaD and hOPC groups received equal volume of vehicle(PBS)and hOPC solution,re-spectively,through the corpus callosum.Survival,migration and differentiation of hOPC in the brain were observed by im-munofluorescence staining at 4 and 12 weeks after transplantation.Twelve weeks after transplantation,the effects of hOPC on mouse brain white matter were detected by immunofluorescence staining of myelin basic protein(MBP),myelin-associ-ated glycoprotein(MAG),neurofilament protein 200(NF200)and non-phosphorylated neurofilament H(using monoclo-nal antibody SMI32),and by water maze experiments.Paracrine signaling by hOPC was explored using immunofluores-cence staining for vascular endothelial growth factor(VEGF).RESULTS:The hOPC survived in the brains of VaD mice for 12 weeks,migrated to damaged white matter areas,and partially differentiated into mature oligodendrocytes(approxi-mately 64%).Twelve weeks after transplantation,hOPC significantly increased the fluorescence intensity of MBP,MAG,and NF200(P<0.05 or P<0.01)and decreased the fluorescence intensity of SMI32(P<0.01).The VEGF expression in hOPC-treated mice was significantly higher than that in sham and VaD groups(P<0.01).The difference in water maze test performance between hOPC and sham groups was not statistically significant(P>0.05).The mice in hOPC group had a shorter latency than those in VaD group(P<0.05 or P<0.01),and performed more platform crossings than those in VaD group(P<0.05).CONCLUSION:The hOPC can survive,migrate and differentiate in the brains of VaD mice,attenuate cerebral white matter lesions,and improve cognitive function.These improvements may be attributed to cell replacement and paracrine effects.

AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective To investigate the characteristics and correlation between peak oxygen uptake(VO?peak)and heart rate recov-ery(HRR)during cardiopulmonary exercise test(CPET)in patients with coronary borderline lesions.Methods From January,2022 to January,2024,183 patients with coronary borderline lesions in Beijing Bo'ai Hospital were divided into low cardiorespiratory fitness(LCF)group(n=61),moderate cardiorespiratory fitness(MCF)group(n=62)and high cardiorespiratory fitness(HCF)group(n=60)based on VO?peak.Their characteristics and CPET parameters including VO?peak,exercise-phase heart rate(HR1,HR2,HR3),and post-exercise heart rate recovery(HRR1,HRR2,HRR3)were analyzed.Results After adjusting for age and body mass index,analysis of covariance showed that the peak heart rate,HR1,HR2 and HR3 were the lowest in LCF group(F>5.388,P<0.01).Repeated-measures analysis of variance showed that the inter-and intra-group effects were significant in HRR(F>14.561,P<0.001).Partial correlation analy-sis showed that VO?peak positively correlated with HRR1(r=0.404,P<0.001),HRR2(r=0.379,P<0.001)and HRR3(r=0.425,P<0.001).Conclusion In patients with coronary artery borderline lesions,VO?peak demonstrated a significant inverse correlation with HRR,the lower the VO?peak,the more delays of HRR.

OBJECTIVE To analyze the plasma-entering components of the ethanol extract of Yu-Ping-Feng-San by ultra-per-formance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UPLC-Q-TOF-MS)technology,so as to pro-vide a reference for the study of the pharmacological substances of Yu-Ping-Feng-San.METHODS Male BALB/c mice were ga-vaged with the ethanol extract of Yu-Ping-Feng-San(6.5 g·kg-1),and plasma samples were collected before administration(0 h)and 1,2,4,6,8,and 12 h after administration.The UPLC-Q-TOF-MS technology was used to analyze and identify the components absorbed into the plasma.RESULTS A total of 73 chemical components in the ethanol extract of Yu-Ping-Feng-San were identi-fied,and 26 plasma-entering components were identified in all plasma samples.Among the plasma-entering components,11 compo-nents were from Saposhnikoviae Radix,and 15 components were from Radix Astragali.CONCLUSION The chemical components and plasma-entering components of the ethanol extract of Yu-Ping-Feng-San were analyzed comprehensively,which provides a reference for further clarifying the pharmacological substance basis and mechanism of action of Yu-Ping-Feng-San.

The 2022 World Health Organization classification of renal cell tumors classifies oncocytoma, chromophobe cell carcinoma, and the intermediate forms between the both as oncocytic and chromophobe renal tumors. The intermediate tumors are named other oncocytic tumors of the kidney including oncocytic renal neoplasms of low malignant potential-not otherwise specified, eosinophilic vacuolated tumor and low-grade oncocytic tumor. These tumors are more common in the elderly and they usually show benign or low-invasive clinical courses. Additionally, molecular features provide certain assistance in typing. This paper reviews the evolution of name and summarizes the clinicopathological characteristics, molecular characteristics and the differential diagnosis of oncocytic and chromophobe renal tumors.

AIM:We investigated the survival,migration and differentiation abilities of human oligodendro-cyte precursor cells(hOPC)in the brains of mice with vascular dementia(VaD),the effects of hOPC on cerebral white matter,and the underlying mechanisms.METHODS:Mouse VaD model was constructed using the bilateral common ca-rotid artery stenosis method,and the mice were randomly divided into sham,VaD and hOPC groups.Eight weeks after model establishment,the mice in VaD and hOPC groups received equal volume of vehicle(PBS)and hOPC solution,re-spectively,through the corpus callosum.Survival,migration and differentiation of hOPC in the brain were observed by im-munofluorescence staining at 4 and 12 weeks after transplantation.Twelve weeks after transplantation,the effects of hOPC on mouse brain white matter were detected by immunofluorescence staining of myelin basic protein(MBP),myelin-associ-ated glycoprotein(MAG),neurofilament protein 200(NF200)and non-phosphorylated neurofilament H(using monoclo-nal antibody SMI32),and by water maze experiments.Paracrine signaling by hOPC was explored using immunofluores-cence staining for vascular endothelial growth factor(VEGF).RESULTS:The hOPC survived in the brains of VaD mice for 12 weeks,migrated to damaged white matter areas,and partially differentiated into mature oligodendrocytes(approxi-mately 64%).Twelve weeks after transplantation,hOPC significantly increased the fluorescence intensity of MBP,MAG,and NF200(P<0.05 or P<0.01)and decreased the fluorescence intensity of SMI32(P<0.01).The VEGF expression in hOPC-treated mice was significantly higher than that in sham and VaD groups(P<0.01).The difference in water maze test performance between hOPC and sham groups was not statistically significant(P>0.05).The mice in hOPC group had a shorter latency than those in VaD group(P<0.05 or P<0.01),and performed more platform crossings than those in VaD group(P<0.05).CONCLUSION:The hOPC can survive,migrate and differentiate in the brains of VaD mice,attenuate cerebral white matter lesions,and improve cognitive function.These improvements may be attributed to cell replacement and paracrine effects.