1.EGR2 maintains neuropathic pain by promoting microglial phagocytosis.
Caiyun XI ; Jianxi ZHANG ; Zhifeng HUANG ; Liqiong HE ; Kailu ZOU ; Xiaoping XU ; Qulian GUO ; Bei SUN ; Changsheng HUANG
Journal of Central South University(Medical Sciences) 2025;50(4):586-601
OBJECTIVES:
Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets.
METHODS:
Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2.
RESULTS:
The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2.
CONCLUSIONS
EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals
;
Microglia/metabolism*
;
Phagocytosis/physiology*
;
Rats, Sprague-Dawley
;
Neuralgia/physiopathology*
;
Early Growth Response Protein 2/metabolism*
;
Male
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Rats
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Spinal Cord/metabolism*
;
Sciatic Nerve/injuries*
2.External diaphragm pacing therapy and correlation analysis of trunk balance and respiratory function in stroke patients
Liqiong ZHANG ; Qinglin SUN ; Yedong CHEN
Chinese Journal of Rehabilitation Medicine 2024;39(12):1839-1846
Objective:To observe the enhancement of trunk balance ability,pulmonary function,and diaphragm function in stroke patients after treatment of extemal diaphragm pacing(EDP),and analyze the potential correlation be-tween trunk balance ability and respiratory function metrics.Method:Thirty stroke patients meeting the inclusion criteria were selected from the department of rehabilitation medicine at the first affiliated hospital of Anhui medical university from January 2023 to August 2023.They were randomly divided into the observation group(n=15)and the control group(n=15).The control group re-ceived conventional rehabilitation therapy,while the observation group received EDP treatment in addition to conventional rehabilitation therapy for 4 weeks.Independent sample t-tests and rank-sum tests were used to compare the modified trunk impairment scale(mTIS)scores,forced vital capacity(FVC),forced expiratory volume in 1 second(FEV1),FEV1/FVC change in percentage of vital capacity from sitting to supine position(△VC),diaphragmatic excursion of quiet breath(DE-QB),diaphragmatic excursion of deep breath(DE-DB),and thickening fraction(TF)between the two groups of patients.Pearson correlation analysis was employed to explore the correlations among these indicators.Result:After 4 weeks of treatment,the mTIS,FVC,FEV1,and DE-DB of the control group were significant-ly improved than before(P<0.05).The mTIS,FVC,FEV1,FEV1/FVC,DE-QB,DE-DB,and TF of the ob-servation group were significantly improved than before(P<0.05);Except for DE-QB,the differences in the in-dicators before and after treatment in the observation group were significantly greater than those in the control group(P<0.05).The mTIS scores of all 30 patients both before and after treatment were positively correlated with DE-QB,DE-DB,and TF(P<0.05),while △VC was negatively correlated with mTIS and DE-DB(P<0.05).Conclusion:EDP treatment can promote the recovery of respiratory function and trunk balance in stroke pa-tients.Additionally,the trunk balance ability in stroke patients displays a correlation with diaphragm function,but not with pulmonary function.
3.External diaphragm pacing therapy and correlation analysis of trunk balance and respiratory function in stroke patients
Liqiong ZHANG ; Qinglin SUN ; Yedong CHEN
Chinese Journal of Rehabilitation Medicine 2024;39(12):1839-1846
Objective:To observe the enhancement of trunk balance ability,pulmonary function,and diaphragm function in stroke patients after treatment of extemal diaphragm pacing(EDP),and analyze the potential correlation be-tween trunk balance ability and respiratory function metrics.Method:Thirty stroke patients meeting the inclusion criteria were selected from the department of rehabilitation medicine at the first affiliated hospital of Anhui medical university from January 2023 to August 2023.They were randomly divided into the observation group(n=15)and the control group(n=15).The control group re-ceived conventional rehabilitation therapy,while the observation group received EDP treatment in addition to conventional rehabilitation therapy for 4 weeks.Independent sample t-tests and rank-sum tests were used to compare the modified trunk impairment scale(mTIS)scores,forced vital capacity(FVC),forced expiratory volume in 1 second(FEV1),FEV1/FVC change in percentage of vital capacity from sitting to supine position(△VC),diaphragmatic excursion of quiet breath(DE-QB),diaphragmatic excursion of deep breath(DE-DB),and thickening fraction(TF)between the two groups of patients.Pearson correlation analysis was employed to explore the correlations among these indicators.Result:After 4 weeks of treatment,the mTIS,FVC,FEV1,and DE-DB of the control group were significant-ly improved than before(P<0.05).The mTIS,FVC,FEV1,FEV1/FVC,DE-QB,DE-DB,and TF of the ob-servation group were significantly improved than before(P<0.05);Except for DE-QB,the differences in the in-dicators before and after treatment in the observation group were significantly greater than those in the control group(P<0.05).The mTIS scores of all 30 patients both before and after treatment were positively correlated with DE-QB,DE-DB,and TF(P<0.05),while △VC was negatively correlated with mTIS and DE-DB(P<0.05).Conclusion:EDP treatment can promote the recovery of respiratory function and trunk balance in stroke pa-tients.Additionally,the trunk balance ability in stroke patients displays a correlation with diaphragm function,but not with pulmonary function.
4. Application and effect evaluation of clohexidine wipes in patients with liver transplantation
Mingrong GAO ; Liqiong LI ; Yujun TANG ; Shouzhen CHENG
Chinese Journal of Practical Nursing 2019;35(32):2543-2547
Objective:
To investigate the application of clohexidine wipes in patients after liver transplantation and the effect of infection prevention.
Methods:
A total of 279 patients who received orthotopic liver transplantation in the first affiliated hospital of sun yat-sen university from January 2017 to December 2018 and were transferred to the intensive care department of our hospital after the surgery were selected as subjects. Among them, 145 patients who received liver transplantation between January and December 2017 were selected as the control group. From January to December, 2018, 134 patients after liver transplantation were enrolled as the intervention group, and were treated with clohexidine 2% gluconate wet wipes, and the hospital infection rate, infection rate, multiple drug-resistant bacteria infection rate, bath time consumption, and adverse reaction rate were compared between the two groups.
Results:
The hospital infection rate of the control group was 20.00% (29/145), the infection rate of patients was 37.93%(55/145), the infection rate of multiple drug-resistant bacteria was 25.52%(37/145), and the infection rate of the intervention group was 11.19% (15/134), 24.63% (33/134), 14.93% (20/134). The differences were statistically significant (
5.Effects of hyperbaric oxygen therapy at different time windows after optic nerve injury in rats by F-VEP
Bing LONG ; Liqiong ZHOU ; Dan YAN ; Shengping LUO ; Xu ZHA ; Xia CAO ; Zhang LI ; Xiaoying SUN ; Ji LI ; Yuanping ZHANG
Chinese journal of nautical medicine and hyperbaric medicine 2019;26(2):108-111,115
Objective To observe flash visual evoked potential (F-VEP)after hyperbaric oxygen (HBO) at different time points after traumatic optic nerve injury (TON) in adult rats,so as to explore the optimal time window for HBO therapy.Methods A total of 40 Sprague-Dawley rats were used to establish an optic nerve contusion model,with the left eye as the optic nerve injury eye and the right eye as the sham surgery control eye.In accordance with different HBO intervention time points of the optic nerve contusion model at 1,3,7 and 14 days,and the animals were divided into 5 groups,i.e.the experimental group 1,group 2,group 3,group 4 and the control group,each consisting of 8 rats.In the course of treatment,F-VEP visual changes in the 5 groups were detected at day 3,day 10 and day 20,and therapeutic effects were evaluated.Results When the detected VEP data of the optic nerve-clamped eye in all the control rats were compared with those of the sham surgical eyes,latent time was prolonged and vibration amplitude was obviously decreased,and statistical significance could be found,when comparisons were made between them (P < 0.05).Compared with the F-VEP data of the control group,latent time of the optic nerve-clamped eye in the experimental group 1 at various time points was considerably shortened,and at day 10 and day 20 after treatment,vibration amplitude was significantly increased,all with statistical significance (P < 0.05).However,latent time of the optic nerve-clamped eye in the experimental group 2 at day 10 and day 20 after treatment was obviously shortened,also with statistical significance (P < 0.05),but no statistical significance could be noted in vibration amplitude,when comparisons were made between them (P > 0.05).When compared with the F-VEP data of the control group,no statistical significance could be found in the changes of latent time and vibration amplitude for the experimental group 3 and group 4 (P > 0.05).Conclusion Early HBO treatment could effectively improve F-VEP of the rats with traumatic optic nerve contusion,and after sustainment of optic nerve injury,the early the HBO intervention,the better therapeutic effects would be achieved.
6.Effects of hyperbaric oxygen therapy at different time windows after optic nerve injury in rats by F-VEP
Bing LONG ; Liqiong ZHOU ; Dan YAN ; Shengping LUO ; Xu ZHA ; Xia CAO ; Zhang LI ; Xiaoying SUN ; Ji LI ; Yuanping ZHANG
Chinese journal of nautical medicine and hyperbaric medicine 2019;26(2):108-111,115
Objective To observe flash visual evoked potential (F-VEP)after hyperbaric oxygen (HBO) at different time points after traumatic optic nerve injury (TON) in adult rats,so as to explore the optimal time window for HBO therapy.Methods A total of 40 Sprague-Dawley rats were used to establish an optic nerve contusion model,with the left eye as the optic nerve injury eye and the right eye as the sham surgery control eye.In accordance with different HBO intervention time points of the optic nerve contusion model at 1,3,7 and 14 days,and the animals were divided into 5 groups,i.e.the experimental group 1,group 2,group 3,group 4 and the control group,each consisting of 8 rats.In the course of treatment,F-VEP visual changes in the 5 groups were detected at day 3,day 10 and day 20,and therapeutic effects were evaluated.Results When the detected VEP data of the optic nerve-clamped eye in all the control rats were compared with those of the sham surgical eyes,latent time was prolonged and vibration amplitude was obviously decreased,and statistical significance could be found,when comparisons were made between them (P < 0.05).Compared with the F-VEP data of the control group,latent time of the optic nerve-clamped eye in the experimental group 1 at various time points was considerably shortened,and at day 10 and day 20 after treatment,vibration amplitude was significantly increased,all with statistical significance (P < 0.05).However,latent time of the optic nerve-clamped eye in the experimental group 2 at day 10 and day 20 after treatment was obviously shortened,also with statistical significance (P < 0.05),but no statistical significance could be noted in vibration amplitude,when comparisons were made between them (P > 0.05).When compared with the F-VEP data of the control group,no statistical significance could be found in the changes of latent time and vibration amplitude for the experimental group 3 and group 4 (P > 0.05).Conclusion Early HBO treatment could effectively improve F-VEP of the rats with traumatic optic nerve contusion,and after sustainment of optic nerve injury,the early the HBO intervention,the better therapeutic effects would be achieved.
7. Relationship between inflammatory indexes of amniotic fluid and pregnancy outcome of women with cervical incompetence
Yinglin LIU ; Ziya FENG ; Jianping TAN ; Liqiong ZHU ; Jianping ZHANG
Chinese Journal of Obstetrics and Gynecology 2018;53(8):517-521
Objective:
To investigate the relationship between the level of amniotic fluid inflammatory factor and the pregnancy outcome in patients with cervical incompetence.
Methods:
A retrospective case-control study was conducted. Totally 110 cases of pregnant women were diagnosed as cervical incompetence for cervical dilation at the medical examination in Sun Yat-sen Memorial Hospital of Sun Yatsen University, from January 1st, 2015 to December 31th, 2016. A total of 32 patients (29.1%, 32/110) were performed cervical cerclage. According to their neonatal outcomes, they were divided into live infant group (23 cases, 72%) and dead infant group (9 cases, 28%) . The demographic and clinical data of two groups were analyzed and compared.
Results:
The mean peripheral blood leucocyte counts, the median amniotic tumor necrosis factor-α (TNF-α) and the median interleukin-8 (IL-8) level of two groups were (10.5±2.8) ×109/L vs (13.6±3.1) ×109/L, 23.80 ng/L (14.9-85.5 ng/L) vs 379.00 ng/L (70.2-418.5 ng/L) , and 3 354 ng/L (1 020-7 500 ng/L) vs 7 500 ng/L (4 210-7 500 ng/L) respectively. The differences were statistically significant (all
8.Meta analysis of incidence of postoperative complications for the modified posterior sagittal anorectoplasty treatment of intermediate or high anorectal malformations.
Liqiong DUAN ; Hongxia REN ; Xiaobing SUN
Chinese Journal of Gastrointestinal Surgery 2016;19(12):1400-1405
OBJECTIVETo evaluate the incidence of postoperative complications of children with intermediate or high anorectal malformations treated by one-stage modified posterior sagittal anorectoplasty(PSARP) by meta-analysis.
METHODSCases with intermediate or high anorectal malformations treated by one-stage modified PSARP nearly a decade at home and abroad were collected by searching in Wanfang Data, CNKI, and PubMed database, then all the papers that recorded the number of cases of postoperative complications were screened out according to inclusion and exclusion criteria. Meta package in RevMan 3.2.5 software was used to perform the meta analysis for rate, and logit conversion method was applied to calculate the merger of the rates. Firstly, heterogeneity inspection was carried out. If the result was P>0.05, it was the homogeneity between the instructions included in the literatures, the fixed effect model was chosen. If the results was P<0.05, the random effect model was chosen. Then rank correlation test was used to estimate the number of research to evaluate publication bias. If P was 0.05 or less, the difference was statistically significant.
RESULTSThirteen related articles were selected and added up to 566 cases with intermediate or high anorectal malformations treated by one-stage modified PSARP. The merged rate of the complications was 28%(95%CI: 19% to 40%). The three highest rate of complications were 8%(95%CI:4% ~ 14%) of corrupt dung, 7%(95%CI:5% ~11%)of fecal incontinence and 5%(95%CI:3% ~ 10%) of rectal mucosa prolapse.
CONCLUSIONThe most common postoperative complications of children with intermediate or high anorectal malformations treated by one-stage modified PSARP are rectal corrupt dung and fecal incontinence.
9.Application of nested PCR in P1-RFLP for genotyping Mycoplasma pneumoniae strains
Guanhua XUE ; Liqiong WANG ; Chao YAN ; Yanling FENG ; Hanqing ZHAO ; Shaoli LI ; Hongmei SUN
Chinese Journal of Microbiology and Immunology 2014;34(2):141-145
Objective To evaluate the efficiency of using nested PCR in restriction fragment length polymorphism analysis (P1-RFLP) for genotyping Mycoplasma pneumonia (M.pneumonia) in clinical specimens.Methods Based on the gene sequence of RepMp4 and RepMp2/3 in P1 gene of reference strains M129 (type 1) and FH (type 2),two sets of inner primers were designed with a HaeⅢ restriction enzyme site (GGCC).The nested PCR was set up to detect the target DNA in clinical specimens.The amplification products were mixed and digested with Hae Ⅲ enzyme.The genotypes were analyzed by comparing with various restriction maps and the results were verified by sequencing analysis.The concentration of DNA extracted from standard and clinical strains were detected by ten-fold dilution to evaluate the sensitivity of nested PCR-P1-RFLP and P1-RFLP.M.pneumonia-positive specimens isolated from Beijing in 2012 were analyzed by the nested PCR-P1-RFLP and the results were compared with those by P1-RFLP analysis.Results The nested PCR-P1-RFLP could effectively genotype M.pneumonia in clinical specimens and the results were consistent with those by sequencing analysis.The sensitivity of new assay was 103 times higher than that of the original P1-RFLP.Of the 115 M.pneumoniae positive clinical specimens,97.4% (112/115) were type 1 and the rest were type 2.Conclusion The nested PCR-P1-RFLP shows high efficiency for genotyping of M.pneumonia in clinical specimens.It might be useful for the surveillance of M.pneumoniae infection.
10.Simultaneous Determination of Five Saponins in Yao-Bi-Tong Capsules by QAMS
Baidong DAI ; Liqiong SUN ; Yanjing LI ; Gang DING ; Xin LI ; Zhenzhong WANG ; Yuan BI ; Wei XIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2014;(10):2227-2232
This study was aimed to establish a quality evaluation method, quantitative analysis of multi-components with a single-marker (QAMS) to determine the contents of five saponins in Yao-Bi-Tong (YBT) capsules. Ginseno-side Rg1 was used as the internal standard; the relative correction factor (RCF) of notoginsenoside R1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd were calculated and evaluated. The contents of 5 saponins were determined by the external standard method and QAMS, respectively. Rationality, feasibility and repeatability of the QAMS method were verified by comparing the results obtained from two different methods. The results showed that RCFs of notoginsenoside R1, ginsenoside Re and ginsenoside Rb1 to ginsenoside Rg1 against YBT capsules were 0.999, 1.228, 0.990 and 1.094, respectively, indicating good reproducibility. These results of two methods had no significant dif-ference. It was concluded that the QAMS method can be accurately, rapidly and reasonably used as a new quality assessment model for ginsenosides in YBT capsules.

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