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
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Microglia/metabolism*
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Phagocytosis/physiology*
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Rats, Sprague-Dawley
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Neuralgia/physiopathology*
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Early Growth Response Protein 2/metabolism*
;
Male
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Rats
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Spinal Cord/metabolism*
;
Sciatic Nerve/injuries*
2.Facilitation of mucosal healing by estrogen receptor β in ulcerative colitis through suppression of branched-chain amino acid transport and subsequent triggering of autophagy in colonic epithelial cells.
Yilei GUO ; Yanrong ZHU ; Jing ZHANG ; Yue HE ; Mianjiang ZHAO ; Haochang LIN ; Zhifeng WEI ; Yufeng XIA ; Yue DAI
Acta Pharmaceutica Sinica B 2025;15(1):168-187
Colonic mucosal healing is the ultimate goal of ulcerative colitis (UC) treatment, but it remains difficult to realize. Given the higher incidence of UC in males and the beneficial effect of estrogen on UC, we conducted this study to examine the therapeutic potential of estrogen receptor β (ERβ), the primary ER subtype in colon, on mucosal healing in UC. Our study is the first to report that ERβ activation degree was positively correlated with mucosal healing in patients with UC. Furthermore, ERβ activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsy-induced colonic injuries. Mechanistically, ERβ activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport, leading to focal adhesion kinase (FAK) activation. Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration, ultimately facilitating mucosal healing. ERβ -/- colitis mice exhibited impaired mucosal healing compared to wild-type littermates, highlighting the crucial effect of ERβ. Importantly, combination with ERβ-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid, a standard UC treatment agent, against mouse colitis. These findings attest to the crucial role of ERβ activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.
3.Research progress on assessment tools for health behavior motivation in patients with cardiovascular diseases
Zhifeng ZHANG ; Lei LIU ; Yikang XU ; Daqiu WANG ; Jiayu WANG ; Yu TIAN ; Kaiwen ZHAN ; Siqi SUN ; Manman LI
Journal of Shenyang Medical College 2025;27(2):198-201
Health behavior motivation significantly affects the quality of life of patients with cardiovascular diseases.Assessing the level of health behavior motivation can measure the health behavior of individuals,help to promote the participation rate of cardiac rehabilitation,reduce the readmission rate of patients,and promote patients'healthy lifestyles.This article reviews the content,characteristics and application of assessment tools for health behavior motivation of patients with cardiovascular diseases at home and abroad,with the aim of providing references for the development and application of such tools in China,and offering a basis for scientifically assessing their health behavior motivation level and formulating effective strategies to promote health behavior motivation.
4.Research progress on assessment tools for the treatment burden of patients with chronic diseases
Kaiwen ZHAN ; Lei LIU ; Daqiu WANG ; Jiayu WANG ; Yu TIAN ; Manman LI ; Siqi SUN ; Zhifeng ZHANG
Journal of Shenyang Medical College 2025;27(1):74-78
The number of patients with chronic diseases in China has been increasing year by year,followed by the increase of treatment burden.It is particularly important to effectively evaluate the treatment burden of patients with chronic diseases.This paper reviews the main contents,application scope,advantages and disadvantages of the assessment tools for the treatment burden of patients with chronic diseases at home and abroad,so as to provide references and basis for medical staff to reasonably select assessment tools and conduct relevant clinical research.
5.Prevalence and Phylogenetic Analysis of Human Parvovirus B19 among Blood Donors in Lanzhou
Kangle WU ; Weirong WANG ; Shulong YANG ; Weiping FENG ; Deng PAN ; Yi GUO ; Zhifeng ZHANG
Journal of Modern Laboratory Medicine 2025;40(2):59-63
Objective To examine the serological and molecular prevalence as well as genotype characteristics of human Parvovirus B19 blood donors in Lanzhou,and to provide evidence for developing a screening strategy to reduce the risk of blood transfusion transmission.Methods A total of 5 722 blood samples collected from Lanzhou blood donors from April 2023 to October 2023 were tested for B19 DNA using real-time quantitative PCR(qRT-PCR).Additionally,383 samples were screened for anti-B19 IgG and anti-B19 IgM using synchronous enzyme-linked immunoassay(ELISA).Viral load and VP1 sequencing were conducted on the B19 DNA-positive samples and the Neighbor-Joining(N-J)method was used to construct an evolutionary tree for the sequenced samples.Results The prevalence of human Parvovirus B19 DNA,IgG antibody and IgM antibody was 0.47%(27/5 722),25.59%(98/383)and 0.26%(1/383),respectively,and the samples positive for B19 DNA,IgG antibody and IgM antibody were 0.26%(1/383).The co-positivity rate for B19 DNA and IgG antibody was 6.27%(24/383),while the positivity rates for B19 DNA or IgG antibody alone were 0.52%(2/383)and 19.06%(73/383),respectively.Viral loads ranged from 4.24 IU/ml to 5.67×102 IU/ml,all below 104 IU/ml.There was no statistical significance in the positive rate of B19 DNA in gender(χ2=0.86,P=0.35),but there was statistical significance in the positive rate of B19 DNA among all age groups(χ2=8.00,P=0.02).The highest positive rate of B19 DNA was 0.65%in the 18~30 age group.There was statistical significance in the positive rate of B19 IgG antibody in gender(χ2=5.03,P=0.02),but there was no statistical significance in the positive rate of B19 IgG antibody among all age groups(χ2=0.51,P=0.77).The highest positive rate of B19 IgG antibody was 29.09%in the age group of 41 to 60.There was no significant difference in the positive rate of B19 IgM antibody in gender(χ2=2.84,P=0.09).The highest positive rate of B19 IgM was 3.85%in the age group of 18~30 years old.Based on the VP1 sequence,the phylogenetic tree revealed that B19 strains in Lanzhou formed a distinct cladistic lineage within genotype 1,predominantly represented by genotype 1b.Conclusion The prevalence of B19 DNA and IgM antibodies among blood donors in the Lanzhou area is low,and so is the viral load.Therefore the risk of transmitting B19 through blood transfusion is relatively small.Since the prevalence of B19 IgG antibody is high,it is suggested to closely monitor the transmission situation in the area,regularly monitor the prevalence of B19 among blood donors,and track the situation of B19 DNA-positive blood donors to recipients to ensure the safety of clinical blood transfusion.
6.Mechanical properties of solid-liquid biphase fiber-reinforced cartilage in developmental dysplasia of hip patients
Yongchang GAO ; Pengfei CHEN ; Zhenxian CHEN ; Jing WEI ; Zhe DONG ; Hui LI ; Zhifeng ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(21):4439-4444
BACKGROUND:Developmental dysplasia of hip causes groin pain in patients with prolonged activity or standing due to the presence of deformities of the acetabulum and femoral head in terms of structure,size and orientation,and if not effectively treated,patients' normal activities will be severely limited.OBJECTIVE:Finite element model of the hip joint of solid-liquid biphase fiber reinforced cartilage based on FEBio was established to explore the biomechanical properties of the cartilage for patients with developmental dysplasia of hip and the normal hip joint.METHODS:A patient with developmental dysplasia of hip and a normal volunteer were chosen to build their left hip models including left pelvis,left femur,and cartilage attached thereto. The solid-liquid biphase fiber reinforced cartilage of normal hip was verified to be effective. The cartilage equal contact stress,fluid pressure,solid effective stress,and fluid support rate differences between the developmental dysplasia of hip patients hip and the normal one in the case of one leg of static load (2130 N) were compared after establishing finite element models of developmental dysplasia of hip patients.RESULTS AND CONCLUSION:(1) Compared with the finite element results of the normal hip model,the cartilage contact position of developmental hip dysplasia patient hip showed obvious edge contact,the peak contact stress (3.86 Mpa) and peak fluid pressure (3.76 Mpa) were both higher than normal hip model. (2) After 1500 s (stable load-bearing capacity),peak contact stress and peak fluid pressure in both models decreased,but the cartilage contact position of developmental hip dysplasia patient hip moved from the edge of cartilage to the center,and fluid support rate decreased from 97.41% to 91.08%. The fluid support rate in normal hip was decreased by 0.58% from 95.24% to 94.66%. (3) It is indicated that under the physiological load of standing on one leg,the cartilage of developmental dysplasia of hip patients showed obvious edge load,and the decrease of peak contact stress,fluid pressure,and fluid formation rate was greater than that of normal cartilage. Considering the solid-liquid biphasic fiber reinforcement characteristics of cartilage,it is of great clinical significance to evaluate the biomechanical properties of hip cartilage in developmental dysplasia of hip patients,to understand the pathophysiological mechanism of developmental dysplasia of hip,and make preoperative plan.
7.Efficacy of Bulleyaconitine A combined with pregabalin in the treatment of herpes zoster neuralgia and its effects on serum neuropeptide, IL-17, CXCL10 and NF-κB levels
Zhifeng ZHANG ; Wenlu YAN ; Ziwei XIA ; Kemei SHI
Journal of Chinese Physician 2025;27(7):999-1003
Objective:To explore the clinical efficacy of Bulleyaconitine A combined with pregabalin in the treatment of herpes zoster neuralgia (HZN), and its effects on serum neuropeptide, interleukin-17 (IL-17), CXC chemokine ligand 10 (CXCL10), and nuclear factor-κB (NF-κB) levels.Methods:A total of 114 HZN patients admitted to the Second Hospital of Tianjin Medical University from January 2021 to December 2022 were selected and divided into observation group ( n=57) and control group ( n=57) by random number table method. The control group was treated with oral pregabalin capsules, and the observation group was treated with Bulleyaconitine A on the basis of the control group for 4 weeks. The clinical efficacy of the two groups was observed. The Visual Analogue Scale (VAS) score for pain, total score of Pittsburgh Sleep Quality Index (PSQI), total score of The MOS 36 Item Short form Health Survey (SF-36), as well as serum neuropeptide [substance P (SP), neuropeptide Y (NPY), β-endorphin (β-EP)] and IL-17, CXCL10, NF-κB levels were compared between the two groups before and after treatment. The occurrence of adverse reactions in the two groups was recorded. Results:The total effective rate of the observation group [82.46%(47/57)] was significantly higher than that of the control group [64.91%(37/57), P<0.05]. Before treatment, there were no significant differences in VAS score, total PSQI score, and total SF-36 score between the two groups (all P>0.05); after treatment, the VAS score and total PSQI score of both groups were significantly decreased (all P<0.05), the total SF-36 score was significantly increased (all P<0.05), and the above indicators in the observation group were better than those in the control group (all P<0.05). Before treatment, there were no significant differences in serum SP, NPY, and β-EP levels between the two groups (all P>0.05); after treatment, serum SP and NPY levels in both groups were significantly decreased (all P<0.05), serum β-EP levels were significantly increased (all P<0.05), and serum SP and NPY levels in the observation group were lower than those in the control group (all P<0.05), serum β-EP levels were higher than those in the control group ( P<0.05). Before treatment, there were no significant differences in serum IL-17, CXCL10, and NF-κB levels between the two groups (all P>0.05); after treatment, serum IL-17, CXCL10, and NF-κB levels in both groups were significantly decreased (all P<0.05), and serum IL-17, CXCL10, and NF-κB levels in the observation group were lower than those in the control group (all P<0.05). There was no significant difference in the adverse reaction rate between the observation group [7.02%(4/57)] and the control group [12.28%(7/57)] ( P>0.05). Conclusions:Bulleyaconitine A combined with pregabalin has good efficacy and safety in the treatment of HZN, which can effectively reduce the degree of neuropathic pain and improve sleep and quality of life. Its mechanism may be related to further regulating the level of neuropeptide and inhibiting the inflammatory state in the body.
8.Effect of Huangqi-Danggui mixture on neural cell pyroptosis in cerebral ischemia/reperfusion rats
Ruikun WANG ; Weijuan GAO ; Xianming HOU ; Zhifeng XING ; Luyao LIU ; Chengxuan CHAI ; Yi ZHANG
Chinese Journal of Pathophysiology 2025;41(7):1267-1274
AIM:To observe the effects of Huangqi-Danggui mixture(HQDG)on the pyroptosis of brain tis-sues in rats with middle cerebral artery occlusion/reperfusion(MCAO/R),and to explore the mechanism of neuroprotec-tion provided by HQDG.METHODS:Sixty-four SD rats were randomly divided into 4 groups:sham group,model group,HQDG group,and Xuesaitong(XST)group.The infarct volume of brain tissues was observed by 2,3,5-triphenyl-tetrazolium chloride staining,while hematoxylin-eosin staining was used to observe the pathological changes of brain tis-sues.Immunofluorescence was employed to assess the expression of nucleotide-binding oligomerization domain-like recep-tor protein 3(NLRP3),cleaved caspase-1 and gasdermin D(GSDMD)in the ischemic penumbra of brain tissues.The se-rum levels of interleukin-1β(IL-1β)and IL-18 were measured using ELISA.Western blot was used to detect NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),IL-1β and IL-18 in brain tissues.RESULTS:Compared with sham group,the neurological deficit scores of the rats in model group were significantly increased(P<0.01),while those in HQDG and XST groups were significantly reduced compared with model group(P<0.01).The cerebral infarct volume ratio was significantly reduced in HQDG and XST groups compared with model group(P<0.01).The pathological damage of brain tissue in HQDG and XST groups was significantly reduced compared with model group.The positive rates of NLRP3,cleaved caspase-1 and GSDMD in the ischemic penumbra of brain tissues were significantly decreased in HQDG group compared with model group(P<0.01).The expression of pyrop-tosis-related proteins,NLRP3,cleaved caspase-1 and ASC,in the ischemic penumbra of brain tissues was significantly el-evated in model group compared with sham group(P<0.01),and significantly decreased in HQDG group compared with model group(P<0.01).The serum levels of IL-1β and IL-18 were significantly increased in model group compared with sham group(P<0.01),and significantly reduced in HQDG group compared with model group(P<0.01).CONCLU-SION:The HQDG effectively attenuates brain tissue injury in rats with MCAO/R,and its mechanism may be related to the inhibition of neural cell pyroptosis.
9.Human resource in disease control and prevention institutions in Jinhua City
PANG Zhifeng ; WANG Juanjuan ; SHOU Geli ; ZHANG Tao
Journal of Preventive Medicine 2025;37(5):530-535
Objective:
To investigate the personnel allocation, structure, and mobility situation of the disease prevention and control (CDC) institutions in Jinhua City, Zhejiang Province from 2018 to 2024, so as to provide insights into strengthening the construction of the talent team within CDC institutions.
Methods:
Basic information of the personnel in the CDC institutions, Jinhua City were collected through the Basic Information Subsystem of the China Disease Control and Prevention Information System. Composition of age, gender, educational background, major, professional title of the in-service and officially employed personnel, as well as the situation of personnel mobility were analyzed using descriptive methods.
Results:
A total of 10 CDCs were established in Jinhua City by the end of 2024, including 1 municipal CDC and 9 county (city, district) CDCs, with an approved staffing of 672 people and 621 in-service and officially employed staff. Compared with 2018, the approved number of staff positions in the CDC institutions of Jinhua City increased by 21.30% in 2024, and the number of in-service and officially employed staff members increased by 22.73%. From 2018 to 2024, the number of CDC staff per 10 000 permanent residents in the CDC institutions of Jinhua City, the municipal CDC, and the county (city, district) CDCs were 0.764 to 0.932, 0.142 to 0.173, and 0.623 to 0.759, respectively. From 2018 to 2024, the overall male-to-female ratio in both the municipal CDC and the county (city, district) CDCs decreased from 1.04∶1 and 0.84∶1 to 0.95∶1 and 0.75∶1, respectively. In the municipal CDC, the proportion of staff aged 25-<45 years old increased from 57.45% to 69.02%; the proportion of staff with a bachelor's degree or above increased from 79.79% to 93.81%; the proportion of staff majoring in public health increased from 37.23% to 49.56%; the proportions of staff with various professional titles were relatively stable; 51 staff members joined, all of whom had a bachelor's degree or above; 32 staff members left, among whom 24 retired and 6 were admitted to civil service positions or other units. In the county (city, district) CDCs, the proportion of staff aged 22-<35 years old increased from 30.59% to 37.40%; the proportion of staff with a bachelor's degree or above increased from 71.85% to 89.76%; the proportion of staff majoring in public health increased from 46.60% to 54.33%; the proportion of staff with a junior professional title or below increased from 34.47% to 43.50%; 198 staff members joined, and 194 of them had a bachelor's degree or above; 102 staff members left, among whom 67 retired and 28 were admitted to civil service positions or other units.
Conclusions
From 2018 to 2024, the number of in-service and officially employed staff in Jinhua CDC institutions increased the academic qualifications and professional composition continue to improve. There are still problems with the number of CDC staff per 10 000 permanent residents being lower than the standard for the personnel establishment in Zhejiang CDCs, a lack of high-level talents, and insufficient personnel stability.
10.Epidemiological investigation of one imported cholera epidemic in Shenzhen in 2024
ZHANG Sheng ; MA Ziqi ; MA Zhifeng
China Tropical Medicine 2025;25(2):253-
Objective To conduct an epidemiological investigation and analysis on one imported cholera case in Shenzhen in 2024, providing a reference for cholera prevention and control. Methods A cholera case and 86 close contacts in 2024 were investigated using methods of field epidemiological investigation. Real-time RT-PCR was employed for Vibrio cholerae nucleic acid detection and typing of collected specimens, followed by isolation culture, whole genome sequencing and analysis. Results One severe cholera case was confirmed in an Indian businessman, who recovered and was discharged after rescue and rehabilitation. The pathogen was identified as the toxigenic strain of Vibrio cholerae O1 serotype Ogawa, and genetic evolution analysis showed that it had a very close genetic relationship with Vibrio cholerae isolated from multiple countries such as Bangladesh and Pakistan. Among the 86 close contacts under medical observation, no abnormalities were found. A total of 75 close contact specimens and 38 environment smear specimens from epidemic sites were collected, all testing negative. Conclusion This is an imported cholera epidemic originating from India. The sensitivity of medical institutions to monitoring key infectious diseases such as cholera needs to be improved.


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