1.Mechanism of p62-NEK7-GSDMD pyroptosis axis in pathogenesis of gouty arthritis in mice
Aihua WANG ; Jingyue GAO ; Wei LIU ; Siwei WANG ; Yuanhao WU ; Yue JIN
Chinese Journal of Pathophysiology 2025;41(11):2175-2183
AIM:To investigate the regulatory role and molecular mechanisms of the p62-NIMA(never in mi-tosis gene A)-related kinase 7(NEK7)-gasdermin D(GSDMD)-mediated pyroptosis axis in a mouse model of gouty arthri-tis.METHODS:C57BL/6 mice were randomly divided into control group,model group,and colchicine group(n=5 per group).Conditional knockout mouse models of p62,GSDMD,and p62-GSDMD were constructed and assigned to p62-/-group,GSDMD-/-group,and p62-/--GSDMD-/-group,respectively(n=5 per group).The gouty arthritis model was in-duced by monosodium urate crystal injection into the ankle joint in all groups except control.The colchicine group re-ceived oral colchicine pretreatment for 3 days prior to MSU injection,continuing for 5 days total.Ankle joint swelling was measured using a vernier caliper at 0,6,12,24,and 48 hours post-injection.Serum levels of p62,GSDMD,caspase-1,interleukin-1β(IL-1β),and IL-18 were quantified by ELISA.Immunohistochemistry staining was performed to assess nu-cleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein contain-ing a caspase recruitment domain(ASC),cleaved caspase-1,and IL-1β expression in joint tissues.Western blot was con-ducted to detect protein expression of p62,GSDMD,NLRP3,ASC,cleaved caspase-1,and IL-1β in mouse ankle joints,while RT-qPCR was used to measure mRNA expression of p62,NEK7,GSDMD,NLRP3,caspase-1 and IL-1β.RE-SULTS:Serum p62 levels and p62 protein and mRNA expression in ankle joints were significantly elevated in the model group.Following p62 gene knockout,the protein expression of NLRP3,ASC,caspase-1,and IL-1β in ankle joints showed a marked increase.Both GSDMD-/-and p62-/--GSDMD-/-groups exhibited attenuated ankle joint swelling,reduced serum levels of caspase-1,IL-1β,and IL-18,along with downregulated expression of p62,NLRP3,ASC,caspase-1,and IL-1β at both mRNA and protein levels in ankle joints.The NEK7 mRNA expression was similarly suppressed in these groups.CONCLUSION:Our findings demonstrate that MSU crystals activate macrophages through the coordinated action of p62,NEK7,and GSDMD,triggering NLRP3 inflammasome-mediated pyroptosis and ultimately promoting joint inflammation in gout mice.The p62-NEK7-GSDMD axis represents a critical regulatory mechanism in the canonical pyrop-tosis signaling pathway.
2.Mechanism of p62-NEK7-GSDMD pyroptosis axis in pathogenesis of gouty arthritis in mice
Aihua WANG ; Jingyue GAO ; Wei LIU ; Siwei WANG ; Yuanhao WU ; Yue JIN
Chinese Journal of Pathophysiology 2025;41(11):2175-2183
AIM:To investigate the regulatory role and molecular mechanisms of the p62-NIMA(never in mi-tosis gene A)-related kinase 7(NEK7)-gasdermin D(GSDMD)-mediated pyroptosis axis in a mouse model of gouty arthri-tis.METHODS:C57BL/6 mice were randomly divided into control group,model group,and colchicine group(n=5 per group).Conditional knockout mouse models of p62,GSDMD,and p62-GSDMD were constructed and assigned to p62-/-group,GSDMD-/-group,and p62-/--GSDMD-/-group,respectively(n=5 per group).The gouty arthritis model was in-duced by monosodium urate crystal injection into the ankle joint in all groups except control.The colchicine group re-ceived oral colchicine pretreatment for 3 days prior to MSU injection,continuing for 5 days total.Ankle joint swelling was measured using a vernier caliper at 0,6,12,24,and 48 hours post-injection.Serum levels of p62,GSDMD,caspase-1,interleukin-1β(IL-1β),and IL-18 were quantified by ELISA.Immunohistochemistry staining was performed to assess nu-cleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein contain-ing a caspase recruitment domain(ASC),cleaved caspase-1,and IL-1β expression in joint tissues.Western blot was con-ducted to detect protein expression of p62,GSDMD,NLRP3,ASC,cleaved caspase-1,and IL-1β in mouse ankle joints,while RT-qPCR was used to measure mRNA expression of p62,NEK7,GSDMD,NLRP3,caspase-1 and IL-1β.RE-SULTS:Serum p62 levels and p62 protein and mRNA expression in ankle joints were significantly elevated in the model group.Following p62 gene knockout,the protein expression of NLRP3,ASC,caspase-1,and IL-1β in ankle joints showed a marked increase.Both GSDMD-/-and p62-/--GSDMD-/-groups exhibited attenuated ankle joint swelling,reduced serum levels of caspase-1,IL-1β,and IL-18,along with downregulated expression of p62,NLRP3,ASC,caspase-1,and IL-1β at both mRNA and protein levels in ankle joints.The NEK7 mRNA expression was similarly suppressed in these groups.CONCLUSION:Our findings demonstrate that MSU crystals activate macrophages through the coordinated action of p62,NEK7,and GSDMD,triggering NLRP3 inflammasome-mediated pyroptosis and ultimately promoting joint inflammation in gout mice.The p62-NEK7-GSDMD axis represents a critical regulatory mechanism in the canonical pyrop-tosis signaling pathway.
3.Anterior temporal lobectomy improved mood status and quality of life in Chinese patients with mesial temporal lobe epilepsy: a single-arm cohort study
Song LU ; Min CHU ; Xian WANG ; Yating WU ; Yue HOU ; Aihua LIU
Chinese Medical Journal 2023;136(4):407-414
Background::Many studies have emphasized that selective resection of epileptic lesions in temoral lobe is associated with better preservation of cognition function; whether this applies to patients with refractory mesial temporal lobe epilepsy (MTLE) remains unknown. The objective of this study was to evaluate changes in cognitive functions, mood status, and quality of life after anterior temporal lobectomy in patients with refractory MTLE.Methods::This single-arm cohort study assessed cognitive function, mood status, and quality of life, as well as electroencephalography findings, in patients with refractory MTLE who underwent anterior temporal lobectomy at Xuanwu Hospital from January 2018 to March 2019. Pre- and post-operative characteristics were compared to evaluate the effects of surgery.Results::Anterior temporal lobectomy significantly reduced the frequencies of epileptiform discharges. The overall success rate of surgery was acceptable. Anterior temporal lobectomy did not result in significant changes in overall cognitive functions (P > 0.05), although changes in certain domains, including visuospatial ability, executive ability, and abstract thinking, were detected. Anterior temporal lobectomy resulted in improvements in anxiety and depression symptoms and quality of life. Conclusions::Anterior temporal lobectomy reduced epileptiform discharges and incidence of post-operative seizures as well as resulted in improved mood status and quality of life without causing significant changes in cognitive function.
4. Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China
Duan WANG ; Xiuli JU ; Feng XIE ; Yan LU ; Feiyu LI ; Huihong HUANG ; Xiuling FANG ; Yuanjun LI ; Jianyun WANG ; Bin YI ; Juxia YUE ; Jing WANG ; Lingxiao WANG ; Bo LI ; Yi WANG ; Bingping QIU ; Zhiyuan ZHOU ; Keliang LI ; Jianhua SUN ; Xuegong LIU ; Guodong LI ; Yongjun WANG ; Aihua CAO ; Yanni CHEN
Chinese Journal of Pediatrics 2020;58(4):E011-E011
Objective:
To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China.
Methods:
A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong.
Results:
The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (
5.Application value of group psychological intervention combined with narrative nursing in the psychological adjustment of patients with colorectal cancer
Suhong LIN ; Shan LANG ; Aihua YUE
Chinese Journal of Modern Nursing 2020;26(27):3808-3812
Objective:To explore the application value of group psychological intervention combined with narrative nursing in the psychological adjustment of patients with colorectal cancer.Methods:Totally 52 patients with colorectal cancer who were admitted into the First Affiliated Hospital of Zhengzhou University from February 2018 to June 2019 were selected by convenient sampling and divided into the control group ( n=26) and the observation group ( n=26) according to the random number table. Patients in the control group received routine care, while patients in the observation group received group psychological intervention combined with narrative nursing. Upon admission and one week after surgery, the nursing staff conducted an in-hospital survey and distributed the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) , the Chinese version of the Ostomy Adjustment Inventory-20 (OAI-20) and the Perceived Derogation-Discrimination Scale (PDDS) to evaluate the patients. The negative emotions, psychosocial adjustment and stigma were compared between the two groups. Results:Before intervention, there was no statistically significant difference in the levels of negative emotions, psychosocial adjustment and stigma between the two groups ( P>0.05) . After intervention, the HAMA, HAMD and PDDS scores of the observation group were lower than those of the control group, and the OAI-20 score was higher than that of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Group psychological intervention combined with narrative nursing is of great significance in the psychological adjustment of patients with colorectal cancer, which can eliminate their stigma and ameliorate their negative emotions, and is worth promoting in clinical practice.
6.A case analysis of conservative treatment of a cesarean scar pregnancy combined with uterine apoplexy
Yue WU ; Aihua WANG ; Chaohong HAN ; Xin FENG
Journal of Pharmaceutical Practice 2016;34(6):552-555
Objective To study the conservative treatment for cesarean scar pregnancy (CSP) with proper medications . Methods One case of CSP with uterine apoplexy was reported .Medication regimens were illustrated as the conservative treat-ments for the patient with β-HCG>20 000 IU/L ,in whom surgery was contraindicated .Results After two times of uterine artery embolization and chemotherapy (MTX50 mg) ,followed by three times of MTX50 mg cervical injection combined with oral mifepristone ,serumβ-HCG dropped to normal level and no adverse reactions were observed .Conclusion Clinical pharma-cists could strengthen the safety and effectiveness of rational drug use by participating in the integrated pharmacy care .
7.Effects of motivational interview on self-efficacy and health related behaviors in patients after coronary artery bypass grafting
Aixue YUE ; Xiaofang WANG ; Haihua ZHU ; Aihua CHEN ; Qinghong LIU ; Fangyun ZHOU
Chinese Journal of Modern Nursing 2016;22(6):783-786,787
Objective To discuss the impacts of motivational interviewing health education on the self-efficacy and the impacts of health-related behaviors in patients after coronary artery bypass grafting (CABG). Methods A total of 84 patients after the first CABG were selected in Department of Cardiac Surgery of Shanghai East Hospital. These patients were divided into 42 cases of intervention group and 42 cases of control group. Conventional methods of health education were used in the control group, and the patients of intervention group received motivational interview plans. After 6 months, self-efficacy and healthy behavior were evaluated in these patients. Results Before the intervention, the scores of self-efficacy and health related behavior′s difference were not statistically significant (P>0. 05); after 6 months intervention, the score of self-efficacy, diet, medication management, movement, stress coping and health related behavior score respectively (47. 5 ± 6. 3), (33. 5 ± 3. 3), (39. 2 ± 4. 3), (14. 0 ± 4. 2), (15. 7 ± 3. 8) (93. 1 ± 6. 2) in the intervention group were higher than that of the control group, except exercise and stress coping dimensions, there were significant differences between the two groups (P <0. 05). Conclusions Motivational interview health education can increase the self-efficacy and health-related behaviors in patients after CABG.
8.The relationship between the prevalence of isolated systolic hypertension and the stages of chronic kidney disease in chronic kidney disease outpatient clinic
Haixia BU ; Litao CHENG ; Aihua ZHANG ; Tao WANG ; Yue WANG ; Minhua FAN
Chinese Journal of Nephrology 2015;31(1):19-23
Objective To investigate the relationship between the prevalence of isolated systolic hypertension (ISH) and the stages of chronic kidney disease (CKD) in chronic kidney disease outpatient clinic.Methods CKD patients of stages 1,2,3,4 and 5 were recruited (n=626).Based on office systolic pressure (SBP) and diastolic pressure (DBP),they were classified into four subtypes:normotension (< 140/90 mmHg),isolated diastolic hypertension (IDH,SBP < 140 mmHg and DBP ≥ 90 mmHg),ISH (SBP≥ 140 mmHg and DBP < 90 mmHg) and systolic-diastolic hypertension (SDH,SBP≥140 mmHg and DBP≥90 mmHg).Results The control rate of blood pressure was 86.4%,75.6%,65.3%,51.0% and 37.0% at CKD stage 1,2,3,4 and 5,respectively,which decreased with the advancement of CKD.There was a stepwise increase in the prevalence of ISH (0,9.2%,23.9%,28.6% and 37.0% at CKD stage 1,2,3,4 and 5,respectively) and SDH (4.5%,8.4%,8.0%,17.3%,21.9% at CKD stage 1,2,3,4 and 5,respectively).Logistic regression analysis showed that age,diabetes and CKD stages were independent predictors of ISH.Compared with CKD stage 1-2,CKD stage 3,4 and 5 showed 2.388,2.697 and 5.980 folds risk in developing ISH.Conclusion The prevalence of ISH increases correspondingly with the advancement of stages of CKD,which may partially contribute to the increased cardiovascular mortality during the progress of CKD.
9.The study of aortic stiffness in different hypertension subtypes in patients with chronic kidney disease
Haixia BU ; Litao CHENG ; Aihua ZHANG ; Tao WANG ; Yue WANG ; Minhua FAN
Chinese Journal of Nephrology 2014;30(4):254-261
Objective To investigate whether there is any difference in aortic stiffness among different hypertension subtypes in patients with chronic kidney disease.Methods Six hundred and twenty-six patients with chronic kidney disease were included in the present analysis.They were classified into four groups:normotension (n =391) with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg; isolated systolic hypertension (ISH,n =141) with SBP≥ 140mmHg and DBP < 90 mmHg; isolated diastolic hypertension (IDH,n =25) with SBP < 140 mmHg and DBP≥ 90 mmHg; systolic-diastolic hypertension (SDH,n =69) with SBP≥ 140 mmHg and DBP≥ 90mmHg.Aortic stiffness was assessed by pulse pressure and pulse wave velocity.Results The IDH group had lower mean age than the other groups(P < 0.01).The percentage of diabetes in the ISH group was higher than that in the other groups.The comparison of aortic stiffness showed that the ISH and SDH groups had higher aortic stiffness than the normotension and IDH groups (P < 0.01),but no significant difference in aortic stiffness was observed neither between the normotension and IDH groups nor between ISH and SDH groups.Conclusion Aortic stiffness is significantly different among different hypertension subtypes,which may be an underlying cause for the different cardiovascular mortality among the hypertension subtypes.
10.In vitro assessment of increasing cytotoxicity of Veratrum nigrum induced by Panax ginseng
Yali LU ; Aihua SUN ; Yue GAO ; Ying JIANG
Military Medical Sciences 2014;(4):285-289
Objective To compare the potential cytotoxicity induced by Veratrum nigrum coadministered with Panax ginseng, and to provide experimental evidence on the mode of herb-herb interaction based on human liver drug metabolizing enzymes.Methods The effect of V.nigrum and coadministration on cultured human hepatoma (HepG2) cells was investi-gated by detecting morphological changes , cell viability , cytomembrane integrity and apoptosis after the cells were treated for 24 h.The mRNA expression levels of drug metabolizing enzymes influenced by P.ginseng were determined by real-time quantitative reverse-transcriptase polymerase chain reaction .Results V.nigrum coadministered with P.ginseng had a better inhibitive effect on the growth of HepG2 cells at the IC50value of (15.18 ±1.03) mg/ml than at the value of IC50 (21.46 ±1.10) mg/ml of V.nigrum.Coadministration more significantly raised the LDH level in cell culture medium than at the same dose of V.nigrum.Moreover, in coadministration group, compared with the same dose of V.nigrum,the total apoptosis and necrosis of HepG2 cells were significantly increased .P.ginseng had effect on the expression of CYP3A4, CYP1A1, CYP1A2, CYP2B6 and CYP2E1 mRNA.Conclution Compatibility of medicines in a prescription also has herb-herb interactions based on drug metabolizing enzymes .The interaction mode is that the P.ginseng inhibits and induces CYPs and the modulated CYP isozymes ,inturn,have an impact on the metabolism of constituens in coadministered herbs causing herb-herb interaction .

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