1.Therapeutic efficacy and influencing factors of ceftazidime/avibactam in lung transplant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli
Zhigang QI ; Chenglong LIANG ; Yating GUO ; Xiaoshan LI ; Hongmei WANG ; Lingzhi SHI ; Bo WU ; Jingyu CHEN ; Xiuhong ZHANG
Chinese Journal of Infection Control 2025;24(7):940-946
Objective To investigate the clinical application of ceftazidime/avibactam(CAZ/AVI)in lung trans-plant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli(CRGNB),and ana-lyze the factors affecting the prognosis.Methods Lung transplant recipients who had CRGNB pulmonary infection and were treated with CAZ/AVI were included in the analysis.Based on 14-day clinical response,14-day microbial response,and 30-day survival status,the recipients were divided into a clinical response group and a clinical failure group,a microbial response group and a microbial failure group,as well as a survival group and a death group,re-spectively.Univariate analysis was conducted on various data from the two groups.Factors affecting therapeutic ef-ficacy and survival were included in a binary logistic regression model.Independent risk factors for CAZ/AVI anti-infective efficacy and all-cause mortality outcomes were analyzed.Results A total of 43 recipients were included.After 14-day anti-infective treatment,32 recipients(74.42%)achieved clinical response,and 30 recipients(69.77%)achieved microbial response.34 recipients(79.07%)survived 30 days after CAZ/AVI treatment.The Charlson comorbidity index(CCI),proportion of renal dysfunction,and incidence of shock in recipients in the clini-cal response group were all lower than those in the clinical failure group(P<0.05),while the serum albumin(ALB)level was higher(P<0.05).The incidence of shock in recipients in the microbial response group was lower than that in the microbial failure group(P<0.05).CCI,proportion of renal dysfunction,and incidence of shock in recipients in the survival group were all lower than those in the death group(all P<0.05),while ALB level was higher during treatment period(P<0.05).Multivariate analysis of 14-day clinical response and 30-day survival showed that higher CCI was an independent risk factor affecting 14-day clinical response of recipients(OR=2.22,95%CI:1.07-4.63),while lower ALB levels(OR=0.72,95%CI:0.54-0.98)and higher CCI(OR=5.27,95%CI:1.18-23.58)were independent risk factors for 30-day all-cause mortality in recipients with pulmonary in-fection after lung transplant.Conclusion CAZ/AVI may be an effective drug for treating pulmonary infection caused by CRGNB in lung transplant recipients.Higher CCI is an independent risk factor for 14-day clinical failure in recipients after CAZ/AVI treatment.Lower ALB level and higher CCI are independent risk factors for increased 30-day mortality in recipients.
2.Neuroprotective mechanism of electroacupuncture in cerebral ischemia-reperfusion model rats
Haiyang WU ; Mian DUAN ; Chenglong LI ; Junyu ZHANG ; Haisheng JI ; Haitao WANG ; Wei MAO ; Ying WANG
Chinese Journal of Tissue Engineering Research 2025;29(18):3811-3818
BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.
3.Study on the staging of cardiovascular-kidney-metabolic syndrome before onset and its impact on prognosis in patients with acute myocardial infarction
Dewei WU ; Mengjin HU ; Xiuling WANG ; Chenglong GUO ; Xuexue HAN ; Tianxing ZHANG ; Jinggang XIA
Chinese Journal of Postgraduates of Medicine 2025;48(3):209-214
Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.
4.Restoration of osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide with psoralen
Chenglong WANG ; Zhilie YANG ; Junli CHANG ; Yongjian ZHAO ; Dongfeng ZHAO ; Weiwei DAI ; Hongjin WU ; Jie ZHANG ; Libo WANG ; Ying XIE ; Dezhi TANG ; Yongjun WANG ; Yanping YANG
Chinese Journal of Tissue Engineering Research 2025;29(1):16-23
BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.
5.Effect of Static Balance Ability on Dual-Task Costs Under Different Walking TaskInterventions in Chinese Older Adults
Chenglong WANG ; Mingjian NIE ; Chenhui XIAO ; Yini WU ; Jingjing WANG
Medical Journal of Peking Union Medical College Hospital 2025;16(3):598-605
To compare gait parameters during single-task and dual-task walking in older adults, and to examine differences in dual-task costs between individuals with high versus low balance abilities under different task conditions. From November to December 2024, community-dwelling older adults were recruited through Hebei Province's national physical fitness monitoring network across multiple communities in Shijiazhuang and Xiong'an New Area. An inertial sensor-based gait analysis system was used to collect spatiotemporal gait parameters during three conditions: single-task walking, motor dual-task walking (simultaneous carrying task), and cognitive dual-task walking (serial subtraction task). Participants were stratified into high-balance and low-balance groups based on median eyes-closed single-leg stance duration (cut-off: 18.40 seconds). Dual-task costs (DTC) were calculated and compared between groups. The study included 133 eligible participants[30 male, 103 female; mean age (66.95±4.75) years]. The low-balance group 66 participants, and the high-balance group 67 participants. Compared to single-task walking, motor dual-task conditions significantly increased stride time and double support phase duration (all While dual-task conditions generally impair gait parameters in older adults, individuals with higher balance abilities maintain more stable gait patterns during motor dual-tasks, demonstrating greater resilience to interference. These findings highlight the importance of balance capacity in preserving functional mobility during daily multitasking activities.
6.Analgesic effect and mechanism of punicalagin on neuropathic pain in rats
Li WANG ; Ling ZHOU ; Chenglong WU
China Pharmacy 2025;36(10):1191-1196
OBJECTIVE To investigate the analgesic effect and potential mechanism of punicalagin on neuropathic pain (NP) rats based on the hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) signaling pathway. METHODS Male SD rats were randomly divided into sham operation group (18 rats) and modeling group (72 rats). NP rat model was established by chronic constriction injury (CCI) of sciatic nerve. The successfully modeled rats were divided into NP group, 2-methoxyestradiol group (HIF-1α antagonist 10 mg/kg), punicalagin group (300 mg/kg), and punicalagin+dimethyloxaloglycine group (punicalagin 300 mg/kg+HIF-1α agonist 175 mg/kg), with 18 rats in each group. Rats in each group were injected intraperitoneally and/or intragastrically with the corresponding solution or 1% dimethyl sulfoxide/normal saline, once a day, for 14 consecutive days. After the last administration, the mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in spinal cord tissue were detected; the morphological changes in the spinal dorsal horn were observed. Apoptosis rate of spinal dorsal horn neurons, the co-localization of NLRP3/ionized calcium binding adapter molecule 1 (Iba-1) (calculated by the number of NLRP3+/Iba-1+ cells) and the protein expressions of HIF-1α, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 in spinal cord tissue were detected. RESULTS Compared with the sham operation group, neurofibril in spinal dorsal horn of rats in NP group was thickened and wound into knots, and vacuolar degeneration containing silver granules was observed; the MWT and TWL were reduced or shortened; the levels of TNF-α, IL-1β and IL-6 in spinal cord tissue, the apoptosis rate of spinal dorsal horn neurons, the number of NLRP3+/Iba-1+ cells, and protein expressions of HIF-1α, NLRP3, ASC and caspase-1 were significantly increased or up-regulated (P<0.05). Compared with the NP group, the above indexes were significantly improved in the 2-methoxyestradiol group and punicalagin group (P<0.05), while dimethyloxaloglycine could significantly reverse the improvement effect of punicalagin on the above indexes (P<0.05). CONCLUSIONS Punicalagin can relieve pain in NP rats, and its analgesic effect may be achieved by inhibiting HIF-1α/NLRP3 signaling pathway and blocking the activation of ma0o4e@163.com NLRP3 inflammasome in spinal dorsal horn microglia.
7.Therapeutic efficacy and influencing factors of ceftazidime/avibactam in lung transplant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli
Zhigang QI ; Chenglong LIANG ; Yating GUO ; Xiaoshan LI ; Hongmei WANG ; Lingzhi SHI ; Bo WU ; Jingyu CHEN ; Xiuhong ZHANG
Chinese Journal of Infection Control 2025;24(7):940-946
Objective To investigate the clinical application of ceftazidime/avibactam(CAZ/AVI)in lung trans-plant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli(CRGNB),and ana-lyze the factors affecting the prognosis.Methods Lung transplant recipients who had CRGNB pulmonary infection and were treated with CAZ/AVI were included in the analysis.Based on 14-day clinical response,14-day microbial response,and 30-day survival status,the recipients were divided into a clinical response group and a clinical failure group,a microbial response group and a microbial failure group,as well as a survival group and a death group,re-spectively.Univariate analysis was conducted on various data from the two groups.Factors affecting therapeutic ef-ficacy and survival were included in a binary logistic regression model.Independent risk factors for CAZ/AVI anti-infective efficacy and all-cause mortality outcomes were analyzed.Results A total of 43 recipients were included.After 14-day anti-infective treatment,32 recipients(74.42%)achieved clinical response,and 30 recipients(69.77%)achieved microbial response.34 recipients(79.07%)survived 30 days after CAZ/AVI treatment.The Charlson comorbidity index(CCI),proportion of renal dysfunction,and incidence of shock in recipients in the clini-cal response group were all lower than those in the clinical failure group(P<0.05),while the serum albumin(ALB)level was higher(P<0.05).The incidence of shock in recipients in the microbial response group was lower than that in the microbial failure group(P<0.05).CCI,proportion of renal dysfunction,and incidence of shock in recipients in the survival group were all lower than those in the death group(all P<0.05),while ALB level was higher during treatment period(P<0.05).Multivariate analysis of 14-day clinical response and 30-day survival showed that higher CCI was an independent risk factor affecting 14-day clinical response of recipients(OR=2.22,95%CI:1.07-4.63),while lower ALB levels(OR=0.72,95%CI:0.54-0.98)and higher CCI(OR=5.27,95%CI:1.18-23.58)were independent risk factors for 30-day all-cause mortality in recipients with pulmonary in-fection after lung transplant.Conclusion CAZ/AVI may be an effective drug for treating pulmonary infection caused by CRGNB in lung transplant recipients.Higher CCI is an independent risk factor for 14-day clinical failure in recipients after CAZ/AVI treatment.Lower ALB level and higher CCI are independent risk factors for increased 30-day mortality in recipients.
8.Study on the staging of cardiovascular-kidney-metabolic syndrome before onset and its impact on prognosis in patients with acute myocardial infarction
Dewei WU ; Mengjin HU ; Xiuling WANG ; Chenglong GUO ; Xuexue HAN ; Tianxing ZHANG ; Jinggang XIA
Chinese Journal of Postgraduates of Medicine 2025;48(3):209-214
Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.
9.Neuroprotective mechanism of electroacupuncture in cerebral ischemia-reperfusion model rats
Haiyang WU ; Mian DUAN ; Chenglong LI ; Junyu ZHANG ; Haisheng JI ; Haitao WANG ; Wei MAO ; Ying WANG
Chinese Journal of Tissue Engineering Research 2025;29(18):3811-3818
BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.
10.Therapeutic Effects of Xiao Xumingtang Combined with Electroacupuncture on Cerebral Ischemia/Reperfusion Injury via NLRP3/GSDMD/Caspase-1 Pathway
Wei MAO ; Haiyang WU ; Ying WANG ; Haitao WANG ; Haisheng JI ; Junyu ZHANG ; Chenglong LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):39-47
ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang (XXMT) combined with electroacupuncture (EA) collaboratively in alleviating cerebral ischemia/reperfusion (I/R) injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling, rats in the XXMT+EA groups were administered XXMT at low (15 g·kg-1), medium (30 g·kg-1), and high (60 g·kg-1) doses, alongside daily 20-min EA treatment (stimulating acupoints GV14 and GV20). Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score, TTC staining, and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 (NLRP3), Gasdermin D (GSDMD), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the ischemic area of the cerebral cortex. ResultCompared with the sham group, the I/R group showed a significant increase in neurological deficit scores and infarct volume (P<0.01), along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05). In contrast, the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume (P<0.01), and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05). The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway, thereby reducing neurological deficits, minimizing brain infarct size, and improving cortical neuronal damage.

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