1.Exosomes Treat Ischemic Stroke by Regulation of Ferroptosis Through the NRF2/SLC7A11/GPX4 Pathway in Mice
Yingtao XU ; Mengmeng WANG ; Ping LIN ; Haitao CHI ; Yi WANG ; Ying BAI
Laboratory Animal and Comparative Medicine 2026;46(1):20-31
ObjectiveA middle cerebral artery occlusion (MCAO) mouse model is established by electrocoagulation of the middle cerebral artery. The study examines the mechanism by which exosomes (EXO) derived from human amniotic mesenchymal stem cells (hAMSCs) improve ischemic stroke and regulate neural ferroptosis-related injury. MethodsThirty-two SPF-grade male C57BL/6J mice aged 6 - 8 weeks were randomly divided into four groups (n=8 per group): sham group (Sham), model group (MCAO), MCAO plus normal saline group (MCAO+NaCl), and MCAO plus exosome group (MCAO+EXO). The mouse MCAO model was established by electrocoagulation of the middle cerebral artery. Mice in the Sham group underwent exposure of the middle cerebral artery without electrocoagulation. Twenty-four hours before MCAO induction, mice in the MCAO+EXO group received a tail vein injection of 100 μL of exosomes derived from the culture supernatant of hAMSCs at a concentration of 9.5×1011 particles/mL. Mice in the MCAO+NaCl group were injected with an equal volume of normal saline via the tail vein. Twenty-four hours after model establishment, neurological deficits were evaluated using the Longa neurological deficit scoring system. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was performed to evaluate morphological changes of neurons in the ischemic brain regions. The contents of ferrous iron (Fe2+), malondialdehyde (MDA), total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) in the infarct core and peri-infarct regions were determined using microcolorimetric assays to evaluate differences among groups. The mRNA expression levels of ferroptosis-related factors, including nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the infarct core and peri-infarct regions were measured by real-time quantitative PCR. Protein expression levels of NRF2, SLC7A11, and GPX4 in the infarct and peri-infarct regions of each group were analyzed by Western blotting. ResultsCompared with the MCAO group, the Longa neurological deficit score was significantly reduced in the MCAO+EXO group (P<0.01). Prominent cerebral infarction was observed in the MCAO group, whereas the infarct volume ratio was markedly decreased in the MCAO+EXO group compared with the MCAO group (P<0.001). Histopathological analysis revealed that mice in the MCAO group exhibited obvious neuronal damage, including cytoplasmic vacuolar degeneration, nuclear pyknosis and fragmentation, unclear nuclear structure, and disorganized neuronal arrangement, compared with the Sham group. In contrast, neurons in the MCAO+EXO group showed relatively preserved morphology, with intact cellular structures and large, regular nuclei located centrally within the cells. Biochemical analysis demonstrated that Fe2+ and MDA levels in the infarct core and peri-infarct regions were significantly increased in the MCAO group compared with the Sham group (P<0.001). These levels were significantly reduced in the MCAO+EXO group compared with the MCAO group (P<0.01). In addition, total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) levels were markedly decreased in the MCAO group relative to the Sham group (P<0.01). Compared with the MCAO group, the MCAO+EXO group exhibited significantly increased levels of total GSH and GSH (P<0.001), while no significant change was observed in GSSG levels (P>0.05). Furthermore, both mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were significantly downregulated in the MCAO group compared with the Sham group (P<0.01, P<0.001). In contrast, both mRNA and protein expression levels of NRF2, SLC7A11, and GPX4 were significantly upregulated in the MCAO+EXO group compared with the MCAO group (P<0.05). ConclusionIn the mouse MCAO model, tail vein injection of exosomes derived from hAMSCs can improve motor function, reduce infarct area, protect neuronal cell morphology, and reduce the degree of nerve injury. Exosomes may exert a protective effect by activating the NRF2/SLC7A11/GPX4 pathway and reducing ferroptosis in neuronal cells of MCAO model mice.
2.Obesity significantly increases the risk of erectile dysfunction: a meta-analysis based on observational studies
Lang JI ; Shaolong HAO ; Haitao SUN ; Wuqing SUN ; Jihong Ma ; Rixing BAI ; Wei HAN
Journal of Surgery Concepts & Practice 2025;30(6):494-502
Objective To quantify the association between obesity and erectile dysfunction (ED) risk through a meta-analysis. Methods Following PRISMA guidelines, systematic searches of Chinese and English databases (up to March 2025) were conducted to include observational studies (cohort, cross-sectional, case-control). Adjusted effect sizes (OR and 95% CI) were extracted. Study quality was assessed using the Agency for Healthcare Research and Quality(AHRQ) scale, and a random-effects model was applied to pool effect sizes. Subgroup analyses (geographic region, obesity definitions) and sensitivity analyses were performed to validate robustness. Results Ten studies (n=230 744), including nine cross-sectional studies, were included. The meta-analysis revealed that obesity significantly increased ED risk (random-effects OR=1.80, 95% CI: 1.29-2.51), with high heterogeneity (I2=99.9%). Subgroup analyses indicated stronger associations in USA populations (OR=2.10, 95% CI: 1.23-3.60) than in Chinese populations (OR=1.16, 95% CI: 1.05-1.28). The highest effect size was observed when using BMI≥25 kg/m3 as the obesity threshold (OR=3.05, 95% CI: 2.06-4.51). Sensitivity analyses confirmed robust results (OR: 1.60-1.94 after excluding any single study). Conclusions Obesity is a critical risk factor for ED, with effect strength influenced by geographic region and obesity definitions. Interventions targeting BMI≥30 kg/m2 in Western populations and metabolic risks at BMI≥25 kg/m3 in Asian populations are recommended.
3.Dynamic changes of lymphocyte subsets in a patient with anti-N-methyl-D-aspartate receptor encephalitis overlaping with myelin oligodendrocyte glycoprotein antibody-associated diseases
Li LI ; Hongzhi GUAN ; Siyuan FAN ; Le ZHANG ; Mange LIU ; Lin BAI ; Haitao REN
Chinese Journal of Neurology 2025;58(7):750-756
Objective:To explore the relationship between the dynamic alterations of immune cell subsets in a patient with autoimmune encephalitis and the clinical relapses.Methods:For a patient with multiple relapses of anti-N-methyl-D-aspartate receptor encephalitis superimposed with myelin oligodendrocyte glycoprotein antibody-associated disease who visited Peking Union Medical College Hospital on July 18, 2018, the lymphocyte subsets were monitored dynamically over a long period and the relationship between lymphocyte subsets and the relapses was summarized.Results:The 38-year old male patient experienced a total of 5 episodes (including 4 relapses) during the six-year immunotherapy and follow-up process, and responded well to first-line and maintenance immunotherapy. His relapses occurred during drug reduction. Finally, the neurological symptoms resolved after rituximab treatment. A total of 39 tests of peripheral blood lymphocyte subsets were conducted during the follow-up, and 5 peaks of elevated CD19 positive B cells, 9 peaks of elevated CD3 positive T cells and 11 peaks of elevated natural killer cells were observed. The peak period of peripheral blood CD19 positive B cells exactly coincided with clinical relapses. While the consistency rates of clinical relapse and the peaks of peripheral blood CD3 positive T cells and natural killer cells were 5/9 and 2/11, respectively.Conclusions:The dynamic alterations of CD19 positive B cells in peripheral blood are correlated with the clinical relapse of autoimmune encephalitis and can predict clinical relapse.
4.Progress in animal models of atopic dermatitis in relation to Chinese and western medicine
Jinling CHEN ; Yuhan CHEN ; Xin LI ; Yanhua OU ; Difen YUAN ; Kunran BAI ; Jiali YUAN ; Yuanyuan DUAN ; Zhongshan YANG ; Haitao NIU
Acta Laboratorium Animalis Scientia Sinica 2025;33(4):581-592
Recent research progress into the use of Chinese medicine has demonstrated good therapeutic effects for increasing numbers of Chinese medicines for immune system diseases.Atopic dermatitis(AD)is an inflammatory disease characterized by type 2 immunity,and research into its pathogenesis and therapeutic immunopharmaceuticals has result ed in various different types of animal models.This review summarizes the existing animal models of AD and their immune-related characteristics,with the aim of providing appropriate references for the selection of future research models related to AD.
5.Dynamic changes of lymphocyte subsets in a patient with anti-N-methyl-D-aspartate receptor encephalitis overlaping with myelin oligodendrocyte glycoprotein antibody-associated diseases
Li LI ; Hongzhi GUAN ; Siyuan FAN ; Le ZHANG ; Mange LIU ; Lin BAI ; Haitao REN
Chinese Journal of Neurology 2025;58(7):750-756
Objective:To explore the relationship between the dynamic alterations of immune cell subsets in a patient with autoimmune encephalitis and the clinical relapses.Methods:For a patient with multiple relapses of anti-N-methyl-D-aspartate receptor encephalitis superimposed with myelin oligodendrocyte glycoprotein antibody-associated disease who visited Peking Union Medical College Hospital on July 18, 2018, the lymphocyte subsets were monitored dynamically over a long period and the relationship between lymphocyte subsets and the relapses was summarized.Results:The 38-year old male patient experienced a total of 5 episodes (including 4 relapses) during the six-year immunotherapy and follow-up process, and responded well to first-line and maintenance immunotherapy. His relapses occurred during drug reduction. Finally, the neurological symptoms resolved after rituximab treatment. A total of 39 tests of peripheral blood lymphocyte subsets were conducted during the follow-up, and 5 peaks of elevated CD19 positive B cells, 9 peaks of elevated CD3 positive T cells and 11 peaks of elevated natural killer cells were observed. The peak period of peripheral blood CD19 positive B cells exactly coincided with clinical relapses. While the consistency rates of clinical relapse and the peaks of peripheral blood CD3 positive T cells and natural killer cells were 5/9 and 2/11, respectively.Conclusions:The dynamic alterations of CD19 positive B cells in peripheral blood are correlated with the clinical relapse of autoimmune encephalitis and can predict clinical relapse.
6.Incidence and influencing factors of late-onset neutropenia after Rituximab treatment in children with primary nephrotic syndrome
Yan YANG ; Xiuxin LIN ; Ying LIN ; Huifang CHEN ; Yan CHEN ; Yang YANG ; Haitao BAI
Chinese Journal of Applied Clinical Pediatrics 2025;40(9):663-667
Objective:To investigate the incidence, clinical management and influencing factors of late-onset neutropenia (LON) in children with primary nephrotic syndrome (PNS) after Rituximab (RTX) treatment.Methods:A retrospective case-control study was conducted.The clinical data of PNS children who received RTX treatment at the First Affiliated Hospital of Xiamen University from March 2020 to August 2024 and were followed up for at least 6 months were collected.The RTX regimen was a single dose of 375 mg/m 2 with a maximum dose of 500 mg, and an additional dose was administered when the reexamination showed that peripheral blood CD19 + B cells were ≥ 1% or nephrotic syndrome relapsed.The patients were divided into an LON group and a non-LON group according to the presence or absence of LON, and then a comparison was made between the groups.The cumulative incidence of LON was estimated by the Kaplan-Meier method.Univariate and multivariate Logistic regression methods were used to identify the influencing factors of LON.Receiver operating characteristic (ROC) curves were plotted to assess the value of each influencing factor for predicting LON. Results:A total of 65 PNS patients were included.The incidence of LON was 19.3%(27/140) after 140 RTX treatment courses, and the first LON appeared 95.0 (64.0, 115.0) days after RTX treatment.Forty-nine patients received repeated RTX treatment.The incidence rates of LON after the first course, the second course, and the third course of RTX were 27.7%(18/65), 10.2%(5/49), and 18.8%(3/16), respectively, with no statistically significant difference ( χ2=5.764, P>0.05). There was also no significant difference in the incidence of LON between patients taking and not taking combined immunosuppressive agents after RTX treatment [35.3%(6/17) vs.37.8%(17/45), χ2=0.033, P>0.05]. Compared with the non-LON group, the LON group had a higher incidence of infections [48.1%(13/27) vs.15.0%(17/113), χ2=14.17, P<0.01], but no serious outcomes were observed in both groups.Multivariate Logistic analysis suggested that the age at treatment with RTX was an independent risk factor for LON after RTX treatment ( OR=0.763, 95% CI: 0.592-0.982). The area under the ROC curve of the age at treatment with RTX for predicting LON was 0.767 (95% CI: 0.628-0.906), with an optimal cutoff of 6.6 years, a sensitivity of 70.6%, and a specificity of 80.0%. Conclusions:The incidence of LON in PNS children after RTX treatment may be underestimated.Children who develop LON are at a higher risk of infections, but the prognosis is favorable.The age at treatment with RTX≤6.6 years is an independent risk factor for LON in PNS children.Close monitoring of neutrophil counts should be emphasized in younger PNS patients receiving RTX therapy.
7.Progress in animal models of atopic dermatitis in relation to Chinese and western medicine
Jinling CHEN ; Yuhan CHEN ; Xin LI ; Yanhua OU ; Difen YUAN ; Kunran BAI ; Jiali YUAN ; Yuanyuan DUAN ; Zhongshan YANG ; Haitao NIU
Acta Laboratorium Animalis Scientia Sinica 2025;33(4):581-592
Recent research progress into the use of Chinese medicine has demonstrated good therapeutic effects for increasing numbers of Chinese medicines for immune system diseases.Atopic dermatitis(AD)is an inflammatory disease characterized by type 2 immunity,and research into its pathogenesis and therapeutic immunopharmaceuticals has result ed in various different types of animal models.This review summarizes the existing animal models of AD and their immune-related characteristics,with the aim of providing appropriate references for the selection of future research models related to AD.
8.Incidence and influencing factors of late-onset neutropenia after Rituximab treatment in children with primary nephrotic syndrome
Yan YANG ; Xiuxin LIN ; Ying LIN ; Huifang CHEN ; Yan CHEN ; Yang YANG ; Haitao BAI
Chinese Journal of Applied Clinical Pediatrics 2025;40(9):663-667
Objective:To investigate the incidence, clinical management and influencing factors of late-onset neutropenia (LON) in children with primary nephrotic syndrome (PNS) after Rituximab (RTX) treatment.Methods:A retrospective case-control study was conducted.The clinical data of PNS children who received RTX treatment at the First Affiliated Hospital of Xiamen University from March 2020 to August 2024 and were followed up for at least 6 months were collected.The RTX regimen was a single dose of 375 mg/m 2 with a maximum dose of 500 mg, and an additional dose was administered when the reexamination showed that peripheral blood CD19 + B cells were ≥ 1% or nephrotic syndrome relapsed.The patients were divided into an LON group and a non-LON group according to the presence or absence of LON, and then a comparison was made between the groups.The cumulative incidence of LON was estimated by the Kaplan-Meier method.Univariate and multivariate Logistic regression methods were used to identify the influencing factors of LON.Receiver operating characteristic (ROC) curves were plotted to assess the value of each influencing factor for predicting LON. Results:A total of 65 PNS patients were included.The incidence of LON was 19.3%(27/140) after 140 RTX treatment courses, and the first LON appeared 95.0 (64.0, 115.0) days after RTX treatment.Forty-nine patients received repeated RTX treatment.The incidence rates of LON after the first course, the second course, and the third course of RTX were 27.7%(18/65), 10.2%(5/49), and 18.8%(3/16), respectively, with no statistically significant difference ( χ2=5.764, P>0.05). There was also no significant difference in the incidence of LON between patients taking and not taking combined immunosuppressive agents after RTX treatment [35.3%(6/17) vs.37.8%(17/45), χ2=0.033, P>0.05]. Compared with the non-LON group, the LON group had a higher incidence of infections [48.1%(13/27) vs.15.0%(17/113), χ2=14.17, P<0.01], but no serious outcomes were observed in both groups.Multivariate Logistic analysis suggested that the age at treatment with RTX was an independent risk factor for LON after RTX treatment ( OR=0.763, 95% CI: 0.592-0.982). The area under the ROC curve of the age at treatment with RTX for predicting LON was 0.767 (95% CI: 0.628-0.906), with an optimal cutoff of 6.6 years, a sensitivity of 70.6%, and a specificity of 80.0%. Conclusions:The incidence of LON in PNS children after RTX treatment may be underestimated.Children who develop LON are at a higher risk of infections, but the prognosis is favorable.The age at treatment with RTX≤6.6 years is an independent risk factor for LON in PNS children.Close monitoring of neutrophil counts should be emphasized in younger PNS patients receiving RTX therapy.
9.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
10.Association between septic shock and tracheal injury in intensive care unit patients with invasive ventilation: a single-centre prospective cohort study
Pei ZHANG ; Qilin YANG ; Chunhua YIN ; Zhigang CAI ; Huaihai LU ; Haitao LI ; Liwen LI ; Ye TIAN ; Long BAI ; Lining HUANG
Chinese Journal of Anesthesiology 2024;44(12):1505-1513
Objective:To evaluate the association between septic shock and tracheal injury in the intensive care unit (ICU) patients with invasive ventilation.Methods:This was a prospective single-centre cohort study. Patients who underwent invasive mechanical ventilation at the Department of Anesthesia Critical Care Medicine of the Second Hospital of Hebei Medical University from May 31, 2020 to March 5, 2022 were selected. The general characteristics of patients, reasons for ICU admission, vital signs, laboratory test results, Acute Physiology and Chronic Health Evaluation Ⅱ scores, Charlson Comorbidity Index, size of endotracheal tube, presence or absence of septic shock, oxygenation index, duration of intubation, consumption of norepinephrine and epinephrine, and tracheal injury scores at the time of extubation were recorded. Univariate linear regression analysis was used to identify the risk factors for tracheal injury, followed by adjustment using multivariate linear regression analysis.Results:Ninety-seven patients were ultimately included, and the average age was (56.6±16.5) yr, with 64.9% being male. The results of adjusted linear regression showed that septic shock was associated with tracheal injury scores ( β=2.99, 95% confidence interval 0.70-5.29). Subgroup analysis revealed a stronger correlation with a duration of intubation≥8 days ( P=0.013). Conclusions:Patients with septic shock exhibit significantly higher tracheal injury scores compared with those without septic shock, suggesting that septic shock may serve as an independent risk factor for tracheal injury.

Result Analysis
Print
Save
E-mail