1.Experimental study on autologous osteochondral transplantation in the treatment of recurrent anterior dislocation of the shoulder joint with articular cartilage defect in rabbits.
Tao LIU ; Sen FANG ; Fang-Xiang LIU ; Ming-Tao ZHANG ; Zhi-Tao YANG ; Bo-Rong ZHANG ; Jun-Wen LIANG ; Xi-Hao WANG ; Jin JIANG ; Xiang-Dong YUN
China Journal of Orthopaedics and Traumatology 2025;38(6):619-625
OBJECTIVE:
To explore clinical effect of autologous osteochondral transplantation (AOT) in the treatment of recurrent anterior dislocation of the shoulder joint with glenoid cartilage defect in rabbits by establishing a model of recurrent anterior dislocation of the shoulder joint with < 20% glenoid cartilage defect in rabbits.
METHODS:
Twenty-four male New Zealand white rabbits, aged 6-month-old, weighed (2.69±0.17) kg were selected. The labrum of shoulder joint of rabbits was artificially destroyed to establish a model of recurrent anterior dislocation of shoulder joint with cartilage defect. They were divided into AOT surgery group and simple suture group, with 12 rabbits in each group. AOT group were underwent AOT surgery, while simple suture group was treated with simple Bankart suture for recurrent shoulder joint dislocation. At 6 and 12 weeks after operation, 6 rabbits between two groups were sacrificed for sampling. The dietary conditions, activity conditions, mental states of rabbits and healing conditions of grafts in the specimens were observed and compared between two groups. HE staining was used to observe cell creep, cell morphology, inflammatory cell infiltration, fibrochondrocytes and their arrangement. Masson staining was used to observe the formation and arrangement of collagen fibers; Safrane-green staining was used to observe the regeneration of articular cartilage, subchondral bone and bone tissue. Bone mineral density (BMD), bone volume (BV) and trabecular thickness (Tb.Th) between two groups were measured by Micro-CT to evaluate the remodeling of shoulder glenoid bone defects by autologous osteochondral cartilage.
RESULTS:
After different surgical interventions were carried out in both groups of rabbits, at 6 weeks after the operation, the abduction, extension, internal rotation and external rotation of the shoulder joint on the operated side showed limited range of motion compared with the contralateral side, while adduction and forward flexion showed no obvious abnormalities compared with the contralateral side. At 12 weeks after operation, the range motion of tshoulder joints in both groups of rabbits had returned to the state before modeling. The effects of HE staining, Masson staining and safrane-green staining at 12 weeks after operation in both groups were stronger than the staining results at 6 weeks after operation. Moreover, the results of HE staining, Masson staining and safranin fixation green staining in AOT group at 6 and 12 weeks after operation were all higher than those in simple suture group. Micro-CT scan results at 6 and 12 weeks after operation showed that BMD (0.427±0.014), (0.466±0.032) g·cm-3, BV(116.171±3.527), (159.327±3.500) mm3, and Tb.Th (0.230±0.006), (0.285±0.009) mm in AOT group, which were higher than those of simple suture group in BMD(0.358±0.011), (0.384±0.096) g·cm-3, BV(72.657±3.903), (118.713±3.860) mm3, and Tb.Th(0.204±0.009), (0.243±0.007) mm;and the differences were statistically significant (P<0.05).
CONCLUSION
AOT procedure could effectively promote osteogenesis and fibrocartilage regeneration in the cartilage defect area of the shoulder glenoid <20%, which is conducive to reshaping the structure of the shoulder glenoid.
Animals
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Rabbits
;
Male
;
Transplantation, Autologous
;
Cartilage, Articular/injuries*
;
Shoulder Dislocation/physiopathology*
;
Bone Transplantation
;
Shoulder Joint/surgery*
2.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
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Aged
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Female
;
Humans
;
Male
;
Middle Aged
;
Arthritis, Rheumatoid/drug therapy*
;
Glucocorticoids/therapeutic use*
;
Medicine, Chinese Traditional
;
Retrospective Studies
3.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
;
Medicine, Chinese Traditional/methods*
;
Practice Guidelines as Topic
;
Drugs, Chinese Herbal/therapeutic use*
4.Association between Fish Consumption and Stroke Incidence Across Different Predicted Risk Populations: A Prospective Cohort Study from China.
Hong Yue HU ; Fang Chao LIU ; Ke Yong HUANG ; Chong SHEN ; Jian LIAO ; Jian Xin LI ; Chen Xi YUAN ; Ying LI ; Xue Li YANG ; Ji Chun CHEN ; Jie CAO ; Shu Feng CHEN ; Dong Sheng HU ; Jian Feng HUANG ; Xiang Feng LU ; Dong Feng GU
Biomedical and Environmental Sciences 2025;38(1):15-26
OBJECTIVE:
The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks.
METHODS:
A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI).
RESULTS:
During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43).
CONCLUSION
Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans
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China/epidemiology*
;
Male
;
Female
;
Stroke/etiology*
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Middle Aged
;
Prospective Studies
;
Incidence
;
Aged
;
Animals
;
Fishes
;
Risk Factors
;
Diet
;
Seafood
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Adult
;
Cohort Studies
5.Alterations in individual differential structural covariance networks of cognitive emotion regulation in young, first-episode and drug-naive patients with major depressive disorder
Meiling GU ; Qiuyu LYU ; Shulin FANG ; Jiayue HE ; Daifeng DONG ; Xiang WANG
Chinese Journal of Neurology 2025;58(4):396-403
Objective:To investigate the alterations in the brain structural network properties related to cognitive emotion regulation strategies in young, first-episode and drug-naive (FEDN) patients with major depressive disorder (MDD).Methods:One hundred and twelve young patients who were diagnosed with FEDN MDD were enrolled in the Second Xiangya Hospital of Central South University between October 2019 and October 2023, and 143 healthy controls (HC) were recruited for reference during the same period. Clinical data and T 1 structural images of high-resolution magnetic resonance imaging were collected from all participants, and the cognitive emotion regulation was assessed using the Chinese version of the Cognitive Emotion Regulation Questionnaire (CERQ-C). The brain structural alterations related to cognitive emotion regulation strategies were explored using whole-brain voxel-based morphometry (VBM) group analysis and individual differential structural covariance network (IDSCN) analysis. Partial correlation analysis was performed between the IDSCN anomalous structural concatenated edge and subdimensions of the CERQ-C. Results:The scores on the sub-dimension of negative cognitive emotion regulation (self-condemnation, rumination, catastrophization, blaming others) in the young FEDN MDD patients in CERQ-C were significantly higher than those in HC (14.28±2.30 vs 12.45±2.00, t=6.501, P<0.001;14.40±2.97 vs 11.31±2.93, t=7.934, P<0.001;12.19±3.75 vs 7.59±2.58, t=10.553, P<0.001;10.26±3.00 vs 8.74±2.89, t=3.916, P<0.001; respectively). There was no statistically significant difference in the VBM group analysis (all P>0.05). However, IDSCN single sample t test results showed significant group differences between the left orbitofrontal inferior gyrus and the left supplementary motor area, the left orbitofrontal middle gyrus and the bilateral precuneus, and the left superior temporal gyrus and the bilateral hippocampus (all P<0.05). With controlling for age, sex, and other factors, partial correlation analysis results showed that the left orbital inferior frontal gyrus-left supplementary motor area connection in patients with MDD was positively correlated with the self-condemnation and acceptance scores of the CERQ-C ( r=0.226, P=0.027; r=0.216, P=0.035), while negatively correlated with the score of blaming others ( r=-0.252, P=0.013). Additionally, connections between the right hippocampus and left superior temporal gyrus were significantly associated with the scores on catastrophization subdimension of the CERQ-C ( r=0.229, P=0.025). Conclusion:Due to its sensitivity to individualized analyses, the IDSCN analysis found that abnormal topological property changes were mainly manifested in the limbic system, the sensorimotor system, and the default network in young FEDN MDD patients, and were linked to their negative cognitive emotion regulation strategies, even though the VBM group analysis did not yield any significant results.
6.Clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris and type 2 diabetes mellitus:A meta-analysis
Xiang GAO ; Fang-yuan LIU ; Xiao-zhen HAN ; Dong-qian SUN ; Chuan-liang LIU
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(5):635-640
Objective:To explore the clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris(UAP)and type 2 diabetes mellitus(T2DM)using meta-analysis.Methods:We searched the databases including Pubmed,Web of Science,EMbase,EBSCO,Cochrane,CBM,CNKI and Wanfang for randomized controlled trials(RCTs)about the therapeutic effect of Shexiang Baoxin pill on patients with UAP and T2DM from the establish-ment to January 20th,2023.RevMan 5.3 software was used to perform meta-analysis to investigate the effect of Shexiang Baoxin pill on angina improvement and blood glucose fluctuation in patients with UAP and T2DM.Results:Six eligible literatures were included,including 346 patients in Shexiang Baoxin pill group and control group respec-tively.The results of meta-analysis showed that compared to participants in control group,those in Shexiang Baox-in pill group had significantly higher clinical overall efficiency(OR=3.13,95%CI 2.01~4.89,P<0.001),and significantly lower angina attack frequency(MD=-0.66,95%CI-0.79~-0.52,P<0.001),duration of angi-na(MD=-3.10,95%CI-4.11~-2.09,P<0.001),and 2-hour postprandial blood glucose(MD=-1.79,95%CI-2.00~-1.57,P<0.001).Conclusion:Shexiang Baoxin pill could improve clinical overall efficiency,an-gina attack frequency and duration,and reduce 2-hour postprandial blood glucose in patients with unstable angina pectoris and type 2 diabetes mellitus.
7.Clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris and type 2 diabetes mellitus:A meta-analysis
Xiang GAO ; Fang-yuan LIU ; Xiao-zhen HAN ; Dong-qian SUN ; Chuan-liang LIU
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(5):635-640
Objective:To explore the clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris(UAP)and type 2 diabetes mellitus(T2DM)using meta-analysis.Methods:We searched the databases including Pubmed,Web of Science,EMbase,EBSCO,Cochrane,CBM,CNKI and Wanfang for randomized controlled trials(RCTs)about the therapeutic effect of Shexiang Baoxin pill on patients with UAP and T2DM from the establish-ment to January 20th,2023.RevMan 5.3 software was used to perform meta-analysis to investigate the effect of Shexiang Baoxin pill on angina improvement and blood glucose fluctuation in patients with UAP and T2DM.Results:Six eligible literatures were included,including 346 patients in Shexiang Baoxin pill group and control group respec-tively.The results of meta-analysis showed that compared to participants in control group,those in Shexiang Baox-in pill group had significantly higher clinical overall efficiency(OR=3.13,95%CI 2.01~4.89,P<0.001),and significantly lower angina attack frequency(MD=-0.66,95%CI-0.79~-0.52,P<0.001),duration of angi-na(MD=-3.10,95%CI-4.11~-2.09,P<0.001),and 2-hour postprandial blood glucose(MD=-1.79,95%CI-2.00~-1.57,P<0.001).Conclusion:Shexiang Baoxin pill could improve clinical overall efficiency,an-gina attack frequency and duration,and reduce 2-hour postprandial blood glucose in patients with unstable angina pectoris and type 2 diabetes mellitus.
8.Alterations in individual differential structural covariance networks of cognitive emotion regulation in young, first-episode and drug-naive patients with major depressive disorder
Meiling GU ; Qiuyu LYU ; Shulin FANG ; Jiayue HE ; Daifeng DONG ; Xiang WANG
Chinese Journal of Neurology 2025;58(4):396-403
Objective:To investigate the alterations in the brain structural network properties related to cognitive emotion regulation strategies in young, first-episode and drug-naive (FEDN) patients with major depressive disorder (MDD).Methods:One hundred and twelve young patients who were diagnosed with FEDN MDD were enrolled in the Second Xiangya Hospital of Central South University between October 2019 and October 2023, and 143 healthy controls (HC) were recruited for reference during the same period. Clinical data and T 1 structural images of high-resolution magnetic resonance imaging were collected from all participants, and the cognitive emotion regulation was assessed using the Chinese version of the Cognitive Emotion Regulation Questionnaire (CERQ-C). The brain structural alterations related to cognitive emotion regulation strategies were explored using whole-brain voxel-based morphometry (VBM) group analysis and individual differential structural covariance network (IDSCN) analysis. Partial correlation analysis was performed between the IDSCN anomalous structural concatenated edge and subdimensions of the CERQ-C. Results:The scores on the sub-dimension of negative cognitive emotion regulation (self-condemnation, rumination, catastrophization, blaming others) in the young FEDN MDD patients in CERQ-C were significantly higher than those in HC (14.28±2.30 vs 12.45±2.00, t=6.501, P<0.001;14.40±2.97 vs 11.31±2.93, t=7.934, P<0.001;12.19±3.75 vs 7.59±2.58, t=10.553, P<0.001;10.26±3.00 vs 8.74±2.89, t=3.916, P<0.001; respectively). There was no statistically significant difference in the VBM group analysis (all P>0.05). However, IDSCN single sample t test results showed significant group differences between the left orbitofrontal inferior gyrus and the left supplementary motor area, the left orbitofrontal middle gyrus and the bilateral precuneus, and the left superior temporal gyrus and the bilateral hippocampus (all P<0.05). With controlling for age, sex, and other factors, partial correlation analysis results showed that the left orbital inferior frontal gyrus-left supplementary motor area connection in patients with MDD was positively correlated with the self-condemnation and acceptance scores of the CERQ-C ( r=0.226, P=0.027; r=0.216, P=0.035), while negatively correlated with the score of blaming others ( r=-0.252, P=0.013). Additionally, connections between the right hippocampus and left superior temporal gyrus were significantly associated with the scores on catastrophization subdimension of the CERQ-C ( r=0.229, P=0.025). Conclusion:Due to its sensitivity to individualized analyses, the IDSCN analysis found that abnormal topological property changes were mainly manifested in the limbic system, the sensorimotor system, and the default network in young FEDN MDD patients, and were linked to their negative cognitive emotion regulation strategies, even though the VBM group analysis did not yield any significant results.
9.Analysis of Thalassemia Gene Mutation Types and Ethnic Distribution Characteristics in Hechi Area,Guangxi
Li-Fang LIANG ; Xiu-Ning HUANG ; Dong-Ming LI ; Bi-Yan CHEN ; Xiang CHEN ; Zhen-Ren PENG ; Sheng HE
Journal of Experimental Hematology 2024;32(4):1191-1196
Objective:To investigate the genotype,mutation type,and ethnic distribution characteristics of thalassemia in the population of Hechi area,Guangxi,and to provide a reference basis for prevention and control of thalassemia and eugenic counseling in the region.Methods:Gap-polymerase chain reaction(gap-PCR)and reverse dot blot(RDB)were used for genetic testing on suspected thalassemia persons,and the results were analyzed.Results:Among 29 136 samples,a total of 17 016(58.40%)positive samples for thalassemia genes were detected,with a higher detection rate in males than in females(X2=49.917,P<0.001).The detection rates of thalassemia genes were significant different among Zhuang,Han,Yao,Mulao,and Maonan ethnic groups(x2=546.121,P<0.001).The α-thalassemia genotypes were mainly--SEA/αα(16.67%),-α3.7/αα(8.90%),αCSα/αα(6.00%).Additionally,four rare genotypes were detected,including--THAI/αα(47 cases),HKαα/αα(2 cases),--SEA/-α21.9(2 cases),and--THAI/αcsα(1 case).The β-thalassemia genotypes were mainly βCD17/βN(7.49%),βCD41-42/βN(6.70%),βCD71-72/βN(0.44%).108 cases of moderate and severeβ-thalassemia were detected,of which 81 cases had a history of blood transfusion,the transfusion frequency of 60 cases was more than 10 times/year,and 10 cases received bone marrow transplantation.Conclusion:Thalassemia in Hechi area is predominantly deletion type--SEA/αα,the detection rate of thalassemia in ethnic minorities is higher than that in Han population.In this area,moderate and severe β-thalassemia have certain incidence,these patients mostly need regular blood transfusion and iron removal treatment,and very few patients have received bone marrow transplantation.This study provides a certain reference basis for prevention and control of thalassemia and eugenic counseling in the region.
10.Research progress on the changes of blood-brain barrier in sepsis-associated encephalopathy
Xiaoyu ZHENG ; Qian XIANG ; Xiaoxu DONG ; Yang SHEN ; Wei FANG ; Hongna YANG
Chinese Critical Care Medicine 2024;36(8):892-896
Sepsis-associated encephalopathy (SAE) is the most common neurological complication of sepsis, with an incidence of up to 70% in sepsis, and contributes to the increased mortality and disability in sepsis. To date, the exact pathogenesis of SAE is not clear. Most of current researches indicated that blood-brain barrier (BBB) dysfunction, active neuroinflammation, glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE. BBB, as a complex cellular structure between the central nervous system and the peripheral system, strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system. During the progress of sepsis, inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB, which helped above species easily enter into the central system. Above these damages caused glial cell activation (microglia and astrocyte), the imbalance of neurotransmitters, mitochondrial dysfunction and neural apoptosis, which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells. Therefore, this review focuses on the structural and functional changes of BBB in SAE, and how these changes lead to the development of SAE, in order to seek a BBB-targeted therapy for SAE.

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