4.Advances in high mobility group box-1 protein mediated multiple organ dysfunction and its potential interventional strategies.
Yong-ming YAO ; Shan XU ; Zhi-yong SHENG
Acta Academiae Medicinae Sinicae 2007;29(4):459-465
High mobility group box-1 protein (HMGB1) has recently been shown as a crucial late mediator of inflammation and sepsis, and is involved in mediating multi-organ functional lesions, including acute lung, liver, and intestine injuries. As a delayed inflammatory cytokine, HMGB1 provides a wider therapeutic time window for clinical intervention. HMGB1 has been proven to be a promising therapeutic target to prevent the development of multiple organ dysfunction syndrome in experimental models of severe sepsis. The pharmacological strategies include neutralization of antibodies or specific HMGB1 antagonists, suppression of HMGB1 secretion (ethyl pyruvate, agonists for alpha7-nicotinic acetylcholine receptors), and down-regulation of HMGB1 expression (sodium butyrate, signaling inhibitors for Janus kinase/signal transducer and activator of transcription).
HMGB1 Protein
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antagonists & inhibitors
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biosynthesis
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physiology
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Humans
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Multiple Organ Failure
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immunology
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metabolism
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prevention & control
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Sepsis
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immunology
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metabolism
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therapy
5.Study on factors in frequency and degree of risky behaviors in adolescents
Yong ZHAO ; Tao ZOU ; Ming LI ; Shuqiao YAO
Chinese Journal of Behavioral Medicine and Brain Science 2010;19(5):453-455
Objective To explore the factors in frequency and degree of risk behavior in adolescents,as well find the way to cope with adolescent mental health. Methods 1369 middle students and college students were measured by Risky Behavior Questionnaire for Adolescents (RBQ-A) ,and analyzed the data. Results (1) There were statistically significant among the different age in difference of risky behaviors except aggressive and/or violent behaviors. Males scored higher than females in unsafe sexual practices, aggressive and/or violent behaviors, dangerous,destructive,and/or illegal behaviors,alcohol and/or drug use and smoking(P<0.05 orP<0.01). Students in city scored higher than rural students in dangerous,destructive,and/or illegal behaviors and alcohol and/or drug use(P<0.05 or P< 0.01). Families with high income scored higher than low income in unsafe sexual practices and rule breaking(P< 0.05 or P< 0.01). Families with low income scored higher than high income residences in dangerous,destructive,and/or illegal behaviors and alcohol and/or drug use(P < 0.05 or P < 0.01). (2) The significant differences were existed in unsafe sexual practices,aggressive and/or violent behaviors,dangerous, destructive,and/or illegal behaviors,alcohol and/or drug use and smoking between males and females (P<0.05 or P<0.01).The significant differences were existed in dangerous,destructive,and/or illegal behaviors and alcohol and/or drug use between groups of 16 years old and 14 ~ 15 years old (P < 0. 05 or P < 0. 01). The significant differences were existed in dangerous,destructive,and/or illegal behaviors between urban and rural students (P< 0.05 orP<0.01).The significant differences were existed in total scores in gender and urban and rural(P<0.05 or P<0.01). Conclusion The significant differences are existed in rate of risky behaviors in gender,age,urban and rural. But there is different degree existed in it.
7.The inhibitory effects of peripheral electrical stimulation on chronic central pain after spinal cord injury
Yong-Gang XIE ; Xiao-Ming ZHANG ; Shang-Long YAO ;
Chinese Journal of Physical Medicine and Rehabilitation 2003;0(09):-
Objective To investigate the mechanisms of the inhibitory effects of peripheral electrical stimu- lation(PES)on chronic central pain(CCP)after spinal cord injury(SCI).Methods Twenty-four male Sprague- Dawley rats with CCP following SCI were randomly divided into three groups:a group without stainless steel needles implanted (NSSN group,n=8),a group with a stainless steel needle implanted but no peripheral electrical stimula- tion applied(NPES group,n=8)and a PES group(PES group,n=8).The rats' CCP was evaluated through ob- serving their response to nociceptive stimulation by means of the paw withdrawal pressure threshold(PWPT)and the paw withdrawal latency(PWL).Spontaneous pain behaviors including autophagia and scratching were observed at the same time.PES was applied via stainless steel needles inserted into standard acupoints on the hind limps and the back.The expression of the NMDA receptor 1(NR-1)subunit in the spinal cord horn was measured using immuno- chemical methods.Results Compared with the NSSN and NPES groups,CCP in the PES group was alleviated, PWPT and PWL were dramatically increased(P<0.01)and the expression of NR-1 was obviously decreased (P<0.01).Conclusion Peripheral electrical stimulation may alleviate chronic central pain after spinal cord injury in rats.
8.Inflammatory response and immune regulation of high mobility group box-1 protein in treatment of sepsis
World Journal of Emergency Medicine 2010;1(2):93-98
Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein (HMGB1), are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGB1-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGB1-targeted Chinese herbal therapies in sepsis.
9.Clinical analysis of patients with actue renal failure at high altitude
Yao-Quan ZHANG ; Yong-Ming DENG ; Shao-Yong LI ; Yun-Bing GONG ; Chuan LI ;
Chinese Journal of Emergency Medicine 2006;0(10):-
Objective To analyze the etiologies,clinical characteristics and prognostic factors of patients with acute renal failure(ARF)admitted to the hospital at high altitude.Method This retrospective study included clinical data of patients with acute renal failure in the General Hospital of Tibet Military Command from May 2001 to April,2006.Results There were 85 male patients and 63 female patients with mean age(42.4?18.1)years old.Among 148 patients with acquired ARF,52.7% was iatrogenic or nosoeomal origin, demonstrating a trend of increasing.The ARF included pre-renal(n=48,32.4%),renal parenchymal(n= 90,60.8%)and post-renal(n=10,6.8%)in origin.Acute high altitude sickness(n=20)was the major causes of pre-renal ARF.Renal parenchymal ARF could be classified into glomerular vascular lesions(n=24), acute tubular necrosis(n=53),acute interstitial nephritides(n=12),and contusion of unitesticle(n=1).of 90 cases of renal parenchymal ARF,39 patients(43.3%)were induced by medicines.Lithiasis was the major causes of post-renal ARF.The mortality of ARF in our study was 42.6%.The mortality of patients contracted ARF in hospital was much higher than that of patients community ARF in community(55.1 vs 23.6%;P=0.01). There was no significant differences of the mortality between the patients with and without dialysis treatment. Univariate analysis showed that prognosis was correlated with age,the presence of hematuria and oliguria or anuria Hb,and the number of organ system failures.The logistic regression showed that age,Hb and the number of organ system dysfunction were the predictors of mortality.Conlusions The major causes of ARF at high altitude were acute high altitude sickness and the use of medicines with nephrotoxicity.The morbility and mortality of nosocomisl ARF increased significantly.Prevention of MODS is a key management to decrease mortality in severe ARF.
10.Novel insights for high mobility group box 1 protein-mediated cellular immune response in sepsis:A systemic review
Li-Feng HUANG ; Yong-Ming YAO ; Zhi-Yong SHENG
World Journal of Emergency Medicine 2012;3(3):165-171
BACKGROUND: High mobility group box 1 protein (HMGB1) is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. METHODS: This systemic review is mainly based on our own work and other related reports. RESULTS: HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells (Tregs), dendritic cells (DCs), macrophages, and natural killer cells (NK cells). Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors (e.g., ethyl pyruvate) and antagonists (e.g., A box), can protect against sepsis lethality and give a wider window for the treatment opportunity. CONCLUSION: HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.