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 ; antagonists & inhibitors ; biosynthesis ; physiology ; Humans ; Multiple Organ Failure ; immunology ; metabolism ; prevention & control ; Sepsis ; immunology ; metabolism ; therapy

Burns ; complications ; diagnosis ; prevention & control ; Humans ; Sepsis ; diagnosis ; etiology ; prevention & control

Objective To investigate the expressions of nitric oxide synthase (NOS) protein and mRNA in the lung of rats with hepatopulmonary syndrome. Methods Male Sprague-Dawley rats were divided into four groups: sham operation (SO), intrahepatic portal hypertension (IHPH), prehepatic portal hypertension (PHPH) and portasymstimic shunt (PCS). Two weeks after preparation of rat models, the following measurements were performed: arterial blood gas analysis; the concentrations of NO in lungs; in situ hybridization of ecNOS and iNOS mRNA expressions in lung tissue sections with digoxin-labeled ecNOS and iNOS oligonucleotide probes; expressions of ecNOS and iNOS proteins by immunohistochemisty; image and semiquantitative analysis of the expressions of ecNOS, iNOS and their mRNA. Results PaO_ 2 was (73.85?6.51) mmHg in IHPH rats, significantly lower than that in PHPH, PCS and SO rats97.39? 1.33, 95.23?2.22 and (99.05?0.75)mmHg, respectively.The level of lung NO of IHPH was(19.78?5.33)?mol per gram of protein,much higher than that of PHPH, PCS and SO 13.21?3.99,13.89?3.16 and (8.71?1.68)?mol per gram of protein,respectively. In capillary endothelia, positive expressions of ecNOS mRNA and ecNOS protein in IHPH(4.96?0.82,4.11?0.28) were significantly higher than those of PHPH (1.81? 0.39, 1.63?0.18), PCS (1.88?0.53,1.83?0.16)and SO(1.19?0.32,0.98?0.20). Conclusion The expressions of NOS protein and mRNA in the lung of rats with hepatopulmonary syndrome were increased, and the level of lung NO was elevated, which seems to play an important role in the pathogenesis of hepatopulmonary syndrome.

Objective To analyze the clinical and ultrasonic features of primary squamous cell carcinoma of the thyroid(PSCCT)and diagnostic value of ultrasonography (US) in PSCCT in order to improve the cognition of PSCCT.Methods The clinical data and ultrasonic characters of 5 patients with PSCCT confirmed by pathology post surgery were retrospectively reviewed.Results The average age of the 5 patients was 62 years (range from 46 to 79).All of 5 patients with PSCCT were presented with a painless neck mass in clinical palpation examination.Of them,2 patients had different degrees of difficulty in breathing and swallowing,2 patients had hoarseness.Four of 5 patients had died after surgery with average survival time of 9.5 months.On US,the size of lesions was large(a maximum diameter of 2.9-5.5 cm),all of 5 lesions appeared as single solid mixed-echogenicity mass including irregular lamellate marked hypoechoic region,with irregular margin and undefined boundary.Of them,2 lesions presented with lobulated,only 1 lesion exhibited microcalcification and another 4 lesions had no calcification,3 lesions exhibited a? sign of breakthrough thyroid envelope.Color Doppler flow imaging showed few blood flow (3/5) and moderate blood flow (2/5),a higher vascular resistance spectrum was detected in 4 lesions (RI 0.72-0.88).Three patients exhibited suspicious cervical lymph nodes.Conclusions The characteristic ultrasonic appearance combined with the clinical features enables a confident preoperative diagnosis of PSCCT.

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.

Objective To explore the effects of polymorphisms of Crohn's disease related NOD2 gene and human beta-defensin 2 (hBD-2) on transcription of hBD-2 gene and its mechanism. Methods HEK293T cells were transfected with hBD-2 gene and NOD2 eukaryotic expression plasmid, and were then stimulated with LPS, TNF-α, or BAY 11-7082 (antagonist of NF-κB), respectively. Transcriptional activity of hBD-2 was detected afterwards. Results LPS could suppress transcription of hBD-2 (P=0. 020), which was increased by TNF-α in a dose-dependent manner (P =0. 004). In the presence of LPS, there was sig-nificant difference in transcriptional activity of hBD-2 between wild-NOD2 transfected group and mutated NOD2 (P268S) transfected group (P=0. 008), but there was no significant difference between wild hBD-2 transfected group and mutated hBD-2 transfected group (P=0. 053). With the stimulation of TNF-α (5 ng/ml), there was a significant difference between mutated hBD-2 transfected group and wild hBD-2 transfected group (P=0. 006), but no significant difference between wild-NOD2 transfected and mutated NOD2 transfected group was defected (P = 0. 064). Pretreatment with BAY 11-7082 before TNF-α (5 ng/ml) significantly inhibited the transcriptional activity of hBD-2 (P < 0. 001). Conclusion The poly-morphism of NOD2 affects the innate expression of hBD-2, the polymorphism of site in hBD-2 promoter (-233) may lead to significant decline of the inducible expression of hBD-2, and NF-κB might be a key pathway that NOD2 protein mediates the expression of defensin.

Objective To investigate the association of two single nuclear peptides(SNPs)polymorphisms(rs11209026 and rs11805303)which lies in interleukin-23 receptor(IL23R)gene with susceptibility to inflammatory bowel disease(IBD).Methods The target SNPs were directly sequenced by polymerase chain reaction(PCR)and gene polymorphisms of 50 healthy and 81 patients with IBD (Crohn's disease in 41 patients and ulcerative colitis in 40 patients)were analyzed using chromassoftware.Results The geno-type frequency and allelic frequency of rs11209026 were 7.3%and 3.7%in patients with Crohn's disease respectively,15.0%and 7.5%in patients with ulcerative colitis respectively as well as 14.0%and 7.0%in normal population respectively(all P value＞0.05).The geno-type frequency and allelic frequency of rs11805303 were 22.0%and 52.4%in patients with Crohn's disease respectively,15.0% and 41.2% in patients with ulcerative colitis respectively as well as 34.0%and 59.0%in normal population respectively(all P value＞0.05).But in allelic frequency there was significant difference between ulcerative colitis patients and normal population(P=0.018).The polymorphisms of rs11805303 loci did not correlate with age,gender,disease duration.activity and site in patients with ulcerative colitis.Conclusions IL23R gene polymorphism is not associated with the susceptibility to Crohn's disease.rs11805303 allele may be related with susceptibility to ulcerative colitis.But no correlation was found between the SNP polymorphisms and the clinical characteristic of ulcerative colitis.

AIM: To analyze the results of phacovitrectomy with internal limiting membrane(ILM) peeling to treat foveoschisis in ultra-high myopia.METHODS: Totally 32 eyes of 32 ultra-high myopia patients with foveoschisis were selected retrospectively.The preoperative refractive errors ranged from-12.00D to-20.00D with the mean of-15.78±2.16D.The best corrected visiual acuity(BCVA) were converted to LogMAR acuity, and the average BCVA was 4.1±0.4.Conventional phacovitrectomy with ILM peeling by ICG dying were performed.Gas tamponade were performed to end the operation.The BCVA and the foveoschisis cavity were observed by 1-9mo after the surgery, with the mean of 4.5mo.RESULTS: The foveoschisis cavity of 30 eyes were healed with BCVA increased and visual distortion alleviated distinctly (94%)(t=-7.91, P<0.05).CONCLUSION: Phacovitrectomy with ILM peeling is useful in treating foveoschisis in ultra-high myopia with visual function preserving.

Objective　To study the expression of p73 in human non-small cell lung cancer (NSCLC) and the relationship between p73 expression and clinico-pathological parameters. Methods　Expression of p7 3 gene was detected by RT-PCR in 32 human NSCLC tissues, tissues adjacent to ca ncer and non-cancer lung tissues. Results　p73 gene expression up-regulated substantially and detected in 87.5%(28/32) of human NSCLC tissues while expressed at low level in tissues adjacent to cancer and non-cancer lung tissues. Conclusion　Marked up-regulation of p73 gene expres sion is found in human NSCLC.

Hepatitis, Viral, Human ; drug therapy ; Humans ; Prostaglandins E ; therapeutic use ; Randomized Controlled Trials as Topic ; Research Design