High-mobility group box 1 (HMGB1) is a non-histone nuclear protein in most eukaryocytes. Inside the nucleus, HMGB1 plays an important role in several DNA events such as DNA repair, transcription, telomere maintenance, and genome stability. While outside the nucleus, it fulfils more complicated functions, including promoting cell proliferation, inflammation, angiogenesis, immune tolerance and immune escape, which may play a pro-tumoral role.Meanwhile, HMGB1 acts as an anti-tumoral protein by regulating immune cell recruitment and inducing immunogenic cell death (ICD) during the carcinogenesis process. Therefore, abnormal expression of HMGB1 is associated with oncogenesis, development, and metastasis of cancer, which may play a dual role of pro-tumor and anti-tumor.
Carcinogenesis ; Cell Proliferation ; HMGB1 Protein/metabolism* ; Humans ; Neoplasms/pathology* ; Neovascularization, Pathologic

OBJECTIVE：To establ ish characteristic pattern of vinegar-processed product of Schisandra chinensis formula granules from different habitats ，and to determine the contents of 5 components. METHODS ：HPLC method was adopted. The determination was performed on Agilent ZORBAX SB-C 18 column with mobile phase consisted of acetonitrile-water （gradient elution）at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃，and detection wavelength was set at 220 nm. The sample size was 10 µL. Using schisandrin as reference ，HPLC characteristic pattern of 19 batches of vinegar-processed S. chinensis formula granules was drawn. The similarity evaluation was performed with Similarity Evaluation System of TCM Chromatographic Fingerprints （2012 edition），and common peaks were confirmed. The contents of schisandrin ，schisandrol， angeloylgomisin H ，schizandrin and deoxyschizandrin were determined by same method. RESULTS ：There were 8 common peaks in 19 batches of vinegar-processed S. chinensis formula granules ，and the similarities were all above 0.996；five of them were identified as schisandrin ，schisandrol，angeloylgomisin H ，schizandrin and deoxyschizandrin ，respectively. The linear range of schisandrin，schisandrol，angeloylgomisin H ，schizandrin and deoxyschizandrin were 0.030-0.380，0.016-0.195，0.009-0.115， 0.006-0.078 and 0.011-0.138 μg（r＞0.999），respectively. RSDs of precision ，stability（24 h）and reproducibility tests were all lower than 2％. Average recoveries were 99.84％，99.54％，99.28％，100.03％，100.27％（RSD＜1.4％，n＝9）. Average contents of five components in 19 batches of samples were in the range of 0.15％-0.36％，0.02％-0.16％，0.02％-0.06％，0.02％-0.08％ and 0.08％-0.17％，respectively；among them ，total contents of five components in sample S 18 and S 19 from Hebei province were relatively high ，while those were relatively low in sample S 16 and S 17（RSD＝42％）；RSD of total content in other samples （S1-S15）was 12％，and was lower than that of Hebei province ；total content of five components were higher in sample from Jilin province. CONCLUSIONS ： Established characteristic pattern and method for the content determination are specific and reproducible，and can be used for the quality evaluation of vinegar-processed S. chinensis formula granules. The total content fluctuation of vinegar-processed product of S. chinensis formula granules from Liaoning ，Jilin and Heilongjiang provinces is lower than that in Hebei province ，and the quality of vinegar-processed Δ 基金项目：国家中药标准化项目（No.ZYB2H-Y-GD-13） ＊主管中药师 ，硕士 。研究方向 ：中药质量标准 。E-mail： S. chinensis formula granules from Jilin province is the best. lzz332@126.com

Objective:To investigate the protective effects of Elabela(ELA) on the renal injury of db/db mice and its possible mechanism.Methods:Sixteen eight-week-old male db/db mice were intraperitoneally injected with ELA(5 mg·kg -1·day -1) or equivalent normal saline( n=8) for 8 weeks. Eight age-matched male db/m mice received equivalent normal saline injection as normal control. At the end of the experiment, blood and urine samples were obtained for HbA 1C and urinary albumin/creatinine(ACR) measurements. Immunohistochemistry was used to observe the expression of ELA. Histopathological changes in kidney tissue were observed by HE staining and Masson staining. The levels of collagen type Ⅳ(Col-Ⅳ) and transforming growth factor-β1(TGF-β1) as well as Yes-associated protein(YAP) phosphorylation in kidney tissue were examined by western blot. Results:Immunohistochemistry results showed that ELA expression was decreased in the renal tissue of db/db mice as compared with that of db/m mice( P<0.05). After ELA treatment, ACR and blood pressure were markedly decreased in db/db mice( P<0.05), but without significant changes in the body weight and HbA 1C. Renal tubular epithelial cells edema, basement membrane thickening, and increased collagen fiber in db/db were improved by ELA administration. Compared with db/m mice, the levels of TGF-β1 and Col-Ⅳ expression, as well as YAP phosphorylation were significantly increased in renal tissue of db/db mice(0.98±0.08 vs 0.68±0.10, 1.10±0.14 vs 0.51±0.08, 3.38±0.72 vs 0.81±0.13, all P<0.05), which were down-regulated after ELA administration(0.80±0.06, 0.51±0.05, 2.21±0.22, all P<0.05). Conclusion:ELA may improve the renal injury of db/db mice by regulating the signaling pathway of YAP, thereby delaying the development of diabetic nephropathy.

Objective: To estimate the prevalence and the risk factors of preoperative coronary angiography (CAG) confirmed coronary stenosis in patients with degenerative valvular heart disease. Methods: A total of 491 patients who underwent screening CAG before valvular surgery due to degenerative valvular heart disease were enrolled from January 2011 to September 2014 in our hospital, and clinical data were analyzed. According to CAG results, patients were divided into positive CAG result (PCAG) group or negative CAG (NCAG) group. Positive CAG result was defined as stenosis ≥50% of the diameter of the left main coronary artery or stenosis ≥70% of the diameter of left anterior descending, left circumflex artery, and right coronary artery.Risk factors of positive CAG result were analyzed by multivariable logistic regression analysis, and Bootstrap method was used to verify the results. Results: There were 47(9.57%)degenerative valvular heart disease patients with PCAG. Patients were older ((68.0±7.6)years vs.(62.6±7.1)years, P<0.001) and the prevalence of typical angina was significantly higher (14.89%(7/47)vs. 2.03%(9/444), P<0.001)in PCAG group than in NCAG group. Multivariable logistic regression analysis showed that age (OR=1.118, 95%CI 1.067-1.172, P<0.001), typical angina (OR=8.970, 95%CI 2.963-27.154, P<0.001), and serum concentration of apolipoprotein B (OR=20.311, 95%CI 4.774-86.416, P<0.001) were the independent risk factors of PCAG in degenerative valvular heart disease patients. Bootstrap method revealed satisfactory repeatability of multivariable logistic regression analysis results (age: OR=1.118, 95%CI 1.068-1.178, P=0.001; typical angina: OR=8.970, 95%CI 2.338-35.891, P=0.001; serum concentration of apolipoprotein B: OR=20.311, 95%CI 4.639-91.977, P=0.001). Conclusions A low prevalence of PCAG before valvular surgery is observed in degenerative valvular heart disease patients in this patient cohort. Age, typical angina, and serum concentration of apolipoprotein B are independent risk factors of PCAG in this patient cohort.

Objective: To explore the plasma chemokines expressions and related clinical implication in patients with Stanford type A aortic dissection (AD). Methods: We retrospectively analyzed the data of 65 patients with Stanford type A aortic dissection, hypertensive patients and 11 healthy subjects admitted in our department from October 2013 to December 2014, they were divided into four groups: NH-CON group (11 healthy subjects), H-AD group (29 AD patients with hypertension), NH-AD group (21 AD patients without hypertension), and H-CON group (14 hypertension patients). Four plasma samples from AD patients and 4 plasma samples from healthy subjects were collected randomly with random numbers table, and the levels of different chemokines were examined by protein array analysis. Then, plasma levels of chemokines including macrophage inflammatory protein 1β(MIP-1β), epithelial neutrophil activating peptide 78(ENA-78), interleukin 16(IL-16), interferon inducible protein 10(IP-10) and FMS-like tyrosine kinase 3(Flt-3) ligand were analyzed by luminex. Pearson analysis was used to determine the correlations between the chemokines and serum C reactive protein (CRP) levels. Results: Plasma levels of MIP-1β(34.0(29.3, 47.2) ng/L vs. 51.0(28.2, 80.7) ng/L, P<0.05) and ENA-78(110.5(59.1, 161.4) ng/L vs. 475.7(299.3, 837.3) ng/L, P<0.05) were significantly lower in H-AD group, while plasma IL-16 level was significantly higher in H-AD group(54.7(16.3, 187.8) ng/L vs. 17.5(11.9, 20.8) ng/L, P<0.05) than in H-CON group. Plasma levels of MIP-1β(48.3(26.4, 62.1) ng/L, P<0.05) were significantly lower in H-AD patients than in NH-AD patients. Plasma level of ENA-78 was significantly lower in NH-AD group than in NH-CON group (95.0(58.0, 155.0) ng/L vs. 257.7(85.2, 397.8) ng/L, P<0.05). The levels of IP-10 and Flt-3 ligand were similar among the 4 groups (all P>0.05). Pearson analysis showed that there were no correlation between MIP-1β(r²=0.01, P>0.05), ENA-78(r²=0.02, P>0.05), IL-16(r²=0.02, P>0.05), IP-10(r²=0.00, P>0.05), Flt-3 ligand(r²=0.02, P>0.05) and CRP levels in patients with Stanford type A aortic dissection. Conclusions Lower plasma levels of MIP-1β and ENA-78 and higher plasma levels of IL-16 may associate with the occurrence and development of type A aortic dissection, but their concentrations are not correlated with serum CRP levels. There is no significant change on plasma levels of IP-10 and Flt-3 in the Stanford type A aortic dissection patients.

Objective To explore the plasma expressions of monocyte chemotaxis proteins(MCPs) in patients with type A aortic dissection and their clinical significance.Methods 51 patients with type A aortic dissection were enrolled,in which 29 combined with hypertension.Fourteen hypertension patients and 1 1 hcalthy subjects were enrolled as control.Plasma samples were collected and we examined the levels of MCP-1,MCP-2 and MCP-4 by enzyme linked immunosorbent assay (ELISA).Results Plasma levels of MCP-1 and MCP-2 significantly decreased in patients with type A aortic dissection compared to healthy subjects(P ＜0.001),while MCP-4 had no change.Type A aortic dissection patients with or without hypertension both showed significant decreased plasma MCP-1 and MCP-2 levels compared to hypertension patients(P ＜0.001).There was no change of MCP-4 among different groups.Furthermore,Spearman correlation analysis showed that there was no correlation between serum CRP levels and plasma MCP-1,MCP-2 concentrations.Conclusion Plasma MCP-1 and MCP-2 may participate in the pathogenesis of type A aortic dissection,and their concentrations were not correlated with hypertension or serum CRP levels.The detailed mechanism needs further observations.

Objective To evaluate the feasibility, safety and effectiveness of interventional occlusion with thin waist occluder for perimembranous ventricular septal defect with pseudoaneurysm. Methods During the period from March 2008 to March 2013 at Shanghai Yodak Cardiothoracic Hospital , interventional occlusion with thin waist occluder was carried out in a total of 96 patients with perimembranous ventricular septal defect (VSD) complicated by pseudoaneurysm. The patient’s age varied from 2 years to 36 years. Before the procedure, routine left ventricular angiography and ascending aortic angiography were carried out. Left ventricular angiography and ascending aortic angiography as well as the transthoracic ultrasonography were performed immediately after the procedure to observe the therapeutic results. Follow-up checkups with transthoracic ultrasonography, EKG and chest X-ray film were conducted at one week as well as at one, 3, 6 and 9 months after the surgery were conducted. Results Successful occlusion of VSD was obtained in 93 patients, with a success rate of 96.8% (93/96). After the surgery, small amount of shunt flow was detected in 8 patients, which disappeared within 48 hours in 7 patients, and in the other one the shunt flow disappeared one month later which was confirmed by follow-up examination. After the treatment, complete right bundle branch block occurred in 4 patients, complete left bundle branch block in 5 patients, and transientⅢdegree atrioventricular block in one patient. The conduction block disappeared at the time of discharge in all patients. The left ventricular end-diastolic diameter (LVEDD) decreased from preoperative (47.5 ± 5.2) mm to postoperative (45.2 ± 5.1) mm, the difference was statistically significant (t = 18.33, P < 0.01). During the follow-up period lasting for 9 months, no delayed cardiac arrhythmia, valve damage or sudden death occurred. Conclusion For the treatment of perimembranous ventricular septal defect with pseudoaneurysm, interventional occlusion with thin waist occluder is safe and effective with excellent mid-term effect. Based on the imaging findings, including the location, shape, ruptured orifice, number of the perimembranous pseudoaneurysm as well as the distance between the pseudoaneurysm and the aortic valve, to select suitable occluder and proper occlusion site is the key to ensure a successful surgery.