3.The predictive value of serum uric acid in the outcome of traumatic brain injury
Du CHEN ; Long BAO ; Feng XU ; Shiqi LU
Chinese Journal of Emergency Medicine 2014;23(11):1244-1248
Objective To investigate the predictive value of serum uric acid for patients with traumatic brain injury.Methods A total of 330 patients with traumatic brain injury (Glasgow Coma Scale score,GCS:3-14) admitted to the First Affiliated Hospital of Soochow University between November 2010 and October 2012 were enrolled.They were divided into a survival group (GOS:2-5) and a non-survival group (GOS:1).The levels of serum uric acid were measured from venous blood in the morning of the second day after admission.Clinical data were analyzed by logistic regression model,spearman correlation,and ROC curve analysis.Results Spearman correlation analysis showed that serum uric acid was significantly correlated with GCS (r =-0.270 1,P =0.000) and GOS (r =-0.251 2,P =0.000).Age,GCS,pupil reaction and serum uric acid were determined as independent predictors for death by logistic model.The adjusted OR of uric acid was 1.0048,(95% CI:1.001 9-1.007 6,P =0.001).The area under the ROC curve was 0.718,(95% CI:0.666-0.766),the optimal cut-off value determined by the Youden index was 304 μmol/L (sensitivity:60.24%,specificity:78.14%,correctly classified:73.64%).In the core model (Age + GCS + Pupil reaction),theR2 value was 0.476 4.With uric acid added into,the predictive power of the model increased to R2 =0.510 5 (7.2% increased).Conclusions The level of serum uric acid is significantly correlated with the severity of TBI and could be used as an independent predictor for death.
4.Fever burden independently contributes to increased poor outcome of patients with traumatic brain injury
Long BAO ; Feng XU ; Li DING ; Weihua LING ; Du CHEN
Chinese Journal of Emergency Medicine 2014;23(5):491-495
Objective To investigate the prognostic value of fever burden in traumatic brain injury (TBI) patients.Methods A retrospective analysis of 355 TBI patients admitted to the emergency department and intensive care unit from November 2010 to October 2012 was performed,and the Glasgow outcome scale (GOS) was followed-up 6 months after the injury.The patients were divided into two groups according to the GOS:good outcome group (4 to 5) and poor outcome group (1 to 3).Relevant clinical findings were studied by statistical description,logistic regression analysis,Spearman correlation analysis and ROC curve analysis.Results Fever burden level was continuously increased with the decrease of GOS from score 5 to 2,except for score 1 of GOS,which was corresponding to a significant lower fever burden.There were significant differences in age,pupil reactivity,Glasgow coma scale (GCS) and fever burden between two groups (P < 0.05).Compared to the good outcome group,the poor outcome group was featured with more advanced average age (P =0.000),poorer pupil reactivity (P =0.000),lower GCS score (P =0.000) and higher fever burden level (P =0.000).Univariate logistic regression analysis suggested that age,GCS,pupil reactivity and fever burden level (OR 1.166,95% CI:1.117-1.217) were associatedwith poor outcome.The fever burden level and the other independent prognostic predictors as age,GCS and pupil reactivity were further included in the multivariate logistic regression model,and the adjusted OR of fever burden level was 1.098 (95% CI:1.031-1.169,P =0.003).ROC curve analysis showed the respective AUC for fever burden was 0.713 (95% CI:0.663-0.760).The relevant analysis revealed a significant negative correlation between the fever burden and the GOS score (r =-0.376,95% CI:-0.462--0.283,P =0.000).Conclusions Fever burden can be considered as an independent predictor of poor outcome of patients with TBI.The TBI patients with early onset of high levels of fever burden will have increased poor outcome risk.
5. Advances in anti-influenza virus of neuraminidase inhibitors
Chinese Pharmaceutical Journal 2015;50(1):7-14
Neuraminidase (NA) is a mushroom-shaped and tetramer structural envelope glycoprotein on the surface of the influenza virus. NA inhibitors can inhibit highly pathogenic influenza virus subtypes and have good safety and drug resistance, hence they are widely used for the prevention and treatment of influenza virus. Based on the present domestic and foreign literatures in this field, this paper summarizes the research status of neuraminidase inhibitors classification and structure-activity relationships. It will help us make better use of existing conditions to design and synthesize better active and more selective anti-influenza drugs.
6.Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy.
Chun-yue DENG ; Ying-ying LONG ; Sha LIU ; Zhang-bao CHEN ; Chong LI
Acta Pharmaceutica Sinica 2015;50(8):1038-1044
In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy.
Animals
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Antineoplastic Agents
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chemistry
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Biotin
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Drug Carriers
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chemistry
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Drug Screening Assays, Antitumor
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Humans
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Micelles
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Pancreatic Neoplasms
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drug therapy
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Photochemotherapy
7.Staged pendulous-prostatic anastomotic urethroplasty followed by reconstruction of anterior urethra for male complex post-traumatic posterior urethral stricture
Deng-Long WU ; San-Bao JIN ; Jiong ZHANG ; Rong CHEN ; Chong-Rui JIN ; Yue-Min XU
Chinese Journal of Urology 2000;0(12):-
Objective To describe a novel surgical technique for male long-segment urethral stric- ture after pelvic trauma using the intact and pedieled pendulous urethra to replace the bulbar and membra- nous urethra,and then reconstructing anterior urethra.Methods Three patients with long-segment post- traumatic bulbar and membranous urethral strictures with short left pendulous urethras who had undergone several failed previous surgeries were treated with staged pendulous-prostatic anastomotic urethroplasty fol- lowed by reconstruction of the anterior urethra.This procedure was divided into 3 stages.The first-stage sur- gery was mobilization of anterior urethra down to the coronary sulcus and then re-routing the prostatic urethra followed by pendulous-prostatic anastomotic urethroplasty with transposition of penis to perineum.The sec- ond-stage surgery was transecting the anterior urethra at the site of coronary sulcus 6 months later when it was re-vaseularized,then straightening the penis and performing urethroperineostomy.The third-stage surgery was reconstruction of anterior urethra 6 months later.Results Case 1 reported satisfactory voiding postopera- tively.Retrograde urethrography showed that the urethra was patent with no post-voiding residual urine (PVR),and bilateral vesicoureteral reflux almost disappeared.The Qmax was 18.8ml/s,and 18ml/s after the third stage surgery and at 2-year follow-up.Case 2 also had satisfactory voiding.A 22F urethral catheter could smoothly pass through the urethra,and Qmax was 19.5 ml/s with no PVR at 2-year follow-up.Case 3 underwent the first stage surgery through perineal and pubic routes.The urethrorectal and urethroperineal fis- tulas were excised and repaired simultaneously.After operation the fistulas healed,but the stenostomia resul- ting from wound infection needed further treatment.Conclusions This procedure is effective for men with complex long-segment post-traumatic bulbar and membranous urethral strictures,especially for those undergo- ing failed previous surgical treatment.
8.Influence of NGF-PEG-PLGA-NPs on neuronal differentiation of neural stem cells and PI3K/Akt signaling pathway
Yan CHEN ; Guoqing BAO ; Feifei LIU ; Jundu ZHANG ; Cuihuan PAN ; Dahong LONG
Chinese Journal of Tissue Engineering Research 2015;(28):4576-4581
BACKGROUND:Our previous studies confirmed that NGF-PEG-PLGA-NPs has good sustained release effect and biological activity in vitro, and can induce the differentiation of PC12 cel s into neuron-like cel s.
OBJECTIVE:To investigate the feasibility of neuronal differentiation of neural stem cel s from septal area of fetal brain induced by NGF-PEG-PLGA-NPs and its influence on PI3K/Akt signaling pathway.
METHODS:According to optimization prescription, NGF-PEG-PLGA-NPs were prepared by multiple emulsion solvent diffusion method. Neural stem cel s were induced to neuronal differentiation in six groups, including control group, NGF group, NGF-PEG-PLGA-NPs group, LY294002 group, LY294002+NGF group and LY294002+NGF-PEG-PLGA-NPs group. Neurons were identified by immunofluorescence, while phosphorylation levels of Akt in PI3K/Akt signaling pathway were detected by western blotting.
RESULTS AND CONCLUSION:The proportions ofβ-Tubulin III-positive neurons in control group, NGF group, NGF-PEG-PLGA-NPs group, LY294002 group, LY294002+NGF group and LY294002+NGF-PEG-PLGA-NPs group were (22.80±2.58)%, (35.80±3.98)%, (35.40±5.77)%, (26.60±3.87)%, (21.20±2.59)%and (25.80±7.22)%, respectively. There were no statistical differences in neuronal differentiation between NGF group and NGF-PEG-PLGA-NPs group (P>0.05), but the ratios of neural differentiation in the two groups were both higher than that in the other four groups (P<0.05). Western blotting results revealed that there were no statistical differences in Akt phosphorylation levels between NGF group and NGF-PEG-PLGA-NPs group (P>0.05), but the phosphorylation levels of Akt were both higher than other four groups (P<0.05). There were also no significant differences between LY294002+NGF and LY294002+NGF-PEG-PLGA-NPs groups and control group (P>0.05), but the phosphorylation levels of Akt were higher than LY294002 group (P<0.05). Results suggest that NGF-PEG-PLGA-NPs promoted neural differentiation of neural stem cel s. The role might be related to increasing phosphorylation levels of Akt in PI3K/Akt signaling pathway.
9.Mechanism Underlying the Role of HIF-1αduring Hepatocyte Apoptosis in Intermittent Hypoxia with Pulmonary Emphysema in Rats
Jingyan ZHAN ; Huaiyong CHEN ; Qi WU ; Xin SUN ; Jing FENG ; Xue LI ; Long XU ; Cuiping BAO
Tianjin Medical Journal 2014;(2):156-159
Objective To investigate the effect of intermittent hypoxia (IH) with pulmonary emphysema on the ex-pression of hypoxia inducible factor-1α(HIF-1α),Bax and Bcl-2, and the mechanism underlying the role of HIF-1αin he-patocyte apoptosis thereof. Methods Sixty rats were randomly divided into four groups: normal control group, rats were treated normally;IH group, rats were treated by 30 s nitrogen and then 90 s air, and rats were treated by from 9:00-17:00 daily;pulmonary emphysema group, rats were treated by smudging for half an hour, twice a day (8:00 and 18:00);IH with pul-monary emphysema group, rats were treated by 30 s nitrogen and then 90 s air from 9:00-17:00 daily. After exposure four-teen weeks, rats were killed. qRT-PCR assay was conducted to detect the expression of HIF-1α mRNA, Bax mRNA and Bcl-2 mRNA in live tissues. Results The expressions of HIF-1αmRNA, Bax mRNA and Bax/Bcl-2 were significantly higher in IH with pulmonary emphysema group than those in control group,IH group and pulmonary emphysema group (P<0.05). The expression level of Bcl-2 mRNA was significantly lower in IH with pulmonary emphysema group than that of con-trol group and pulmonary emphysema group (P < 0.05), but no significant difference compared with that of IH group (P >0.05). The levels of HIF-1αand Bax were positively correlated with the level of Bax/Bcl-2 (r=0.732 and 0.699),but the lev-els of HIF-1αand Bax were negatively correlated with the level of Bcl-2 (r=-0.705). Conclusion The expression levels of HIF-1αmRNA, Bax mRNA and Bcl-2 mRNA were over-regulated in hepatocytes induced by intermittent hypoxia with pul-monary emphysema. The HIF-1αexpression was correlated with Bax and Bcl-2, suggesting that HIF-1αmay promote the hepatocyte apoptosis through transcriptional co-activators, Bax and Bcl-2.
10.Oxidative stress injury of myocardial cells induced by emphysema with intermittent hypoxia in rats
Jianmin DUAN ; Huaiyong CHEN ; Qi WU ; Xin SUN ; Jing FENG ; Xue LI ; Long XU ; Cuiping BAO
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2014;(1):22-25
Objective To observe the effect of exposure of emphysema with intermittent hypoxia on oxidative stress injury of myocardial cells in rats. Methods Sixty male Wistar rats were divided randomly into four experimental groups(each n=15). The normal control group was bred normally. The emphysema group was exposed to cigarette smoke twice a day(once 30 minutes). The intermittent hypoxia(IH)group was exposed to intermittent hypoxia circumstance 8 hours/day,and the emphysema with IH group was exposed to cigarette smoke twice a day (once 30 minutes)and intermittent hypoxia circumstance 8 hours/day. Each group was exposed for 8 weeks. At the beginning of 9 weeks,the blood gas analysis was performed in 5 rats selected randomly from each group,and the rest rats were sacrificed and their hearts and lungs were taken. Under light microscope,the lung tissues stained with hematoxylin-eosin(HE)were examined. The lung pathology and the results of blood gas analysis showed that the emphysema with IH rat model was established successfully. The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)in rat myocardium were measured by enzyme-linked immunosorbent assay(ELISA),and the subunit p22phox mRNA expressions of nicotinamide adenine dinucleotide phosphate(NADPH)-oxidase were detected by real-time reverse transcription-polymerase chain reaction(RT-PCR). Results Compared with the normal group, the MDA levels and p22phox mRNA expressions were increased obviously in emphysema group, IH group and emphysema with IH group〔MDA(μmol/g):2.93±0.54, 3.58±0.63, 4.51±0.72 vs. 1.75±0.56, p22phox mRNA:0.043±0.004,0.067±0.015,0.123±0.016 vs. 0.018±0.002,all P<0.05〕,but the activities of SOD were decreased significantly(U/mg:36.07±4.79,33.51±7.12,24.29±5.36 vs. 46.08±5.12,all P<0.05). In emphysema with IH group,the increase of MDA levels and p22phox mRNA expressions and decrease of SOD levels were more remarkable compared with those in emphysema group and IH group(all P<0.05). The expression of p22phox mRNA was positively correlated with MDA level(r=0.734,P<0.001). Conclusion The myocardial tissue oxidative stress injury in rats induced by emphysema with intermittent hypoxia exposure is more serious than that induced by exposure of either emphysema or intermittent hypoxia alone,NADPH oxidase possibly being the important medium of myocardial cell response to oxidative stress.