Objective To investigate the protective effect of sulodexide (SDX) on oxidized low density lipoprotein (ox-LDL) induced damage to human umbilical vein endothelial cell (HUVEC),and to discuss its mechanism.Methods By using CCK-8 method,the ox-LDL intervention HUVEC dose and the concentration of SDX were determined.The reactive oxygen species (ROS) assay kit was used to verify the protective effect of SDX on HUVEC.Real time fluorescent quantitation-polymerase chain reaction (RT-PCR) was employed to test the endothelial nitric oxide synthase (eNOS) and caveolin-1 mRNA expression;immunoblot assay was adopted to check the protein expression of phosphorylated eNOS (p-eNOS) and caveolin-1.The ability of cell migration was assessed by Transwell assay.Results Stimulated by 100 μg/ml concentration of ox-LDL,the cell viability of HUVEC decreased significantly (P＜0.01).After adding 125 LRU/ml concentration of LDX,the cell viability of HUVEC was remarkably improved (P＜0.01) and the production of ROS was strikingly decreased (P＜0.01).SDX could down-regulate the expression of caveolin-1 (P＜0.05) and up-regulate the expression of eNOS mRNA and p-eNOS (P＜0.05) for ox-LDL-damaged HUVEC,and markedly improve the migration ability of damaged HUVEC (P＜0.01).Conclusion By regulating the caveolin-1/eNOS signal route,SDX can improve impaired HUVEC cell migration ability,thus,to protect endothelial cells.

Objective To summarize clinical experience of one-station therapy for infected seriouslyischemic diabetic foot.Methods The clinical data of 15 patients (15 diseased limbs in total) with infected seriously-ischemic diabetic foot,who were admitted to authors' hospital during the period from June 2015 to April 2016 to receive treatment,were retrospectively analyzed.For all patients,one-station sequential therapy was carried out,which included endovascular revascularization (EVR) to open occluded vessel,surgical debridement and closed negative pressure wound drainage and antiseptic moisturizing wound dressing.The healing rate of infected wound and the limb salvage rate were evaluated.Results The 15 patients included 10 males and 5 females,with a median age of 77 years old.Lower extremity angiography showed that multiple segmental lesions of lower limb were detected in 13 patients and simple leg lesions in 2 patients.According to TASC Ⅱ update classification,leg artery disease of grade D was observed in 13 patients and artery disease of grade C in 2 patients.After EVR therapy,at least one branch of leg arteries was reopened in 14 limbs.Intact arterial arch of pedal-plantar loop (PPL) was seen in 6 patients,semi-arterial arch in 7 patients,and absent of arterial arch in 2 patients.After surgical debridement,the wound was washed by using negative pressure wound therapy (NPWT) device as well as serf-made washing equipment.The time to control wound infection was (7.85±2.84) days.After discharge,the patients were followed up every 3-4 days,at the same time wound dressing exchange with antibacterial moisturizing sulfadiazine silver lipid hydrogel was conducted.Wound healing was achieved in 12 patients,and the mean healing time was (3.70±0.87) months.The wound failed to heal in 3 patients,among them below knee amputation had to be performed in 2 patients (13.3％,both patients showed absent of arterial arch of PPL),and the remaining one patient died of cardiovascular event.Statistically significant difference in PPL pathological changes existed between wound healing group and wound un-healing group (P=0.006 7).Conclusion The treatment of infected seriouslyischemic diabetic foot is rather complicated.Being one-station therapy,the sequential managements,which include EVR,NPWT device together with washing equipment and use of antibacterial moisturizing wound dressing,can effectively increase the blood supply to the affected limb,shorten the time to control infection and lower amputation rate.Therefore,one-station therapy should be regarded as the preferred method for infected seriously-ischemic diabetic foot.

OBJECTIVE:To discuss the way to realizing clinical pharmacists’prescribing rights,and to provide reference for the revise of related policies and regulations. METHODS:The clinical pharmacists prescribing rights and its necessity were inter-preted. Referring to pharmacists’prescribing rights in Canadian limited prescription mode,British dispensatory mode,United States consultative prescription mode,clinical pharmacists’prescribing rights in China were expounded. RESULTS & CONCLU-SIONS:It is necessary and feasible to achieve clinical pharmacists’prescribing rights in China. Clinical pharmacists’prescribing rights can be realized and the pharmaceutical role of clinical pharmacists can be played through conducting clinical pharmacist pre-scription training,establishing chronic disease,common disease,mild disease and other disease dispensatory,gradually revising the concept of“prescription”and“prescribing rights”,promoting the legislation of pharmacists and clinical pharmacists’prescrib-ing rights,promoting the realization of the prescription right of clinical pharmacist,prompting clinical pharmacist to play the role of pharmacy.

BACKGROUND:Compared with the cone stem,short stem holds good matching with femoral canal,and remarkably reduces the risk of prosthesis loosening.OBJECTIVE:To further investigate the clinical efficacy of Accolade Ⅱ stem for Crowe type Ⅰ developmental dysplasia of the hip.METHODS:Clinical data of 16 patients with Crowe type Ⅰ developmental dysplasia of the hip undergoing total hip arthroplasty using Accolade Ⅱ stem were collected,the length of both lower limbs before and after surgery was compared,and the Visual Analogue Scale,functional recovery of the hip and general conditions were observed at 12 weeks postoperatively.RESULTS AND CONCLUSION:(1) The change in length of both lower limbs before and after surgery had significant difference (P ＜ 0.05),and 10 patients (62％) with the same length of both lower limbs before surgery,and 15 cases (94％) after surgery.(2) The postoperative acetablar abducent angle was 41°-54° (average 46.9°).(3) The Visual Analogue Scale and Harris hip scores after surgery were significantly improved compared with baseline (P ＜ 0.05).(4) The intraoperative blood loss was 147 mL on average,the mean operation time was 72 minutes,and the hospitalization time was 7.2 days.(5) All patients recovered well and no complications occurred at 3 months postoperatively.(6) To conclude,Accolade Ⅱ stem is safe and reliable for Crowe type Ⅰ developmental dysplasia of the hip,and exhibits good functional recovery of the hip.

OBJECTIVE: To study the change of laryngeal carcinoma cell apoptosis before and after radiotherapy. METHOD: Living tissue of diseased region obtained from 27 cases of laryngeal carcinoma before and during radiotherapy 10, 30 and 60 Gy were used in this study. With terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL), the spontaneous and radiation-induced apoptotic rate (AR)were examined. RESULT: The AR of living tissue of laryngeal carcinoma before and during radiotherapy 10, 30 and 60 Gy were (21.0 +/- 0.7)%, (60.0 +/- 1.5)%, (42.0 +/- 1.3)%, (25.0 +/- 1.9)%, respectively. The radiation-induced apoptotic rate was significantly higher than that of spontaneous apoptotic rate (P< 0 . 5). In laryngeal carcinoma, spontaneous apoptosis was positively correlated with the radiation-induced apoptosis. CONCLUSION Detecting of AR of laryngeal carcinoma cells before and during radiotherapy may be helpful to predict the sensitivity of radiotherapy in laryngeal carcinoma patients.
Adult ; Aged ; Aged, 80 and over ; Apoptosis ; radiation effects ; Carcinoma, Squamous Cell ; pathology ; radiotherapy ; Dose-Response Relationship, Radiation ; Female ; Humans ; In Situ Nick-End Labeling ; Laryngeal Neoplasms ; pathology ; radiotherapy ; Male ; Middle Aged

Objective: : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. Methods: : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. Results: : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.

Purpose: RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers—such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context. Materials and Methods: We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1. Results: We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)–negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression. Conclusion These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

OBJECTIVETo study clinical characteristics and resistance of wound surface infections, so as to guide clinical diagnosis and rational administration.

METHODSThe clinical setting and laboratory results were collected by analyzing 20 strains of Bacillus cereus isolated from clinical samples in patients from our hospital from October 2011 to June 2012, including 18 males and 2 females,ranging in age from 22 to 67 years old, averaged (47.30 +/- 11.16) years old. The courses of disease ranged from 5 to 20 days. All the patients were treated with nutrition support therapy, debridement and the corresponding antibiotic therapy. The patients had anemia, low protein hyperlipidemia and wound contamination history while Bacillus cereus infected. Thirty people were selected as normal group, including 23 males and 7 females,with an average age of (45.20 +/- 15.05) years old. Infection control condition was assessed by comparing culture for pathogens and patients wound redness or exudation cases before and after treatment. Antimicrobial susceptibility test was conducted by K-B method.

RESULTSA total of 20 stains of Bacillus cereus were isolated from wound surface infections in department of orthopedics of our hospital. Among them,the infections were correlated with the wound contamination (16/20), malnutrition (20/20), and open-fracture (20/20), operation time (15 cases > 3 h). The laboratory blood test showed that the levels of TP [(49.94 +/- 8.24) g/L], ALB [(29.54 +/- 5.45 ) g/L] and Hb [(103.20 +/- 11.79) g/L] in the infection group was lower than those of control group; in the contrast, the levels of WBC [(8.35 +/- 2.31) x 10(9)/L], NEUT [(6.98 +/- 1.99) x 10(9)/L], hs-CRP [(73.60 +/- 55.14) mg/L] and CK [(900.10 +/- 1 259.12) IU/L] were higher in the infection group than those of control group, and the differences were statistically significant (P < 0.01). The diameter of inhibition zone in penicillin, cefazolin, cefuroxime, ceftazidime, cefepime, cotrimoxazole, erythromycin were less than 15 mm, and suggested that Bacillus cereus resisted to these antibiotics. However, the diameter of inhibition zone in clindamycin, vancomycin, gentamicin, ciprofloxacin, imipenem were larger than 20 mm and this data indicated that the bacteria were highly sensitive to these antibiotics.

CONCLUSIONOrthopedic patients who immunocompromised, hypoproteinemia and accompanied by open wounds and contaminated wound susceptible to infect Bacillus cereus; sensitive antimicrobial drugs should be selected on the basis of supplement albumin, symptomatic and supportive treatment.

Adult ; Aged ; Anti-Bacterial Agents ; pharmacology ; Bacillus cereus ; drug effects ; isolation & purification ; Female ; Humans ; Male ; Middle Aged ; Orthopedics ; Wound Infection ; microbiology

Ansamycins, such as rifamycin and ansamitocin, usually consist of a group of structural similar components. Geldanamycin, a benzenic ansamycin, has been found to consist of four structural similar components. We analyzed the geldanamycin (GDM) preparation from Streptomyces hygroscopicus 17997 by LC-ESI(+)-MS/MS, and discovered five novel and one known GDM analogues in trace amounts. Based on the ESI(+)-MS/MS spectra of these GDM analogues, and the present understanding of GDM biosynthesis, we proposed the possible chemical structures of these GDM analogues. Three novel GDM analogues, all having the same molecular formula of C29H42N2O10, were GDM biosynthetic derivatives with one of the three C-C double bonds between C2-C3, C4-C5 and C8-C9 in GDM changed to mono-hydroxylated C-C single bond. The other two novel GDM analogues, having the same molecular formula of C28H38N2O8, were 17(or 12, or 4)-desmethoxylgeldanamycin and 4,5-dihydro-10,11-dehydrate-17-desmethyl-17-hydroxylgeldanamycin, respectively. The known GDM analogue, having the molecular formula of C29H42N2O9, was 4, 5-dihydrogeldanamycin, an intermediate in GDM biosynthesis. The discovery of novel GDM analogues provided us new insights in understanding the biosynthetic details of GDM, and clues of obtaining GDM derivatives by gene-disruption and combinatorial biosynthesis.
Anti-Bacterial Agents ; chemistry ; Benzoquinones ; analysis ; chemistry ; Chromatography, Liquid ; methods ; Lactams, Macrocyclic ; analysis ; chemistry ; Tandem Mass Spectrometry ; methods

BACKGROUND: Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. METHODS: In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1. RESULTS: The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein. CONCLUSION Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
Adaptor Proteins, Signal Transducing ; Adult ; Arteriosclerosis Obliterans/genetics* ; Autophagy ; GRB2 Adaptor Protein ; Humans ; Phosphoproteins/metabolism* ; Phosphorylation ; Protein Binding ; Signal Transduction