Objective: To prepare exenatide-loaded poly (lactic-co-glycolicacid)(PLGA) microspheres and to evaluate their release behavior in vitro. Methods: Exenatide-loaded PLGA microspheres were prepared by W/O/O method using PLGA as vectors. An HPLC approach was established to determine the content and in vitro cumulative release. The physicochemical characteristics of microspheres, including the mean diameter, morphology, drug entrapment efficiency and loading efficiency, were evaluated. Results: The prepared microspheres were well-shaped, with a mean diameter of (51.2±1.97) μm. The drug loading was (4.50±0.13)% and the encapsulation efficiency was (96.5±2.68)%. The first day burst release was (13.19 ± 1.39)% and the in vitro 28-day-cumulative-release was (88.6 ± 0.73)%. Conclusion: The W/O/O method is stable, controllable, and repeatable for preparing exenatide-loaded microspheres using biodegradable polymers PLGA as the vector; the microspheres yield a one-month continuous release and have a bright future in treatment of diabetes mellitus.

BACKGROUNDCerebral venous thrombosis (CVT) may lead to serious neurological disorders; however, little is known about the risk factors for recurrent CVT. Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol (HDL-C) levels with recurrent CVT.

METHODSThis retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital, Capital Medical University from August 2005 to September 2009. Demographic and clinical variables were collected, as well as laboratory parameters, including plasma fibrinogen and HDL-C. Patients with CVT were followed for recurrent symptomatic CVT. Follow-up was through the end of September 2010. Potential predictors of recurrence were analyzed using Cox survival analysis.

RESULTSAt the end of the follow-up, 95 patients were eligible for the study. Twelve of 95 patients (12.6%) had recurred CVT. The median time of recurrence was 7 months (range: 1-39 months). Eight of these 12 (66.7%) experienced recurrence within the first 12 months after their initial CVT. The recurrence rate of CVT was 2.76 per 100 patient-years. Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen (>4.00 g/L) and low HDL-C (<1.08 mmol/L) levels at baseline was the only independent predictor for recurrent CVT (hazard ratio: 4.69; 95% confidence interval: 1.10-20.11; P < 0.05). Of the twelve patients with recurrent CVT in our study, 7 (58.3%) had high fibrinogen plus low HDL-C levels. All 7 of these patients took warfarin for 3-12 months, and 6 of 7 had recurrent CVT after the discontinuation of anticoagulant treatment.

CONCLUSIONSConcomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.

Adolescent ; Adult ; Aged ; Cholesterol, HDL ; metabolism ; Cohort Studies ; Female ; Fibrinogen ; metabolism ; Humans ; Intracranial Thrombosis ; metabolism ; pathology ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Young Adult

OBJECTIVETo compare the clinical characteristics of triple-negative (TN) breast cancer and non-triple-negative (NTN) breast cancer, enrich the information of TN patients, and provide evidences for individualized combined treatment.

METHODSThe data of 408 cases received operation in the year of 2002 was enrolled in this study. TN patients were confirmed according to the immunohistochemical (IHC) test of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu. The clinical characteristics, recurrence, metastasis and survival were compared between the two groups.

RESULTSSeventy-seven patients (18.9%) were confirmed TN cases. The median follow-up was 64 months (range, 3-79 months). Of all the cases, 58 occurred local recurrence or metastasis and 51 died, it was 19 and 12 in TN group. Compared with the NTN group, the TN patient tended to be younger and the tumor mass larger (P=0.015 and 0.011). However, axillary lymph nodes metastasis occurred more often in NTN patients than in TN patients (P=0.001). The rate of local recurrence and metastasis in TN group was significantly higher than in NTN group (P=0.005 and 0.025), and TN cases were more likely to develop lung metastasis than NTN patients (P<0.01). The 3-year and 5-year overall survival rate in TN group were significantly lower than in NTN group (86.4% vs. 93.4%, P=0.0205; 77.7% vs. 87.9%, P=0.0215). The 3-year and 5-year disease-free survival rate in TN group were also significantly lower than in NTN group (78.4% vs. 92.4%, P=0.0038; 72.8% vs. 85.8%, P=0.0041). Tumor size, lymph node status and triple-negative were the most important factors influencing the prognosis on multivariate Cox regression analysis.

CONCLUSIONSTN breast cancer haa some specific clinical characteristics. The prognosis of TN patients is worse than that of NTN patients. Further study is needed to find individualized treatment for TN breast cancer patients.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; metabolism ; pathology ; therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, Epidermal Growth Factor ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Analysis ; Young Adult

AIMTo investigate the effects of RLI on plasma nitric oxide (NO) and NO synthase (NOS) isoforms of healthy humans.

METHODS30 healthy human subjects (aged from 40 - 70 years old) were recruited. RLI was induced by five 5 min cycles of ischemia of non dominant arm (200 mmHg, 5 min interval). Blood pressure, heart rate, and the feelings of ischemic arm were continuously monitored. Venous plasma was collected in contralateral arm at Pre, Post-0 h, Post-4 h, and Post-24 h. Plasma level of NO was measured by Griess reaction, and NOS was measured by chemical method.

RESULTSBlood pressure and heart rate varied in normal range. The uncomfortable feeling was decreased with the increasing numbers of ischemic cycles. Plasma level of NO, and iNOS in plasma were significantly increased at Post-0 h, Post-4 h, and Post-24 h compared to Pre (P < 0.05). tNOS was also significantly increased at Post-0 h and Post-4 h compared to Pre (P < 0.05). No significant change in plasma cNOS was shown at following three time points than Pre.

CONCLUSIONThese findings suggest that RLI can elevate plasma level of NO, tNOS, and iNOS in healthy humans. RLI might be a safe method as a rIPC, and it would have important possibility to be performed in clinic.

Adult ; Aged ; Arm ; blood supply ; Female ; Humans ; Ischemia ; blood ; physiopathology ; Ischemic Preconditioning ; methods ; Male ; Middle Aged ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; metabolism ; Reperfusion Injury ; physiopathology ; prevention & control

Objective To evaluate the efficacy and safety of acute ureteroscopy for the treatment of ureterie stones during middle and late pregnancy.Methods From June 1998 to March 2005,17 pregnant women(mean age,27 years;age range,21-35 years)with ureteric stones were treated by ureteroscopy when the fetus was at 20-36 weeks of gestation(mean,29 weeks).All the cases presented with urgent symptoms such as recurrent renal colic(11 cases),fever(4)or acute obstructive anuria(2).Among 17 cases,the stones(between 6 mm?7 mm and 13 mm?21 mm)were located in the upper(8 cases),middle(5)or lower ureter(4);and on the left side(5 eases),on the right(10)and on both(2)of the lower ureter. Mild hydronephrosis were observed in 6 cases and moderate hydronephrosis in 11,Of the 17 cases,14 under- went ureteroscopic pneumatic lithotripsy;in 1 case the calculi were pushed to the renal pelvis;and 2 cases were treated by Double-J catheter drainage.Results All the urgent symptoms in 17 cases were relieved after treatment.The stone-free rate of initial treatment was 82.4%(14 of 17).Three cases with residual stones were treated by Douhle-J catheters,which were replaced every 3 months until the calculi were re- moved.No abortion,premature delivery or complications such as ureter perforation occurred.Mild renal colic occurred in 1 case after insertion of Douhle-J catheter,and it was relieved 3d later;gross hematuria occurred in l case and disappeared 6 d later without treatment.All 17 patients had normal delivery and gave birth to healthy children.Conclusions Ureteroscopy is a safe and reliable method for the treatment of ureteric calculi during middle and late pregnancy.

OBJECTIVETo explore the feasibility of a dual-energy computed tomographic angiography (DECTA) protocol using test-bolus injection with reduction of contrast material (CM) dose in second generation dual-source CT system.

METHODSTotally 57 consecutive patients underwent CT angiography scan covering the cervical and cerebral arteries. CT was performed with second generation dual-source CT system. The time to peak (T) using a test-bolus injection was calculated. The patients were divided into three groups (A, B, and C) with different CM doses (40, 45, and 50 ml) and different delay time points [ (T+1) , (T+1) , and (T+2) s] . All the patients were followed by a 48 ml saline flush. Arterial enhancements were quantified by measuring attenuation values of the aortic arch, bifurcation of common carotid artery, contralateral internal jugular vein of the CM injection, superior vein cava, proximal middle cerebral artery, basilar artery, and straight sinus on source images. Visualizations of intracranial artery and ipsilateral venous effect of the CM injection were rated on a four-point grading scale on CTA images for qualitative assessment.

RESULTSAlthough the attenuation of internal jugular vein and straight sinus were significantly lower in group A than in groups B and C (P<0.05) , the attenuation of aortic arch, superior vein cava, common carotid artery, middle cerebral artery, and basilar artery vessels showed no significant differences among these three groups. The scores of the visualizations of intracranial artery and ipsilateral venous effect of the CM injection were also not significantly different among these three groups.

CONCLUSIONBased on the delay time calculated by a test-bolus injection, a reduced-dose contrast material may provide an equal degree of arterial attenuation and a lower attenuation of vein for dual-energy CTA covering the craniocervical region in second generation dual-source CT system.

Adult ; Aged ; Angiography ; methods ; Contrast Media ; administration & dosage ; Feasibility Studies ; Female ; Head ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Neck ; diagnostic imaging ; Radiation Dosage ; Tomography, X-Ray Computed ; methods

Objective To collect the laboratory parameters and clinical parameters of blood culture positive samples,and analyze the composition and laboratory characteristics of real pathogens by combining with clinical follow-up and anti-infectious treatment outcomes.Methods We conducted a prospective study to isolate the 483 strains of pathogens from 4313 cases of blood samples for clinical examination between March 2013 and March 2015.The results of laboratory and clinical infections were collected for each positive culture and were followed up for clinical follow-up to understand the responsible doctors' experience-based judgment and targeted clinical treatment of antibiotics.After comprehensive analysis we determined the real pathogens and contaminants.Results Of the 483 positive cultures,331 were finally determined as pathogenic ones,accounting for 68.5% of the number of positive isolates; 97 were contaminated bacteria (20.1%); and 55 strains with uncertain pathogenic nature (11.4%).Escherichia coli accounted for the highest proportion (41.2%)of pathogenic bacteria.Coagulase-negative staphylococci took up the highest proportion (75.3%)of the contaminated bacteria.As many as 253 strains (52.4%)were detected from the aerobic or anaerobic bottles.The detection rate of Escherichia coli in anaerobic bottles (23.9%)was higher than that in aerobic bottles (13.8%)(P <0.05).Of 97 strains of positive isolates,only one bottle was reported positive for 90 strains,accounting for (92.8%),and more than two bottles of 7 positive strains,accounting for (7.2%)(P <0.05).34 positive in 24 h (35.1%),77 positive in 48 h (79.4%),the positivebacteria ratio within 48 h (79.4%)was higher than that of bacteria contamination ratio within 24 h (χ2 =38.935, P =0.000),with a significant difference.Conclusion Establishment of contaminated bacteria in blood culture cannot rely solely on laboratory or clinical parameters.It should be combined with the experience of clinicians to determine the clinical response to comprehensive judgments.For the laboratory to determine the presence of contamination,the number of positive bottles and the amount of sun are still two factors of important value.Paying attention to inspection of anaerobic bottles is more conducive to the detection of Escherichia coli.

Disorders of iron utilization caused by abnormal elevation of hepcidin levels are the main mechanism of anemia of chronic disease. Hepcidin is mainly produced by the liver. Recently it has been found that monocytes are another source of hepcidin. The increased hepcidin in serum and urine of multiple myeloma patients may be one cause of anemia of chronic disease (ACD). However it is unclear whether the peripheral blood monocyte hepcidin is involved in the pathogenesis of anemia of chronic disease. This study was purposed to investigate the role of monocyte hepcidin in multiple myeloma patients with anemia of chronic disease. The clinical data and peripheral venous blood of multiple myeloma patients were collected.Serum concentration of IL-6 and TNF-α was detected by ELISA. Peripheral blood monocytes were isolated by CD14(+) magnetic beads. Hepcidin, IL-6 and TNF-α mRNA of monocytes were detected by real time quantitative PCR. The results showed that the expression level of monocyte hepcidin mRNA in myeloma patients was higher than that in normal controls. In untreated patients, the expression level of monocyte hepcidin mRNA was negatively correlated with hemoglobin, and positively correlated with serum ferritin and IL-6 levels, but unrelated with TNF-α levels.It is concluded that the increased monocyte hepcidin levels in multiple myeloma patients may play an etiologic role in ACD.
Adult ; Aged ; Anemia ; etiology ; Case-Control Studies ; Chronic Disease ; Female ; Ferritins ; blood ; Hepcidins ; blood ; Humans ; Interleukin-6 ; blood ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Monocytes ; metabolism ; Multiple Myeloma ; blood ; complications ; Tumor Necrosis Factor-alpha ; blood

Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; complications ; pathology ; physiopathology ; Liver ; pathology ; physiopathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the in vitro effect of erythropoietin (EPO) on hepcidin of monocytes and its molecular mechanisms.

METHODSHepcidin and signaling molecules including C/EBPalpha, Smad1/5/8, p-Smad1/5/8 and p-STAT3 were detected by real time PCR and Western blot. THP-1 monocytes were stimulated by interleukin-6 (IL-6) or lipopolysaccharide (LPS). EPO receptor (EPOR) antibody was added to observe its antagonistic effect on EPO and impact on the signaling proteins.

RESULTSEPO suppressed mRNA expression of THP-1 hepcidin of monocytes induced by 20 ng/ml IL-6 or 1 microg/ml LPS in both dose and time dependent manner. The most decrease of hepcidin expression was observed at 2 IU/ml EPO for 6 hours. EPO also down-regulated hepcidin protein induced by 20 ng/ml IL-6. At 2 IU/ml EPO for 6 hours hepcidin protein was down-regulated, as was C/EBPalpha, p-Smad1/5/8 and p-STAT3. Antibody to EPOR antagonized the down-regulation of EPO on hepcidin and signaling proteins.

CONCLUSIONSMonocytes hepcidin can be reduced by EPO when stimulated by IL-6 or LPS. The mechanism of which may be at least in part, via suppression of C/EBPalpha, p-Smad1/5/8 and p-STAT3 signaling.

Antimicrobial Cationic Peptides ; metabolism ; Cells, Cultured ; Erythropoietin ; pharmacology ; Hepcidins ; Humans ; Interleukin-6 ; pharmacology ; Lipopolysaccharides ; pharmacology ; Monocytes ; drug effects ; metabolism ; Signal Transduction