Objective To explore the potential mechanisms of regulating adiponectin secretion and expression in vivo in rats.Methods To observe the regulation of adiponectin by fasing-refeeding and β-adrenergic agonists, male Wistar rats were fasted for 18 h and allowed to refeed or a β3-adrenergic receptor agonist was infused into refeeding rats.The effects of insulin clamp on adiponectin secretion and expression, including euglycemichyperinsulinemic clamp and hyperglycemic-hyperinsulinemic clamp, were also investigated.Plasma adiponectin level was determined by radioimmunoassay.Adiponectin mRNA expression in adipose tissue of rats was detected by realtime PCR.Results (1) Refeeding 18 h fasted rats increased plasma adiponectin concentration (about 2-fold) and adipose tissue adiponectin expression (about 3-fold), which were completely blocked by administration of β-adrenergic agonist.(2) Hyperinsulinemic clamp increased plasma adiponectin concentration and adiponectin gene expression in adipose tissue.Conclusions Adiponectin secretion and expression are acutely regulated in vivo by nutritional status.Insulin and β-adrenergic agonists regulate adiponectin secretion and expression in adipose tissue.

Objective To investigate the value of central venous pressure (CVP) combined with visual left ventricular ejection fraction(LVEF) as an indicator of fluid responsiveness in patients with septic shock.Methods A retrospective analysis of 83 patients with septic shock receiving fluid challenge was conducted.The hemodynamic changes were evaluated with the pulse indicator continuous cardiac output (PiCCO) monitor,and all the patients were divided into two groups:the responded group (△CI％ ≥15％)and the unresponded group(△CI ＜ 15％),according to the change in CI(△CI％).Those patients were divided into several subgroups,including low CVP group (CVP ＜ 8 mmHg) and high CVP group (CVP ≥ 8 mmHg),low LVEF group(LVEF ＜ 50％) and high LVEF group(LVEF ≥ 50％),according to the initial value of CVP and LVEF.The changes in hemodynamic variables were compared before and after fluid challenge in each subgroup.The ability of CVP and visual LVEF was evaluated to predict fluid responsiveness with receiver operating characteristic curves.Results Fifty three (63.9％) patients responded to the fluid challenge,and lower CVP and higher LVEF patients were more frequency in responded group.The threshold value of 8 mmHg CVP for prediction of fluid responsiveness revealed the area under the curve (AUC) of 0.646 (P =0.219),and 50％ visual LVEF revealed AUC of 0.729 (P =0.023).CVP in combination with visual LVEF for prediction of fluid responsiveness showed an AUC of 0.817 (P =0.001) with a sensitivity of 76.3％ and a specificity of 88.2％.Conclusions Visual LVEF alone and combined with CVP can be used as an indicator of fluid responsiveness in patients with septic shock.

Objective To investigate the accuracy of careful clinical evaluation in hemodynamic status and guidance of PiCCO monitor in clinical treatment.Methods A total of 96 hemodynamic unstable cases were evaluated prior to the insertion of the PiCCO catheter.The attending physician in charge of the patient was required to complete a questionnaire to predict the range of key hemodynamic variables for CI,GEDI,SVRI and EVLWI.Additionally,the attending was also asked to indicate a plan for therapy based on the predicted hemodynamic profile and decide if the predicted therapy plan was altered after the the first measurement of hemodynamic variables.Results The accurate prediction of hemodynamic variables was CI (55.2％),GEDI(60.4％),SVRI(63.5％) 和 EVLWI (78.1％),among which EVLWI had a higher accuracy(P ＜ 0.05).49％ doctors altered their planned therapy according to the result of the PiCCO information.Doctors had more difficulty in accurately predicting hemodynamic values in critical patients which APACHE Ⅱ scored 15 ～25 (42.3％ vs 67.9％ and 42.3 ％ vs 75.0％,x2 =4.755,5.231,P ＜ 0.05).The prediction of patients with acute myocardial infarction was more accurate than those of without acute myocardial infarction,and less to alter the planned therapy(21.1％ vs 55.8％,x2 =7.382,P =0.007).The patients of impaired oxygenation had less accurate predictions and less therapy alterations(32.3％ vs 56.9％,x2 =5.110,P =0.024).Attending was able to predict the hemodynamic status more accurately(63.9％ vs 40％,x2 =5.152,P =0.023) and alter the predicted therapy less(39.3％ vs 65.7％,x2 =6.189,P =0.013) in patients who were enrolled later.Conclusions Clinical evaluation in hemodynamic status of critically ill patients had a lower accuracy,the information obtained by PiCCO often instruct clinical doctors to choose the optimal treatment.

ObjectiveTo assess the effect of PM2.5 on sympathetic innervation and the relationship with cardiac nerve growth factor in healthy rat hearts,identify the ability to the sympathetic nerve reconstruction,and explore the possible arrhythogenic mechanism of PM2.5.MethodsForty healthy SD rats were instilled into trachea with two different solutions twice per week for four weeks:control group with saline and experimental group with PM2.5 25 mg/kg.Then these rats were killed,and biatrial appendages,two ventricular anterior walls were left.Immune cytochemical staining of cardiac nerves was performed using anti-tyrosine hydroxylase antibodies and cardiac nerve growth factor was detected by western blotting.ResuitsCompared with the control group,both the density of sympathetic nerves and the expression of cardiac NGF protein in the experimental group were much higher in the left ventricular anterior wall ( P＜0.01 and P＜0.05) and in the right ventricular anterior wall ( P＜0.01 and P＜0.05).ConclusionsPM2.5 can induce regional sympathetic hyperinnervation in both ventricular anterior walls in healthy rats by stimulating the NGF protein secretion,and the sympathetic nerve reconstruction effect of PM2.5 was confirmed.

This study was aimed to establish an UFLC fingerprint of Tibetan medicine Pterocephalus hookeir samples from different habitats. UFLC-PDA was adopted to analyse 21 batches of P. hookeir samples from different habitats. The chromatographic condition was as follow: Agilent proshell 120 SB-C18 column (4.6 mm x 100 mm, 2.7 microm) eluted with the mobile phases of acetonitrile and 0.2% phosphoric acid water in gradient mode. The flow rate was 1.0 mL x min(-1), and the detection wavelength was set at 238 nm. The fingerprints of 21 batches P. hookeir were carried out by similarity comparation, and 15 chromatographic peaks were extracted as the common peaks of fingerprint, of which 5 peaks were identified as chlorogenic acid, loganin, sweroside, sylvestroside III, triplostoside A. The similarity degrees of 18 batchs of samples were above 0.9, and the other 3 batchs of samples were below 0.9. This is the first established fingerprint of P. hookeir by using UFLC-PDA. This method has good precision, stability and repeatability that it could provide basis for quality control and evaluation of P. hookeir.
Caprifoliaceae ; chemistry ; China ; Chromatography, High Pressure Liquid ; instrumentation ; methods ; Drugs, Chinese Herbal ; analysis ; Quality Control

OBJECTIVETo investigate the clinical application of the ureteral dilation catheter combined with the balloon catheter under the ureteroscope in the treatment of urethral stricture in men.

METHODSUnder the ureteroscope, 45 male patients with urethral stricture received placement of a zebra guide wire through the strictured urethra into the bladder and then a ureteral dilation catheter along the guide wire, followed by dilation of the urethra from F8 initially to F14 and F16. Again, the ureteroscope was used to determine the length of the strictured urethra, its distance to the external urethral orifice, and whether it was normally located. An F24 balloon catheter and then a metal urethral calibrator was used for the dilation of the strictured urethra. After removal of the F18-F22 urethral catheter at 8 weeks, the urinary flow rate was measured immediately and again at 3 months.

RESULTSAll the operations were successfully performed without serious complications. The maximum urinary flow rate was (13.3-29.9) ml/s (mean [17.7 ± 3.2] ml/s) at the removal of the catheter and (15.2-30.8) ml/s (mean [19.8 ± 3.9] ml/s) at 3 months after it. Smooth urination was found in all the patients during the 6-24 months follow-up.

CONCLUSIONThe application of the ureteral dilation catheter combined with, the balloon catheter under the ureteroscope is a good option for the treatment of male urethral stricture for its advantages of uncomplicatedness, safety, effectiveness, few complications, less pain, high success rate, and repeatable operation.

Catheterization ; Humans ; Male ; Ureteroscopes ; Urethra ; Urethral Stricture ; therapy ; Urinary Bladder ; Urinary Catheters ; Urination

Objective To investigate the relationship between plasma concentration of B type natri uretic peptide (BNP) and the severity and prognosis of patients with acute spontaneous intracerebral hemorrhage (ICH).Methods Review of 86 cases of patients with spontaneous intracerebral hemorrhage analysis in our hospital Department of Emergency/Surgical Intensive Care Unit (ED/S1CU) were admitted within 6 hours of admission to collect blood samples,head CT,biochemical index,Glasgow Coma Scale (GCS) score and other clinical data,and detected within 6 hours after admission,the admission of third days and 7 days of plasma BNP concentration.The blood volume of cerebral hemorrhage was computed.The GCS was used to evaluate nerve function after admission.The survival of 28 days was observed.Results The concentration of BNP detected at 3 time points increased with the increase of the amount of bleeding in patients with acute cerebral hemorrhage and increased with the decrease of GCS score at admission (P ＜0.01).The BNP concentration was mild higher in the small amount of bleeding group than that of the control group (P =0.094),while that of the other two groups were significantly higher (P ＜ 0.01).Concentration of BNP detected within 6 hours of admission was positively correlated with cerebral hemorrhage (r =0.551).The a mount of BNP in the 6 hours after admission of the GCS ＞ 8 group was significantly higher than those of the control group (P ＜ 0.05),and the GCS ≤ 8 group was significantly higher than that of the control group and GCS ＞ 8 group (P ＜ 0.01).The BNP concentration was negatively correlated with GCS score at admission (r =-0.532).The 28-day mortality was predicted by BNP ＞ 168 pg/ml for 6 hours,AUC was 0.814,the sensitivity was 75.0％ and the specificity was 81.4％.Conclusions The concentration of BNP in patients with acute spontaneous intracerebral hemorrhage increased with the increase amount of bleeding and the decrease of GCS score at admission.The concentration of BNP in the 6 hours after admission was correlated with the severity and the prognosis of the disease,which can be used as the important reference indicators for evaluating severity and prognostic prediction.

Objective: To explore risk factors including prostate-specific antigen (PSA) kinetics for the prediction of castration-resistant prostate cancer (CRPC), and to build a practical model for predicting the progression to CRPC after androgen deprivation therapy(ADT) so as to facilitate clinicians in decision-making for prostate cancer patients receiving ADT.Methods: A total of 185 patients with prostate cancer who had received ADT as the primary therapy in Department of Urology of Peking University First Hospital from 2003 to 2014 were enrolled retrospectively.All the patients were diagnosed with prostate cancer via prostate biopsy and followed up every four weeks from the initiation of ADT.All the patients received ADT with luteinizing hormone-releasing hormone agonists (LHRH-A) or surgical castration accompanied with an antiandrogen (bicalutamide or flutamide, combined androgen blockade).The clinical information of the patients were collected including age, clinical TNM stage, Gleason score (GS), risk groups of prostate cancer, PSA at the initiation of ADT, PSA nadir after ADT, PSA decline velocity, and the time to PSA nadir.The end point of this study was the diagnosis of CRPC, which was based on the European Association of Urology (EAU) Guideline 2016.Cox proportional hazards regression models were established to analyze and estimate their effects on the time of progression to CRPC.Results: In this study, 185 patients with prostate cancer who had received ADT as the primary therapy were included.The mean age was (71.02±8.67) years.The median time to progression to CRPC in this cohort was 38 months (ranging from 4 to 158 months).On univariate analysis, we found clinical T stage, N stage, the metastasis state before ADT, risk groups of prostate cancer, PSA decline velocity, and PSA nadir were all related to the time to CRPC progression, P<0.01 for all the above variables.And on multivariate analysis, the presence of distant metastasis before ADT (HR=6.030, 95% CI: 3.229-11.263, P=0.001), higher PSA nadir (HR=1.185, 95% CI: 1.080-1.301, P=0.001), higher PSA decline velocity>11 μg/(L·month) (HR=2.124, 95% CI: 1.195-3.750, P=0.001), and time to PSA nadir ≤ 9 months (HR=3.623, 95% CI: 1.640-4.817, P=0.004) were found to be significantly associated with an increased risk of progression to CRPC.Conclusion: Patients with rapid decreasing of PSA in the initial ADT were more likely to progress to CRPC.

To study the in situ intestinal absorption kinetics of flrubiprofen in rats, the absorption of flurbiprofen in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC. The effects of drug concentration on the intestinal absorption were investigated. The K(a) and P(app) values of flurbiprofen in the small intestine and colon had no significant difference (P > 0.05). Drug concentration (4.0, 10.0 and 16.0 mg x L(-1)) had no significant influence on the K(a) values (P > 0.05). However, when concentration was 4.0 mg x L(-1) and 10.0 mg x L(-1), significant effect on the P(app) values (P < 0.05) was found, but significant effect on the P(app) values was not shown between 10.0 mg x L(-1) and 16.0 mg x L(-1) (P > 0.05). The K(a) and P(app) values of flurbiprofen on the perfusion flow rate had significant difference (P < 0.05). Flurbiprofen could be absorbed at all segments of the intestine in rats and had no special absorption window. The absorption of flurbiprofen complies with the facilitated diffusion in the general intestinal segments, and accompany with the cytopsistransport mechanism probably. The perfusion flow rate had significant effect on the K(a) and P(app).
Analgesics ; administration & dosage ; pharmacokinetics ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Colon ; metabolism ; Dose-Response Relationship, Drug ; Duodenum ; metabolism ; Female ; Flurbiprofen ; administration & dosage ; pharmacokinetics ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Male ; Perfusion ; Rats ; Rats, Sprague-Dawley

AIM:To investigate the stemness of mouse triple-negative breast cancer (TNBC) 4T1 cells induced by doxorubicin (DOX) and the underlying mechanism.METHODS:The 4T1 cells and MDA-MB-468 cells were treated with DOX at different concentrations (0, 0.05, 0.1 and 0.5μmol/L) for 24 h, and the shape and viability of the cells were observed.The concentration of DOX at 0.1μmol/L was chosen as the optimal concentration for the following experiments.The 4T1 cells and MDA-MB-468 cells resistant to DOX were established by continuous stimulation with DOX for 4 weeks, and named as 4T1-DOX and MDA-MB-468-DOX.Sphere formation assay was used to detect the stemness of 4T1cells and MDA-MB-468 cells.The expression of CD133 was observed by immunofluorescence staining.The expression of CD44 was analyzed by flow cytometry.The protein levels of Stat3, phosphorylated Stat3 (p-Stat3) and Oct-4 were determined by Western blot.RESULTS:The sphere formation ability of the 4T1-DOX cells was stronger than that of the 4T1control cells.The 4T1-DOX cells expressed high levels of the stemness markers CD133 and CD44 as compared with the 4 T1 cells (P<0.05).Furthermore, the 4T1-DOX cells exhibited enhanced activation of Stat3 (p-Stat3) and increased expression of Oct-4 (P<0.05) , while the expression of total Stat3 had no obvious variation.In addition, when activation of Stat3 was inhibited by WP1066, the protein levels of p-Stat3, Oct-4 and CD44 were down-regulated (P<0.05).Furthermore, inhibition of Stat3 phosphorylation reduced the sphere formation ability of the 4T1-DOX cells (P<0.05).CONCLUSION:DOX induces the stemness of mouse TNBC 4T1 cells through Stat3-Oct-4 signaling pathway.