Objective: To study the correlation between brain natriuretic peptide (BNP) in plasma and functional outcome in patients with acute ischemic stroke after intravenous thrombolysis and its clinical significance. Methods: An analysis was performed on 141 cases of acute ischemic stroke patients with intravenous thrombolysis. According to the modified Rankin Scale (mRS) 3 months after thrombolysis, the patients were divided into the good outcome group (mRS≤1) and the poor outcome group (mRS>1). BNP level indicators after thrombolysis were compared between the two groups. The receiver operator characteristic (ROC) curve was used to analyze the ability of BNP level to predict the functional outcome 3 months after thrombolysis, and the influence of some other relevant factors was adjusted by Logistic regression analysis. Results: Compared with the good outcome group, the level of BNP in the poor outcome group was significantly increased (P=0.003). According to ROC curve analysis, the elevated BNP level (BNP>202.6 pg/mL) had a certain predictive ability for poor functional outcome 3 months after intravenous thrombolysis in patients with acute ischemic stroke. Elevated BNP level was an independent predictor of functional outcome 3 months after intravenous thrombolysis in patients with acute ischemic stroke (OR=2.406, 95% CI 1.069-5.417, P=0.034). Conclusion: Elevated plasma BNP level after thrombolysis is significantly associated with poor functional outcome in patients with acute ischemic stroke after intravenous thrombolysis, suggesting a predictive role of BNP for poor outcome 3 months after intravenous thrombolysis.

The inter-species differences of thienorphine metabolism were investigated in human, Beagle dog and rat liver microsomes, by comparing enzyme kinetics of the parent drug and the formation of its major metabolites. The incubation systems of thienorphine with liver microsomes of the three species were optimized in terms of thienorphine concentration, microsomal protein content and incubation time. The concentrations of thienorphine and its metabolites in incubates were measured by a LC-MS/MS method. The biotransformation of thienorphine by human liver microsomes was the lowest among the three species. The K(m), V(max), CL(int) and T1/2 of thienorphine obtained from human liver microsomes were (4.00 +/- 0.59) micromol x L(-1), (0.21 +/- 0.06) micromol x L(-1) x min(-1), (117 +/- 3.19) mL x min(-1) x kg(-1) and (223 +/- 6.10) min, respectively. The corresponding kinetic parameters for dog and rat liver microsomes were (3.57 +/- 0.69) and (3.28 +/- 0.50) micromol x L(-1), (0.18 +/- 0.04) and (0.14 +/- 0.04) micromol x L(-1) x min(-1), (213 +/- 1.06) and (527 +/- 7.79) mL x min(-1) x kg(-1), (244 +/- 1.21) and (70.7 +/- 1.05) min, respectively. A total of six phase I metabolites were observed in liver microsomes, including one N-dealkylated metabolite, three oxidative metabolites and two N-dealkylated oxidation metabolites. All these six metabolites were detected in the liver microsomes of the three species. However, the relative amounts of the metabolites generated were different in three species. The results indicated that the major phase I metabolic pathway of thienorphine was similar in the liver microsomes from all three species. However, the inter-species differences observed were relative amounts of the metabolites as well as the metabolic characteristics of thienorphine in liver microsomal incubates.
Animals ; Biotransformation ; Buprenorphine ; analogs & derivatives ; metabolism ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Dogs ; Humans ; Male ; Microsomes, Liver ; metabolism ; Rats ; Rats, Sprague-Dawley ; Species Specificity ; Tandem Mass Spectrometry ; methods

OBJECTIVETo investigate the relationship of interleukin-10 gene (IL-10) polymorphism and the serum IL-10 level with restenosis after percutaneous coronary intervention (PCI) in Tianjin Chinese Han population and study the effect of IL-10 gene polymorphism on serum IL-10 level.

METHODSFour hundred and thirty-seven patients who successfully underwent PCI with a follow-up angiography were divided into a restenosis group (n = 166) and non-restenosis group (n = 271). The IL-10 gene promoter polymorphism at position -592 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Meanwhile their serum IL-10 level before and 24 h after PCI was determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS(1) There was no significant difference in frequencies of -592 genotypes and alleles between the two groups (P > 0.05); (2) The 24 h post-PCI IL-10 serum level of restenosis group was significantly lower than that of the non-restenosis group [(82.67 ± 35.02) ng/L vs. (95.08 ± 32.26) ng/L, P < 0.05]; (3) The serum level of the A allele carriers (AA+AC) was significantly lower than that of the CC carriers [(86.13 ± 34.77) ng/L vs. (102.50 ± 27.52) ng/L, P < 0.05]; (4) In the restenosis group, the 24 h post-PCI serum level of IL-10 in the A allele carriers was also significantly lower than that in those without the A allele [(78.51 ± 34.09) ng/L vs. (102.19 ± 33.66) ng/L, P < 0.05]; (5) Logistic regression analysis revealed positive correlations between acute coronary syndrome patients, pre-PCI degree of stenosis, length of target stenosis lesion and restenosis (OR = 5.90, 1.86, 2.83 respectively); and there were negative correlations between 24 h post-PCI serum level of IL-10, the stent diameter, the diameter of reference vessel before stent implantation and restenosis(OR = 0.99, 0.70, 0.46 respectively).

CONCLUSION(1) The IL-10 gene -592 C/A polymorphism was not associated with restenosis in the Tianjin Chinese Han population; (2) IL-10 is an early post-PCI inflammatory cytokine, 24 h post-PCI serum IL-10 level was an independent predictive factor for restenosis, the IL-10 A allele carriers may have increased incidence of in-stent restenosis (ISR) by reducing the serum IL-10 levels.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; Asian Continental Ancestry Group ; genetics ; Coronary Restenosis ; genetics ; Female ; Genotype ; Humans ; Interleukin-10 ; blood ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Stents

The biotransformation, CYP reaction phenotyping, the impact of CYP inhibitors and enzyme kinetics of 3-cyanomethyl-4-methyl-DCK (CMDCK), a new anti-HIV preclinical candidate belonging to DCK analogs, were investigated in human intestinal microsomes and recombinant cytochrome P450 (CYP) enzymes. CMDCK (4 micromol L(-1)) was incubated with a panel of rCYP enzymes (CYP1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remaining parent drug in incubates was quantitatively analyzed by a LC-MS method. CYP3A4 was identified as the principal CYP isoenzyme responsible for its metabolism in intestinal microsomes. The major metabolic pathway of CMDCK was oxidation and a number of oxidative metabolites were screened with LC-MS. The Km, Vmax, CLint and T1/2 of CMDCK obtained from human intestinal microsome were 45.6 micromol L(-1), 0.33 micromol L(-1) min(-1), 12.1 mL min(-1) kg(-1) and 25.7 min, respectively. Intestinal clearance of CMDCK was estimated from in vitro data to be 3.3 mL min(-1) kg(-1), and was almost equal to the intestinal blood flow rate (4.6 mL min(-1) kg(-1)). The selective CYP3A4 inhibitors, ketoconazole, troleandomycin and ritonavir demonstrated significant inhibitory effects on CMDCK intestinal metabolism, which suggested that co-administration of CMDCK with potent CYP3A inhibitors, such as ritonavir, might decrease its intestinal metabolic clearance and subsequently improve its bioavailability in body.
Anti-HIV Agents ; metabolism ; pharmacokinetics ; Biological Availability ; Bridged Bicyclo Compounds, Heterocyclic ; metabolism ; pharmacokinetics ; Coumarins ; metabolism ; pharmacokinetics ; Cytochrome P-450 CYP3A ; Cytochrome P-450 CYP3A Inhibitors ; Humans ; Intestines ; metabolism ; Ketoconazole ; pharmacology ; Metabolic Clearance Rate ; Microsomes ; metabolism ; Ritonavir ; pharmacology ; Troleandomycin ; pharmacology

Objective This research aimed to explore the mental status of public hospital medical personnel and social support for them, social support they perceive, and their coping styles. This study was designed to investigate on the relationship between their anxiety and social support, perceived social support and their coping styles. Methods A questionnaire was adopted to collect data, including participants’ background, measurement of anxiety, as well as social support, perceived social support and their coping styles. Results(1)The anxiety level of medical personnel was significantly higher than that of domestic norm 37.23±12.59(t=14.370, P<0.001);(2)Anxiety levels appeared to be significantly different in occupation, educational background and working years;(3)Results shown in the three scales were different among participants with different levels of anxiety in perspectives of every dimension in the scales； (4) With the help of Spearman correlation analysis, it showed that anxiety levels of medical personnel was negatively correlated with objective support (r=-0.098, P=0.051), subjective support (r=-0.189, P<0.001) ,utilization of social support (r=-0.164, P=0.001), friend support (r=-0.356, P<0.001),family support (r=-0.330, P<0.001),other support (r=-0.238, P<0.001) and positive response (r=-0.282, P<0.001), and positively correlated with negative response (r=0.385, P<0.001). Conclusions Mental health of medical personnel should be noticed and enhanced, and social support for public hospital medical personnel should be strengthened. Thus, the performance of the medical team can be developed in order to support further public medical service construction.

OBJECTIVETo evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.

METHODSTwo hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.

RESULTSTwo hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.

CONCLUSIONSOral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.

Adenocarcinoma ; drug therapy ; pathology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Drug Combinations ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Neoplasm Staging ; Oxonic Acid ; administration & dosage ; adverse effects ; Paclitaxel ; administration & dosage ; adverse effects ; Prospective Studies ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Tegafur ; administration & dosage ; adverse effects

Objective · To evaluate the influence of cathepsin S(CatS) on the severity of communicating hydrocephalus in a kaolin injected mouse model.Methods · Kaolin suspension was injected to 8 CatS knock-out (CatS -/-) mice and 12 wild type (WT) C57BL/6 mice through cisterna magna to establish communicating hydrocephalus mouse model. Cerebral magnetic resonance imaging (MRI) was used before and 1 week after kaolin injection to compare lateral ventricular volume. Lateral ventricular index was calculated to analyze the severity of hydrocephalus. Results · One week after kaolin injection,1 in CatS -/- group and 2 in WT group died. The mortality rate was 12.5% each and there was no significant difference (P=1.000). MRI results showed varying degrees of ventriculomegaly in both groups. Lateral ventricular index of CatS -/-group (n=8) and WT group (n=16) before kaolin injection was 0.05±0.01 and 0.04±0.01 respectively (P=0.720). One week after kaolin injection, lateral ventricular index of CatS-/- group (n=7) and WT group (n=14)was 0.13±0.02 and 0.11±0.01 respectively (P=0.950). In each group, in 71.4% of mice, lateral ventricular index enlarged twice or more. Conclusion · One week after kaolin injection into cisterna magna, lateral ventricles enlarges obviously, indicating hydrocephalus occurs, with high success rate. CatS gene deficiency has no significant influence on the development of communicating hydrocephalus.

OBJECTIVE: To observe the effect of standardized Jin's three-needle therapy on limb motor function and nerve function defect in stroke patients, and to evaluate the placebo control method. METHODS: A total of 66 patients with stroke were randomly divided into a Jin's three-needle group (33 cases, 3 cases dropped off) and a placebo needle group (33 cases, 4 cases dropped off). All the patients were treated with conventional medication and rehabilitation treatment. In addition, the patients in the Jin's three-needle group were treated with standardized Jin's three-needle therapy at temporal three points, spirit four points, hand three points, foot three points, upper extremity spasm three points, lower extremity spasm three points, etc.; while the patients in the placebo needle group were treated with placebo needling at identical points. All the treatments were given once a day, 5 days a week, and 3-week treatment was given with an interval of 2 days between weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were observed before treatment, 10 d and 21 d into treatment, and the blind evaluation was conducted after treatment. RESULTS: On the 10 d and 21 d into treatment, the FMA scores in both groups were higher than those before treatment (P<0.01), and the NIHSS scores were lower than those before treatment (P<0.01). On the 10 d and 21 d into treatment, the FMA scores in the Jin's three-needle group were higher than those in the placebo needle group (P<0.05); on the 10 d into treatment, the NIHSS score in the Jin's three-needle group was were lower than that in the placebo needle group (P<0.05). There was no significant difference between the two groups on judging the type of treatment (P>0.05), and the consistency with the real situation was poor (Cohen's kappa coefficient<0.20). CONCLUSION The standardized Jin's three-needle therapy could effectively improve the limb motor function and nerve function defect in stroke patients. The placebo control method used in this study shows good clinical operability and masking effect.
Humans ; Acupuncture Therapy/methods* ; Acupuncture Points ; Stroke/therapy* ; Lower Extremity ; Needles ; Treatment Outcome ; Stroke Rehabilitation

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.
Pregnancy ; Female ; Mice ; Humans ; Animals ; Spleen ; Ghrelin ; Fetal Weight ; Cholesterol, LDL ; Diarrhea

Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO₂) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO₂, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO₂ and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO₂ showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO₂ showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO₂ higher than female(r=-0.229, P<0.001); PeakVO₂ of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO₂ (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO₂(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO₂(t=-5.43, -0.31, respectively, all P<0.05). PeakVO₂ of male was higher than female(t=-6.03, P<0.05), and peakVO₂ of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R²=0.29) could be constructed: peakVO₂=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO₂. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.
Chronic Disease ; Cross-Sectional Studies ; Female ; Heart Failure ; Heart Rate ; Humans ; Male ; Oxygen Consumption/physiology* ; Prognosis ; Retrospective Studies ; Stroke Volume/physiology*