A HPLC-MS/MS multiple-reaction monitoring (MRM) quantitative analysis was made to establish a determination method for drug concentrations of costunolide (Co) and dehydrocostuslactone (De) in blood samples in the positive ion mode, with diazepam as the internal standard substance, in order to study the pharmacokinetic process of sesquiterpene lactones costunolide and dehydrocostuslactone after the oral administration of Weichang'an pills, and provide an theoretical basis for further studies on the substance basis for the anti-diarrhea effect of Weichang'an pills. In the blood samples, Co and De showed a good linearity within concentration ranges 0.700 0-769.7, 2.510-956.0 μg x L(-1), respectively. The results of precision, stability and recovery experiences proved the stability and reliability of the plasma concentration determination method. After the oral administration, the concentrations of Co and De in plasma increased with the increase in dose, with T(max) between 10.65-12.98 h, indicating a long time to reach peak plasma concentrations; C(max) of costunolide and dehydrocostuslactone ranged between 3.750-5.450,15.34-44.52 μg x L(-1), respectively. The in vivo adsorption of Co and De conformed to the one-compartment model, with a longer time to attain the peak plasma concentrations. These results provided an experimental basis for revealing the active substance basis and clinical medication of Weichang'an pills.
Administration, Oral ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Lactones ; administration & dosage ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Wistar ; Sesquiterpenes ; administration & dosage ; blood ; pharmacokinetics ; Tablets ; administration & dosage ; chemistry ; pharmacokinetics

Objective:Using lasso regression analysis to screen out the blood lipid indexes closely related to coronary heart diseaseMethods:The clinical data of 3 062 patients with coronary heart disease who were hospitalized in the Department of Cardiology, Affiliated Hospital of Jining Medical College from May 2013 to November 2015 were retrospectively analyzed.They were divided into control group ( n=2 427) and coronary angiography group ( n=635). R language was used for statistical analysis.Multiple logistic regression models were established for indicators of blood lipid related to CAD, and their multicollinearity severity was assessed.LASSO regression was used to screen out the representative lipid parameters in the CAD prediction model. Results:A total of 3 062 patients were enrolled, including 2 427 patients in coronary heart disease group and 635 patients in control group.The inclusion of lipid parameters into multiple logistic regression model leads to serious multicollinearity.Stepwise regression can only partially reduce multicollinearity severity, while LASSO regression model significantly reduces multicollinearity severity.Low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) were found to be the representative lipid indexes for predicting coronary heart disease by LASSO regression analysis.Conclusion:LASSO regression has advantages in processing multicollinearity data.LASSO regression showed that LDL-C, HDL-C and non-HDL-C were representative lipid indicators for predicting coronary heart disease..

Objective To investigate the alterations of connexin 43 (Cx43) expression and its distribution at different stages of myocardial infarction (MI) in rats after transplantation of allogenic mesenchymal stem cells (MSCs).Methods Wistar rats were ligated on the left anterior descending coronary artery to make MI models.They were injected with allogenic MSCs,which were induced by 5-aza and labelled by DAPI,during the second operation after 7 days of MI.In subgroups,MSCs were detected by fluorescence microscope.Cx43 expression and GJ distribu-tion were examined by immunohistochemistry after 4,8 or 12 weeks respectively.Results MSCs differentiated into cardiac muscle cell-like cells which were capable of pulsing spontaneously,expressing cTnT and forming myofilament in vitro.Transplanted MSCs can survive in MI host and upregulate Cx43 expression and normalize Cx43 distribution at ischemic zones after 4,8 and 12w.No change of Cx43 was seen at infarcted zones.Conclusion MSCs have the plasticity of differentiating into cardiac muscle cell-like cells which can continuously upregulate Cx43 expression and normalize Cx43 distribution at ischemic zones after 4,8 and 12w.

Objective To observe the effect of liver disease special-purpose enteral nutrition preparation on protein metabolism and liver function in children with liver injury.Methods Sixty cases of severe ill with liver injury in hospital,with mean age of (7.8?6.3) years old.All patients were randomly divided into experimental group (n=30) and control group(n=30).The experimental group was treated by adding the liver disease special-purpose enteral nutrition preparation homogenized diet and control group was treated by adding entire protein entire nutrition type enteral nutrition preparation.All patients in both 2 groups were nasally fed with intestinal nutrition,which contained 418-628 kJ/(kg?d).One day before nutritional support and 14 days after nutritional support,the liver function,total serum protein,albumin,hemoglobin were recorded.SPSS 11.5 software was used to analyze the data.Results The baseline indicators were similar before nutritional supports.Fourteen days after nutritional support,alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were all significantly lower in experimental group than in control group(Pa

OBJECTIVEThis study aimed to assess the association between emergency-room visits for respiratory tract infection (RTI) with diurnal temperature range (DTR), a weather parameter closely associated with urbanization and global climate change.

METHODSWe conducted a semiparametric time-series analysis to estimate the percentage increase in emergency-room visits for RTI associated with changes in DTR after adjustment for daily weather conditions (temperature and relative humidity) and outdoor air pollution.

RESULTSDTR was significantly associated with daily emergency-room visits for RTI. An increase of 1 °C in the current-day (L0) and in the 2-day moving average (L01) DTR corresponded to a 0.94% [95% confidence interval (CI), 0.34%-1.55%] and 2.08% (95% CI, 1.24%-2.93%) increase in emergency-room visits for RTI, respectively.

CONCLUSIONDTR was associated with increased risk of RTI. More studies are needed to understand the impact of DTR on respiratory health.

China ; Emergency Service, Hospital ; statistics & numerical data ; Humans ; Respiratory Tract Infections ; epidemiology ; Temperature

OBJECTIVE: To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. MATERIALS AND METHODS: This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. RESULTS: Liver T1rho and PDFF values were significantly different (p < 0.001), whereas the T2* (p = 0.766) values were similar, among the three groups. Mean liver T1rho values in the fibrotic group (52.6 ± 6.8 ms) were significantly higher than those of healthy subjects (44.9 ± 2.8 ms, p < 0.001) and fatty liver group (45.0 ± 3.5 ms, p < 0.001). Mean liver T1rho values were similar between healthy subjects and fatty liver group (p = 0.999). PDFF values in the fatty liver group (16.07 ± 10.59%) were significantly higher than those of healthy subjects (1.43 ± 1.36%, p < 0.001) and fibrosis group (1.07 ± 1.06%, p < 0.001). PDFF values were similar in healthy subjects and fibrosis group (p = 0.984). Mean T1rho values performed well to detect fibrosis at a threshold of 49.5 ms (area under the ROC curve, 0.855), had a moderate correlation with liver stiffness (r = 0.671, p = 0.012), and no correlation with PDFF, T2* values, subject age, or body mass index (p > 0.05). CONCLUSION: T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver.
Body Mass Index ; Fatty Liver* ; Fibrosis ; Healthy Volunteers ; Humans ; Liver Cirrhosis* ; Liver* ; Magnetic Resonance Imaging ; Prospective Studies* ; Protons ; ROC Curve

OBJECTIVETo evaluate the clinical efficiency and safety of two-micron laser resection of the prostate-tangerine technique (TmLRP-TT) for the treatment of large-volume ( > 70 ml) prostate in patients with benign prostatic hyperplasia (BPH).

METHODSThis retrospective analysis included 80 BPH patients with the prostatic volume larger than 70 ml, all treated by TmLRP-TT. We comparatively analyzed the levels of hemoglobin and serum sodium before and after surgery, recorded intra- and post-operative com- plications, and followed up the patients at 6 and 12 months after operation for International Prostate Symptom Score (IPSS), quality of life (QOL), maximum flow rate (Qmax), and postvoid residual urine volume (PVR).

RESULTSAll the operations were successfully completed. The mean hemoglobin decreased (0.68 +/- 0.43) g/dl intraoperatively, but no apparent reduction was observed in serum sodium. Lower urinary tract symptoms were relieved significantly in all the cases. At 12 months after surgery, IPSS was decreased by 73.89% as compared with the baseline (20.03 +/- 6.9 vs 5.23 +/- 3.59), QOL by 64.55% (4.09 +/- 1.19 vs 1.45 +/- 1.36), and PVR by 79.30% (97.31 +/- 57.90 vs 20.14 +/- 24.20 ml), while Qmax increased by 140.42% ([8.04 +/- 3.62] vs [19.33 +/- 3.28] ml/s). The incidence of complications was low either intraoperatively or during the 12 months after operation.

CONCLUSIONTmLRP-TT is a safe and effective surgical endoscopic approach to the treatment of large-volume prostate in BPH patients.

Aged ; Follow-Up Studies ; Humans ; Laser Therapy ; methods ; Male ; Middle Aged ; Prostatic Hyperplasia ; surgery ; Retrospective Studies ; Transurethral Resection of Prostate ; methods ; Treatment Outcome

OBJECTIVETo investigate the changes of NF-kappa B binding activity, the expression of PPARr and their correlation in the liver of rats with fatty liver disease (FLD) induced by different pathogenic factors and to investigate the molecular mechanism of the inflammation in FLD.

METHODS40 Wistar rats were randomly divided into 4 groups of ten each: normal group, alcohol group, fat-rich diet group, alcohol adding fat-rich diet group. The rats were sacrificed at the end of the 16th week from the starting day of the experiment. Serum and liver specimens were collected. Histological specimens were stained with HE, SudanIV, and Masson and then studied microscopically. The ultrastructural changes were also checked under an electron microscope. NF-kappa B binding activity and the expression of PPARr mRNA were determined by electrophoretic mobility shift assay (EMSA) and RT-PCR respectively. The correlations between NF-kappa B binding activity and the expression of PPARr and the biochemical indexes were analyzed.

RESULTSSteatosis, inflammation, necrosis and fibrosis were present in livers of the rats of all the experimental groups, and were most severe in the alcohol adding fat-rich diet group. NF-kappa B binding activity was markedly increased in the livers of the alcohol group (142+/-16.32) and of the alcohol adding fat-rich diet group (238+/-19.14) in comparison to the livers of the normal (73+/-9.24, F = 6.36, 17.93) and those of the fat-rich diet group (84+/-10.38, F = 5.96, 16.20). Binding activity was higher in the alcohol adding fat-rich diet group than that in the simple alcohol group, but there was no difference between those of the fat-rich diet and normal groups. The level of PPARr mRNA was lower in the livers of the alcohol, fat-rich diet, alcohol adding fat-rich diet groups (0.2530+/-0.069, 0.3647+/-0.082, 0.1226+/-0.054) than that of the controls (0.8097+/-0.094) (F = 15.43, 7.24, 21.45). NF-kappa B binding activity was correlated positively with the level of serum TNF alpha (r = 0.527, 0.639) and the content of MDA in the liver homogenates (r = 0.723, 0.537), but negatively with the expression of PPARr in the livers of the alcohol and the alcohol adding fat-rich diet groups (r = -0.568, -0.891).

CONCLUSIONThe enhanced nuclear factors NF-kappa B binding activity and decreased expression of PPARr play a pivotal role in the inflammatory response of FLD induced by alcohol and fat-rich diet. It may provide a new idea for treating FLD effectively.

Animals ; Fatty Liver ; metabolism ; Liver ; metabolism ; Male ; NF-kappa B ; metabolism ; PPAR gamma ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo investigate the relationship between genetic polymorphism in exon 12 C1236T, exon 21 G2677T/A and exon 26 C3435T of the multidrug resistance 1 (MDR1) gene and the risk of childhood acute lymphocytic leukemia (ALL).

METHODA total of 176 patients with ALL and a cohort of 170 matched healthy subjects were included. SNaPshot SNP typing was used to determine the genotypes of MDR1 C1236T, G2677T/A, C3435T. Based on the clinical data, the relationship between genetic polymorphism of MDR1 and the risk of childhood ALL was analyzed.

RESULTThere was significant difference in the distribution of genotype of MDR1 C3435T between the group of controls and cases. The mutant homozygous TT genotype was found to be associated with occurrence of ALL (P = 0.000; OR = 4.504). The data show evidence of pairwise linkage disequilibrium between the three common SNPs (C1236T-G2677T/A-C3435T). The haplotypes of TTT, TGC, CGC and CAC were predominant. The haplotype CGT distributed significantly differently between the groups of controls and cases (P = 0.034). The frequency of the haplotype TTT/TTT in the high risk group was higher than the other groups (P = 0.037).

CONCLUSIONThe present findings suggest that 3435C→T polymorphism in MDR1 gene may be a genetic susceptibility factor for ALL. The haplotype of MDR1 (C1236T-G2677T/A-C3435T) could be the clinical parameter at diagnosis.

ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Acute Disease ; Asian Continental Ancestry Group ; genetics ; Child, Preschool ; China ; ethnology ; Exons ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Infant ; Linkage Disequilibrium ; Male ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Risk Factors

OBJECTIVETo study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.

METHODSTM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.

RESULTSCFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.

CONCLUSIONThe CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.

Actins ; metabolism ; Animals ; Benzoates ; pharmacology ; Chloride Channels ; physiology ; Cystic Fibrosis Transmembrane Conductance Regulator ; antagonists & inhibitors ; Cytoskeleton ; drug effects ; Male ; Mice ; Sertoli Cells ; drug effects ; metabolism ; Spermatogenesis ; Thiazolidines ; pharmacology ; Time Factors