Integrated identification, qualification and quantification strategy for pharmacokinetic profile study of Guizhi Fuling capsule in healthy volunteers.

Guizhi Fuling capsule (GZFL), a traditional Chinese medicine formulation, is widely used in China to relieve pain from dysmenorrhea and is now in a Phase II clinical trial in the USA. Due to the low exposure of the five main medicative ingredients (amygdalin, cinnamic acid, gallic acid, paeoniflorin and paeonol) of GZFL in human, a strategy was built to qualitatively and quantitatively identify the possible metabolites of GZFL and to describe the pharmacokinetic profiles of GZFL in human. In this strategy, LC-Q-TOF/MS was used to identify and structurally elucidate the possible metabolites of GZFL in vivo; and a time-based metabolite-confirming step (TBMCs) was used to confirm uncertain metabolites. The simultaneously quantitation results by LC-MS/MS showed low exposure of the five medicative ingredients. According to the strategy we built, a total of 36 metabolites were found and structurally elucidated. The simultaneously semi-quantitative analysis by LC-MS/MS showed that obvious time-concentration curves could be established for 12 of the metabolites, and most of them showed a relatively higher exposure. This study provides a better understanding of the metabolic processes of GZFL in human.

Isoflavones and phytosterols contained in Xuezhikang capsules modulate cholesterol homeostasis in high-fat diet mice.

AIM: Xuezhikang (XZK), an extract of red yeast rice, has been widely used in traditional Chinese medicine to treat cardiovascular disease. Three fractions F1, F2 and F3 (primarily containing isoflavones, monacolins or phytosterols, respectively) are extracted from Xuezhikang capsules. In this study we evaluated the lipid-lowering effects of these fractions and explored the potential mechanisms of actions. METHODS: Mice treated with a high-fat diet (HFD) were orally administered lovastatin (10 mg·kg(-1)·d(-1)), XZK (1200 mg·kg(-1)·d(-1)), F1 (27.5 mg·kg(-1)·d(-1)), F2 (11.3 mg·kg(-1)·d(-1)) or F3 (35 mg·kg(-1)·d(-1)) for 10 weeks. Lipids were measured using commercial enzymatic kits, and the mRNA and protein levels of genes involved in cholesterol and bile acid homeostasis were evaluated using qRT-PCR and Western blot analysis, respectively. RESULTS: XZK increased the fecal excretion of lipids and bile acids, reduced serum TC, TG and LDL-C levels by 40%, 55% and 46%, respectively, and increased serum HDL-C by 31%. Administration of F1 repressed serum TC and TG by 24% and 52%, respectively, and elevated hepatic synthesis of CYP7A1. It also increased hepatic elimination of bile acids in the fecal excretions by 79% through upregulating BSEP and downregulating NTCP. Administration of F3 decreased serum TC, TG and LDL-C levels by 33%, 29% and 39%, respectively, and increased serum HDL-C by 28%, significantly reduced intestinal absorption of cholesterol by inhibiting the transcription of NPC1L1, and elevated excretion of TC, FC and CE by 96%, 72% and 101%, respectively. Administration of F2 showed pharmacological effects similar to those of lovastatin. CONCLUSION: Isoflavones and phytosterols in XZK exert cholesterol-lowering effects in HFD mice through mechanisms that differ from those of lovastatin. Isoflavones and phytosterols act in a complimentary manner: through enhancing the elimination of bile acids and reducing intestinal cholesterol absorption, respectively.

4-(4-Chloro-phen-yl)-3-cyano-7-(4-meth-oxy-phen-yl)-5-oxo-5,6,7,8-tetra-hydro-4H-chromen-2-aminium methano-late.

In the cation of the title organic ion pair compound, C(23)H(20)ClN(2)O(3) (+)·CH(3)O(-), the cyclo-hexyl ring shows a half-boat conformation and the dihedral angles between two benzene rings and the pyran ring are 83.14 (7) and 73.18 (9)°. In the crystal, centrosymmetrically related cations are linked into a dimer by pairs of N-H⋯N hydrogen bonds, generating an R(2) (2)(12) ring motif. The anion inter-acts with the dimer through an N-H⋯O hydrogen bond. π-π inter-actions between pyran rings of adjacent dimers, with a centroid-centroid distance of 3.861 (2) Å, are also observed.

(4R,7S)-2-Amino-4-(3,4-dimeth-oxy-phen-yl)-5-oxo-7-phenyl-5,6,7,8-tetra-hydro-4H-chromene-3-carbonitrile monohydrate.

The title compound, C(24)H(22)N(2)O(4)·H(2)O, was obtained by the reaction of 3,4-dimeth-oxy-benzaldehyde, malononitrile and 5-phenyl-cyclo-hexane-1,3-dione. The cyclo-hexyl and pyran rings show half-boat and V-shaped conformations, respectively. The dihedral angle between the phenyl and benzene ring planes is 30.67 (9)°. The organic mol-ecules are packed in a two-dimensional network parallel to the bc plane stabilized by inter-molecular N-H⋯N and N-H⋯O hydrogen bonds.

[Anlysis on features of dead cases with human Streptococcus suis infections].

OBJECTIVE: To describe the clinical and epidemiological features of dead cases with human Streptococcus suis infections, and to find the target population for preventing death and the related indicators. METHODS: Epidemiological investigation on human Streptococcus suis infections was implemented used unified questionnaires. Analysis on dead cases and survival cases (as contrast) was done. RESULTS: The population with highest fatality rate was in 40-49 age group. 97.37% of dead cases had toxic shock syndrome. The mean interval from onset to admission was 0.76 days, and the mean course was 2.11 days. The progression among dead cases was faster than that among survival cases. Chief clinical manifestations of dead cases that are more frequent than survival cases are purpura (73.68%), diarrhea (50.0%), dyspnea (21.05%), conjunctival congestion (34.21%), etc. Renal impairment and liver involvement in dead cases were more significant than that in survival cases. No significant difference between mean incubation period, exposure rates of main risk factors in dead cases and in survival cases was found. CONCLUSION: Preventing toxic shock syndrome might reduce the fatality rate. The target population for preventing death is aged > or = 40. Liver function and renal function testing might be indicators for monitoring the progression of human Streptococcus suis infections.

[Matched case-control study for risk factors of human Streptococcus suis infection in Sichuan Province, China].

OBJECTIVE: To study the potential risk factors of human infecting with Streptococcus suis. METHODS: 1: M matched case-control study was conducted. 29 human cases of Streptococcus suis infection in the early phase were included in the case group, Patients' family members, neighbors and peoples who had worked together with patients to handle deceased or sick pigs in the last week were recruited as matched controls. There were 147 controls in total. Both cases and controls received questionnaire investigation including the ways to contact sick/dead pigs. Conditional logistic regression was employed to analyze matching data. RESULTS: According to the results of multivariate analysis, slaughtering (OR = 11.978, 95% CI: 3.355-42.756), carcasses cutting and processing (OR = 3.008, 95% CI: 1.022-8.849) sick/dead pigs were associated with cases related to human Streptococcus suis infection. The attributable risk proportion were 91.65% and 66.76% respectively. The other types of exposures to sick/ dead pigs, including feeding, selling, burying and eating, were not associated with the human Streptococcus suis infection in our study population. CONCLUSION: Slaughtering, carcasses cutting and processing sick/dead pigs were important risky behavior for humans to be infected by Streptococcus suis.

[Clinical study on two internal fixation methods Kaneda and Z-plate in the operation of anterior surgical approach after thoracolumbar fractures].

OBJECTIVE: To study the difference between two internal fixation methods Kaneda and Z-plate in the operation of anterior surgical approach and decompression after thoracolumbar fractures. METHODS: The bio-mechanical structure of the internal fixture, install when operating, complications and time of the operation were compared in the cases by Kaneda and Z-plate. RESULTS: Z-plate method had the following characteristics: reasonable of the bio-mechanical structure; stability after internal fixture being installed; capability of completely propping up the injured centrum and keeping the height of middle-column; simple operation when installing internal fixture and shorter time of operation (1.1 hours, P < 0.05); fewer complications. CONCLUSION: Z-plate is an ideal internal fixation method in the operation of anterior surgical approach after thoracolumbar fractures.