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A 22-year-old female has complained of hirsutism, acanthosis nigricans, enlarged clitoris, and menstrual disorders since puberty. Laboratory examinations revealed hyperandrogenemia. Severe insulin resistance and diabetes were found during hospitalization in our hospital. She was diagnosed with type A insulin resistance syndrome finally. After treatment with metformin, the acanthosis nigricans was significantly relieved, blood glucose was controlled satisfactorily, and the menstrual cycle was restored.患者女性，22岁。自青春期起逐渐出现多毛、黑棘皮征、阴蒂增大及月经紊乱等临床表现。曾多次查雄激素水平明显升高。我院住院期间发现存在严重胰岛素抵抗、糖尿病。胰岛素受体基因检测提示存在致病性突变，诊断为A型胰岛素抵抗综合征。予二甲双胍治疗后患者黑棘皮征有明显缓解，血糖控制满意，月经周期恢复。.

The study investigated the effects of increasing content of corn distillers' dried grains with solubles (DDGS) in the diets of laying ducks on oxidative status, laying performance, egg quality, and egg yolk fatty acid composition. Longyan females (1080) with similar BW at 17 wk of age were randomly assigned to 6 treatment groups, each consisting of 6 replicates of 30 birds. The basal diet (I) was a typical corn-soybean ration while the experimental diets (II to VI) substituted corn DDGS for soybean meal and wheat bran and a small reduction of corn. The level of substitution in diets (II to VI) was 6%, 12%, 18%, 24% and 30%. The experiment lasted for 18 wk. Average egg weight decreased linearly as the level of corn DDGS inclusion increased (P 0.001). Haugh unit, albumen weight, and proportion declined as linear responses to corn DDGS substitution (P 0.05), but yolk color linearly increased (P 0.001); the proportions of oleic (C18:1) and total monounsaturated fatty acids in egg yolk linearly decreased with increasing corn DDGS and many of the key polyunsaturated fatty acids (PUFAs) like linoleic (C18:2n-6), arachidonic (C20:4n-6) and α-linolenic (C18:3n-3) acids linearly increased (P 0.001), but not those of eicosapentaenoic (C20:5n-3) and docoshexaenoic (C22:6n-3) acids. The PUFAs n-6/n-3 ratio linearly increased with increasing corn DDGS level (P 0.001). Increasing corn DDGS linearly increased hepatic expression of GPX1, HO-1, and Nrf2 and hepatic activity of GSH-Px and the liver content of MDA (P 0.001). There were no treatment effects on egg production, egg mass, feed conversion ratio, eggshell thickness, strength, and yolk cholesterol content (P 0.05). In conclusion, the current study indicates that the use of corn DDGS is possible as a replacement, primarily for soybean meal at levels up to 18% in the diets of laying ducks without affecting laying performance, egg quality, and antioxidant status. Increasing amounts of corn DDGS linearly increased egg yolk concentrations of key fatty acids like like C18:2n-6 and C18:3n-3 and the antioxidant enzyme activity of GSH-Px through the Nrf2 pathway to avoid oxidative stress.

The effect of postoperative chemoradiotherapy (CRT) for esophageal carcinoma (EC) was investigated. Patients who can obtain benefit from this treatment modality have not yet been well identified. We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies published from January 1993 to July 2016. Research comparing surgery alone (SA) with postoperative CRT in patients with resectable EC was procured; collected articles were written in English. Nine studies comparing of postoperative CRT versus SA (n = 1650) in patients with resectable EC met the inclusion criteria. No survival benefit was achieved for postoperative CRT compared with SA. Subgroup analysis was conducted for patients under resection with positive lymph node carcinoma; there was a significant survival benefit at 1 year [risk ratio (RR) = 0.55 95% CI: 0.37–0.82; P = 0.003], 3 years (RR = 0.71 95% CI: 0.61–0.83; P

The aim of this study was to explore whether the mechanism of Irbesartan (IRB) in the treatment of rats with myocardial ischemia-reperfusion injury (MIRI) was related to the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) signaling pathway.The rat model of MIRI was first successfully established. All rats were randomly divided into 5 groups, including the Sham group (sham operation control group, ligation only), Model group (MIRI rat model group), IRB12.5 group [low-dose IRB (12.5 mg/kg/d) group], IRB50.0 group [medium-dose IRB (50.0 mg/kg/d) group] and IRB200.0 group [high-dose IRB (200.0 mg/kg/d) group]. After treatment of IRB in MIRI rats, the activities of four myocardial enzyme indexes, including creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT), were detected via enzyme-linked immunosorbent assay (ELISA). The effect of IRB on myocardial apoptosis in MIRI rats was detected via Annexin V-fluorescein isothiocyanate/Propidium Iodide (FITC/PI) double staining. Meanwhile, the messenger ribonucleic acid (mRNA) levels of ERK, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in myocardial cells after treatment of IRB were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Furthermore, the protein levels of ERK and p-ERK were detected via Western blotting.Different concentrations of IRB could protect myocardium from MIRI. IRB at doses of 50.0 mg/kg/d and 200.0 mg/kg/d could significantly downregulate myocardial enzyme indexes in MIRI (p0.01). Meanwhile, both the doses could markedly inhibit myocardial apoptosis in MIRI rat model by regulating the expressions of apoptosis-related genes (Bcl-2 and Bax) (p0.01), eventually improving myocardial pathological damage. At the same time, it could also significantly decrease the mRNA and protein levels of ERK in the MAPK-ERK signaling pathway (p0.05).The cardioprotective mechanism of IRB in MIRI rats may be related to the inhibition of the activation of the MAPK-ERK signaling pathway.

Fructose is essential for plant development as well as for fruit sugar composition and fruit quality. Fructose is one of the major sugars in the mature loquat (Eriobotrya japonica Lindl.) fruit, which is popular because of its flavor and availability in early summer. The elucidation of the mechanism of fructose metabolism is of great importance for fruit quality improving. Fructose is primarily phosphorylated by fructokinase (FRK). In order to understand the fructose metabolism in the loquat fruit, a putative loquat FRK full-length cDNA designated as EjFRK was isolated in this study. The EjFRK encoding FRK possesses conserved regions inherent to plant FRKs. Transient expression of 35S:EjFRK-GFP fusion protein in onion epidermal cells showed that EjFRK was mainly expressed in the cytosol. The real-time RT-PCR analysis indicated that EjFRK was expressed in all loquat tissues. Monitoring the dynamic changes of EjFRK transcripts and FRK enzymatic activities demonstrated that EjFRK expression was at a relative high level during early fruit developmental stages and dropped to the lower level during maturation, similar with the changes in FRK activity, which was opposite to the fructose levels during fruit development. The results indicated that the high FRK enzymatic activity was not conducive to fructose accumulation in loquat fruit. The EjFRK transcript level in leaves of loquat seedlings was significantly enhanced after 6 h of treatment with 10 and 100 mM fructose or glucose, which indicates that EjFRK is modulated by fructose and glucose in vivo.

Based on forms and structures of Wronskian determinant, a novel Wronskian form expansion method is presented to find new interaction solutions for (3+1)-dimensional Zakharov–Kuznetsov equation and the functions used in Wronskian determinants that do not satisfy linear partial differential equations. Results have shown that this method is a powerful tool not only to construct a number of traveling wave solutions but also to construct interaction solutions between two different kinds of functions for nonlinear wave equations in mathematical physics and engineering.

To investigate the prevalence and influencing factors of visual hallucinations in patients with Parkinson's disease(PD), and to analyze the relationship between visual hallucinations and sleep disorders.We recruited 187 patients with PD(H-Y Ⅰ-Ⅲ) from outpatient department in Beijing Hospital. The patients were investigated for general information and the use of medicine. The patients were divided into visual hallucination(VH) group and non-hallucination(non-VH) group. A comparison study was conducted between two groups. We investigated the sleep disorders of PD patients according to Non Motor Symptom Quest(NMSquest) and Parkinson's disease sleep scale(PDSS). Logistic stepwise multiple regression procedures were used to determine the best predictive model of visual hallucinations in patients with PD.(1) 42 cases(22.5%) of PD patients were accompanied by visual hallucinations; (2) the VH group and non-VH group had no difference in age, sex, duration of illness, the scores of Minimum Mental State Examination(MMSE) and levodopa equivalent doses (LED). The scores of Unified Parkinson's Disease Rating Scale(UPDRS) Ⅰ, the Hamilton Rating Scale for Anxiety(HAMA) and the Hamilton Rating Scale for Depression(HAMD) in VH group were significantly higher than those in non-VH group[3.5(2, 5) vs 2 (1, 3); 10(6.75, 15) vs 8(5, 11); 11(7.75, 17) vs 9(5, 13); P0.05]; (3) the incidences of vivid dreams and REM sleep behavior disorder(RBD) in VH group were significantly higher than those in non-VH group(61.9% vs 40.7%, 71.4% vs 47.6%, P0.05). There were no significant differences in incidences of excessive daytime sleepiness and restless legs between two groups(P0.05). The score of PDSS in VH group was significantly lower than that in non-VH group[111(92.75, 128.25) vs 123(109, 135), P0.05]; (4) the Logistic stepwise multiple regression revealed that vivid dreams(P=0.045) and the score of PDSS(P=0.006) were the independent influencing factors for VH in PD patients.The incidence of VH in PD with H-Y staging Ⅰ-Ⅱ is 22.5%. The presence of vivid dreams and severe sleep disorder are independently associated with VH in PD.

The current evidence implicates that psychosocial stress, especially pregnancy-specific stress, is associated with the risk of spontaneous preterm birth. The aim of the present study was to determine the effect of pregnancy-specific stress on spontaneous preterm birth among Chinese people.A total of 2,189 pregnant women were enrolled and followed up until parturition from February 2011 to January 2012. Maternal pregnancy-specific stress was assessed using the revised Pregnancy Stress Rating Scale (PSRS) at third trimester in pregnancy. Socio-demographic and psychological data were collected through interviews, medical, and obstetrical examination records.High levels of maternal pregnancy-specific stress during the third trimester increased risk of spontaneous preterm birth compared with the low and medium levels (adjusted risk ratios, 2.92; 95% confidence interval, 1.12-7.58). The first stressor from the revised PSRS includes a risk factor for the safety of infants.High level of pregnancy-specific stress in third trimester might predict spontaneous preterm birth.

The C/C-SiC composites are prepared by the reaction molten infiltration process of silicon powders, using porous C/C composites as preform. C/C composite frameworks with various bulk densities are prepared by the chemical vapor infiltration (CVI) combined with the resin impregnation-pyrolysis methods, using needled-carbon fiber felts as preform. Characterization of the microstructure was conducted with a digital microscope (VHX-500) and a polarized light microscopy, respectively. The hardness (H) and the elastic modulus (E) of the composites are measured using a nano indentor. The results show that the indentation behaviors of the pyrolytic carbon and resin carbon are elastic while silicon and silicon carbide show a plastic deformation behavior. The hardness of the resin carbon as well as the pyrolytic carbon is 2.1GPa and 1.3~1.6GPa, respectively. E of SiC varied from 360 to 259GPa and H from 36 to 21GPa. For Si, the value of E and H are 155-170GPa and 11.7GPa, respectively. The relationship between microstructure and mechanical properties of C/C-SiC composites were analyzed.

Phase transformations and mechanical properties of both Ti-29Nb-13Ta-4 center dot 6Zr and Ti-39Nb-13Ta-4 center dot 6Zr (wt-%) alloys were investigated. The microstructure of the 29Nb alloy is sensitive to solution and aging treatment. Ice water quenching from the solution treatment temperature resulted in (beta+alpha '') microstructure but air or furnace cooling led to a mixture of (beta+omega). The formation of the orthorhombic alpha '' martensite thus suppresses omega formation in the ice water quenched 29Nb alloy. Cooling rate from the solution treatment temperature also has a significant effect on the formation of alpha and omega phases during subsequent isothermal aging below the omega start temperature: slow cooling enhances omega but depresses alpha formation. This cooling rate dependence of aged microstructure was attributed to alpha '' martensite acting as precursor of the alpha phase, thus providing a low energy path to the precipitation of alpha at the expense of omega. Phase transformation in the 39Nb alloy is more sluggish than that in the 29Nb alloy, owing to the presence of the higher content of beta stabiliser Nb. For the 29Nb alloy, Young's modulus and mechanical properties are sensitive to the fraction of phases, and change significantly during aging, in contrast with the 39Nb alloy.

The influences of heat treatment, variation in Nb content, surface modification and counterface materials on the wear characteristics of new beta type Ti-Nb-Ta-Zr alloys and conventional metallic implant alloy Ti-6Al-4V were investigated, using a reciprocal pin-on-disc wear device in a 0.9% NaCl solution. For the wear test of sliding on stainless steel disc, experimental results show that the wear resistance of Ti-29Nb-13Ta-4.6Zr and Ti-6Al-4V is insensitive to their mechanical properties, such as hardness and ultimate tensile strength. Increase in Nb content results in an improvement of the wear resistance of the beta type alloy to some degree. The wear resistance of Ti-29Nb-13Ta-4.6Zr improved significantly after oxidation treatment, due to the presence of Nb2O5 oxide particles on the diffusion hardened surface of the alloy. For wear test of sliding on ultra-high molecular weight polyethylene (UHMWPE) and bone of pig, the wear losses of both Ti-Nb-Ta-Zr and Ti-6Al-4V are much less compared with that sliding on stainless steel and there is almost no wear on the surface of oxided Ti-29Nb-13Ta-4.6Zr. (C) 2004 Elsevier B.V. All rights reserved.

A mean-field-type model was established to describe the concentration of point defects in binary NiAl by taking into account the effects of crystal expansion and off-stoichiometry. Different from some recent studies, this analysis shows that constitutional vacancies are present only in Al-rich NiAl at T = 0 K but that the vacancy concentration decreases with increasing temperature until diffusion is activated and thereafter becomes nearly independent of temperature. Such vacancy formation behaviour in Al-rich NiAl belongs to the category of metastable constitutional type according to a method of classifying vacancy formation in B2 crystals proposed in this letter.

We present a chain-of-atoms model where heat is rectified, with different fluxes from the hot to the cold baths located at the chain boundaries when the temperature bias is reversed. The chain is homogeneous except for boundary effects and a local modification of the interactions at one site, the "impurity". The rectification mechanism is due here to the localized impurity, the only asymmetrical element of the structure, apart from the externally imposed temperature bias, and does not rely on putting in contact different materials or other known mechanisms such as grading or long-range interactions. The effect survives if all interaction forces are linear except the ones for the impurity., 5 pages, 5 figures

Ti-25Al-10Nb-3V-1Mo alloy has been prepared by gas atomization with atomizing pressure above 8 MPa. The cooling rate of 5 x 10(3) similar to 3x 10(5) K s(-1) was obtained according to secondary dendritic arm spacing, as the particle size is 30 similar to 300 mu m. It is known that in the big particles two dendrite morphologies can be found, cellular dendrite and well-developed dendrite, and in small particles there exists only well-developed dendrite. The surface of particles is characteristic of solidification that is identical to the observation on the cross-sectional views. The micrographs of cross-sectional views show that the big particles, whether of cellular dendrite or well-developed dendrite, solidify by multiple nucleation events while the small particles of well-developed dendrite solidify from a single nucleation event. The microstructure of the alloy consists of single beta(0) phase.

The microstructure of rapidly solidified Ti3Al−2Nb alloy consists of an ordered orthorhombic α″0 phase. In the foil samples for transmission electron microscopy prepared by chemical thinning, the α″0 → β0 transformation took place due to the charging of hydrogen during thinning. The β0 → α″0 transition in the rapidly solidified alloy can be explained by a shape deformation mechanism, and the β0/α″0 interface (habit) plane is near to {334}β0. The orientation relationships between the β0 and α″0 phases are , and .

A variety of heat treatments have been employed to explore the microstructure in Ti-25Al-10Nb-3V-1Mo alloy prepared by gas atomization and hot pressing. These treatments include quenching by oil cooling and water cooling and aging at temperatures between 530 degrees C and 950 degrees C. Quenching transformations from the beta-phase field include the formation of O phase in oil quenching and beta (disordered) + O phase in water quenching. The metastable beta phase decomposes into O + ''omega'', O, or alpha(2) + beta(0)/B2 phase when the as-quenched alloy is aged at various temperatures. By comparing the selection area diffraction patterns, it has been found that the ordered omega phase in the alloy studied in this article is distinct in structure to the ''omega type'' (P3m1) and B8(2) phase which are formed in the parent matrix of the ordered beta(B2,D0(3)) phases. It has also been shown by X-ray diffraction (XRD) analyses that the lattice parameters of the as-aged O phase do not remain constant in the alloy at various temperatures.

The microstructure of rapidly solidified Ti3Al-Nb (Nb < 5 at%) alloys prepared by the hammer-and-anvil technique consists of alpha''(0) martensite with D-2(2) (P222(1)) structure. In the martensite there are a number of twins whose twin planes are determined to be {111} by trace analysis. The twinning forms through rotation of the martensite phase (matrix) 180 degrees and it is inferred from the analysis of the martensite transition and structure of alpha''(0) martensite.

The metabolism of the hepatotoxic otonecine-type pyrrolizidine alkaloid (PA), clivorine, was investigated using rat liver microsomes. The metabolites dehydroretronecine (DHR), 7-glutathionyldehydroretronecine (7-GSH-DHR), 7, 9-diglutathionyldehydroretronecine (7,9-diGSH-DHR), and clivoric acid were identified using chromatographic and mass spectrometric analyses. NMR characterizations were also performed on the isolated clivoric acid and the synthetic 7-GSH-DHR and 7,9-diGSH-DHR. The results indicated that the two glutathione (GSH) conjugates were formed by reaction of the unstable toxic pyrrolic ester with GSH added in the microsomal incubation system, whereas DHR was generated from hydrolysis of the unstable pyrrolic ester, and that clivoric acid was produced from all these further conversions of the unstable pyrrolic ester. Furthermore, tissue-bound pyrroles were also determined to be present after microsomal incubation of clivorine. Clivoric acid has not been previously identified, and DHR and 7, 9-diGSH-DHR were found, for the first time, as metabolites of an otonecine-type PA, while 7-GSH-DHR was previously reported by us to be a microsomal metabolite of clivorine. The in vitro metabolic pathway of clivorine was delineated to be the initial formation of the unstable pyrrolic ester, which then may undergo hydrolysis, GSH conjugations, or covalent binding with hepatic tissues that may lead to hepatotoxicity. The present definitive identification of four pyrrolic ester-related metabolites of clivorine and indirect determination of bound pyrroles provide the strongest evidence to date to support the hypothesis that the formation of an unstable pyrrolic ester plays a key role in otonecine-type PA-induced hepatotoxicity.

Ginseng (Panax ginseng C.A. Meyer) is a herbaceous perennial plant cultivated in Korea, China, Japan and North America. Its roots have been used as traditional medicine for oriental people since ancient times. The crude root extracts possess wide range of saponins and sapogenins and are known to have anabolic, adaptogenic, antibiotic, minor hyperglycemic and anti-cancer activities (Brekman, Dardymov 1969). However, the commercial production of ginseng requires growth periods of four to six years and skillful techniques to manage the soil, climate and prevention of pests. Therefore, biotechnological approach as alternative method to produce saponin in vitro has been made. Since Butenko et al.(1968) first reported the conditions for tissue culture of ginseng root, ginseng cell and tissue for the production of the ginsenosides has been successfully achieved (Jhang et al. 1974, Furuya et al. 1983, Choi et al. 1990, 1995). Moreover, saponin production by cultures of transformed roots with Agrobacterium rhizogenes showed 2.4 times higher contents than native root (Yoshikawa, Furuya 1987). But high fluctuation of saponin content in cell cultures and problems related with human safety in transformed roots are big obstacles for commercialization. There has been very few reports on saponin production by adventitious or ordinary root culture in vitro. In this report, we demonstrated that the adventitious-root culture system by bioreactor is quite feasible for saponin production.

The formation of the pyrrolic alcohol glutathione (GSH) conjugates of two different types of pyrrolizidine alkaloids (PAs), i.e. clivorine (an otonecine-type PA) and retrorsine (a retronecine-type PA), was investigated with rat microsomes in the presence of GSH. Two GSH conjugates identified as metabolites of retrorsine were the pyrrolic alcohol conjugated with one [7-GSH-dehydroretronecine (DHP)] or two (7,9-diGSH-DHP) molecules of GSH. diGSH-DHP, the less abundant of the two conjugates, had not been previously identified as a metabolite of PAs. In the case of clivorine, 7-GSH-DHP was identified. This is the first unequivocal identification of a pyrrolic metabolite of an otonecine-type PA. Consequently, this study provides the strongest evidence obtained to date to support the hypothesis, suggested25 years ago, that the mechanism of hepatotoxicity induced by otonecine-type PAs involves key metabolic steps similar to those for retronecine-type PAs.

The metabolism of hainanensine derivative HH07A has been studied in vitro with rat microsomes. A method of HPLC-DAD was developed for screening the metabolites from the microsomal incubation system. Two metabolites were found according to their UV spectra. One of them was extracted and purified with preparative HPLC and TLC, its chemical structure was identified by UV, IR, MS and NMR.

The in vitro metabolism of 6-chloro-butyl phthalide (CBP) was studied by rat hepatic microsomes. The constitution of the incubation system was optimized and a RP-HPLC-DAD method was developed for the on-line analysis of CBP and its metabolites. The difference of the metabolism profiles of CBP by rat liver microsomes induced by phenobarbital (PB) and 3-methylcholanthrene (3-MC) was also compared. TLC, column chromatography and preparative HPLC were used for the isolation and purification of the major metabolites and they were identified as (R/S) gamma-hydroxy-CBP and (R/S) beta-hydroxy-CBP by UV, NMR and MS.

An interatomic potential is proposed for the Cu-Hf-Al system and applied in molecular dynamics/statics simulations. Simulations predict a hexagonal composition region for the Cu-Hf-Al metallic glass formation. Kinetically, a local maximum driving force, defined by energy difference between the solid solution and disordered state, is predicted to be at Cu48Hf41Al11, close to the experimentally measured optimized composition. Moreover, Voronoi tessellation analysis shows that though the icosahedron and icosidihedron are dominant configurations, the fractions of both icosihexahedron and icosioctahedron decrease with increasing Al content, correlating closely with the atomic radii and the heat of mixing of the component metals.

In this paper, a HPLC method was developed for the determination of alkaloids in Sophora flavescens Ait. Experimental evidences indicate that a system of a LiChrosorb-NH2 column (4.0 mm x 250 mm) as stationary phase and CH3CN--H3PO4(pH2)--CH3CH2OH(80:8:10) as mobile phase can separate the five alkaloids, sophocarpine, matrine, sophoridine, oxysophcarpine and oxymatrine very well. This method is very easy and efficient and takes only 15 min for one run.

Forsythia suspensa is a widely used traditional Chinese herb. Because of the need to evaluate its quality, a HPLC method was developed to analyze the active ingredients in its fruits and leaves. One g of powdered plant material was cold macerated over-night with 10 ml of methanol added then supersonic extracted for 20 min. Four ml of the extract were mixed with 1 ml of water, centrifuged (400 x g, 15 min), and then analyzed by HPLC with a Nucleosil C--18 column. The mobile phase for gradient elusion consisted of MeOH(containing 1% tetrahydrofuran) and H2O (containing 0.01 mol/L KH2PO4,pH 3.2) and monitored by UV absorption at 280 nm. The identity and purity of the peaks were checked by photodiode array detector and in comparison with standards. By this procedure, the active constituents caffeic acid, rutin, forsythoside A, forsythin, and forsythigenin were separated successfully, and the quantity of each compound was determined by peak area. Some fruit samples obtained from various sources and the leaf sample made as tea were analyzed by this method.

The metabolic transformation of schizandrin, isolated from the kernel of Schizandra chinensis Bill, was studied in vitro with phenobarbital-induced rat liver microsomal fractio containing the NADPH-generating system. The major metabolites were isolated by preparative HPLC and identified as 7,8-dihydroxy-schizandrin, 7,8-dihydroxy-2-demethyl schizandrin and 7,8-dihydroxy-3-demethyl schizandrin by UV, NMR, MS spectral analysis. The 7,8-dihydroxy-schizandrin was confirmed further by comparison with spectral and chromatographic behavior of the authentic compound. The metabolic biotransformation of schizandrin in vivo was also determined.

In this paper, the metabolism of homoharringtonine has been studied in vitro with liver microsomes from rats and rabbits. A method of HPLC-DAD (photodiode array detector) with gradient elution was developed for screening the metabolites from the microsomal incubation system. Only one main metabolite, whose formation was independent of NADPH and NADH, was found. The metabolite was extracted and purified with preparative HPLC technique. Its chemical structure was identified as 2'-hydroxy-2'(alpha-acetic acid)-6'-hydroxy-6'-methyl-heptanoyl cephalotaxine by UV, IR, NMR, MS analysis, and confirmed further by comparison with the authentic compound, the spectra and chromatographic behavior were all the same. The rates of the metabolite formation was markedly increased in the phenobarbital pretreated liver microsome system.

K-II is an analogue of U-50488, a selective kappa-opioid agonist. Comparison of pharmacological profile of K-II and U-50488 was studied using in vitro and in vivo methods. The results showed that the IC50 values of K-II and U-50488 on electrically induced contraction of the rabbit vas deferens were 0.42 nmol/L and 26.5 nmol/L, respectively. ED50 values of K-II and U-50488 in impairing motor function of mouse in the horizontal screen test were 1.7 and 15.3 mg/kg, respectively. The effect of K-II in reducing spontaneous activity of mouse was 6 times as potent as U-50488. These results suggest that K-II is a more potent kappa agonist in pharmacological effects than U-50488.