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Objective To summarize the clinical and EEG characteristics of anti ⁃ leucine ⁃ rich glioma⁃inactivated 1 (LGI1) antibody⁃associated encephalitis. Methods and Results The clinical data and EEG characteristics of 27 patients diagnosed with anti⁃LGI1 antibody⁃associated encephalitis in Beijing Tiantan Hospital, Capital Medical University from April 2014 to May 2019 were retrospectively analyzed. 1) Clinical features: the main manifestations were memory loss [70.47% (20/27)] and mental abnormality [51.60% (14/27)]. 2) Laboratory examination: serum anti⁃LGI1 antibody was positive in all patients, 92.59% (25/27) cerebrospinal fluid anti ⁃ LGI1 antibody was positive, some patients were accompanied by hyponatremia [66.67% (18/27)], elevated tumor markers [33.33% (9/27)], and cytomegalovirus IgG was positive [36.36% (8/22)]. 3) Imaging features: head FLAIR showed hyperintensity in 51.85% (14/27) mainly accumulated temporal lobe and hippocampus, and 18F⁃FDG PET showed high metabolism in 14/17 mainly accumulated temporal lobe, hippocampus and basal ganglia. 4) EEG characteristics: there were 19 cases (70.37%) of EEG abnormalities, including 10 cases of faciobrachial dystonic seizures (FBDS) alone, 4 cases of focal onset with disturbance of consciousness, 3 cases of FBDS with focal onset and disturbance of consciousness, one case of FBDS with focal onset, one case of focal onset alone. Abnormal waves occurred in 15 cases (55.56%), including focal slow wave activity in 9 cases, diffuse slow wave activity in 3 cases, focal radiating sharp wave activity with slow wave activity in 2 cases, focal fast activity with slow wave activity in one case. Abnormal electrical activity occurred in 8 cases (29.63%) within 10 s after the onset of the movement, including 4 cases in the frontal and anterior mesotemporal region, 2 cases in the parietal, occipital and posterior temporal region, one case in the central region, and one case in a wide range of low voltage. Epileptiform discharge was observed in 8 cases (29.63%), including 6 cases in the frontal and anterior mesotemporal regions, 2 cases in the parietal, occipital and posterior temporal regions. In 9 cases (33.33%), the origin of seizures could be determined, including 5 cases in the anterior mesotemporal region, 2 cases in the central and parietal regions, and 2 cases in the parietal, occipital and posterior temporal regions. Conclusions The abnormal rate of EEG in anti⁃LGI1 antibody⁃associated encephalitis was high, and the background changes were mostly slow background and low amplitude. There were mainly scattered sharp waves and slow waves in the interattack period, which was consistent with the EEG characteristics of marginal lobe encephalitis. Epileptiform discharges were predominate in frontal and temporal lobes during seizures and clinical periods.

Objective To investigate the dysregulated genes, pathways and networks involved in type 2 diabetes-derived brain dysfunctions via performing whole transcriptome sequencing on the cerebral cortex of db/db and wild-type (WT) mice. Methods Male db/db and WT mice were divided into two groups (n=9). The body weight and blood glucose were measured at week 8 and 24. The 24-week-old animals were sacrificed for cerebral cortex collection. RNA-sequencing and analysis of differentially expressed genes (DEGs), GO functional enrichment, KEGG pathway enrichment and PPI network were performed. Results A total of 306 differential transcripts, including 178 up-regulated and 128 down-regulated ones were identified in the db/db mice as compared to WT ones. Among all differentially expressed genes, 43 genes (such as Clcnka and Trim17) were found to be up-regulated and 59 genes (such as Arih1 and Nectin-3) were down-regulated. The protein-protein interaction network was constructed with thirteen nodes as hub genes. All the nodes were down-regulated genes and majorly belonged to mitochondrially encoded families. The GO functional enrichment showed changes in various categories as compared to WT. KEGG enrichment analysis revealed that target genes were mainly enriched in metabolic pathways, Parkinson's disease, Alzheimer's disease, and the involved DEGs mainly regulate oxidative phosphorylation process. Conclusions The relationship between type 2 diabetes and central nervous system impairments, and the potentially related genes, pathways and networks are identified.

Crystalline and amorphous SiO2/Al2O3 nanocomposite powders were prepared by a sol-gel method. The structure and morphology of the nanocomposite powders were characterized by X-ray diffraction and transmission electron microscopy, while the in-frared stealth property was detected by Fourier transform infrared spectroscopy spectrometry. The results show that both the nanocom-posite powders have irregular shapes, in which the average grain size of the crystalline one is about 18 nm. The crystalline nanocom-posite powder is a kind of composite nanomaterial with low infrared emissivity, and its average emissivity is 45.65% in 3-5μm and 46.19% in 8-14μm, which are lower than those of the amorphous one in 2.5-25μm.

Ag@Pt core-shell nanoparticles(Ag@Pt NPs) composed of an Ag nanoparticle core and a Pt shell were prepared by the seed-mediated growth method and self-assembly technology. The electrocatalytic properties of Ag@Pt NPs to methanol before and after invalidation were measured and compared during the electrocatalytic process. The invalidation mechanism was studied by transmission electron microscopy,high-resolution electron microscopy,and X-ray photoelectron spectroscopy. The results show that the cavitation phenomena of Ag@Pt NPs occur during the cyclic voltammetry process with a threshold voltage of 0.5 V and become more obvious with the increase of time. Ag@Pt particles turn into Pt hollow shells coated by Ag after cavitation,which is the reason that the catalytic property of Ag@Pt NPs to methanol distinctly decreases during the electrocatalytic process.

Fish growth is one of the most complex traits that may be influenced by many physiological processes. Among them, feeding is a necessary prerequisite to ensure the growth, development and survival of fish. In order to study the effects of feeding promoting and feeding inhibiting genes on genetic regulation of growth and starvationrefeeding, cDNA sequences of neuropeptide Y (HynNPY) and pro-opiomelanocortin (HynPOMC) genes were cloned in bighead carp (Hypophthalmichthys nobilis) in this study. By using qRT-PCR, expression levels of NPY and POMC genes were studied in hypothalamus and intestine of extreme growth and starvation-refeeding of bighead carp by setting control (feeding), starvation, and starvation-refeeding group, respectively. The full-length cDNA of NPY and POMC genes were 839 and 799 bp, encoding 96 and 218 amino acids, respectively. Phylogenetic analysis showed that NPY and POCM are highly conserved in teleosts. The expression of NPY in hypothalamus was the highest, followed by intestine and brain. The expression of POMC in intestine was the highest, followed by hypothalamus and liver. In the hypothalamus and intestine of extreme large (mean 42.4 g) and extreme small (mean 18.8 g) individuals cultured in the same pond, the expression of NPY in extremely large group was higher than that of extremely small group, while the expression of POMC in extreme small group was significantly higher than that of extreme small group. Starvation increased the expression of NPY in hypothalamus and intestine. After starvation, the expression of NPY increased in the hypothalamus and increased significantly in the intestine. After refeeding, the expression of NPY decreased in the hypothalamus and intestine. The expression of POMC in hypothalamus and intestine of starvation group increased significantly, and decreased to the level of control group after refeeding. Histological observations showed that structure of intestine in extremely large group is better than that of extremely small group, meanwhile, broken intestinal villi and leukocyte infiltration in starvation group tend to recover gradually after refeeding. In short, NPY promotes the intake of more food and POMC supresses appetite, and both of them are involved in feeding mediation of central and peripheral nerve systems of bighead carp. NPY and POMC may directly or indirectly affect the growth of bighead carp by controlling feeding behavior, intake of feed nutrition and GH secretion. These results would provide insights into further understanding of molecular mechanisms for differential growth in bighead carp and gene resources for genetic improvement. [ABSTRACT FROM AUTHOR]

The strains that can biotransform limonene to α -terpineol were screened based on the researches of hops endophytic bacteria, and the physiological, biochemical and molecular indicators of these endophytic bacteria were determined, subsequently the bioconversion conditions of limonene by endophytic bacteria were optimized. Results showed that, the F0-1 bacteria strain was Pseudomonas oryzihabitans. The optimal bioconversion conditions were determined as follows: system temperature of 30, pH value of 6.0, rotate speed of 200 r/min, preincubation time of 38 h in NA medium, limonene/ethanol solution addition of 20%, limonene concentration of 880 mg/L and bioconversion time of 12 h. After optimization, the product presented α-terpineol concentration of 97.54±3.34 mg/L, which was 10.6 times of the original conversion result 9.24±1.67 mg/L. [ABSTRACT FROM AUTHOR]

To explore the practical role of enhanced vegetation index (EVI) time series data in improving the accuracy of forest type recognition could promote the deep application of optical remote sensing data in forest resources investigation and monitoring. With Cuigang Forest Farm of Xinlin Forestry Bureau in Daxing' anling as the object, we constructed six classification schemes, using random forest algorithm with spectral feature, texture feature and EVI time series feature. The data sources were 20-view Landsat 8 OLI time series data from 2014 to 2018, 56 fixed plots data from 2017-2019, and the 2016 Class II survey data. Our aims were to realize the classification of forest types in Cuigang Forest Farm and to evaluate the accuracy of different classification schemes. The results showed the EVI values of Larix gmelinii forest, Betula platyphylla forest, coniferous-broadleaved mixed forest, coniferous mixed forest and broadleaved mixed forest were significantly different in non-growing seasons (36-111 days and 287-367 days), with the EVI value of mixed conifer forest being significantly higher, and that of mixed broadleaf forest being always lower than the other four forest types. In the early growing season (111-143 days), the EVI value of B. platyphylla forest were higher than L. gmelinii forest, which could effectively distinguish the two forests. Among the six classification schemes, spectral feature, texture feature, and EVI time series feature had the highest classification accuracy, with a Kappa of 0. 82 and a classification accuracy of 86. 1%. The comparison results showed that the overall accuracy of adding vegetation index time series feature was improved by 14.3% compared with that of spectral feature. The random forest algorithm with combined spectral, texture and EVI time series features could effectively classify forest stand types in Cuigang Forest Farm, with good recognition accuracy and confidence. [ABSTRACT FROM AUTHOR]

In order to meet the requirements of the suspended solids(SS) and iron concentration in the influent of anaerobic ammonia oxidation process, the coagulation technology was used to pretreat the sludge dewatering solution from anaerobic digestion. Through aeration test and orthogonal test, the optimal aeration intensity, aeration time and coagulation process conditions of anaerobic digestion sludge dewatering liquid were determined. Based on single factor test, the best process conditions were obtained as follows: (250 r/min) 90 s of fast stirring, (90 r/min)120 s of slow stirring, 30 s of coagulant aids dosing time, 15 min of standing time, 20 mg/L of polyaluminium chloride (PAC), 1 mg/L of polyacrylamide (PAM), 7.0 of pH value. At this time, turbidity and total iron removal rates in anaerobic digested sludge dewatering solution were 97.63% and 98.21%, respectively. The effluent treated by coagulation can not only improve the removal effect of pollutants, but also meet the influent requirements of sub-sequent anaerobic ammonium oxidation process. [ABSTRACT FROM AUTHOR]

Objective To assess the efficacy and safety of interferon-beta (IFN-β) as monotherapy versus placebo for patients with relapsing-remitting multiple sclerosis (RRMS). Methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, LILACS, PEDRO, China Biology Medicine Disc (CBMDisc), as well as clinical trial registries and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP, retrieval deadline: June 2014). Furthermore, we checked reference lists of published reviews and retrieved articles, and communicated personally with investigators and biotechnology companies participating in trials of IFN-β in an effort to identify further studies or unpublished data. Two review authors independently screened studies, extracted data and evaluated the risk of bias. Formal Meta - analysis were conducted by using Review Manager software (Version 5.3.3) and the impacts of limitations in study design or execution (risk of bias), inconsistency in results, imprecision of results, indirectness of evidence and publication bias on the quality of the body of evidence were assessed. Results A total of 576 articles were retrieved. After screening of titles and abstracts, 26 studies were provisionally selected. The full text of papers were obtained for further assessment of eligibility. Finally, 5 studies were included, involving 2129 patients with RRMS (high-dose IFN-β group: N = 1076; placebo group: N = 1053). All studies were randomized, double-blind, controlled, parallel-group clinical trials with a follow-up for at least one year, evaluating IFN-β versus placebo as monotherapy for patients with RRMS. Most studies had methodological limitations, mainly on a high risk of attrition bias. Moreover, the intention to treat (ITT) principle was not used in data analysis. Data from only 919 patients (43.17%) were available to calculate the primary outcomes at 2 years of follow-up. Meta- analysis indicated IFN-β slightly reduced the number of patients with at least one relapse [risk ratio (RR) = 0.810, 95%CI: 0.740-0.890; P = 0.000] and the number of patients with disability progression during the first 2 years of follow-up (RR = 0.700, 95%CI: 0.550-0.880; P = 0.002). However, the sensitivity analysis (worst-case scenario analysis) showed no treatment effect (RR = 1.110, 95%CI: 0.730-1.680, P = 0.620; RR = 1.310, 95%CI: 0.600-2.890, P = 0.500, respectively). Data from 1581 patients (74.26%) were available to analyze the number of patients with at least one relapse during the first year of follow-up (RR = 0.740, 95% CI: 0.590-0.930; P = 0.010). Absolute risk reduction (ARR) was 13.24% and number needed to treat (NNT) was 8, which meant 8 patients were needed to treat to prevent one patient against relapse. However, the pooled results showed no treatment effect on the annualized relapse rate. The adverse events frequently caused by IFN - β included injection - site reactions, chills, pyrexia, myalgia, influenza - like symptoms, headache, increased alanine aminotransferase (ALT) and increased aspartate aminotransferase (AST). However, the incidences of lymphocytopenia, leucopenia, depression and committed or attempted suicide were not significantly increased by IFN-β. Conclusions There is high-quality evidence to support that IFN-β slightly reduces the number of patients with RRMS having relapse during the first year of follow-up, but the clinical effect beyond one year is uncertain. There is insufficient evidence to determine the efficacy of IFN-β in reducing the number of patients with disability progression. New randomized controlled trials of high quality are needed to assess the long-term efficacy. [ABSTRACT FROM AUTHOR]

The port logistics finance has been developed rapidly under the port low-carbon transition development. It was very urgent for research on port logistics pledge loan portfolio optimization decision-making theory under the low-carbon transition. In this study, the port pledge loan under the low-carbon transition theory was set up, which including the principle of pledge loan options, low-carbon, the pledge risk and credit risk control. On this basis, the port logistics pledge loan portfolio under the low-carbon transition optimization model was built up, with pledge loan put option portfolio return, ports and customers, low-carbon structure constraint, single loan VaR pledge rate, pledge loan portfolio average credit risk control conditions. The model solved the drawbacks of existing research focused single port pledge loan and neglecting the pledge loan portfolio under low-carbon transition constraints, etc. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of bosutinib on the malignant behavior of thyroid papillary carcinoma B-CPAP cells and its possible mechanisms. Methods: Thyroid papillary carcinoma B-CPAP cells were cultured in vitro with a concentration gradient of(1、2、3、4 and 5 μmol/L)bosutinib intervened for 24 hours, DMSO was used as the control group. Five parallel compound holes were set in each group. Cell counting kit (CCK-8 method) method was used to detect cell proliferation. Transwell assay and cell wound healing assay were used to detect cell invasion and migration. TUNEL staining assay and flow cytometry were used to detect cell apoptosis. Western blot was used to detect the expressions of autophagic proteins (Beclin-1, LC3, p62) and signal pathway proteins (SIK2, p-mTOR, mTOR, p-ULK1, ULK1). Results: Compared with the control group, the cell proliferation activity, migration ability and invasion ability were decreased ( P ＜0.01), while the cell apoptosis rate was increased ( P ＜0.01) in the bosutinib concentration groups of 2, 3, 4 and 5 μmol/L . In the concentration groups of 4 and 5 μmol/L, the expression of Beclin-1 ( P ＜0.05), LC3- Ⅱ/LC3- Ⅰ ( P ＜0.05), SIK2 ( P ＜0.01) and p-ULK1 ( P ＜0.01) protein was decreased, while the expression of p62 ( P ＜ 0.05) and p-mTOR ( P ＜0.01) protein was increased. Conclusion: Bosutinib may inhibit the autophagy of thyroid papillary carcinoma cells through SIK2-mTOR-ULK1 signaling pathway to inhibit their proliferation, invasion and migration and promote apoptosis, thereby weakening their malignant behavior.

To explore the practical role of enhanced vegetation index (EVI) time series data in improving the accuracy of forest type recognition could promote the deep application of optical remote sensing data in forest resources investigation and monitoring. With Cuigang Forest Farm of Xinlin Forestry Bureau in Daxing'anling as the object, we constructed six classification schemes, using random forest algorithm with spectral feature, texture feature and EVI time series feature. The data sources were 20-view Landsat 8 OLI time series data from 2014 to 2018, 56 fixed plots data from 2017-2019, and the 2016 Class II survey data. Our aims were to realize the classification of forest types in Cuigang Forest Farm and to evaluate the accuracy of different classification schemes. The results showed the EVI values of Larix gmelinii forest, Betula platyphylla forest, coniferous-broadleaved mixed forest, coniferous mixed forest and broadleaved mixed forest were significantly different in non-growing seasons (36-111 days and 287-367 days), with the EVI value of mixed conifer forest being significantly higher, and that of mixed broadleaf forest being always lower than the other four forest types. In the early growing season (111-143 days), the EVI value of B. platyphylla forest were higher than L. gmelinii forest, which could effectively distinguish the two forests. Among the six classification schemes, spectral feature, texture feature, and EVI time series feature had the highest classification accuracy, with a Kappa of 0.82 and a classification accuracy of 86.1%. The comparison results showed that the overall accuracy of adding vegetation index time series feature was improved by 14.3% compared with that of spectral feature. The random forest algorithm with combined spectral, texture and EVI time series features could effectively classify forest stand types in Cuigang Forest Farm, with good recognition accuracy and confidence.

Landscape water is an important part of urban water systems, and excessive nitrogen affects its ecological functions. This study aimed to investigate the temporal and spatial distribution characteristics and driving factors of the community structure of denitrifying bacteria from landscape water. The functional gene nirS was used as a functional marker to explore the community of denitrifying bacteria in the water and sediment of landscape water. Based on parameters of the water and sediment, the temporal and spatial distribution characteristics and driving factors of the community of denitrifying bacteria were studied. The results showed significant seasonal differences in water parameters and spatial differences in sediment nitrogen ( P <0.001). No significant difference ( P >0.05) was observed in α-diversity; the EC and SOEF-NH 4 + -N were important factors affecting the α -diversity of the water and sediment. Denitrifying bacteria mainly belonged to the phylum Proteobacteria and the genera Dechloromonas, Rhodocyclaceae, Pseudomonas, Rhodobacter , and Thauera . Principal coordinate analysis revealed that the community of denitrifying bacteria in the water and sediment exhibited significant spatial differences ( P <0.001); keystone denitrifying bacteria in the water also exhibited significant spatial differences ( P <0.001). RDA and RF analysis showed that the permanganate index and TP were the main environmental factors affecting the total and keystone denitrifying bacteria in the water; SOEF-NH 4 + -N, IEF-NH 4 + -N, and WAEF-NO 3 - -N were the main environmental factors affecting the total and keystone denitrifying bacteria in the sediment. These findings could serve as a reference to understand the interaction mechanism between nitrogen and denitrification bacterial communities in landscape water.

Objective: To investigate the characteristics of 18 F-FDG PET/CT images of multiple myeloma secondary extramedullary infiltration in order to improve recognition., Methods: Twenty-one patients with multiple myeloma secondary extramedullary infiltration confirmed by pathology or follow-up from January 2012 to October 2020 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. All the patients underwent 18 F-FDG PET/CT imaging before treatment, and the PET/CT characteristics of extramedullary infiltration and bone marrow were analyzed., Results: Twenty-one patients included 12 males and 9 females, aged from 41 to 77 years old, with an average of 58.3±10.0; 9 cases of extramedullary infiltration involving lymph nodes; lung, stomach, spleen, and kidney were involved respectively in 2 cases; retroperitoneal, right auricle, subcutaneous nodule, and spinal meninges involvement were reported in each one case respectively. The maximum SUVmax value of extra-medullary lesions was 21.2, the minimum value was 2.1, and mean was 7.7±5.3. The maximum SUVmax value of bone marrow was 33.5, the minimum was 2.4, and mean was 6.6±3.6. There was no statistically significant difference in SUVmax value between extra-medullary lesions and bone marrow (Z=-1.195, P=0.232)., Conclusion: 18 F-FDG PET/CT not only has a good diagnostic value for multiple myeloma, but also a good evaluation value for secondary extramedullary infiltration, which provides reference for clinical treatment and prognosis.

Breast tumor has become one of the malignant tumors with the highest incidence, and is a serious threat to human health, especially to women. Chemotherapy is an important anti-breast tumor therapy, which can be used in almost every stage of breast tumor therapy alone or in the combination with surgery and radiation therapy. Alkaloids are a kind of ubiquitous natural products, and important active components of various medicinal plants. A large number of studies have shown that alkaloids could exert an anti-breast tumor effect by inhibiting proliferation, metastasis and angiogenesis, resisting mitosis, promoting apoptosis and autophagy, and triggering cell cycle arrest. The extensive anti-breast tumor effect makes alkaloids an important candidate drug source. This paper reviews the anti-breast tumor mechanism of natural products of alkaloids.

Riparian buffer zone is important ecological transitional region between river and upland. Restoring the degraded vegetation system is important for preventing soil erosion, improving ecological environment and helping to achieve the sustainable development of ecosystems. Based on the scenario simulation of vegetation pattern and flow length index, we analyzed the responses of hydrological connectivity to vegetation pattern under different vegetation coverages and slope gradients, and explored the optimal vegetation pattern of soil and water conservation in riparian buffer zone in the lower reaches of the Yellow River. The results showed that the midslope-coarsness-clustered distribution of vegetation configuration, which exhibited the shortest flow length and the weakest hydrological connectivity, being the optimal vegetation pattern for controlling slope runoff generation and flow concentration. For the optimal vegetation pattern, its flow length increased with increasing slope length, namely, the longer slope length the more significant difference of hydrological connectivity between different slope gradients. Meanwhile, flow length of the optimal vegetation pattern decreased with increasing vegetation coverage. The differences between different slope gradients were obvious under low vegetation coverage, while it was unobvious on slope with vegetation coverage of 45%. Compared with the irregular variation trend of flow length on the actual vegetation slope, there was a consistent trend of first increase and then decrease on the simulated slope with the optimal vegetation pattern. Within the pre-set slope gradient range (5°-20°), the optimal vegetation pattern changed the variation of flow length between different slope gradients in the process of coverage change, which highlighted the influence of riparian buffer zone vegetation pattern on hydrological connectivity.

Osteonecrosis of the femoral head(ONFH), a refractory disease characterized by death of the osteocytes and the bone marrow due to inadequate blood supply caused by various mechanisms, usually leads to the collapse of the femoral head and malfunction of the hip joint. The crux is to diagnose ONFH early in the precollapse stage and prevent subsequent progression of collapsing through early interventions, thus delaying or avoiding the replacement of the hip joint. A number of joint salvaging operation treatments for early stage ONFH are available. However, there has been no consensus with regard to the ideal treatment. The main trend now is to unite core decompression with bone-grafting, tantalum rod, bone marrow mesenchymal stem cell (BMSC) and other treatments. Also there are ways of osteotomy altering the angle of the femoral neck to relocate necrotic tissue from the weight-bearing segment. The implanting of tantalum rod remains controversial and the advent of bone marrow mesenchymal stem cell (BMSC) holds huge potential., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2017 by the China Journal of Orthopaedics and Traumatology Press.)

Donafenib is the deuterium derivative of sorafenib, and is an anti-tumor drug in clinical trials. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of donafenib and its N-oxide metabolite in human plasma. The analytes and internal standards (sorafenib and sorafenib N-oxide) were extracted from plasma by protein precipitation with acetonitrile, and separated on a Gemini C18 (50 mm × 2.0 mm, 5 μm) column using a gradient elution procedure. The mobile phase consisted of acetonitrile and 5 mmol ·L−1 ammonium acetate (0.2% formic acid) at a flow rate of 0.7 mL·min−1. The total run time was 5.0 min. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 468.2 → 273.2 for donafenib and m/z 465.2 → 270.2 for its internal standard sorafenib, m/z 484.2 → 289.2 for donafenib N-oxide and m/z 481.2 → 286.2 for its internal standard sorafenib N-oxide. The standard curves were linear in the range of 5.00−5 000 ng·mL−1 for donafenib, and 1.00−1 000 ng·mL−1 for donafenib N-oxide. The method was validated and successfully applied to the pharmacokinetics study of donafenib tosylate tablets in volunteers.

Anaprazole is a proton pump inhibitor clinically used for curing peptic ulcer. A rapid, sensitive and convenient LC-MS/MS method was first established for the determination of anaprazole in human plasma. d(3), (13)C-anaprazole was used as internal standard (IS). After extraction from human plasma by protein precipitation with acetonitrile, all components were separated on an Extend C(18) column (100 mm × 4.6 mm, 3.5 μm). The assay was linear over the concentration range of 5.00-3 000 ng·m L(-1) (r(2) > 0.995). The method was successfully applied to a pharmacokinetic study of 40 mg anaprazole enteric-coated tablets in 14 Chinese healthy volunteers under fasting or high fat diet conditions. C(max) was (1 020 ± 435) ng·m L(-1) and AUC(0-t) was (2 370 ±754) h·ng·m L(-1) under fasting condition. And C(max) was (538 ± 395) ng·m L(-1) and AUC(0-t) was (1 610 ± 650) h·ng·m L(-1) under high fat diet condition. The plasma results suggest that the exposure of anaprazole is reduced by the high fat diet.

A simple and rapid method was developed based on high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to determine sivelestat and its metabolite XW-IMP-A in human plasma. After a simple protein precipitation, the samples and internal standards were analyzed on a C18 column by a gradient elution program. The mobile phase consisted of 30% acetonitrile in methanol and 5 mmol · L(-1) ammonium acetate at a flow rate of 0.7 mL · min(-1). The mass spectrometric data was collected in multiple reaction monitoring mode (MRM) in the negative electrospray ionization. The standard curves were linear in the range of 10.0-15,000 ng · mL(-1) for sivelestat, and 2.50-1000 ng · mL(-1) for XW-IMP-A. The low limits of quantitation were identified at 10.0 and 2.50 ng · mL for sivelestat and XW-IMP-A, respectively. The intra- and inter-day precision were within 11.3% and 13.1% for sivelestat and XW-IMP-A, and accuracy was 0.3% and 0.6% for sivelestat and XW-IMP-A, within the acceptable limits across all concentrations. The method was successfully validated in the pharmacokinetic study of sivelestat in healthy Chinese volunteers.

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

This study aims to develop a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of ivabradine and N-demethylivabradine in human plasma, and investigate effects of stable isotope labeled (SIL) internal standard (IS) on ivabradine. The analytes and IS were extracted from plasma by protein precipitation with acetonitrile, and chromatographied on a Capcell PAK C18 (100 mm x 4.6 mm, 5 μm) column using a mobile phase of methanol and 5 mmol x L(-1) ammonium acetate. Multiple reaction monitoring with electrospray ionization (ESI) was used in the positive mode for mass spectrometric detection. The effect of ivabradine isotope peak [M+H+3] + on IS and the effect of SIL IS purity on ivabradine were evaluated. An appropriate concentration of SIL IS was chosen to permit method selectivity and linearity of the assay over the required range. The standard curves were demonstrated to be linear in the range of 0.100 to 60.0 ng x mL(-1) for ivabradine, and 0.050 0 to 20.0 ng x mL(-1) for N-demethylivabradine. The intra and inter day precision and accuracy were within the acceptable limits for all concentrations. Besides, the interaction between IS and ivabradine did not impact the determination of analytes. This method was successfully applied to a pharmacokinetic study of hydrogen sulfate ivabradine sustained release tablets on Chinese healthy volunteers.

To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.

A sensitive, rapid and accurate liquid chromatography-tandem mass spectrometric (LC-MS/MS) method with pre-column derivatization was developed for the simultaneous determination of erdosteine and its thiol-containing active metabolite in human plasma. Paracetamol and captopril were chosen as the internal standard of erdosteine and its active metabolite, respectively. Aliquots of 100 microL plasma sample were derivatized by 2-bromine-3'-methoxy acetophenone, then separated on an Agilent XDB-C18 (50 mm x 4.6 mm ID, 1.8 microm) column using 0.1% formic acid methanol--0.1% formic acid 5 mmol x L(-1) ammonium acetate as mobile phase, in a gradient mode. Detection of erdosteine and its active metabolite were achieved by ESI MS/MS in the positive ion mode. The linear calibration curves for erdosteine and its active metabolite were obtained in the concentration ranges of 5-3 000 ng x mL(-1) and 5-10 000 ng x mL(-1), respectively. The lower limit of quantification of erdosteine and its active metabolite were both 5.00 ng x mL(-1). The pharmacokinetic results of erdosteine and its thiol-containing active metabolite showed that the area under curve (AUC) of the thiol-containing active metabolite was 6.2 times of that of erdosteine after a single oral dose of 600 mg erdosteine tables in 32 healthy volunteers, The mean residence time (MRT) of the thiol-containing active metabolite was (7.51 +/- 0.788) h, which provided a pharmacokinetic basis for the rational dosage regimen.

With the increasing public access to urban water bodies for aesthetical and recreational purposes, it is of critical importance for densely populated urban areas to conduct microbial risk assessment and accordingly implement effective risk management. Based on the methodology of quantitative microbial risk assessment, a case study was conducted on three typical urban water bodies for aesthetical and recreational uses in a southern city in China. Exposure assessment was carried out through water quality monitoring, field survey and literature review, and accordingly human health risk was assessed with different dose-response equations based on fecal coliforms (FC), Escherichia coli (EC) and Enterococci (ENT). Microbial risk estimated by different dose-response equations was found consistent with and comparable to each other. Stream B located in a residential area was not suitable for primary- or secondary-contact recreational uses, and its microbial risk to the public mainly came from water abstraction for household miscellaneous uses. Stream C and Lake E, located in a public open space and a scenic area respectively, could meet the current recreational requirements, and their microbial risk to the public was generally attributed to various recreational activities. It was necessary to address the public health risk associated with the unauthorized or inappropriate water uses (e.g. abstraction for household miscellaneous uses) of urban aesthetical and recreational water bodies.

Objective: To compare the effect of intestinal flora on the metabolism of the Banxia Xiexin Tang (BXT) full prescription group, the sweet-nourishing group and saponins contained in single ingredients ginseng and liquorices., Method: The anaerobic incubation technology for intestinal flora in vitro was adopted to incubate the BXT full prescription group, the sweet-nourishing group and extracting solution of the single ingredients, under anaerobic conditions at 37 degrees C. Samples of different incubating time points were collected. The high-speed separation and content determination of various prototypes and metabolites were conducted with LC-MS/MS method, and then their degradation rate K was calculated to observe the difference and characteristics in metabolism of different compatible groups., Result: Intestinal flora could transform saponins into their metabolites. Having comparing spss one factor variance, we learned the difference in saponin metabolites of different compatible groups. As for the degradation rate of glycyrrhizic acid, the sweet-nourishing group > the full prescription group > the single prescription group (P < 0.05). Rb1 degraded the most slowly in the full prescription group. As for the degradation rate of Re, the single prescription group > the sweet-nourishing group > the full prescription group (P < 0.05)., Conclusion: The sweet-nourishing group and the sweet-nourishing group have different effect in inducing or inhibiting intestinal flora. The single prescription group shows in inhibition in metabolites of Rb1 and Rg1. Glycyrrhizic acid metabolites are promoted by glycyrrhetinic acid, which facilitates the efficacy of drug absorption. The compatibility of compounds has no impact on metabolites of Rb1 and Rg3.

Objective: To compare the bioequivalence and pharmacokinetics of national made and imported atorvastatin in healthy male Chinese volunteers after single oral administration., Methods: This randomized sequence, open-label, two-period crossover study with a one-week washout period between doses was performed in 24 fasting healthy Chinese males. They were randomly assigned to receive 20 mg of either the test (national made) or reference (imported) formulation orally. The blood samples were collected over a 72-hour period. Plasma concentrations of parent atorvastatin (AT), ortho-hydroxy-atorvastatin (o-OAT) and para-hydroxy-atorvastatin (p-OAT) were simultaneously determined using the validated liquid chromatography-tandem mass spectrometry method, the bioequivalence was also evaluated throughout the study., Results: The main pharmacokinetic parameters of test and reference formulations were as follows: the values of C(max) for AT were (10.6 ± 11.9) µg/L and (10.6 ± 9.8) µg/L, t(1/2z) were (11.4 ± 3.9) h and (11.4 ± 5.3) h, AUC(0-t) were (54.2 ± 37.4) µg×h(-1)×L(-1) and (51.7 ± 34.1) µg×h(-1)×L(-1), respectively. The values of C(max) for o-OAT were (7.8 ± 4.5) µg/L and (7.6 ± 4.3) µg/L, t(1/2z) were (12.3 ± 4.2) h and (11.9 ± 3.4) h, AUC(0-t) were (96.8 ± 48.2) µg×h(-1)×L(-1) and (92.3 ± 44.4) µg×h(-1)×L(-1), respectively. The values of C(max) for p-OAT were (0.5 ± 0.4) µg/L and (0.4 ± 0.3) µg/L, t(1/2z) were (18.4 ± 12.4) h and (23.3 ± 17.8) h, AUC(0-t) were (15.9 ± 12.3) µg×h(-1)×L(-1) and (13.8 ± 8.11) µg×h(-1)×L(-1), respectively. The relative bioavailability of AT and o-OAT in test formulation were (105.3 ± 20.7)% and (107.8 ± 23.2)%, respectively. The 90% confidence interval of the test/reference geometric mean ratios of AUC(0-t) for AT and o-OAT were (97.7 - 110.5)% and (98.3 - 111.3)%, C(max) for AT and o-OAT were (75.8 - 114.0)% and (90.6 - 122.9)%, they were all located within the bioequivalence criteria range (80% - 125% for AUC, and 70% - 143% for C(max))., Conclusion: The result demonstrated that two formulations were bioequivalent.

To study the drug-drug interaction of morinidazole and warfarin and its application, a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of R-warfarin/S-warfarin in human plasma. In a random, two-period crossover study, 12 healthy volunteers received a single oral dose of 5 mg racemic warfarin in the absence and presence of morinidazole. Blood samples were collected according to a pre-designed time schedule. R-warfarin, S-warfarin and methyclothiazide were extracted with ethylether : methylenechloride (3 : 2), then separated on a Astec Chirobiotic V (150 mm x 4.6 mm ID, 5 microm) column using 5 mmol x L(-1) ammonium acetate (pH 4.0) - acetonitrile as mobile phase at a flow-rate of 1.5 mL x min(-1). The mobile phase was splitted and 0.5 mL x min(-1) was introduced into MS. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM). The resolution of warfarin enantiomers is 1.56. The linear calibration curves for R-warfarin and S-warfarin both were obtained in the concentration range of 5 - 1 000 ng x mL(-1). Intra- and inter-day relative standard deviation (RSD) for R-warfarin and S-warfarin over the entire concentration range across three validation runs was both less than 10%, and relative error (RE) ranged from -4.9% to 0.7%, separately. The method herein described is effective and convenient, and suitable for the study of metabolic interaction between morinidazole and warfarin. The results showed that coadministration of warfarin with morinidazole did not affect the pharmacokinetics of either R-warfarin or S-warfarin.

Objective: To identify the differences in maxillary growth vector with different vertical skeletal patterns of skeletal class I before and after growth spurts., Methods: One hundred and ninety four cases with different vertical skeletal patterns of skeletal class I were selected and categorized into six groups according to their vertical skeletal patterns and cervical vertebral stages: cervical vertebral maturation stage (CVMS)1,2-horizontal pattern (n=30); CVMS1,2-average pattern (n=32); CVMS1, 2-vertical pattern (n=33); CVMS5, 6-horizontal pattern (n=34); CVMS5, 6-average pattern (n=29); and CVMS5, 6-vertical pattern (n=36). Lateral cephalograms were taken on all of the cases. The angle SN-C axis (theta) and angel PP-C axis (alpha) were measured., Results: (1) The skeletal class I with a vertical growth pattern had larger angle SN-C axis than those with a horizontal or average growth pattern before growth spurts (P(average-vertical) < 0.05, P(horizontal-vertical) < 0.001). (2) The skeletal class I with a vertical growth pattern had the largest angle SN-C axis after growth spurts, followed by those with an average growth pattern. Those with a horizontal growth pattern had the smallest angle SN-C axis. The differences were statistically significant (P(horizontal-average) < 0.05, P(horizontal-vertical) < 0.001, P(average-vertical) < 0.001). (3) The skeletal class I with the same vertical growth pattern had slightly larger angle SN-C axis after growth spurts than before growth spurts, but without statistical significance. (4) The skeletal class I had relatively stable angle PP-C axis and no significant differences were found before and after growth spurts or among those with various vertical skeletal facial types., Conclusion: The magnitude of angle SN-C axis is closely associated with vertical growth patterns and is weakly influenced by maxillofacial growth and development.

This paper is aimed to develop rapid, sensitive and convenient HPLC-MS/MS methods for the quantification of levosimendan and its metabolites OR-1855 and OR-1896 in human plasma. According to the different natures of the compounds, two sets of liquid chromatography and ionization modes were used for determination the concentration of levosimendan and its metabolites OR-1855 and OR-1896 in human plasma, separately. Following protein precipitation with methanol, the levosimendan and internal standard (rosuvastatin) were separated on a Capcell MG III C18 column (35 mm x 2.0 mm ID, 3 microm) with the mobile phase consisted of methanol-15 mmol x L(-1) ammonium acetate-formic acid (55: 45: 0.02, v/v/v). A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in the negative ion mode. Its metabolites OR-1855, OR-1896 and internal standard doxofylline were extracted from plasma by liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Zorbax Extend C18 column (150 mm x 4.6 mm ID, 5 microm) with the mobile phase consisted of methanol-15 mmol x L(-1) ammonium acetate-formic acid (65 :35 :0.1, v/v/v). A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated at the positive ion mode. The linear concentration ranges of the calibration curves for levosimendan and OR-1855 and OR-1896 were 0.10-50.0 ng x mL(-1), 0.20-100 ng x mL(-1), 0.20-100 ng x mL(-1), respectively. The lower limits of quantification of levosimendan and OR-1855 and OR-1896 were 0.10 ng x mL(-1), 0.20 ng x mL(-1), 0.20 ng x mL(-1), respectively. The methods proved to be sensitive, simple and rapid, and suitable for the pharmacokinetic study of levosimendan injection.

Objective: To study the feasibility and the characteristics of recombinant baculovirus as spiral ganglion cells (SGC) gene transfer vector., Methods: After the generation of baculovirus- green fluorescent protein( Bac-GFP) according to Bac-to-Bac baculovirus expression system, SGC were infected by Bac-GFP with different multiplicities of infection (MOI) and different concentrations of sodium butyrate. The transfection cell rate and mean fluorescence strength (MFS) were detected by fluorescence microscopy and flow cytometry. Toxicity effects of recombinant baculovirus vectors and sodium butyrate on SGC were determined by spectroscopic measurement of 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-diphenytetrazoliumromide (MTF)., Results: Baculovirus was able to infect primary SGC cultures. The dose-response characteristics of Bac-GFP were determined on SGC, and the expression level could be up-regulated by sodium butyrate. Infection with Bac-GFP in the absence or presence of sodium butyrate (< or =10 mmol/L) was considered to be non-cytotoxic to primary SGC. GFP had been expressed in SGC at 6 h post-infection and the highest numbers of cells expressing GFP were observed at approximately 48 h post-infection., Conclusions: Baculovirus is a novel and promising tool for gene transferring into the cochlear nervous system both for studies of the function of foreign genes and the development of gene therapy strategies.

A sensitive and selective LC-MS/MS method for determination of citalopram in human plasma was established to study the bioequivalence of different formulations containing citalopram. The samples were simply pretreated by protein precipitation using acetonitrile, and then analyzed on a Zorbax Extend C8 column. The mobile phase consisted of acetonitrile-water-formic acid (60:40:0.2), at a flow-rate of 0.5 mL x min(-1). A Thermo Finnigan TSQ Quantum Ultra tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring using the precursor to product ion combinations of m/z 325 --> m/z 109 and m/z 265 --> m/z 167 was performed to quantify citalopram and the internal standard, respectively. The pharmacokinetic parameters of citalopram in different formulations were calculated by non-compartment model. The linear calibration curves were obtained in the concentration range of 0.10-100 microg x L(-1). The lower limit of quantification was 0.10 microg x L(-1). The intra- and inter-day relative standard deviation (RSD) over the entire concentration range was less than 5.2%. Accuracy determined at three concentrations (0.25, 8.00 and 90.0 microg x L(-1) for citalopram) ranged from -4.7% to 1.3%. Each plasma sample was chromatographed within 3.0 min. The method was successfully used in bioequivalence study of citalopram in human plasma after oral administration of 20 mg citalopram. Calculated with AUC(0-120 h), the bioavailability of two formulations was (102.1 +/- 10.9)%. The method is rapid, selective, robust and is proved to be suitable for bioequivalence evaluation of different formulations containing citalopram.

Objective: To investigate the inhibitory effects of (188)Re-labeled herceptin on the proliferation in vitro of breast carcinoma cell line (SKBR-3) overexpressing HER-2/neu proto-oncogene., Methods: Herceptin was radiolabeled with (188)Re through a direct labeling method. SKBR-3 cells were cultured with (188)Re-Herceptin at different radioactivity doses (3.7x10(4), 18.5x10(4), 37x10(4), 55.5x10(4) and 74x10(4) Bq/ml) or with (188)Re-nmIgG and (188)ReO(4)(-) for comparison. The cell proliferation inhibition was determined with MTT colorimetric assay., Results: (188)Re-Herceptin could markedly inhibit the growth of SKBR-3 cells in a radioactivity dose-dependent fashion, while the effect of (188)Re-nmIgG and (188)ReO(4)(-) showed rather poor inhibitory effect in vitro. The 50% inhibition doses (IC(50)) of (188)Re-Herceptin, (188)Re-nmIgG and (188)ReO(4)(-) were 76.1x10(4) Bq/L, 139.2x10(4) Bq/L and 175x10(4) Bq/L, respectively., Conclusion: (188)Re-Herceptin can effectively inhibit the growth of in vitro cultured breast cancer cells overexpressing HER-2/neu, and shows much potential for clinical use in beast cancer radioimmunotherapy.

Aim: To develop and validate a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the determination of risperidone in human plasma., Methods: Risperidone and the internal standard, diphenhydramine, were isolated from plasma by liquid-liquid extraction with etherdichloromethane (3:2, v/v) , then chromatographed on a Zorbax Extend-C18 column (150 mm x 4.6 mm ID, 5 microm) using a mobile phase consisted of acetonitrile-water-formic acid (40:60: 0.5, v/v), at a flow rate of 0.7 mL x min(-1). A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor product ion combinations of m/z 411-->191 and m/z 256-->167 were used to quantify risperidone and diphenhydramine (IS) , respectively., Results: The linear concentration range of the calibration curve for risperidone was 0.025 - 50 microg L(-1). The lower limit of quantification was 0.025 microg x L(-1). The intra- and inter-day relative standard deviation (RSD) across three validation running over the entire concentration range was less than 7.1%. The accuracy was within +/- 3.8%. Each sample was chromatographed within 2.7 min., Conclusion: The method was proved to be rapid, sensitive and suitable for pharmacokinetic investigations of risperidone.

Aim: To investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam., Methods: CYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately., Results: After a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001)., Conclusion: CYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.

Aim: To develop a sensitive and specific LC/MS/MS method for direct determination of dextrorphan in human plasma and to study the pharmacokinetics of dextrorphan., Methods: After a single oral dose of 60 mg dextromethorphan hydrobromide to 18 healthy Chinese male volunteers, the plasma concentration of dextrorphan, an active metabolite of dextromethorphan, was determined. Dextrorphan and internal standard chlorpheniramine were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax Extend C18 column. The mobile phase consisted of methanol-water-formic acid (70:30:1), at a flow-rate of 0.5 mL x min(-1). A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor to product ion combinations of m/z 258 to 157 and m/z 275 to 230 was performed to quantify dextrorphan. The pharmacokinetic parameters of dextrorphan were calculated by non-compartment model statistics., Results: The linear calibration curves were obtained in the concentration range of 0.2 - 80 microg x L(-1) Each plasma sample was chromatographed within 3.0 min. The intra- and inter-day relative standard deviation (RSD) across three validation runs over the entire concentration range was less than 8%. Accuracy determined at three concentrations (0.5, 6.0 and 70 microg x L(-1) for dextrorphan) ranged from 98.8% to 100.6%. Pharmacokinetic parameters of dextrorphan was obtained as follows: Tmax was (2.1 +/- 0.7) h, Cmax was (14 +/- 8) microg x L(-1), T1/2 was (3.8 +/- 1.8) h, AUC0-t was (60 +/- 37) microg x h x L(-1)., Conclusion: Plasma concentration of the active metablite dextrorphan was directly determined. The method is sensitive and convenient, and is proved to be suitable for clinical investigation of dextrorphan pharmacokinetics and bioequivalence evaluation of formulations containing dextromethorphan.

Aim: To study the chiral inversion of dextropantoprazole in human., Methods: Three healthy Chinese male volunteers after an oral dose of 40 mg dextropantoprazole. An HPLC method was developed and used to determine the total plasma concentrations of each enantiomer. The ratios of the enantiomers in plasma samples were measured on a Chiral-AGP column. The plasma concentration of each enantiomer was then calculated using the ratios of enantiomers and total concentrations of the two enantiomers previously measured., Results: The AUC0-t of levopantoprazole was only 1.5% of the total AUC0-t of enantiomers., Conclusion: The chiral inversion from dextropantoprazole to levopantoprazole does not occur in the three healthy Chinese male volunteers after an oral dose of 40 mg dextropantoprazol.

Aim: To develop a sensitive and specific LC/MS/MS method for determination of lornoxicam in human plasma and investigate pharmacokinetics of single dose of lornoxicam in healthy Chinese volunteers., Methods: Lornoxicam and the internal standard piroxicam were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax XDB-C8 column. The mobile phase consisted of methanol-water-formic acid (80:20:0.5) at a flow-rate of 0.7 mL.min-1. A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor-->product ion combinations of m/z 372-->121 and m/z 332-->121 was used to quantify lornoxicam and internal standard, respectively., Results: The linear calibration curves were obtained in the concentration range of 2.0-1,600 micrograms.L-1. The limit of quantitation was 2.0 micrograms.L-1. The method was successfully used in the pharmacokinetic study for lornoxicam. The main parameters obtained after an oral dose of 8 mg lornoxicam to 18 Chinese male volunteers were as follows: the value of T1/2 was (4.7 +/- 1.1) h, AUC0-infinity was found to be (5.5 +/- 2.4) mg.h.L-1. However, T1/2 of 105 h and AUC0-infinity of 189.5 mg.h.L-1 were obtained for another volunteer., Conclusion: The method is proved to be suitable for clinical investigation of lornoxicam pharmacokinetics, which offers advantages of specificity, speed, and higher sensitivity over the previously reported methods.

Objective: To investigate factors affecting the determination of the percent carboxyhemoglobin saturation (HbCO%) of blood in an attempt to offer further data for results interpretation and sample storage requirement., Methods: The HbCO% of blood samples stored in various conditions were detected by three spectrophotometries during the succeeding 30 days., Results: The data detected by reductive double-wavelength spectrophotometry and double-wavelength spectrophotometry were more stable than mono-wavelength spectrophotometry. The HbCO% of blood was significantly related with the storage conditions which include temperature, time and the degree of exposure to air., Conclusion: Determinations of HbCO% are reliable which performed by reductive double-wavelength spectrophotometry and double-wavelength spectrophotometry, combine with spectral scans. During 30 days, blood stored at 4 degrees C exposed to a limited volume of air does not influence the determination of HbCO%.