p-Cresol-Enabled Nickel-Catalyzed Intermolecular Redox-Economical Coupling of Allyl Alcohols with Alkynes through oxa-Nickelacycle.

An intermolecular redox-economical coupling reaction of allyl alcohols with alkynes, catalyzed by Ni-Brønsted acid cocatalysis, has been developed. This method allows for the synthesis of a diverse range of γ,δ-unsaturated ketones with yields ranging from 40% to 94%, while maintaining excellent compatibility with various functional groups. The transformation of the resulting product demonstrates the significant practical value of this method. Further mechanistic investigations have revealed that the reaction proceeds through the formation of an oxa-nickelacycle intermediate.

A retrospective assessment of real-world experience with venetoclax and azacitidine therapy in elderly acute myeloid leukemia.

This study aimed to examine the effect of venetoclax coupled with azacytidine in treating older adults with relapsed and refractory (R/R) acute myeloid leukemia (AML). The clinical data of 10 senior patients with AML over 65 years old who were treated with venetoclax and azacytidine, including six patients with R/R AML, were retrospectively evaluated. This study comprised seven males and three females with a median age of 71 years. Five patients had at least one relapse, and one patient did not achieve remission after four cycles of azacytidine monotherapy, considering it resistant. AML with myelodysplasia-related changes was found in four cases. One of the 10 patients died early after 1-13 cycles of venetoclax plus azacytidine treatment due to a protracted period of neutropenia and severe lung infection induced by medications. Six of the remaining nine patients, including six R/R patients, achieved a complete remission (CR) or a CR with incomplete hematologic recovery (CRi). After two cycles of therapy, one patient did not react. Neutropenia lasted an average of 10.5 (6-15) days in all patients, with the most severe cases occurring in the second and third weeks of therapy. Three patients who tested positive for the TP53 gene mutation had the following outcomes: One relapsed patient has been in progression-free remission (PFS) for the past 24 months, whereas another has been in full remission but relapsed 2 months later. Another patient experienced complete remission in myelology for 4 months, but the variable allele fraction (VAF) value steadily rose, suggesting that the illness was on the verge of progressing. IDH2 gene alterations were found in three of four patients who obtained maintained CR for more than 18 months following recurrence. Venetoclax in combination with azacytidine is a successful and well-tolerated therapy for R/R AML in the elderly. Venetoclax and azacytidine may help patients with TP53 mutations and reduce VAF. The IDH2 mutation might be a good predictor of veneclax sensitivity. A notable adverse response in the treatment phase of the regimen is severe infection induced by neutropenia.

Assessment of macular structures and vascular characteristics in highly myopic anisometropia using swept-source optical coherence tomography angiography.

Purpose: This study aimed to explore the macular structures and vascular characteristics of more myopic (MM) and contralateral eyes with highly myopic anisometropia. Methods: Comprehensive ophthalmic examinations were performed for 33 patients with highly myopic anisometropia. Macular structures (total retinal layer [TRL], ganglion cell and inner plexiform layer [GCIPL], inner nuclear layer [INL], outer retinal layer [ORL], nerve fiber layer [NFL], choroidal layer [CHL]) and vascular characteristics (superficial vascular complex density [SVD], deep vascular complex density [DVD], choriocapillaris perfusion area [CCPA]) were assessed using swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). Macular structures and vascular characteristics of each subregion were compared to those of the Early Treatment of Diabetic Retinopathy Study (ETDRS). Results: With highly myopic anisometropia, the thicknesses of the TRL, GCIPL, INL, and ORL in MM eyes were smaller than those in contralateral eyes in at least one quadrant of the perifoveal and parafoveal circles (all p < 0.05), with no changes in the foveal and temporal quadrants of perifoveal regions (all p > 0.05). A thicker NFL (p = 0.018) was found in MM eyes than in contralateral eyes in the superior perifoveal quadrant. The CHL (all p < 0.05) in MM eyes was thinner in all regions than in the contralateral eyes according to the ETDRS. There were no statistical differences in the SVD, DVD, and CCPA of MM and contralateral eyes (all p > 0.05). Conclusion: All retinal layers, except the NFL, tended to be thinner in all subregions, except the temporal perifoveal and foveal quadrants in MM eyes, and choroidal thickness was thinned in all areas.

Assessment of Long-Term Effects on Pulmonary Functions Between Severe and Non-Severe Convalescent COVID-19 Patients: A Single-Center Study in China.

Objective: To explore the long-term effects of SARS-Cov-2 infection on the pulmonary function in the severe convalescent COVID-19 patients for 6 to 9 months follow-up in Beijing, China. Methods: A total of 64 cases of COVID-19 patients were recruited for the study and discharged from the Beijing Ditan Hospital, Capital Medical University, for 6 to 9 months. COVID-19 patients were divided into non-severe (mild and moderate) and severe groups. The follow-up investigated the lung function tests, the novel coronavirus antibody (IgM and IgG), chest CT and blood tests. Results: About 25.00% (16/64) patients had pulmonary ventilation dysfunction and 35.9% (23/64) had diffusion dysfunction. In the severe group, 56.50% (13/23) individuals showed decreased diffusion function. The diffusion dysfunction of the severe group was significantly decreased than the non-severe group (P = 0.01). Among 56 cases, the positive rate of IgG titers was 73.2% (41/56). The result of chest CT showed 55.36% (31/56) cases in nodules, 44.64% (25/56) in strip-like changes, 37.5% (21/56) in-ground glass shadow, and 5.36% (3/56) in grid shadow, which was significantly different between the severe group and the non-severe group. Patients tended to have ground glass changes in the severe group while nodules in the non-severe group. Conclusion: For the 6 to 9 months in convalescent COVID-19 patients, 56.50% (13/23) of severe patients had pulmonary diffusion dysfunction. Convalescent COVID-19 patients should have their pulmonary function regularly tested, especially those with severe illness.

Investigating weighted fishing hooks for seabird bycatch mitigation.

Fisheries bycatch threatens the viability of some seabird populations and reduces fishing efficiency. Albatross bycatch in a US North Pacific tuna longline fishery has increased over the past decade and now exceeds 1000 annual captures. Seabirds interacting with this fishery reach hooks at depths up to 1 m. A branchline weight's mass and distance from the hook affect seabird catch rates. We conducted experimental fishing to compare the commercial viability of a weighted hook relative to conventional gear with weights attached 0.75 m from the hook. We used a Bayesian random effects meta-analytic regression modelling approach to estimate pooled expected species-specific log relative risk of capture on conventional versus experimental gear. There was a significant 53% (95% HDI: - 75 to - 25%) decrease in retained species' catch rates on experimental hooks, indicating an unacceptable economic cost, and no significant effect for discarded species. Using a Bayesian general linear mixed regression modelling approach, experimental hooks sank to 85 cm ca. 1.4 times (95% HDI: 1.37-1.48) faster than control hooks. Given their potential to reduce seabird catch rates, eliminate safety risks from bite-offs and facilitate robust compliance monitoring, it is a priority to find a weighted hook design with acceptable catch rates.

Assessment of serum Vit A, D and zinc nutritional status and related dietary and exercise behaviors of children and adolescents in rural and urban area.

Vitamin A and vitamin D deficiency in children and adolescents has a negative impact on their growth and development. This study aimed to learn the nutritional status of vitamin A and D among rural children and adolescents and to explore related dietary and exercise behaviors. A total of 10 counties (cities, districts) from 90 counties (cities, districts) in Zhejiang Province were selected by the method of random cluster sampling. Children and adolescents were investigated and their food and nutrient intake were calculated. The concentration of serum vitamin A in urban area was 0.38 ng/ml, which was higher than that in rural area (p < 0.05); while the concentration of serum vitamin D in urban area was 21.25 mg/L, which was lower than that in rural area (p < 0.05). The concentration of serum zinc was 101 µg/dl in urban area and 107 µg/dl in rural area (p < 0.05). The intake of dietary fiber, calcium, vitamin A, vitamin B1, vitamin B2, and vitamin C was lower than the recommended value. In rural area, the intakes of cereals, tubers and beans, livestock, poultry and meat of children and adolescents were higher than the recommended values; while the intake of vegetables, fruits, eggs, milk, fish and shrimp, soybean and nuts was lower than the recommended value. The intake of edible oil and salt is higher than the recommended value. The time of medium and high intensity exercise time in rural area is more than that in urban area in the age group of 12-17 years, while the sitting time is less than that in urban area. Children and adolescents living in rural area should be guided to eat reasonably, and to choose foods with high nutrient density and with low oil, salt and sugar.

Developmental population pharmacokinetics-pharmacodynamics and dosing optimization of cefoperazone in children.

OBJECTIVES: To evaluate the population pharmacokinetics of cefoperazone in children and establish an evidence-based dosing regimen using a developmental pharmacokinetic-pharmacodynamic approach in order to optimize cefoperazone treatment. METHODS: A model-based, open-label, opportunistic-sampling pharmacokinetic study was conducted in China. Blood samples from 99 cefoperazone-treated children were collected and quantified by HPLC/MS. NONMEM software was used for population pharmacokinetic-pharmacodynamic analysis. This study was registered at ClinicalTrials.gov (NCT03113344). RESULTS: A two-compartment model with first-order elimination agreed well with the experimental data. Covariate analysis showed that current body weight had a significant effect on the pharmacokinetics of cefoperazone. Monte Carlo simulation showed that for bacteria for which cefoperazone has an MIC of 0.5 mg/L, 78.1% of hypothetical children treated with '40 mg/kg/day, q8h, IV drip 3 h' would reach the pharmacodynamic target. For bacteria for which cefoperazone has an MIC of 8 mg/L, 88.4% of hypothetical children treated with 80 mg/kg/day (continuous infusion) would reach the treatment goal. A 160 mg/kg/day (continuous infusion) regimen can cover bacteria for which cefoperazone has an MIC of 16 mg/L. Nevertheless, even if using the maximum reported dose of 160 mg/kg/day (continuous infusion), the ratio of hypothetical children reaching the treatment target was only 9.9% for bacteria for which cefoperazone has an MIC of 32 mg/L. CONCLUSIONS: For cefoperazone, population pharmacokinetics were evaluated in children and an appropriate dosing regimen was developed based on developmental pharmacokinetics-pharmacodynamics. The dose indicated in the instructions (20-160 mg/kg/day) can basically cover the clinically common bacteria for which cefoperazone has an MIC of ≤16 mg/L. However, for bacteria for which the MIC is >16 mg/L, cefoperazone is not a preferred choice.

Assessment of three methods for removing massive air in a cardiopulmonary bypass circuit: simulation-based multi-discipline training in West China Hospital.

BACKGROUND AND OBJECTIVE: A multi-discipline cardiac and cardiopulmonary bypass (CPB) team simulation scenario was established to compare three different de-airing approaches dealing with massive air embolism in CPB, so as to formulate a standardized procedure to handle this adverse acute event more proficiently and ensure clinical safety. METHOD: A simulation-based clinical CPB massive air embolism scenario was developed by a cardiac and CPB team. Study Objects: Five licensed perfusionists and five CPB trainees were matched randomly into five pairs. Each pair would simulate the three different de-airing approaches separately as followed: (1) Conventional Method: arterial line filter (ALF) de-airing purge line and oxygenator self-recirculation bypass were used to de-air; (2) Arterial-Venous Loop (A-V Loop) Method: surgeons reconnected the arterial and venous lines to de-air by restoring the original priming A-V loop configuration; (3) Isolation of the ALF Method: this ensures de-bubbling of the CPB circuit, but bypasses the ALF function. Assessment Criteria: (1) Times to recovery (duration of the circulation suspension); (2) Subjective evaluation of skill and non-skill performances. RESULTS: As to times to recovery, the Conventional Method group took 290.6 s ± 36.2, the A-V Loop Method group took 196.8 s ± 52.0 and the Isolation of ALF group took 99.4 s ± 15.1. The statistical difference is significant among the three groups (p<0.01). The subjective evaluation of training performance indicates that this simulation-based training is effective in assessing both skill and non-skill abilities. CONCLUSION: CPB simulation-based training was effective in comparing de-airing strategies and can instruct perfusion practices how to optimize techniques. For well-trained, multi-discipline cardiac teams, the A-V Loop Method is highly efficient and reliable in managing CPB massive air embolism. For cardiac teams that do not have this sophisticated training, the Isolation of ALF Method should be their alternative option.

Leaf turgor loss point is correlated with drought tolerance and leaf carbon economics traits.

Leaf turgor loss point (πtlp) indicates the capacity of a plant to maintain cell turgor pressure during dehydration, which has been proven to be strongly predictive of the plant response to drought. In this study, we compiled a data set of πtlp for 1752 woody plant individuals belonging to 389 species from nine major woody biomes in China, along with reduced sample size of hydraulic and leaf carbon economics data. We aimed to investigate the variation of πtlp across biomes varying in water availability. We also tested two hypotheses: (i) πtlp predicts leaf hydraulic safety margins and (ii) it is correlated with leaf carbon economics traits. Our results showed that there was a positive relationship between πtlp and aridity index: biomes from humid regions had less negative values than those from arid regions. This supports the idea that πtlp may reflect drought tolerance at the scale of woody biomes. As expected, πtlp was significantly positively correlated with leaf hydraulic safety margins that varied significantly across biomes, indicating that this trait may be useful in modelling changes of forest components in response to increasing drought. Moreover, πtlp was correlated with a suite of coordinated hydraulic and economics traits; therefore, it can be used to predict the position of a given species along the 'fast-slow' whole-plant economics spectrum. This study expands our understanding of the biological significance of πtlp not only in drought tolerance, but also in the plant economics spectrum.

Malaria from hyperendemicity to elimination in Hekou County on China-Vietnam border: an ecological study.

BACKGROUND: Malaria control and elimination are challenged by diversity and complexity of the determinants on the international border in the Great Mekong Sub-region. Hekou, a Chinese county on the China-Vietnam border, was used to document Chinese experiences and lessons for malaria control and elimination. METHODS: The design was an ecological study. Malaria burden before 1951 and procedures of 64 years (1952-2015) from malaria hyperendemicity to elimination are described. Single and bilinear regression analysis was utilized to analyse the relationship between the annual malaria incidence (AMI) and gross domestic product (GDP), urbanization rate, and banana planting area (BPA). RESULTS: There was a huge malaria burden before 1951. AMI was reduced from 358.62 per 1000 person-years in 1953 to 5.69 per 1000 person-years in 1960. A system of primary health services, comprising three levels of county township hospitals and village health stations maintained malaria control and surveillance activities in changing political and social-economic settings. However, potential under-reported of malaria and market-oriented healthcare led to a malaria epidemic in 1987. Strong political commitment reoriented malaria from a control to an elimination programme. High coverage of malaria intervention and population access to intervention was crucial for malaria control and elimination; meanwhile, AMI was closely associated with socio-economic development, correlation coefficients (R) -0.6845 (95% CI -0.7978, -0.6845) for national GDP, -0.7014 (-0.8093, -0.7014) for national urbanization rate and -0.5563 (-0.7147, -0.3437) for BPA. CONCLUSIONS: Multifactor, including political commitment, effective interventions, social and economic development and changing ecological environment, and the complicated interactions between these factors contribute to malaria elimination in Hekou County.

[Application Potential and Assessment of Metallurgical Contaminated Soil After Remediation in Tongguan of Shaanxi].

There has been a growing interest in soil replacement and in-situ stabilization techniques in recent years. Many techniques in the remediation of contaminated soils have been proven to be effective methods. In this study, lime and calcium phosphate were added to immobilize the heavy metals in contaminated soils. The long-term application potential of these techniques were evaluated by taking the demonstration project of the soil remediation in Tongguan of Shaanxi as the case study.The status of heavy metal contamination in the study area resulted from artisanal gold mining was discussed. The strategies of remediation and the evaluation of the remediation results including the safety of agricultural practices were also studied. The results showed that soil was seriously contaminated in the study area with Cd, Pb, and Hg, and the residue mining waste was the main source. The potential ecological risk index ranged from 668 to 10969, suggesting that all the samples posed a very strong ecological hazard. Based on the pollution status, the soil replacement method and stabilization method were applied. Acceptable remediation results were obtained with lower total metal content (except Cd) and decreased heavy metal availability. However, the metal content of agricultural products was higher than the permissible value according to GB 2762-2012, which means that agricultural practices pose risks on remediated soils. Soil replacement and stabilization would be practical techniques for heavy metal polluted soil remediation. However, a consecutive investigation should be conducted for the assurance of food safety.

Different leaf cost-benefit strategies of ferns distributed in contrasting light habitats of sub-tropical forests.

BACKGROUND AND AIMS: Ferns are abundant in sub-tropical forests in southern China, with some species being restricted to shaded understorey of natural forests, while others are widespread in disturbed, open habitats. To explain this distribution pattern, we hypothesize that ferns that occur in disturbed forests (FDF) have a different leaf cost-benefit strategy compared with ferns that occur in natural forests (FNF), with a quicker return on carbon investment in disturbed habitats compared with old-growth forests. METHODS: We chose 16 fern species from contrasting light habitats (eight FDF and eight FNF) and studied leaf functional traits, including leaf life span (LLS), specific leaf area (SLA), leaf nitrogen and phosphorus concentrations (N and P), maximum net photosynthetic rates (A), leaf construction cost (CC) and payback time (PBT), to conduct a leaf cost-benefit analysis for the two fern groups. KEY RESULTS: The two groups, FDF and FNF, did not differ significantly in SLA, leaf N and P, and CC, but FDF had significantly higher A, greater photosynthetic nitrogen- and phosphorus-use efficiencies (PNUE and PPUE), and shorter PBT and LLS compared with FNF. Further, across the 16 fern species, LLS was significantly correlated with A, PNUE, PPUE and PBT, but not with SLA and CC. CONCLUSIONS: Our results demonstrate that leaf cost-benefit analysis contributes to understanding the distribution pattern of ferns in contrasting light habitats of sub-tropical forests: FDF employing a quick-return strategy can pre-empt resources and rapidly grow in the high-resource environment of open habitats; while a slow-return strategy in FNF allows their persistence in the shaded understorey of old-growth forests.

Evolution of cooperation in spatial traveler's dilemma game.

Traveler's dilemma (TD) is one of social dilemmas which has been well studied in the economics community, but it is attracted little attention in the physics community. The TD game is a two-person game. Each player can select an integer value between [Formula: see text] and [Formula: see text] ([Formula: see text]) as a pure strategy. If both of them select the same value, the payoff to them will be that value. If the players select different values, say [Formula: see text] and [Formula: see text] ([Formula: see text]), then the payoff to the player who chooses the small value will be [Formula: see text] and the payoff to the other player will be [Formula: see text]. We term the player who selects a large value as the cooperator, and the one who chooses a small value as the defector. The reason is that if both of them select large values, it will result in a large total payoff. The Nash equilibrium of the TD game is to choose the smallest value [Formula: see text]. However, in previous behavioral studies, players in TD game typically select values that are much larger than [Formula: see text], and the average selected value exhibits an inverse relationship with [Formula: see text]. To explain such anomalous behavior, in this paper, we study the evolution of cooperation in spatial traveler's dilemma game where the players are located on a square lattice and each player plays TD games with his neighbors. Players in our model can adopt their neighbors' strategies following two standard models of spatial game dynamics. Monte-Carlo simulation is applied to our model, and the results show that the cooperation level of the system, which is proportional to the average value of the strategies, decreases with increasing [Formula: see text] until [Formula: see text] is greater than the critical value where cooperation vanishes. Our findings indicate that spatial reciprocity promotes the evolution of cooperation in TD game and the spatial TD game model can interpret the anomalous behavior observed in previous behavioral experiments.

Effects of breeds and dietary protein levels on the growth performance, energy expenditure and expression of avUCP mRNA in chickens.

The physiological mechanisms of thermogenesis, energy balance and energy expenditure are poorly understood in poultry. The aim of this study was designed to investigate the physiological roles of avian uncoupling protein (avUCP) regulating in energy balance and thermogenesis by using three chicken breeds of existence striking genetic difference and feeding with different dietary protein levels. Three chicken breeds including broilers, hybrid chickens, and non-selection Wuding chickens were used in this study. Total 150 chicks of 1 day of age, with 50 from each breed were reared under standard conditions on starter diets to 30 days. At 30 days of age, forty chicks from each breed chicks were divided into two groups. One group was fed low protein diet (LP, 17.0 %), and the other group was fed high protein diet (HP, 19.5 %) for 60 days. Wuding chickens showed the lowest feed conversion efficiency (FCE) and the highest expressions of avUCP mRNA association with high plasma T3 and insulin concentrations. Hybrid chickens showed the lowest expressions of avUCP mRNA association with high FCE and energy efficiency. Expressions of avUCP mRNA association with diet-induced thermogenesis (DIT) were only observed in broiler and hybrid chickens. The expressions of avUCP mRNA were positive association with plasma insulin, T3 and NEFA concentrations. Age influence on the expression of avUCP mRNA were observed only for hybrid and broiler chickens. It seems that both roles of avUCP regulation thermogenesis and lipid utilisation as fuel were observed in the present study response to variation in dietary protein and breeds.

[Assessment on dietary iodine intake in three areas of Zhejiang province, 2009].

OBJECTIVE: To assess the level of dietary iodine intake in three areas of Zhejiang and the related policy on universal salt iodization in the province. METHODS: The study involved 497 residents from 180 families living in Hangzhou, Taizhou, Zhoushan cities, representing coastal and inland areas in Zhejiang province in 2009. A total diet study was applied to obtain the typical diet samples at three study areas through food consumption, aggregation, sampling and preparation processes. The contents of iodine in diet samples were determined by tetramethylammonium hydroxide extraction-inductively coupled plasma-mass spectrometry. The amount of dietary iodine intake was calculated by timing the food consumption data and the iodine content in different dietary samples. The safety of dietary iodine intake was evaluated according to the recommended nutrient intake (RNI) and tolerable upper intake level (UL) published by the Chinese Nutrition Society in 2001. RESULTS: The dietary iodine intake of reference person in three areas of Zhejiang province was 421.0 µg/d. The levels of P5, P25, median, P75, P90, P95 dietary iodine intake were 145.7 µg/d, 267.6 µg/d, 358.5 µg/d, 495.6 µg/d, 774.1 µg/d and 1273.0 µg/d respectively. Daily dietary iodine intake at UL accounted for 5.2%, 87.5% and 7.2% of all the participants respectively. Without considering the loss through cooking, salt iodine provided 81.6% of the dietary iodine source. The resources of dietary iodine would include vegetables, cereals and marine food, proportionally, as 57.2%, 13.0% and 8.5%, respectively. Participants whose daily dietary iodine intake exceeded the UL level would consume more marine algae products than those whose dietary iodine intakes were lower than RNI or between RNI-UL. CONCLUSION: Dietary iodine intake among most residents and their average level were among reasonable ranges. Meanwhile, deficiency and excess of iodine intake coexisted. Salt iodine was the main resource of dietary iodine. Participants whose dietary iodine intakes exceeding the UL level, would prefer consume more marine algae products.

[Exposure assessment on dietary lead and cadmium of residents in three areas of Zhejiang province from 2009 to 2010].

OBJECTIVE: To assess the safety of dietary lead and cadmium intake in 3 areas of Zhejiang province. METHODS: Using the total dietary study method, the study was conducted in 3 regions which represented coastal, city and rural areas in Zhejiang province from 2009 to 2010. The dietary survey was conducted on the residents (512 subjects) and the categories and volume of food consumption were obtained. The analytical food samples were obtained by food consumption survey, food aggregation, food sampling and preparation. The food samples were detected by inductively coupled plasma mass spectrometry (ICP-MS). The safety of dietary lead and cadmium intake was evaluated. RESULTS: The median dietary lead intake (P50) in Zhejiang province was 37.8 µg/d. The 97.5% dietary lead intake (P97.5) was 72.3 µg/d. The P50 dietary lead intakes of different age and gender groups ranged from 23.2 to 44.2 µg/d. The P97.5 dietary lead intakes of different age and gender groups ranged from 34.2 to 88.1 µg/d. The P50 dietary cadmium intake in Zhejiang province was 9.6 µg/d. The P97.5 dietary cadmium intake was 15.7 µg/d. The P50 dietary cadmium intakes of different age and gender groups ranged from 6.4 to 11.4 µg/d, accounting 15.6% - 42.6% of PTMI (provisional tolerable monthly intake, 25 µg/kg). The P97.5 dietary cadmium intakes of different age and gender groups ranged from 10.5 to 21.4 µg/d, accounting 27.5% - 77.6% of PTMI. Vegetable (11.3 µg), cereal (11.0 µg) and meat (9.8 µg) were the first three food sources which accounted for 84.9% of dietary lead (P50: 37.8 µg/d). Cereal (3.6 µg), vegetable (2.1 µg) and legume (0.9 µg) were the first three food sources which accounted for 68.8% of dietary cadmium (P50: 9.6 µg/d). CONCLUSION: Dietary lead and cadmium intakes of most residents in 3 areas of Zhejiang province as well as the average level are safe.

Determination of duloxetine in human plasma via LC/MS and subsequent application to a pharmacokinetic study in healthy Chinese volunteers.

BACKGROUND: The pharmacokinetics of duloxetine hydrochloride have been well studied after its approval for clinical use. However, few such data have been reported in the English language literature. We developed a method to determine the pharmacokinetics of duloxetine enteric-coated capsules in healthy Chinese volunteers. METHODS: A rapid and sensitive liquid chromatography-mass spectrometric (LC/MS) method for the determination of duloxetine in human plasma using flupentixol as the internal standard (I.S.) was developed and validated. Sample preparation of the plasma involved deproteination with acetonitrile twice, repeatedly. Samples were then analyzed by HPLC on a Thermo Hypersil-Hypurity C18 column (150 x 2.1 mm, 5 microm). A single-quadrupole mass spectrometer with an electrospray interface was operated in the selected-ion monitoring mode to detect the [M+H](+) ions at 298 m/z for duloxetine and at 435 m/z for the internal standard. RESULTS: Pharmacokinetics were measured in 12 healthy Chinese male volunteers (6 males and 6 females) who received a single regimen with 3 different dosages at 22.4, 44.8 and 67.2 mg of duloxetine enteric-coated capsules. CONCLUSION: A sensitive and specific method for quantifying duloxetine levels in human plasma has been devised and successfully applied to a clinic pharmacokinetic study of an enteric-coated capsule of duloxetine hydrochloride administered as a single oral dose.

Determination of perospirone by liquid chromatography/electrospray mass spectrometry: application to a pharmacokinetic study in healthy Chinese volunteers.

Perospirone is a novel atypical antipsychotic with a unique combination of 5-HT(1A) receptor agonism as well as 5-HT(2A) and D(2) receptor antagonism. A simple rapid and selective LC-MS method utilizing a single quadrupole mass spectrometer was developed and validated for the determination of perospirone hydrochloride in human plasma. N-hexane was used to extract perospirone hydrochloride and amlodipine benzenesulfonate (internal standard (IS)) from an alkaline plasma sample. LC separation was performed on a XTerra MS C(18) column (100mmx2.1mm, i.d. 3.5microm) using methanol -10mM ammonium acetate (84:16, v/v) as a mobile phase. The quantification of target compounds was obtained by using a selected ion monitoring (SIM) at m/z 427.5 [M+H](+) for perospirone hydrochloride, and at m/z 431.4 [M+Na](+) for IS (amlodipine benzenesulfonate). Perospirone and IS eluted as sharp, symmetrical peaks with retention times of 3.11+/-0.01min and 4.15+/-0.2min, respectively. Calibration curves of perospirone hydrochloride in human plasma at concentrations ranging from 0.10 to 21.1ng/mL exhibited excellent linearity (r(2)=0.9997). The mean absolute recovery of the drug from plasma was more than 85%. Intra- and inter-day relative standard deviations were less than 6.43% and 11.9% for perospirone hydrochloride at the range from 0.32 to 10.6ng/mL. Stability characteristics of the drug-containing plasma were thoroughly evaluated to establish appropriate conditions to process, store and prepare for chromatographic analysis without inducing significant chemical degradation. The following pharmacokinetic parameters were elucidated after administering a single dose of 8mg perospirone hydrochloride. The area under the plasma concentration versus time curve from time 0 to 24h (AUC(0-24)) was 15.48+/-4.23microg/Lh; peak plasma concentration (C(max)) was 2.79+/-0.78microg/L; time to C(max) (T(max)) was 1.79+/-0.45h; and elimination half-life (t(1/2)) 6.78+/-1.38h. The described assay method showed acceptable precision, accuracy, linearity, stability, and specificity and can be used for pharmacokinetic studies, therapeutic drug monitoring, and drug abuse screening.