Effects of shift work on sleep quality and cardiovascular function in Taiwanese police officers.

This study aimed to investigate the effects of shift work on sleep quality, cardiovascular function, and physical activity (PA) levels in Taiwanese police officers. Twenty-one male police officers aged 26.9 ± 4.1 years old located in Taipei voluntarily participated in this study. The participants completed the resting heart rate (HR) and hemodynamic variables (e.g. blood pressure, BP) before and after day-time (DTW) and night-time (NTW) shift work phases (5 working days and 2 resting days for each phase). Additionally, an actigraphy was administered to measure PA and sleep patterns in the last 3 working days. The average total sleep time and sleep efficiency were 278.5 ± 79. 6 min and 72.9 ± 10%, respectively, in the NTW phases, which were significantly lower than that in the DTW phases. A comparison of the PA characteristics between the two phases revealed that a lower proportion of moderate-vigorous PA (1.2 ± 0.8%) and a greater proportion of sedentary behaviour PA (74.8 ± 6.4%) was found in the NTW phases. The results of hemodynamic measures demonstrated that the police officers have significantly elevated systolic BP by 3.3% and diastolic BP by 3.9% after the NTW phases. Furthermore, the NTW phases exhibited a significantly higher percentage change ratio of systolic BP and diastolic BP compared to the DTW phases. Compared with the DTW phases, the NTW phase was significantly more likely to report higher decreasing parasympathetic-related HR variability with a range of -5.9% to -7.8%. In conclusion, night-time shift work resulted in negative physiological changes leading to adverse effects on the health and well-being of Taiwanese police officers.

Assessment of sources and health risks of heavy metals in metropolitan household dust among preschool children: The LEAPP-HIT study.

The most common construction material used in Taiwan is concrete, potentially contaminated by geologic heavy metals (HMs). Younger children spend much time indoors, increasing HM exposure risks from household dust owing to their behaviors. We evaluated arsenic (As), cadmium (Cd), and lead (Pb) concentrations in fingernails among 280 preschoolers between 2017 and 2023. We also analyzed HM concentrations, including As, Cd, Pb, chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn), in 90 household dust and 50 road dust samples from a residential area where children lived between 2019 and 2021 to deepen the understanding of sources and health risks of exposure to HMs from household dust. The average As, Cd, and Pb concentrations in fingernails were 0.12 ± 0.06, 0.05 ± 0.05, and 0.95 ± 0.77 µg/g, respectively. Soil parent materials, indoor construction activities, vehicle emissions, and mixed indoor combustion were the pollution sources of HMs in household dust. Higher Cr and Pb levels in household dust may pose non-carcinogenic risks to preschoolers. Addressing indoor construction and soil parent materials sources is vital for children's health. The finding of the present survey can be used for indoor environmental management to reduce the risks of HM exposure and avoid potential adverse health effects for younger children.

Associations between parental and postnatal metal mixture exposure and developmental delays in a Taiwanese longitudinal birth cohort of preschool children.

Studies have evaluated the impact of environmental exposure to neurotoxic metals on developmental delays (DDs). However, comprehensive understanding regarding the associations between parental and postnatal exposure to metal mixtures and the occurrence of DDs in offspring is limited. In this study, we assessed the relationships between parental and postnatal exposure to three metals (arsenic [As], cadmium [Cd], and lead [Pb], levels of which were measured in toenails) and suspected DDs (SDDs) in preschool children within a Taiwanese longitudinal birth cohort. In total between 2017 and 2021, 154 pairs of parents and their children under the age of 6 years were recruited, and 462 toenail samples and 154 completed questionnaires were collected. Metal concentrations in toenails were quantified using inductively coupled plasma-mass spectrometry after acid digestion of the toenails. We applied multivariable logistic regression and Bayesian kernel machine regression to evaluate the overall effect and to identify key components of the metal mixture that were associated with the SDD risk. Higher concentrations of As, Cd, and Pb were found in the toenails of the parents of children with SDDs compared with the toenails of the parents of children without SDDs. Our examination of the combined effects of exposure to the metal mixture revealed that As concentration in the father's toenail and Cd concentration in the mother's toenail were positively correlated with the risk of SDDs in their offspring. Notably, the effect of exposure to the metal mixture on the risk of SDDs was stronger in boys than in girls. Our findings suggest that parents taking measures to minimize their exposure to metals might enhance their children's developmental outcomes.

Oral and inhalation bioaccessibility of mercury in contaminated soils and potential health risk to the kidneys and neurodevelopment of children in Taiwan.

Health risk assessments of exposure to mercury (Hg) from soils via ingestion and inhalation are indispensable for Taiwanese people living in the vicinity of Hg-contaminated sites. In this study, anthropogenic soils were collected from various polluted sources in Taiwan. In vitro oral and inhalation bioaccessible fractions of Hg were analyzed to avoid from overestimating the exposure risk. Discrepancies in oral and inhalation bioaccessible levels of Hg in soils were found using different in vitro assays with different pH levels and chemical compositions. The freshly contaminated soil (soil S7) polluted by chlor-alkali production activity sampled before the site was remediated had the highest total Hg concentration of 1346 mg/kg, with the highest oral bioaccessibility of 26.2% as analyzed by SW-846 Method 1340 and inhalation bioaccessibility of 30.5% as analyzed by modified Gamble's solution. The lesser extent of aging of Hg in soil S7 increased the Hg availability for humans, which was also found based on results of a sequential extraction procedure. Results of the hazard quotient showed that soil ingestion was the main pathway causing non-carcinogenic risks for children and adults. Children were also exposed to higher risks than were adults due to higher frequencies of hand-to-mouth behaviors and lower body weights. Furthermore, hazard index results adjusted for oral and inhalation bioaccessible Hg were lower than those obtained based on the total Hg content; however, an unacceptable value of the non-carcinogenic risk (> 1) for children living near soil S7 was still observed. This study suggests that children living near sites polluted for a short period of time may suffer potential renal effects regardless of the bioaccessibility. Our findings provide suggestions for decision makers on setting new strategies for managing risks of Hg-contaminated soils in Taiwan.

Air Pollution-Related Respiratory Diseases and Associated Environmental Factors in Chiang Mai, Thailand, in 2011-2020.

The unfavorable effects of global climate change, which are mostly the result of human activities, have had a particularly negative effect on human health and the planet's ecosystems. This study attempted to determine the seasonality and association of air pollution, in addition to climate conditions, with two respiratory infections, influenza and pneumonia, in Chiang Mai, Thailand, which has been considered the most polluted city on Earth during the hot season. We used a seasonal-trend decomposition procedure based on loess regression (STL) and a seasonal cycle subseries (SCS) plot to determine the seasonality of the two diseases. In addition, multivariable negative binomial regression (NBR) models were used to assess the association between the diseases and environmental variables (temperature, precipitation, relative humidity, PM2.5, and PM10). The data revealed that influenza had a clear seasonal pattern during the cold months of January and February, whereas the incidence of pneumonia showed a weak seasonal pattern. In terms of forecasting, the preceding month's PM2.5 and temperature (lag1) had a significant association with influenza incidence, while the previous month's temperature and relative humidity influenced pneumonia. Using air pollutants as an indication of respiratory disease, our models indicated that PM2.5 lag1 was correlated with the incidence of influenza, but not pneumonia. However, there was a linear association between PM10 and both diseases. This research will help in allocating clinical and public health resources in response to potential environmental changes and forecasting the future dynamics of influenza and pneumonia in the region due to air pollution.

Management of Ventilator-Associated Pneumonia: Quality Assessment of Clinical Practice Guidelines and Variations in Recommendations on Drug Therapy for Prevention and Treatment.

Purpose: To assess the quality of clinical practice guidelines (CPGs) related to drug therapy for prevention and control of ventilator-associated pneumonia (VAP) and compare the differences and similarities between recommendations. Methods: Electronic databases (including PubMed, Cochrane library, Embase, Web of Science), guideline development organizations, and professional societies were searched to identify CPGs for VAP from 20 January 2012 to 20 January 2022. The Appraisal of Guidelines Research & Evaluation (AGREE) II instrument was used to evaluate the quality of the guidelines. The recommendations on drug therapy for prevention and treatment for each guideline were extracted, and then a descriptive synthesis was performed to analyze the scope/topic, and consistency of the recommendations. Results: Thirteen CPGs were included. The median score and interquartile range (IQR) in each domain are shown below: scope and purpose 72.22% (63.89%,83.33%); stakeholder involvement 44.44% (38.89%,52.78%); rigor of development 43.75% (31.25%,57.29%); clarity and presentation 94.44% (77.78%,94.44%); applicability 20.83 (8.34%,33.34%) and editorial independence 50% (33.33%,66.67%). We extracted 21 recommendations on drug therapy for prevention of VAP and 51 recommendations on drugs used for treatment. Some controversies remained among the included guidelines. Conclusion: There is considerable variability in the development processes and reporting of VAP guidelines. Despite many similarities, the recommendations still had some inconsistencies in the details. For the prevention and treatment of VAP, local microbial epidemiology and antibiotic sensitivity must be considered, and recommendations should be regularly revised as new evidence emerges.

Associations of maternal food safety-related risk perceptions and protective behaviors with daily mercury intake and internal doses of Taiwanese women and their preschool children.

Mercury (Hg) is a well-known toxicant that can affect children's neurodevelopment. This study attempted to evaluate the internal dose of Hg in hair and fingernails and external Hg exposure from dietary consumption in 283 pairs of mothers and their children aged under 6 years in Taiwan. Mean Hg levels in hair and fingernail samples were 1.07 ± 0.67 and 0.42 ± 0.34 µg/g for mothers, and 1.11 ± 1.22 and 0.36 ± 0.26 µg/g for children, respectively. Our results showed that 42% of mothers and 41% of children had hair Hg levels exceeding the US Environmental Protection Agency recommended value of 1 µg/g. Hg exposure in children was greater than that of their mothers. Estimated daily intake (EDI) levels of Hg among preschool children were 3.3-times higher than those of their mothers. A sensitivity analysis indicated that fish consumption was the main potential factor of Hg exposure among both mothers and their children. External Hg exposure using estimated daily dietary ingestion by mothers was a surrogate for internal hair Hg concentrations. However, poor correlations were found between EDI Hg levels and hair Hg levels among children aged 4-6 years. Exposure sources from food and other media, such as soil and dust, need to be considered to arrive at more-valid risk assessments for younger children's exposure to Hg. Children of mothers who did not have food safety-related risk perceptions or protective behaviors had significantly higher hair Hg concentrations compared to children whose mothers had risk perceptions and protective behaviors. Hg exposure of women of childbearing age and preschool children in Taiwan is still an area of great concern. Providing food safety information and risk-benefits of fish consumption for mothers may avoid harm to the developing nervous systems of their children.

Estimation of Soil and Dust Ingestion Rates from the Stochastic Human Exposure and Dose Simulation Soil and Dust Model for Children in Taiwan.

This study focuses on estimating the probabilistic soil and dust ingestion rates for children under 3 years old by the Stochastic Human Exposure and Dose Simulation Soil and Dust (SHEDS-S/D) model developed by the U.S. Environmental Protection Agency. The health risk of children's exposure to heavy metals through soil and dust ingestion and dermal absorption was then assessed in three exposure scenarios. In the exposure scenario of direct contact with soil, the average soil and dust ingestion rates for children aged 24 to 36 months were 90.7 and 29.8 mg day-1 in the sand and clay groups, respectively. Hand-to-mouth soil ingestion was identified as the main contributor to soil and dust ingestion rates, followed by hand-to-mouth dust ingestion and object-to-mouth dust ingestion. The soil-to-skin adherence factor was the most influential factor increasing the soil and dust ingestion rate based on a sensitivity analysis in the SHEDS-S/D model. Furthermore, the modeled soil and dust ingestion rates based on the SHEDS-S/D model were coincident with results calculated by the tracer element method. Our estimates highlight the soil ingestion rate as the key parameter increasing the risk for children, while a higher frequency of hand washing could potentially reduce the risk.

Sub-100-micron calcium-alginate microspheres: Preparation by nitrogen flow focusing, dependence of spherical shape on gas streams and a drug carrier using acetaminophen as a model drug.

We developed a miniature gas-liquid coaxial flow device using glass capillaries, aiming to produce sub-100-µm Ca-alginate microspheres. Depending on collecting distance and the flow rates of nitrogen gas and alginate solution, however, Ca-alginate microparticles of different shapes were obtained. Spherical, monodisperse microparticles (microspheres) could only be obtained at certain gas flow rates and within a corresponding range of collecting distance. The result suggests that, for particles of this size, the gas flow rate and collecting distance are crucial for the formation of the spherical shape. We evaluated, as an example of its applications, the microsphere as a drug carrier using acetaminophen as a model drug. Large (~150 µm) and small (~70 µm) drug-loaded microspheres were prepared using two respective devices. Specifically, the drug-loaded microspheres were complexed with chitosan of different molecular weights. The dependence of in vitro drug release on the microsphere size and the chitosan molecular weight was examined. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Alginic acid sodium salt (PubChem CID: 5102882); Chitosan (PubChem CID: 71853); Calcium chloride (PubChem CID: 5284359); Sodium chloride (PubChem CID: 5234); Acetaminophen (PubChem CID: 1983); Polydimethylsiloxane (PubChem CID: 24771); n-Octadecyltrimethoxysilane (PubChem CID: 76486).

Effects of soil lead exposure and land use characteristics on neurodevelopment among children under 3 years of age in northern Taiwan.

Lead (Pb) exposure increases the risks of neurodevelopmental disorders in children. Child-specific activities and land use scenarios may lead to elevated opportunities for Pb exposure through the soil. Therefore, we investigated hair and fingernail Pb concentrations among young children in northern Taiwan, in relation to soil Pb pollution and land use characteristics. We also explored the effect of the Pb exposure burden and land use scenarios on neurobehavioral development. In total, 139 healthy children under 3 years of age were recruited in October 2011 to April 2014. Pb levels in hair and fingernail samples were determined using an inductively coupled plasma/mass spectrometer. Pb concentrations in soils and land use types surrounding the children's homes were accessed by a geographic information system to identify any associations with hair Pb levels. The Bayley Scales of Infant and Toddler Development (Bayley-III) were used to evaluate the cognitive, language, and motor development of the children. A multivariable regression model was performed to assess the effects of soil Pb levels and land-use status on Pb exposure in children, as well as associations of Pb exposure and land-use scenarios with neurodevelopmental abilities. Geometric mean Pb concentrations in hair, fingernails, and soil were 2.9 ± 4.8 µg/g, 0.8 ± 5.1 µg/g, and 20.8 ± 4.3 mg/kg, respectively. The multivariable analysis indicated that soil Pb concentrations and green areas around residences had potential links with Pb exposure among children in northern Taiwan. Hair Pb concentrations were negatively associated with expressive language scores. Soil Pb exposure was positively associated with hair Pb concentrations. Land use types around the children's homes in northern Taiwan were associated with their neurodevelopment. Increased green areas were negatively associated with hair Pb concentrations. Living near a highway may have had negative impacts on gross motor scores. A healthy residence can avoid potential health risks for children during their early life.

Influence of soil properties on the bioaccessibility of Cr and Ni in geologic serpentine and anthropogenically contaminated non-serpentine soils in Taiwan.

Serpentine minerals with high levels of geologic chromium (Cr) and nickel (Ni) and non-serpentine farmlands polluted by irrigation water causing high anthropogenic Cr and Ni levels are both found in Taiwan. Elevated levels of Cr and Ni in these soils are a concern due to their potential to promote cancer mortality in humans. Bioaccessibility is a crucial factor determining the actual health risk via oral ingestion when children are exposed to metal-contaminated soils. Furthermore, the bioaccessibility of metals varies with the source, soil properties, and fractionation of metals in the soil. Therefore in this study, soil pH, total organic carbon (TOC), texture, and the total concentrations, fractionation, and bioaccessibility of Cr and Ni were analyzed and correlated for soils collected from serpentine mineral-containing deposits and contaminated non-serpentine farmlands. The low bioaccessibility and low mobility of Cr and Ni in serpentine soils suggested that incidental ingesting of soils posed a low health risk; however, the higher bioaccessibility and mobility of Ni in non-serpentine soils contaminated by electroplating wastewater could lead to potential risks for humans. Additionally, a significant difference in the bioaccessibility of Ni was observed between serpentine and non-serpentine soils, but this was not shown for Cr. Accordingly, a correlation analysis showed that Cr bioaccessibility was positively correlated with TOC, with no distinction between serpentine and non-serpentine soils. In contrast, TOC and the fractions of the sequential extraction procedure were significantly correlated with Ni bioaccessibility both in anthropogenically contaminated non-serpentine soils and in natural serpentine soils.

Distribution of mercury and methylmercury in surface water and surface sediment of river, irrigation canal, reservoir, and wetland in Taiwan.

In Taiwan, because of the co-use of some irrigation and drainage canals, a portion of industrial wastewater was directly discharged into irrigation canals or even flowed into rivers or wetlands, causing the heavy metal pollution in waters and sediments. Mercury (Hg) contamination in rivers, irrigation canals, and wetlands has been found in Taiwan, but a thorough investigation on the distribution of Hg and methylmercury (MeHg) in these waters and sediments, which may be present in a greater level with elevating total Hg (THg) concentration and markedly impact human health, is still lacking. In this study, surface waters and surface sediments were sampled from five major rivers, two irrigation canals, two reservoirs, and one wetland in Taiwan, and their THg and MeHg concentrations were quantified. Additionally, statistical analysis was carried out to understand the relationship between sediment properties and MeHg levels. The results showed that irrigation canal sediments were relatively more polluted by Hg and the THg concentrations of some sampling points exceeded the upper limit (i.e., 0.87 mg kg-1) of sediment quality index (SQI) for THg promulgated by Taiwan Environmental Protection Administration, which may be attributed to the co-use of irrigation and drainage canals. Furthermore, the MeHg concentration in irrigation canal sediments was the highest; rivers came in second followed by wetlands. In addition, the Siangshan Wetland was analyzed to have the greatest THg and MeHg concentrations in its surface water. Linear regression analysis also indicated that total organic carbon and clay content substantially affected the MeHg production in sediments.

Advanced Microfluidic Device Designed for Cyclic Compression of Single Adherent Cells.

Cells in our body experience different types of stress including compression, tension, and shear. It has been shown that some cells experience permanent plastic deformation after a mechanical tensile load was removed. However, it was unclear whether cells are plastically deformed after repetitive compressive loading and unloading. There have been few tools available to exert cyclic compression at the single cell level. To address technical challenges found in a previous microfluidic compression device, we developed a new single-cell microfluidic compression device that combines an elastomeric membrane block geometry to ensure a flat contact surface and microcontact printing to confine cell spreading within cell trapping chambers. The design of the block geometry inside the compression chamber was optimized by using computational simulations. Additionally, we have implemented step-wise pneumatically controlled cell trapping to allow more compression chambers to be incorporated while minimizing mechanical perturbation on trapped cells. Using breast epithelial MCF10A cells stably expressing a fluorescent actin marker, we successfully demonstrated the new device design by separately trapping single cells in different chambers, confining cell spreading on microcontact printed islands, and applying cyclic planar compression onto single cells. We found that there is no permanent deformation after a 0.5 Hz cyclic compressive load for 6 min was removed. Overall, the development of the single-cell compression microfluidic device opens up new opportunities in mechanobiology and cell mechanics studies.

Using raw and sulfur-impregnated activated carbon as active cap for leaching inhibition of mercury and methylmercury from contaminated sediment.

Sulfur-impregnated activated carbon (SAC) has been reported with a high affinity to Hg, but little research has done on understanding its potential as active cap for inhibition of Hg release from contaminated sediments. In this study, high-quality coconut-shell activated carbon (AC) and its derived SAC were examined and shown to have great affinity to both aqueous Hg2+ and methylmercury (MeHg). SAC had greater partitioning coefficients for Hg2+ (KD = 9.42 × 104) and MeHg (KD = 7.661 × 105) as compared to those for AC (KD = 3.69 × 104 and 2.25 × 105, respectively). However, AC appeared to have greater inhibition in total Hg (THg) leaching from sediment (14.2-235.8 mg-Hg/kg-sediment) to porewater phase as compared to SAC. 3 wt% AC amendment in sediment (235.8 mg/kg Hg) was the optimum dosage causing the porewater THg reduction by 99.88%. Moreover, significant inhibition in both THg and MeHg releases within the 83-d trial microcosm tests was demonstrated with active caps composed of SAC + bentonite, SAC + clean sediment, and AC + bentonite. While both AC and SAC successfully reduce the porewater Hg in sediment environment, the smaller inhibition in Hg release by SAC as compared to that by raw AC may suggest that possibly formed HgS nanoparticles could be released into the porewater that elevates the porewater Hg concentration.

Cell-sized mechanosensitive and biosensing compartment programmed with DNA.

The bottom-up construction of cell-sized compartments programmed with DNA that are capable of sensing the chemical and physical environment remains challenging in synthetic cell engineering. Here, we construct mechanosensitive liposomes with biosensing capability by expressing the E. coli channel MscL and a calcium biosensor using cell-free expression.

Low-dose Simvastatin Increases Skeletal Muscle Sensitivity to Caffeine and Halothane.

Objective To determine whether the myotoxic side effects of statin simvastatin affect skeletal muscle's sensitivity to caffeine and halothane.Methods Primary cultured neonate rat skeletal myotubes were treated with 0.01-5.0 µmol/L simvastatin for 48 hours. MTT was used to evaluate cellular viability. The gross morphology and microstructure of the myotubes were observed with a light and electron microscope, respectively. The intracellular calcium concentrations ([Ca2+]i) at rest and in response to caffeine and halothane were investigated by fluorescence calcium imaging. Data were analyzed by analysis of variance (ANOVA) test.Results Simvastatin (0.01-5.0 µmol/L) decreased myotube viability, changed their morphological features and microstructure, and increased the resting [Ca2+]i in a dose-dependent manner. Simvastatin did not change myotube's sensitivity to low doses of caffeine (0.625-2.5 mmol/L) or halothane (1.0-5.0 mmol/L). In response to high-dose caffeine (10.0 mmol/L, 20.0 mmol/L) and halothane (20.0 mmol/L, 40.0 mmol/L), myotubes treated with 0.01 µmol/L simvastatin showed a significant increase in sensitivity, but those treated with 1.0 µmol/L and 5.0 µmol/L simvastatin showed a significant decrease. The sarcoplasmic reticulum Ca2+ storage peaked in the myotubes treated with 0.01 µmol/L simvastatin, but it decreased when cells were treated with higher doses of simvastatin (0.1-5.0 µmol/L).Conclusions The myotoxic side effect of simvastatin was found to change the sensitivity of myotubes in response to high-dose caffeine and halothane. When dose was low, sensitivity increased mainly because of increased Ca2+ content in the sarcoplasmic reticulum, which might explain why some individuals with statin-induced myotoxic symptoms may show positive caffeine-halothane contracture test results. However, when the dose was high and the damage to the myotubes was severer, sensitivity was lower. It is here supposed that the damage itself might put individuals with statin-induced myotoxic symptoms at greater risks of presenting with rhabdomyolysis during surgery or while under anesthesia.

Lack of Association between rs2067474 Polymorphism in Histamine Receptor H2 Gene and Breast Cancer in Chinese Han Population.

Histamine H2 receptor (HRH2) was previously suggested to affect the proliferation of breast cancer cells and disease-free survival of breast cancer patients. Furthermore, a common polymorphism, rs2067474, was identified in an enhancer element of the HRH2 gene promoter and was reported to be associated with various diseases including cancer. However, the relationship between this polymorphism and breast cancer risk and malignant degree remains unclear. The aim of this study was to clarify the clinical association of rs2067474 polymorphism with breast cancer. A total of 201 unrelated Chinese Han breast cancer patients and 238 ethnicity-matched health controls were recruited and rs2067474 polymorphism was genotyped. Logistic regression analyses were performed to calculate the odds ratios (ORs) as a measure of association of genotype with breast cancer according to 3 genetic models (dominant, recessive, and additive). Although the percentage of hormone receptor negative cases tended to be higher in AA genotypes, we did not find any significant associations of rs2067474 polymorphism with breast cancer risk or with related clinicopathological parameters in the present study, which indicates that rs2067474 polymorphism of HRH2 gene might not be a risk factor in the development of breast cancer in Chinese Han population.

Effect of ulinastatin combined rivaroxaban on deep vein thrombosis in major orthopedic surgery.

OBJECTIVE: To explore the effect of ulinastatin (UTI) continuous infusion combined Rivaroxaban on the deep vein thrombosis in patients undergoing major orthopedic surgery. METHODS: Forty-five patients undergoing major orthopedic surgery were randomly divided into three groups:ulinastatin continuous infusion (Uc) group, ulinastatin single injection (Us) group and control (C) group. All patients received patient-controlled intravenous analgesia (PCIA) after operation, and took Rivaroxaban 10 mg orally 12 hours after operation. Ulinastatin (5 000 U/kg) was given intravenously to both Uc and Us groups preoperatively. Group C was given isometric normal saline, group Uc was pumped UTI continuous intravenously at the end of surgery (10 000 U/kg) to 48 hours through PCIA pump. The values of hematocrit (HCT), thrombomodulin (TM), Interleukin (IL-6), thrombin-antithrombin complex (TAT), D-Dimer (D-D) were normally tested before surgery (T1), at the end of the surgery (T2), 12 hours (T3), 24 hours (T4) and 48 hours (T5) after surgery. RESULTS: Compared with T1, there was an upward tendency in TM, IL-6, TAT, and D-D after operation in group C group (P<0.05). The values of them were significantly increased from nearly 24-hour after surgery in Us group (P<0.05). In group Uc, there were no significant changes in these indices after operation (P>0.05). CONCLUSIONS: During the perioperative period, ulinastatin continuous infusion combined Rivaroxaban can correct blood hypercoagulability through different approaches in patients undergoing major orthopedic surgery.

Pharmacokinetics and bioavailability of cimicifugosides after oral administration of Cimicifuga foetida L. extract to rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga foetida L., a traditional Chinese medicine, has been used as an anti-inflammatory, antipyretic and analgesic remedy. The primary active constituents are believed to be present in the triterpene glycoside fraction. MATERIALS AND METHODS: To develop an LC-MS/MS assay for four major cimicifugosides [cimicifugoside H-1 (Cim A), 23-epi-26-deoxyactein (Cim B), cimigenolxyloside (Cim C) and 25-O-acetylcimigenoside (Cim D)] obtained from C. foetida L. and apply it to investigate their pharmacokinetic (PK) properties and bioavailabilities through oral administration of C. foetida L. extract (12.5, 25 and 50mg/kg) and single intravenous (i.v.) doses (5mg/kg) of the individual cimicifugosides in rat. PK parameters were estimated by non-compartmental analysis. RESULTS: All calibration curves showed excellent linear regressions (all r>0.995) within the range of tested concentrations. The intra- and inter-day variations were <15% in terms of RSD. The molar ratio of Cims A, B, C, and D in the extract was 20.7:1.4:2.9:1. PK parameters for Cims A, B, C, and D following oral administration of the extract were respectively: C(max) 4.05-17.69, 90.93-395.7, 407.1-1180 and 21.56-45.09pmol/mL; T(max) 0.46-1.28, 2.00-4.67, 14.67-19.67 and 8.08-14.27h; absolute oral bioavailability (F) 1.86-6.97%, 26.8-48.5%, 238-319% and 32.9-48%. PK parameters after i.v. administration of individual cimicifugosides were respectively: elimination half-life 1.1, 2.5, 5.7 and 4.2h; clearance 15.7, 0.48, 0.24 and 1.13mL/hkg. CONCLUSIONS: Systemic exposure to Cims B, C and D following oral administration of the extract was significantly greater than to Cim A despite the predominance of Cim A in the extract. Significantly different clearance and interconversion from Cim A to Cim C probably accounts for the different exposure to the four cimicifugosides.