Efficacy and safety of controlled-release oxycodone/naloxone versus controlled-release oxycodone in Korean patients with cancer-related pain: a randomized controlled trial

Background: Controlled-release oxycodone/naloxone(OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone(OX-CR) for the control of cancer-related pain in Korean patients.Methods: In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale(NRS) pain score ≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat(ITT) population were randomized(1:1) to OXNCR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks.The primary efficacy endpoint was the change in NRS pain score from baseline to week4, with non-inferiority margin of-1.5. Secondary endpoints included analgesic rescue medication intake, patientreported change in bowel habits, laxative intake, quality of life(QoL), and safety assessments.Results: Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group(n = 58) and the OX-CR group(n = 59)(-1.586 vs.-1.559,P = 0.948). The lower limit of the one-sided 95% confidence interval(-0.776 to 0.830) for the difference exceeded the non-inferiority margin(P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments.Conclusions: OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation.Trial registration ClinicalTrials.gov NCT01313780, registered March 8。

Trends in oxycodone and oxycodone-containing analgesics administration for back pain in emergency departments in the USA(2007–2018)

BACKGROUND:To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments(EDs) in the USA from 2007 to 2018.METHODS:Data were gathered from the National Hospital Ambulatory Medical Care Survey(NHAMCS) from 2007 to 2018.The study population included individuals of all ages presenting to USA EDs.The NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back pain.The main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time period.RESULTS:There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007(244,000 visits) to 2018(92,000 visits).The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older(from 43.8% to 57.6%),female patients(from 54.5% to 62.0%),black patients(from 22.5% to 30.4%),and Hispanic/Latino patients(from 9.4% to 19.6%).Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007,with a decrease to 68.5% in 2018.Pure oxycodone was the second most prescribed medication,accounting for 6.1% in 2007 and 31.5% in 2018.CONCLUSION:The overall number of oxycodone-containing analgesics decreased significantly from 2007 to 2018.However,that number trended upward in 45-year-old and older,female,black,or Hispanic/Latino patients from 2007 to 2018.The total amount of pure oxycodone increased significantly from 2007 to 2008.

Effects of mixed fertilizers formed by the compounding of two targeted controlled-release nitrogen fertilizers on yield,nitrogen use efficiency,and ammonia volatilization in double-cropping rice

One-time application of mixed fertilizer formed by the compounding of two controlled-release nitrogen fertilizers(CRUs)with targeted N supply during the periods from transplantation(TS)to panicle initiation(PI)and from PI to heading(HS)is expected to synchronize the double-peak N demand of rice.However,its effects on the yield and N use efficiency(NUE)of labor-intensive double-cropping rice were unknown.Two targeted CRU(CRU_(A)and CRU_(B))were compounded in five ratios(CRU_(A):CRU_(B)=10:0,7:3,5:5,3:7,and 0:10)to form five mixed fertilizers(BBFs):BBF1-5.A field experiment was performed to investigate the characteristics of N supply in early and late seasons under different BBFs and their effects on N uptake,yield,and ammonia volatilization(AV)loss from paddy fields of double-cropping rice.Conventional high-yield fertilization(CK,three split applications of urea)and zero-N treatments were established as controls.The N supply dropped significantly with the increased compound ratio of CRU_(B)during the period from TS to PI,but increased during the period from PI to HS.With the exception of the period from TS to PI in the late rice season,the N uptake of early and late rice maintained close synchronicity with the N supply of BBFs during the double-peak periods.Excessive N supply(BBF1 and BBF2)in the late rice season during the period from TS to PI increased N loss by AV.The effect of BBF on grain yield increase varied widely between seasons,irrespective of year.Among the BBFs,the BBF2 treatment of early rice not only stabilized the spikelets per panicle but also ensured a high number of effective panicles by promoting N uptake during the period from TS to PI and a high grain-filling percentage by appropriately reducing the N supply at the later PI stage,resulting in the highest rice yield.While stabilizing the effective panicle number,the BBF4 treatment of late rice increased the number of spikelets per panicle by promoting N uptake during the period from PI to HS,resulting in the highest rice yield.The two-year average yield and apparent N recovery efficiency of the BBF2 treatment during the early rice season were 9.6 t ha 1 and 45.3%,while those of late rice in BBF4 were 9.6 t ha 1 and 43.0%,respectively.The yield and NUE indexes of BBF2 in early rice and BBF4 in late rice showed no significant difference from those of CK.The AVs of BBF2 during the early rice season and of BBF4 during the late rice season were 50.0%and 76.8%lower,respectively,than those of CK.BBF2 and BBF4 could effectively replace conventional urea split fertilization in early and late rice seasons,ensuring rice yield and NUE and reducing AV loss in paddy fields.

Application of Silica Aerogel Carrier via Supercritical Drying for Fragrance Controlled-release

Silica aerogel with different hydrophilicities were prepared from tetramethoxysilane,Methymethoxysilane,tetramethoxysilane-propyltrimethoxysilane,or tetramethoxysilane-phenyltrimethoxysilane mixtures via supercritical drying process(labelled as TMOS-AG Me-TMOS-AG,Pr-TMOS-AG,or Ph-TMOS-AG,respectively).Three fragrances,including geraniol,ethyl vanillin,and menthol,were loaded to TMOS-AG.The thermal analysis confirmed all loading fragrances are stable until over 200℃.And among all fragrances,geraniol presented the maximum loading contents(L_(m)).Concentration dependences indicated the geraniol was mono layer absorbed.Py-GC/MS of geraniol in TMOS-AG under both N_(2)and mimic air atmosphere(90%N_(2)and 10%O_(2))confirmed that loaded geraniol could be thermally controlled-released beginning at 200℃.As N_(2)absorption confirmed,even absorption/desorption equilibrium constant(k)was determined mainly by hydrophilicity of silica aerogels,and the maximum loading contents(L_(m))were influenced more by the pore size.Due to mono layered absorption,bigger pores usually give less specific areas and less absorbing sites for geraniol,and then present lower L_(m).

Combining controlled-release urea and normal urea with appropriate nitrogen application rate to reduce wheat stem lodging risk and increase grain yield and yield stability

A mixture of controlled-release urea and normal urea(CRUNU)is an efficient nitrogen(N)fertilizer type,but little is known about its effects on stem lodging resistance,grain yield,and yield stability of wheat.In this study,a 4-year field experiment(from 2017 to 2021)was conducted to analyze the effects of N fertilizer types(CRUNU and normal urea(NU))and application rates(low level(L),135 kg ha^(–1);medium level(M),180 kg ha^(–1);high level(H),225 kg ha^(–1))on population lodging resistance,basal internode strength,lignin content and synthetase activity,stem lodging resistance,grain yield,and yield stability of wheat.Our results showed that the two N fertilizer types had the highest lodging rate under high N application rates,and the M-CRUNU treatment showed the lowest lodging rate.Compared with NU,CRUNU improved the wheat population lodging resistance under the three N application rates,mainly related to improving wheat population characteristics and breaking the strength of the second basal internode.Correlation analysis showed that the breaking strength of the second basal internode was related to the physical characteristics,chemical components,and micro-structure of the internode.Compared with NU,CRUNU significantly increased wheat grain yield by 4.47,14.62,and 3.12%under low,medium,and high N application rates,respectively.In addition,CRUNU showed no significant difference in grain yield under medium and high N application rates,but it presented the highest yield stability under the medium N application rate.In summary,CRUNU,combined with the medium N application rate,is an efficient agronomic management strategy for wheat production.

Subsurface banding of blended controlled-release urea can optimize rice yields while minimizing yield-scaled greenhouse gas emissions

Controlled-release urea(CRU)is widely reported to supply crop nitrogen(N)demand with one basal application,thus effectively replacing split applications of urea without diminishing grain yield and N use efficiency(NUE).However,its use for replacement for high-yield split applications of urea(CK)for rice is untested.In addition,the degree to which greenhouse gas(GHG)emissions in rice systems are affected when CRU is substituted for CK remains unclear.During 2017 and 2018,we sampled plant growth and gas emissions in a rice paddy field treated with three CRU types(sulfur-coated urea[SCU],polymer-coated urea[PCU],and bulk blended CRU[BBU])applied via two methods(surface broadcasting on the soil and subsurface banding at 5 cm depth),with CK as a control.The three CRUs led to different soil NH_(4)^(+)-N dynamics,and the N supply pattern under BBU was more beneficial for rice seedling establishment than under SCU and PCU,resulting in grain yield and NUE comparable to those under CK.CRU type showed no significant effect on either CH_(4) emissions or N_(2)O emissions,and broadcast CRUs exhibited significantly higher total GHG emissions than CK.However,banded CRUs significantly reduced the total GHG emissions in comparison with broadcast CRUs,by 9.2%averaged across the two years.Reduced CH_(4) emissions,particularly during the period prior to the middle drainage,contributed largely to the GHG difference.With comparably high grain yield and low total GHG emissions,banded BBU showed a low yield-scaled GHG(GHG emissions divided by grain yield)comparable to that under CK in both years.Overall,our study suggested that N management synchronized with rice demand and contributing to a high NUE tended to minimize yield-scaled GHG.Broadcast CRU can hardly substitute for CK in terms of either grain yield or GHG emissions,but banded BBU is a promising N management strategy for sustaining rice production while minimizing environmental impacts.

Controlled-release fertilizer(CRF): A green fertilizer for controlling non-point contamination in agriculture

Fertilizers contribute greatly to high yields but also result in environmental non-point contamination, including the emission of greenhouse gas(N 2O) and eutrophication of water bodies. How to solve this problem has become a serious challenge, especially for China as its high ecological pressure. Controlled-release fertilizer(CRF) has been developed to minimize the contamination while keeping high yield and has become a green fertilizer for agriculture. Several CRFs made with special coating technology were used for testing the fertilizer effects in yield and environment through pot experiment and field trial. The result indicated that the CRFs had higher N use efficiency, thus reducing N loss through leaching and volatilization while keeping higher yields. Comparing with imported standard CRFs, the test on CRFs showed similar fertilizer effect but with much lower cost. CRFs application is becoming a new approach for minimizing non-point contamination in agriculture.

Controlled-release Properties of Microencapsulated Disperse Dyes

Some disperse dyes were microencapsulated by means of in- situ polymerization. These microencapsulated disperse dyes was extracted respectively by ethanol under certain conditions. The controlled-release properties of disperse dyes through the shell of microcapsules were measured by spectrophotometer. According to the results, it was drawn that the type of disperse dyes, the auxiliaries contained in disperse dyes, the quantity of system controlling medium used and the core/shell ratio of microcapsules play important roles in controlling the release properties of microcapsules. The different controlled- release properties of microcapsules, which were prepared under given conditions, however, would in turn influence the performance of microcapsules in multiple-transfer printing.

Studies on the Mechanism of Single Basal Application of Controlled-Release Fertilizers for Increasing Yield of Rice (Oryza sativa L.)

This paper was to explore the mechanism of single basal application of controlled-release fertilizers for increasing yield of rice （Oryza sativa L.）. Pot trials and cylinder trials were carried out from 2002 to 2005 to study the influences of single basal application of 3 controlled-release fertilizers on the changes of soil available N, root development, senescence and lodging resistance at late growth stages. Results showed that at 30 days after fertilization, single basal application of controlled-release fertilizers coated with vegetal-substance （CRF1） and polymer materials （CRF3） increased soil available N to 12.0 and 147.9%, respectively, in comparison to split fertilization of rice-specific fertilizer （RSF1）. Treatments of the two CRFs obviously benefited the development of root system, resulting in greater rice root weights with extensive distribution and higher root activity. In addition, the two CRF treatments, in comparison to RSF1, enhanced chlorophyll consents of the flag leaves to 9.5 and 15.5%, and soluble protein up to 89.7 and 108.0% respectively. Application of the two CRFs also made the base of rice stems strong and large, declined the proportion of shoot and root, increased root depth index. Though relatively low K rate, single basal application of the CRF3 coated with NH4MgPO4 could also promote the development of root system, enhance root activity and some physiological functions of flag leaves. Based on these results, it was concluded that major mechanisms for increasing rice yield by single basal application of the CRFs should be attributed to grater soil available N supply, superior development of root systems, better nutrient absorption capacity, slower senescence and enhancement of lodging resistance at late stages.

Shifts in soil bacterial communities induced by the controlled-release fertilizer coatings

Coated controlled-release fertilizers （CRFs） have been widely applied in agriculture due to their increased efficiency. However, the widespread and a lot of coated CRFs application may leave undesired coating residues in the soil due to their slow degradation. Limited information is available on the effects of substantial residual coatings on the soil bacterial community. By adding 0, 5, 10, 20, and 50 times quantities of residual coating from conventional application amount of resin and water-soluble coated CRFs, we studied the responses of soil properties and bacterial community composition to these two residual coatings in black soil. The results showed that the resin and water-soluble coatings did not essentially alter the properties of black soil or cause dramatic changes to bacterial diversity within the test concentration range. The residual resin and water-soluble coatings also did not distinctly alter the relative abundance of the top ten bacteria at phylum level. Heatmap results suggested that the treatments were basically clustered into two groups by concentration rather than types of coating material. Pearson correlation analysis showed that the Simpson＇s diversity index of the bacterial community was significantly correlated with microbial biomass carbon （MBC, r=0.394, P〈0.05）, and the richness index abundance-based coverage estimator （ACE） of the bacterial community was significantly correlated with microbial biomass nitrogen （MBN, t=0.407, P〈0.05）. Overall, results of this study suggested that substantial residual resin and water-soluble coatings with 0-50 times quantities of residual coating from conventional application amount of coated CRFs did not generate obviously negative impacts on the bacterial community in black soil.

Application of imidacloprid controlled-release granules to enhance the utilization rate and control wheat aphid on winter wheat

During winter wheat production, aphids need to be controlled with pesticides for the entire growth period. Controlled-release technology has been regarded as an alternative method for the improvement of pesticide efficiency. This study investigated two types of imidacloprid controlled-release granule (CR-GR): 2% imidacloprid CR-GR and 0.2% imidacloprid pesticide-fertilizer controlled-release granule (PF-CR-GR) when wheat was sown in winter. The release performance, utilization rate, terminal residues in edible parts, control effect on aphids, and achieved winter wheat yield were evaluated for both laboratory experiments and field application. Imidacloprid PF-CR-GR released more quickly in aqueous medium than CR-GR because of its good water solubility. After CR-GR treatments, the concentrations in wheat roots and soil were similar throughout the entire sampling period, and the concentrations in shoots were about 10–20% of those in roots. Imidacloprid was better absorbed when CR-GR was used as root treatment, compared with foliar treatment. Field application showed that imidacloprid CR-GR and PF-CR-GR controlled aphids throughout the entire growth period of winter wheat and improved the wheat yield. These findings identified application of imidacloprid CR-GR and PF-CR-GR on winter wheat as an effective way to enhance the pesticide utilization rate and ensure adequate yield. This paper provides a theoretical basis for the scientific use of pesticides and guides scientific pesticide application.

Physiological Basis of Photosynthetic Function and Senescence of Rice Leaves as Regulated by Controlled-Release Nitrogen Fertilizer

The physiological mechanism of photosynthetic function and senescence of rice leaves was studied by using early rice variety Baliangyou 100 and late rice variety Weiyou 46, treated with controlled-release nitrogen fertilizer （CRNF）, urea and no nitrogen fertilizer. CRNF showed obvious effects on delaying the senescence and prolonging photosynthetic function duration of rice leaves. Compared with urea, CRNF could significantly increase the chlorophyll content of functional leaves in both early and late rice varieties, and this difference between the treatments became larger as rice growth progressed; CRNF increased the activities of active oxygen scavenging enzymes super oxide dismutase （SOD） and peroxidase （POD）, and decreased the accumulation amount of malondialdehyde （MDA） in functional leaves during leaf aging; Photosynthetic rate of functional leaves in CRNF treatment was significantly higher than that in urea treatment. The result also indicated that CRNF could effectively regulate the contents of indole-3-acetic acid （IAA） and abscisic acid （ABA） in functional leaves; IAA content was higher and ABA content was lower in CRNF treatment than those in urea treatment. Therefore, application of CRNF could increase the rice yield significantly due to these physiological changes in the functional leaves.

Effects of different types of slow-and controlled-release fertilizers on rice yield

This experiment explored the effects of single application of seven types of slow-and controlled-release fertilizers on rice yield and various population characteristics.Based on a study of the nitrogen(N)release characteristics of these fertilizers,pot experiments were conducted in 2018 and 2019 with split fertilization(CK,urea applied split equally at basal and panicle initiation stages,respectively)as control,which assessed the effects on SPAD value,yield and yield components,dynamic changes of rice tillers and dry matter accumulation.The results showed that the N release characteristics of different types of slow-and controlled-release fertilizers were significantly different.Polymer-coated urea(PCU)showed a controlledrelease mode and provided sustained release throughout the whole growth stages.Sulfur-coated urea(SCU)exhibited a slow-release mode,providing insufficient release at the middle and late stages.Urease inhibitor urea(AHA)and ureaformaldehyde(UF)yielded a rapid-release mode,with an explosive N release at the early stage and no release at the middle and late stages.These results showed that PCU delayed the peak seedling stage.Compared with CK,dry matter accumulation and SPAD showed no significant differences,and due to the continuous release of N throughout the growth stages,rice yield,spikelets per panicle,seed setting rate,and 1000-grain weight were all increased.Owing to the lack of N supply at the late stage and the low number of spikelets,SCU led to a reduction of rice yield,which is nevertheless not statistically significant.AHA and UF were susceptible to environmental factors and had varying effects on rice yield.The results of this experiment indicated that given a fixed amount of N applied in a pot,the stronger the N supply capacity and the longer the effective duration time of the fertilizer,the higher the dry matter accumulation at the late growth stage,and the higher the rice yield.

Advances in the clinical application of oxycodone in the perioperative period

To review the research progress of pure opioid receptor agonist oxycodone.The research progress of oxycodone in terms of pharmacokinetics,pharmacodynamics,adverse reactions,clinical application,combined medication and new progress in clinical application was summarized by referring to the literature.Oxycodone is a semi-synthetic thebaine derivative of opioid alkaloids,and is a pure opioidμandκreceptor agonist.The main action sites are the central nervous system and visceral smooth muscle.Due to its advantages of low adverse reactions,good analgesic effects,and a wide range of safe doses,the drug has been widely used in the control of acute and chronic postoperative pain,as well as malignant and non-malignant pain.Since the end of the 20^(th) century,researchers have begun to formulate antipyretic analgesics,opioid receptor agonists,opioid receptor antagonists,dopamine receptor antagonists and other drugs with oxycodone in different proportions to enhance the analgesic effect.At the same time,it can reduce the dosage of oxycodone and reduce its adverse reactions,so as to achieve the purpose of limiting opioid abuse.With the continuous research on the efficacy and safety of oxycodone in the perioperative period at home and abroad,oxycodone has become the only dual-opioid potent analgesic that can be used in clinical work.

Use of seed gums from Tamarindus indica and Cassia fistula as controlled-release agents

Most seed gums have been widely used in oral and topical pharmaceutical formulations, cosmetics, and food products because of their hydrophilic properties. Gums from Tamariudus indica and Cassia fistula seeds were chemically modified by carboxymethylation to improve their functionalities. The objective of the present study was to characterize and evaluate crude and carboxymethylated gums from T. indica and C. fistula seeds to achieve the controlled-release of diclofenac sodium(DS) in matrix tablet form. Both crude and carboxymethylated gums were characterized by Fourier transform infrared spectroscopy, Xray diffraction, and scanning electron microscopy. The results revealed that the gums were successfully modified by carboxymethylation and that the modified gums were amorphous in structure and had better flow properties. The carboxymethylated gums from both plant seeds did not exhibit cytotoxicity at concentrations lower than 0.5 mg/ml. All gum samples used as polymeric controlled-release agents were formulated into DS matrix tablets. Hardness and thickness tests were conducted as in-process tests. Drug content estimation and in vitro drug release studies were carried out to evaluate the matrix tablets. Increasing the concentration of gums increased compression time and hardness while it reduced the thickness. Furthermore, the results fitted well with the Korsmeyer–Peppas model. Moreover, the DS tablets were found to release the drug by super case II transport(relaxation). In summary, the carboxymethylated gum from T. indica and C. fistula seeds is an excellent, naturally sourced gum with high physicochemical and functional qualities, and can potentially be used in pharmaceutical applications as a disintegrant, diluent, and drug release-controlling agent.

Controlled-Release Analysis of Potassium Permanganate Using PMMA Matrix

Excess amount of potassium permanganate has often been used in-situ for chemical oxidation of contaminated sites. The consequences are not limited to secondary contamination and cost but also inefficient remediation. Encapsulation of permanganate using PMMA enables controlled dissolution of the oxidant and aids long-term processes. This paper focuses on the oxidant release efficiency from polymer matrix and analysis of data using existing models for glassy polymers. The efficiency profile obtained using mass ratios of 2:1, 4:1, and 8:1 of PMMA to KMnO4 showed a decrease in the extent of release with increasing mass ratio with 79%, 55.35% and 33.59% respectively. Patches were noticed on the surfaces of PMMA after the release of KMnO4, these were attributed to crevices created by the non-fickian diffusion of the oxidant.

Increase in yield and nitrogen use efficiency of double rice with long-term application of controlled-release urea

Controlled-release urea(CRU)has better characteristics than conventional urea for synchronizing nitrogen(N)release with plant uptake.Understanding the effects of CRU on crop yield and N use efficiency(NUE)has long been the key to evaluate the performance of CRU.A long-term experiment over five consecutive years was conducted in Changsha,Hunan Province,China,to investigate the effects of polyethylene-coated urea with a 90-d release period on the yield and NUE of double rice(early and late crops are grown in the same year),the amount of residual soil mineral N and the soil–plant N balance,as well as on the economic benefits.Four N fertilizer treatments including CK(no N fertilizer),U(conventional urea),CRU1(polyethylene-coated urea with equal N application rate to U)and CRU2(20%reduction in N application rate of CRU1)were established.The results indicated that CRU1 application increased the yield and NUE of double rice by 11.0 and 13.5%,respectively,compared with U.Higher yield and NUE of late rice were found than in early rice in CRU treatments.Compared with conventional U,the yield and NUE of early rice in the CRU1 treatment were increased by 6.0 and 10.2%,respectively,and those of late rice were increased by 15.4 and 13.8%,respectively.There was no significant difference between CRU1 and CRU2 in double rice yield.Furthermore,CRU treatments(including CRU1 and CRU2)had higher apparent residual Nmin rate(ARNR)and apparent N recovery rate(ANRR),but lower apparent N loss(NS)than the conventional U treatment.Concentrations of NH_(4)^(+)-N and NO_(3)^(-)-N were greater in the surface soil(0–20 cm)and lower in the deeper soil layer(40–60 cm)with CRU treatments than in the U treatment after harvest.Moreover,CRU application produced a greater economic benefit than conventional U application.In general,CRU outperformed U fertilizer in terms of rice yield,NUE,soil–plant N balance,economic benefit,and CRU2 provided greater comprehensive benefits than CRU1.It is suggested that CRU application is beneficial for solving N management challenges in the production of rice.

Effects of Controlled-Release Fertilizers and Their Application Methods on Germination and Seedling Growth of Dent and Sweet Corns

Effects of controlled-release fertilizers (CRFs) (C-AS, polyolefin coated ammonium sulfate, 50-day-type; Dd-LP, polyolefincoated urea with dicyandiamide, 40-day-type; C-ANP, polyolefin coated ammonium nitrate phosphate, 40-day-type; andC-DAP, polyolefin coated diammonium acid phosphate, 40-day-type), ammonium sulphate and no fertilizer control, andtheir application methods (spot, band, surface and mixed) on germination and seedling development of sweet corn (Zeamays L.var. saccharata Sturt.) and dent corn (Zea mays L.var. indentata Sturt.) were investigated in a greenhouse. Underco-situs application (band and spot) of CRFs, there were no obvious differences in the germination speed and rate for bothdent corn and sweet corn relative to control. Mortality rates of sweet corn seedlings under co-situs application were highin experiment 1, but were very low in experiment 2, because the environmental conditions were different in the twoexperiments. That is, under lower temperature and weaker sunlight, young seedlings easily die due to high soil nutrientconcentration and slow growth speed of corn. Shoot weight of both dent and sweet corn did not greatly decrease inexperiment 1. In experiment 2, there were no significant differences in shoot and root weight of both corns between co-situs and surface or mixed application methods. However, with spot and band application of ammonium sulfate, shoot androot weight were significantly reduced. Soil EC and pH were considerably affected by co-situs application, especially atthe fertilizer application site. For both dent and sweet corn, EC in the 0-3 cm soil was significantly higher under co-situsapplication and surface application than that under mixed application, whereas in the 3-6 cm soil depth the situation wasreversed. Compared with control, mixed application of CRFs decreased soil pH slightly (0-3 cm depth) or greatly (3-6 cmdepth).

Simultaneous determination of acetaminophen and oxycodone in human plasma by LC–MS/MS and its application to a pharmacokinetic study

A simple and rapid liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was de- veloped and validated for simultaneous determination of acetaminophen and oxycodone in human plasma. Acetaminophen-d4 and oxycodone-d3 were used as internal standards. The challenge en- countered in the method development that the high plasma concentration level of acetaminophen made the MS response saturated while the desired lower limit of quantification （LLOQ,） for oxycodone was hard to reach was well solved. The analytes were extracted by protein precipitation using acetonitrile. The matrix effect of the analytes was avoided by chromatographic separation using a hydrophilic C18 column coupled with gradient elution. Multiple reaction monitoring in positive ion mode was performed on tandem mass spectrometer employing electrospray ion source. The calibration curves were linear over the concentration ranges of 40.0-8000 ng/mL and 0.200-40.0 ng/mL for acetaminophen and oxycodone, respectively. This method, which could contribute to high throughput analysis and better clinical drug monitoring, was successfully applied to a pharmacokinetic study in healthy Chinese volunteers.

Effect of dexmedetomidine combined with oxycodone on systemic stress response in recovery of gynecological laparoscopic operation

Objective:To study the effect of dexmedetomidine combined with oxycodone on systemic stress response in recovery period of gynecological laparoscopic operation.Methods:A total of 86 patients who received laparoscopic operation in the Second Affiliated Hospital of Kunming Medical University between June 2014 and December 2016 were selected and randomly divided into the dexmedetomidine combined with oxycodone group (DO group) and control group (C group). Before anesthesia induction (T1), at the end of the surgery and before micro pump injection of dexmedetomidine and oxycodone hydrochloride (T2) and in recovery period (T3), serum levels of pituitary-target gland axis-related hormones, vascular activity-related hormones and oxidative stress-related molecules were determined.Results: At T1 and T2, serum TSH, T3, T4, ACTH, Cor, NE, E, ADH, AT-II, ROS, MDA, SOD and HO-1 levels of DO group were not significantly different from those of C group;at T3, serum TSH, T3, T4, ACTH, Cor, NE, E, ADH, AT-II, ROS and MDA levels of DO group were significantly lower than those of C group while SOD and HO-1 levels were significantly higher than those of C group.Conclusions: Dexmedetomidine combined with oxycodone can inhibit the systemic stress response in recovery of gynecological laparoscopic operation.