Relationship between emotional intelligence and job well-being in Chinese clinical nurses: multiple mediating effects of empathy and communication satisfaction.

BACKGROUND: Nursing work is associated with great pressure, and nurses are often overwhelmed. Therefore, correct emotional regulation is essential to improve nurses' job well-being and promote better engagement in nursing work. The purpose of this study was to establish a structural model to estimate the impact of Chinese clinical nurses' emotional intelligence on job well-being, using multiple intermediaries to explain the internal mechanisms underlying the relationship. METHODS: This was a cross-sectional study of 1475 registered nurses from a Chinese hospital who provided responses to emotional intelligence, empathy, communication satisfaction, and job well-being scales. Path analysis using a multiple mediation model was performed using AMOS 23.0. RESULTS: Among all clinical nurses who participated in the survey, 1475 (98.33 %) completed the questionnaire. The nurses' job well-being score was 83.61 ± 12.63. There was a significant positive correlation between job well-being and communication satisfaction, emotional intelligence, and empathy ability (r = 0.346-0.570, P < 0.001). Empathy and communication satisfaction partially mediated the relationship between emotional intelligence and job well-being, with effect sizes of 0.047 and 0.227, respectively. The chain mediating effect of empathy and communication satisfaction had a value of 0.045. CONCLUSIONS: It is recommended that hospital managers take actions to improve nurses' emotional intelligence level, and conduct professional psychological training to improve nurses' empathy and communication satisfaction, and ultimately improve their job well-being.

Population pharmacokinetic/pharmacodynamic modeling of H018, a selective JAK1 inhibitor, in healthy Chinese volunteers.

H018 is an orally administered, selective, small-molecule inhibitor of Janus kinase 1 (JAK1) made for the treatment of rheumatoid arthritis. A population pharmacokinetic/pharmacodynamic analysis was conducted to characterize the pharmacokinetic and pharmacodynamic profile of H018 and its active metabolite using data from 48 healthy Chinese volunteers who received a single dose of 10-160 mg of H018 in a phase I clinical study. A two-compartment model with delayed absorption and linear elimination adequately described the pharmacokinetic data of H018. The apparent clearance of H018 was estimated to be 39.0 L/h, and triglyceride was identified as a covariate on it. Pharmacokinetic data of the active metabolite could be well described by a two-compartment model with linear elimination. The exposure-effect relationships in terms of pSTAT1 inhibition were well described by a direct response model, with exposure captured by an active moiety that consisted of H018 and its metabolite, weighted by the ratio of in vitro JAK1 inhibitory activity (1.13). The estimated EC50 value for the active moiety is 601 nM. In the simulation using the final model, the inhibitory effect appeared to have reached a plateau in the high-dose groups, with max inhibition rates of 81.42 %, 88.42 %, and 91.89 % for 80, 120, and 160 mg dose groups, respectively. Taken together, this study will provide an instructive reference of dose selection for subsequent clinical trials.

MiRNA-296-5p promotes the sensitivity of nasopharyngeal carcinoma cells to cisplatin via targeted inhibition of STAT3/KLF4 signaling axis.

Improving drug sensitivity is an important strategy in chemotherapy of cancer and accumulating evidence indicates that miRNAs are involved in the regulation of drug sensitivity, but the specific mechanism is still unclear. Our previous study has found that miR-296-5p was significantly downregulated in nasopharyngeal carcinoma (NPC). Here, we aim to explore whether miR-296-5p is involved in regulating cisplatin sensitivity in NPC by regulating STAT3/KLF4 signaling axis. The cell proliferation and clonogenic capacity of NPC cells were evaluated by CCK8 Assay and plate colony assay, respectively. The Annexin V-FITC staining kit was used to determine and quantify the apoptotic cells using flow cytometry. The drug efflux ability of NPC cells were determined by Rhodamine 123 efflux experiment. The expression of miR-296-5p, apoptosis-related genes and protein in NPC cell lines were detected by qPCR and Western blot, respectively. Animal study was used to evaluate the sensitivity of NPC cells to DDP treatment in vivo. Our results showed that elevated miR-296-5p expression obviously promoted the sensitivity of NPC cells to DDP by inhibiting cell proliferation and clonogenic capacity, and inducing apoptosis. In addition, we found that miR-296-5p inhibited the expression of STAT3 and KLF4 in NPC cells, while overexpression of exogenous STAT3 reversed miR-296-5p-mediated enhancement in cell death of DDP-treated NPC cells. In vivo studies further confirmed that miR-296-5p promotes the sensitivity of NPC cells to DDP treatment. miRNA-296-5p enhances the drug sensitivity of nasopharyngeal carcinoma cells to cisplatin via STAT3/KLF4 signaling pathway.

1-(3-Chloro-phen-yl)-5-(2,4-di-hydroxy-benzo-yl)pyridin-2(1H)-one.

The chloro-phenyl group of the title compound, C18H12ClNO4, is disordered over two orientations with occupancies of 0.331 (8) and 0.669 (8). An intra-molecular hydrogen bond is formed between a hy-droxy group and the acyclic carbonyl group. In the crystal, molecules are linked into chains along [110] by O-H⋯O and C-H⋯O hydrogen bonds, forming a ladder motif.

Comparative Pharmacokinetics and Safety Studies of Dexibuprofen Injection and a Branded Product Ibuprofen Injection in Healthy Chinese Volunteers.

Ibuprofen, a nonsteroidal anti-inflammatory drug, is considered a safe and effective analgesic for treating different types of pain and joint disorders. Dexibuprofen, S-(+)-ibuprofen, is the single pharmacologically active enantiomer of ibuprofen. It is more potent than the racemic formulation of ibuprofen in terms of analgesic and anti-inflammatory properties and causes less acute gastric damage. For the first time, in the present single-dose, randomized, open-label, 2-period crossover study, the safety and pharmacokinetic (PK) characteristics of a single-dose dexibuprofen injection (0.2 g) were evaluated in healthy Chinese subjects and compared with the PK characteristics of a 0.2-g ibuprofen injection. Five consecutive men and women were randomly administered a single dose of the 0.2-g ibuprofen or 0.2-g dexibuprofen injection after fasting in every period during the 5-day interval. Then, plasma samples were collected for liquid chromatography-tandem mass spectrometric analysis. WinNonlin software was used for calculating the PK parameters. The geometric mean ratios of the 0.2-g dexibuprofen injection/ibuprofen injection for maximal plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable time point, and AUC from time 0 to infinity were 184.6%, 136.9%, and 134.4%, respectively. The dexibuprofen plasma exposure of the 0.15-g dexibuprofen injection was comparable to that of the 0.2-g ibuprofen injection, calculated using AUC from time 0 to infinity.

Comparing the pharmacokinetics, safety, and immunogenicity of HLX02 to US- and EU-approved trastuzumab in healthy Chinese male subjects: A Phase I, randomized, double-blind, parallel-group study.

BACKGROUND: HLX02, the first China-manufactured trastuzumab biosimilar, is approved in Europe (EU) and China. This study evaluated bioequivalence between HLX02 and US-approved trastuzumab (US-trastuzumab). METHOD: In this double-blind, parallel-group, Phase I study, healthy Chinese men were randomized (1:1:1) to receive a single 6 mg/kg dose of HLX02, reference US-trastuzumab, or reference EU-approved trastuzumab (EU-trastuzumab). Equivalence in PK profiles was demonstrated if the 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for the difference between the least square means of the area under the curve (AUC) from time 0 to infinity (AUC∞) were 0.8-1.25. RESULTS: Pharmacokinetic profiles of the three trastuzumab products were similar in 111 Chinese men. Equivalence was confirmed between HLX02 and US-trastuzumab (GMR for AUC∞ 1.009, 90% CI 0.950-1.072); HLX02 and EU-trastuzumab (GMR for AUC∞ 1.068, 90% CI 1.005-1.135); and EU- and US-trastuzumab (GMR for AUC∞ 0.945, 90% CI 0.889-1004). Exploratory analysis of all other PK parameters also demonstrated equivalence between any two of the three trastuzumab products. HLX02 had similar safety and immunogenicity profiles to US- and EU-trastuzumab. CONCLUSION: HLX02 is bioequivalent to US-trastuzumab and EU-trastuzumab, with similar safety and immunogenicity profiles. US- and EU-trastuzumab were also bioequivalent to each other.

MicroRNA-199a-3p suppresses the invasion and metastasis of nasopharyngeal carcinoma through SCD1/PTEN/AKT signaling pathway.

MicroRNAs (miRs) are 18-25 nucleotides non-coding RNAs, which contribute to tumorigenesis. Previous studies have demonstrated that miR-199a-3p is dysregulated in human nasopharyngeal carcinoma (NPC), but its role in NPC progression still largely unknown. The current study aimed to determine the potential role of miR-199a-3p in NPC progression and the underlying mechanisms. In this study, miR-199a-3p was found to be prominently down-regulated in NPC tissues and cells. The cellular assay showed that transfection of miR-199a-3p markedly repressed the migration, invasion and induced epithelial-mesenchymal transition (EMT) in both 5-8F and CNE-2 cell lines. By dual-luciferase reporter, western blotting and gas chromatography assays, we found that SCD1 is not only highly expressed in NPC tissues and negatively associated with the prognosis of NPC patients but also can be apparently downregulated by miR-199a-3p in NPC cells, suggesting that SCD1 is a direct target gene of miR-199a-3p. Moreover, inhibition of miR-199a-3p expression activated PI3K/Akt signaling and up-regulated the expression of MMP-2. With tumor xenograft models in nude mice, we also showed that miR-199a-3p repressed tumor growth in vivo. Our study demonstrated that miR-199a-3p inhibited migration and invasion of NPC cells through downregulating SCD1 expression, thus providing a potential target for the treatment of NPC.

Pharmacokinetics, Bioequivalence, and Safety Studies of a Generic Selective Tyrosine Kinase Inhibitor Nilotinib Capsule Versus a Branded Product in Healthy Chinese Volunteers.

Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved in the United States and Europe as a treatment for patients with newly diagnosed chronic myeloid leukemia (CML)-chronic phase (CP) and patients with CML-CP or chronic myeloid leukemia-accelerated phase (CML-AP) who are resistant or intolerant to imatinib (a first-generation TKI). This study compared the bioequivalence and safety of the test nilotinib capsule and reference nilotinib capsule (Tasigna, Novartis) in healthy Chinese volunteers under fasting conditions for marketing authorization in China. The results of the study are reported for the first time. This was a single-dose, randomized, open-label, two-period, and cross-over study. Thirty healthy volunteers were randomly assigned to receive a single dose of a 200-mg test or reference capsule under fasting conditions in each period with a 10-day washout. Plasma samples were analyzed with liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated with WinNonlin software. The geometric mean ratio and the corresponding 90% confidence intervals of Cmax , AUC0-t , and AUC0-∞ for nilotinib between the two fixed-dose combination formulations were within the bioequivalence acceptance range of 80%-125%, therefore the generic and branded formulations were bioequivalent in healthy Chinese volunteers.

Additional Use of Prostacyclin Analogs in Patients With Pulmonary Arterial Hypertension: A Meta-Analysis.

Background: Combination therapy has become an attractive option in pulmonary arterial hypertension (PAH) treatment. The aim of this study was to investigate whether additional use of prostacyclin analogs could exert any additional benefits over background targeted therapies in PAH patients. Methods: Searches were performed on PubMed, Embase, and ClinicalTrials.gov from inception to 1 October 2021. Randomized controlled trials were included if patients had been treated with prostacyclin analog-containing combination therapy and compared with the use of other PAH-specific background therapies. The bias risk and statistical analysis of the enrolled studies were performed with RevMan 5.1. Sensitivity analysis and funnel plot were used to evaluate the stability and publication bias, respectively. PROSPERO registered number CRD42021284196. Results: Ten trials involving 1828 patients were included. Prostacyclin analog treatment was associated with greater improvement in clinical worsening (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.57-0.86), 6-min walk distance (mean difference [MD], 37.17 m; 95% CI, 3.01-71.33 m), NYHA/WHO functional class (RR, 1.58; 95% CI, 1.21-2.05), mean pulmonary artery pressure (MD, -9.23 mmHg; 95% CI, -17.44 to -1.03 mmHg), and cardiac index (MD, 0.41 L/min/m2; 95% CI, 0.26-0.55 L/min/m2) than the control group. No significant differences in pulmonary vascular resistance (MD, -137.22 dyn·s/cm5; 95% CI, -272.61 to -1.84 dyn·s/cm5) and all-cause mortality (RR, 0.96; 95% CI, 0.57-1.61) were found between the prostacyclin analog group and control group. Of note, more adverse events (RR, 1.07; 95% CI, 1.02-1.13) occurred in the prostacyclin analog group but no significant increase in serious adverse events (RR, 1.25; 95% CI, 0.75-2.11). Conclusion: Additional prostacyclin analog treatment exerted benefits on clinical worsening, exercise capacity, functional class, mean pulmonary artery pressure, and cardiac index in PAH patients, but it was associated with overall risk of adverse events. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284196, identifier CRD42021284196.

Application analysis on the different neutron gamma density (NGD) logging methods.

Neutron gamma density (NGD) logging is the most promising alternative to the traditional density logging (GGD), which is of significance for resolving the radiation and safety issues in oil industry. However, due to the different HI correction methods, multiple NGD methods based on the fast neutron, thermal neutron, and capture gamma detection coexist in the well-logging field, and show considerable differences in the tool specifications. To clarify these differences and guide the NGD development, three typical NGD methods using the fast neutron count ratio, thermal neutron count ratio, and capture gamma count ratio (abbreviated as NGD-FC, NGD-TC, and NGD-CC methods) are selected as representatives for comparative study. Using the Monte Carlo simulation, an integrated NGD tool model was established for studying the differences of three NGD methods in the logging responses, data processing methods, and environmental applications. Research shows that, although the three NGD methods have different measurement systems and data processing methods, the three methods can get rid of the HI effect and obtain accurate formation density. The changes of wellbore size and wellbore fluid have similar and significant impact on the three NGD methods and lead to large density errors, especially for the large-size wellbore or wellbore gas conditions. In the different lithology conditions, three methods have good performances, but the NGD-FC and NGD-CC methods have smaller density errors than NGD-TC method. Compared to the other two NGD methods, the NGD-FC method also has a perfect performance in the oil or gas-saturated formation, while NGD-TC and NGD-CC methods have extremely large errors in the gas-saturated formation. Besides, the NGD-FC method are hardly affected by the formation water salinity, the NGD-TC method is slightly affected, while the NGD-CC method is greatly affected. This study can provide a guidance for the tool design, data processing and environment correction of the NGD technology.

An alternative method for sourceless density measurement with boron sleeve gamma detectors.

Neutron gamma density measurement using dual gamma detectors (NGD-GD) is a popular density measurement method. Compared with other NGD methods, the NGD-GD method has many advantages in tool optimization, cost control, and density precision; however, it is easily affected by the salinity of formation water. To improve the NGD-GD method, the influence mechanism of formation water salinity was discussed, and a feasible improvement scheme using characteristic gamma information was proposed. A special boron sleeve gamma detector was designed to record the capture gamma rays from the boron-10 element. By analyzing the gamma spectrum, pure boron-10 gamma information was extracted from the total capture gamma spectrum for density calculation. Finally, a new NGD method with boron sleeve gamma detectors (NGD-BD) was developed. Results depict that although the NGD-BD method has a slight decrease in density accuracy and precision compared with the NGD-GD method, its performance is significantly improved in high-brine formations, and oil and gas formations. In addition, the NGD-BD method exhibits better performance in terms of density accuracy, density precision, and environmental impact than another NGD method that uses hydrogen capture gamma information. Moreover, the NGD-BD method is easily implemented with low cost and has little impact on existing NGD tools, and hence, it can coexist with other NGD methods to improve logging quality. Overall, the NGD-BD method is a very promising alternative to the NGD-GD method.

Pharmacokinetics, Pharmacodynamics, and Safety of a Single Escalating Dose and Repeated Doses of Rasagiline Transdermal Patch in Healthy Chinese Subjects.

A rasagiline transdermal patch can be used to offer continuous rasagiline to patients with Parkinson's disease who cannot take their usual oral medications. This was the first study to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects. Thirty subjects were randomized to 3 groups with 10 subjects in each group. The 10 subjects of group 1 received a single 1-mg dose of rasagiline as a tablet; the 20 subjects of groups 2 and 3 received a single transdermal patch (48-hour patch-on period) containing 1.25 mg and 2.5 mg rasagiline, respectively. After a 2-week washout period, the subjects of group 1 were assigned to receive 1 mg of rasagiline tablets every 24 hours for 7 days, and the subjects of group 2 were assigned to receive 1.25-mg rasagiline transdermal patches (48-hour patch-on period) every 72 hours for 5 time periods. The absorption of rasagiline from the transdermal patch was significantly improved, although the peak plasma concentration was obviously reduced. There was slight accumulation of rasagiline dose after multiple administrations. Inhibition of platelet monoamine oxidase-B (MAO-B) activity was dose dependent. The 80% inhibition maintained for at least 48 hours after multiple-dose administration of 1 mg tablets, and for 72 hours after multiple-dose administration of 1.25 mg/48 h patch. Compared with rasagiline tablets, the transdermal patch had a prolonged duration of 80% inhibition and increased maximal inhibition of MAO-B activity. These characteristics permitted an interval of 3 days of dosing, which was convenient for patients to use.

[Direct determination of copper and manganese in Pinellia ternata by atomic absorption spectrometry using secondary sensitive wavelength].

A method for the direct determination of copper and manganese in Pinellia ternata by flame atomic absorption spectrometry with secondary sensitive wavelength was developed. This method can greatly decrease the analytical errors caused by small amount of samples orbig dilution multiple, so its accuracy is better than that with normal atomic absorption spectrometry using sensitive line when determining Cu-rich and Mn-rich Pinellia ternata samples. The detection limits of Cu-rich and Mn-rich are 0-25 mg x (-1) and 0-12 mg x L(-1), the relative standard deviations are 0.42% and 0.66%, and the recovery rates 96%-103% and 97%-102%, respectively. It was found that the method is simple, rapid, useful, accurate and free from the interference of coexistent ions. It has been widely applied to the determination of Pinellia ternata samples with satisfactory results.

Pharmacokinetics and Safety of Levetiracetam Extended-Release Tablets and Relative Bioavailability Compared with Immediate-Release Tablets in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: Levetiracetam is a second-generation antiepileptic drug and distributed ubiquitously in the central nervous system. The extended-release formulation of levetiracetam was developed to provide patients with the convenience of once-daily dosing, to improve drug compliance and tolerability. The objective of this study was to evaluate the pharmacokinetics and safety of levetiracetam extended-release (ER) tablets in healthy Chinese subjects following single and multiple doses. METHODS: Two panels of 34 healthy subjects were enrolled. Trial 1 was a two-way crossover between levetiracetam ER tablets and immediate-release (IR) tablets under fasting conditions. Trial 2 was a four-way crossover single-dose study between levetiracetam ER fasted and ER with food. RESULTS: Intake of single and multiple levetiracetam ER tablets resulted in a 42.3% lower maximum plasma concentration (Cmax) and a 33.6% lower minimum steady-state plasma concentration (Css min) than IR tablet intake, while the median time to Cmax (tmax) was significantly delayed. The 90% CI of the ER/IR ratios for area under the curve (AUC) from zero to last measurable sample (AUC0-t), AUC from zero to infinity (AUC0-∞), AUC at steady state (AUCss, τ = 24 h), Cmax at steady state (Css max) and average concentration at steady state (Css av) were contained within the 80-125% range of bioequivalence. The Cmax and AUC were dose proportional across the dose cohorts. Following a high-fat meal, levetiracetam ER tablets resulted in a 14.4% higher Cmax. The 90% confidence interval (CIs) of the fed/fasted ratios for Cmax and AUC were entirely contained within the 80-125% range of bioequivalence acceptance, except the tmax was delayed (P < 0.05). The most frequent treatment-emergent adverse events were somnolence, dizziness and thirst. CONCLUSIONS: After single and multiple doses, the absorption of levetiracetam ER was equal to IR, the tmax was significantly delayed, and the Cmax and Css min were significantly decreased. Food did not affect the absorption of the levetiracetam ER tablet, but the Cmax increased and the tmax was delayed. The levetiracetam ER tablet was well tolerated and found to be dose proportional from 500 to 2000 mg in healthy Chinese subjects.

Pharmacokinetics, Pharmacodynamics, and Safety of Rasagiline Transdermal Patch: A Preliminary Study in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: Rasagiline tablet is an oral MAO-B inhibitor applied in early or advanced Parkinson's disease (PD). However, when patients with PD cannot take their usual oral medications, a rasagiline transdermal patch can be used as a way to offer continuous rasagiline while avoiding plasma concentration peaks and troughs. The objectives of this study were to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects. METHODS: This single-dose, open-label, randomized, parallel-group study was conducted in 15 healthy subjects. Fasted subjects received a single dose of rasagiline (either by transdermal patch-1.25 mg/24 h, 1.25 mg/48 h, 2.5 mg/48 h, or 2.5 mg/72 h, or orally-in the form of a 1-mg tablet) and were monitored over a 168-h observation period to assess pharmacokinetics, pharmacodynamics, and safety. RESULTS: After administration of a single-dose rasagiline transdermal patch, the mean terminal elimination half-life (t 1/2) was 6.06-9.41 h, which was longer than with the 1-mg tablet dose (2.32 ± 0.28 h). The mean dose-normalized maximum plasma concentration (C max,norm(dose)) of the 1-mg tablet dose was twofold higher than that of the transdermal patch groups. The mean dose-normalized areas under the concentration-time curve (AUCnorm(dose)) of 1.25 and 2.5 mg for the rasagiline transdermal patch doses were fourfold and sevenfold higher than that of the 1-mg tablet dose, respectively. Cumulative urinary excretion was about 0.2% of the total dose. Inhibition of MAO-B activity was dose dependent, and the maximal inhibition was 73.9-94.1% at doses ranging from 1.25 to 2.5 mg. The reported adverse events were mild or moderate. CONCLUSION: The prolonged t 1/2, increased AUC0-t , and more stable plasma drug concentration of the rasagiline patch may permit a longer dosing interval compared to the oral tablet. The rasagiline transdermal patch was safe and well tolerated in healthy Chinese subjects.

A method for determining density based on gamma ray and fast neutron detection using a Cs2LiYCl6 detector in neutron-gamma density logging.

With the increasing demand for radioisotope-free operations, pulsed neutron-gamma density (NGD) has become increasingly important for logging-while-drilling (LWD) development. However, current NGD tools, adopting the multiple-detector array design, are not conducive to the simplification of instrument design and measurement system. To break obstacles, based on the fast neutron-gamma coupled theory, a new density measurement method was proposed. Further, combined with the neutron-gamma simultaneous detection characteristics of the Cs2LiYCl6 (CLYC) detector, an NGD measurement system consisting of a D-T source and one CLYC detector was used. Results show that the new method is capable of determining formation density using a single CLYC detector, which can not only avoid complex instrument systems but also improve density sensitivity. Moreover, the applicability of the new density method was well verified by Monte Carlo simulation. Additionally, the method was successfully applied in a simulated well, and density results are in good agreement with the benchmarked formations. The research provides theoretical guidance for NGD instrument design.

A method to describe inelastic gamma field distribution in neutron gamma density logging.

Pulsed neutron gamma density logging (NGD) is of great significance for radioprotection and density measurement in LWD, however, the current methods have difficulty in quantitative calculation and single factor analysis for the inelastic gamma field distribution. In order to clarify the NGD mechanism, a new method is developed to describe the inelastic gamma field distribution. Based on the fast-neutron scattering and gamma attenuation, the inelastic gamma field distribution is characterized by the inelastic scattering cross section, fast-neutron scattering free path, formation density and other parameters. And the contribution of formation parameters on the field distribution is quantitatively analyzed. The results shows the contribution of density attenuation is opposite to that of inelastic scattering cross section and fast-neutron scattering free path. And as the detector-spacing increases, the density attenuation gradually plays a dominant role in the gamma field distribution, which means large detector-spacing is more favorable for the density measurement. Besides, the relationship of density sensitivity and detector spacing was studied according to this gamma field distribution, therefore, the spacing of near and far gamma ray detector is determined. The research provides theoretical guidance for the tool parameter design and density determination of pulsed neutron gamma density logging technique.

Comparative effect of ciprofloxacin and moxifloxacin on the modulation of bile acid profiles and gut microbiota in rats

Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.

Population pharmacokinetic modeling of oxcarbazepine active metabolite in Chinese patients with epilepsy.

The aim of the study was to develop a population pharmacokinetic (PPK) model of oxcarbazepine and optimize the treatment of oxcarbazepine in Chinese patients with epilepsy. A total of 108 oxcarbazepine therapeutic drug monitoring samples from 78 patients with epilepsy were collected in this study. The pharmacologically active metabolite 10,11-dihydro-10-hydrocarbamazepine (MHD) was used as the analytical target for monitoring therapy of oxcarbazepine. Patients' clinical data were retrospectively collected. The PPK model for MHD was developed using Phoenix NLME 1.2 with a non-linear mixed-effect model. MHD pharmacokinetics obeys a one-compartment model with first-order absorption and elimination. The effect of age, gender, red blood cell count, red blood cell specific volume, hemoglobin (HGB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatine were analyzed. Bootstrap and data splitting were used simultaneously to validate the final PPK models. The mean values of volume of distribution and clearance of MHD in the patients were 14.2 L and 2.38 L h(-1), respectively. BUN and HGB influenced the MHD volume of distribution according to the following equation: V = tvV × (BUN/4.76)(-0.007) × (HGB/140)(-0.001) × e (ηV) . The MHD clearance was dependent on ALT and gender as follows: CL = tvCL × (ALT/30)(0.181) × (gender) × 1.083 × e (ηCL). The final PPK model was demonstrated to be suitable and effective and it can be used to evaluate the pharmacokinetic parameters of MHD in Chinese patients with epilepsy and to choose an optimal dosage regimen of oxcarbazepine on the basis of these parameters.

The effect of food intake on the pk of rhein released from diacerein

Diacerein is a symptomatic slow-acting drug used for treating osteoarthritis. This drug is completely metabolized into the active metabolite rhein before reaching the systemic circulation. This study evaluated the effects of food on the pharmacokinetics of rhein released from diacerein in healthy Chinese subjects. This was a single-center, randomized, single-dose, open-label, two-period, cross-over study. Twenty-four healthy subjects were randomly selected to receive a single oral dose of 50 mg diacerein capsule in either fasted or fed state on two separate visits. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters were calculated using WinNonlin software. In the fasted and fed states, the main pharmacokinetic parameters of diacerein capsule were as follows: Cmax were (4471 ± 936), (3225 ± 755) ng/mL, t1/2 were (4.22 ± 0.42), (4.19 ± 1.05) h, tmax were (2.61 ± 1.25), (3.81 ± 1.29) h, AUC0-24 h were (24223 ± 4895), (24316 ± 5856) h·ng/mL, and AUC0-∞ were (24743 ± 5046), (25170 ± 6415) h·ng/mL. The absorption rate of diacerein capsule was obviously delayed by food intake but the absorption degree remained unaffected.