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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 C

As the critical parameter of hydraulic fracture evaluation, fracture density is significant for fracturing model optimization and production prediction. To compensate for the low response sensitivity of fracture density and the saturation of fracture evaluation in nonradioactive technology (NRT), we have developed a method based on modifying the neutron self-shielding effect to quantitatively calculate fracture density. The gamma counts of elements with content that did not change before and after fracturing are used to calculate the self-shielding correction factor. We establish the mathematical relationship between the corrected gamma counts of boron and fracture density to achieve a quantitative calculation of fracture density. Compared to NRT, the new method uses measured energy spectral information to eliminate the effect of neutron self-shielding on fracture density and improve calculation accuracy. Meanwhile, the scope or range of accurate fracture density estimation extends from the original 4% to more than 10%. Moreover, we further examine fracture response under different formations and borehole conditions using the Monte Carlo N-particle transport code. The salinity of formation water and borehole water has the most significant impact on fracture density calculation, shale content and porosity, lithology, and fluid type of formation; in contrast, borehole parameters are the least significant. Finally, in this paper, we illustrate the feasibility of the method through a continuous-depth numerical calculation.

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.

With the increasing demand for the radioisotope-free operations, using pulsed neutron gamma density (NGD) instead of gamma-gamma density (GGD) has become increasingly important for the development of logging while drilling (LWD) technology. However, due to the different logging mechanisms, there are huge differences between GGD and NGD in the instrument designs, measurement methods, and instrument specifications. To further promote the NGD development, a comparative study on GGD and NGD was carried out from theoretical and simulation aspects. Based on the theoretical methods, the differences between GGD and NGD in the gamma sources, field distribution, methods for density measurement and instrument specifications were systematically elaborated. Then, using the Monte Carlo simulation, the GGD and NGD models were built to quantitatively verify the theoretical results. Last, the detailed performances of NGD and GGD methods in different logging environments were compared. Results showed that the theoretical results are highly consistent with the simulation results. The density sensitivity of NGD is less than half that of GGD, but the depth of investigation (DOI) approaches twice that of GGD. The density precision and vertical resolution of NGD are less than those of GGD. Additionally, compared to GGD, NGD also has an excellent performance in different pore fluid and lithology formations, but it is easily affected by borehole factors. The research can provide quantitative performance evaluations for the NGD replacing GGD in LWD 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.

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.

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.

Neutron lifetime logging can measure the thermal-neutron capture cross-section of the formation using the neutron/gamma time spectrum information, and has a wide application in dynamic monitoring and recovery of remaining oil. However, the current time-spectrum processing technology is easily interfered by the borehole information and counting statistics in the neutron/gamma time spectrum, especially in a complex logging environment. To ensure the accuracy of neutron lifetime logging, a new time-spectrum processing technology based on regularized non-negative least squares (RNNLS) method was proposed. By presetting an array composed of different capture cross-section values, a multi-exponential decay function was established to describe the decay law of the time spectrum. Taking the multi-exponential decay function as a reference, an overdetermined linear equation system was constructed using time spectrum data. Finally, using the regularized non-negative least squares (RNNLS) method to solve the equation system, the contribution distribution of different cross-section values in the preset array to the time spectrum was obtained to indicate the capture cross-section of the formation. Studies show that, the new technology can automatically separate the cross-section contribution of the wellbore and formation to the time spectrum, and the cross-section contribution distribution has an obvious contribution peak which can be used for evaluating the real formation cross-section. In addition, by adopting the RNNLS method, this new method successfully gets rid of the influence of noise information and counting statistics on the capture cross-section results. Compared with the original technology, the new time-spectrum processing technology is no longer limited by the selection of time gates, and shows more accurate results in various logging environments.

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.

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.

Tight gas has become an important part of unconventional petroleum exploration and development. The evaluation of gas content is of great significance for reservoir prediction and oil & gas production. Pulsed neutron technology has been widely used for gas content evaluation in cased hole. The accurate evaluation of gas content under different types of gas reservoir is a huge challenge for pulsed neutron technology. In this paper, for closed gas reservoirs, the apparent gas saturation which utilizes the captured gamma ratio of near to extra-far detector is proposed to evaluate gas content. To accurately determine gas content, the responses of apparent gas saturation under different environment conditions were studied by Monte Carlo simulation. The result shows that lithology and clay content have a great influence on the use of the captured gamma ratio to calculate the apparent gas saturation. At the same time, the gas content in the wellbore is also an important interference factor. These factors should be considered in the actual evaluation of gas content. At last, the actual measurement data and interpretation results verify the validity of the method.

Compensated porosity logging tool utilizing deuterium-tritium (D-T) source shows a lower sensitivity to the variation of formation porosity compared with that adopting Am-Be source. In order to improve the sensitivity, the factors of an infinite homogeneous formation influencing slowing-down length and the near to far counts ratio are analyzed. Then Monte Carlo simulation method is used to build well logging models to study the responses of a neutron porosity logging tool to hydrogen index and formation density. It shows that in addition to hydrogen index, the variation of the density also has a great impact on slowing-down length and the ratio which reduces the response sensitivity to porosity. A new model depicts the relationship between the count ratio and porosity is proposed. When the model is used to process the measured ratio, the ratio shows improved dynamic range and sensitivity to porosity compared with the values without processing.

Hydraulic fracturing plays an important role in enhancing oil and gas production of unconventional formations. The quantitative fracture evaluation is essential for the optimization of fracturing model and production prediction of oil or gas. In this paper, based on the high thermal-neutron absorption capacity of tagged proppants containing gadolinium oxide, the thermal neutron detection technology is proposed to determine the fracture parameters including the height and width. By Monte Carlo simulation method, the spatial distributions of the thermal neutron before and after fracturing are analyzed. The relationships of the thermal neutron count versus gadolinium content and proppant filling are studied. On this basis, a mathematical relationship between the change of thermal neutron count VTn and fracture parameters was established to quantitatively evaluate the fracture height and width. In addition, the fracture responses of VTn under different formation backgrounds including porosity, salinity and lithology width were studied. Results show that the variations of porosity, salinity and lithology have non-ignorable influence on the determination of fracture width. Therefore, the better method on the fracture-width inversion is combining the thermal neutron count with the formation parameters. A simulated fracturing case with different formation porosities, lithologies and fracture conditions is given, which presented the feasibility of the method under different measurement environments. After the corrections of porosity, salinity, and other formation backgrounds, the new method shows a good performance: the calculated results of the fracture width and height are consistent with the realistic parameters, and the error in fracture calculation is less than 10%.

Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects.

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 Cs

Accurate determination of the proppant placement and propped fracture height are important for evaluating and optimizing stimulation strategies. A technology using non-radioactive proppant and a pulsed neutron gamma energy spectra logging tool to determine the placement and height of propped fractures is proposed. Gd2O3 was incorporated into ceramic proppant and a Monte Carlo method was utilized to build the logging tools and formation models. Characteristic responses of the recorded information of different logging tools to fracture widths, proppant concentrations and influencing factors were studied. The results show that Gd capture gamma rays can be used to evaluate propped fractures and it has higher sensitivity to the change of fracture width and traceable proppant content compared with the exiting non-radioactive proppant evaluation techniques and only an after-fracture measurement is needed for the new method; The changes in gas saturation and borehole size have a great impact on determining propped fractures when compensated neutron and pulsed neutron capture tool are used. A field example is presented to validate the application of the new technique.

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses. L-3-n-butilftalida (L-NMP) é um antioxidante natural, que pode ser utilizado para o tratamento do acidente isquêmico agudo e demência vascular. Este estudo avaliou segurança, tolerância e farmacocinética de comprimidos de L-NBP em chineses voluntários sadios. Este foi um estudo monocêntrico, randomizado, duplo cego, com controle por placebo e doses única e múltipla. Os indivíduos receberam dose única de comprimido de L-NBP de 80, 160, 320 ou 480 mg (n=40) e doses múltiplas de 160 mg duas vezes ao dia, por sete dias (n=12). Amostras de plasma foram analisadas com LC-MS/MS. Os parâmetros farmacocinéticos do L-NBP foram calculados utilizando análise não compartimental, com o programa WinNonlin. A análise estatística foi realizada utilizando-se o programa SPSS. Todos os eventos adversos (EAs) foram moderados e de duração limitada. EAs nesse estudo ocorreram menos frequentemente e mais moderadamente do que os EAs relacionados para cápsulas moles de DL-NBP. Não se observaram eventos adversos graves (EAG), morte ou abandono do estudo. Com dose única, atingiu-se o Cmax em cerca de 1 hora e o t1/2 médio foi de, aproximadamente, 13,76 h. A área sob a curva (ASC) e o Cmax aumentaram com o aumento da dose, mas não se observou proporcionalidade na faixa acima de 160 a 480 mg. No estudo de dose múltipla, o equilíbrio foi alcançado em três dias, com pequeno acúmulo. Em resumo, o comprimido de L-NMP foi bem tolerado em indivíduos chineses saudáveis. O acúmulo pequeno apareceu após doses repetidas.

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. 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. 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. 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.

Triflusal presents comparable antiplatelet activity to aspirin while presenting a more favourable safety profile, and is used in the treatment of thrombosis. The study aimed to evaluate the pharmacokinetics and safety of triflusal and its major metabolite 2-(hydroxyl)-4-(trifluoromethyl)- benzoic acid (HTB) in healthy Chinese subjects. 30 healthy subjects were recruited in this randomized, single-center, and open-label, parallel, single ascending doses (300, 600, 900 mg) and multiple doses (600 mg, once daily for 7 days) study. Plasma samples were analyzed with a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. Safety was assessed by adverse events, ECG, laboratory testing, and vital signs. Triflusal was safe and well tolerated. After single-dose administration, triflusal was rapidly absorbed with a mean T max of 0.55–0.92 h and a mean t 1/2 kel of 0.35–0.65 h, HTB was absorbed with a mean T max of 2.35–3.03 h and a mean t 1/2 kel of 52.5–65.57 h. C max and AUC for triflusal and HTB were approximately dose proportional over the 300–900 mg dose range. In the steady state, the accumulation index (R) indicated that the exposure of triflusal increased slightly with repeated dosing, and the exposure of HTB increased obviously. 3 adverse events certainly related to the investigational drugs occurred in the multiple-dose phase. Following oral dosing under fasting condition, triflusal is promptly absorbed and rapidly depleted from the systemic circulation. HTB is quickly generated from triflusal and slowly eliminated. Triflusal accumulates slightly in the body. HTB plasma concentration builds up progressively toward steady-state.

Summary A density logging instrument with three gamma detectors has been developed to improve the vertical resolution. The numerical simulation models of the instrument were built with MCNP code to further increase its performance. K.A. Eyl(1994) and C. Stoller(1997) have proposed a high resolution density logging device using a three detector. In this paper, we built the numerical simulation model of logging instrument based on the logging results in the experimental material, and then, calculated the zero source spacing of the instrument. On basis of these results, it was optimized that the short spacing of the density logging instrument. The vertical resolution was studied with numerical simulation and experiment in calibration well. The comparison results between old logging device and the optimized one show that the improvements are effective.

Summary This article introduces a development of pulsed neutron uranium logging instrument. By analyzing the temporal distribution of epithermal neutrons generated from the thermal fission of 235 U, we propose a new method with a uranium-bearing index to calculate the uranium content in the formation. An instrument employing a D-T neutron generator and two epithermal neutron detectors has been developed. The logging response is studied using Monte Carlo simulation and experiments in calibration wells. The simulation and experimental results show that the uraniumbearing index is linearly correlated with the uranium content, and the porosity and thermal neutron lifetime of the formation can be acquired simultaneously.

Our previous studies revealed that berberine-mediated GLP-1 secretion was a possible mechanism for berberine exerting good effects on hyperglycemia. This study was designed to ascertain whether berberine-induced secretion of GLP-1 was related with activation of bitter taste receptors expressed in gastrointestinal tract. Western blotting results showed that TAS2R38, a subtype of bitter taste receptor, was expressed on human enteroendocrine NCI-H716 cells. GLP-1 secretion induced by berberine from NCI-H716 cells was inhibited by incubation with anti-TAS2R38 antibody. We further performed gene silencing using siRNA to knockdown TAS2R38 from NCI-H716 cells, which showed that siRNA knockdown of the TAS2R38 reduced berberine-mediated GLP-1 secretion. We adopted inhibitors of PLC and TRPM5 known to be involved in bitter taste transduction to investigate the underlying pathways mediated in berberine-induced GLP-1 secretion. It was found that PLC inhibitor U73122 inhibited berberine-induced GLP-1 release in NCI-H716 cells, while TRPM5 blocker quinine failed to attenuate berberine-induced secretion of GLP-1. The present results demonstrated that berberine stimulated GLP-1 secretion via activation of gut-expressed bitter taste receptors in a PLC-dependent manner. Because berberine was found to be a ligand of bitter taste receptor, the results of present study may provide an explanation for some bitter taste substance obtain hypoglycemic effect.

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.

Landiolol is an ultra-short-acting β-blocker that appears to be more cardioselective and less toxic than esmolol. The main objective of this study was to investigate the pharmacokinetics, pharmacodynamics, and safety of landiolol hydrochloride in healthy Chinese volunteers. We set 2-dose regimen (L and H groups) [L (low): 0.125 mg/kg/min (1 min) loading→0.02 mg/kg/min (20 min) continuous, H (high): 0.25 mg/kg/min (1 min) loading→0.04 mg/kg/min (20 min) continuous]. 20 healthy subjects of either sex were allocated randomly to the L and H groups (n=10, and 10). Blood samples were collected over 1 h after continuous infusion and were determined using a validated liquid chromatography/mass spectrometry (LC/MS/MS) assay. The safety of landiolol hydrochloride was assessed by adverse events recording, 12-lead ECG findings, physical examination, laboratory testing, and vital signs. The main pharmacokinetic parameters of landiolol hydrochloride in healthy Chinese subjects were as follows: doses of 2 groups (L and H); C max of 400±110 and 731±246 ng/mL; C 21min of 327±109 and 508±141 ng/mL; T max of 10.1±6.5 and 6.2±5.7 min; t 1/2 of 4.7±1.6 and 6.5±1.7 min. Landiolol hydrochloride was safe. There were no adverse events in any subject. The heart rates and blood pressures of subjects administered landiolol hydrochloride decreased, but no clinically significant changes were observed. The concentration of landiolol hydrochloride rapidly reached steady state levels, and rapidly dissipated after completion of administration. Landiolol hydrochloride appears to have rapid onset and short action.

The chloro­phenyl group of the title compound, C18H12ClNO4, is disordered over two orientations with occupancies of 0.331 (8) and 0.669 (8). An intra­molecular hydrogen bond is formed between a hy­droxy 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.