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Online retail platforms such as Amazon and Tmall have the ability to create personalized recommendations based on the consumer's browsing history, purchase history, and preferences by investing in data analytics capability. In practice, manufacturers may encroach on the retail market through the agency channel that sells products directly to online consumers in addition to wholesale products to retail platforms through the reselling channel. In this study, we develop a game-theoretic model to study the interplay between the manufacturer's encroachment and the online retail platform's data analytics capability investment. Our outcomes reveal that the conditions for the manufacturer to encroach become more lenient if the platform invests in data analytics capability, and we show that the investment in data analytics capability can lead to a Pareto improvement and the manufacturer can free ride on the platform's investment. Moreover, we found that the manufacturer's encroachment always creates more incentives for the platform to enhance the investment level in data analytics capability. Our research in this study provides useful insights for managers to make encroachment decisions and data analytics capability investment decisions with the manufacturer who sells through the online retail platform. [ABSTRACT FROM AUTHOR]

Huangqi Guizhi Wuwu decoction (HGWWD) is a classic traditional Chinese medicine prescription for the treatment of ischemic stroke, etc. However, the material basis of its efficacy remains unclear, seriously affecting drug development and clinical applications. In the present study, an ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry method was developed to separate and identify the chemical components of HGWWD. A total of 81 compounds were identified and tentatively characterized. Eight compounds were accurately identified by comparing the retention time and mass spectrometry data with those of reference substances, the remaining compounds were characterized by comparing the mass spectrometry data and reference information. Based on the results of compound attribution, 35 compounds were from Astragali Radix, six compounds were from Cinnamomi Ramulus, 23 compounds were from Paeoniae Radix Alba, eight compounds were from Zingiberis Rhizoma Recens and nine compounds were from Jujubae Fructus. The results showed that monoterpenoids, flavonoids, organic acids, triterpenes, amino acids, gingerols, alkaloids, and glycosides were the main chemical components of HGWWD. This analytical method is suitable for characterizing the chemical constituents of HGWWD, and the results provide important information for elucidating its pharmacodynamic material basis and mechanism of action. [ABSTRACT FROM AUTHOR]

Autoimmune pancreatitis (AIP) is a fibro‐inflammatory disease characterized by inflammation and fibrosis of the pancreas. It is a systemic disease that can affect multiple organs, including the bile ducts, kidneys, lungs, and other organs. However, due to its complex presentation, AIP is often challenging to diagnose, and misdiagnosis with pancreatic tumors can occur. In our study, we reviewed three cases of atypical AIP where patients had normal serum IgG4 levels, leading to initial misdiagnosis with pancreatic tumors. Delayed diagnosis resulted in irreversible pathologies such as retroperitoneal fibrosis. All three patients had bile duct involvement, and imaging findings were similar to those of tumors, further complicating the diagnosis. The correct diagnosis was confirmed only after diagnostic therapy. Our study aims to raise awareness of atypical AIP and improve diagnostic efficiency by analyzing the clinical characteristics of these patients. [ABSTRACT FROM AUTHOR]

The differences between Bismuth IIIa and IIIb types of hilar cholangiocarcinoma are unclear. Thus, this study aimed to compare the clinical characteristics of the Bismuth IIIa and IIIb types of hilar cholangiocarcinoma. A case series analysis was designed to explore the clinical and pathological findings and survival of 144 patients with hilar cholangiocarcinoma who underwent curative hepatectomy between 2007 and 2018. The patients in the IIIa group received portal vein embolization and transfusion more frequently than those in the IIIb group (18.3% vs. 0.0%, P < 0.05 and 36.6% vs. 25.0%, P < 0.05). The incidence of posthepatectomy liver failure and serious surgical complications (≥ grade B) was significantly higher in the IIIa group than in the IIIb group (12.2% vs. 4.5%, P < 0.01 and 32.9% vs. 9.1%, P < 0.01). Tumors of the patients in the IIIa group had more advanced T and N stages than those of the patients in the IIIb group (P < 0.01). The patients in the IIIa group had poorer disease-free and overall survival rates than those in the IIIb group (P = 0.014 and P = 0.048). N stage and lymphovascular invasion were independently correlated with disease-free survival, whereas T and N stages were independently correlated with overall survival in the IIIb group. Meanwhile, T stage, N stage, and lymphovascular invasion were independently correlated with disease-free survival, whereas posthepatectomy liver failure, complication, and T stage were independently correlated with overall survival in the IIIa group. Hepatic and portal vessel metastasis occurred more frequently in the IIIa group than in the IIIb group (7.3% vs. 0.0%, P < 0.05). In our centers, patients with Bismuth IIIb hilar cholangiocarcinoma exhibited better disease-free and overall survival rates with more favorable clinicopathological characteristics than those with IIIa hilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: The risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients. Methods: We performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018. Results: The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30–40 (P = 0.047). Conclusions: AYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied. [ABSTRACT FROM AUTHOR]

Fangji Huangqi Decoction is composed of Stephaniae Tetrandrae Radix, Astragli Radix, Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix Et Rhizoma. It is a classic traditional Chinese medicine formula for the treatment of chronic glomerulonephritis in China. However, its pharmacokinetic characteristics in vivo are still unclear. In this study, a method for quantifying fangchinoline, tetrandrine and calycosin-7-O-β-D-glucoside, the main active constituents of Fangji Huangqi Decoction, in rat plasma by using ultrahigh-performance liquid chromatography–tandem mass spectrometry technique was developed. Plasma samples were processed with a deproteinization procedure using acetonitrile, followed by chromatographic separation on a Shim-pack XR-ODS C18 column using gradient elution of 0.1% aqueous formic acid and acetonitrile at 0.4 mL/min. The analytes and internal standard, diphenhydramine hydrochloride, were detected using positive electrospray ionization in multiple reactions monitoring mode. The optimized mass transition ion-pairs (m / z) were 609.3/367.3 for fangchinoline, 623.3/174.3 for tetrandrine, 447.2/285.1 for calycosin-7-O-β-D-glucoside and 256.2/167.1 for diphenhydramine hydrochloride, respectively. The developed method was validated for intraday and interday precision and accuracy whose values fell in the acceptable limits. Recovery efficiency of all the analytes was found to be >90.5%. Matrix effect was found to be negligible. Stability results showed that the analytes were stable under all conditions. The validated method was successfully used for studying the pharmacokinetics of the three compounds in rat plasma after oral administration of Fangji Huangqi Decoction. [ABSTRACT FROM AUTHOR]

Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a common type of pancreatic cancer with one of the worst survival rate of all malignancies. Recent studies have identified that immunosuppressive B cells could employ the PD‐1/PD‐L1 pathway to suppress antitumour T cell responses; hence, we examined the expression and function of PD‐L1 in B cells. We found that the PD‐L1 expression was significantly enriched in tumour‐infiltrating (TI) B cells than in peripheral blood (PB) B cells from the same patients. Additionally, the PB B cells from stage III and stage IV PDAC patients presented significantly higher PD‐L1 than the PB B cells from healthy controls. High PD‐L1 expression in PB B cells could be achieved by stimulation via CpG and less effectively via anti‐BCR plus CD40L, but not by coculture with pancreatic cancer cell lines in vitro. Also, STAT1 and STAT3 inhibition significantly suppressed PD‐L1 upregulation in stimulated B cells. CpG‐stimulated PB B cells could inhibit the IFN‐γ expression and proliferation of CD8 T cells in a PD‐L1‐dependent manner. Also, TI CD8 T cells incubated with whole TI B cells presented significantly lower IFN‐γ expression and lower proliferation, than TI CD8 T cells incubated with PD‐L1+ cell‐depleted TI B cells, suggesting that PD‐L1+ B cells could also suppress CD8 T cells in the tumour. Overall, this study identified that B cells could suppress CD8 T cells via PD‐L1 expression, indicating a novel pathway of immuno‐regulation in pancreatic cancer. [ABSTRACT FROM AUTHOR]

A rapid, selective, and sensitive ultra‐high performance liquid chromatography‐tandem mass spectrometry method was developed for simultaneous determination of ferulic acid, paeoniflorin, and albiflorin, the major active constituents of Danggui‐Shaoyao‐San, in rat plasma using geniposide as the internal standard. The plasma samples were processed by protein precipitation with acetonitrile, and then separated on a Shim‐Pack XR‐ODS C18 column (75 mm × 3.0 mm, 2.2 μm) using gradient elution program with a mobile phase consisting of 0.1% aqueous formic acid and acetonitrile at a flow rate of 0.4 mL/min. The detection was achieved on a 3200 QTRAP mass spectrometer equipped with electrospray ionization source in negative ionization mode. Quantification was performed using multiple reaction monitoring mode by monitoring the fragmentation of m/z 192.9→134.0 for ferulic acid, m/z 525.0→120.9 for paeoniflorin, m/z 525.2→121.0 for albiflorin, and m/z 433.1→225.1 for the internal standard, respectively. The calibration curve was linear in the range of 5–2500 ng/mL for all the three analytes (r ≥ 0.9972) with the lower limit of quantitation of 5 ng/mL. The intraday and interday precisions were below 12.1% for all the analytes in terms of relative standard deviation, and the accuracy was within ±11.5% in terms of relative error. The extraction recovery, matrix effect and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of ferulic acid, paeoniflorin, and albiflorin after oral administration of Danggui‐Shaoyao‐San to rats. [ABSTRACT FROM AUTHOR]

Zhi‐Zi‐Hou‐Po Decoction, consisting of Gardenia jasminoides Ellis, Magnolia officinalis Rehd. et Wils., and Citrus aurantium L, is a classical Traditional Chinese Medicine formula for the treatment of depression. In order to make good and rational use of this formula in the future, a sensitive, selective, and reliable ultra high performance liquid chromatography with tandem mass spectrometry method was developed for simultaneous determination of two iridoid glycosides (geniposide and genipin gentiobioside), two lignans (honokiol and magnolol), four flavonoid glycosides (isonaringin, naringin, hesperidin, and neohesperidin), the major bioactive constituents of Zhi‐Zi‐Hou‐Po Decoction, in rat plasma using paeoniflorin as internal standard. Plasma samples were pretreated by a simple protein precipitation with acetonitrile. Chromatographic separation was performed on a shim‐pack XR‐ODS C18 column (75 × 3.0 mm, 2.2 µm) using gradient elution with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.5 mL/min. Mass spectrometric detection was conducted on a 3200 QTRAP mass spectrometry equipped with electrospray ionization source in negative ionization mode. Quantification was performed using multiple reactions monitoring mode. Calibration curves exhibited good linearity (r > 0.9947) over a wide concentration range for all analytes, and the lower limits of quantification were 10, 5, 1, 5, 1, 5, 1, and 5 ng/mL for geniposide, genipin gentiobioside, honokiol, magnolol, isonaringin, naringin, hesperidin, and neohesperidin, respectively. The intraday and interday precisions at three quality control levels were less than 12.3% and the accuracies ranged from −11.2 to 10.7%. Extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of the eight analytes after oral administration of Zhi‐Zi‐Hou‐Po decoction to rats. [ABSTRACT FROM AUTHOR]

Highlights • Development of UHPLC-MS/MS method for simultaneous determination of four active constituents in rat plasma. • The method was successfully applied to a pharmacokinetic study of HGWWD. • PK profiles of the four analytes of HGWWD were revealed for the first time. Abstract Huangqi Guizhi Wuwu Decoction (HGWWD), consisting of Radix Astragali, Cinnamomi Ramulus, Paeoniae Radix Alba, Zingiberis Rhizoma Recens and Jujubae Fructus, is a widely used Traditional Chinese Medicine (TCM) formula for the treatment of human blood impediment in China for nearly 2000 years. In order to make good and rational use of this formula in the future, a rapid, sensitive and robust ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for simultaneous determination of calycosin-7-O-β-D-glucoside, cinnamic acid, paeoniflorin and albiflorin, the main active constituents of HGWWD, in rat plasma using geniposide as internal standard (IS). The plasma samples were extracted by protein precipitation with acetonitrile and separated on a Shim-pack XR-ODS C 18 column (75 mm × 3.0 mm, 2.2 μm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.4 mL/min. Mass spectrometric detection was performed on 3200 QTRAP mass spectrometry equipped with electrospray ionization source in negative ionization mode. Quantification was performed using multiple reaction monitoring (MRM) by monitoring the fragmentation of m / z 491.1→282.9 for calycosin-7-O-β-D-glucoside, m / z 147.0→103.1 for cinnamic acid, m / z 525.0→120.9 for paeoniflorin, m / z 525.2→121.0 for albiflorin and m / z 433.1→225.1 for IS, respectively. The method was well validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves had good linearity (r >0.9977) over the concentration range from 0.1–50 ng/mL for calycosin-7-O-β-D-glycoside, 50–25000 ng/mL for cinnamic acid, 5–2500 ng/mL for paeoniflorin and albiflorin. The intra-day and inter-day precisions (relative standard deviation) were within 11.8%, the accuracy (relative error) ranged from −9.4% to 9.1%, and the lower limit of quantification (LLOQ) were 0.1, 50, 5, 5 ng/mL for calycosin-7-O-β-D-glucoside, cinnamic acid, paeoniflorin and albiflorin, respectively. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of calycosin-7-O-β-D-glucoside, cinnamic acid, paeoniflorin and albiflorin after oral administration of HGWWD to rats. [ABSTRACT FROM AUTHOR]

The antimicrobial triclocarban (TCC) is frequently found in various personal care products (PCPs), and recent studies have demonstrated that it shows a high unintended biological activity on humans and wildlife. To evaluate the toxicity of TCC at the protein level, the effect of TCC on bovine serum albumin (BSA) has been investigated using various spectroscopic methods in combination with molecular modeling. Analysis of fluorescence quenching data of BSA revealed the formation of a ground state BSA-TCC complex with a binding constant of 2.58 × 10 4  M −1 at 298 K. The values of the thermodynamic parameters suggested that the binding of TCC to BSA was driven mainly by hydrophobic interaction and hydrogen bond. Site marker competitive experiments coupled with molecular docking studies confirmed that site I was the main binding site for TCC on BSA. Furthermore, TCC binding to BSA led to conformational and structural alterations of BSA as revealed by multi-spectroscopic studies. In addition, the stability of BSA and BSA-TCC complex were well analyzed by the molecular dynamics studies. In short, this work indicated that TCC could interact with BSA and impact the conformation of BSA, which could provide valuable information to understand the toxicity mechanism of TCC. [ABSTRACT FROM AUTHOR]

Abstracts 2-(2-Hydroxypropanamido) benzoic acid (HPABA) is a potential anti-inflammatory agent isolated from the marine fungus Penicillium chrysogenum . In vivo tissue distribution and excretion of HPABA were unknown. Therefore, the purpose of this paper was to establish an UHPLC–MS/MS method for the determination of HPABA and proceed to apply for the study of tissue distribution and excretion in rats. The results obtained indicated that HPABA in tissues was rapidly distributed and cleared. The highest level was found in intestine and stomach, followed by kidney, liver, lung and heart. These observations showed that HPABA was well distributed into abundant blood-supply tissues, suggesting that the blood flow or perfusion rate of organs plays a major role. A small amount of HPABA was detected in brain indicated that the ability of it in crossing the blood brain barrier (BBB) was very weak in rats. Excretion studies demonstrated that HPABA was mainly excreted by kidney. The total cumulative excretion of HPABA were 54.3% and 44.1% in male and female rats, respectively. In addition, gender-related differences in the excretion and distribution profile of HPABA were observed in rats. [ABSTRACT FROM AUTHOR]

Tianshu Capsule, consisting of Ligusticum chuanxiong Hort and Gastrodia elata Blume, is a widely used Traditional Chinese Medicine preparation for the treatment of migraine. Ferulic acid and gastrodin are main active constituents in Ligusticum chuanxiong Hort and Gastrodia elata Blume, and have been used as marker components for quality control of Tianshu Capsule. In this study, a selective, sensitive, and reliable ultra-fast liquid chromatography with tandem mass spectrometry method was developed for simultaneous determination of ferulic acid and gastrodin in rat plasma using geniposide as internal standard. The plasma samples were extracted by protein precipitation with methanol after acidification and separated on a Shim-Pack XR-ODS C18 column (75 × 3.0 mm, 2.2 μm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.6 mL/min. Detection was performed on 3200 QTRAP mass spectrometry equipped with turbo ion spray source in negative ionization mode. Validation parameters were within acceptable ranges. The validated method was applied to compare the pharmacokinetic profiles of ferulic acid and gastrodin in normal and migraine rats. Our results showed that there were remarkable differences in the pharmacokinetic properties of the analytes between the normal and migraine groups. [ABSTRACT FROM AUTHOR]

To monitor rolling bearing operating status with casings in real time efficiently and accurately, a fusion method based on n -dimensional characteristic parameters distance ( n -DCPD) was proposed for rolling bearing fault diagnosis with two types of signals including vibration signal and acoustic emission signals. The n -DCPD was investigated based on four information entropies (singular spectrum entropy in time domain, power spectrum entropy in frequency domain, wavelet space characteristic spectrum entropy and wavelet energy spectrum entropy in time-frequency domain) and the basic thought of fusion information entropy fault diagnosis method with n -DCPD was given. Through rotor simulation test rig, the vibration and acoustic emission signals of six rolling bearing faults (ball fault, inner race fault, outer race fault, inner-ball faults, inner-outer faults and normal) are collected under different operation conditions with the emphasis on the rotation speed from 800 rpm to 2000 rpm. In the light of the proposed fusion information entropy method with n -DCPD, the diagnosis of rolling bearing faults was completed. The fault diagnosis results show that the fusion entropy method holds high precision in the recognition of rolling bearing faults. The efforts of this study provide a novel and useful methodology for the fault diagnosis of an aeroengine rolling bearing. [ABSTRACT FROM AUTHOR]

Heme oxygenase-1 has been identified to protect allograft from ischemia/reperfusion and immunologic rejection. Activity of heme oxygenase-1 is regulated by a guanine-thymine dinucleotide length polymorphism in the heme oxygenase-1 gene promoter. In this study, we aimed to explore the impact of the heme oxygenase-1 gene promoter polymorphism of donors and recipients on the orthotopic liver graft function after transplantation. Sixty recipients and their accompanying donors of orthotopic liver allografts were included retrospectively in this study. Heme oxygenase-1 gene promoter polymorphism was assessed using genomic DNA isolated from cryopreserved splenocytes or peripheral blood mononuclear cells and analyzed by genetic analyzer. Small allele of the donor heme oxygenase-1 gene polymorphism significantly prolonged the graft survival ( p = 0.017). Recipients of allografts from a class of small-allele carrier had significantly lower serum total bilirubin compared with recipients of a nonclass small-allele donor liver ( p < 0.01). Additionally, in recipients of small-carrier allografts, cold ischemia time (<10 h or ≥10 h) did not affect the total bilirubin significantly. Our study suggested a protective function of donor-derived heme oxygenase-1 gene promoter polymorphism on orthotopic liver allograft function after transplantation. [ABSTRACT FROM AUTHOR]

A RP-HPLC method was developed and validated for the degradation kinetic study of 2-(2-hydroxypropanamido) benzoic acid (HPABA), a promising anti-inflammatory drug, which would provide a basis for further studies on HPABA. The effects of pH, temperature, buffer concentration and ionic strength on the degradation kinetics of HPABA were discussed. Experimental parameters such as degradation rate constants ( k ), activation energy ( E a ), acid and alkali catalytic constants ( k ac , k al ), shelf life ( t 1/2 ) and temperature coefficient ( Q 10 ) were calculated. The results indicated that degradation kinetics of HPABA followed zero-order reaction kinetics; degradation rate constants ( k ) of HPABA at different pH values demonstrated that HPABA was more stable in neutral and near-neutral conditions; the function of temperature on k obeyed the Arrhenius equation ( r = 0.9933) and HPABA was more stable at lower temperature; with the increase of ionic strength and buffer concentration, the stability of HPABA was decreased. The major unknown degradation product of HPABA was identified by UHPLC/TOF–MS/MS with positive electrospray ionization. Results demonstrated that the hydrolysis product was the primary degradation product of HPABA and it was deduced as anthranilic acid. [ABSTRACT FROM AUTHOR]

An ultra high performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) method was developed to investigate the in vivo metabolism of 2-(2-hydroxypropanamido) benzoic acid (HPABA), a marine-derived anti-inflammatory drug, for the first time. Plasma, urine, feces and bile samples were collected from male and female rats after a single intragastric administration of HPABA at a dose of 100 mg/kg. Besides the parent drug, a total of 13 metabolites (3 phase I and 10 phase II metabolites) were detected and tentatively identified through comparing their mass spectrometry profiles with those of HPABA. Results demonstrated that metabolic pathways of HPABA in rats included decarboxylation, hydroxylation, dehydrogenation, glucuronidation, glycine conjugation and N-acetyl conjugation. In summary, this work provided valuable information regarding the metabolism of HPABA in rats, which would contribute to better understanding of its safety and mechanism of action. [ABSTRACT FROM AUTHOR]

Deng-yan granule, consisting of Herba Erigerontis Breviscapi, Rhizoma Corydalis Yanhusuo and Radix Astragali Mongolici, is a widely used Traditional Chinese Medicine preparation for treatment of coronary heart disease. Scutellarin and tetrahydropalmatine are main active constituents in Herba Erigerontis Breviscapi and Rhizoma Corydalis Yanhusuo, and have been used as marker components for quality control of Deng-yan preparations. In order to make good and rational use of Deng-yan granule in the future, a rapid, sensitive and high throughput ultra-fast liquid chromatography with tandem mass spectrometry (UFLC-MS/MS) method was developed for the simultaneous determination of scutellarin and tetrahydropalmatine in rat plasma using rutin as internal standard (IS). The plasma samples were extracted by liquid–liquid extraction with ethyl acetate after acidification and separated on a Shim-pack XR-ODS C 18 column (75 mm × 3.0 mm, 2.2 μm) with a mobile phase consisting of methanol–0.1% formic acid water (50:50, v / v ) at a flow rate of 0.4 mL/min. Mass spectrometric detection was conducted on an API 3200 QTRAP mass spectrometry equipped with electrospray ionization source in positive ionization mode. Quantification was performed using multiple reaction monitoring (MRM) by monitoring the fragmentation of m / z 463.2 → 287.1 for scutellarin, m / z 356.1 → 192.1 for tetrahydropalmatine and m / z 611.2 → 303.2 for IS, respectively. The linear range was 10–5000 ng/mL for both scutellarin and tetrahydropalmatine with lower limit of quantitation (LLOQ) of 10 ng/mL. The intra- and inter-day precisions were below 12.2% for scutellarin and below 9.7% for tetrahydropalmatine in terms of relative standard deviation (RSD), and the accuracy was within ±9.1% for scutellarin and within ±11.2% for tetrahydropalmatine in terms of relative error (RE). Extraction recovery, matrix effect and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of scutellarin and tetrahydropalmatine after oral administration of Deng-yan granule to rats. [ABSTRACT FROM AUTHOR]

Highlights: [•] Development of a UHPLC–MS/MS method to determine HPABA in rat plasma. [•] The total analysis time was 2.0min. [•] The method was applied to pharmacokinetic study of HPABA in rats. [•] HPABA showed linear pharmacokinetic properties and high absolute bioavailability. [ABSTRACT FROM AUTHOR]

• Polyphenols could inhibit the oxidative degradation of HSA in the order: Hto > Bra > Hte. • Three polyphenols bound to HSA by static quenching mechanism with moderate binding affinity. • The binding of polyphenols to HSA resulted in the conformational changes of HSA. • Polyphenols bound to the site I of HSA through non-covalent bonds. Brazilin (Bra), hematoxylin (Hto) and hematein (Hte) are structurally similar polyphenols having rich biological activities, but their antioxidant ability has not been well studied. Here, their protective ability against human serum albumin (HSA) oxidative degradation were investigated using 2,2′-Azobis (2-methylpropionamidine) dihydrochloride (AAPH), NaClO and Fenton like reactions methods. The results indicated that polyphenols inhibited the oxidative injuries of HSA in the order: Hto > Bra > Hte. Additionally, the biological effects of polyphenols were mostly influenced by their binding to protein. Therefore, the structure-affinity relationships of polyphenols binding to HSA were also explored. Fluorescence experiments indicated that polyphenols bound to HSA through static quenching mechanism. Furthermore, some conformational changes of HSA could be observed in the presence of polyphenols. Altogether, molecular structure of polyphenols played a significant role in their protective effect against HSA oxidative damage and binding ability, which provided fundamental insights into their application as health care foods. [ABSTRACT FROM AUTHOR]

In order to overcome ablation on the rail–armature contact region and increase electromagnetic thrust force, a structure of armature arm with interference fit is designed in augmented quadrupole electromagnetic launcher (EML). Good contact characteristic between the armature and rails plays an important role in the success of EML. The electromagnetic-structure coupling model based on the finite element analysis is presented to investigate the contact characteristic, the distribution of current density, and the electromagnetic force (EMF) and the contact pressure is given, which indicates the EMF needs to be loaded unevenly on the armature arm. Finally, based on electromagnetic-structure coupling model, some important parameters including the contact area, the contact efficiency, the contact counterforce, and maximal contact pressure are analyzed with the different interference, different length, and different thickness of armature arm after the pulse current is loaded. The dependences of nonuniform contact parameters on the nonuniform EMF are obtained. [ABSTRACT FROM AUTHOR]

The weight of projectiles and magnetic shield are two important factors influencing an electromagnetic launch (EML). The quadrupole rail launcher forms a cylindrical area in the middle of a launcher with very small magnetic field intensity, which can shield electromagnetic radiation and protect precision electronic components inside a projectile. However, the offset magnetic field weakens the electromagnetic thrust and decreases the launch efficiency. To solve the mentioned problem, the structure of a series-connected augmented quadrupole rail launcher is presented, the electromagnetic model based on the numerical analysis and the finite element method for nonaugmented and augmented quadrupole rail launcher is built. In addition, the distribution characteristic of current density, magnetic field intensity, and electromagnetic force of the two launchers is analyzed, respectively. The simulation results show that the current density distribution of rail in the nonaugmented launcher is O-like shape and the augmented launcher is C-like shape. Under given conditions, the electromagnetic thrust of the augmented launcher is larger about 3.7 times than that of the nonaugmented launcher. Meanwhile, a large magnetic shielding area can be kept in the augmented launcher. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease with unknown causes. The initiation of PBC is associated with bacterial infections and abnormal immune correlates, such as the presence of self-reactive anti-mitochondrial antibodies and shifted balance of T cell subsets. In particular, the CD4 + CXCR5 + follicular helper T (Tfh) cells are highly activated in PBC patients and are significantly associated with PBC severity, but the underlying reasons are unknown. In this study, we found that the circulating CD4 + CXCR5 + T cells were enriched with the interferon (IFN)-γ-secreting Th1-subtype and the interleukin (IL)-17-secreting Th17-subtype, but not the IL-4-secreting Th2 subtype. We further demonstrated that a host of microbial motifs, including Pam3CSK4, poly(I:C), LPS, imiquimod, and CpG, could significantly stimulate IFN-γ, IL-17, and/or IL-21 from circulating CD4 + CXCR5 + T cells in PBC patients, especially in the presence of monocytes and B cells. Whole bacterial cells of Escherichia coli , Novosphingobium aromaticivorans , and Mycobacterium gordonae , could also potently stimulate IFN-γ, IL-17, and/or IL-21 production from circulating CD4 + CXCR5 + T cells. But interestingly, while the whole cell could potently stimulate circulating CD4 + CXCR5 + T cells from both healthy controls and PBC patients, the cell protein lysate could only potently stimulate circulating CD4 + CXCR5 + T cells from PBC patients, but not those from healthy controls, suggesting that circulating CD4 + CXCR5 + T cells in PBC patients had distinctive antigen-specificity from those in healthy individuals. Together, these data demonstrated that bacterial antigen stimulation is a potential source of aberrant Tfh cell activation in PBC patients. [ABSTRACT FROM AUTHOR]

The rostral ventromedial medulla (RVM) plays a critical role in pain signal transmissions. However, the mechanisms of RVM in type 2 diabetic neuropathy are still poorly understood. Therefore, we evaluated the mechanisms within the RVM in the modulation of neuropathic pain in type 2 diabetes. To this end, we used Zucker diabetic fatty (ZDF) rats to examine the levels of TNFα, IL-1β, and NF-κB in the RVM during the development of neuropathic pain in type 2 diabetes, and evaluated the effects of intra-RVM microinjections of thalidomide on the levels of TNFα, IL-1β, and NF-κB in the RVM and mechanical allodynia and thermal hyperalgesia induced by type 2 diabetes. We found that ZDF rats became hyperglycemic and exhibited increased levels of TNFα, IL-1β, and NFκB in the RVM at the age of 13 weeks. Intra-RVM administrations of thalidomide dose-dependently attenuated mechanical allodynia and thermal hyperalgesia, and this phenomenon was associated with reduced levels of TNFα, IL-1β, and NFκB in the RVM, without altering serum levels of TNFα or IL-1β. These results suggested that supraspinal mechanisms of thalidomide play a critical role in modulations of type 2 diabetes induced neuropathic pain, which is likely mediated by TNFα and IL-1β in the RVM. [ABSTRACT FROM AUTHOR]

Objectives R adix G entianae is a traditional Chinese medicine derived from medicinal plants of the family G entianaceae. Its pharmacological effects have been primarily attributed to the presence of a number of secoiridoid glycosides, in particular gentiopicroside and swertiamarin. In this study, a rapid and sensitive method based on ultrafast liquid chromatography-tandem mass spectrometry has been developed for the simultaneous determination of gentiopicroside and swertiamarin in rat plasma using paeoniflorin as internal standard ( IS). Methods After liquid-liquid extraction with ethyl acetate-isopropanol (95 : 5, v/ v), separation was achieved on a Shim-pack XR-ODS C18 column (75 mm × 3.0 mm, 2.2 μm) with a mobile phase consisting of methanol : 0.1% formic acid (30 : 70, v/ v) at a flow rate of 0.4 ml/min. Detection on an API 3200 QTRAP mass spectrometer equipped with an electrospray ionization source operated in the negative ionization mode was performed by multiple reaction monitoring of the precursor-to-product ion transitions of gentiopicroside, swertiamarin and IS at m/z 401.0 → 179.0, 419.0 → 179.1 and 525.1 → 121.0 respectively. The calibration curves were linear over the concentration range of 20-10 000 and 2-1000 ng/ml for gentiopicroside and swertiamarin with corresponding lower limits of quantification of 20 and 2 ng/ml. The limits of detection were 4 and 0.5 ng/ml for gentiopicroside and swertiamarin, respectively. The intraday and interday precisions were below 11.9% for gentiopicroside and below 9.5% for swertiamarin in terms of relative standard deviation, and the accuracy was within ±8.3% for gentiopicroside and within ±10.2% for swertiamarin in terms of relative error. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. The method was fully validated and applied to a pharmacokinetic study involving oral administration of a R adix G entianae extract to groups of male and female rats. Key findings Results showed that in female rats, both compounds were absorbed to a greater extent and eliminated more slowly than in male rats, although the rate of absorption was similar in the two groups. Conclusions There were remarkable differences in pharmacokinetic properties of gentiopicroside and swertiamarin between male and female rats. The results will provide helpful information for the development of suitable dosage forms and clinical references on rational administration. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is critically involved in the regulation of a wide variety of physiological and pathophysiological processes. However, the role of NO in the pathogenesis of noise-induced hearing loss (NIHL) is complex and remains controversial. Here we reported that treatment of CBA/J mice with l -arginine, a physiological precursor of NO, significantly reduced noise-induced reactive oxygen species accumulation in outer hair cells (OHCs), attenuated noise-induced loss of OHCs and NIHL consequently. Conversely, pharmacological inhibition of endothelial nitric oxide synthase exacerbated noise-induced loss of OHCs and aggravated NIHL. In HEI-OC1 cells, NO also showed substantial protection against H 2 O 2 -induced oxidative stress and cytotoxicity. Mechanistically, NO increased S-nitrosylation of pyruvate kinase M2 (PKM2) and inhibited its activity, which thus diverted glucose metabolic flux from glycolysis into the pentose phosphate pathway to increase production of reducing equivalents (NADPH and GSH) and eventually prevented H 2 O 2 -induced oxidative damage. These findings open new avenues for protection of cochlear hair cells from oxidative stress and prevention of NIHL through NO modulation of PKM2 and glucose metabolism reprogramming. [Display omitted] • NO levels are increased compensatorily in the cochlea following noise exposure. • Supplementation with l -arginine increases NO levels and prevents NIHL in mice. • NO increases S-nitrosylation of PKM2 and NADPH production in HEI-OC1 cells. • NO protects against oxidative stress through glucose metabolism reprogramming. [ABSTRACT FROM AUTHOR]

Abstract: A rapid, sensitive and high throughput ultra-fast liquid chromatography with tandem mass spectrometry (UFLC–MS/MS) method was established and validated for the determination of schisandrin B in rat plasma and various tissues (including heart, liver, spleen, lung, and kidney). The biological samples were prepared by protein precipitation, and the separation was achieved on a shim-pack XR-ODS C18 column (75mm×3.0mm, 2.2μm) with a mobile phase consisting of methanol–0.1% formic acid water (85:15, v/v) at a flow rate of 0.4mL/min. The MS/MS detection was performed on an API 3200 QTRAP mass spectrometry equipped with electrospray ionization (ESI) source using multiple reactions monitoring (MRM) mode by monitoring the fragmentation of m/z 401.2→300.2 for schisandrin B and m/z 271.2→203.1 for imperatorin (internal standard, IS). The calibration curve was linear in the range of 1–500ng/mL for plasma and tissue homogenates (r ≥0.9927). The lower limit of quantification (LLOQ) was 1ng/mL. The validated method was successfully applied to the pharmacokinetics and tissue distribution study of schisandrin B after oral administration to rats. The pharmacokinetic curve showed double peaks after oral administration, which demonstrated that a hepatoenteral circulation may exist. Tissue distribution showed the highest level was observed in liver, then in kidney, which indicated schisandrin B was mainly accumulated in liver and renal excretion might be a main elimination route. [Copyright &y& Elsevier]

[Display omitted] Amorphous solid dispersions (ASD) are one of most commonly used supersaturating drug delivery systems (SDDS) to formulate insoluble active pharmaceutical ingredients. However, the development of polymer-guided stabilization of ASD systems faces many obstacles. To overcome these shortcomings, co-amorphous supersaturable formulations have emerged as an alternative formulation strategy for poorly soluble compounds. Noteworthily, current researches around co-amorphous system (CAS) are mostly focused on preparation and characterization of these systems, but more detailed investigations of their supersaturation ("spring-parachute" process), stability, in vivo bioavailability and molecular mechanisms are inadequate and need to be clarified. In present study, we chose pharmacological relevant BCS II drugs to fabricate and characterize "felodipine-indomethacin" CAS. To enrich the current inadequate but key knowledge on CAS studies, we carried out following highlighted investigations including dissolution/solubility, semi-continuous "spring-parachute" process, long-term stability profile of amorphous state, in vivo bioavailability and underlying molecular mechanisms (molecular interaction, molecular miscibility and crystallization inhibition). Generally, the research provides some key information in the field of current "drug-drug" CAS supersaturable formulations. [ABSTRACT FROM AUTHOR]

F-box and WD repeat domain containing 10 (FBXW10) is a member of the FBXW subgroup that contains the WD40 domain. FBXW10 has been rarely reported in colorectal cancer (CRC) and its mechanism is unclear. To investigate the role of FBXW10 in CRC, we conducted in vitro and in vivo experiments. Through the database and our clinical samples, we found that FBXW10 expression was up-regulated in CRC, and it was positively correlated with CD31 expression. CRC patients with high FBXW10 expression levels had a poor prognosis. Overexpression of FBXW10 up-regulated cell proliferation, migration and vascular formation, while knockdown of FBXW10 had the opposite effects. Studies on the mechanism of FBXW10 in CRC showed that FBXW10 could ubiquitinate large tumor suppressor kinase 2 (LATS2) and promote its degradation with the Fbox region of FBXW10 played an essential role in this process. In vivo studies demonstrated that knockout of FBXW10 inhibited tumor proliferation and reduced liver metastasis. In conclusion, our study proved that FBXW10 was significantly overexpressed in CRC and was involved in the pathogenesis of CRC by affecting angiogenesis and liver metastasis. Mechanistically, FBXW10 degraded LATS2 through ubiquitination. Therefore, FBXW10-LATS2 can be used as a therapeutic target for CRC in subsequent studies. [Display omitted] [ABSTRACT FROM AUTHOR]

The high incidence of thrombosis in the portal venous system following splenectomy (a frequently adopted surgery for treating portal hypertension in patients with splenomegaly and hypersplenism) is a critical clinical issue. The aim of this study was to address whether quantification of postsplenectomy hemodynamics has potential value for assessing the risk of postsplenectomy thrombosis. Computational models were constructed for three portal hypertensive patients treated with splenectomy based on their preoperative clinical data to quantify hemodynamics in the portal venous system before and after splenectomy, respectively. Each patient was followed up for three or five months after surgery and examined with CT to screen potential thrombosis. The area ratio of wall regions exposed to low wall shear stress was small before splenectomy in all patients, which increased markedly after splenectomy and exhibited enlarged inter-patient differences. The largest area ratio of low wall shear stress and most severe flow stagnation after splenectomy were predicted for the patient suffering from postsplenectomy thrombosis, with the wall regions exposed to low wall shear stress corresponding well with the CT-detected distribution of thrombus. Further analyses revealed that postoperative hemodynamic characteristics were considerably influenced by the anatomorphological features of the portal venous system. Postoperative hemodynamic conditions in the portal venous system are highly patient-specific and have a potential link to postsplenectomy thrombosis, which indicates that patient-specific hemodynamic studies may serve as a complement to routine clinical assessments for refining risk stratification and postoperative patient management. • Low wall shear stress and prolonged flow stagnation are related to postsplenectomy thrombosis. • Anatomorphological features dominate hemodynamic characteristics in the portal venous system. • Hemodynamic analysis has potential value for assessing the risk of postsplenectomy thrombosis. [ABSTRACT FROM AUTHOR]

A high-performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FT-ICR MS) method was developed to study the in vivo metabolism of salidroside for the first time. Plasma, urine, bile, and feces samples were collected from male rats after a single intragastric gavage of salidroside at a dose of 50 mg/kg. Besides the parent drug, a total of seven metabolites (three phase I and four phase II metabolites) were detected and tentatively identified by comparing their mass spectrometry profiles with those of salidroside. Results indicated that metabolic pathways of salidroside in male rats included hydroxylation, dehydrogenation, glucuronidation, and sulfate conjugation. Among them, glucuronidation and sulfate conjugation were the major metabolic reactions. And most important, the detection of the sulfation metabolite of p-tyrosol provides a clue for whether the deglycosylation of salidroside occurs in vivo after intragastric gavage. In summary, results obtained in this study may contribute to the better understanding of the safety and mechanism of action of salidroside. [ABSTRACT FROM AUTHOR]

Intervertebral disc (IVD) disease, the most common cause of disc failure and low back pain, is characterized by age-related changes in the adult disc. In this study we aimed to analyze the potential of thalidomide for the treatment of IVD disease, through identifying and explaining its anti-inflammatory and anti-catabolic activity in both in vitro IVD cell culture and in vivo animal model. Inflammatory response was induced by IL-1β, then the activity and expression of inflammatory mediators and pathways were assessed in the presence or absence of thalidomide. The p38 inhibitor SB203580 was also used to investigate the involvement of the MAPK pathway in the observed effects. Moreover the analgesic properties of thalidomide were analyzed by the von Frey filament test in Sprague–Dawley rats. Our results indicated that thalidomide significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB. Our current study strongly supports the potential of thalidomide for the treatment of pain and inflammation in degenerative disc disease. [ABSTRACT FROM AUTHOR]

The management of patients with neuropathic pain is challenging. Monotherapy with a single pain relief drug may encounter different difficulties, such as short duration of efficacy and hence too many times of drug administration, and inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have been proved to provide promising strategies for efficient drug loading, delivery, and release. In the present study, we developed poly(ethylene glycol) methyl ether functionalized graphene oxide ( GO) bearing two commonly used drugs of lidocaine ( LDC) and thalidomide ( THD) as an agent for the treatment of neuropathic pain. The sequential drug release of LDC and THD from the developed LDC- THD- GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro and in vivo, as evidenced by the increased pain threshold in mechanical allodynia and hyperalgesic response tests, and the improved inhibition of proinflammatory cytokines TNF-α, IL-1β, IL-6, and nitric oxide. We believed that the present study herein would hold promise for future development of a new generation of potent agents for neuropathic pain relief. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3851-3860, 2015 [ABSTRACT FROM AUTHOR]

A simple and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of cinnamaldehyde, cinnamic acid, and 2-methoxy cinnamic acid in rat whole blood. It was the first time to study the pharmacokinetics of 2-methoxy cinnamic acid in rat whole blood. Samples were processed by a one-step protein precipitation with acetonitrile-37% formaldehyde (90:10, v:v). Chromatographic separation was performed on a Thermo Scientific C18 column (2.1 mm × 50 mm, 1.9 μm) at room temperature. The total run time was 4 min. The detection was accomplished by using positive and negative ion electrospray ionization in multiple reaction monitoring mode. The method was linear for all of the analytes over 1000 times concentration range with correlation coefficients greater than 0.99. The lower limits of quantification (LLOQ) were 0.1 ng/mL for cinnamaldehyde, 5.8 ng/mL for cinnamic acid, and 10 ng/mL for 2-methoxy cinnamic acid, respectively. To our knowledge, this was the first time that the LLOQ for cinnamaldehyde in validated methods for biological samples was as low as 0.1 ng/mL. Intra- and inter-day precision and accuracy were within ±9% for all of the analytes during the assay validation. Assay recoveries were higher than 80% and the matrix effects were minimal. The half-life were 8.7 ± 0.7 h for cinnamaldehyde, 1.0 ± 0.5 h for cinnamic acid, and 1.4 ± 0.4 h for 2-methoxy cinnamic acid, respectively. The validated assay was firstly applied to the simultaneous quantification of cinnamaldehyde, cinnamic acid, and 2-methoxy cinnamic acid, especially for 2-methoxy cinnamic acid in rat whole blood after oral administration of 15 mg/kg essential oil of Cinnamoni Ramulus. It was observed that the C max and AUC of 2-methoxy cinnamic acid (0.01% in essential oil of Cinnamoni Ramulus) were greater than those of cinnamaldehyde (83.49% in essential oil of Cinnamoni Ramulus), which implied that 2-methoxy cinnamic acid might be the major bioactive constitutes in essential oil of Cinnamoni Ramulus. [ABSTRACT FROM AUTHOR]

Zhi-Zi-Da-Huang decoction (ZZDHD), consisting of Gardenia jasminoides Ellis, Rheum palmatum L., Citrus aurantium L. and Sojae Semen Praeparatum, is a widely used traditional Chinese medicine preparation for the treatment of acute or chronic hepatic diseases. In the present study, a sensitive and selective ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC–Q-TOF-MS) method was developed to separate and identify the absorbed components and metabolites in rat plasma after oral administration of ZZDHD. The plasma samples were pretreated by protein precipitation and separated on a Shim-pack XR-ODS C 18 column (75 mm × 3.0 mm, 2.2 μm) using a gradient elution program. Mass spectrometric detection was performed on an Agilent 6520 Q-TOF mass spectrometer equipped with electrospray ionization (ESI) source in positive and negative ion modes. By comparing the retention time, high resolution mass data of blank plasma and dosed plasma, a total of 43 constituents, including 21 prototype compounds and 22 metabolites were identified or tentatively characterized. Results indicated that glucuronidation and sulfation were the main metabolic pathways of iridoid glycosides and anthraquinones, glucuronidation was the main metabolic pathways of flavanone-related compounds. It is concluded the developed UHPLC–Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the absorbed components and metabolites of ZZDHD, and the results will provide essential data for further studying the relationship between the chemical components and pharmacological activity of ZZDHD. [ABSTRACT FROM AUTHOR]

Thalidomide was introduced to the market in 1957 as a sedative and antiemetic agent, and returned to the market for the treatment of myelodysplastic syndrome and multiple myeloma. There are reports and studies of thalidomide as an analgesic or analgesic adjuvant in clinic. However, the underlying mechanism is quite elusive. Many studies suggest that the analgesic effect of thalidomide may be due to its immunomodulatory and anti-inflammatory properties as it suppresses the production of tumor necrosis factor α (TNF-α) selectively. However, it is not clear whether any other mechanisms are implicated in the pain relief. In this study, we demonstrated that the peripheral vanilloid receptor 1 (TRPV1) channel was also involved in the analgesic effect of thalidomide in different cell and animal models. During the activation by its agonist capsaicin, the cation inward influx through TRPV1 channels and the whole-cell current significantly decreased after TRPV1-overexpressed HEK293 cells or dorsal root ganglion (DRG) neurons were pre-treated with thalidomide for 20 minutes. And such attenuation in the TRPV1 activity was in a dose-dependent manner of thalidomide. In an acetic acid writhing test, pre-treatment of thalidomide decreased the writhing number in the wild type mice, while it did not happen in TRPV1 knockout mice, suggesting that the TRPV1 channel was involved in the pain relief by thalidomide. Taken together, the study showed that TRPV1 channels were involved in the analgesic effects of thalidomide. Such alteration in the action of TRPV1 channels by thalidomide may help understand how thalidomide takes analgesic effect in the body in addition to its selective inhibition of TNF-α production. [ABSTRACT FROM AUTHOR]

In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid–liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C 18 column (50 mm × 2.1 mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5 → 397.3, 435.3 → 415.3 and 393.3 → 355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1–1000 ng/ml for TAP and 0.5–500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of −8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7–104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs. [ABSTRACT FROM AUTHOR]

A sensitive and reliable ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was established to separate and identify the chemical constituents of Zhi-Zi-Da-Huang decoction, a classic traditional Chinese medicine formula. The chromatographic separation was achieved on a Shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 μm) using a gradient elution program. The detection was performed on a Waters Xevo G2 Q-TOF mass spectrometer equipped with electrospray ionization source in both positive and negative modes. With the optimized conditions, a total of 82 compounds were identified or tentatively characterized. Of the 82 compounds, 21 compounds were identified by comparing the retention time and MS data with reference standards, the rest were characterized by analyzing MS data and retrieving the reference literature. In addition, 31 compounds were identified from Gardenia jasminoides Ellis, ten compounds were identified from Rheum palmatum L., 33 compounds were identified from Citrus aurantium L., and eight compounds were identified from Sojae Semen Praeparatum. Results indicated that iridoids, anthraquinones, flavonoids, isoflavonoids, coumarins, glycosides of crocetin, monoterpenoids, and organic acids were major constituents in Zhi-Zi-Da-Huang decoction. It is concluded that the developed ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of Zhi-Zi-Da-Huang decoction, and the analysis provides a helpful chemical basis for further research on Zhi-Zi-Da-Huang decoction. [ABSTRACT FROM AUTHOR]

Highlights: [•] A selective, sensitive and reliable UFLC-MS/MS method was developed. [•] Simultaneous determination of eight analytes in rat plasma. [•] LLOQ were 4.0, 0.5, 2.0, 0.1, 1.0, 2.0, 1.0, 2.0ng/mL for analytes. [•] The method was applied to a comparative pharmacokinetic study. [•] Pharmacokinetic profiles in normal and cholestatic liver injury rats are revealed. [Copyright &y& Elsevier]

Abstract: A novel gastro-mucoadhesive delivery system based on ion-exchange fiber has been developed. Rriboflavin-5′-phosphate sodium salt (RF5P), which is site-specifically absorbed from the upper gastrointestinal tract, was used as model drug. A modified dissolution system, which can also be called ‘flow through diffusion cell’ (FTDC), was used to study the drug release from the drug fibers. Gastrointestinal transit studies of the RF5P fiber complexes in rats and gamma imaging study in volunteer was carried out to evaluate the gastro-retentive behavior of the fiber. The pharmacokinetic profile and parameters of riboflavin via analysis of urinary excretion of riboflavin on man were measured. Study on rat and man provide evidence for the validity of the hypothesis that the drug fiber provided good mucoadhesive properties in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms. [Copyright &y& Elsevier]

A correction to the article "Metabolic profile of salidroside in rats using high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry" that was published online on January 18, 2016 issue is presented.