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BACKGROUND Atopic dermatitis (AD) is a chronic skin inflammation with a heterogeneous immunological profile. Leukocyte cell-derived chemotaxin 2 (LECT2) is a liver-derived multifunctional cytokine that has been studied due to its important role in inflammatory and autoimmune diseases. However, the relationship between AD and LECT2 has not been defined. This study was performed to investigate the levels of LECT2 in patients with AD and to determine whether it was associated with the severity and clinical characteristics of AD. METHODS The study included 42 AD patients and 30 healthy controls from the Affiliated Hospital of Medical School of Ningbo University. Participants' serum levels of LECT2 were measured using enzyme-linked immunosorbent assay kits. The values in the patient group and control group were statistically compared. The relationships between the different markers were evaluated by correlation analysis. RESULTS The serum levels of LECT2 were significantly higher in AD patients than those in the controls. In addition, LECT2 was significantly correlated with the Scoring of Atopic Dermatitis (SCORAD) index, the level of immunoglobulin E (IgE), and eosinophils (P

GEN-0828, a proposed clinical candidate for hemophilia and trauma hemorrhage treatment, is a novel recombinant activated human factor VII (rFVIIa). The purpose of this paper is to compare the pharmacokinetics and pharmacodynamics of GEN-0828 in hemophilia B mice with those of NovoSeven®, the only marketed rFVIIa product worldwide., GEN-0828 and NovoSeven® showed similar affinity bioactivity to recombinant tissue factor (rTF) in vitro. Pharmacodynamics data indicated a generally similar hemostatic efficacy (ED

MicroRNAs (miRNAs) are important regulators in the process of cardiac hypertrophy and heart failure. Previous studies have shown that miR-199a is upregulated in pressure-overload cardiac hypertrophy and that inhibition of miR-199a attenuates cardiac hypertrophy in vitro. However, the therapeutic role of anti-miR-199a treatment in the cardiac hypertrophy in vivo model is less known. Here, we show an efficient and useful method to treat mouse cardiac hypertrophy and restore cardiac function through injection of adeno-associated virus (AAV)-mediated anti-miR-199a tough decoys (TuDs). RNA-seq transcriptome analysis indicated that genes related to cytoplasmic translation and mitochondrial respiratory chain complex assembly were upregulated in anti-miR-199a-treated recovered hearts. We further validated that PGC-1α is the direct target of miR-199a involved in the therapeutic effect and the regulation of the PGC-1α/ERRα axis and that the downstream pathway of mitochondrial fatty acid oxidation and oxidative phosphorylation constitute the underlying mechanism of the restored mitochondrial structure and function in our anti-miR-199a-treated mice. Our study highlights the important regulatory role of miR-199a in cardiac hypertrophy and the value of the AAV-mediated miRNA delivery system., Graphical Abstract, Previous studies showed that miR-199a is upregulated in pressure-overload cardiac hypertrophy, and inhibition of miR-199a attenuated cardiac hypertrophy in vitro. This study showed an efficient and useful way to treat mice cardiac hypertrophy and restored cardiac function through injection of adeno-associated virus-mediated anti-miR-199a tough decoys targeting the PGC-1α/ERR axis.

At present, whole-brain radiation therapy/stereotactic radiosurgery is one of the main local treatments for brain metastasis of non-small-cell lung cancer (NSCLC). Currently, it has been proved that radiotherapy (RT) can regulate the immune response, and small-sample studies have shown that patients with NSCLC brain metastases (BMs) can benefit from RT combined with immunotherapy (IO). However, the efficacy and safety of the combination treatment have not been deeply elaborated. Notably, as a challenge that is still being explored, the timing of RT combined with IO is likely to be an important factor affecting efficacy and prognosis. This article reviews the current application and challenges of RT combined with IO from the perspectives of molecular mechanism, combination timing, safety, and efficacy. The purpose is to provide information on clinical evidence-based medicine of combination between RT with IO. For further investigation, we also discuss the major challenges and prospects of RT combined with IO in NSCLC BMs.

Heparin-like biomacromolecules (HepLBm), exhibiting similar chemical structure and biological properties to heparin, can be obtained by modifying either synthetic biopolymers or natural biomacromolecules with physical or chemical methods. In this work, a low-cost and biocompatible sodium alginate was chosen as a model biomacromolecule to design anticoagulant HepLBm with a similar sulfation degree to heparin. FTIR, 1H NMR, and element analysis data were used to confirm the chemical structure of HepLBm. Hemolysis tests, clotting time, complement activation, and contact activation tests were carried out to determine the in vitro anticoagulant activity of HepLBm. In addition, systematic studies of blood cell count, coagulation function, and histopathology were performed to demonstrate the in vivo anticoagulant activity and toxicity of HepLBm with SD rat experiments. Furthermore, a series of linear molecules containing carboxyl groups, sulfonic groups, and hydroxyl groups were selected and their clotting time was tested to provide a mechanism analysis for the excellent anticoagulant activity of HepLBm. With the excellent in vitro/in vivo anticoagulant activity, good biocompatibility, and low cost, the HepLBm synthesized in this work would have great potential for substitution of heparin in many application fields, such as the surface modification of biomedical devices, extracorporeal anticoagulants, and other clinical fields.

Background: Gonadotropin-releasing hormone analogs (GnRHas) are used for treating central precocious puberty (CPP). However, their roles in the regulation of immune cells especially regulatory T cells (Tregs) remains elusive. Therefore, we characterized buserelin-induced phenotypical and functional changes of Tregs.Methods: A rat CPP model was established followed by administration of buserelin acetate. Flow cytometry was used to evaluate the expression of functional molecules in splenic Tregs. The suppressive activity of Tregs was determined by the suppression assay. GnRHR expression in Tregs was assessed by flow cytometry analysis and Immunoblotting. Normal Tregs were then stimulated and treated with buserelin acetate in vitro. After that, Foxp3 expression, Treg proliferation, and cytokine production were analyzed by flow cytometry. Intracellular signaling was evaluated by Immunoblotting, and Treg function was determined by the suppression assay.Results: After in vivo buserelin treatment, the frequency of splenic Tregs was decreased, with the reduction in the expression of Foxp3, IL-10, and TGF-β. The suppressive activity of Tregs was weakened. Buserelin down-regulated Foxp3 expression while promoting the expression of RORγt and IL-17 in Tregs through activating the protein kinase A (PKA) pathway in vitro. The PKA inhibitor H-89 abolished the effect of buserelin and enhanced Treg function.Conclusion: Buserelin impaired the immunosuppressive activity of Tregs through the PKA signal pathway. Buserelin-induced activation of PKA signaling down-regulated Foxp3 expression while promoting RORγt expression in Tregs, and subsequently weakened Treg function. Our study indicates the necessity of monitoring Treg activity in CPP patients to avoid potential autoimmunity or inflammation.

Frontal polymerization was successfully used to prepare two series of copolymers from a tetraphenylporphyrin-containing monomer (TPP-TEG-MA) and poly(ethylene glycol) methyl ether acrylate (PEGMA) or di(ethylene glycol) methyl ether methacrylate (DEGMA). Tricaprylmethylammonium (Aliquat) persulfate (APSO) was used as radical initiator to obtain highly fluorescent hydrogels with different chromophore contents. The obtained hydrogels, PEGTPP and DEGTPP series, were characterized by FT-IR spectroscopy, and the successful incorporation of TPP-TEG-MA monomer into the polymer backbone was observed. Their thermal properties were determined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The swelling behavior of the obtained hydrogels was measured at 25 °C and pH = 7. The swelling ratio increased until equilibrium was reached after 24 h. Furthermore, the pH and temperature responses of the obtained hydrogels were measured. The optical properties of these materials were studied by absorption and fluorescence spectroscopies. They exhibited an absorption band at 418 nm (Soret band) and an emission band at 653 nm, which are typical of the porphyrin moiety.

To assess the value of contrast-enhanced ultrasound (CEUS) and color Doppler ultrasound (DUS) on hemodynamic changes and cerebral perfusion quantitative analyses in Sprague-Dawley (SD) rats with focal permanent ischemic stroke.Sixteen SD rats with thin skulls were subjected to establish middle cerebral artery occlusion (MCAO) model. CEUS images were performed before modeling (TA total of 12 rats were successfully modeled and completed with mNSS score 9-11. No blood flow signals were observed on the right MCA and ACA in the 12 rats at TCEUS and DUS can reveal the intracranial hemodynamics and brain tissue perfusion trends of MCAO rats, which could be new methods in assessment of ischemic stroke model at multiple time points.

Background: Chronic spontaneous urticaria (CSU) is a skin disorder with an important immunologic profile. S100A8, S100A9, and S100A12 are the members of S100 family that have been reported to play important role in autoimmune diseases, but the characteristics of these three S100 members have not been defined in CSU. Aims: This study was performed to investigate the levels of these three S100s in patients with CSU and to study whether they were associated with the severity and clinical characteristics of CSU. Materials and Methods: The levels of plasma S100A8, S100A9, and S100A12 were measured in 51 CSU patients and 20 healthy controls using enzyme linked immunosorbent assay kits. The values in the patient group and that of the healthy controls were statistically compared. The relationships between the different markers were evaluated by correlation analysis. Results: The plasma levels of S100A8, S100A9, and S100A12 were significantly higher in CSU patients than those in controls. Interestingly, the level of S100A12 was significantly correlated with S100A8 and S100A9 in CSU patients (P < 0.05 and P < 0.001, respectively). In addition, S100A8, S100A9, and S100A12 were all significantly inversely correlated with blood basophil percentage. Conclusions: Plasma S100A8, S100A9, and S100A12 levels were elevated in CSU patients. They might be useful biomarkers of CSU, with the potential role in the pathogenesis of CSU.

Background Oral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis. Methods Based on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated. Findings Our results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema – patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89. Interpretation Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy., Highlights • The oral microbiota of NPC patients are different to that of healthy persons. • The biodiversity of oral microbiota changed significantly as mucositis progressed during radiotherapy. • Oral microbiota represents a potential strategy for predicting the aggravation of severe mucositis during radiotherapy. Oral or oropharyngeal mucositis is the most common side effect of radiation therapy for head and neck cancers. In this prospective cohort study, we found that changes in an oral microbial community correlated with the progression and aggravation of radiotherapy-induced mucositis in the patients with nasopharyngeal carcinoma; and patients who eventually developed severe mucositis transiently harbored a notably higher proportion of Actinobacillus during a mild phase of mucositis, which may potentially play a role in the aggravation of severe mucosal lesions. Moreover, our findings also showed that microbiota-based strategies can be used for the early prediction of the incidence of severe mucositis during radiotherapy.

To determine the value of applying multimodal ultrasound (mUS) in SD rats of cerebral ischemic model at super early stage (5-15 min after modeling).Fifteen focal cerebral ischemic models were established in SD rats with thinning skulls using the suture method. Gray-scale ultrasound, contrast-enhanced ultrasound, and enhanced color Doppler (CECDUS) were performed before and immediately after the modeling to observe the location of the in-cranial suture, perfusion of the right hemisphere, and color flow signal of the middle cerebral artery and the anterior cerebral artery, respectively.A modified neurological deficit score (mNSS) and 2, 3, 5-triphenyltetrazolium chloride (TTC) stains were obtained three hours later to confirm the successful modeling as the gold standard. The positive rate detected by mUS was compared with the gold standard using McNemar tests.One rat died and 14 rats completed the experiment.mUS imaging detected 71% (10/14) positive signals, no significant difference compared with the gold standard (64%, 9/14) (Multimodal ultrasound can assess modeling success quickly and accurately immediately after the establishment of ischemic model of SD rats.

In order to investigate the effect of temperature on the cellulose-degrading bacteria and denitrifying bacteria, the denitrification and phosphorus removal of solid carbon source of cellulose corncob+sulfur/sponge iron nitrogen and phosphorus removal composite system, abbreviated as SCSC-S/Fe, was analyzed under different temperature conditions, and the surface structure and microbial properties of corncob before and after reaction were analyzed by scanning electron microscope (SEM) and MiSeq high-throughput sequencing technologies. The results indicated that when temperature increased from 15, 20, 25 to 30℃, the average TN removal rate of the system increased from 78.88% to 92.70%, the average removal rate of TP increased from 82.58% to 89.15%;microbial properties showed that the surface reaction after corncob was dominated by spherical and rod-shaped microorganisms; the proportion of cellulose-degrading bacteria was 11.01% higher at 30℃ than 20℃, and the proportion of denitrifying bacteria decreased by 21.26%. It can be seen that the cellulose -degrading bacteria were more sensitive to the temperature than the denitrification bacteria, and more obviously affected by the temperature.

In order to improve the phosphorus removal effect in the denitrification and phosphorus synchronous removal process by sulfur/sponge iron composite fillers, the phosphorus removal effect by different fillers with the coupling microorganisms was studied to analyze the denitrifying phosphorus removal mechanism of the microbial coupling sulfur/sponge iron composite fillers. The research result showed that the phosphorus removal ratio of sponge iron/sulfur composite fillers was over 95%, which was increased by 30% as compared to only sponge iron filler. In addition, the effluent TP concentration was reduced to less than 0.1 mg·L

To improve the quality of the tailings water from a wastewater treatment plant (WWTP), a denitrification biofilter (DNBF) with a composite filler composed of a new slow-release organic-carbon source (SOC-F), sponge iron, and activated carbon was tested. Studies were conducted in the combined process of DNBF-O

To study the effects of sulfur/sponge iron ratio on denitrification and phosphorus removal, a series of static experiments were conducted using different ratios of sulfur and sponge iron. The results showed that the denitrification and phosphorus removal effect of sulfur/sponge iron composite fillers was significantly higher than that of single filler, and sulfur/sponge iron ratio was one of the key factors influencing nitrogen and phosphorus removal by composite fillers. When the volume ratio was equal to or greater than 1:1, the removal efficiency of TN and TP reached 85% and 97%, respectively. The denitrification and phosphorus removal process of the composite fillers both fitted second-order kinetic equation, the denitrification was dependent on heterotrophic denitrification and sulfur autotrophic denitrification; the phosphorus removal was mainly chemical phosphorus removal caused by sponge iron corrosion.

The advanced manufacturing technology (AMT) is the important symbol of the national industrial modernization level. Because of fuzzy and uncertainty of reference information for decision,traditional evaluation methods often determined not accurately and efficiently. According to the evaluation of problem, based on the Fuzzy control technology, this paper firstly put forward a method of fuzzy group multi-criteria decision-making, which applies with the information of either weight coefficient or policymakers weight coefficient incompletely and decision makers having risk attitudes. Then on the basis of constructing the evaluation criterion system of advanced manufacturing technology, an example of some enterprise with AMT selecting project evaluation is given to explain the feasibility and availability of this method for helping decision-makers in determining the optimal conditions of AMT in uncertain environment.

A novel polyelectrolyte complex (PEC) of carboxymethyl starch (CMS) and chitosan was prepared, characterized and tested in vitro as a carrier for oral drug delivery. This PEC, containing 14% (w/w) of chitosan, showed a polymorphism with a lower order degree than those of CMS and of chitosan. Under conditions simulating the gastrointestinal transit, NMR imaging analysis showed slower fluid diffusion inside PEC monolithic tablets than inside CMS tablets. The PEC seems to be a more suitable drug carrier for colon targeting than CMS, since it can prolong acetaminophen release time from 8 h to 11 h and aspirin release time from 13 h to 30 h. In contrast, chitosan used as a coexcipient accelerated aspirin release from matrices based on a CMS:chitosan physical mixture.

To evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients.A prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment.After three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P0.05]. Scores for CM syndromes, BASDAI, night pain index, spinal pain index, PGA, CRP were improved in the BSG group (P0.05, P0.01). The incidence of adverse events in the BSG group was lower than that of the control group.BSG based on Shen supplementing, Du-channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.

As a widespread phenomenon in living system, molecular self-assembly has become the meeting point of multidisciplinary research including chemistry, biology, materials science and medicine. In recent years, the rapid development in molecular self-assembly of peptide technology is showing a great potential in the application of tissue engineering, drug delivery, bionic medicine, cosmetology field, optical and electronic product development, etc. Especially, the remarkable hemostatic effect of self-assembling peptides (SAP) on organs, nerves and brain wounds successfully promoted its application to the material science and clinical medicine. This review focuses on the hemostatic effects and characteristics of SAP on different bleeding wound models, action mechanism, its benefits and limitations as well as its adrancing trends.

Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion. Materials and Methods: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors. Results: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval (CI) 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643). Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.

A novel method was used to synthesize cholic acid hydrophobic-modified dextrans (CAH–Dex) which form nanoparticles in aqueous solution. The stabilization and drug-loading of the formed nanoparticles were investigated. Dextran was oxidized by sodium periodate to dextran dialdehyde which was then conjugated with cholic acid hydrazide through an acyl hydrazone linkage. The self-aggregation behavior of the resulting conjugates was investigated using nuclear magnetic resonance, fluorescence and photo correlation spectrometry. The conjugates were found to have low critical aggregate concentrations (CAC) (0.46–0.96 × 10−2 mg mL−1) which is characteristic, depending on both the oxidization and substitution degrees. Above the CAC the conjugates tend to form nanoparticle aggregates with inner hydrophobic environment. The diameters of the nanoparticles rely on the pH of the medium due to the aldo–enol transition of the dextran dialdehyde. By crosslinking the aldehyde groups located on the surface using adipic dihydrazide, the nanoparticles were obviously stabilized. The drug-loading and release behavior of the nanoparticles was investigated using indomethacin as a hydrophobic model drug. Copyright © 2006 Society of Chemical Industry

A series of hydrogels based on N -isopropylacrylamide, sodium acrylate, and N -tert-butylacrylamide were synthesized by free radical polymerization in a mixture of dioxane and water with tetra(ethylene glycol) diacrylate as the crosslinker and benzoyl peroxide as the initiator. The swelling behavior including the swelling rate of the crosslinked gels in water was studied with gravimetric method. The swelling ratio of the gel (0.1 mol% crosslinking) can reach 420 g/g at 20 °C and such a gel can release 96% of the water absorbed at 40 °C. The lower critical swelling temperature (LCST) of the copolymers can be adjusted by changing the chemical composition of the polymers. Such crosslinked gels can be potentially used as thermosensitive superabsorbent because of their high water uptake and thermal sensitivity.

In dilute heteropolymer solutions, a limited number of the chains, just like proteins, could collapse and associate to form a stable/metastable mesoglobular phase between single-chain globules and macroscopic precipitates. Recently, we found that inserting more hydrophobic comonomers into a thermally sensitive chain backbone surprisingly led to the formation of smaller mesoglobules in water. This apparent contradiction to our conventional wisdom can be satisfactorily explained in terms of the overlooked viscoelastic effect; namely, hydrophobic association inside each mesoglobule increases the chain relaxation time (τe). When it becomes much longer than the interaction time (τc) of two colliding mesoglobules, each mesoglobule behaves like a tiny nonadhesive “glass” ball. This stabilization mechanism is completely different from thermodynamic consideration in which one normally tries to make the particle surface hydrophilic so that τc is reduced.

Thermosensitive copolymers of poly(N-isopropyl acrylamide)-co-2-hydroxyethyl methacrylate (NIPA-co-HEMA) macroporous resins were synthesized in the form of beads by inverse suspension polymerization. The copolymerization was carried out in aqueous solutions of the comonomers dispersed by cyclohexane with stabilizers. A series of resins with different molar ratios of NIPA : HEMA, and different crosslinking degrees was obtained. The compositions of the copolymers were determined by elemental analysis. The results showed that the content of HEMA in a copolymer was higher than that of the corresponding feed mixture from which the copolymer was made. IR spectra also confirmed the structure of the copolymers. The porous parameters such as true densities, apparent densities, pore volumes, and porosities of the resins were measured by means of pycnometry. The determination of equilibrium swelling ratios and measurement of differential scanning calibration indicated that the resins exhibited thermosensitivity in aqueous solutions. Finally, the loading of hydroxyl groups was determined by titration. The resins have potential applications as supports in solid-phase synthesis after being functionalized. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1792–1797, 2004

Regarding the controversial investigations characterizing the role of KRAS status for predicting patients' response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small-cell lung cancer (NSCLC), we conducted a meta-analysis in unselected patients and a further subset analysis in EGFR wild-type advanced NSCLC to get a more accurate evaluation.We did systematically searches following the retrieval strategies. The end points were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR).Twelve prospective intervention trials comprised of 1,859 unselected advanced NSCLC patients were identified. KRAS mutation was associated with shorter OS and PFS [hazard ratio (HR) 2.09, 95 % confidence interval (CI) 1.56-2.80; HR 1.82, 95 % CI 1.50-2.20] and lower ORR (relative ratio 0.25, 95 % CI 0.11-0.59) in unselected advanced NSCLC. After subgroup analysis, the association with survival was strengthened in second- or later-line EGFR-TKIs treatment group, with an HR of 2.45 for OS (95 % CI 1.27-4.74) and 1.86 for PFS (95 % CI 1.51-2.29), while the association with response to EGFR-TKIs became nonsignificant (P = 0.153). Four retrospective studies on the role of KRAS status in EGFR wild-type advanced NSCLC were deemed eligible and presented that KRAS mutation was associated with none of the outcomes in EGFR wild-type patients treated with EGFR-TKIs.In unselected advanced NSCLC patients, KRAS mutations could be used as a potential negative predictor of clinical benefit from EGFR-TKIs. However, KRAS testing is of limited value to identify patients for EGFR-TKIs when EGFR status is considered.

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.

Gastric cancer (GC) is one of the most common malignancies in China. B-cell translocation gene 3 (BTG3) has been identified as a tumor suppressor in several tumors, but its role in GC remains unknown. This study aimed to detect the expression of BTG3 and its prognostic value in GC tissues and determine its function in the progression of GC.The expression of BTG3 was detected in GC cell lines and tissues by real-time RT-PCR, Western blot or immunohistochemistry. A series of in vitro and in vivo assays were performed to evaluate the effect of BTG3 on proliferation, migration and invasion of GC cells.B-cell translocation gene 3 was obviously down-regulated in GC tissues. Its expression was positively correlated with distant metastasis (P0.05). Patients with lower BTG3 expression had shorter overall survival time (P = 0.015). BTG3 suppressed the proliferation of GC cells in vitro and in vivo. It also inhibited migration and invasion of GC cells in vitro.Down-regulation of BTG3 is closely associated with proliferation, migration and invasion in GC. It may be a novel prognostic biomarker for GC patients.

We have shown that the addition of cholestyramine (CHA, a resin known to bind bile salts in the gastrointestinal tract) to ochratoxin A (OTA)-contaminated rat diets reduced plasma levels of the toxin and prevented OTA-induced nephrotoxicity. To elucidate the mechanism of action of CHA, we carried out in vitro experiments to determine whether the resin may bind the toxin. For comparative purposes, binding of bile salts to the resin was also examined. Results showed that CHA binds both OTA and bile salts (taurodeoxycholate [TDC] and taurocholate [TCA]). Also, CHA showed greater affinity for OTA and TDC than for TCA. At 1 mM concentration, 96% of OTA and 80% of TDC were bound to the resin, while for TCA binding was only 50%. However, saturation of the resin was reached at higher levels with bile acids compared to OTA (3.67 mmol/g resin for TCA and 3.71 mmol/g resin for TDC versus 2.85 mmol/g resin for OTA). To characterize the nature of the binding of the toxin to CHA, NaCl (0 to 200 mM) was added to a fixed amount of OTA or bile acids. As expected, TCA absorption was decreased by the addition of NaCl (50 mM), indicating electrostatic binding. However, OTA and TDC sorption was decreased only at high concentrations of NaCl (150 mM), suggesting a stronger binding to the resin than that shown with TCA. Sequential competitive studies demonstrated that CHA binds more OTA than TCA. The results of the in vivo study show the role of bile salts in OTA absorption. The toxin's plasma levels at 1 and 3 h after a single oral dose of OTA were significantly decreased in bile salt-depleted rats compared to the control. Thus, the alteration of the bile salt biliary pool and OTA enterohepatic circulation may be an additional mechanism of action of the resin against mycotoxin toxicity.

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

This paper proposes the construction of the information management platform of logistics parks with functions such as overall perception, systematic analysis, mass data mining and information decision analysis through the application of the Internet of Things and cloud computing, probes into the 8-layer framework mode of the system, analyzes the key technologies including the realization of real-time data acquisition and realization of intelligent push technology as well as completes the design of decision support layer by adopting Agent-middleware technology.

The purpose of this study was to investigate the effect of paclitaxel in combination with 20(s)-ginsenoside Rg3 on its anti-tumour effect in nude mice. In the Caco-2 transport assay, the apparent permeability from the apical side to the basal side (P(app)) (A-B) and P(app) (B-A) of paclitaxel were measured when co-incubated with different concentrations of 20(s)-ginsenoside Rg3. The results indicated that the penetration of paclitaxel through the Caco-2 monolayer from the apical side to the basal side was facilitated by 20(s)-ginsenoside Rg3 in a concentration-dependent manner. Meanwhile, 20(s)-ginsenoside Rg3 inhibited P-glycoprotein (P-gp), and the maximum inhibition was achieved at 80 µM (p0.05). The pharmacokinetic parameters of paclitaxel after oral co-administration of paclitaxel (40 mg/kg) with various doses of 20(s)-ginsenoside Rg3 in rats were investigated by an in vivo pharmacokinetic experiment. The results showed that the AUC of paclitaxel co-administered with 20(s)-ginsenoside Rg3 was significantly higher (p0.001 at 10 mg/kg) compared with the control. The relative bioavailability (RB) % of paclitaxel with 20(s)-ginsenoside Rg3 was 3.4-fold (10 mg/kg) higher than that of the control. The effect of paclitaxel orally co-administered with 20(s)-ginsenoside Rg3 against human tumour MCF-7 xenografts in nude mice was also evaluated. Paclitaxel (20 mg/kg) co-administered with 20(s)-ginsenoside Rg3 (10 mg/kg) exhibited an effective anti-tumour activity with the relative tumor growth rate (T/C) values of 39.36% (p0.05). The results showed that 20(s)-ginsenoside Rg3 enhanced the oral bioavailability of paclitaxel in rats and improved the anti-tumour activity in nude mice, indicating that oral co-administration of paclitaxel with 20(s)-ginsenoside Rg3 could provide an effective strategy in addition to the established i.v. route.

To explore the iodine level in the environment and the iodine status among the general population as well as the prevalence of thyroid nodules in Hangzhou city. Relationship between the prevalence of thyroid nodules and the policy of universal salt iodization in Hangzhou was also analyzed.Questionnaire, a 3-day weighed dietary record method, and 3 days' 24-hour dietary recall method were used to understand the iodine nutrition status and dietary intake of iodine among the general population in the city. Drinking water, edible salt and morning urine were collected to determine iodine content. All objects under survey underwent the thyroid B ultrasonic examination. Statistical analysis was done by SPSS 13.0 and SAS 9.1.(1) In total, 12 620 effective questionnaires were available, with 221 water samples, 12 730 urine samples, and 3593 salt samples collected. 12 515 objects underwent B ultrasonic examination, and 1848 received dietary investigation. (2) Water iodine level of Hangzhou was in the range of 0.20 - 5.99 µg/L, with the median level as 2.58 µg/L. (3) Average daily dietary intake of iodine for adult males in Hangzhou was 289.2 µg/d. The contribution of iodine intake from iodized salt was 74.4%. (4) The median of Hangzhou residents' urinary iodine was 178.80 µg/L, with the urinary iodine levels at 100 µg/L-, 200 µg/L-,100 µg/L, and ≥ 300 µg/L groups were 37.14%, 23.11%, 21.05%, and 18.69% respectively. Urinary iodine of pregnant women was 141.0 µg/L. (5) Incidence of thyroid nodules in females (28.6%) was higher than that of males (20.1%). The detection rate increased with age (6.4% at group 6-, 10.9% at 12-, 12.0% at 18-, 24.4% at 40-, and 38.8% at 65-); with the highest in urban area (29.8%), followed by suburbs (23.3%) and in rural area it showed the least (20.3%). Urinary iodine level was found lower among the population who had been detected with thyroid nodules (160.36 µg/L) than those among the undetected population (182.00 µg/L).Hangzhou appeared to be an area where the environmental was iodine deficient. Iodized salt was the major source of iodine intake. The iodine status among the general population seemed to be safe and suitable, but the iodine level for pregnant women was not sufficient. There was still no evidence indicating that the universal salt iodization policy in Hangzhou was associated with the prevalence of thyroid nodules.

This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in ratin dogin humanin monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

The paper is to report the pharmacokinetic character of a series of chemical compounds in vitro and in vivo. Metabolism stability of a series of chemical compounds was screened by using rat liver microsomes. The samples of different chemical compounds were combined and then simultaneously detected by LC-MS/MS. Compounds y13, y12 and y11 were screened out by microstability assay in vitro. The pharmacokinetics of compounds y11, y12 and y13 was evaluated by using SD rat. The plasma samples were pooled at the same time. The plasma concentrations were determined by LC-MS/MS. The pharmacokinetic character of two compounds y13, y11 was good by screening in vivo, so they were developed for further research. High-throughput screening of drug candidates in vitro and in vivo was effective, to provide information for the chemical structure information and lower the drug development risk.

to study the correlation of polymorphisms of CYP1A1 MspI, GSTM1 null genotype, cooking oil fumes independently and in combination with the risk of non-smoking lung cancer in females.one hundred and sixty female non-smoking patients with primary lung cancer and 160 controls were enrolled from Xiangya Hospital of Central South University. PCR-RELP and PCR were used to detect the distribution of CYP1A1 MspI and GSTM1 genotypes respectively. The correlation of these genes and cooking oil fumes with the susceptibility to lung cancer was analyzed.There was a significant difference in the frequencies of cooking oil fumes exposure between cancer cases and controls (χ(2) = 10.734, P0.01);but there was no statistical difference in CYP1A1 MspI polymorphisms between the 2 groups (χ(2) = 3.731, P0.05). The combination of CYP1A1 polymorphisms and cooking oil fumes significantly increased the risk of lung cancer. The frequencies of GSTM1 null genotype was significantly different between cancer cases and controls (χ(2) = 0.518, P0.05). The risk of lung cancer was higher in those with the GSTM1 null genotype and the OR was 1.697 (95%CI 1.090 - 2.640). Individuals with both GSTM1 null genotype and exposure to cooking fumes had a higher risk of cancer than those with only one of them, the OR being 3.617 (95%CI 1.899 - 6.891). The combination of the two genes significantly increased the risk of lung cancer.cooking oil fumes exposure was a risk factor for non-smoking lung cancer in females. The combination of CYP1A1 with cooking oil fume increased the risk of female lung cancer. GSTM1 null genotype was associated with risk of lung cancer in non-smoking females. The combination of GSTM1 null genotype and cooking oil fumes significantly increased the risk of female lung cancer. The combination of CYP1A1 and GSTM1 significantly increased the risk of lung cancer.

Acenaphthalene was copolymerized with acrylamide in water to form poly(acrylamide- co -acenaphthalene) [P(AAm- co -ACE)] with molecular weight ≈2 × 10 6 g mol −1 . A variety of fluorescence experiments were carried out at 0.8 wt% polymer concentration. Time-resolved fluorescence depolarization measurements gave a mean rotational correlation time for backbone motion of 30 ns. Time-resolved and steady-state fluorescence quenching experiments were carried out using acrylamide as the quencher. In the case of polymer-bound chromophore, we were able to follow the transient effect in the diffusion-controlled quenching process. The mutual diffusion coefficient D characterizing this reaction is a factor of six slower than the self-diffusion coefficient D AAm = 9.15 × 10 −6 cm 2 s −1 for acrylamide in water, measured by pulsed gradient n.m.r. We interpret this result to mean that acrylamide diffusion is significantly slower inside the P(AAm) coil than it is in bulk water.