italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC₅₀ values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

?AIM:To compare the coherence and difference on the fundus examination made with two kinds of optical coherence tomography ( OCT): Angio-OCT and fourier domain-optical coherence tomography ( FD-OCT) .?METHODS:Using Angio-OCT and FD-OCT to measure the retinal nerve fiber layer ( RNFL ) thickness, optic parameters, and ganglion cell complexes ( GCC ) thickness from 20 subjects respectively.The coherence was tested with Pearson's correlation coefficient, the difference was tested with paired Student t testing.?RESULTS:The total correlation of the RNFL thickness, optic parameters, GCC thickness made with two kinds of OCT was between 0.7-0.8;the RNFL thickness, optic disk area etc.made with the Angio-OCT were lower than those made with FD-OCT except for the GCC thickness.?CONCLUSION: The results made with two kinds of OCT from the same subject has certain coherence, but cannot be compared directly.

As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.

OBJECTIVETo investigate the effect of herba schizonepetae volatile oil (STO) on the activity of 5-lipoxygenase (5-LO), so as to elucidate its mechanisms of anti-inflammatory action which is related to the arachidonic acid (AA) metabolism.

METHODThoracic cavity leukocytes from the pleurisy model rat induced by injecting 1%-carrageenan into the pleural cavity were collected. Then 0. 4 mL cell suspension including 2 x 10(7) cells per millilitre were used as the reaction system in vitro. STO in different concentrations (final concentration 0.011, 0.022, 0.043, 0.087, 0.179, 0.255, 0.364 g x L(-1)), zileuton (final concentration 0.625 x 10(-3) g x L(-1)), and DMSO in the same volume were added into the reaction tube respectively. The reaction tubes were incubated at 37 degrees C for 20 min and CaCl2 (final concentration 2 mmol x L(-1)), MgCl2 (final concentration 0.5 mmol x L(-1)), exogenous AA (final concentration 200 micromol x L(-1)) and A23187 (final concentration 5 micromol x L(-1)) were added in turns during this period. The reaction tubes were mixed and continuously incubated at 37 degrees C for 30 min. After terminating reaction by adding methanol, the metabolites of 5-LO, leukotriene B4 (LTB4) and 5-hydroxy-6, 8, 11, 14-eicosatetraenoic acid (5-HETE), were extracted, separated and detected by means of RP-HPLC.

RESULTCompared with control group, STO significantly inhibited the biosynthesis of LTB4 and 5-HETE at final concentration between 0. 022 g x L(-1) and 0.364 g x L(-1) (P < 0.05 or 0.001) in dose dependence manner, and its IC50 value was 0.124 g x L(-1) and 0.142 g x L(-1) for LTB4 and 5-HETE, respectively.

CONCLUSIONSTO can inhibited the activity of 5-LO, which is an important enzyme of AA metabolism, in rat thoracic cavity leukocytes in a dose-dependent manner in vitro. It is suggested that the mechanism of anti-inflammatory action of STO is related to its inhibiting the activity of 5-LO and decreasing the level of major inflammatory mediators LTB4.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Arachidonate 5-Lipoxygenase ; metabolism ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Leukocytes ; drug effects ; enzymology ; Male ; Oils, Volatile ; pharmacology ; Plant Oils ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thoracic Cavity ; drug effects ; enzymology ; immunology

Compared with single therapy, radiotherapy combined with chemotherapy, endocrine therapy, molecular targeted therapy and immunological therapy can not only shorten the treatment cycle, but also improve the local control rate and prolong the survival of patients. However, the safety of combined therapy still needs to be further clarified to comprehensively evaluate the feasibility. Therefore, exploring the efficacy and safety of radiotherapy combined with systematic therapy will provide evidence for clinical benefits.

Objective To investigate the injury characteristics of Beagle dogs after warship multi cabin explosion.Methods Forty-eight adult male Beagle dogs were placed in the simulated blast-cabin and adjacent cabin (24 each),and ammunitions respectively containing 0.75kg TNT and 3.50kg TNT were then detonated in the blast-cabin.The survival situation,fluctuation of vital signs,morphological changes of organs and the incidence of various types of injury of the dogs were observed immediately after the explosion to 24h after injury,and the neurological functions score was performed.Results Twenty dogs died immediately after the explosion,and another 9 dogs died 24h after the explosion.The total mortality was 60.42％(29/48),and the mortalities in blastcabin and adjacent cabin were 79.17％(19/24) and 41.67％(10/24),respectively.The dog's skull was penetrated by bomb fragments,and congestion and bleeding were observed in brain tissue,lung,heart,stomach,bowels,liver and kidneys.Extremities fracture,soft tissue contusions,perforation and rupture were also checked out after explosion.The fatality rate of bomb fragment injury,blast injury and combined bomb fragment-blast injury was 27.59％(8/29),17.24％(5/29) and 55.17％(16/29),respectively.Conclusions The combined bomb fragment-blast injury show high incidence and make high fatality rate and serious injury.Combatants should effectually shield themselves with occluded objects as far as possible to avoid damage and reduce fatality.The key of early treatment is to treat the multiple injuries promptly.Intravenous fluid therapy should be practiced after hemodynamic monitoring.

PURPOSE: The purpose of this study was to evaluate the long-term clinical outcome and toxicity of induction chemotherapy (IC) followed by concomitant chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC). MATERIALS AND METHODS: A total of 194 locoregionally advanced nasopharyngeal carcinoma patients youngerthan 21 years who received CCRT with or without IC before were included in the study population. Overall survival (OS) rate, progression-free survival (PFS) rate, locoregional recurrence-free survival (LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified and compared between two groups. RESULTS: One hundred and thiry of 194 patients received IC+CCRT. Patients who were younger and with more advanced TNM stage were more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition of IC before CCRT failed to improve survival significantly. The matched analysis identified 43 well-balanced patients in both two groups. With a median follow-up of 51.5 months, no differences were found between the IC+CCRT group and the CCRT group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355), LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition of IC was associated with increased rates of grade 3 to 4 neutropenia. CONCLUSION: This study failed to demonstrate that adding IC before CCRT could provide a significant additional survival benefit for LACANPC patients. Further investigations are warranted.
Adolescent* ; Chemoradiotherapy* ; Child* ; Cohort Studies* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Induction Chemotherapy* ; Methods ; Neutropenia ; Radiotherapy

Poria is an important medical herb in clinic. The authors isolated a polysaccharide(PCP-Ⅰ) from Poria in previous studies, which is composed of galactose, mannose, fucose and glucose. PCP-Ⅰ exhibited significant adjuvant effects on H1N1 influenza vaccine, hepatitis B surface antigen and anthrax protective antigen, and its adjuvant activity was stronger than aluminium adjuvant. However, little is known about the chemical structure of PCP-Ⅰ at present. In this study, weak acid hydrolysis was used to obtain the backbone oligosaccharide of PCP-Ⅰ. Then periodate oxidation, Smith degradation, methylation analysis, Fourier transform infrared spectroscopy(FT-IR), nuclear magnetic resonance(NMR) and gas chromatography-mass spectrometry(GC-MS) were performed to investigate the chemical structural features of PCP-Ⅰ and its hydrolytic oligosaccharide(PCP-Ⅰ-hy-1). These results suggested that the backbone of PCP-Ⅰ was composed of galactose with α anomeric carbon and β anomeric carbon. The linking residues of galactan are(1→),(l→6) and(1→2,6).
Adjuvants, Vaccine ; Poria ; Hydrolysis ; Spectroscopy, Fourier Transform Infrared ; Galactose ; Influenza A Virus, H1N1 Subtype ; Polysaccharides/chemistry* ; Oligosaccharides ; Carbon

OBJECTIVETo investigate the neuro-protective effects of Acanthopanax senticosus Harms (EAS) on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson's disease (PD).

METHODSThe chemical fingerprint analysis of the extract of Acanthopanax senticosus Harms (EAS) was performed using the ultra performance liquid chromatograph and time of flight mass spectrometry. Thirty mice were randomly divided into the control group, the MPTP model group, and the EAS treated group with MPTP (MPTP+EAS group, 10 in each group). The MPTP model group and the MPTP+EAS group received MPTP-HCl (30 mg/kg i.p) once a day for 5 days. The control group received an equal volume of saline (20 mL/kg i.p) once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride daily (MPTP-HCl, 30 mg/kg) for 5 days, the PD mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral testing of mice was carried out using the pole-climbing test. The integrity and functions of neurons were examined in mesencephalic mitochondria in a PD mouse model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 1 (MT-ND1), succinate dehydrogenase complex subunit A (SDHA), and succinate dehydrogenase cytochrome b560 subunit (SDHC).

RESULTSAfter treatment with EAS, the behavioral changes induced by MPTP were attenuated significantly (P<0.05). EAS protected the mesencephalic mitochondria from swelling and attenuated the decreases in their membrane potential (both P<0.05), which was supported by an ultra-structural level analysis. The changes in reactive oxygen species (ROS), malonic dialdehyde (MDA), oxidative phosphorylation (OXPHOS) system 4 subunits levels and PD-related proteins expressions (parkin, Pink1, DJ-1, α-synuclein, and Lrrk2) reverted to near normal levels (all P<0.05), based on the results of immune-histological and Western blotting observations.

CONCLUSIONSThe neuro-protective effects of EAS are linked to protecting mice against MPTP-induced mitochondrial dysfunction and structural damage. Therefore, EAS is a promising candidate for the prevention or treatment of mitochondrial neurodegenerative disorders, such as PD.

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.