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@#Carboxymethylcysteine (CMC) is a common drug for the clinical treatment of chronic obstructive pulmonary disease, yet its long-term use can cause severe irritation to the gastrointestinal tract.As the substrate of nitric oxide (NO) synthase (NOS), L-arginine can be converted in the body into NO beneficial to the cardiovascular system, the gastrointestinal tract and so on.As a basic amino acid, L-arginine can be salified with some compounds containing acidic groups to improve the water solubility of the parent drug and may enhance the activity and alleviate side effects due to NO release.In this study, we designed and synthesized carboxymethylcysteine L-arginate (CMCA), and tested its physico-chemical properties, and the abilities to scavenge reactive oxygen species (ROS), inhibit apoptosis and release NO in cigarette smoke-induced injury model of human bronchial epithelial cells.The results revealed that CMCA is superior to CMC or L-arginine in that it could capture ROS, release NO and suppress apoptosis, suggesting that CMCA is worthy of further research and development.
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Fruquintinib is an effective, highly selective and oral VEGFR 1, 2 and 3 tyrosine kinase inhibitor. It was discovered and developed by Hutchison MediPharma for the treatment of solid tumors. In September 2018, fruquintinib received its first global approval in China for use in the treatment of metastatic colorectal cancer (CRC) patients who have failed at least two prior systemic anti-neoplastic therapies. Clinical studies have shown that it has the advantages of low off-target toxicity, good drug resistance and strong curative effect. This article reviews the molecular structure, mechanism of action, pharmacokinetics, clinical efficacy and safety of fruquintinib, as well as its potential clinical applications in other tumor types.
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Objective To evaluate the effect of honokiol on the activation of transient receptor potential (TRP) channel in rat spinal dorsal root ganglion cells and pruritus in mouse models.Methods Healthy male ICR mice aged 4-6 weeks were used to establish histamine-induced and acetone/ether/water (AEW)-induced itching models separately.Totally,mice were randomly divided into 7 groups (histamineinduced model experiment) or 6 groups (AEW-induced model experiment):normal control group and model group both gavaged with sodium chloride physiological solution,solvent group gavaged with sodium carboxymethylcellulose solution,chlorphenamine group (only set up in the histamine-induced model experiment) gavaged with chlorphenamine,50,25 and 12.5 mg/kg honokiol groups gavaged with 50,25 and 12.5 mg/kg honokiol respectively.In the histamine-induced model experiment,the mice were all injected with histamine except the normal control group injected with sodium chloride physiological solution 24 hours after the gavage treatment,while the mice in the AEW-induced model experiment were all topically treated with AEW except the normal control group topically treated with sodium chloride physiological solution for 4 days,followed by gavage with different drugs.The anti-itch effect of each treatment was evaluated by counting the scratching frequency within 30 minutes.Rat spinal dorsal root ganglion (DRG)cells were isolated and subjected to a primary culture.Then,the DRG cells were divided into 6 groups:capsaicin or allyl isothiocyanate (AITC)-induced model group pre-incubated with Hank's balanced salt solution (HBSS),500 μmol/L capsazepine or 10 μmol/L HSC030031 group pre-incubated with capsazepine or HSC030031,solvent group pre-incubated with dimethyl sulfoxide (DMSO),3 honokiol groups preincubated with 7.81,15.63 and 31.25 mg/L honokiol respectively,and Ca2+ fluorescence imaging system was used to observe changes of Ca2+ influx in these cells after capsaicin or AITC stimulation.Statistical analysis was carried out with SPSS 20.0 software by using one-way analysis of variance and Dunnett-t test.Results In the histamine-induced mouse models,the scratching frequency was significantly lower in the 50 and 25 mg/kg honokiol groups than in the model group (21.88 and 21.14 vs.63.70,t =3.48,3.49 respectively,both P =0.003),while no significant difference in the scratching frequency was observed between the 12.5 mg/kg honokiol group and the model group (t =2.01,P =0.062).After the treatment with 50 mg/kg honokiol in the AEW-induced mouse models,the scratching frequency significantly decreased compared with the model group (61.4 vs.101.17,t =0.45,P =0.009),while there were no significant differences among the 25,12.5 mg/kg honokiol groups and the model group (all P ＞ 0.05).Compared with the capsaicin or AITC-induced model group,the increase of Ca2+ fluorescence signal in the DRG cells was significantly inhibited in the 31.25 mg/L honokiol group:at the 45th second,the rate of relative fluorescence intensity change (AF/F0) was 1.11 in the model group,but-0.11 in the 31.25 mg/L honokiol group in the capsaicin-induced model experiment,and 0.56 in the model group,but 0.00 in the 31.25 mg/L honokiol group in the AITC-induced model experiment.Conclusion Honokiol shows an inhibitory effect on mouse models of pruritus induced by histaminergic or non-histaminergic factors,likely by inhibiting Ca2+ influx through activated TRPV 1 and TRPA 1 channels in the DRG cells.
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Objective To explore the surgical efficacy of meningioma patients with epilepsy as the main symptoms. Methods A retrospective analysis of 124 meningioma patients with epilepsy as the main symptoms between January 2010 and January 2016,follow-up effect of epilepsy control. Results There were 94 cases of Simpson I orⅡgrade resection,27 cases of gradeⅢresection and 3 cases of grade Ⅳ resection. The surgical out-comes of patients were evaluated based on Engel′s classification. There were 98 cases(79.0%)of EngelⅠgrade, 11 cases(8.9%)of EngelⅡgrade,Engel Ⅲ and Ⅳ grade were 12 cases(9.7%)and 3 cases(2.4%). Among them,87 of 94 patients with Simpson I orⅡ grade resection epilepsy were well controlled,the satisfaction rate of epilepsy control was 92.6%. Conclusions Epilepsy as the main symptoms of meningioma patients need to clear about the seizure onset area preoperative,need to pay special attention to whether there is an independent epilepsy starting area of the distant site of the tumor. On the basis of the tumor resection as much as possible,at the same time dealing with the abnormal release of the cortex can effectively improve the efficacy of postoperative epilepsy control.
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Objective To compare the ear baric function between 4000m altitude chamber test with inhaling air and 6900m altitude chamber test with inhaling pure oxygen.Methods Eleven healthy male volunteers attended two tests as two groups by self-comparison. As the air group the volunteers inhaled air at 4000m, while as the pure oxygen group they inhaled pure oxygen at 6900m altitude, and the time interval between the two tests was more than two weeks. During the test, the volunteers breathed air or pure oxygen at random for 1h, and then were exposed at a speed of 20m/s to the target altitude for 5min. Hereafter they were sent back to the ground at the same speed. The changes of subjective symptoms, degree of tympanic congestion, acoustic immitance index and pure-tone auditory threshold were recorded before and after the test. The acoustic impedance index and pure-tone threshold were statistically analyzed.ResultsFour volunteers (4 ears) in air group and 7 volunteers (7 ears) in pure oxygen group reported ear pain in altitude chamber exposures, respectively. The pain-triggering altitude was higher in the pure oxygen group. Immediately after tests, there were 3 (3 ears) and 5 volunteers (5 ears) with Ⅲ degree congestion of the tympanic membrane in the two groups respectively. Four volunteers (6 ears) developed gradually aggravated hemorrhages after altitude exposure. And the tympanic membrane congestion difference between groups was statistically significant at 3 and 24h after tests (P<0.01). The type A tympanogram appeared in 11 (15 ears) and 11 (14 ears) volunteers respectively immediately after tests. The increase of static compliance value was significantly greater in pure oxygen group than in air group immediately after tests (P<0.05), the decrease of middle ear pressure was more significant in pure oxygen group than in air group at 3 and 24h after tests (P<0.05). Both the two altitude exposure tests resulted in eustachian tube dysfunction. At 3 and 24h after the tests, the increase of individual frequency pure-tone threshold was significantly higher in pure oxygen group than in air group (P<0.05).Conclusion Breathing pure oxygen and lifting height could increase the screening degree of ear baric function test in hypobaric chamber, and have greater influence on degree of tympanic congestion, acoustic immittance and pure-tone auditory threshold in 24 hours.
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Objective To explore the surgical treatment of epilepsy in rolandic and immediate perirolan dic cortex.Methods 376 patients accepted surgical treatment in our hospital from January 2010 to January 2016,of whom 48 patients fulfilled eligibility criteria and were included in the study.Patients were divided into 2 groups for analysis:patients with resections in the rolandic cortex (A group,n =28),and patients with resections in immediate perirolandic cortex and simultaneous sensorimotor multiple subpial transections (B group,n =20).Postoperative seizure outcome and neurologic deficits were analyzed.Results According to classification of Engel,Engel Ⅰ was in 22 (45.8％),Engel Ⅱ in 7 (14.6％),Engel Ⅲ in 10 (20.8％) and Engel Ⅳ in 9(18.8％).Seizure outcome satisfaction rate (Engel Ⅰ +Engel Ⅱ) in the group A was significantly higher than the group B (P =0.036);temporary and transient neurological deficits in the two groups had no statistically significant (P =0.569,P =0.418).Conclusions It is possible to achieve complete dissection of epileptic foci in rolandic and immediate perirolandic cortex without damage.The good prognosis is not related to the degree of excision of epilepsy and has no definite correlation with neurological dysfunction.
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Objective Metabonomics method based gas chromatography-mass spectrometry (GC/MS)were used to analyze the urine samples of patients with hyperlipidemic pancreatitis (HLP) to describe the characteristics of metabolism changes of HLP,identify potential biomarkers,and investigate the role of metabonomics study in the management of AP.Methods 24 patients of HLP and 40 age,sex matched volunteers were enrolled and their urine samples were collected.The urine samples underwent preparation,derivation and GC/MS analysis,Orthogonal-Projection to Latent Structures-Discriminant Analysis (OPLS-DA)were performed to detect the metabolic profile difference between the HLP and control group.Results HLP patients can be precisely distinguished from healthy controls.21 metabolites (credibility ＞ 700 ) were identified using the reference compounds available in the libraries of NIST and Wiley.It was identified that levels of nicotinic acid,aconitie acid,citric acid,hippurie acid,hydroxyphenylacetic acid,hydroxyphenylpropionicacid were decreased,while the levels of tryptophan,tyrosine,tyramine,16-hexadecanoic acid,18octadecanoie acid were increased.It was also suggested that there was change in tricarboxylic acid cycle and gut bacterial flora,as well as fat metabolism and metabolism of amino acid.Conclusions There are differences between healthy controls and HLP patients in the term of GC/MS metabolic profiling,and the biomarkers in the metabolites could be found through metabonomics analysis,and the mechanisms of the metabolic changes could be explored.It was noted that the research of metabolites in the urine samples may be a useful tool to help diagnose and understand the pathogenesis of HLP.Metabonomics analysis is a promising research method.
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Objective To study the corelation of mucosal involvement and corticosteroid dosage in the control of bullous pemphigoid(BP). Methods One hundred and three in-patients with bullous pemphigoid hospitalized during 1988 - 2002 were retrospectively analyzed for their mean corticosteroid dosage for controlling the disease and the duration for complete relieving the skin lesions, as well as the duration to start corticosteroid tapering. All the patients were divided into two groups: group A (37 cases) with mucosal involvement and group B (66 cases) without mucosal involvement. Results The mean corticosteroid dosage used to control the disease in group A was much higher than that in group B (t = 3.488, P 0.05). Conclusion Patients with mucosal involvement require a higher dosage of corticosteroids to control the disease.
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Objective To develop the measuring system used for the parameters of onboard oxygen supply equipment in the hypobaric chamber. Methods The programmable controller was applied to acquisition, processing and analysis of the data from the sensor. The host computer was used to accomplish control and information display. Results The system could display the parameters through digital, simulating meters, and recording curve. The numerical value in the recording curve was marked by the date and time. All data were saved in the computer for futural analysis and procession. Conclusion The measurement system of oxygen supply parameters can satisfy the desired requirements for the performance and precision.