Human rhinoviruses (HRVs) are the causative pathogens in more than half of viral upper respiratory tract infections. Currently, no antiviral agents that are active against HRVs are available for clinical use. Because only higher primates are susceptible to HRVs, the screening of new drug is most commonly based on the cell line model. In this study, isolated rabbit airway smooth muscles (ASM) tissue model has been established, and the airway responsiveness with different treatment has been examined. Relative to control tissues, the maximal constrictor (Tmax) response to ACh increased significantly 150% in ASM inoculated with HRV, and relaxation to isoproterenol has been attenuated to 63%. And the abnormal responsiveness can be inhibited in presence of pretreatment with several new compounds which have been exhibited effective anti-HRV activity on cell lines. The results demonstrate that the established ASM model will be applied to screening the anti-HRVs drugs.

AIMTo further elucidate the role of agmatine on the pharmacological effects of opioids. METHODSThe effect of L-arginine and L-arginine decarboxylase(L-ADC) antibodies on pain threshold, morphine ntinociception and tolerance were investigated in mouse acetic acid writhing test, mouse radiant heat tail flick test and mouse hot plate test. RESULTSIn mouse acetic acid writhing test, intracerebroventricular injection of L-arginine dose-ependently inhibited the writhing of mice compared with saline control. L-arginine did not influence the tail flick latency itself in mouse radiant heat tail flick test, but enhanced antinociceptive effect of morphine in a dose-dependent manner. The possible maximal analgesia percentage of morphine 2.5 mg*kg-1 was increased from 23% to 71%. Furthermore, L-arginine inhibited acute tolerance induced by morphine 100 mg*kg-1in mouse radiant heat tail flick test. The effect of L-arginine as mentioned above could be antagonized by idazoxan (3 mg*kg-1, ip), which is a selective antagonist of imidazoline receptors. L-ADC specific antibodies inhibited morphine antinociception and promoted the development of tolerance to morphine in mouse radiant heat tail flick test and 55℃ hot plate test. CONCLUSIONL-Arginine and L-ADC play important roles in the formation of pain threshold, morphine antinociception and tolerance.

Objective:To study the tissue speciality of endothelium-dependent vascular relaxation mediated by endothelial protein activated by acetylcholine (EPA)and its relationship with atherosclerosis.Methods:The tension of the isolated artery preparations was recorded using isometric-tension method and the isolated endothelium-intact vessels derived from normal and hyperlipidemic animal artery.Results:The EPA-mediated endothelium-dependent vascular relaxation was exhibited in rabbit aorta, renal, femoral, carotid, pulmonary arteries and cat aorta, renal, femoral, mesentery, coronary arteries but with different EC50. The sensitivity of EPA to ACh in descending order: pulmonary>renal>aorta>femoral>carotid arteries in rabbits. In cats,coronary>aorta>femoral>mesentary>renal. The endothelium-dependent vascular relaxation mediated by EPA in aorta, carotid and pulmonary arteries decreased significantly in hyperlipidemia rabbits.Conclusions:EPA effect existed wildly in testing artery and was of different tissue sensitivity. The decrease in EPA potency was closely related to occurence of atheroclerosis.

Aim To investigate the effects of Y-IP5 on morphine-induced behavioral sensitization and CPP in mice.Methods Locomotor activity was detected after Y-IP5 administration or co-administration of Y-IP5 with morphine in mice.Mice were treated with morphine to induce behavioral sensitization. Then the effects of Y-IP5 on the development, transfer and expression of morphine-induced behavioral sensitization were investigated. Mice were treated with morphine to induce CPP. Then the effect of Y-IP5 on the acquisition of morphine-induced CPP was studied.Results Y-IP5 itself didn′t influence locomotor activity of mice.Co-administration of Y-IP5 with morphine inhibited morphine-induced hyperactivity (P<0.05) and the development of morphine-induced behavioral sensitization in mice (P<0.05), however, did not influence the transfer and expression of morphine-induced behavioral sensitization.Co-administration of Y-IP5 with morphine also inhibited the acquisition of morphine-induced CPP (P<0.05).Conclusion Y-IP5 may inhibit the psychological dependence induced by morphine.

Background and purpose: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is of advantage in treating non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, their clinical effects vary individually. This study aimed to evaluate whether the EGFR ligand, plasma transforming growth factor α (TGF-α), could act as a predictor for the EGFR-TKI treatment e?ciency in NSCLC patients with EGFR mutations and the association between TGF-α and prognosis in these patients. Methods: Seventy-five NSCLC patients with EGFR gene positive mutation were included in the current study from May 2012 to Jul. 2014 in Ruikang Hospital A?liated to Guangxi University of Chinese Medicine. Plasma TGF-α was measured using enzyme-linked immunosorbent assay (ELISA) in all of the patients before EGFR-TKI treatment. The radiographic evaluation was performed 2 months after the therapy. The association between TGF-α and clinical outcome and its prediction e?ciency were determined, followed by the further analysis of the association between TGF-α and overall survival (OS) as well as progression-free survival (PFS). Results: After EGFR-TKI treatment, there were 20 patients with partial response (PR), 25 with stable disease (SD) and 30 with progression disease (PD) in all 75 NSCLC patients harboring EGFR positive mutation. The disease control (DC) rate reached 60%. Patients in PD group presented statistically significant higher plasma TGF-αthan patients in the DC group (P<0.01). Multivariate COX model indicated that smoking status, lymph node metastasis and plasma TGF-α levels were independent risk factors for prognosis in these patients. The ROC analysis revealed that baseline plasma TGF-α showed good prediction e?ciency [area under the curve (AUC)=0.926] and the cut-off point of TGF-α was 16.75 pg/mL. Higher level of TGF-α (≥16.75 pg/mL) was associated with smoking history, clinical stage, lymph node metastasis and clinical outcome of the patients (P<0.05). In comparison to patients with low TGF-α, the patients with high TGF-α concentration presented significantly reduced median OS and PFS (log-rank P<0.05). Conclusion: Higher plasma TGF-α (≥16.75 pg/mL) had a predictive role in EGFR-TKI resistance and poor prognosis.

Objective To explore the relationship between traditional Chinese medicine (TCM) syndromes of state of evil domination and clinical and laboratory indicators of IgA nephropathy. Methods A prospective study was used to collect data on clinical and laboratory examination of IgA nephropathy in multi clinical centers. Patients’ TCM syndrome types were determined according to the national diagnostic criteria at the same time. Totally 266 patients with IgA nephropathy were included in the study to establish a database for analyzing the relationship between TCM syndrome of state of evil domination and clinical and laboratory indicators. Results In the relationship between syndromes of state of evil domination distribution and clinical subtypes, patients of wind-heat syndrome had more macroscopic hematuria;patients of phlegm-damp syndrome had more nephrotic syndrome;patients of damp-heat syndrome had more chronic nephritis type Ⅰ;patients of blood stasis syndrome had more chronic nephritis type Ⅱ. In the relationship between syndrome of state of evil domination distribution and clinical manifestation, the incidence of hypertension was higher in patients of blood stasis syndrome than in other three types. It was more serious for hematuresis in the patients of wind-heat syndrome. For patients of phlegm-damp syndrome, the incidence of heave proteinuria was highest. In the relationship between syndrome of state of evil domination distribution and laboratory examination, 24-hour urinary protein quantification was higher than in patients of wind-heat and damp-heat syndrome, but the level of blood albumin was lowest. For patients of blood stasis syndrome, serum creatinine level was significantly higher than in other three types;the level of eGFR was just the opposite. The levels of blood cholesterol and triglyceride in patients of phlegm-damp syndrome were higher than in other three types. The activated partial thromboplastin time (APTT) levels in patients of blood stasis and phlegm-damp syndrome were lower than in other patients, but the FIB level was the exact opposite of APTT. In the relationship between syndrome of state of evil domination distribution and the stages of chronic kidney disease (CKD), patients of wind-heat syndrome were more in the first stage of CKD;patients of blood stasis syndrome were more in the third stage of CKD. Conclusion There is relative correlation between TCM syndromes of state of evil domination and clinical and laboratory indicators in IgA nephropathy, which would provide some reference to narrow the gap in the information of the four methods of TCM with clinical and laboratory indicators to enhance accurate diagnosis of TCM syndrome.

Objective To compare the clinical efficacy of cold snare endoscopic mucosal resection(CS-EMR)with conventional endoscopic mucosal resection(EMR)in the treatment of＜20 mm colorectal laterally spreading tumor(CLST).Methods A total of 248 CLST patients undergoing endoscopic resection treated in the First People's Hospital of Huzhou from January 2020 to June 2022 were selected and divided into EMR group and CS-EMR group according to random number table method,with 124 cases in each group.The general data,focal features,surgical indicators and complication rate of two groups were statistically compared.Results There were no significant differences in en bloc resection rate,complete resection rate and postoperative recurrence rate between two groups(P＞0.05).The operation time and hospital stay in CS-EMR group were significantly shorter than those in EMR group,the number of titanium clips and hospitalization costs were significantly lower than those in EMR group,and the incidence of intraoperative bleeding,delayed bleeding and delayed perforation were significantly lower than those in EMR group(P＜0.05).Conclusion In treatment of CLST with a maximum diameter of＜20mm,CS-EMR not only retains the advantages of fewer surgery-related complications,but also has similar therapeutic effect as EMR,and reduces the cost burden of patients,which is worthy of clinical reference and promotion.

Objective To investigate the effect and its mechanism of ziyuglycoside Ⅱ on prolifer-ation,migration,invasion and apoptosis of colon cancer cells HT-29.Methods The effect of ziyugly-coside n on cell proliferation of colon cancer cells HT-29 was determined by CCK-8 method;the effect of ziyuglycoside Ⅱ on cell migrative capacity of colon cancer cells HT-29 was determined by scratch assay;the effect of ziyuglycoside n on cell invasive capacity of colon cancer cells HT-29 was determined by transwell assay;the effects of ziyuglycoside n on cell apoptosis of colon cancer cells HT-29 was determined by flow cytometry;the effects of ziyuglycoside Ⅱ on mRNA and protein expres-sion of protein kinase B(AKT)/phosphatidylinositol-3-kinase(PI3K)signal pathway were determined by real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)and western-blot,respectively.Results Ziyuglycoside n(0,1,5,10,20,40,60 and 80 μmol/mL)inhibited pro-liferation of colon cancer cells HT-29 in a dose-dependent manner.Ziyuglycoside n(5,10 and 20 μmol/mL)inhibited migration of colon cancer cells HT-29 in a dose-dependent manner.Ziyuglyco-side Ⅱ(5,10 and 20 μmol/mL)inhibited invasion of colon cancer cells HT-29 in a dose-dependent manner.Ziyuglycoside Ⅱ(5,10 and 20 μmol/mL)promoted apoptosis of colon cancer cells HT-29 in a dose-dependent manner.Ziyuglycoside Ⅱ(5,10 and 20 μmol/mL)increased mRNA expression of AKT and PI3K,decreased mRNA expression of Caspase-3 and Caspase-9.Ziyuglycoside Ⅱ(5,10 and 20 μmol/mL)increased protein expression of phosphorylated protein kinase B(p-AKT)and phosphorylphosphatidylinositol-3-kinase(p-PI3K),increased the expression of Cleaved-Caspase-3 and Cleaved-Caspase-9 protein.Conclusion Ziyuglycoside Ⅱ can inhibit proliferation,migration and invasion of colon cancer cells HT-29,and promote the apoptosis of colon cancer cells HT-29.Its mechanism may be related to regulating the signal pathway of AKT/PI3K via promoting phospho-rylation of AKT and PI3K protein,activation of Caspase-3 and Caspase-9 protein.