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Objective:To explore the efficacy of precision hepatectomy in the treatment of single hepatocellular carcinoma with microvascular invasion (MVI) of and the risk factors of positive incisal margin after operation.Methods:The clinical data of 212 patients with single hepatocellular carcinoma with MVI treated in Affiliated Hospital of Panzhihua University from July 2016 to July 2019 were analyzed retrospectively. 152 patients were treated with precision hepatectomy and 60 patients with traditional hepatectomy. According to the pathological results of postoperative liver resection, the patients treated with precision hepatectomy were divided into two groups: negative group ( n=129) and positive group ( n=23). The operation-related indexes, postoperative complications and disease-free survival rate of precision hepatectomy and traditional hepatectomy were compared, and the general data of patients with negative and positive liver cutting edge were compared. multivariate analysis of the factors affecting the positive liver cutting edge after operation; to construct a line chart prediction model to predict the positive liver cutting edge after operation, and to evaluate its predictive efficiency. Normally distributed measurement data are represented by mean±standard deviation ( Mean± SD), independent t-test is used for comparison between groups; count data are represented by the number of cases and percentages, and χ2 test is used for comparison between groups. Results:The operative time, intraoperative blood loss, postoperative hospital stay, positive rate of surgical margin, total incidence of postoperative complications, AFP negative conversion rate 6 months after operation, and 1-year disease-free survival rate of precision hepatectomy were (328.62±38.74) min, (496.83±59.76) mL, (15.28±3.61) d, 15.13% (23/152), 3.95% (6/152), 81.58% (124/152), 67.11% (102/152), respectively. The mean values of traditional hepatectomy were (315.29±40.95) min, (681.46±58.27) mL, (23.87±4.65) d, 28.33% (17/60), 21.67% (13/60), 66.67% (40/60) and 46.67% (28/60), respectively, the difference was statistically significant ( P<0.05). Univariate analysis showed that the positive liver resection margin after precision liver resection was related to the maximum diameter of the tumor, vascular tumor thrombus, TNM staging, BCLC staging, liver cirrhosis, AFP 2 months after surgery, and the distance between the tumor and the resection margin ( OR=3.645, 5.248, 4.285, 4.462, 3.883, 3.964, 3.872; 95% CI: 2.875-4.415, 4.426-6.070, 3.271-5.299, 3.354-5.570, 3.062-4.704, 3.248-4.680, 2.987-4.757; P<0.05). Maximum tumor diameter >5 cm, vascular tumor thrombus, TNM stage Ⅲ, BCLC stage C, liver cirrhosis, postoperative AFP ≥20 μg Uniql, the distance between the tumor and the resection margin was <1 mm were the risk factors of positive incisal margin after precision hepatectomy in patients with single liver cancer with MVI( OR=6.685, 8.425, 7.758, 7.854, 7.124, 7.246, 6.926; 95% CI: 5.828-7.542, 7.6385-9.212, 6.926-8.590, 7.062-8.646, 6.583-7.665, 6.618-7.874, 6.028-7.824; P<0.05). The constructed line chart prediction model had better differentiation and higher accuracy. Conclusions:Precision hepatectomy in the treatment of single hepatocellular carcinoma with MVI has the advantages of less intraoperative bleeding, faster postoperative recovery, less postoperative complications, low positive rate of liver incisal margin and high disease-free survival rate. The construction of a risk prediction model with positive surgical margin provides a reference for improving the survival rate of patients in clinic.
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OBJECTIVE: To explore biomarkers for early auxiliary diagnosis of pneumoconiosis in coal workers(CWP) and its clinical significance. METHODS: Sixty-nine male coal miners exposed to dust were selected as control group, and sixty-seven CWP male patients were chosen as CWP group by purposive sampling method. Serum samples were collected from subjects of the two groups. The levels of malonaldehyde(MDA) and superoxide dismutase(SOD) were determined by colorimetric method. The enzyme-linked immunosorbent assay was used to measure the level of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α). The acetylcholinesterase(AChE) activity was determined by modified Ellman method. The logistic regression model was used to analyze the risk factors of CWP. The receiver operating characteristic(ROC) curve was established to analyze the sensitive indicators in the pathogenesis of CWP. RESULTS: The serum SOD activity decreased(median: 65.1 vs 59.2 kU/L, P<0.05), and the MDA, IL-6 and TNF-α levels increased in the CWP group(median: 4.92 vs 6.68 μmol/L, 129.82 vs 163.18 ng/L, 63.90 vs 70.93 ng/L, P<0.05) compared with the control group. The logistic regression analysis results showed that AChE was the protective factor of CWP, while age, chronic respiratory symptoms, IL-6 and MDA were the risk factors of CWP(P<0.05). The ROC curve showed that IL-6 and MDA can be used as early indicators for the diagnosis of CWP in dust-exposed workers. CONCLUSION: The serum IL-6 and MDA levels can be used as biomarkers for early auxiliary diagnosis of CWP.
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Objective To find the efficient modification groups of anti-proteinase hydrolyzation in polypeptide by investigat-ing and comparing the relation between the functional groups and their ability to inhibit proteinase hydrolyzation. Methods Reverse phase-high performance liquid chromatography(RP-HPLC)method was developed to investigate in vitro metabolisms of new drug LXT101 and its structural modified analogs LZN series and LMP series in pancreatin system. All the separations of peptide drugs and their digested fragments were monitored at 225 nm. Results The good linear range was 4.0-400 μg/ml(r>0.9990)for new drug LXT101 and its structural modified analogs,i.e.,LZN series and LMP series. The recoveries of all peptide drugs ranged from 95.0%to 98.7%in pancreatin systems. The relative standard derivations(RSD)of intra-day and inter-day were less than 1.5%and 2.5%,re-spectively. The revealed order of digested half-life of the peptide drugs was LZN series>LMP series>LXT101. Conclusion The study of different sites and different functional groups on the lifetime indicates that the half-lives of peptides are prolonged by introducing the functional groups in the suitable sites of peptide,which feature as proteinase inhibitors,such as carbamoyl(Cbm),acetyl(Ac),para-amino-phenylalanine(Aph)or para-uramido-phenylalanine(Uph),which work as either proton donor or acceptor. Our results can pro-vide some useful and valuable information on structural design of peptide drug with long lifetime and high activity.
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HIV-1 fusion inhibitors are a new class of anti-HIV compounds, which block the entry of HIV into target cells through preventing the fusion between viral and cell plasma membrane and thus interrupt the initial steps of viral replication. T-20 (enfuvirtide), which has been clinically approved as the first fusion inhibitor of HIV-1 by U.S. FDA in 2003, can suppress replication of HIV variants with multi-drug resistance to reverse transcriptase and protease inhibitors. Peptides and small molecules display potent anti-HIV fusion activities by targeting gp41 thus inhibit its fusogenic function. In recent years, with the development of studies on the molecular mechanism of HIV membrane fusion process and the function of gp41, many new fusion inhibitors are found and some have been in advanced clinical trials. This review discusses recent progress in the development of HIV-1 fusion inhibitors targeting the gp41.
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AIM: To evaluate the cytotoxicity of a novel anticholinergic drug penehyclidine hydrochloride (PHC) and its four optical isomers R-1, R-2, S-1, and S-2. METHODS: Two in vitro assays, MTT assay and neutral red uptake assay, were used to evaluate the cytotoxicity following PHC and its isomers exposure to HepG2 cells at different concentrations. RESULTS: PHC and its isomers induced decreases of viability of HepG2 cells in a concentration-dependent manner. Comparison of the cytotoxicity of the five anticholinergic agents with 50% inhibitory concentration (IC50) values indicated that the order of potency was PHC>R-2>R-1>S-2>S-1 for MTT assay, and R-2>PHC≈R-1>S-2>S-1 for neutral red uptake assay. CONCLUSION: With respect to the cytotoxicity of the four isomers on HepG2 cells, the R configuration was more potent than the S configuration, and R-2 was the most potent isomer whereas S-1 was the least potent isomer among the four optical isomers.
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Aim Series of compounds,which were considered to be the antagonists of ET-1 receptor,were synthesized by Beijing Institute of Pharmacology and Toxicology.The biological activity of these compounds was screened and some active compounds were selected for further pharmacological characterization on pulmonary hypertension.Methods Radioligand binding assay was performed to study the binding affinity of compounds for ETA and ETB receptors.The biological activity of compounds was evaluated in isolated rat aortic ring and in systemic arterial pressure(SAP)of anesthetized rat experiments.In addition,hypotensive effect of compounds was investigated on monocrotaline induced pulmonary hypertension in rats.Results Compounds bind to ETA receptor had over 10 000 fold higher affinity than to ETB receptor.Contraction induced by ET-1 in isolated rat aortic ring was inhibited by compounds,and 1 ?mol?L-1 ETP-508 shifted the cumulative concentration-contraction response curve to ET-1 to right with no change in the maximal response.In vivo,the increase in SAP induced by ET-1 〔3.7 ?g?(0.5 ml)-1?kg-1〕 was inhibited by 2 mg?kg-1 compounds by intravenous infusion.Furthermore,BQ-485 and ETP-508 by intravenous infusion(0.4 mg?h-1)significantly inhibited 80 mg?kg-1(sc)monocrotaline induced pulmonary hypertension in rats.Conclusions These results indicate that ETP-508 and BQ-485 are highly selective ETA receptor antagonists and significantly inhibite monocrotaline induced pulmonary hypertension in rats.
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In recent years, the importance of tyrosine phosphorylation in the nervous system of mammalian is gaining recognition. Tyros ine protein kinases exert important modulatory effect on the proliferation, diff erentiation, migration and metabolism-related singal transduction pathways in c ells. In this paper we reviewed the signal cascade process of three different ty rosine protein kinase families, including Trk, Src and Eph tyrosine protein kina se families. Furthermore, we discussed important role and possible mechanisms of these tyrosine protein kinases on the neuron synapse plasticity and learning an d memory process.
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The fifth muscarinic receptor (M5), the last one of the mus ca rinic receptor family to be cloned, has the same basic formation characterizatio n as G-protein coupled receptor family. M5 transduces signals by coupling with G-proteins, which then modulate the activities of a number of effector enzymes and ion channels. As M5 also plays a variety of prominent physiological roles by regulating central transmitters NO and DA, it has been considered as a novel dr ug therapy target for drug addiction, dysfunction of dopamine-ergic nervous sys tem, Alzheimers disease and cerebral ischemia.
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AIM To evaluate the antagonizing activity of iQWcF, a modified tripeptide, to endothelin receptors. METHORDS ①Vasoconstriction experiments with aorta strips of rats. ② In vivo experiments:male normotensive Wistar rats were anesthetized with pentobarbital Na (50 mg?kg -1 ),and catheterized into the carotic artery for measurement of blood pressure, and into the femoral vein for administration of iQWcF (30 mg?kg -1 ) and ET 1(0 9 nmol?kg -1 ). The test compound was given intravenously 5 min before the bolus injection of ET 1. Control animals received saline on the same time schedule.The blood pressure was recorded at different time interval after injecting ET 1. RESULTS ①iQWcF prohibited the vascontriction of aorta induced by ET 1 in a concentration dependent fashion.②The compound(30 mg?kg -1 .iv) markedly antagonized ET 1 induced the long lasting pressor phase mediated by ET A without affecting early transient depressor phase by ET B. CONCLUSION iQWcF is one of ET A selective antagonists.