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@#Due to the complex components of polysorbate 80, analysis is time-consuming and labor-intensive, so there is an urgent need to find a method for rapid analysis of polysorbate 80 components.In this study, 10 batches of samples collected from 3 domestic and foreign enterprises were analyzed by UHPLC-HRMS, with the being further results were analyzed by the ExcipientProfiler software and supplemented by the extended database.The results showed that the ExcipientProfiler software could quickly identify the [M+Na]+ peak in the mass spectrogram, and obtain the information of component distribution, the numbers of components and the degree of polymerization of the sample.Meanwhile, the numbers of components obtained by the ExcipientProfiler software could be used to distinguish the injection grade samples from the ordinary grade samples by systematic clustering analysis.In addition, it was found through further supplement that the sample contained other fatty acid ester components by manually searching the relevant extended database.The polyoxyethylene sorbitan tetraoleate components were found in the sample according to the analysis of mass spectrum data.Therefore, although this method is fast and simple, it is necessary to add polyoxyethylene sorbitan tetraoleate components and other fatty acid ester components to further supplement the information in the ExcipientProfiler software, so that it can be better used for the analysis of polysorbate 80.
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Hepatocellular carcinoma has a high morbidity and mortality, which has seriously harmed human health. Several targeted therapies have been approved for the first- and second-line treatment of advanced hepatocellular carcinoma. The emergence of immunotherapy has brought the treatment of hepatocellular carcinoma into a new era. Targeted and immunotherapeutic agents have synergistic effects in mechanism, also the combination of these two therapies has been clinically beneficial to patients with advanced hepatocellular carcinoma. At the same time, in addition to the systemic therapy of targeted combined immunological, applying appropriate local therapy can provide a longer survival period or even a chance of cure for that some patients. The authors introduce the diagnosis and treatment of a case of advanced hepatocellular carcinoma who achieved pathological complete remission by first-line immunotherapy combined with anti-angiogenesis targeted therapy.
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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs. .
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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.
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Protein kinase B( Akt)is an intermediate signal molecule in PI3K-Akt-mTOR signaling pathway which plays an important role in development and incidence of colorectal cancer when activated by phosphorylation. As target of drugs,Akt has become a focus in the treatment of colorectal cancer. Clinical trials research proves that many kinds of Akt inhibitors have good antitumor activity. In recent years,the Akt inhibi-tors are more and more be taken seriously in colorectal cancer treatment.
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Total mRNA was extracted from lymphocytes separated from the peripheral blood of allergic patients, and then variable region of heavy chain (VH) and variable region of light chain (VL) cDNA library were constructed by RT-PCR. Human scFv templates for rabbit reticulocyte lysate ribosome display were assembled by primers and linker peptide (Gly4Ser)3. mRNA bound in antibody-ribosome-mRNA complexes was recovered using in-situ single primer RT-PCR, and three rounds of anti-IgE scFv DNA were enriched. The target DNA fragments were double enzyme digested and ligated into plasmid pET22b (+), followed by transformation in E. coli Rosseta (DE3). Positive clones were screened using clone PCR, Dot blotting and antigen ELISA. The correct lengths of VH (400 bp) and VL (710 bp) PCR products were obtained. The expected 1,000 bp ribosome display templates were also observed in agarose gel electrophoresis. After three rounds of ribosome display target sequences were effectively enriched, leading to a library of 10(13) members. Antibodies with the highest ELISA value for IgE were generated in the strain pET-IgE-6. A human anti-IgE scFv library was successfully constructed as described herein. Ribosome display using single primer in-situ RT-PCR as the recovery procedure effectively enriched target sequences. Anti-IgE scFv with high affinity and specificity were identified. The prepared human anti-IgE scFv fragment might be self-developed to a lead drug for treating asthma. Our study provides an alternative method for rapid discovery of human antibodies of therapeutic importance.
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The prognosis in patients with cerebral hemorrhage is poor. Studies have shown that cerebral microbleeds are closely related with intracerebral hemorrhage. Cerebral microbleeds may be a precursor to the occurrence or recurrence of intracerebral hemorrhage. This article reviews the relationship between cerebral microbleeds and intracerebral hemorrhage from the aspects of epidemiology, etiology, pathophysiology, clinical observation, and complications of cerebral hemorrhage.
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In order to observe the therapeutic effect of acupuncture plus facial paralysis rehabilitative exercise in the treatment of facial paralysis, 49 cases were treated by acupuncture plus facial paralysis rehabilitative exercise, and 45 cases were treated by single acupuncture for comparison. The total effective rate was 91.8% in the former and 62.2% in the latter. There is a significant difference (P ＜ 0.01) in the effective rate between the two groups.
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0.05,group 1 or group 2 vs group 3 P
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Objective: To study the influence of repeated firings on the PFM bond strength. Methods: 25 specimens of PFM in the diameter of 13.0 mm and thickness of (1.0?0.02) mm were prepared and fired at 920 ℃ for 1, 3, 5, 7 or 9 times(5 samples for each time). The remained porcelain rate(RPR) was measured by Mackert method and used to evaluate the bond strength.Results: After 3 firings, the RPR of PFM decreased obviously, and additional firings had no obvious effect on the RPR. Conclusion: 3 times firing or more may decrease the bond strength of PFM.
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0.05).Meanwhile,the percentage of elongation increased following each recasting(P
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s〕 Objective:To investigate the influence of repeated firings on the color of porcelain fused to metal crown(PFM) . Methods: 5 PFM samples were prepared and fired for 9 times.The color of the samples was measured following firing with CIE1976 L*a*b* color system . The color difference ?E ab *,hue angle h ab * and chroma C ab * were calculated according to the following calculations:?E ab * ={(?L*) 2 +(?a*) 2 +(?b*) 2} 1/2 , C ab * ={(a*) 2+(b*) 2} 1/2 , h ab *=tg 1 b*/ a*, L* presented brightness. Results: After repeated firing, L* value of PFM , C ab * and L* value of dentin layer and h ab * value of opaque layer increased. Conclusion: The color of PFM after repeated firing may become brighter. The color change is resulted from the increase of L* and C ab * of dentin layer.
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To reverse drug resistance mediated by the MDR1 gene product P-glycoprotein(P-gp) in tumor cells in a specific manner, a hammerhead ribozymes which can cleave the GUC sequence in codon 196 of MDR1 mRNA was designed and cloned into a recombinant retroviral vector pDOR-neo at BamH I restriction sites and packaged with packaging cell line PA317 cells.The viral supernatant was used to infect the multidrug-resistant human hepatocarcinoma cell line BEL-7402/DOX. After selection with G418,resistant colonies were obtained.Stable expression of retroviruses in both PA317 and infected BEL-7402/DOX cells was confirmed by Northern Blot hybridization. Down-regulation of P-gp and even of MDR1 mRNA was found in BEL-7402/DOX infected with ribozyme construct. The rate of BEL - 7402/DOX infected cell defected by flow cytometric analysis was 8.2 ~ 14.6% while in uninfected cell it was 93 .4 ~ 97.5% . The BEL-7402/ DOX cell infected with ribozyme construct was found back to drug-sensitivity to a series of drugs by MTT colorimetric assay . The results demonstrated that the recombinant retroviral vector expressing ribozyme transfecting human hepatocarcinoma BEL-7402/DOX could inhibit MDR1 gene expression and reverse tumor MDR phenotype back to drug-sensitive condition.
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This paper deals with the regularity of the changes in 'serum specific IgM and IgG, and the relationship between the antibody level and infected worm stage of Brugia malayi.The jirds (Meriones unguiculatus) and BALB/cCR mice infected with three different methods were used in the experiment.The antibody level in BALB/cCR mice after infection was higher than that in jirds.The occurrence of IgM in infected jirds and mice was earlier than that of IgG,reached its peak at 4-8th week, and maintained a certain level during 30 weeks.The responses of IgM and IgG were considered as an immunological characteristic of parasitic helminth infection probably.