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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. In recent years, with the rapid development of immunotherapy, checkpoint inhibitors, especially programmed death factor-1 (PD-1)/programmed death factor ligand-1 (PD-L1) inhibitors, have made breakthrough progress in the treatment of NSCLC, breaking the pattern of low efficiency and extensive resistance to targeted therapy of traditional chemoradiotherapy, bringing survival benefits to patients. This article reviews the clinical research progress of PD-1/PD-L1 inhibitors in advanced NSCLC.
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Heat shock protein A9 (HSPA9), a member of the heat shock protein family, is a putative receptor for Tembusu virus (TMUV). By using Western blot and co-immunoprecipitation assays, E protein domains I and II were identified as the functional domains that facilitate HSPA9 binding. Twenty-five overlapping peptides covering domain I and domain II sequences were synthesized and analyzed by using an HSPA9 binding assay. Two peptides showed the capability of binding to HSPA9. Dot blot assay of truncated peptides indicated that amino acid residues 19 to 22 and 245 to 252 of E protein constitute the minimal motifs required for TMUV binding to HSPA9. Importantly, peptides harboring those two minimal motifs could effectively inhibit TMUV infection. Our results provide insight into TMUV-receptor interaction, thereby creating opportunities for elucidating the mechanism of TMUV entry.
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Humans , Blotting, Western , Heat-Shock Proteins , Hot Temperature , Immunoprecipitation , Peptides , Protein Structure, TertiaryABSTRACT
Objective To examine the stability of high-density lipoprotein cholesterol (HDL-C)during serum incubation at different temperature and time periods.Methods Ten healthy volunteers (4 males and 6 females,aged 24 to 59 years)from Beijing Hospital were recruited in May 2015.Fasting venous blood samples were collected and centrifuged to separate the sera.Serum samples were incubated at 4℃ for 24 h,25℃for 0,1,8 and 24 h (with or without an LCAT inhibitor).Serum to-tal cholesterol (TC),total free cholesterol (TFC)HDL-C and HDL-FC were measured by the HPLC Method.Results HDL-FC and HDL-C changed -6.91% and -2.17% during serum incubation at 4℃for 24h.TFC,HDL-FC and HDL-C changed significantly (averaged -13.70%,-25.88% and -1.53% respectively)during serum incubation at 25℃ for 24 h,in which the decrease of TFC and HDL-FC were inhibited by the addition of the LCAT inhibitor.The decrease of HDL-C was even higher in the presence of the LCAT inhibitor.Conclusion Serum TFC,HDL-C and HDL-FC levels changed during serum incubations,which were caused by the LCAT and CETP activities and the transfer of cholesterol among lipoproteins. For accurate measurement of serum HDL-C,prolonged serum storage should be avoided in clinical laboratories.
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Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. vaccae Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. vaccae BCG revealed that M. vaccae was more malignant than M. vaccae in mice. We also demonstrated that serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺ cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.
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Animals , Mice , Bacillus , Bacteria , Chemokine CCL2 , Flow Cytometry , Injections, Intraperitoneal , Interferon-gamma , Interleukin-10 , Interleukin-12 , Interleukins , Lymph Nodes , Mycobacterium bovis , Mycobacterium , Pathology , Transforming Growth Factor beta , Tumor Necrosis Factor-alphaABSTRACT
Objective To evaluate the efficacy of first-line CHOP or CHOP-like regimen on patients with advanced staged angioimmunoblastic T-cell lymphoma (AITL).Methods Between Aug 2006 and Sep 2014,twenty-nine AITL patients who were newly diagnosed without prior treatment were included in study.The clinical features,efficacy and survival were analyzed retrospectively.Results Median age of these patients was 59 years old.All patients had stage Ⅲ/Ⅳ disease.17 (58.6 %) cases presented with B symptoms.26 (89.7 %) cases had an international prognostic index (IPI) score ≥2,and 20 (69.0 %) cases had elevated LDH,9 (31.0 %) cases had ≥2 extranodal involvements.The median follow-up time was 20 months.Overall response rate was 69.0 % (20/29).Five (17.2 %) patients achieved complete remission (CR+CRu),15 (51.7 %) patients achieved partial remission,and 3 (10.3 %) patients had stable disease (SD),6 (20.7 %) patients had progressive diseases(PD).Median progression-free survival (PFS) was 6 months.1-and 2-year PFS rates were 39.0 % and 20.0 %.1-,2-and 5-year overall survival (OS) rates for all patients were 76.8 %,53.4 % and 17.1%,respectively.PFS was significantly better in chemotherapy-sensitive patients (P < 0.001).The responses to chemotherapy had a tendency of affecting the OS,but it failed to reach statistical significance (P > 0.05).Conclusions The CHOP or CHOP-like regimen maybe induce unfavorable efficacy in AITL patients.Further therapeutic options are required to improve the outcome.
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A total of 101 patients undergoing operations for malignant gastrointestinal tumors (stage Ⅱ to Ⅲ) were enrolled and randomly assigned to receive intraperitoneal hyperthermal chemotherapy plus intravenous chemical injection (treatment group, n=51) or routine intravenous chemical injection (control group, n=50). Our results indicated that the recurrence rate and the metastatic rate in the treatment group were significantly lower than those in the control group (25.5% vs. 50.0%, 13.7% vs. 30.0%, both P< 0. 05), although the 3-and 5 year-survival rates were significantly higher (both P < 0. 05). Our data suggest that intraperitaneal hyperthermal chemotherapy plus general chemotherapy after surgery for malignant gastrointestinal tumors could effectively reduce tumor recurrence and metastases and improve long-term survival.
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Sixty-one patients with moderate to severe malignant ascites were enrolled and randomly assigned to receive intraperitoneal hyperthermal chemotherapy+intravenous chemical injection (treatment group; n=31) or routine intravenous chemical injection (control group; n=30). Short-term response and reverse effects were observed. Our results indicated that the complete remission rate, part remission rate,and clinical benefit rate in the treatment group was significantly higher than those in the control group (38.71% vs 13.33% ,41.94% vs 16. 67%, and 90.32% vs 66.67%, respectively). No difference in reverse effects was found between the two groups. Our data suggest that intraperitoneal hyperthermal chemotherapy plus general chemotherapy may effectively control the malignant ascites, and the reverse effects might be well tolerated.
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0. 05) while UDS was induced by Polygala tenyi folia willd with various doses comparing with normal control. Nevertheless, Polygala tenyi folia willd in doses ranged from 1. 0 to 4. 0 g ? kg-1 inhibited strikingly UDS induced by Pb (CH3COO)2 (P
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Objective To study the effect of anti-mutation of Chinese medicinal herb Poly gala tenui folia willd on T lymphocyte proliferation in spleen. Methods The micronucleus test of mouse bone marrow cell (MNT): thirty mice were divided into six groups (n = 5) , negative control (NS) , cyclophosphamide group (CP 3. 0 mg ? kg-1) , Poly gala tenui folia willd antimutagenesis groups (Polygala tenui folia willd with dosage of 0.5, 1.0. 2.0, 4.0 g ? kg-1 + CP 30 mg ? kg-1 ). The improved method was used to detect the micro-nuclei frequency. Lymphocyte transformation test: twenty-four mice were divided into four groups (n = 6), saline control , CP control (3.0 mg ? kg-1), Polygala tenui folia willd (2.0 g ? kg-1), Polygala tenui folia willd + CP (2. 0 g ? kg-1 Polygala tenuifolia willd + CP 30 mg ? kg- ) group. MTT assay was used to calculate the stimulation index (SI). Results The micro-nuclei frequency was significant difference between Poly gala tenui folia willd antimutagenesis groups and CP groups (P
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Objective To survey the prevalence of greenhouse farmer's lung and related risk factors in part of rural areas of Liaoning Province.Methods Using uniform scheme,procedures and questionnaire,a survey for 5420 farmers(2660 men and 2760 women)with complete data who work inside greenhouses was performed in Shenyang,Xinmin,Chaoyang,and Jinzhou between August 2006 and June 2009.Pulmonary function tests was performed for every active farmer.Results Greenhouse farmer's lung was diagnosed in 308 cases,205 men(66.55%,205/308)and 103 women(33.44%,103/308),a prevalence of 5.7%(308/5420).The prevalence rate of greenhouse farmer's lung in males was significantly higher than that in females(?2=39.93,P0.05).In the 308 cases,the number of patiernts presented with fever chill,cough/sputum,chest tightness/shortness of breath were 180(58.44%),192(62.34%),160(51.95%)respectively,and the number of crepitations,radiological changes,spirometry abnormalities and serum IgE antibodies(+)was 164(53.25%),153(49.68%),147(47.73%)and 136(44.16%)at the time of the study.62.34%(192/308)of patients with greenhouse farmer's lung were mild and 38.66%(116/308)were severe.Conclusion The total prevalence rate of greenhouse farmer's lung in part of rural areas of Liaoning Province was 5.7% and multiple risk factors were associated with the disease.