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INTRODUCTION: Hyperglycaemia induces the production of a large quantity of reactive oxygen species (ROS) and activates the transforming growth factor ß1 (TGF-ß1)/Smad signalling pathway, which is the main initiating factor in the formation of diabetic nephropathy. Indoxyl sulphate (IS) is a protein-binding gut-derived uraemic toxin that localizes to podocytes, induces oxidative stress, and inflames podocytes. The involvement of podocyte damage in diabetic nephropathy through the TGF-ß1 signalling pathway is still unclear. METHODS: In this study, we cultured differentiated rat podocytes in vitro and measured the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, and α-SMA by quantitative real-time PCR (qRT-PCR) and Western blotting after siRNA-mediated TGF-ß1 silencing, TGF-ß1 overexpression, and the presence of the ROS inhibitor acetylcysteine. We detected the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, small mother against decapentaplegic (Smad)2/3, phosphorylated-Smad2/3 (p-Smad2/3), Smad7, NADPH oxidase 4 (NOX4), and ROS levels under high glucose (HG) and IS conditions. RESULTS: The results indicated that nephrin, synaptopodin, CD2AP, and SRGAP2a expressions were significantly upregulated, and α-SMA expression was significantly downregulated in the presence of HG under siRNA-mediated TGF-ß1 silencing or after the addition of acetylcysteine. However, in the presence of HG, the expressions of nephrin, synaptopodin, CD2AP, and SRGAP2a were significantly downregulated, and the expression of α-SMA was significantly upregulated with the overexpression of TGF-ß1. IS supplementation under HG conditions further significantly reduced the expressions of nephrin, synaptopodin, CD2AP, and SRGAP2a; altered the expressions of Smad2/3, p-Smad2/3, Smad7, and NOX4; and increased ROS production in podocytes. CONCLUSION: This study suggests that IS may modulate the expression of nephrin, synaptopodin, CD2AP, and SRGAP2a by regulating the ROS and TGF-ß1/Smad signalling pathways, providing new theoretical support for the treatment of diabetic nephropathy.
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Nefropatías Diabéticas , Indicán , Podocitos , Especies Reactivas de Oxígeno , Transducción de Señal , Factor de Crecimiento Transformador beta1 , Indicán/toxicidad , Indicán/farmacología , Podocitos/metabolismo , Podocitos/patología , Animales , Ratas , Especies Reactivas de Oxígeno/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Proteínas Smad/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas de Microfilamentos/metabolismo , Células Cultivadas , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/genéticaRESUMEN
BACKGROUND: Specific tumor markers have yet to be identified in rectal cancer. This study aims to identify a novel genetic signature in rectal cancer to provide clues for survival and immunotherapy. METHODS: DEGs were obtained from two GEO datasets of rectal cancer. By using data from TCGA and GSE133057, two cohorts of rectal cancer were applied to establish and evaluate the signature. A nomogram was constructed for training and validation. We integrated the risk-score with clinicopathological features and assessed its interplay with immune cells and molecules. Finally, our study performed functional annotations, gene-targeted miRNAs, and single-cell analysis. RESULTS: A total of 468 DEGs were identified, and a signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected to calculate the risk-score. The model exhibited high performance in time-dependent ROC and a nomogram. Further results showed that overall survival was significantly worse in the high-risk group. As an independent prognostic factor, the risk-score was associated with vascular invasion. There was a dramatic difference in nonregulatory CD4+ and CD8+ T cells between the high and low-risk groups, and the 5 genes were correlated with immune inhibitors. There was a considerable difference in autophagy, immune, cell cycle, infection, and apoptosis-associated terms and pathways in GO and KEGG. The functional states of differentiation, apoptosis, and quiescence were closely related to the 5-gene signature in single-cell analysis. CONCLUSION: Our results suggest that the signature could serve as a novel prognostic biomarker in rectal cancer, which might benefit decision-making regarding immunotherapy.
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BACKGROUND: The aim of this study was to investigate the infection and antimicrobial resistance of Ureaplasma urealyticum (U. urealyticum) and Mycoplasma hominis (M. hominis) in patients with genital tract diseases in Jiangsu, China. METHODS: A total of 3,321 patients suspected with genital tract infectious diseases were enrolled in this study from September 2017 to September 2020. The Mycoplasma detection and antimicrobial susceptibility were tested using the commercially available Mycoplasma kit. RESULTS: Among the 3,321 specimens tested, 1,503 (45.3%) were positive for Mycoplasmas, and the proportion of mono-infection of U. urealyticum is highest (79.5%). The overall infection rate has been increasing in the past 3 years. The positive rate in females (68.7%) was higher than in males (25.0%), and the main infection age group was 20 - 39 (81.2%). Besides, U. urealyticum and M. hominis displayed relative lower resistance rates to gatifloxacin, josamycin, minocycline, and doxycycline (6.0%, 6.5%, 3.1%, and 3.2%, respectively). However, the antimicrobial resistance rates to azithromycin, clindamycin, roxithromycin, sparfloxacin, and ofloxacin were relatively high (45.4%, 42.1%, 34.9, 36.0, and 65.5%, respectively). Antimicrobial resistance of U. urealyticum and M. hominis to these 14 drugs have been changing in the past 3 years. CONCLUSIONS: In total, these preliminary data showed the prevalence and antimicrobial resistance status of U. urealyticum and M. hominis in patients suspected with genital tract infectious diseases, which has use for reference on both prevention and treatment of diseases caused by them.
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Enfermedades Transmisibles , Infecciones por Mycoplasma , Mycoplasma , Infecciones del Sistema Genital , Infecciones por Ureaplasma , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Infecciones por Mycoplasma/tratamiento farmacológico , Infecciones por Mycoplasma/epidemiología , Mycoplasma hominis , Prevalencia , Infecciones del Sistema Genital/tratamiento farmacológico , Infecciones del Sistema Genital/epidemiología , Infecciones por Ureaplasma/diagnóstico , Infecciones por Ureaplasma/tratamiento farmacológico , Infecciones por Ureaplasma/epidemiología , Ureaplasma urealyticumRESUMEN
Vascular calcification (VC), in which vascular smooth muscle cells (VSMCs) undergo differentiation and osteogenic transition, is a common complication of chronic kidney disease (CKD). Recent findings show that nuclear factor-erythroid-2-related factor 2 (NRF2) is an evolutionarily conserved antioxidant and beneficial in preventing vascular senescence and calcification. The roles of NRF2 in the initiation and progression of VC in CKD still need further investigation. CKD-associated VC model rats exhibited significant upregulation of NRF2, NAD(P)H: quinone oxidoreductase-1 (NQO1), osteogenic markers such as alkaline phosphatase (ALP), runt-related transcription factor-2 (RUNX2) and osteopontin (OPN), and ß-catenin compared to CKD rats. Immunohistochemistry further verified these results. In addition, rat aortic VSMCs were isolated and subjected to four treatments: normal control, phosphorus-induced (Pi), Pi + NRF2 activator DMF, and Pi + NRF2 inhibitor ML385. The reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, and calcium deposition of the four treatments were determined. The mRNA and protein expression levels of NRF2, NQO1, and haem oxygenase 1 (HO1) and the osteogenic markers ALP, Runx1, OPN, bone morphogenetic protein 2 (BMP2), and ß-catenin were quantified by RT-PCR and western blotting. VSMC apoptosis was calculated by flow cytometry. The in vitro results suggested that intracellular oxidative stress and calcification were closely associated with NRF2 activity and that the activation of NRF2 could significantly suppress osteogenic transition and apoptosis in VSMCs. Thus, this study indicated that the NRF2-related antioxidant pathway can positively respond to and protect against the initiation and progression of VC in CKD by reducing oxidative stress. This study may contribute insights facilitating the application of the NRF2 antioxidative system as a therapeutic treatment for vascular diseases such as CKD.
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Antioxidantes/metabolismo , Aorta/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Insuficiencia Renal Crónica/metabolismo , Transducción de Señal , Calcificación Vascular/metabolismo , Animales , Antígenos de Diferenciación/biosíntesis , Modelos Animales de Enfermedad , Hemo Oxigenasa (Desciclizante)/biosíntesis , Masculino , NAD(P)H Deshidrogenasa (Quinona)/biosíntesis , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To investigate the safety and efficacy of regional citrate anticoagulation (RCA) on elderly patients at high risk of bleeding after continuous renal replacement therapy (CRRT). METHODS: A total of 31 patients at high risk of bleeding who received CRRT in the intensive care unit were collected. The patients were divided into RCA group (n = 17) and no anticoagulation group (NA, n = 14) according to whether RCA was used or not. The levels of creatinine (Cr), blood urea nitrogen (BUN), prothrombin time (PT), activated partial thromboplastin time (APTT), total calcium (tCa), ionized calcium ion (iCa2+), sodium ion (Na+), bicarbonate ion (HCO3-), tCa/iCa2+ ratio, and pH were observed after treatment. The filter use time, number of filters used, filter obstruction events, clinical outcomes, and safety evaluation indexes were compared post-treatment. RESULTS: After treatment, serum Cr and BUN levels, APTT and PT levels in the RCA group were significantly lower than the NA group. The tCa, iCa2+, HCO3-, tCa/iCa2+, and pH were within the normal range after RCA treatment while Na+ levels saw a significant increase. In the RCA group, the filter using time was significantly longer, with significantly reduced numbers of filter use within 72â h and filter disorder events. Additionally, patients in the RCA group showed significant recovery of renal function and a significant reduction in bleeding events and in-hospital mortality. CONCLUSION: RCA treatment significantly improves clinical outcome of patients at high risk of bleeding after CRRT, safely and effectively prolongs the filter life and avoids coagulation incidences.
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Anticoagulantes/uso terapéutico , Coagulación Sanguínea/fisiología , Terapia de Reemplazo Renal Continuo/métodos , Hemorragia/tratamiento farmacológico , Citrato de Sodio/metabolismo , Anciano , Anticoagulantes/farmacología , Femenino , Hemorragia/patología , Humanos , Masculino , Estudios Prospectivos , Factores de RiesgoRESUMEN
Objective: To investigate the inhibitory effect on Burkholderia pseudomallei (B. pseudomallei) strain HNBP001 of a bacillomycin D-like cyclic lipopeptide compound named bacillomycin DC isolated from Bacillus amyloliquefaciens HAB-2. Methods: The antibacterial effect of bacillomycin DC on B. pseudomallei was determined using the disk diffusion method. The minimum inhibitory concentrations were evaluated by microdilution assay. In addition, transmission electron microscopy was performed and quantitative real-time polymerase chain reaction assay was carried out to determine the expression of MexB, OprD2, and qnrS genes. Results: Bacillomycin DC produced an inhibition zone against B. pseudomallei with minimum inhibitory concentration values of 12.5 μg/mL 24 h after treatment and 50 μg/mL at 48 and 72 h. Transmission electron microscopy showed that bacillomycin DC resulted in roughening cell surface and cell membrane damage. Quantitative real-time polymerase chain reaction analysis showed low expression of MexB, OprD2 and qnrS genes. Conclusions: Bacillomycin DC inhibits the growth of B. pseudomallei and can be a new candidate for antimicrobial agents of B. pseudomallei.
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Objective To evaluate the efficacy of low frequency pulsed electromagnetic field (LFPEMF) on peritumoral edema in patients with glioma, providing a theoretical basis for clinical treatment of peritumoral edema. Methods This study included 32 patients with recurrent cerebral glioma with peritumoral edema after the operation of glioma in department of glioma, Beijing Shijitan Hospital, Capital Medical University from March 2017 to December 2018.The period of LFPEMF treatment was 10-14 days.The clinical symptoms related to brain edema were recorded before and after treatment.The National Institutes of Health Stroke Scale (National Institute of health stroke scale, NIHSS), Karnofsky quality of life score (KPS), brain edema and tumor range in cranial MRI, T lymphocyte subgroup CD4+/CD8+, superoxide dismutase (SOD) were recorded.The SPSS21.0 statistical analysis software was used to carry out analysis by using self controlled study.P < 0.05 was statistically significant. Results After the treatment of LFPEMF, the results showed that LFPEMF was effective in 25 patients, invalid in 7 patients, and the total effective percentage was 78.13%.The area of brain edema was significantly improved after using LFPEMF(P < 0.05).There was no significant improvement in the area of brain tumor after using LFPEMF therapy (P>0.05).KPS and NIHSS scores improved significantly after using LFPEMF (P < 0.05). Conclusion In the patients with peritumoral edema of glioma, the application of LFPEMF in the patients′ Yongquan point and Lao Gong point can reduce peritumoral edema, and improve clinical symptoms.
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Objective To evaluate the efficacy of low frequency pulsed electromagnetic field (LFPEMF) on peritumoral edema in patients with glioma, providing a theoretical basis for clinical treatment of peritumoral edema. Methods This study included 32 patients with recurrent cerebral glioma with peritumoral edema after the operation of glioma in department of glioma, Beijing Shijitan Hospital, Capital Medical University from March 2017 to December 2018.The period of LFPEMF treatment was 10-14 days.The clinical symptoms related to brain edema were recorded before and after treatment.The National Institutes of Health Stroke Scale (National Institute of health stroke scale, NIHSS), Karnofsky quality of life score (KPS), brain edema and tumor range in cranial MRI, T lymphocyte subgroup CD4+/CD8+, superoxide dismutase (SOD) were recorded.The SPSS21.0 statistical analysis software was used to carry out analysis by using self controlled study.P < 0.05 was statistically significant. Results After the treatment of LFPEMF, the results showed that LFPEMF was effective in 25 patients, invalid in 7 patients, and the total effective percentage was 78.13%.The area of brain edema was significantly improved after using LFPEMF(P < 0.05).There was no significant improvement in the area of brain tumor after using LFPEMF therapy (P>0.05).KPS and NIHSS scores improved significantly after using LFPEMF (P < 0.05). Conclusion In the patients with peritumoral edema of glioma, the application of LFPEMF in the patients′ Yongquan point and Lao Gong point can reduce peritumoral edema, and improve clinical symptoms.
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Objective: To investigate the inhibitory effect on Burkholderia pseudomallei (B. pseudomallei) strain HNBP001 of a bacillomycin D-like cyclic lipopeptide compound named bacillomycin DC isolated from Bacillus amyloliquefaciens HAB-2. Methods: The antibacterial effect of bacillomycin DC on B. pseudomallei was determined using the disk diffusion method. The minimum inhibitory concentrations were evaluated by microdilution assay. In addition, transmission electron microscopy was performed and quantitative real-time polymerase chain reaction assay was carried out to determine the expression of MexB, OprD2, and qnrS genes. Results: Bacillomycin DC produced an inhibition zone against B. pseudomallei with minimum inhibitory concentration values of 12.5 μg/mL 24 h after treatment and 50 μg/mL at 48 and 72 h. Transmission electron microscopy showed that bacillomycin DC resulted in roughening cell surface and cell membrane damage. Quantitative real-time polymerase chain reaction analysis showed low expression of MexB, OprD2 and qnrS genes. Conclusions: Bacillomycin DC inhibits the growth of B. pseudomallei and can be a new candidate for antimicrobial agents of B. pseudomallei. Rajaofera Mamy 1 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Kang Xun 2 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Jin Peng-Fei 3 Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests (Hainan University), Ministry of Education, Haikou 570228, Hainan Chen Xin 4 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Li Chen-Chu 5 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Yin Li 6 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Liu Lin 7 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Sun Qing-Hui 8 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Zhang Nan 9 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Chen Chui-Zhe 10 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan He Na 11 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Xia Qian-Feng 12 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Miao Wei-Guo 13 Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests (Hainan University), Ministry of Education, Haikou 570228, Hainan Kung CT, Lee CH, Li CJ, Lu HI, Ko SF, Liu JW. 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Serra C, Bouharkat B, Tir Touil-Meddah A, Guénin S, Mullié C. MexXY multidrug efflux system is more frequently overexpressed in ciprofloxacin resistant french clinical isolates compared to hospital environment ones. Front Microbiol 2019; 10: 366. Cai S, Chen Y, Song D, Kong J, Wu Y, Lu H. Study on the resistance mechanism via outer membrane protein OprD2 and metal ß-lactamase expression in the cell wall of Pseudomonas aeruginosa. Exp Ther Med 2016; 12(5): 2869-2872. Kamjumphol W, Chareonsudjai P, Chareonsudjai S. Antibacterial activity of chitosan against Burkholderia pseudomallei. Microbiologyopen 2018; 7(1). Doi: 10.1002/mbo3.534 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-AAC) method. Methods 2001; 25(4): 402-408. Baindara P, Mandal SM, Chawla N, Singh PK, Pinnaka AK, Korpole S. 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Antibiotic-resistant Escherichia coli bacteria, including strains with genes encoding the extended-spectrum beta-lactamase and QnrS, in waterbirds on the Baltic Sea Coast of Poland. Appl Environ Microb 2010; 76(24): 8126-8134. Wang J, Zhang X, Sun G, Wang Q, Lu L, Feng X, et al. Utility of multiple-locus variant-repeat analysis method for the outbreak of the Pseudomonas aeruginosa isolates. Clin Lab 2014; 60(7): 1217-1223. El-Badawy MF, Alrobaian MM, Shohayeb MM, Abdelwahab SF. Investigation of six plasmid-mediated quinolone resistance genes among clinical isolates of pseudomonas: A genotypic study in Saudi Arabia. Infect Drug Resist 2019; 12: 915-923. Martín-Gutiérrez G, Rodríguez-Martínez JM, Pascual Á, Rodríguez-Beltrán J, Blázquez J. Plasmidic qnr genes confer clinical resistance to ciprofloxacin under urinary tract physiological conditions. Antimicrob Agents Chemother 2017; 61(4): e02615-e02616. Paiva MC, Reis MP, Costa PS, Dias MF, Bleicher L, Scholte LLS, et al. 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Objective: To perform a retrospective analysis of the prognosis and influence factors of radiotherapy concurrent with che-motherapy and adjuvant temozolomide therapy in adult patients with high-grade brainstem glioma. Methods: Twenty-nine patients with pathological diagnosis of high-grade glioma (World Health Organization [WHO] Ⅲ and Ⅳ) from June 2012 to December 2013 were eligible for inclusion in the analysis. Demographic and clinical characteristics including age, gender, the time from morbidity to operation, the size of the lesion, the method of operation, the Karnofsky Performance Status (KPS) score, and the pathological grade were examined. The significance of related prognostic factors was evaluated via univariate and multivariate Logistic regression analy-sis. A P-value of<0.05 was considered to be statistically significant. Results: The median overall survival (OS) was 11.5 months. Univari-ate analysis showed that low WHO grade index was associated with better outcome (P<0.05). Multivariate analysis suggested that high KPS score (>60) and low WHO grade were associated with better survival. Conclusions: In this study, low pathological grade and high KPS score were independently associated with better survival among patients with high-grade brainstem glioma.
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Background@#Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of highgrade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value.@*Methods@#During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data.@*Results@#The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence.@*Conclusions@#HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.
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BACKGROUND@#Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of high-grade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value.@*METHODS@#During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data.@*RESULTS@#The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence.@*CONCLUSIONS@#HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Glioma , Genética , Metabolismo , Mortalidad , Terapéutica , Inmunoterapia , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos T , Química , Genética , Factores de TiempoRESUMEN
BACKGROUND@#Non-small cell lung cancer (NSCLC) with neuroendocrine differentiation (NED) was a new pathologic type and uncommon in clinics. The aim of this study is to observe the relationship between clinical pathologic characteristics, imagination, biological behavior and prognosis in NSCLC-NED.@*METHODS@#The clinical data of 47 patients with NSCLC-NED admitted from January 2009 to November 2017 in the Fifth Medical Center of General Hospital of People's Liberation Army were collected. The demographic data and imaging characteristics were summarized. Pathological features, treatment and prognosis, analysis of the correlation between different factors and prognosis.@*RESULTS@#Of the 47 patients with NSCLC-NED, the median age was 61 years (45 years-78 years), 38 males and 9 females; 37 were poorly differentiated cancer with NED, and 10 were middle differentiated cancer with NED; 2 cases of driving gene positive (1 case of EGFR sensitive mutation, 1 case of ALK fusion), objective response rate (ORR) of first-line chemotherapy was 34.5%, and median progression-free survival (PFS) was 4 months; the median overall survival (OS) was 11 months, and only 2 cases (4.2%, 2/47) of OS were over 2 years.@*CONCLUSIONS@#NSCLC-NED is different from simple NSCLC or pulmonary neuroendocrine tumors. Males, ≤70 years old, severely smoking, and patients with lower tumor differentiation often have NED, and most of them are stage IV. This type of patient-driven gene positive proportion is lower than the general adenocarcinoma population, less sensitive to chemotherapy, and the overall survival is shorter, indicating a poor prognosis.
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BACKGROUND@#Anaplastic lymphoma kinase (ALK) positive in non-small cell lung cancer (NSCLC) was about 5%-7% and ALK tyrosine kinase inhibitor (TKI) was the standard treatment in NSCLC. The aim of this study is to evaluate the efficacy and safety of crizotinib in patients with advanced ALK gene-positive or recurrent NSCLC.@*METHODS@#Three methods were used to screen patients with advanced or recurrent NSCLC harboring ALK gene fusion/translocation. The patients with ALK positive tested by flourescence in situ hybridization (FISH) was given orally crizotinib, 250 mg, bid. The objective response rate (ORR), progression-free survival (PFS) and safety were evaluated.@*RESULTS@#A total of 226 patients were screened, 39 of whom had ALK fusion or translocation, and 37 were enrolled in the study. 35 patients were evaluated for objective response, ORR was 70.3%, and disease control rate (DCR) was 94.6%, and median PFS was 11.8 mon. The main adverse reactions were elevated transaminase (Grade 1, 91.7%), elevated transaminases (Grade 2, 23.4%), nausea (Grade 1, 75.6%), anemia (Grade 1-2, 62.3%), visual impairment (Grade 1, 21.8%), weight loss (Grade 1, 31.4%), pneumonia (Grade 2, 3.5%).@*CONCLUSIONS@#Crizotinib can be used for the treatment of advanced NSCLC with ALK fusion/translocation. It is highly effective and well tolerated.
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Background:Burkholderia pseudomallei (Bp) is a gram-negative environmental bacterium that causes melioidosis. It has high mortality and relapse rates regardless of powerful antibiotic therapy. Bacterial pathogens display versatile gene expression to adapt to changing surroundings, especially when they are infected by drugs. A cyclic lipopeptide was isolated from Bacillus amyloliquefaciens HAB-2, which is a bacillomycin D-like compound, named as bacillomycin DC. It is a potent fungicide against Colletotrichum gloeosporioides Penz.Methods:We used this kind of bacillomycin DC to be inhibitor of Bp and in order to find out how does it infect the bacterial pathogens. We observed the morphological changes under transmission electron microscope (TEM) and scanning electron microscopy (SEM) when BP is in the minimum inhibitory concentration (MIC) of ceftazidime and bacillomycin DC. Then we used quantificationgene Real-Time PCR (qRT-PCR) to measure the expression of three drug-assistant genes including MexB, qnrS and oprD2, respectively.Results:Bacillomycin DC treatment caused changes in the shape and microstructure, and the bacterial outer membrane were damaged, the leakage of the cell were observed. The expression level of mexb gene was not high until 72h after ceftazidime and bacillomycin DC treatment. Both ceftazidime and bacillomycin DC caused high expression of oprD2, but higher expression level proves that the DC works more efficiently and quickly. Bacillomycin DC increased the expresssion level of bacteria qnrS gene in 24 h, which proved this compound injured the DNA helicase and topoisomerase of the bacteria in a short time. The results showed that the bacillomycin DC had better inhibitory effects. We also found out that different mechanism of action between ceftazidime and bacillomycin DC.Conclusion:The bacillomycin DC makes bacterial pathogen display more oprD2 and qnrS, which respectively means bacterial pathogen are sensitive to the bacillomycin DC and its DNA gyrase are injured. In short, our study showed for the first time that bacillomycin DC can inhibit Bp in a short time.
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As a common primary intracranial tumor,malignant glioma accounts for 81% of all central nervous system malignancies.Af-ter standard treatment,such as surgery combined with external radiotherapy and chemotherapy,glioblastoma patients'survival is on-ly 14.4 months.Hence,the traditional treatment is difficult to meet patients'needs of survival and life quality.In recent years,chloro-genic acid(CGA),as plant extract polyphenols,has received widespread attention.Its antitumor properties,through its effects on the immune system,anti-oxidation properties,cell cycle regulation,and inhibition of tumor cell metastasis and invasion,have been exten-sively studied.This article will discuss the mechanisms involved in glioma treatment,synergism with other drugs,and metabolism in the human body,to provide a reference for the application of CGA in the treatment of the condition.
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Objective:To retrospectively analyze and summarize the clinical characteristics of 15 glioma cases that led to leptomenin-ges and spinal cord metastases in Department of Glioma, Beijing Shijitan Hospital, Capital Medical University since 2011. Methods:A total of 15 cases were considered, including 5 patients with World Health Organization gradeⅡ, 6 patients with gradeⅢ, and 4 pa-tients with gradeⅣ. One patient had a tumor at the brain stem, two patients had tumors at the spinal cords, and the other patients had tumors at the hemispheres. One case received biopsy, 4 cases received subtotal resection, and 10 cases received complete resec-tion. Results: Symptoms included low back pain, sensory and motor dysfunction, incontinence, and seizures. After the metastases spread to the cerebrospinal region, patients were treated with chemotherapy, whole spine radiotherapy, intrathecal chemotherapy, and target therapy. The median time of leptomeninges and spinal cord metastasis dissemination appearance was 10 months (1.5-80 months) since surgery. The median overall survival time of the 15 patients was 20 months (9-83 months), and the median survival time was 6 months (2-48 months) after leptomeninges and spinal cord metastases. Conclusion:The prognosis of glioma patients with lepto-meninges and spinal cord metastases was poor, and a proportion of the patients who received appropriate treatment might have a better survival.
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Coal resource is the main primary energy in our country, while Shanxi Province is the most important province in resource. Therefore Shanxi is an energy base for our country and has a great significance in energy strategy. However because of the heavy development of the coal resource, the ecological environment is worsening and the farmland is reducing continuously in Shanxi Province. How to resolve the contradiction between coal resource exploitation and environmental protection has become the imperative. Thus the concept of "green mining industry" is arousing more and more attention. In this assay, we will talk about the basic mode of land reclamation in mine area, the engineering study of mine land reclamation, the comprehensive model study of mine land reclamation, and the design and model of ecological agricultural reclamation in mining subsidence.
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Conservación de los Recursos Naturales , Minería , Agricultura , China , Ecología , Modelos TeóricosRESUMEN
Objective:The poor prognosis of patients with malignant gliomas (MG) has led to the search for new therapeutic strat-egies. Recently, nimotuzumab has been studied as a new anti-EGFR-receptor humanized monoclonal antibody in patients with MG, who showed improvement of outcome and good tolerability. We conducted phase I of our study to determine the toxicity, tolerated dose, and clinical feasibility of nimotuzumab in combination with concurrent chemoradiotherapy for Chinese MG patients after surgical resection. Methods:Patients with pathologically proven grades 3 and 4 glioma were enrolled in the study. The protocol included infu-sions of nimotuzumab plus standard Stupp schedule (postoperative radiotherapy in a total dose of 60 Gy in combination with daily te-mozolomide). Patients received 6 weekly infusions of nimotuzumab at three levels (100, 200, and 400 mg/week). If none of the first three patients enrolled at a dose level experienced dose-limiting toxicity (DLT), the dose was increased, as appropriate. If DLT was ob-served, another three patients were added to the dose level. Results:Nine patients with MG were enrolled, including 7 with grade 3 MG and 2 with glioblastoma. The treatment was well tolerated, and no evidence of grade 3 or 4 adverse events was detected, even at the highest level (400 mg/week). Grade 1 or 2 myelosuppression was the most common toxicity. Three months after treatment, stable dis-ease occurred in 5 patients, whereas progression disease was observed in 4 patients. Conclusion:Nimotuzumab combined with concur-rent chemoradiotherapy was associated with mild toxicity in Chinese MG patients.