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Objective:To investigate the clinical value of peripheral monocyte and neutrophil count in predicting the response of patients with metastatic non-small cell lung cancer (mNSCLC) to immunosuppressive checkpoint inhibitors (ICI).Methods:The clinical data of 34 adult mNSCLC patients who received nafulizumab or pabolizumab in Danzhou People's Hospital of Hainan Province from January 2017 to March 2019 were retrospectively analyzed. The correlation of the demographic characteristics, clinical data, hematological examination results in the first two weeks before the treatment and two weeks after ICI treatment with prognosis was recorded and observed.Results:The baseline mean monocyte count [(0.52±0.09)×10 9/L vs. (0.60±0.12)×10 9/L] and neutrophil count [(4.27±0.87)×10 9/L vs.(5.39±1.02)×10 9/L] of patients with ICI reaction were lower than those of patients without ICI reaction, and the differences were statistically different ( t = -2.572, -2.727, all P < 0.05). However, there was a negative correlation between the monocyte count of the patients who responded to ICI and the reaction time ( r = -0.507, P < 0.05). The median reaction time in patients with monocyte count >0.70×10 9/L was shorter than that in patients with monocyte count ≤0.70×10 9/L (8 weeks vs. 12 weeks, χ2=4.162, P = 0.041). There was no correlation between monocyte count and time of reaction duration, progression of free survival (PFS) and overall survival (OS) ( r = -0.214, 0.182, 0.232, all P > 0.05). The decrease rate of neutrophil count in response group was higher than that in non-response group (22% vs. 2%, P < 0.05). After the first administration, cutoff value of neutrophil count was 4.2×10 9/L; the response rate of patients with neutrophil count ≤ 4.2×10 9/L was higher than that of patients with neutrophil count > 4.2×10 9/L [86.7% (13/15) vs. 36.8% (7/19), χ2=6.657, P < 0.05]. Conclusion:Peripheral blood monocyte and neutrophil count can predict the response to ICI therapy in patients with mNSCLC.
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Aspergillus niger is a vital industrial workhouse widely used for the production of organic acids and industrial enzymes. This fungus is a crucial cell factory due to its innate tolerance to a diverse range of abiotic conditions, high production titres, robust growth during industrial scale fermentation, and status as a generally recognized as safe (GRAS) organism. Rapid development of synthetic biology and systems biology not only offer powerful approaches to unveil the molecular mechanisms of A. niger productivity, but also provide more new strategies to construct and optimize the A. niger cell factory. As a new generation of genome editing technology, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated (Cas) system brings a revolutionary breakthrough in targeted genome modification for A. niger. In this review, we focus on current advances to the CRISPR/Cas genome editing toolbox, its application on gene modification and gene expression regulation in this fungal. Moreover, the future directions of CRISPR/Cas genome editing in A. niger are highlighted.
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Aspergillus niger/genetics , CRISPR-Cas Systems/genetics , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Gene Editing , GenomeABSTRACT
In industrial biotechnology, microbial cell factories utilize renewable resources to produce energy, materials and chemicals. Industrial biotechnology plays an increasingly important role in solving the resource, energy and environmental problems. Systems biology has shed new light on industrial biotechnology, deepening our understanding of industrial microbial cell factories and their bioprocess from "Black-box" to "White-box". Systems-wide profiling of genome, transcriptome, proteome, metabolome, and fluxome has proven valuable to better unveil network operation and regulation on the genome scale. System biology has been successfully applied to create microbial cell factories for numerous products and derive attractive industrial processes, which has constantly expedited the development of industrial biotechnology. This review focused on the recent advance and applications of omics and trans-omics in industrial biotechnology, including genomics, transcriptomics, proteomics, metabolomics, fluxomics and genome scale modeling, and so on. Furthermore, this review also discussed the potential and promise of systems biology in industrial biotechnology.
Subject(s)
Biotechnology , Genomics , Industrial Microbiology , Metabolic Engineering , Metabolomics , Systems BiologyABSTRACT
Objective To investigate the distribution of chronic disease and geriatric syndrome in hospitalized elderly patients with multimorbidity by chronic disease investigation and comprehensive geriatric assessment.Methods A total of 176 patients aged ≥60 years admitted into the geriatric department in our hospital were selected,and demographic factors were collected.Their chronic diseases and geriatric syndrome were recorded.The comprehensive geriatric assessment was consummated,and the biochemical indicators for chronic disease and geriatric syndrome were detected.Results All patients suffered from two or more kinds of chronic diseases.The top three most common diseases were hypertension (112 cases),diabetes (94 cases),and respiratory diseases (73cases).The sum of chronic diseases kinds were ≥3 in 137 patients,≥4 in 78 patients,≥5 in 40 patients.The amount of chronic diseases showed an increased tendency along with ageing.Totally 175 patients had more than one geriatric syndrome,the top three most common types were frailty and prefrailty(133 cases),visual impairment (117 cases),impaired daily activities (107 cases).There were significant differences in the number of geriatric syndrome among different age groups(x2 =16.989,P < 0.001).Spearman analysis showed that the number of patients with geriatric syndrome were positively correlated with age(r =0.307,P<0.001).Conclusions The prevalence of chronic disease and geriatric syndrome is high in hospitalized elderly patients with multimorbidity,which is increased with aging.We should pay attention to the screening of chronic disease and geriatric syndrome in multimorbid elderly patients
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Objective To investigate the relationship between levels of mean platelet volume (MPV) and carotid atherosclerosis in patients with acute cerebral infarction.Methods A total of 99 patients were chosen for the observation group.Another 30 healthy people were for control group.The level of mean platelet volume in all subjects was detected bby enzymatic cycling assay and the carotid intimamedia thickness(IMT) of all patients was checked using color Doppler echocardiography.According to IMT degree,the patients in observation group were divided into IMT nomal group,IMT mild stenosis group and IMT moderate,severe stenosis group.According to the size of area of skull CT or MRI brain infarction,groups can be divided into a small area of cerebral infarction group,middle area of cerebral infarction group,the large area cerebral infarction group.The level of mean platelet volume between observation group and control group as well each subgroup of observation group was compared,and its correlation with IMT was also analyzed.Results The level of mean platelet volume in observation group was higher than in healthy control group (P < 0.05).Cerebral infarction patients with different degree of carotid stenosis group of peripheral blood MPV comparative difference was statistically significant(P =0.000).Pearson correlation analysis displayed that the level of mean platelet volume was positively correlated with IMT(r =0.331,P =0.000),and positively correlated with Cerebral infarction volume.The optimal cut-off value of MPV was 11.45,with a sensitivity of 41.4% and a specificity of 86.7% for predicting ischemic stroke.Conclusion Increased MPV is closely associated with carotid artery stenosis and its degree in cerebral infarction patients.
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Objective To investigate the expression and significance of ADAMDEC1 in glioma.Methods We prospectively observed the expression of ADAMDEC1 in 77 glioma patients,of which 28 cases were grade Ⅳ glioma,26 were grade Ⅲ glioma (high-grade glioma);of which 23 cases were Grade Ⅱ glioma,5 were grade Ⅰ glioma (low-grade glioma).For 10 cases in the control group,brain tissue samples were collected from internal decompression patients with heavy traumatic brain injury.The expression of ADAMDEC1 in glioma tissue was detected immunohistochemistry,RT-PCR,and Western blot.With follow-up survey we explored the relationship between the survival time and the expression of ADAMDEC1 in the patients with high-grade gliomas and low-grade gliomas.Results Compared with the low-grade glioma group and the control group,qPCR,immunohistochemistry and Western blotting all showed that the protein and mRNA levels of ADAMDEC1 in high-grade glioma group were significantly increased,while ADAMDEC1 was expressed little in low-grade glioma group and not expressed in control group (P < 0.05).The survey results showed that the survival time of high-grade glioma patients was significantly shorter than low-grade glioma patients;however,the expression level of ADAMDEC1 in the highgrade glioma tissue was significantly higher than in low-grade glioma tissue (x2=5.031,P<0.05).Conclusion The expression of ADAMDEC1 is closely related to the malignant degree of glioma cells and the prognosis of glioma patients.Therefore,ADAMDEC1 can be used as an index to evaluate the malignance degree of glioma and the prognosis of glioma.
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Cold-adapted lipases are attractive biocatalysts that can be used at low temperatures as additives in food products, laundry detergents, and the organic synthesis of chiral intermediates. Cold-adapted lipases are normally found in microorganisms that survive at low temperatures. A fungi strain XMZ-9 exhibiting lipolytic activity was isolated from the soil of glaciers in Xinjiang by the screening plates using 1% tributyrin as the substrate and Victoria blue as an indicator. Based on morphological characteristics and phylogenetic comparisons of its 18S rDNA, the strain was identified as Penicillium sp. The partial nucleotide sequences of these two lipase related genes, LipA and LipB, were obtained by touchdown PCR using the degenerate primers designed according to the conservative domains of lipase. The full-length sequences of two genes were obtained by genome walking. The gene lipA contained 1 014 nucleotides, without any intron, comprising one open reading frame encoding a polypeptide of 337 amino acids. The gene lipB comprised two introns (61 bp and 49 bp) and a coding region sequence of 1 122 bp encoding a polypeptide of 373 amino acids, cDNA sequences of both lipA and lipB were cloned and expressed in Escherichia coli BL21 (DE3). The recombinant LipA was mostly expressed as inclusion bodies, and recovered lipase activity at low temperature after in vitro refolded by dilution. Differently, the recombinant LipB was expressed in the soluble form and then purified by Ni-NTA affinity chromatography Column. It showed high lipase activity at low temperature. These results indicated that they were cold-adapted enzymes. This study paves the way for the further research of these cold-adapted lipases for application in the industry.