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In this study, we conducted an assembly and analysis of the organelle genomes of Aconitum carmichaelii. Our investigation encompassed the examination of organelle genome structures, gene transfer events, and the environmental selection pressures affecting A. carmichaelii. The results revealed distinct evolutionary patterns in the organelle genomes of A. carmichaelii. Especially, the plastome exhibited a more conserved structure but a higher nucleotide substitution rate (NSR), while the mitogenome displayed a more complex structure with a slower NSR. Through homology analysis, we identified several instances of unidirectional protein-coding genes (PCGs) transferring from the plastome to the mitogenome. However, we did not observe any events which genes moved from the mitogenome to the plastome. Additionally, we observed multiple transposable element (TE) fragments in the organelle genomes, with both organelles showing different preferences for the type of nuclear TE insertion. Divergence time estimation suggested that rapid differentiation occurred in Aconitum species approximately 7.96 million years ago (Mya). This divergence might be associated with the reduction in CO2 levels and the significant uplift of the Qinghai-Tibet Plateau (QTP) during the late Miocene. Selection pressure analysis indicated that the dN/dS values of both organelles were less than 1, suggested that organelle PCGs were subject to purification selection. However, we did not detect any positively selected genes (PSGs) in Subg. Aconitum and Subg. Lycoctonum. This observation further supports the idea that stronger negative selection pressure on organelle genes in Aconitum results in a more conserved amino acid sequence. In conclusion, this study contributes to a deeper understanding of organelle evolution in Aconitum species and provides a foundation for future research on the genetic mechanisms underlying the structure and function of the Aconitum plastome and mitogenome.
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Aconitum , Filogenia , Aconitum/genética , Aconitum/química , Aconitum/metabolismo , Organelas/genética , TibetRESUMO
Species in Gentiana section Cruciata are important alpine plants with a center of diversity and speciation in Qinghai-Tibet Plateau (QTP), and some of these species are sympatrically distributed in northeastern QTP. Studies on genome features and natural selection signatures of sympatric species in section Crucata have been impeded by a lack of genomic resources. Here, we showed transcript characterizations and molecular footprints of selection effects on G. straminea, G. dahurica and G. officinalis based on the comparative transcriptome. A total of 62.97 Gb clean reads were obtained with unigene numbers per species ranging from 141,819 to 236,408 after assembly. We found that these three species had similar distribution of functional categories in different databases, and key enzyme-encoding genes involved in the iridoids biosynthesis were also obtained. The selective pressure analyses indicated that most paired orthologs between these three species were subject to negative selection, and only a low proportion of the orthologs that underwent positive selection were detected. We found that some positive selected genes were involved in "catalytic activity", "metabolic process", "response to stimulus" and "response to stress". Besides, large numbers of SSR primer pairs with transferabilities were successfully designed based on the available transcriptome datasets of three Gentiana species. The phylogenetic relationships reconstructed based on 352 single-copy nuclear genes provided a rough phylogenetic framework for this genus and confirmed the monophyly of section Cruciata. Our study not only provides insights for the natural selection effects on sympatric Gentiana species, but also enhances future genetic breeding or evolutionary studies on Qinjiao species.
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Gentiana , Gentiana/genética , Filogenia , Melhoramento Vegetal , Tibet , Perfilação da Expressão Gênica , Transcriptoma/genéticaRESUMO
In vivo simultaneous monitoring of blood flow and changes of concentration of oxyhemoglobin (ΔHbO2) in brain is a key important method for the research of cerebrovascular disease. In this study, a new monitoring system, combining laser speckle contrast imaging method and spectral analysis method, was proposed, which could be utilized to measure the cerebral blood flow and ΔHbO2 on mice during traumatic brain injury. The principle of the present system was studied and the hardware platform of the detection system was built. Then, user interface software and algorithms were implemented based on Labview and Matlab software. Finally, the performance of the present system was verified by the in vivo experiments.
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Gasometria , Circulação Cerebrovascular , Oxigênio , Algoritmos , Animais , Gasometria/instrumentação , Encéfalo , Lasers , Camundongos , Oxigênio/análiseRESUMO
Cervical cancer is a common female malignant tumor. It has been increasing and rejuvenating in recent years. Early screening of cervical cancer is an effective control method to block cancer. In this study, a diffuse reflectance spectrum detection and analysis system based on LabWindows development software and MariaDB database was developed, which can acquire and save the spectral data to the database. The method of a neural network model based on spectral database was built to distinguish the cervical tissue and the normal tissue. The nude mouse tumor model test and human volunteer test were performed respectively, which verified that the system can distinguish between normal tissue and tumor tissue, and can be applied to the screening of cervical precancerous lesions.
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Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Camundongos , Camundongos Nus , Redes Neurais de Computação , Análise Espectral , Neoplasias do Colo do Útero/diagnóstico por imagemRESUMO
BACKGROUND: Discomfort evoked by stereoscopic depth has been widely concerned. Previous studies have proposed a comfortable disparity range and considered that disparities exceed this range would cause visual discomfort. Brain activity recordings including Electroencephalograph (EEG) monitoring enable better understanding of perceptual and cognitive processes related to stereo depth-induced visual comfort. METHODS: EEG data was collected using a stereo-visual evoked potential (VEP) test system by providing visual stimulus to subjects aged from 21 to 25 with normal stereoscopic vision. For each type of visual stimulus, data were processed using directed transfer function (DTF) and adaptive directed transfer function (ADTF) in combination with subjective feedbacks (comfort or discomfort). The topographies of information flow were constructed to compare responses stimulated by different stereoscopic depth, and to determine the difference in comfort and discomfort situations upon stimulation with same stereoscopic depth. RESULTS: Based on EEG analysis results, we found that the occipital P270 was moderately related to the disparity. Moreover, the ADTF of P270 showed that the information flows at frontal lobe and central-parietal lobe changed when stimulation with different stereoscopic depth applied. As to the stereo images with same stereoscopic depth, the DTF outflows at the temporal and temporal-parietal lobes in δ band, central and central-parietal lobes in α and θ bands, and the comparison of inflows in these three bands could be considered as discriminated indexes for matching the stereoscopic effect with viewers' comfort or discomfort state impacted by disparity. The subjective feedbacks indicated that the comfort judgments remained as a result of cumulative effect. CONCLUSIONS: This study proposed a short-term stereo-VEP experiment that shorted the duration of each stimulus in the experimental scheme to minimize the interference from other factors except the disparity. The occipital P270 had a mid-relevance to the disparity and its ADTF showed the affected areas when viewers are receiving stimulations with different disparities. DTF could be considered as discriminated indexes for matching the stereoscopic effect with viewers' comfort or discomfort state induced by disparity. This study proposed a preferable experiment to observe the single effect of disparity and provided an intuitive and easy-to-read result in a more convenient manner.
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Percepção de Profundidade/fisiologia , Eletroencefalografia , Estimulação Luminosa , Visão Ocular , Encéfalo/fisiologia , Córtex Cerebral , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Processamento de Sinais Assistido por Computador , Lobo Temporal , Adulto JovemRESUMO
Cucurbitaceae is the fourth most important economic plant family with creeping herbaceous species mainly distributed in tropical and subtropical regions. Here, we described and compared the complete chloroplast genome sequences of ten representative species from Cucurbitaceae. The lengths of the ten complete chloroplast genomes ranged from 155,293 bp (C. sativus) to 158,844 bp (M. charantia), and they shared the most common genomic features. 618 repeats of three categories and 813 microsatellites were found. Sequence divergence analysis showed that the coding and IR regions were highly conserved. Three protein-coding genes (accD, clpP, and matK) were under selection and their coding proteins often have functions in chloroplast protein synthesis, gene transcription, energy transformation, and plant development. An unconventional translation initiation codon of psbL gene was found and provided evidence for RNA editing. Applying BI and ML methods, phylogenetic analysis strongly supported the position of Gomphogyne, Hemsleya, and Gynostemma as the relatively original lineage in Cucurbitaceae. This study suggested that the complete chloroplast genome sequences were useful for phylogenetic studies. It would also determine potential molecular markers and candidate DNA barcodes for coming studies and enrich the valuable complete chloroplast genome resources of Cucurbitaceae.
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Cucurbitaceae/genética , Genoma de Cloroplastos , Códon , Biologia Computacional/métodos , Cucurbitaceae/classificação , Evolução Molecular , Variação Genética , Genômica/métodos , Repetições de Microssatélites , Anotação de Sequência Molecular , Filogenia , Seleção GenéticaRESUMO
Gynostemma pentaphyllum is an important medicinal herb of the Cucurbitaceae family, but limited genomic data have hindered genetic studies. In this study, transcriptomes of two closely-related Gynostemma species, Gynostemma cardiospermum and G. pentaphyllum, were sequenced using Illumina paired-end sequencing technology. A total of 71,607 nonredundant unigenes were assembled. Of these unigenes, 60.45% (43,288) were annotated based on sequence similarity search with known proteins. A total of 11,059 unigenes were identified in the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) database. A total of 3891 simple sequence repeats (SSRs) were detected in 3526 nonredundant unigenes, 2596 primer pairs were designed and 360 of them were randomly selected for validation. Of these, 268 primer pairs yielded clear products among six G. pentaphyllum samples. Thirty polymorphic SSR markers were used to test polymorphism and transferability in Gynostemma. Finally, 15 SSR makers that amplified in all 12 Gynostemma species were used to assess genetic diversity. Our results generated a comprehensive sequence resource for Gynostemma research.
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Etiquetas de Sequências Expressas , Genes de Plantas/genética , Marcadores Genéticos , Gynostemma/classificação , Gynostemma/genética , Repetições de Microssatélites/genética , Transcriptoma , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência Molecular , Análise de Sequência de DNARESUMO
BACKGROUND: Increasing evidence has shown that hypoxia is a biomarker of tumor proliferation and metastasis. This research aimed to identify a hypoxia-associated gene prognostic index (HAGPI) in head and neck squamous cell carcinoma (HNSCC) and based on HAGPI-defined subgroups to predict prognosis and response to immune checkpoint inhibitors therapy. METHODS: RNA-sequencing transcriptomic data for patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA). Protein-protein interaction network analysis was performed to select hypoxia-related hub genes. Univariate and multivariate cox regression analyses were used to identify hub genes to develop the HAGPI. Afterward expression data were imported into CIBERSORT to evaluate the relative proportion of 22 immune cells and compared the relative proportions of immune cells between the 2 HAGPI subgroups. The relationship between immunopheno score (IPS) and HAGPI was validated for immune checkpoint inhibitors (ICIs) response in TCGA cohorts. RESULTS: The HAGPI was constructed based on HS3ST1, HK1, PGK1, STC2, SERPINE1, PKLR genes. In high-HAGPI patients, the primary and secondary endpoint events in TCGA and GEO cohorts were significantly lower than low-HAGPI groups (Pâ <â .05). HAGPI-high patients exhibited a poorer prognosis than HAGPI-low patients did. The abundance of M2 macrophages and NK cell were significantly enhanced in the high-HAGPI while T cells regulatory and T cells CD8, were markedly elevated in the low-HAGPI. Meanwhile, patients in the low-HAGPI patients had higher levels of immunosuppressant expression and less aggressive phenotypes. Furthermore, IPS analysis showed that the low-HAGPI group with higher IPS represented a more immunogenic phenotype. CONCLUSION: The current study developed and verified a HAPGI model that can be considered as an independent prognostic biomarker and elucidated the tumor immune microenvironment of HNSCC.
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Neoplasias de Cabeça e Pescoço , Inibidores de Checkpoint Imunológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Prognóstico , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Medição de Risco/métodos , Mapas de Interação de Proteínas/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Transcriptoma , Hipóxia , IdosoRESUMO
Analyzing polysorbate 20 (PS20) composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance. The similar structures and polarities of PS20 components make accurate separation, identification, and quantification challenging. In this work, a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) to separate 18 key components with multiple esters. The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) with an identical gradient as the HPLC-CAD analysis. The polysorbate compound database and library were expanded over 7-time compared to the commercial database. The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship. UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources. The method observed the impact of 4 degradation conditions on peak components, identifying stable components and their tendencies to change. HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences, distinguishing quasi products.
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OBJECTIVE: To explore the clinical value of constructing a nomogram model based on apparent diffusion coefficient values within 1 cm of the residual tumor cavity to predict the postoperative progression of gliomas. METHODS: Clinical data of patients with glioma who underwent surgery were retrospectively retrieved from the First Hospital of Qinhuangdao. The mean apparent diffusion coefficient (mADC) was measured using a picture archiving and communication system. The Kaplan-Meier survival curve was constructed with the optimal mADC threshold determined by the X-tile. A nomogram was developed based on the independent risk factors determined using the Cox proportional hazards model (Cox regression model) to predict the progression of postoperative glioma. A receiver operating characteristic curve was drawn to evaluate the prediction accuracy of the model, and decision curve analysis was performed to assess the clinical value of the nomogram. RESULTS: There was good agreement between the mADC values of the 2 repeated measurements before and after, with a consistency correlation coefficient of 0.83. Multivariate Cox regression analysis showed that peritumoral mADC values, degree of peritumoral enhancement, age, pathological grading, and degree of tumor resection were independent risk factors for predicting postoperative progression of glioma (all P < 0.05). The receiver operating characteristic curves of the nomogram predicting 1, 2, and 3 years postoperative progression were 0.86, 0.82, and 0.91, respectively. The calibration curve showed good consistency between the observed and predicted values in the model. The curve showed that the nomogram model has a good clinical application value. CONCLUSIONS: The peritumoral mADC values, degree of peritumoral enhancement, age, pathological grade, and degree of tumor resection were independent factors affecting the postoperative progression of glioma. The nomogram model established for the first time based on mADC values within 1 cm of the tumor can predict the postoperative condition of patients with glioma intuitively and comprehensively. It can provide a relatively accurate prediction tool for neurosurgeons to individualize the evaluation of survival and prognosis, and formulate treatment plans for patients.
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Glioma , Nomogramas , Humanos , Estudos Retrospectivos , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Imagem de Difusão por Ressonância Magnética , PrognósticoRESUMO
Gynostemma pentaphyllum (Thunb.) Makino is a perennial creeping herbaceous plant in the family Cucurbitaceae, which has great medicinal value and commercial potential, but urgent conservation efforts are needed due to the gradual decreases and fragmented distribution of its wild populations. Here, we report the high-quality diploid chromosome-level genome of G. pentaphyllum obtained using a combination of next-generation sequencing short reads, Nanopore long reads, and Hi-C sequencing technologies. The genome is anchored to 11 pseudo-chromosomes with a total size of 608.95 Mb and 26 588 predicted genes. Comparative genomic analyses indicate that G. pentaphyllum is estimated to have diverged from Momordica charantia 60.7 million years ago, with no recent whole-genome duplication event. Genomic population analyses based on genotyping-by-sequencing and ecological niche analyses indicated low genetic diversity but a strong population structure within the species, which could classify 32 G. pentaphyllum populations into three geographical groups shaped jointly by geographic and climate factors. Furthermore, comparative transcriptome analyses showed that the genes encoding enzyme involved in gypenoside biosynthesis had higher expression levels in the leaves and tendrils. Overall, the findings obtained in this study provide an effective molecular basis for further studies of demographic genetics, ecological adaption, and systematic evolution in Cucurbitaceae species, as well as contributing to molecular breeding, and the biosynthesis and biotransformation of gypenoside.
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Cadherin epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a planar cell polarity protein involved in the transmission of directional cues to align either individual cells within an epithelial sheet or multicellular clusters. CELSR1 has been suggested to play a role in glioma, breast cancer, and chronic lymphocytic leukemia development; however, whether it has a role in the pathogenesis of ovarian cancer remains unknown. The aim of this study was to determine the role of CELSR1 in ovarian cancer and elucidate its underlying molecular mechanisms. By analyzing gene expression data downloaded from the Cancer Genome Atlas database, we found that CELSR1 expression was upregulated in ovarian cancer tissues compared to that in normal ovarian tissues. High CELSR1 expression levels were associated with poor prognosis in patients with ovarian cancer. Cell proliferation, scratch, and transwell assays revealed that CELSR1 promoted the proliferation, migration, and invasion of ovarian cancer cells in vitro. In addition, transcriptome sequencing analysis revealed that CELSR1 knockdown in T29H cells resulted in the dysregulation of the expression of 1320 genes. Further analysis revealed that genes involved in proliferation- and migration-associated signaling pathways were regulated by CELSR1. Our study demonstrates that CELSR1 is highly expressed in ovarian cancer cells and regulates their proliferation and migration, suggesting its potential as a diagnostic marker and therapeutic target.
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Caderinas , Neoplasias Ovarianas , Feminino , Humanos , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/metabolismo , Regulação para CimaRESUMO
Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.
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Neoplasias Esofágicas , Interleucina-6 , Humanos , Recidiva Local de Neoplasia , Tolerância a Radiação/fisiologia , Neoplasias Esofágicas/radioterapiaRESUMO
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of â¼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.
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DNA , Proteínas de Membrana , Masculino , Humanos , Proteína Beclina-1 , Proteínas de Membrana/metabolismo , DNA/metabolismo , Nucleotidiltransferases/metabolismo , Fosfatidilinositol 3-Quinase , AutofagiaRESUMO
Gynostemma microspermum C. Y. Wu et S. K. Chen is an endemic creeping herbaceous species mainly distributed in dense forests on limestone in northwestern China. Here, the complete chloroplast genome sequence of G. microspermum was obtained by Illumina pair-end sequencing. The circular complete chloroplast genome of G. microspermum is 158,692 bp in length and contains a large single copy region (87,452 bp), a small single copy region (19,068 bp) and two short inverted repeat regions (26,086 bp). The genome sequence encodes 133 genes including 87 protein-coding genes, 37 transfer RNA genes, 8 ribosomal RNA genes and 1 pseudogene. The maximum likelihood (ML) phylogeny estimation shows that G. microspermum is sister to all other analyzed species of the genus Gynostemma with high bootstrap support.
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Gentiana macrophylla is a perennial herb in the Gentianaceae family, whose dried roots are used in traditional Chinese medicine. Here, we assembled a chromosome-level genome of G. macrophylla using a combination of Nanopore, Illumina, and Hi-C scaffolding approaches. The final genome size was ~1.79 Gb (contig N50 = 720.804 kb), and 98.89% of the genome sequences were anchored on 13 pseudochromosomes (scaffold N50 = 122.73 Mb). The genome contained 55,337 protein-coding genes, and 73.47% of the assemblies were repetitive sequences. Genome evolution analysis indicated that G. macrophylla underwent two rounds of whole-genome duplication after the core eudicot γ genome triplication event. We further identified candidate genes related to the biosynthesis of iridoids, and the corresponding gene families mostly expanded in G. macrophylla. In addition, we found that root-specific genes are enriched in pathways involved in defense responses, which may greatly improve the biological adaptability of G. macrophylla. Phylogenomic analyses showed a sister relationship of asterids and rosids, and all Gentianales species formed a monophyletic group. Our study contributes to the understanding of genome evolution and active component biosynthesis in G. macrophylla and provides important genomic resource for the genetic improvement and breeding of G. macrophylla.
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Gentiana , Plantas Medicinais , Genômica , Gentiana/genética , Iridoides , Plantas Medicinais/genéticaRESUMO
BACKGROUND: The aim of this study is to investigate the changes of peripheral blood lymphocyte subsets before and after treatment with pembrolizumab for non-small cell lung cancer and its clinical significance. METHODS: A total of 32 patients with non-small cell lung cancer who received pembrolizumab treatment in The Affiliated Hospital of Qingdao University and Weifang People's Hospital of Shandong Province from January 2015 to December 2020 were selected as the observation group, and 30 healthy people during the same period were selected as the control group. Before treatment and in cycles 1, 2 and 4 after treatment, fluid cytometry was used to detect changes in the levels of lymphocyte subsets in the peripheral blood of patients. RESULTS: The CD3âº, CD4âº, CD4âº/CD8⺠indexes of patients with non-small cell lung cancer before the treatment were significantly lower than those in the control group (P<0.05), and the CD8⺠level was significantly increased (P<0.05); After 1 cycle of pembrolizumab treatment, there was no significant difference in the changes of lymphocyte subsets compared with before immunotherapy; After 2 cycles of the treatment, the CD3âº, CD4âº, CD4âº/CD8⺠values were higher than before the treatment (P>0.05), and the CD8⺠index was slightly lower than before the treatment (P<0.05); After the fourth cycle of treatment, the CD3âº, CD4âº, CD4âº/CD8⺠values were significantly improved compared to before the treatment (P<0.05), and the CD8⺠index was significantly lower than before the treatment (P<0.05); In the treatment process of patients with stable disease (SD)/partial response (PR), the CD3âº, CD4âº, CD4âº/CD8⺠values of the fourth cycles were higher than before the treatment (P<0.05), and the CD8⺠index was lower than before the treatment (P<0.05); During the treatment of progressive disease (PD) patients, the changes of lymphocyte subsets in the fourth cycles were not significantly different from those before the treatment (P>0.05). At the same time, this article shows through analysis that the expression of programmed cell death ligand 1 (PD-L1) and pathological types have no obvious influence on the effect of immunotherapy. Multi-factor analysis shows that it is more meaningful to observe the changes of CD3âº, CD4⺠and CD8⺠at the same time to predict the effect of immunotherapy. CONCLUSIONS: Pembrolizumab can regulate the changes of T lymphocyte subsets in patients with non-small cell lung cancer, improve the immune status of the patients, and there is no obvious adverse reaction. At the same time, monitoring the changes of lymphocyte subsets during treatment can predict the effect of immunotherapy.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Subpopulações de Linfócitos T/efeitos dos fármacos , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologiaRESUMO
Background: Low-intensity transcranial ultrasound (LITUS) may have a therapeutic effect on Parkinson's disease (PD) patients to some extent. Fractional anisotropy (FA) and relaxation time T2∗ that indicate the integrity of fiber tracts and iron concentrations in brain tissue have been used to evaluate the therapeutic effects of LITUS. Purpose: This study aims to use FA and T2∗ values to evaluate the therapeutic effects of LITUS in a PD rat model. Materials and Methods: Twenty Sprague-Dawley rats were randomly divided into a hemi-PD group (n = 10) and a LITUS group (n = 10). Single-shot spin echo echo-planar imaging and fast low-angle shot T2WI sequences at 3.0 T were used. The FA and T2∗ values on the right side of the substantia nigra (SN) pars compacta were measured to evaluate the therapeutic effect of LITUS in the rats. Results: One week after PD-like signs were induced in the rats, the FA value in the LITUS group was significantly larger compared with the PD group (0.214 ± 0.027 vs. 0.340 ± 0.032, t = 2.864, P = 0.011). At the 5th and 6th weeks, the FA values in the LITUS group were significantly smaller compared with the PD group (5th week: 0.290 ± 0.037 vs. 0.405 ± 0.027, t = 2.385, P = 0.030; 6th week: 0.299 ± 0.021 vs. 0.525 ± 0.028, t = 6.620, P < 0.0001). In the 5th and 6th weeks, the T2∗ values in the injected right SN of the LITUS group were significantly higher compared with the PD group (5th week, 12.169 ± 0.826 in the LITUS group vs. 7.550 ± 0.824 in the PD group; 6th week, 11.749 ± 0.615 in the LITUS group vs. 7.550 ± 0.849 in the PD group). Conclusion: LITUS had neuroprotective effects and can reduce the damage of 6-OHDA-induced neurotoxicity in hemi-PD rats. The combination of FA and T2∗ assessments can potentially serve as a new and effective method to evaluate the therapeutic effects of LITUS.
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Tryptophan 2,3dioxygenase (TDO2) is a key ratelimiting enzyme in the kynurenine pathway and promotes tumor growth and escape from immune surveillance in different types of cancer. The present study aimed to investigate whether TDO2 serves a role in the development of ovarian cancer. Reverse transcriptionquantitative PCR and western blotting were used to detect the expression of TDO2 in different cell lines. The effects of TDO2 overexpression, TDO2 knockdown and TDO2 inhibitor on ovarian cancer cell proliferation, migration and invasion were determined by MTS, colony formation and Transwell assays. The expression of TDO2 in ovarian cancer tissues, normal ovarian tissues and fallopian tube tissues were analyzed using the gene expression data from The Cancer Genome Atlas and GenotypeTissue Expression project. Immune cell infiltration in cancer tissues was evaluated using the single sample gene set enrichment analysis algorithm. The present study found that RasV12mediated oncogenic transformation was accompanied by the upregulation of TDO2. In addition, it was demonstrated that TDO2 was upregulated in ovarian cancer tissues compared with normal ovarian tissues. TDO2 overexpression promoted proliferation, migration and invasion of ovarian cancer cells, whereas TDO2 knockdown repressed these phenotypes. Treatment with LM10, a TDO2 inhibitor, also repressed the proliferation, migration and invasion of ovarian cancer cells. The present study indicated that TDO2 can be used as a new target for the treatment of ovarian cancer.