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ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.
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【Objective】 To analyze the independent influencing factors of repeated extracorporeal shock wave lithotripsy (ESWL) in the treatment of upper urinary calculi (UUC), based on which a nomogram model was established to predict the efficacy. 【Methods】 Clinical and imaging data of 203 patients receiving repeated ESWL during Jan.2020 and Dec.2022 were collected, including 117 cases in the successful group and 86 cases in the unsuccessful group.The patients’ age and sex, stone volume (SV), surface area (SA), skin-to-site distance (SSD), maximum CT value, mean stone density (MSD), and stone heterogeneity index (SHI) were compared between the two groups.The independent predictors were analyzed with logistic regression and the meaningful variables (P<0.05) were used to establish a nomogram.The efficacy of the model was evaluated using receiver operating characteristic (ROC) curve and decreasing curve analysis (DCA).Internal validation was also performed. 【Results】 Stepwise regression showed that SV, SSD, MSD and SHI were independent influencing factors (P<0.05).The area under the ROC curve (AUC), optimal threshold, sensitivity and specificity were 0.793 (95%CI: 0.674-0.911), 0.619, 77.1% and 74.0%, respectively.The DCA curve was above two extreme curves.Hosmer-Lemeshow test and calibration curve showed that the nomogram had a good fitting degree (χ2=5.526, P=0.489), and the correction C-index was 0.746. 【Conclusion】 SV, SSD, MSD and SHI are independent predictors of the efficacy of repeated ESWL in the treatment of UUC.The nomogram established based on the above indicators has good predictive efficiency and clinical applicability.
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Diabetic retinopathy(DR)is one of the most common retinal complications of diabetes could cause irreversible loss of central vision in the working-age population. Current studies showed that systemic risk factors, inflammatory response, and oxidative stress played a central role in the development of DR. Although traditional sequencing methods have provided valuable insights into the pathogenesis of DR, offering crucial guidance for clinical diagnosis and treatment, they still possess certain limitations. In recent years, the emerging single-cell RNA sequencing technology(scRNA-seq)has enabled precise analysis of mRNA transcriptomes at the single-cell level. This technique accurately identifies novel cell subtypes in retinal diseases, detects rare cells, and reveals intercellular heterogeneity. It contributes to elucidating the pathogenesis and development of retinal diseases, and facilitates exploration of gene regulatory relationships associated with these disorders to provide valuable insights for future precision medicine. This article reviews the technology of single-cell sequencing and its application in DR research. It also explores the mechanisms of different types of cells associated with DR, aiming to enhance the utilization of scRNA-seq in DR research and identify potential therapeutic targets to improve clinical diagnosis and treatment of DR.
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Abstract The northwestern portion of the Upper Paraná Atlantic Forest ecoregion is one of the most disturbed and fragmented areas in the Atlantic Forest, and little is known about the local avifauna. In this study, we have described the composition and diversity of the aquatic avifauna of this region and analyzed the patterns of similarity with respect to the seasonal as well as spatial distribution. We used the line transect sampling technique in six distinct humid areas (including lentic and lotic water bodies) during the dry and rainy seasons of 2012 and 2013. A total of 52 species of waterfowl were recorded. The species richness of the studied areas was surprisingly distinct; only seven waterfowl species, namely Cairina moschata (Linnaeus, 1758), Tigrisoma lineatum (Boddaert, 1783), Rosthramus sociabilis (Vieillot, 1817), Aramus guarauna (Linnaeus, 1766), Vanellus chilensis (Molina, 1782), Jacana jacana (Linnaeus, 1766), and Arundinicola leucocephala (Linnaeus, 1764), were common to these six studied areas. This indicated that the other bird species that were observed might be habitat selective. Moreover, the analysis of the composition of birds in the two seasons (dry and rainy) combined with their spatial distributions showed significant dissimilarities between the areas with lotic (river and constructed wetland) and lentic (lagoons) characteristics. Nevertheless, despite the small extent and low total richness of the entire study area, it was found to be home to 1/3 of all freshwater aquatic birds documented in the state of São Paulo, with the record of 5 migratory species and 11 new species added to the northwest of the state. The heterogeneity of local aquatic environments, habitat selection combined with seasonality, and the absence of other humid locations in the surroundings can explain the diversity and distribution of these birds in the water bodies of this uninvestigated Atlantic Forest ecoregion.
Resumo A porção noroeste da ecorregião Floresta Atlântica do Alto Paraná é uma das mais alteradas e fragmentadas da Mata Atlântica, da qual pouco se sabe sobre a avifauna local. Nosso objetivo foi descrever a diversidade e composição da avifauna aquática, bem como analisar os padrões de similaridade quanto a distribuição temporal e espacial destas aves nesta ecorregião. Utilizamos a transecção linear para amostragem em seis áreas úmidas (corpos d'água lênticos e lóticos), nos períodos de seca e chuva entre 2012 e 2013. Registramos 52 espécies de aves aquáticas e as riquezas das áreas mostraram-se distintas, pois apenas Cairina moschata (Linnaeus, 1758), Tigrisoma lineatum (Boddaert, 1783), Rosthramus sociabilis (Vieillot, 1817), Aramus guarauna (Linnaeus, 1766), Vanellus chilensis (Molina, 1782), Jacana jacana (Linnaeus, 1766), and Arundinicola leucocephala (Linnaeus, 1764) foram comuns às seis áreas, o que indica seleção de habitat. Quando analisada a composição das aves nos dois períodos aliada à distribuição espacial, encontramos dissimilaridades temporais acentuadas entre os ambientes com características lóticas (rio e aterro) e lênticas (lagoas). Isto mostra que, além das diferentes épocas sazonais, é necessário analisar separadamente os diferentes tipos de áreas úmidas. Por fim, apesar da extensão pequena e baixa riqueza total, a área amostrada abrigou 1/3 das aves aquáticas de água doce para o estado de São Paulo, cinco espécies migratórias e 11 novas espécies para o noroeste do estado. A heterogeneidade de ambientes aquáticos locais, forte seleção de habitat aliada à sazonalidade e ausência de outros locais úmidos em seu entorno, explicam a diversidade e distribuição destas aves estreitamente relacionadas aos corpos d'água desta desconhecida ecorregião da Mata Atlântica.
الموضوعات
Animals , Birds , Biodiversity , Seasons , Brazil , Forests , Ecosystemالملخص
Objective:To explore the classification and influencing factors of family resilience and post-traumatic growth in patients with spinal tumor.Methods:A cross-sectional investigation was conducted among 219 inpatients with spinal tumor admitted from July 2021 to July 2022. The General Demographic Information questionnaire, Chinese-Family Resilience Assessment Scale, Posttraumatic Growth Inventory, Family Crisis-Oriented Personal Evaluation Scales (F-COPES), and Social Support Rating Scale (SSRS) were used in the study. The ordinal and multivariate logistic regression analyses was applied to identify the factors associated with the classification of family resilience and post-traumatic growth.Results:Of the 219 patients, there were 62 cases of primary spinal tumors (28.3%). According to the results of latent profile analysis, the respondents were classified into three categories by family resilience and post-traumatic growth, namely family difficulty-resistant type ( n=38, 17.4%), general resilience-struggle type ( n=99, 45.2%) and family adaptation-growth type ( n=82, 37.4%). There were significant differences in occupational status, commitment to housework, family atmosphere( χ2=10.75, P=0.025; χ2=6.95, P=0.031; χ2=11.37, P=0.017), and total score of F-COPES and SSRS ( F=25.95, P<0.001; F=19.06, P<0.001)among three groups. Ordinal and multivariate logisitc regression analyses showed that retirement ( OR=2.928, 95% CI:1.098-7.808, P<0.05), family coping ( OR=1.113, 95% CI:1.063-1.165, P<0.05), and social support ( OR=1.226, 95% CI:1.103-1.362, P<0.05) were independently associated with family resilience and post-traumatic growth in patients with spinal tumor. Conclusion:Patients with spinal tumor have significant differences in characteristics by family resilience and post-traumatic growth. As a result, more targeted interventions should be provided for different categories of spinal tumor patients in the future.
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Diabetic retinopathy (DR) is one of the main causes of vision loss and irreversible blindness in the working-age population, closely regarded as the destruction of the retinal neurovascular unit (NVU). As an important component of the NVU, retinal microglia (RMG) plays a vital role in the progression of DR. In recent years, single-cell RNA sequencing (scRNA-seq) technology has emerged as an important tool in transcriptomic analysis. This latest method reveals the heterogeneity and complexity of RNA transcriptional profiles within individual cells, as well as the composition of different cell types and functions. Utilizing scRNA-seq technology, researchers have further revealed the role of RMG in the occurrence and development of DR, discovering phenotypic heterogeneity, regional heterogeneity, and cell-to-cell communication in RMG. It is anticipated that in the future, more omics technologies and multi-omics correlation analysis methods will be applied to DR and even other ophthalmic diseases, exploring potential diagnostic and therapeutic targets, providing different perspectives for the clinical diagnosis, treatment, and scientific research of DR, and truly promoting clinical translation through technological innovation, thereby benefiting patients with DR diseases.
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Objective This study aimed to explore the prognostic value of 18F-FDG PET/CT Metabolic and Heterogeneity Parameters Combined with Clinical Features Before Definitive Chemoradiotherapy(D-CRT)in predicting the prognosis of esophageal squamous cell carcinoma(ESCC)Patients.Methods A retrospective analysis was conducted on clinical data from 106 patients with ESCC who received D-CRT at the first affiliated Hospital of University of Science and Technology of China between January 2017 and December 2021.All patients underwent 18F-FDG PET/CT examination before the treatment.The primary tumor′s metabolic and heterogeneity parameters were obtained through data processing.All patients were followed up for overall survival.The Kaplan-Meier method and Cox proportional hazards models were used to analyze the association between clinical features,tumor metabo-lism and heterogeneity parameters and patient prognosis.Results The 1-and 1.5-year overall survival rates of all patients were 77.4%and 51.9%.The median survival time was 20 months.Univariate analysis showed that N stage,M stage,metabolic tumor volume,total lesion glycolysis,heterogeneity index-2(HI-2),and coefficient of variation with a threshold of 40%maximum standard uptake value(CV40%)were correlated with the prognosis of ESCC(all P<0.05).Multivariate analysis showed that N stage and CV40%were independent predictors of prognosis in patients with ESCC(P = 0.039 and P<0.001,respectively).Conclusion N stage and tumor metabolic heterogeneity parameter CV40%,which offering a degree of predictive value,are closely related to the prognosis of patients with ESCC treated with D-CRT.
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Glioblastoma is the most common primary malignant tumor of brain in adults.Although great efforts have been made to improve prognosis in recent years,the median survival is still less than 20 months,and less than 5％of patients survive longer than 20 months.The standard treatment is maximum surgical excision combined with radiotherapy and temozolomide chemotherapy.Single cell RNA sequencing(scRNA-seq)technology accurately analyzes each unique cell,enabling us to better understand the heterogeneity of tumors,the evolution process of tumor cells,the special functions of various types of cells in the immune microenvironment,and the interactions between cells,thus providing new ideas for personalized clinical therapy.This review focuses on the application of scRNA-seq in the study of glioblastoma heterogeneity,tumor immune microenvironment,cell communication and treatment.
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BACKGROUND:Astrocytes are the most abundant cells in the central nervous system,and various subsets of astrocytes are heterogeneous,performing a variety of special functions.Single-cell RNA sequencing(scRNA-seq)technology developed in recent years has extended our understanding of astrocyte heterogeneity from the perspective of transcriptome profiling. OBJECTIVE:To summarize the heterogeneity of scRNA-seq technology in different time and space,and pathological states and expand our knowledge of astrocyte heterogeneity on both molecular and functional levels. METHODS:The relevant articles on astrocyte heterogeneity and scRNA-seq were searched on PubMed,Elsevier,and CNKI databases.The search terms were"astrocytes,scRNA-seq,heterogeneity,Alzheimer disease,spinal cord injury,multiple sclerosis"in Chinese and English.Finally,74 articles were selected for viewing after screening according to inclusion criteria. RESULTS AND CONCLUSION:scRNA-seq studies related to the heterogeneity of astrocytes have shown that astrocyte is significantly heterogeneous across four aspects:species,developmental stage,central nervous system region,and pathological state.(1)Unique expression of certain genes occurs in astrocytes of different species,and the discovery of species-specific genes is beneficial for the translation of clinical studies.(2)During astrocyte development,differential gene expression emerged in the cellular subtypes identified at each stage,which further refined the cellular lineage of astrocytes and laid the foundation for the study of astrocyte developmental trajectories and mechanisms.(3)The discovery of differential gene expression allows regional localization of different astrocyte subpopulations and assists in the diagnosis and treatment of neurological diseases.(4)Astrocyte heterogeneity revealed by scRNA-seq can provide specific markers at the time of disease diagnosis and identify potential therapeutic targets.(5)The heterogeneity of astrocytes exists in many aspects,interacts with each other and is complex.The mechanisms of its generation,maintenance and transformation remain unclear.At present,molecular research on the single-cell level is still lacking.Linking transcriptionally defined astrocyte subpopulations to cellular activity,behavior and disease markers in real time remains one of the great challenges in the field.
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BACKGROUND:Osteonecrosis due to drugs is a serious adverse reaction occurring after the application of such drugs.Increasing evidence suggests that the gut microbiota composition is associated with osteonecrosis due to drugs.However,the causal relationship of the gut microbiota to osteonecrosis due to drugs is still unclear. OBJECTIVE:To evaluate the potential causal relationship between the gut microbiota and the risk of osteonecrosis due to drugs using the Mendelian randomization method. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis(n=13 266)conducted by the MiBioGen consortium as well as the summary statistics of osteonecrosis due to drugs obtained from the FinnGen consortium R9 release data(264 cases and 377 013 controls).Inverse variance weighted,MR-Egger,weighted median,weighted model and simple model were used to examine the causal association between gut microbiota and osteonecrosis due to drugs.Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable.Reverse Mendelian randomization analysis was performed on all the bacteria as an outcome for effect analysis and sensitivity analysis. RESULTS AND CONCLUSION:Inverse variance weighted estimates suggested that Lentisphaerae(phylum),Lentisphaeria(class),Melainabacteria(class),Gastranaerophilales(order),Rhodospirillales(order),Victivallales(order)and Bifidobacterium(genus)had protective causal effects on osteonecrosis due to drugs.Methanobacteria(class),Bacillales(order),Methanobacteriaceae(family),Lachnospiraceae(family),Methanobacteriales(order),Holdemania(genus),Holdemania(UCG010 group)(genus),Odoribacter(genus)and Tyzzerella3(genus)had negative causal effects on osteonecrosis due to drugs.According to the results of reverse Mendelian randomization analysis,Clostridiaceae1(family),Peptostreptococcaceae(family),Streptococcaceae(family),Clostridiumsensustricto1(genus)and Streptococcus(genus)showed negative causal effects on osteonecrosis due to drugs.However,Eisenbergiella(genus)showed protective causal effects on osteonecrosis due to drugs.None of the bidirectional sensitivity analysis revealed heterogeneity or horizontal pleiotropy.When gut microbiota were used as exposure and osteonecrosis due to drugs as the outcome,Mendelian randomization analysis found that seven bacterial traits were positively correlated to osteonecrosis due to drugs,nine bacterial traits were negatively related to osteonecrosis due to drugs.When osteonecrosis due to drugs were used as exposure and gut microbiota as the outcome,reverse Mendelian randomization analysis found a negative correlated relationship with five bacterial traits and a positive causal relationship with one bacterial trait.By changing the diversity and composition of gut microbiota,it is expected to improve the incidence and prognosis of osteonecrosis due to drugs,providing new ideas for the study of orthopedic diseases.
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The heterogeneity of sepsis plays critical roles in determining the response of clinical intervention and the outcome of sepsis.Based on the host-response revealed from multiomics,the new idea of the endotype of sepsis was revealed from multiple perspectives,such as transcriptome,proteome,epigenome,and exosome signature spectrum,etc.In recent years,in the field of sepsis endotype,the research of clinical subtype,metabolic subtype,and immune subtype is booming.This concept has gradually penetrated into multiple aspects,including the diagnosis,severity assessment,patients screening for clinical research,and the reference for individualized clinical treatment.It brings a new perspective for clinical individualized treatment of sepsis.
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Fragile X syndrome(FXS)is caused by abnormal duplication and amplification of the FMR1 gene CGG.This article reports a pair of brothers diagnosed with FXS by genetic testing.Two patients,aged 15 and 14 years old respectively,both had clinical manifestations such as language disorders,intellectual disabilities,attention deficit disorder,autism spectrum disorder,and FXS's characteristic facial features.The proband had a rare late-onset epileptic seizure,which was well treated with levetiracetam,while his younger brother had no electroencephalogram abnormalities after repeated follow-up.This pair of cases suggests that the clinical phenotype of FXS has diversity and heterogeneity.
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Objective:To analysis the job preference and heterogeneity of medical students by distinguishing their birthplaces,and to provide reference for optimizing the management of primary health care resources.Methods:Using a cluster sampling method,an online survey of discrete choice experiment was conducted with 925 medical students from six teaching hospitals in Beijing,741 valid questionnaires were obtained,the effective recovery rate was 80.1%.The mixed logit model was used to perform regression analysis on six job attributes and estimate the willingness to pay.Results:There were significant differences in the choice of work location among medical students from different birthplaces.The subgroup results showed that compared to medical students from city,undergraduates from rural and county district preferred a work with sufficient career development opportunities.The results of undergraduate subgroup showed that undergraduates from rural district preferred a work with good environment than those from other birthplaces.Conclusion:There is heterogeneity in job preferences of medical students from different birthplaces.Policy makers should pay attention to the medical students'birthplace,also take the educational level into account to optimize the diversified job attributes,formulating targeted intervention to attract primary health care talents.
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Abstract The northwestern portion of the Upper Paraná Atlantic Forest ecoregion is one of the most disturbed and fragmented areas in the Atlantic Forest, and little is known about the local avifauna. In this study, we have described the composition and diversity of the aquatic avifauna of this region and analyzed the patterns of similarity with respect to the seasonal as well as spatial distribution. We used the line transect sampling technique in six distinct humid areas (including lentic and lotic water bodies) during the dry and rainy seasons of 2012 and 2013. A total of 52 species of waterfowl were recorded. The species richness of the studied areas was surprisingly distinct; only seven waterfowl species, namely Cairina moschata (Linnaeus, 1758), Tigrisoma lineatum (Boddaert, 1783), Rosthramus sociabilis (Vieillot, 1817), Aramus guarauna (Linnaeus, 1766), Vanellus chilensis (Molina, 1782), Jacana jacana (Linnaeus, 1766), and Arundinicola leucocephala (Linnaeus, 1764), were common to these six studied areas. This indicated that the other bird species that were observed might be habitat selective. Moreover, the analysis of the composition of birds in the two seasons (dry and rainy) combined with their spatial distributions showed significant dissimilarities between the areas with lotic (river and constructed wetland) and lentic (lagoons) characteristics. Nevertheless, despite the small extent and low total richness of the entire study area, it was found to be home to 1/3 of all freshwater aquatic birds documented in the state of São Paulo, with the record of 5 migratory species and 11 new species added to the northwest of the state. The heterogeneity of local aquatic environments, habitat selection combined with seasonality, and the absence of other humid locations in the surroundings can explain the diversity and distribution of these birds in the water bodies of this uninvestigated Atlantic Forest ecoregion.
Resumo A porção noroeste da ecorregião Floresta Atlântica do Alto Paraná é uma das mais alteradas e fragmentadas da Mata Atlântica, da qual pouco se sabe sobre a avifauna local. Nosso objetivo foi descrever a diversidade e composição da avifauna aquática, bem como analisar os padrões de similaridade quanto a distribuição temporal e espacial destas aves nesta ecorregião. Utilizamos a transecção linear para amostragem em seis áreas úmidas (corpos dágua lênticos e lóticos), nos períodos de seca e chuva entre 2012 e 2013. Registramos 52 espécies de aves aquáticas e as riquezas das áreas mostraram-se distintas, pois apenas Cairina moschata (Linnaeus, 1758), Tigrisoma lineatum (Boddaert, 1783), Rosthramus sociabilis (Vieillot, 1817), Aramus guarauna (Linnaeus, 1766), Vanellus chilensis (Molina, 1782), Jacana jacana (Linnaeus, 1766), and Arundinicola leucocephala (Linnaeus, 1764) foram comuns às seis áreas, o que indica seleção de habitat. Quando analisada a composição das aves nos dois períodos aliada à distribuição espacial, encontramos dissimilaridades temporais acentuadas entre os ambientes com características lóticas (rio e aterro) e lênticas (lagoas). Isto mostra que, além das diferentes épocas sazonais, é necessário analisar separadamente os diferentes tipos de áreas úmidas. Por fim, apesar da extensão pequena e baixa riqueza total, a área amostrada abrigou 1/3 das aves aquáticas de água doce para o estado de São Paulo, cinco espécies migratórias e 11 novas espécies para o noroeste do estado. A heterogeneidade de ambientes aquáticos locais, forte seleção de habitat aliada à sazonalidade e ausência de outros locais úmidos em seu entorno, explicam a diversidade e distribuição destas aves estreitamente relacionadas aos corpos dágua desta desconhecida ecorregião da Mata Atlântica.
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Abstract Objectives We aimed to explore the heterogeneity and differentiation trajectories of epithelial cells and NK/T-cells in Laryngeal Squamous Cell Carcinoma (LSCC). Methods We downloaded the GSE150321 data set containing LSCC01 and LSCC02 samples single cell RNA data from Gene Expression Omnibus. The UMAP analysis was performed to identify the cell subpopulations and cell locations of subpopulations. Seurat package was used to analyze the differential expression of genes. The function of differential expression genes was analyzed using DAVID database. The monocle2 package was used to analyze differentiation trajectories. We used the CellChat package to observe the signaling pathways and ligand-receptor pairs for epithelial cells and NK/T-cells. Results All the LSCC cells were divided into 16 subpopulation that included 7 epithelial cell subsets, 3 T-cell subsets. The function analysis indicated that epithelial cells and NK/T-cells mainly participated in different process, such as cell cycle, immune response, and cell migration. Then, the results of differentiation trajectory indicated that the ability of migration, and the activation of the immune system increases, while the ability of apoptosis, and glucose metabolic process decreases as pseudotime. Migration-related epithelial cells act on all T-cells via the CNTN2-CNTN2 ligand-receptor pair, which suggested that CNTN2 might be an important biomarker for regulating migration of epithelial cells. Conclusions Our study characterized the heterogeneity of LSCC, which provided novel insights into LSCC and identified a new mechanism and target for clinical LSCC threapies. Evidence IV.
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Background: Much controversies have been associated with the pathogenicity of Mycoplasma hominis but little has been done to unravel the mystery behind the different views. This study aimed at investigating the genetic variants abounding within M. hominis and the distribution of the virulent genes among the variants. Methodology: Twenty (20) M. hominis isolates from high vaginal swabs of women (11 from pregnant women and 9 from women presenting with infertility) attending the Obstetrics and Gynaecology clinics of Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria, were sequenced using 16S rRNA universal gene target for the purpose of phylogenetic analysis and epidemiological typing. The isolates were also screened for the presence of M. hominis variable adherence antigen (vaa) and p120 virulent genes using primer constructs from the respective genes in a conventional PCR protocol. Results: Of the 20 M. hominis vaginal isolates, 4 phylogenetic strains were detected; strain MHS43 constituted 10/20 (50.0%) [2/9 (22.2%) from infertile women and 8/11 (72.7%) from pregnant women]; strain MHBS constituted 3/20 (15%) [3/9 (33.3%) from infertile women and 0/11 (0%) from pregnant women]; strain MHSWP2 constituted 4/20 (20.0%) [3/9 (33.3%) from infertile women and 1/11 (9.1%) from pregnant women]; while strain MHKC87 constituted 3/20 (15%) [1/9 (11.1%) from infertile women and 2/11 (18.2%) from pregnant women].Each of vaa and p120 genes was detected in 14 of 20 isolates, while 6 isolates did not carry the genes. A 2-way ANOVA test showed that none of the genes was significantly associated with a particular strain (p=0.8641). Conclusions: The different views regarding the pathogenicity of M. hominis may be linked to the heterogeneity within the species and lack of homogeneity in the virulent genes as witnessed both in the intra species and intra strain levels.
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Humans , Mycoplasma hominis , Virulence Factors , Sprains and Strains , Virulence , Population Characteristics , Pregnant Womenالملخص
Aim To investigate the effect of AICAR on the expression of the proto-oncogene c-Myc and cell proliferation rates in specific cancer cell lines. Methods The mRNA levels of c-Myc were evaluated using fluorescence-based qRT-PCR to examine the effect of AICAR treatment on c-Myc mRNA expression levels. Western blot was used to evaluate the protein levels of c-Myc following AICAR treatment. RNA interference was employed to determine whether the regulatory effect of AICAR on c-Myc was dependent on AMPK and the downstream metabolic enzymes relating to AICAR. Actinomycin D and cycloheximide were used to assess the effect of AICAR on the stability of cMyc mR-NA and protein. Western blot was used to examine the regulatory effect of AICAR on c-Myc in various cancer cell lines. The MTT assay was used to determine the effect of AICAR on cell viability in these cell lines. Results AICAR significantly up-regulated c-Myc at both mRNA and protein levels. The protein level of c-Myc reached a plateau 12 h after the AICAR treatment. The up-regulatory effect of c-Myc induced by AICAR was not dependent on either the AMPK signaling pathway or the downstream metabolites of AICAR. AICAR could significantly enhance the mRNA stability of c-Myc but did not affect the protein stability. The up-regulation of c-Myc induced by AICAR was cell-type specific. AICAR up-regulated c-Myc in SW1990, 786-0, and A549, while down-regulated c-Myc in HepG2, MCF7, and U20S. In HepG2 cells, AICAR treatment decreased cell viability. However, in SW1990 and A549 cells, AICAR treatment did not lead to any significant difference in cell viability. AICAR decreased the cell viability only when c-Myc was knocked down in SW1990 and A549 cells. Conclusions AICAR directly up-regulates c-Myc expression in an AMPK-independent manner. The up-regulation effect is cell-type dependent. The regulation of c-Myc expression by AICAR is linked to the inhibitory effect of AICAR on tumor cell proliferation.
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Pericytes are essential components of vessel mural cells that function to regulate blood flow, clear or phagocytose debris, and are contractile cells enwrapping capillaries throughout the body. It controls vascular permeability and is involved in the development of blood vessels and is an important regulator and potential drug target of angiogenesis and vascular function. Pericytes are also thought to play a key role in the tumor microenvironment, especially during tumor growth and distal metastasis. Therefore,in this review we discuss the relationship between pericytes involved in tumor angiogenesis and tumor metastasis, as well as the use of targeted pericytes to treat tumors,with a view to providing a basis for subsequent studies.
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Although the body has a strong immune system which can resists the invasion of leukemia cells, leukemia cells disseminate systemically and form an immunosuppressive microenvironment through a variety of mechanisms, including regulation of antigen presentation, utilization of immunosuppressive enzyme AXL, immune cell inhibitory checkpoint NKG2A and immunoregulatory gene VISTA, resulting in immune escape. Therefore, most types of leukemia are inevitable for the affliction of drug resistance or relapse, and the immune efficacy is not as significant as that of other hematological tumors and the prognosis is suboptimal. This article reviews the immune heterogeneity of leukemia microenvironment from many aspects, including anti-leukemia immunity and immune escape. In addition, it also reviews the latest progress and future prospects of immune checkpoint inhibition, adoptive cell therapy and vaccine therapy in leukemia, providing a theoretical basis for the development of personalized combination therapy strategies with less toxic side effects.
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Humans , Immunotherapy/methods , Leukemia/therapy , Immunity , Combined Modality Therapy , Prognosis , Tumor Microenvironmentالملخص
Primary liver cancer includes three types: Hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular carcinoma and cholangiocarcinoma. Among them, hepatocellular carcinoma accounts for 75% to 85%, posing a serious threat to human life and health. The screening and monitoring of high-risk populations for hepatocellular carcinoma is crucial for early detection, diagnosis, and treatment, as well as for improving the prognosis of liver cancer. Serum biomarkers play an important role in monitoring and diagnosing hepatocellular carcinoma. In recent years, new serum biomarkers such as AFP heterogeneity, abnormal prothrombin/de-γ-carboxyprothrombin, Golgi protein 73, Dickkopf-associated protein 1, aldehyde ketone reductase-AKR1B10, gypican 3, liquid biopsies and microRNAs have been recommended for screening and monitoring hepatocellular carcinoma, and some have been included as auxiliary diagnostic measures in liver cell carcinoma guidelines. This article summarizes the progress of relevant basic research and clinical evaluation of these novel biomarkers, which may provide a reference for future clinical application.