Neutrophils are the most abundant myeloid-derived eukaryotic cells in human blood with increasingly recognized as important regulators of cancer progression. However, the functional importance of tumor-associated neutrophils (TANs) is often overlooked due to their short-lived, terminally differentiated, non-proliferative properties. In recent years, a wealth of evidences obtained from experimental tumor models and cancer patients had indicated that TANs had obvious heterogeneity in morphology and function, and TANs had dual functions of pro- and anti-tumor in cancer patients. This review provides an adequate overview of the heterogeneity and distinct roles of neutrophils.
Randomized controlled trials are the gold standard for evaluating the effects of medical interventions, primarily providing estimates of the average effect of an intervention in the overall study population. However, there may be significant differences in the effect of the same intervention across sub-populations with different characteristics, that is, treatment heterogeneity. Traditional subgroup analysis and interaction analysis tend to have low power to examine treatment heterogeneity or identify the sources of heterogeneity. With the recent development of machine learning techniques, causal forest has been proposed as a novel method to evaluate treatment heterogeneity, which can help overcome the limitations of the traditional methods. However, the application of causal forest in the evaluation of treatment heterogeneity in medicine is still in the beginning stage. In order to promote proper use of causal forest, this paper introduces its purposes, principles and implementation, interprets the examples and R codes, and highlights some attentions needed for practice.
Objective To summarize the advancement of breast cancer stem cells and genotyping and analyze the correlation between the two. Methods Relevant literatures about breast cancer stem cells and genotyping, which were published recently were collected and reviewed. Results Cancer stem cell origin theory was supported by researches of correlation between breast cancer stem cells and genotyping, which also explained the complexity of intrinsic subtypes and heterogeneity of breast cancer. Conclusions A new way can be detected to study the formation mechanism and biological characteristics of breast cancer at the cellular and molecular level by researches of correlation between breast cancer stem cells and genotyping, which are expected to provide new strategies and tools for diagnosis and treatment of breast cancer.
ObjectiveWhen using multi-center data to construct clinical prediction models, the independence assumption of data will be violated, and there is an obvious clustering effect among research objects. In order to fully consider the clustering effect, this study intends to compare the model performance of the random intercept logistic regression model (RI) and the fixed effects model (FEM) considering the clustering effect with the standard logistic regression model (SLR) and the random forest algorithm (RF) without considering the clustering effect under different scenarios. MethodsIn the process of forecasting model establishment, the prediction performance of different models at the center level was simulated when there were different degrees of clustering effects, including the difference of discrimination and calibration in different scenarios, and the change trend of this difference at different event rates was compared. ResultsAt the center level, different models, except RF, showed little difference in the discrimination of different scenarios under the clustering effect, and the mean of their C-index changed very little. When using multi-center highly clustered data for forecasting, the marginal forecasts (M.RI, SLR and RF) had calibrated intercepts slightly less than 0 compared with the conditional forecasts, which overestimated the average probability of prediction. RF performed well in intercept calibration under the condition of multi-center and large samples, which also reflected the advantage of machine learning algorithm for processing large sample data. When there were few multiple patients in the center, the FEM made conditional predictions, the calibrated intercept was greater than 0, and the predicted mean probability was underestimated. In addition, when the multi-center large sample data were used to develop the prediction model, the slopes of the three conditional forecasts (FEM, A.RI, C.RI) were well calibrated, while the calibrated slopes of the marginal forecasts (M.RI and SLR) were greater than 1, which led to the problem of underfitting, and the underfitting problem became more prominent with the increase in the central aggregation effect. In particular, when there were few centers and few patients, overfitting of the data could mask the difference in calibration performance between marginal and conditional forecasts. Finally, the lower the event rate the central clustering effect at the central level had a more pronounced impact on the forecasting performance of the different models. ConclusionThe highly clustered multi-center data are used to construct the model and apply it to the prediction in a specific environment. RI and FEM can be selected for conditional prediction when the number of centers is small or the difference between centers is large due to different incidence rates. When the number of hearts is large and the sample size is large, RI can be selected for conditional prediction or RF for edge prediction.
The assumption of fixed-effects model is based on that the true effect of the each trial is same. However, the assumption of random-effects model is based on that the true effect of included trials is normal distributed. The total variance is equal to the sum of within-trial variance and between-trial variance under the random-effects model. There are many estimators of the between-trial variance. The aim of this paper is to give a brief introduction of the estimators of between-trial variance in trial sequential analysis for random-effects model.
Objective To summarize and review the heterogeneity of bone marrow derived stem cells (BMDSCs) and its formation mechanism and significance, and to analyze the possible roles and mechanisms in intestinal epithel ial reconstruction. Methods The related l iterature about BMDSCs heterogeneity and its role in intestinal epithel ial repair was reviewed and analyzed. Results The heterogeneity of BMDSCs provided better explanations for its multi-potency. The probable mechanisms of BMDSCs to repair intestinal epithel ium included direct implantation into intestinal epithel ium, fusion between BMDSCs and intestinal stem cells, and promotion of injury microcirculation reconstruction. Conclusion BMDSCs have a bright future in gastrointestinal injury caused by inflammatory bowl disease and regeneration.
Through collecting and synthesizing the paper concerning the method of dealing with heterogeneity in the meta analysis, to introduce the multi-levels statistical models, such as meta regression and baseline risk effect model based on random effects, and random effects model based on hierarchical bayes, and to introduce their application of controlling the meta analysis heterogeneity. The multi-levels statistical model will decompose the single random error in the traditional model to data structure hierarchical. Its fitting effect can not only make the meta-analysis result more robust and reasonable, but also guide clinical issues through the interpretation of association variable.
Compared with traditional head to head meta-analysis, network meta-analysis has more confounding factors and difficulties to handle. Due to the mutual transitivity of evidence in network meta-analysis, heterogeneity may be brought into indirect meta-analysis. Hence, effective differentiation and correct handling of heterogeneity are being current focus. In order to ensure the reliability of the results of network meta-analysis, the concept of homogeneity is proposed and a series of methods are developed for differentiation and handling of homogeneity. Based on the extension of Bucher methods, current methods for differentiation and handling of homogeneity has extended to ten quantitative measures (eg., node analysis method, hypothesis tests, and two-step method). However, because of the differences and the focus of fundamental methodological theories as well as the limitation of statistics power, no highly-effective method has been worked out. Therefore, the exploration of highly-effective, simple and high-resolved methods are still needed.
ObjectiveTo summarize the expression and role of CD146 in mesenchymal stem cells (MSCs).MethodsThe literature related to CD146 at home and abroad were extensively consulted, and the CD146 expression in MSCs and its function were summarized and analyzed.ResultsCD146 is a transmembrane protein that mediates the adhesion of cells to cells and extracellular matrix, and is expressed on the surface of various MSCs. More and more studies have shown that CD146+ MSCs have superior cell properties such as greater proliferation, differentiation, migration, and immune regulation abilities than CD146- or unsorted MSCs, and the application of CD146+ MSCs in the treatment of specific diseases has also achieved better results. CD146 is also involved in mediating a variety of cellular signaling pathways, but whether it plays the same role in MSCs remains to be demonstrated by further experiments.ConclusionThe utilization of CD146+ MSCs for tissue regeneration will be conducive to improving the therapeutic effect of MSCs.
ObjectiveTo understand the single-cell RNA sequencing (scRNA-seq) and its research progress in the tumor microenvironment (TME) of breast cancer, in order to provide new ideas and directions for the research and treatment of breast cancer. MethodThe development of scRNA-seq technology and its related research literature in breast cancer TME at home and abroad in recent years was reviewed. ResultsThe scRNA-seq was a quantum technology in high-throughput sequencing of mRNA at the cellular level, and had become a powerful tool for studying cellular heterogeneity when tissue samples were fewer. While capturing rare cell types, it was expected to accurately describe the complex structure of the TME of breast cancer. ConclusionsAfter decades of development, scRNA-seq has been widely used in tumor research. Breast cancer is a malignant tumor with high heterogeneity. The application of scRNA-seq in breast cancer research can better understand its tumor heterogeneity and TME, and then promote development of personalized diagnosis and treatment.