Background
Body mass index(BMI) in children appears to be associated with Otitis media with effusion(OME) in observational studies, but the causal relationship is not clear.
Methods
A two-sample ...Mendelian randomization (MR) study was used to explore the causal relationship between childhood BMI and OME in people of European ancestry. Genome-wide association studies (GWAS) of childhood BMI were used as exposures (n = 61,111), while GWAS of OME were used as outcomes (n = 429,290). The weighted inverse variance method (IVW) was used as a baseline method to test for causality. In addition, MR-Egger, simple mode analysis, weighted median, and weighted mode were used as complementary methods.MR-PRESSO analysis, MR-Egger intercept analysis, and Cochran’s Q statistical analysis were also used to detect possible directional heterogeneity and polymorphism. To assess this association, we used ratios (OR) with 95% confidence intervals (ci). All statistical analyses were performed in R.
Results
We selected 22 genome-wide significant single nucleotide polymorphisms (SNPs) from GWAS as instrumental variables (IVW). the IVW approach showed evidence supporting a causal relationship between BMI and OME in children (β = 0.265, SE = 0.113, P = 0.018). MR-Egger regression showed that targeted polymorphisms were unlikely to bias the results bias (intercept=-0.022; P = 0.488), but there was no causal relationship between BMI and OME (β = 0.584, SE = 0.465, P = 0.224). Although the results of the IVW and MR Egger analyses were not consistent, the IVW analysis maintained higher precision, and the Cochran Q test, heterogeneity and polymorphism tests showed no heterogeneity, no directionality and no polymorphism.
Conclusions
MR studies suggest that genetically predicted body mass index in childhood is associated with an increased risk of OME. Notably, given the limitations of this study, the mechanism of association between body mass index and OME in childhood needs further investigation. These results support the importance of effective management of obesity, which may reduce OME occurrence and decrease OME recurrence.
Purpose The aim of the present study was to investigate the prognostic value of tumor-infiltrated lymphocytes (TILs), especially the prognostic value of Foxp3+ regulatory T cells (Tregs), CD8+ CTLs ...and Tregs/CD8+ ratios in gastric cancer patients after R0 resection. Patients and methods From 133 patients, CD4+, CD8+ and Foxp3+ TILs were assessed by immunohistochemistry in tissue microarrays and N1 regional lymph nodes sections containing gastric cancer. The prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff, while the effects of Foxp3+/CD8+ ratios were evaluated using the value determined by ROC cure analysis as cutoff. Results It was found that CD4+ and CD8+ TILs were not associated with overall survival (OS). In the tumor sites, higher Foxp3+ Tregs/CD8+ ratio was an independent factor for worse OS (multivariate analysis HR = 2.827, P = 0.037). The 1-year, 2-year and 3-year OS rates were 90, 77.5 and 70% for the group with intratumoral high Tregs/CD8+ ratio, compared with 100, 94.3 and 90.5% for the group with intratumoral low ratio. At the same time, the presence of intratumoral high Foxp3+ Tregs was also associated with worse OS (log rank test, P = 0.025); however, it was not an independent predictor and correlated with intratumoral Foxp3+ Tregs/CD8+ ratio (χ ² test, P < 0.001). Although the infiltration of Foxp3+ Tregs in N1 regional lymph nodes was associated with lymph node metastasis (P = 0.028), it was not associated with prognosis (P = 0.458). Conclusions Intratumoral high Foxp3+ Tregs/CD8+ ratio was an independent predictor for the prognosis of gastric cancer. It can be inferred that a combination of deletion of Tregs and stimulation of CD8+ effector T cells may be an effective immunotherapy to prolong survival after surgery.
To investigate the correlation between environmental-meteorological factors and daily visits for acute otitis media (AOM) in Lanzhou, China.
Data were collected in 2014–2016 by the Departments of ...Otolaryngology-Head and Neck Surgery at two hospitals in Lanzhou. Relevant information, including age, sex and visiting time, was collected. Environmental data included air quality index, PM10, PM2.5, O3, CO, NO2 and SO2, and meteorological data included daily average temperature (T, °C), daily mean atmospheric pressure (AP, hPa), daily average relative humidity (RH, %) and daily mean wind speed (W, m/s). The SPSS22.0 software was used to generate Spearman correlation coefficients in descriptive statistical analysis, and the R3.5.0 software was used to calculate relative risk (RR) and to obtain exposure-response curves. The relationship between meteorological-environmental parameters and daily AOM visits was summarized.
Correlations were identified between daily AOM visits and CO, O3, SO2, CO, NO2, PM2.5 and PM10 levels. NO2, SO2, CO, AP, RH and T levels significantly correlated with daily AOM visits with a lag exposure-response pattern. The effects of CO, NO2, SO2 and AP on daily AOM visits were significantly stronger compared to other factors (P < 0.01). O3, W, T and RH were negatively correlated with daily AOM visits. The highest RR lagged by 3–4 days.
The number of daily AOM visits appeared to be correlated with short-term exposure to mixed air pollutants and meteorological factors from 2014 through 2016 in Lanzhou.
The main obstacle to a patient's recovery following a tonsillectomy is complications, and bleeding is the most frequent culprit. Predicting post-tonsillectomy hemorrhage (PTH) allows for accurate ...identification of high-risk populations and the implementation of protective measures. Our study aimed to investigate how well machine learning models predict the risk of PTH.
Data were obtained from 520 patients who underwent a tonsillectomy at The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army. The age range of the patients was 2-57 years, and 364 (70%) were male. The prediction models were developed using five machine learning models: decision tree, support vector machine (SVM), extreme gradient boosting (XGBoost), random forest, and logistic regression. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was used to interpret the results of the best-performing model.
The frequency of PTH was 11.54% among the 520 patients, with 10.71% in the training group and 13.46% in the validation set. Age, BMI, season, smoking, blood type, INR, combined secretory otitis media, combined adenoidectomy, surgical wound, and use of glucocorticoids were selected by mutual information (MI) method. The XGBoost model had best AUC (0.812) and Brier score (0.152). Decision curve analysis (DCA) showed that the model had a high clinical utility. The SHAP method revealed the top 10 variables of MI according to the importance ranking, and the average of the age was recognized as the most important predictor variable.
This study built a PTH risk prediction model using machine learning. The XGBoost model is a tool with potential to facilitate population management strategies for PTH.
The aim of this study was to investigate the prognostic value of chemokine receptor CCR7 expression and intratumoral FOXP3(+) regulatory T cells (Tregs) in gastric cancer. CCR7(+) tumor cells and ...FOXP3(+) Tregs were assessed by immunohistochemistry in tissue microarrays containing gastric cancer from 133 patients. Prognostic effects of low or high CCR7 and FOXP3 expression were evaluated by Cox regression and Kaplan-Meier analysis, as well as the correlation between CCR7 positive score and intratumoral FOXP3(+) cell number in a longitudinal assessment. The analysis showed that the high expression levels of CCR7 and FOXP3 were detected in 69.9% and 65.4% of cases, respectively. High CCR7 expression in gastric cancer cells was significantly associated with poor overall survival (OS) (P = 0.010) and lymph node metastasis (P = 0.009), and was an independent factor for worse OS (P = 0.023) by multivariate analysis. High numbers of intratumoral FOXP3(+) Tregs significantly correlated with shorter OS (P = 0.021) and lymph node metastasis (P = 0.024), and was also an independent factor for adverse OS (P = 0.035). Furthermore, there was a significantly positive correlation between CCR7 positive score and intratumoral FOXP3(+) cell number (r = 0.949, P<0.001). These results revealed that CCR7 expression in gastric cancer cells and intratumoral FOXP3(+) Tregs could be considered as a co-indicator of clinical prognosis of gastric cancer.
Angiogenesis is a well-established target in anti-cancer therapy. Although vascular endothelial growth factor (VEGF)-mediated angiogenesis apparently requires the Rho GTPases Rac1 and Cdc42, the ...relevant mechanisms are unclear. Here, we determined that activated Rac1/Cdc42 in MCF-7 breast cancer cells could decrease p53 protein levels and increase VEGF secretion to promote proliferation and tube formation of human umbilical vein endothelial cells (HUVECs). However, these effects are reversed after ubiquitin-proteasome breakage. In exploring potential mechanisms for this relationship, we confirmed that activated Rac1/Cdc42 could enhance p53 protein ubiquitination and weaken p53 protein stability to increase VEGF expression. Furthermore, in a xenograft model using nude mice that stably express active Rac1/Cdc42 protein, active Rac1/Cdc42 decreased p53 levels and increased VEGF expression. Additionally, tumor angiogenesis was inhibited, and p53 protein levels were augmented, by intratumoral injection of the ubiquitin-proteasome inhibitor MG132. Finally in 339 human breast cancer tissues, our analyses indicated that Rac1/Cdc42 expression was related to advanced TNM staging, high proliferation index, ER status, and positive invasive features. In particular, our data suggests that high Rac1/Cdc42 expression is correlated with low wt-p53 and high VEGF expression. We conclude that activated Rac1/Cdc42 is a vascular regulator of tumor angiogenesis and that it may reduce stability of the p53 protein to promote VEGF expression by enhancing p53 protein ubiquitin.
In order to achieve the United Nations 2030 Sustainable Development Goals (SDGs) related to green spaces, monitoring dynamic urban green spaces (UGSs) in cities around the world is crucial. ...Continuous dynamic UGS mapping is challenged by large computation, time consumption, and energy consumption requirements. Therefore, a fast and automated workflow is needed to produce a high-precision UGS map. In this study, we proposed an automatic workflow to produce up-to-date UGS maps using Otsu’s algorithm, a Random Forest (RF) classifier, and the migrating training samples method in the Google Earth Engine (GEE) platform. We took the central urban area of Beijing, China, as the study area to validate this method, and we rapidly obtained an annual UGS map of the central urban area of Beijing from 2016 to 2020. The accuracy assessment results showed that the average overall accuracy (OA) and kappa coefficient (KC) were 96.47% and 94.25%, respectively. Additionally, we used six indicators to measure quality and temporal changes in the UGS spatial distribution between 2016 and 2020. In particular, we evaluated the quality of UGS using the urban greenness index (UGI) and Shannon’s diversity index (SHDI) at the pixel level. The experimental results indicate the following: (1) The UGSs in the center of Beijing increased by 48.62 km2 from 2016 to 2020, and the increase was mainly focused in Chaoyang, Fengtai, and Shijingshan Districts. (2) The average proportion of relatively high and above levels (UGI > 0.5) in six districts increased by 2.71% in the study area from 2016 to 2020, and this proportion peaked at 36.04% in 2018. However, our result revealed that the increase was non-linear during this assessment period. (3) Although there was no significant increase or decrease in SHDI values in the study area, the distribution of the SHDI displayed a noticeable fluctuation in the northwest, southwest, and northeast regions of the study area between 2016 and 2020. Furthermore, we discussed and analyzed the influence of population on the spatial distribution of UGSs. We found that three of the five cold spots were located in the east and southeast of Haidian District. Therefore, the proposed workflow could provide rapid mapping and dynamic evaluation of the quality of UGS.
Lysophosphatidic acid (LPA) is an active phospholipid signaling molecule that binds to six specific G protein-coupled receptors (LPA1-6) on the cell surface and exerts a variety of biological ...functions, including cell migration and proliferation, morphological changes, and anti-apoptosis. The earliest study from our group demonstrated that LPA treatment could restore cochlear F-actin depolymerization induced by noise exposure, reduce hair cell death, and thus protect hearing. However, whether LPA could protect against cisplatin-induced ototoxicity and which receptors play the major role remain unclear. To this end, we integrated the HEI-OC1 mouse cochlear hair cell line and zebrafish model, and found that cisplatin exposure induced a large amount of reactive oxygen species accumulation in HEI-OC1 cells, accompanied by mitochondrial damage, leading to apoptosis and autophagy. LPA treatment significantly attenuated autophagy and apoptosis in HEI-OC1 cells after cisplatin exposure. Further investigation revealed that all LPA receptors except LPA3 were expressed in HEI-OC1 cells, and the mRNA expression level of LPA1 receptor was significantly higher than that of other receptors. When LPA1 receptor was silenced, the protective effect of LPA was reduced and the proportion of apoptosis cells was increased, indicating that LPA-LPA1 plays an important role in protecting HEI-OC1 cells from cisplatin-induced apoptosis. In addition, the behavioral trajectory and in vivo fluorescence imaging results showed that cisplatin exposure caused zebrafish to move more actively, and the movement speed and distance were higher than those of the control and LPA groups, while LPA treatment reduced the movement behavior. Cisplatin caused hair cell death and loss in zebrafish lateral line, and LPA treatment significantly protected against hair cell death and loss. LPA has a protective effect on hair cells in vitro and in vivo against the cytotoxicity of cisplatin, and its mechanism may be related to reducing apoptosis, excessive autophagy and ROS accumulation.
CCL21 is known to attract dendritic cells (DCs) and T cells that may reverse tumor-mediated immune suppression. The massive infiltration of tumors by regulatory T cells (Tregs) prevents the ...development of a successful helper immune response. In this study, we investigated whether elimination of CD4(+) CD25(+) Tregs in the tumor microenvironment using anti-CD25 monoclonal antibodies (mAbs) was capable of enhancing CCL21-mediated antitumor immunity in a mouse hepatocellular carcinoma (HCC) model. We found that CCL21 in combination with anti-CD25 mAbs (PC61) resulted in improved antitumor efficacy and prolonged survival, not only inhibited tumor angiogenesis and cell proliferation, but also led to significant increases in the frequency of CD4(+), CD8(+) T cells and CD11c(+) DCs within the tumor, coincident with marked induction of tumor-specific CD8(+) cytotoxic T lymphocytes (CTLs) at the local tumor site. The intratumoral immune responses were accompanied by the enhanced elaboration of IL-12 and IFN-γ, but reduced release of the immunosuppressive mediators IL-10 and TGF-β1. The results indicated that depletion of Tregs in the tumor microenvironment could enhance CCL21-mediated antitumor immunity, and CCL21 combined with anti-CD25 mAbs may be a more effective immunotherapy to promote tumor rejection.
Table 1: thumbnail Download: * PPT PowerPoint slide * PNG larger image * TIFF original image Table 3: thumbnail Download: * PPT PowerPoint slide * PNG larger image * TIFF original image Figures ...Citation: Ma J, Xue Y, Liu W, Yue C, Bi F, Xu J, et al. (2013) Correction: Role of Activated Rac1/Cdc42 in Mediating Endothelial Cell Proliferation and Tumor Angiogenesis in Breast Cancer.
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