Immunotherapies have become the backbone of cancer treatment. Among them, chimeric antigen receptor (CAR) T cells have demonstrated great success in the treatment of hematological malignancies. However, CAR T therapy against solid tumors is less effective. Antigen targeting; an immunosuppressive tumor microenvironment (TME); and the infiltration, proliferation, and persistence of CAR T cells are the predominant barriers preventing the extension of CAR T therapy to solid tumors. To circumvent these obstacles, the next-generation CAR T cells will require more potent antitumor properties, which can be achieved by gene-editing technology. In this review, we summarize innovative strategies to enhance CAR T cell function by improving target identification, persistence, trafficking, and overcoming the suppressive TME. The construction of multi-target CAR T cells improves antigen recognition and reduces immune escape. Enhancing CAR T cell proliferation and persistence can be achieved by optimizing costimulatory signals and overexpressing cytokines. CAR T cells equipped with chemokines or chemokine receptors help overcome their poor homing to tumor sites. Strategies like knocking out immune checkpoint molecules, incorporating dominant negative receptors, and chimeric switch receptors can favor the depletion or reversal of negative T cell regulators in the TME.
The purpose of this study was to explore the relevant factors that affect the risk of cesarean scar diverticulum (CSD). A retrospective, case-control study was designed among women with a history of cesarean section (CS) who were admitted in Zhejiang Tongde Hospital from January 2017 to December 2019. Women with missing information were excluded. The basic clinical characteristics and the risk factors for CSD were assessed using univariate analysis and multivariate logistic regression analysis. A total of 216 women were analyzed, including 87 patients with CSD and 129 cases without CSD as control. Significant differences in number of CS, trial of labor (elective or urgent CS), CS interval, uterine position, intraoperative hemorrhage, and dysmenorrhea between CSD group and control group (P < .05). Multivariate logistic regression analysis showed that number of CS, trial of labor, interval of CS, and uterine position were independent risk factors of CSD. In women with a history of CS, multiple cesarean deliveries, elective CS, cesarean interval of less than 5 years, and retroflexed position of the uterus may be associated with an elevated risk of CSD.
Background: Several previous randomized controlled trials (RCTs) evaluated the efficacy of metformin combined with simvastatin in the treatment of polycystic ovary syndrome (PCOS), yet the results of the researches are not consistent. It is necessary to conduct a meta-analysis to explore the efficacy and safety of metformin combined with simvastatin in the treatment of PCOS, to provide evidence supports for the treatment of PCOS.Methods: We searched PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese biomedical literature databases online to identify the RCTs evaluating the efficacy of metformin combined with simvastatin in the treatment of PCOS. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to evaluate the synthesized effects.Results: Nine RCTs with a total of 746 PCOS patients were included. The synthesized results indicated that the combined use of metformin and simvastatin are more beneficial to reduce the total cholesterol (SMD -2.66, 95% CI -3.65 to -1.66), triglycerides (SMD -1.25, 95% CI -2.02 to -0.49), low density lipoprotein (SMD -2.91, 95% CI -3.98 to -1.84), testosterone (SMD -0.64, 95% CI -1.13 to -0.15), fasting insulin (SMD -1.17, 95% CI -2.09 to -0.26) than metformin alone treatment in PCOS patients (all P < .001), and there was no significant difference in the high density lipoprotein (SMD -0.05, 95% CI -0.56-0.46), luteinizing hormone (SMD -0.58, 95% CI -1.66 to -0.50), follicle stimulating hormone (SMD 0.41, 95% CI -0.78-1.59), prolactin (SMD -1.38, 95% CI -2.93-0.17), fasting blood sugar (SMD 0.23, 95% CI -0.52-0.97), and insulin sensitivity index (SMD -0.17, 95% CI -0.48-0.15) between experimental and control groups (all P > .05).Conclusions: Metformin combined with simvastatin is superior to metformin alone in the treatment of PCOS patients with more advantages in improving the levels of sex hormones, blood lipids, and blood sugar. However, the safety of this therapy still needs to be further explored in clinical studies with high-quality and large samples. Abbreviations: 95% CI = 95% confidence interval, FBS = fasting blood sugar, FIN = fasting insulin, FSH = follicle stimulating hormone, HDL = high density lipoprotein, LDL = low density lipoprotein, OR = odds ratio, PCOS = polycystic ovary syndrome, RCT = randomized controlled trial, SMD = standardized mean difference, T = testosterone, TC = total cholesterol, TG = triglycerides.
Little is known about the prognostic risk factors of endometrial cancer. Therefore, finding effective prognostic factors of endometrial cancer is the vital for clinical theranostic. In this study, we constructed an inflammatory-related risk assessment model based on TCGA database to predict prognosis of endometrial cancer. We screened inflammatory genes by differential expression and prognostic correlation, and constructed a prognostic model using LASSO regression analysis. We fully utilized bioinformatics tools, including ROC curve, Kaplan–Meier analysis, univariate and multivariate Cox regression analysis and in vitro experiments to verify the accuracy of the prognostic model. Finally, we further analyzed the characteristics of tumor microenvironment and drug sensitivity of these inflammatory genes. The higher the score of the endometrial cancer risk model we constructed, the worse the prognosis, which can effectively provide decision-making help for clinical endometrial diagnosis and treatment.
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