Search

Brain tissue segmentation plays a critical role in the diagnosis, treatment, and study of brain diseases. Accurately identifying these boundaries is essential for improving segmentation accuracy. However, distinguishing boundaries between different brain tissues can be challenging, as they often overlap. Existing deep learning methods primarily calculate the overall segmentation results without adequately addressing local regions, leading to error propagation and mis-segmentation along boundaries. In this study, we propose a novel mis-segmentation-focused loss function based on a two-stage nnU-Net framework. Our approach aims to enhance the model’s ability to handle ambiguous boundaries and overlapping anatomical structures, thereby achieving more accurate brain tissue segmentation results. Specifically, the first stage targets the identification of mis-segmentation regions using a global loss function, while the second stage involves defining a mis-segmentation loss function to adaptively adjust the model, thus improving its capability to handle ambiguous boundaries and overlapping anatomical structures. Experimental evaluations on two datasets demonstrate that our proposed method outperforms existing approaches both quantitatively and qualitatively.

Objective To analyze the causes of a case of hemolytic disease of the fetus and newborn (HDFN),and investigate the genetic background of maternal Rh deletion D--formation. Methods Blood samples of maternal and fetus were collected, and ABO blood typing, Rh blood typing, antibody screening and identification test were performed to explore the blood group serological characteristics of Rh deletion type D--, and Rh gene sequence was performed on parturient. Results The maternal blood group was identified to be O type, D--, and the anti-Hr0 antibody against Rh high-frequency antigen was suspected to be caused by multiple pregnancies which passes through the placental barrier and enable fetus to obtain anti Hr0 antibody, leading to HDFN, with genetic testing result as RH RHCE* Ce/RHCE* Ce. Conclusion In-depth research on the formation mechanism of Rh D-- in parturient should be conducted to provide clinical value for HDFN blood exchange treatment and blood transfusion in special blood group population.

ObjectiveThis review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.MethodsWe conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic review and meta-analysis.Results59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the post-hoc analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy.ConclusionOur study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier 345350.

BackgroundPD-1/PD-L1 inhibitors have significantly improved the outcomes of those patients with various malignancies. However, the incidence of adverse events also increased. This meta-analysis aims to systematically evaluate the risk of cardiovascular toxicity in patients treated with PD-1/PD-L1 inhibitors.Materials and methodsWe searched PubMed, Embase, the Cochrane Library databases for all randomized controlled trials (RCTs) comparing all-grade and grade 3-5 cardiovascular toxicity of single-agent PD-1/PD-L1 inhibitors to placebo/chemotherapy, PD-1/PD-L1 inhibitors combined with chemotherapy to chemotherapy, or PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors to single-agent immune checkpoint inhibitors (ICIs) and pooled our data in a meta-analysis stratified by tumor types and PD-1 or PD-L1 inhibitors. The Mantel-Haenszel method calculated the odds ratio (OR) and its corresponding 95% confidence intervals (CIs).ResultsA total of 50 trials were included in the analysis. Single-agent PD-1/PD-L1 inhibitors increased the risk of all-grade cardiotoxicity compared with placebo (OR=2.11, 95%CI 1.02-4.36, P=0.04). Compared with chemotherapy, patients receiving PD-1/PD-L1 inhibitors combined with chemotherapy had a significant higher risk of all-grade (OR=1.53, 95%CI 1.18-1.99, P=0.001) and grade 3-5 cardiotoxicity (OR=1.63, 95%CI 1.11-2.39, P=0.01) cardiotoxicity, especially patients with non-small cell lung cancer (NSCLC) [all-grade cardiotoxicity (OR=1.97, 95%CI 1.14-3.41, P=0.02) and grade 3-5 cardiotoxicity (OR=2.15, 95%CI 1.08-4.27, P=0.03)]. Subgroup analysis showed that PD-1 inhibitors combined with chemotherapy were associated with a higher risk of grade 3-5 cardiotoxicity (OR=2.08, 95%CI 1.18-3.66, P=0.01). Compared with placebo or chemotherapy, single-agent PD-1/PD-L1 inhibitors did not increase the risk of all-grade of myocarditis, arrhythmia and hypertension. However, PD-1/PD-L1 inhibitors combined with chemotherapy increased the risk of all-grade arrhythmia (OR=1.63, 95%CI 1.07-2.46, P=0.02) [PD-L1 inhibitor-containing treatment (OR=1.75, 95%CI 1.09-2.80, P=0.02)], and the risk of all-grade hypertension (OR=1.34, 95%CI 1.02-1.77, P=0.04) and grade 3-5 hypertension (OR=1.54, 95%CI 1.10-2.15, P=0.01).ConclusionsOur results suggest that single-agent PD-1/PD-L1 inhibitors increase the risk of all-grade cardiotoxicity, PD-1/PD-L1 inhibitors combined with chemotherapy increase the risk of all-grade and grade 3-5 cardiotoxicity, especially in those patients treated with PD-1 inhibitor-containing treatment and those with NSCLC. In addition, PD-1/PD-L1 inhibitors combined with chemotherapy increase the risk of arrhythmia and hypertension. Therefore, this evidence should be considered when assessing the benefits and risks of PD-1/PD-L1 inhibitors in treating malignancies.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022303115.

Lung cancer is the leading cause of cancer-related deaths worldwide. As the most prevalent molecular mutation subtypes in non-small cell lung cancer (NSCLC), EGFR-TKIs are currently a standard first-line therapy for targeting the mutated EGFR in advanced NSCLC patients. However, 20-30% of this subset of patients shows primary resistance to EGFR-TKIs. Patients with co-mutations of EGFR and several other genes have a poor response to EGFR-TKIs, whereas the prognostic and predictive significance of EGFR/TP53 co-mutation in NSCLC patients remains controversial. Meanwhile, little is known about how to choose an optimal therapeutic strategy for this subset of patients. Presently, no drugs targeting TP53 mutations are available on the market, and some p53 protein activators are in the early stage of clinical trials. A combination of EGFR-TKIs with antiangiogenic agents or chemotherapy or other agents might be a more appropriate strategy to tackle the problem. In this review, we describe the prognostic and predictive value of EGFR/TP53 co-mutation in NSCLC patients, investigate the mechanisms of this co-mutation affecting the response to EGFR-TKIs, and further explore optimal regimens effectively to prolong the survival time of the NSCLC patients harboring this co-mutation.

Background and Objective Rho family is closely related with the growth , differentiation and metastasis of tumer cells. The objective of this work is to investigate the expression of RhoE in lung and breast carcinoma and their corresponding adjacent tissues, as well as its relationship between the expression and clinical pathological grades. The results of this study provide evidences for exploring the biological functions and clinical significance of RhoE. Methods The expression of RhoE was detected by immunohistochemistry in 62 lung carcinoma samples and 34 breast carcinoma samples, and their corresponding adjacent tissues were taken as control.Results RhoE was generally expressed in normal tissues, but the expression level of RhoE in carcerous tissueswas decreased or absent. The stained value of breast carcinoma was 3.65+/-0.62, but the adjacent cancerous tissueswas 10.53+/-0.44, significantly higher than that of the adjacent cancerous tissues (t=12.402, P

Background Human umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) offer an attractive alternative to bone marrow-derived MSCs (BMMSCs) for cell-based therapy as it is a less invasive source of biological material. However, limited studies have been conducted with hUCMSCs as compared to BMMSCs. The present study was conducted to evaluate the effects of hUCMSCs in esophageal carcinoma (EC). Methods hUCMSCs together with EC cells were transplanted subcutaneously into BALB/c nude mice to observe the effects of hUCMSCs on tumor establishment. hUCMSCs injected through the caudal vein to the mice with pre-established EC to observe the effects of hUCMSCs on tumor outgrowth. In order to elucidate the underlying mechanisms, we also performed in vitro experiments including directly co-culture, transwell assay, proliferation assay and western blotting analysis. Results hUCMSCs promoted EC formation in nude mice. In the in vivo model of pre-established EC, intravenously injected hUCMSCs potently promoted tumor growth. When in vitro cocultured with hUCMSCs, EC cells proliferation increased. After co-cultured with hUCMSCs through transwell system, EC cells showed increased proliferation. Through transwell assay, we also observed that EC cells recruited MSCs, and MSCs promoted EC cells migration and invasion. Western blotting data showed that the expressions of proliferation related proteins Bcl-2, survivin and metastasis related proteins MMP-2 and MMP-9 were up-regulated in the EC cells transwell co-cultured with hUCMSCs. Conclusions Our results indicated that hUCMSCs could favor tumor growth in vivo and in vitro. Thus, the exploitation of hUCMSCs in new therapeutic strategies should be cautious under the malignant conditions. [ABSTRACT FROM AUTHOR]