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ObjectiveThis study aimed to explore the efficacy of transarterial chemoembolization (TACE) combined with microwave ablation (MWA) adjuvant to lenvatinib and anti–PD–1 antibodies for patients with hepatocellular carcinoma (HCC).MethodsA retrospective analysis of 67 patients with HCC treated at our hospital between October 2018 and May 2022 was conducted. All patients underwent a combination of TACE and MWA. Among them, 29 received postoperative treatment with molecular–targeted agents, like lenvatinib, along with anti–PD–1 antibodies such as sindilizumab, karelizumab, or tirilizumab. The remaining 38 patients did not receive postoperative systemic therapies, like targeted or immunotherapy. The survival and prognosis of all patients were analyzed.ResultsNine patients in the observation group and 29 patients in the control group experienced recurrence, and the median progression–free survival 1 (PFS1) was not reached ‘Not Applicable’(NA) and 17.05 months (P=0.035), respectively. Failure to combine adjuvant therapy was identified as an independent risk factor for tumor recurrence, and the observation group had a 0.245 times lower risk of recurrence compared to that in the control group (P=0.005). Multivariable Cox regression analysis confirmed that the maximum tumor size, and tumor number were risk factors for tumor recurrence. Patients with a large maximum tumor size had a 1.519 times higher risk of recurrence compared to those with a small maximum tumor size (P=0.006), and patients with a large number of tumors had a 5.978 times higher risk of recurrence compared to those with a small number of tumors (P=0.02). The median PFS2 of the two groups was 11.795 and 21.257 months, respectively, though not statistically significant (P=0.955). However, there was a disparity in the percentage of BCLC stages associated with recurrence between the two groups. In the observation group approximately 22.22% of patients progressed to stage C, while in the control group, this proportion was 34.48%. The observation group exhibited a lower risk of distant metastasis compared to the control group.ConclusionAdjuvant treatment of HCC following TACE combined with MWA improved PFS and achieved better clinical outcomes compared to that with TACE combined with MWA alone.

Exosomes are progressively being detected as an indicator for the diagnosis and prognosis of cancer in clinical settings. Many clinical trials have confirmed the impact of exosomes on tumor growth, particularly in anti-tumor immunity and immunosuppression of exosomes. Therefore, we developed a risk score based on genes found in glioblastoma-derived exosomes. In this study, we used the TCGA dataset as the training queue and GSE13041, GSE43378, GSE4412, and CGGA datasets as the external validation queue. Based on machine algorithms and bioinformatics methods, an exosome-generalized risk score was established. We found that the risk score could independently predict the prognosis of patients with glioma, and there were significant differences in the outcomes of patients in the high- and low-risk groups. Univariate and multivariate analyses showed that risk score is a valid predictive biomarker for gliomas. Two immunotherapy datasets, IMvigor210 and GSE78220, were obtained from previous studies. A high-risk score showed a significant association with multiple immunomodulators that could act on cancer immune evasion. The exosome-related risk score could predict the effectiveness of anti-PD-1 immunotherapy. Moreover, we compared the sensitivity of patients with high- and low-risk scores to various anti-cancer drugs and found that patients with high-risk scores had better responses to a variety of anti-cancer drugs. The risk-scoring model established in this study provides a useful tool to predict the total survival time of patients with glioma and guide immunotherapy.

Breast cancer is the most common malignancy and the leading cause of cancer-related deaths in women. Recent studies have investigated the prognostic value of the tumor microenvironment (TME)-related genes in breast cancer. The purpose of this research is to identify the immune-associated prognostic signature for breast cancer evaluate the probability of their prognostic value and compare the current staging system. In this study, we comprehensively evaluated the infiltration patterns of TME in 1,077 breast cancer patients downloaded from TCGA by applying the ssGSEA method to the transcriptome of these patients. Thus, generated two groups of immune cell infiltration. Based on two groups of low infiltration and high infiltration immune cell groups, 983 common differentially expressed genes were found using the limma algorithm. In addition, studying potential mechanisms, the GSEA method was used to indicate some pathways with remarkable enrichment in two clusters of immune cell infiltration. Finally, the seven immune-associated hub genes with survival as prognostic signatures were identified by using univariate Cox, survival, and LASSO analyses and constructed a TME score. The prognostic value of the TME score was self-validated in the TCGA cohort and further validated in an external independent set from METABRIC and GEO database by time-dependent survival receiver operation. Univariate and multivariate analyses of clinicopathological characteristics indicated that the TME score was an independent prognostic factor. In conclusion, the proposed TME score model should be considered as a prognostic factor, similar to the current TNM stage, and the seven immune-related genes can be a valuable potential biomarker for breast cancer.

Traditional electric transmission line fittings, which are always manufactured from thick metal slabs, possess the disadvantage of heavy weight. In this study, a new type of electrical-connection-fitting, clevis-clevis component made of high-strength steel is developed to reduce weight, and a new hot-stamping process for multilayered sheets is proposed to manufacture the component efficiently. First, the structure of the new clevis-clevis component is designed, and the corresponding tool is developed. Second, a flat-tool heat transfer experiment is conducted. The influence of the number of layers and contact pressure on the cooling rate of each sheet is investigated. The optimizing number of layers and contact pressure for the multilayered-sheet, hot-stamping process are obtained. The optimal number of layers is two, and the optimal contact pressure is more than 20 MPa. The final microstructure of each sheet is fully martensitic, and the strength is about 1500 MPa. Finally, U-shaped, double-layer-sheet hot stamping is implemented to produce a typical electrical-connection-fitting, clevis-clevis component. The bearing capacity of a four-layered clevis-clevis is tested through numerical and experimental methods. The new connection-fitting clevis-clevis component exhibits a high load capacity of 280 kN. Compared with that of the traditional component, the weight of the new component is reduced by 60%.

Recently the sonic hedgehog (shh) signaling pathway has been shown to play an important role in regulating repair and regenerative responses after brain injury, including ischemia. However, the precise cellular components that express and upregulate the shh gene and the cellular components that respond to shh signaling remain to be identified. In this study, using a distal MCA occlusion model, our data show that the shh signal is upregulated both at the cortical area near the injury site and in the adjacent striatum. Multiple cell types upregulate shh signaling in ischemic brain, including neurons, reactive astrocytes and nestin-expressing cells. The shh signaling pathway genes are also expressed in the neural stem cells (NSCs) niche in the subventricular zone (SVZ). Conditional deletion of the shh gene in nestin-expressing cells both at the SVZ niche and at the ischemic site lead to significantly more severe behavioral deficits in these shh iKO mice after cortical stroke, measured using an automated open field locomotion apparatus (Student's t-test, p0.05). In summary, our data demonstrate that shh signaling plays critical and ongoing roles in response to ischemic injury and modulation of shh signaling in vivo alters the functional outcome after cortical ischemic injury.

Breast cancer has become an important factor threatening women's health, and its incidence currently ranks first among female malignancies in China. Tumor infiltrating lymphocytes are lymphocyte-dominated cell populations that exist in tumors. After being activated by antigen or mitogen stimulation, and in the case of certain tumor growth, lymphocytic alpha is produced. It regulates immune response, induces the expression of multiple cellular antigens, and has a killing effect on multiple tumor cells. In addition, digital holographic phase microscopy only images biological cell samples in one direction, and cannot obtain accurate three-dimensional morphological structure imaging. The combination of tomography technology and digital holographic phase microscopy technology has made the research on the three-dimensional morphological structure and substructure imaging of biological cells enter a new stage. Based on the above background, the research content of this article is to analyze the correlation between tumor infiltrating lymphocytes and the clinicopathological characteristics and prognosis of breast cancer under a microscope. This article first discusses the observation methods and techniques of tumor cells under a microscope, and then the clinical pathology of breast cancer An example simulation was performed, and the results showed that the positive expression rates of P21 in invasive ductal carcinoma, invasive lobular carcinoma, and benign diseases were 68.2%, 62.7%, and 23.2%, respectively. The differences were statistically significant. The combined detection of OPN and P21 may be able to Become a potential marker for molecular typing of breast cancer. [ABSTRACT FROM AUTHOR]