Leber’s hereditary optic neuropathy (LHON) is a paradigm maternal hereditary eye disease, mainly involving the retinal and macular fibers of the optic disc in the anterior ethmoid plate of the sclera. LHON has the characteristics of sex bias among males and incomplete penetrance. Primary mitochondrial DNA mutations m.11778G>A, m. 14484T>C, m.3460G>A are the molecular basis of LHON. However, other risk factors, such as secondary mitochondrial DNA mutations, mitochondrial haplotypes, nuclear modification genes, estrogen, vitamin B12 and environmental factors, work together to affect its phenotypic expression. The clinical diagnosis of LHON mainly limited to the detection of the primary mutation site of mitochondrial DNA. Therefore, comprehensive analysis of multiple risk factors of LHON will facilitate to construct multi-dimensional model of prevention, diagnosis and treatment system, which provide accurate and individualized medical services for patients. These may alleviate the incidence in LHON families. It also provides new ideas and different angles for the in-depth study of the pathogenesis of LHON.
Objective To summarize the changes in the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) in the context of immunotherapy and their impact on treatment outcomes. MethodsA systematic review of recent studies on the TME of PDAC was carried out to analyze the immune properties, intercellular interactions, and biological functions of its cellular and non-cellular components, disclose the molecular mechanisms of immunotherapy affects on the TME, explore the advancements in targeted therapy and potential biomarkers, and analyze the challenges in clinical applications and their impacts on the quality of life of patients. ResultsThe TME of PDAC exhibits highly immunosuppressive and heterogeneous characteristics, rich in diverse cells (such as pancreatic cancer cells, stellate cells, cancer-associated fibroblasts, immune cells) and non-cellular components (such as extracellular matrix). Immunotherapy is capable of regulating the immune balance in the TME and enhancing the anti-tumor response. Despite the progress made in multiple immunotherapy strategies (such as immune checkpoint inhibitors, chimeric antigen receptor cell therapy), challenges such as difficulty in selecting targets, drug resistance, and side effects still persist. Meanwhile, potential biomarkers such as leukemia inhibitory factor offer new directions for individualized treatment. ConclusionsThe TME of PDAC undergoes continuous changes during immunotherapy. In the future, it is requisite to integrate new technologies to deeply explore targets and biomarkers, optimize multimodal precise treatment strategies, enhance the safety and efficacy of immunotherapy, and improve the prognosis of patients.
Stem cells have been regarded with promising application potential in tissue engineering and regenerative medicine due to their self-renewal and multidirectional differentiation abilities. However, their fate is relied on their local microenvironment, or niche. Recent studied have demonstrated that biophysical factors, defined as physical microenvironment in which stem cells located play a vital role in regulating stem cell committed differentiation. In vitro, synthetic physical microenvironments can be used to precisely control a variety of biophysical properties. On this basis, the effect of biophysical properties such as matrix stiffness, matrix topography and mechanical force on the committed differentiation of stem cells was further investigated. This paper summarizes the approach of mechanical models of artificial physical microenvironment and reviews the effects of different biophysical characteristics on stem cell differentiation, in order to provide reference for future research and development in related fields.
ObjectiveTo review the relative researches about mechanical stimulation of stem cells differentiation in stem cells microenvironment in vitro. MethodsThe recent related literature about stem cells differentiation in vitro was reviewed and summarized. ResultsThe mechanical loads (including shear stress, mechanical strain, and stress), substrates stiffness, substrates nanotopography, and cell shape were the 4 important aspects of mechanical factors regulating stem cells differentiation. The mechanical stimulation can simulate the in vivo microenvironment, which can alter the size, shape, alignment, and differentiation state of stem cells, can change the expression of their differentiation markers, and can affect the lineage commitment of stem cells. ConclusionMechanical stimulation play an important role in regulating stem cells differentiation and cells morphology in addition to chemical and biological factors.
ObjectiveTo detect the expression of programmed cell death ligand 1 (PD-L1) in papillary thyroid carcinoma (PTC) and PTC with coexistent Hashimoto’s thyroiditis (HT) tissues, and to explore its clinical significance of its expression.MethodsThe PTC patients who underwent thyroidectomy at the Thyroid Surgery Department of the Affiliated Hospital of Guizhou Medical University from March 2017 to May 2019 were retrospectively collected. Immunohistochemical staining was used to detect the expression of PD-L1 in the PTC tissues, PD-L1 staining positive cells ≥20% was judged as positive expression, <20% was judged as negative expression. The relationship between PD-L1 positive expression rate and clinicopathologic characteristics of patients with PTC were analyzed, and the correlation between the presence of HT in PTC tissues and PD-L1 positive expression was studied.ResultsA total of 138 patients with PTC were included in this study, including 104 patients with PTC alone and 34 PTC patients with coexistent HT. The positive rate of PD-L1 expression in the 138 cases of PTC tissues was 35.5% (49/138), among which was 43.3% (45/104) in the pure PTC tissues, and 11.8% (4/34) in the PTC tissues with HT, the latter was significantly lower than the former (P=0.001). The results of univariate analysis showed that the positive rate of PD-L1 expression was related to the tumor size, the presence or absence of extraglandular invasion and HT in PTC patients (P<0.05), and the results of Spearman correlation analysis showed that the positive rate of PD-L1 expression was positively correlated with tumor size (rs=0.173, P=0.041) and extraglandular invasion (rs=0.197, P=0.021), and negatively correlated with whether TH was merged (rs=–0.284, P=0.001). The multivariate analysis results showed that the positive rate of PD-L1 expression was closely related to whether PTC with coexistent HT [OR=5.720, 95%CI (1.879, 17.411), P=0.002], and it was not found to be related to tumor size and presence of extraglandular invasion (P>0.05).ConclusionsPositive rate of PD-L1 expression has a certain relationship with tumor size and presence or absence of extraglandular invasion, and which in PTC patients with or without HT is significantly different, that is, positive rate of PD-L1 expression in PTC with HT is lower suggests that coexistent HT might be an inhibitory factor in occurrence of PTC, and immune microenvironment-related factors of PTC might be involved in occurrence and development of thyroid cancer.
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.
Lung cancer has a high morbidity and mortality, and invasion is one of the major factors that cause recurrence and death in lung cancer patients. Tumor-associated macrophages (TAMs) are cells that have the potential to secrete cytokines, growth hormones, inflammatory substrates, and protein hydrolases, which are associated with the growth, invasion and metastasis of tumors. In this article, we will explore the various chemicals that are manufactured to promote the invasion of lung cancer, as well as the numerous clinical therapeutic features that TAMs possess in the treatment of lung cancer. In addition, we look at the possibility that TAMs might be beneficial in the treatment of lung cancer. We have an innovative investigation of the huge variety of complex substances generated by TAMs, with the goal of determining whether or not the molecules under investigation have the potential to serve as new therapeutic targets. Throughout the whole of the presentation, a significant focus is placed on doing in-depth research to ascertain whether TAMs have the capability to reinforce as viable carriers for unique and creative medications. This not only provides novel concepts for the creation of new targeted therapies but also leads to the development of brand-new, cutting-edge methods for the manufacture of individualized medicines and drug carriers.
ObjectiveTo explore optimal conditions of isolation, culture and labeled with superparamagnetic iron oxide (SPIO) in vitro of rat bone marrow endothelial progenitor cells, and lay the foundations for the further EPCs tracer study in vivo. MethodsThe EPCs derived from rat bone marrow were isolated and cultured by using density gradient centrifugation, which were labeled with different concentrations SPIO, Prussian blue staining was used to detect the cells labeling rate, MTT assay was used to detect the cells proliferation activity, and Trypan blue staining was used to detect the cells vitality. ResultsEPCs gradually growed in monolayer arrangement about 7 d after cultured. When the concentration of SPIO was 50μg/mL, the highest labeling rate of Prussian blue staining was 90%, the growth state of labeled EPCs were good, and could normal adherent growth and passage. At this time, the cell viability and proliferation activity were the highest through trypan blue staining and MTT assay. ConclusionsEPCs can be labeled with SPIO easily and efficiently when the concentration was 50μg/mL?without interference on the viability and proliferation activity, which lay the foundations for the further EPCs tracer study in vivo.
The number of people with physical disabilities is increasing year by year, and the trend of population aging is more and more serious. In order to improve the quality of the life, a control system of accessible home environment for the patients with serious disabilities was developed to control the home electrical devices with the voice of the patients. The control system includes a central control platform, a speech recognition module, a terminal operation module, etc. The system combines the speech recognition control technology and wireless information transmission technology with the embedded mobile computing technology, and interconnects the lamp, electronic locks, alarms, TV and other electrical devices in the home environment as a whole system through a wireless network node. The experimental results showed that speech recognition success rate was more than 84% in the home environment.
Objective To summarize the research progress on the regulation of hepatic sinusoidal microenvironment to promote liver regeneration based on liver sinusoidal endothelial cells (LSECs), aiming to further clarify the mechanism of liver regeneration and provide new ideas and methods for clinical promotion of liver regeneration and prevention of liver failure. Method The basic and clinical research studies on LSECs and liver regeneration at home and abroad in recent years were searched and reviewed. Results Differentiated LSECs played an important role in liver regeneration, regulated the homeostasis of hepatic sinusoid microenvironment by paracrine and autocrine, and participated in the whole process of promoting liver regeneration, such as hepatocyte proliferation and neovascularization after acute and chronic liver injury. Conclusion In the process of liver regeneration after all kinds of acute and chronic liver injury, LSECs promote liver regeneration by regulating hepatic sinusoid microenvironment, which will provide new strategies and methods for clinical promotion of liver regeneration and prevention of liver failure after hepatectomy.