Expression and clinical significance of NKG2A and HLA-E in advanced laryngeal carcinoma.

OBJECTIVES: The purpose was to detected features of the expression levels of NKG2A and its ligand HLA-E, a new member of the immune checkpoints, in advanced laryngeal carcinoma and their clinicopathologic significance. MATERIAL AND METHODS: We analyzed the expression levels of HLA-E and NKG2A in multiple types of tumors utilizing the Tumor Immune Estimation Resource (TIMER) database and immunohistochemistry and qRT-PCR analysis of paraffin embedded tissue samples to reveal the correlations of the clinicopathological factors with the expression of these two proteins in advanced laryngeal carcinoma as well as their prognostic significance. RESULTS: KLRC1 (the coding gene of NKG2A) and HLA-E are substantially overexpressed in various human cancers than normal tissues. HNSCC is also included. KLRC1 is differentially expressed in different HPV subgroups of patients, with higher expression in the HPV-positive group. Consistent with this, immunohistochemical results also revealed the high expression of these two proteins in tumor tissue. In addition, immunohistochemical staining also displayed a preference for the distribution of NKG2A-positive cells in tumor tissue. Clinicopathological analyses also displayed that the density of NKG2A-positive cells of the HPV-positive group infiltrating laryngeal carcinoma tissue was larger than that in the HPV-negative group. Prognostic analyses indicated that the expression of this immune checkpoint does not affect the overall survival length of patients, but the highly expressed HLA-E is significantly correlated with local recurrence in the patients. CONCLUSIONS: The findings suggest that the expression levels of HLA-E and NKG2A is upregulated in advanced laryngeal carcinoma. The NKG2A-positive cells infiltrating the tumor are mainly distributed in the cancer nest, while infiltrating cell number may be regulated by HPV. The highly expressed HLA-E may promote local recurrence in patients with advanced laryngeal carcinoma.

Pathological mechanisms of cold and mechanical stress in modulating cancer progression.

Environmental temperature and cellular mechanical force are the inherent factors that participate in various biological processes and regulate cancer progress, which have been hot topics worldwide. They occupy a dominant part in the cancer tissues through different approaches. However, extensive investigation regarding pathological mechanisms in the carcinogenic field. After research, we found cold stress via two means to manipulate tumors: neuroscience and mechanically sensitive ion channels (MICHs) such as TRP families to regulate the physiological and pathological activities. Excessive cold stimulation mediated neuroscience acting on every cancer stage through the hypothalamus-pituitary-adrenocorticoid (HPA) to reach the target organs. Comparatively speaking, mechanical force via Piezo of MICHs controls cancer development. The progression of cancer depends on the internal activation of proto-oncogenes and the external tumorigenic factors; the above two means eventually lead to genetic disorders at the molecular level. This review summarizes the interaction of bidirectional communication between them and the tumor. It covers the main processes from cytoplasm to nucleus related to metastasis cascade and tumor immune escape.

Association between UGS patterns and residents' health status: A report on residents' health in China's old industrial areas.

BACKGROUND: Old industrial areas have low quality and spatial differentiation of urban green space (UGS), which makes it difficult to meet the public's physical activity needs and leads to increased health risks. The purpose of this study is to explore the equity of UGS patterns in old industrial areas and its internal relationship with residents' health status. METHODS: This study selecteds relevant indicators to evaluate the equity of UGS patterns in the Harbin area and used linear regression analysis to explore the correlation between attributes of old industrial areas and UGS patterns. Additionally, this study explored the spatial correlation of UGSs using Moran's index and hotspot analysis. Finally, a report on residents' health was generated through a questionnaire survey, using linear regression analysis to explore the factors affecting residents' self-rated health and the significance of their correlation. RESULTS: The results showed that there is an excess supply around the core industrial zone in the west, while the rural areas in the south face a serious shortage of supply. The significance between the factors representing age and income in industrial attributes and UGS pattern was less than 0.05. We observed that residents' self-rated health was positively affected by the intensity of physical activity (low intensity B = 2.073, medium intensity B = 2.359, high intensity B = 2.512) and the frequency of physical activity (B = 1.174). Ages (B = -0.597) and three generations living together (B = -3.191), which represent the industrial attributes, had a negative impact on residents' self-rated health. CONCLUSION: To a certain extent, industrial attributes aggravate the mismatch of UGS patterns, leading to abnormal areas in spatial clustering. The quality of UGS in the old industrial zone is low and the movement is not strong; thus, the population characteristics and income have become the important factors affecting the health of residents.

Recent advances and pathological mechanisms in photodynamic and sonodynamic therapy in the treatment of bone tumors (Review).

Given the recent advances that have been made with photodynamic therapy (PDT) combined with sonodynamic therapy (SDT) (PDT/SDT; also known as SPDT), the application of this combination therapy in the clinic has provided another major breakthrough in the medical field, especially with regard to the treatment of deep tumors. Concerning its application in the treatment of bone tumors, numerous pathological mechanisms have been taken advantage of to overcome the barrier of tissue hypoxia, and SPDT is expected to achieve radical effects, with high penetration depth and low aggressiveness. In the present review, it is comprehensively shown how, according to the histoanatomy of bone tumors, PDT and SDT target cells in a coordinated manner, affecting such processes as necrotizing apoptosis, pyroptosis, autophagy and ferroptosis on the macroscopic level, and crucially, thrombosis at the vascular level, which leads to the triggering of immunogenic cell death in local and distant locations. Additionally, PDT and SDT have been shown to have roles in: i) degrading the extracellular matrix; ii) influencing the receptor activator of nuclear factor­κB (RANK)/RANK ligand signaling pathway; iii) disrupting the equilibrium between glutathione peroxidase 4 and reactive oxygen species (ROS); and iv) destroying the microscopic structure of the bone tumor. Upon PDT/SDT stimulation, several mechanisms act in concert to ensure that the targeted bone tumor is eliminated. Furthermore, widely distributed ROS have been revealed to promote osteoclast formation and osteogenic mineralization through the regulation of macrophages, processes that greatly improve the effects of postoperative repair. Finally, the developmental prospects of bone tumor engineering in the future are discussed in the present review.

The effect of the street environment on two types of essential physical activity in industrial neighborhoods from the perspective of public health: a study from the Harbin low-income population health survey, China.

A large number of low-income residents in industrial neighborhoods rarely engage in recreational and physical activities in green spaces in extremely cold weather. This study mainly explores the relationship between the street environment and physical activities under special industrial properties and extreme cold weather conditions. In addition, we further divide essential physical activity into two categories, life-type and traffic-type physical activity, to explore and refine the related studies.We use principal component analysis to classify the street environment indicators and use multiple linear regression to analyze the impact of each indicator on different physical activities. The conclusions are as follows. For low-income people, the street environment in industrial neighborhoods has a much greater impact on life-type physical activity than traffic-type physical activity, and there is a conflict between the two. In addition, a high greening density is not conducive to either type of physical activity in the street environment. It reduces the paved area of streets and create sports conflicts between people undertaking different physical activities. The findings contribute to the development and optimization of public health research on environmental interventions in industrial neighborhood streets and enable effective recommendations for increasing outside physical activity among low-income people in severe weather conditions. In future studies, we will use the physical environment as a mediator to explore the relationship between the street environment and high-frequency chronic diseases in old industrial neighborhoods.

Interactive regulation of laryngeal cancer and neuroscience.

Nerve fibres are distributed throughout the body along with blood and lymphatic vessels. The intrinsic morphological characteristics of nerves and the general characteristics of secretions in the tumour microenvironment provide a solid theoretical basis for exploring how neuronal tissue can influence the progression of laryngeal cancer (LC). The central nervous system (CNS) and the peripheral nervous system (PNS) jointly control many aspects of cancer and have attracted widespread attention in the study of the progression, invasion and metastasis of tumour tissue banks. Stress activates the neuroendocrine response of the human hypothalamus-pituitary-adrenal (HPA) axis. LC cells induce nerve growth in the microenvironment by releasing neurotrophic factors (NTFs), and they can also stimulate neurite formation by secreting axons and axon guides. Conversely, nerve endings secrete factors that attract LC cells; this is known as perineural invasion (PNI) and promotes the progression of the associated cancer. In this paper, we summarize the systematic understanding of the role of neuroregulation in the LC tumour microenvironment (TME) and ways in which the TME accelerates nerve growth, which is closely related to the occurrence of LC.

The Relationship Between Human Papillomavirus, OFD1 and Primary Ciliogenesis in the Progression of Oropharyngeal Cancer: A Retrospective Cohort Study.

PURPOSE: Infection with human papillomavirus (HPV) has been indicated to be a important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Primary ciliogenesis defects contribute to tumorigenesis, and OFD1 at centriolar satellites is a crucial suppressor of primary ciliogenesis. To identify novel markers associated with HPV-induced carcinogenesis, the interactions between HPV infection and primary ciliogenesis in the tumorigenesis and progression of OPSCC were investigated in this study. PATIENTS AND METHODS: The 1530 OPSCC patients recruited in this research were treated from 2000 to 2017. Immunohistochemistry and RT-PCR were performed on tissue samples to compare the expression of p16, TSLP, TGFß1, IFNγ, OFD1, and their relationship with clinical characteristics of patients. RESULTS: We speculate that the positive expression of p16 is related to early primary OPSCC, and the survival rate of p16 positive patients after radiotherapy and surgery is higher. Expression of TSLP on dendritic cells in HPV-positive OPSCC correlated with the expression of OFD1. HPV-positive OPSCC showed increased expression of OFD1 combined with reduced ciliogenesis. Hence, TSLP induced by HPV infection may reduce the invasive potential of OPSCC cells by promoting OFD1 expression, thereby inhibiting primary ciliogenesis. CONCLUSION: Our study demonstrated that HPV may be related to the progression of OPSCC by regulating OFD1 expression and primary ciliogenesis, making this protein a potential therapeutic target.

Ciliated Muconodular Papillary Tumors of the Lung: Distinct Molecular Features of an Insidious Tumor.

INTRODUCTION: Ciliated muconodular papillary tumors (CMPTs) are rare special peripheral pulmonary nodule composed of different cell proportions, characterized by papillary structures and significant alveolar mucus. Because of their rarity, underrecognized processes, the full range clinical course and histogenesis of CMPTs remains uncertain. METHODS: Molecular features of 5 CMPTs cases (one case with mucinous adenocarcinoma simultaneously) were observed by whole exon gene detection. The histological features of CMPTs and the development trends of three major constituent cells were studied by immunohistochemistry and PCR. RESULTS: NGS revealed 77 gene mutations in the patient's tumor tissue and 31 mutations in the border tissue. TMB of CMPT tends to TMB of cancer tissues, and both are higher than normal tissues, CMPT share the same phylogenetic tree with cancer tissues. Moreover, PDL1, B7H3, and B7H4 were overexpressed in high columnar cells and eosinophilic ciliated cells of CMPT, tends to cancer tissues, while LAG3 and siglec15 were not found in CMPT. CONCLUSION: The high prevalence of driver gene mutations in CMPTs, similar TMB and phylogenetic tree with cancer tissues indicate their malignant potential. Distinct molecular and immune check point features of each component support the notion that ciliated columnar cells in CMPT are insidious with immune escape.

Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles.

The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic therapy (PDT) which not only generates reactive oxygen species (ROS) but also induces a variety of anti-tumor immunity, is to kill tumors. In addition, due to strong efficacy in clinical treatment with minimal invasion and negligible side effects, it has received extensive attention and research in recent years. In this paper, the generations of nanomaterials in PTT and PDT are described separately. In clinical application, according to the different combination pathway of nanoparticles, it can be used to treat different diseases such as tumors, melanoma, rheumatoid and so on. In this paper, the mechanism of pathological treatment is described in detail in terms of inducing apoptosis of cancer cells by ROS produced by PDT, immunogenic cell death to provoke the maturation of dendritic cells, which in turn activate production of CD4+ T cells, CD8+T cells and memory T cells, as well as inhibiting heat shock protein (HSPs), STAT3 signal pathway and so on.

Analysis of microbial changes in the tonsillar formalin-fixed paraffin-embedded tissue of Chinese patients with IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a prevalent chronic glomerular disease contribution to end-stage renal failure (ESRD). The tonsillar microbiota is closely associated with IgAN diseases based on the mucosal immune response. However, the composition and function of in tonsillar microbiota in participant patients with IgAN remains unknown. In this study, we detected the tonsillar microbiota changes of IgAN patients in Heilongjiang province located in northeast China. MATERIAL AND METHODS: We collected from 21 patients with IgAN and 16 patients with chronic tonsillitis (CT) who had undergone tonsillectomy previously. Histological review of all samples from formalin-fixed paraffin-embedded (FFPE) tissue were performed. Extracted DNA from FFPE tissue blocks, after that V4 regions of 16S ribosomal RNA (rRNA) sequencing and comparative analyses of tonsillar flora between two groups were performed. The statistical analysis used the SPSS version of 21. RESULTS: Visualization of microorganisms by Gram and Warthin-Starry (WS) silver stains, preliminarily observed the morphological characteristics of microbiome in FFPE tissue cases, such as bacteria or fungi. Tonsillar FFPE samples from the IgAN patients and CT controls showed significant differences in tonsillar microbial certain compositions and functions. We found that there were eight dominant genera that can be available to distinguish IgAN patients from CT controls. Compared with CT controls, at genus level, the relative abundances of Methylocaldum and unclassified_f_Prevotellaceae were significantly higher, while the abundances of Anaerosphaera, Halomonas, Trichococcus, Peptostreptococcus, norank_f_Synergistaceae and unclassified_k_norank_d_Bacteria were significantly lower in IgAN patients. Principal co-ordinates analysis (PCOA) distinguished IgAN patients from CT controls, and receiver operating characteristic (ROC) curves analysis confirmed that the diagnosis of disease has certain diagnostic significance. In addition, Functional analysis revealed that partly Enzymes and KOs were increased in the IgAN patients. CONCLUSIONS: Histological screening results were very helpful for further gene sequencing, not only to supplement the observation of bacterial morphology and structure, but also to prepare for subsequent gene sequencing and bioinformatics analysis. We elucidated subtle relevance between changes in tonsillar microbiota and IgAN patients, which can be utilized to predict the incidence of IgAN disease. In addition, we predicted that some enzymes, and KOs were closely related to IgAN.