Different Degrees Of Differentiation Research Articles

Proteomic analysis of differentially expressed proteins in gastrointestinal neuroendocrine tumors and their liver metastasis

Objective: To investigate the differences of protein expressions in the primary tumors, adjacent tissues, and metastatic tumors of gastrointestinal neuroendocrine neoplasms. Methods: Nine patients with gastrointestinal neuroendocrine tumors (GI-NENs) with liver metastasis who underwent surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from July 2015 to April 2019 were selected. The protein expressions of the primary tissues, liver metastatic tissues, and adjacent tissues were detected by the data independent acquisition (DIA) technology. P<0.05 and | log2FC|>0.5 (FC as the difference multiple) were used as the criteria to identify the differentially expressed proteins in the primary tissues vs adjacent tissues, primary tissues vs liver metastatic tissues, primary tissues with different degrees of differentiation, and liver metastatic tissues with different degrees of differentiation. The differentially expressed proteins were investigated by volcano map analysis, cluster analysis, Gene Ontology (GO) function analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: Compared with adjacent tissues, 85 proteins were downregulated and 42 proteins were upregulated in the primary tissues of gastric NENs. The differentially expressed proteins were mainly enriched in the biological processes related to the regulation of guanosidase triphosphate activity and the catabolism of deoxyribonucleoside monophosphate, the glycosaminoglycan biosynthesis chondroitin sulfate/dermatan sulfate, pantothenate, and CoA biosynthesis signaling pathways. 114 proteins were downregulated and 155 proteins were upregulated in the primary tissues of intestinal NENs. The differentially expressed proteins were mainly enriched in the biological processes related to glutathione metabolism and sulfur compound metabolism, collecting duct acid secretion, and taurine and hytaurine metabolism signaling pathways. Compared with the primary tissues of neuroendocrine cancers (NECs), 168 proteins were downregulated and 278 proteins were upregulated in G1-2 differentiation primary tissues. The differentially expressed proteins were significantly enriched in biological processes such as DNA metabolism and DNA replication, as well as replication, mismatch repair, and other pathways. Compared with the metastatic tissues of NECs, 95 proteins were downregulated and 97 proteins were upregulated in G1-2 differentiated metastases. The differentially expressed proteins were significantly enriched in the activity and catalytic activity of transcriptional coactivators, base excision repair, and protein efflux pathways. Compared with G1 differentiated primary tissues, 530 proteins were downregulated and 211 proteins were upregulated in G1 differentiated metastatic tissues. Compared with G2 differentiated primary lesions, 53 proteins were downregulated and 96 proteins were upregulated in G2 differentiated metastatic tissues. Compared with the primary lesions of NECs, 109 proteins were downregulated and 92 proteins were upregulated in the metastatic tissues of NECs. In G1 and G2 differentiated GI-NENs, there are many similar signal pathways enriched in differentially expressed proteins between primary lesions and metastases, while only one signal pathway enriched in differentially expressed proteins between primary and metastatic tissues of NECs is the same as that enriched in differentially expressed proteins between primary and metastatic tissues of GI-NENs, which is the drug metabolism signal pathway. The differentially expressed proteins in G1 differentiated primary and metastatic tissues were mainly expressed in cytoplasm (20.26%), mitochondria (18.67%), and nucleus (15.48%). The differentially expressed proteins in the primary and metastatic tissues of G2 differentiation were mainly expressed in the cytoplasm (20.24%), nucleus (18.25%), and cell membrane (15.08%). The differentially expressed proteins in the primary and metastatic tissues of NECs were mainly expressed in the nucleus (23.78%), cytoplasm (22.7%), and cell membrane (11.35%). Conclusion: The protein expressions of GI-NENs in the primary tissues, adjacent tissues, and metastatic tissues were significantly different in different sites and degrees of differentiation.

Different clinicopathological features between young and older patients with pulmonary adenocarcinoma and ground-glass opacity

After the recommendation of computed tomography as a routine procedure for lung cancer screening, an increasing number of young adults have been diagnosed with pulmonary ground-glass opacity (GGO). Up to 63% of pulmonary nodules with a GGO component can be malignant. Since young cancer patients have limited exposure to environmental mutagens, they have special characteristics and needs. This study sought to compare the clinicopathological characteristics of young and old patients with GGO-associated lung adenocarcinoma (GGO-LUAD). Clinicopathological data from 203 patients who underwent video-assisted thoracoscopic surgery between January 2018 and April 2020 for pulmonary GGO component nodules were reviewed. Lung nonmucinous adenocarcinoma patients younger than 40 years old and older than 40 years old were enrolled: 103 patients ≤ 40 years old and 100 patients > 40 years old. The relevant clinicopathological features, including sex, smoking status, tumor size, pathological characteristics, radiographic features and prognosis of pulmonary nodules, were evaluated. Univariate analyses were applied for comparisons between groups. The differences in baseline characteristics (sex, smoking status, tumor location) between the different age groups were not significant. Young patients were more likely to have tumors < 1 cm in size, while older patients predominantly had tumors > 2 cm in size. The mean percentage of invasive adenocarcinoma was greater in the elderly group. Young and older patients seemed to have similar subtypes of adenocarcinoma (p > 0.05) but had different degrees of differentiation (p < 0.001). The 3-year overall survival (OS) and recurrence-free survival (RFS) of the young group were 100% and 99.03%, respectively, while the 3-years OS and RFS of the older group were 99% and 98%, respectively. Our work revealed that young patients with malignant pulmonary nodules and GGOs have distinct pathological subtypes. Patients with GGOs of different ages have different clinicopathological characteristics. The 3-year prognosis of young patients with malignant pulmonary nodules with GGOs is satisfactory.

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract, and endoscopic submucosal dissection (ESD) is the preferred treatment for early-stage gastric cancer. The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD. AIM To analyze the features of gastric mucosal tumors at different differentiation levels, and to explore the prognostic factors of ESD. METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021, according to the latest Japanese guidelines (sixth edition), and divided them into low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and differentiated and undifferentiated early carcinoma. They are followed up by endoscopy, chest and abdominal computed tomography at 3, 6 and 12 months after ESD. We compared clinicopathologic characteristics, ESD efficacy, and complications with different degrees of differentiation, and analyzed the related factors associated with ESD. RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients (P &lt; 0.001) and accounted for more 0-IIc (P &lt; 0.001), atrophic gastritis was common (P &lt; 0.001), and irregular microvascular patterns (IMVPs) and demarcation lines (DLs) were more obvious (P &lt; 0.001). There was more infiltration in the undifferentiated carcinoma tissue (P &lt; 0.001), more abnormal folds and poorer mucosal peristalsis (P &lt; 0.001), and more obvious IMVPs, irregular microsurface patterns and DLs (P &lt; 0.05) than in the LGIN and HGIN tissues. The disease-free survival rates at 2, 5, and 8 years after ESD were 95.0%, 90.1%, and 86.9%, respectively. Undifferentiated lesions (HR 5.066), white moss (HR 7.187), incomplete resection (HR 3.658), and multiple primary cancers (HR 2.462) were significantly associated with poor prognosis. CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics, which are closely related to the safety and efficacy of ESD.

Investigation of Trpa1 and Trpc1 Immunreactivities in Colon Adenocarcinomas.

As the normal colon epithelium differentiates into adenoma, invasive cancer and metastatic cancer, the cell acquires new characteristics such as apoptosis, proliferation, differentiation, invasion and metastasis. Many mechanisms are effective in acquiring these qualities. One of these is the regulation of the functioning of ion channels. This study aimed to examine TRPA1 and TRPC1 expression in colorectal adenocarcinomas showing different degrees of differentiation. We examined the biopsy specimens of 60 patients diagnosed with colorectal adenocarcinomas, including those of patients with well-differentiated (n = 20), moderately differentiated (n = 20) and poorly differentiated (n = 20) carcinomas. Moreover, 20 biopsy specimens of individuals with normal colonic mucosa were examined. Histoscores were calculated for TRPA1 and TRPC1 based on the extent of diffusion and intensity of immunoreactivity, and these scores were compared statistically. A statistically significant increase in both TRPA1 and TRPC1 immunoreactivity was observed in low-grade and high-grade colon adenocarcinomas compared to the control group (p<0.001). A statistically significant decrease in both TRPA1 and TRPC1 immunoreactivity was observed in high-grade colon adenocarcinomas compared to low-grade colon adenocarcinomas (p<0.001). TRPA1 and TRPC1 immunoreactivites are increased in colorectal adenocarcinoma tissue compared with the healthy tissue. Furthermore, the immunoreactivity decreases as the grade of cancer increases.

Immunohistochemical characteristics of epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma

The epithelial-mesenchymal transition (EMT) plays a crucial role in the development of pancreatic ductal adenocarcinoma (PDAC). There are insufficient and contradictory data in the scientific literature on the peculiarities of epithelial and mesenchymal marker expression in PDAC ducts and EMT zone, which requires further research on the role of EMT in the development and progression of PDAC. Aim: to conduct a comprehensive assessment of epithelial and mesenchymal markers of EMT in the PDAC ducts and EMT zone at different degrees of differentiation. Materials and methods. A comprehensive pathomorphological and immunohistochemical examination including 49 cases of surgical material from patients with PDAC, divided into groups of moderate (G2) and low degree of tumor differentiation (G3). Results. PDAC was characterized by low levels of E-cadherin expression in both ducts and EMT – Me = 22.58 % [12.81; 36.23] and Me = 25.17 % [19.04; 35.37], respectively (p &gt; 0.05). Only membrane expression of the marker was detected in the ducts and membrane-cytoplasmic one – in the EMT zone without significant differences in the groups. There was a significant decrease in the ductal β-catenin expression (p &lt; 0.05) in G2 with membrane-cytoplasmic staining (Me = 15.58 % [10.42; 26.24]), in G3 – with membrane (Me = 4.42 % [2.35; 5.93]); in the EMT zone, only membrane-cytoplasmic expression was observed in both groups without significant difference (p &gt; 0.05). Membrane expression of CK7 was positive in 100 % of PDAC, significantly lower at G2 (Me = 19.51 % [10.70; 27.24]; Me = 26.19 % [20.93; 30.05], p &lt; 0.05), and CK18 (Me = 21.34 % [9.68; 29.96] – in G2, in G3 – Me = 22.50 % [8.24; 40.08], p &gt; 0.05). Expression of α-SMA and Vim was seen in spindle-shaped stromal cells, around tubular and trabecular structures with membrane-cytoplasmic staining. There was no significant difference between α-SMA in G2 and G3, the level of vimentin was significantly lower in G3 (p &lt; 0.05). Conclusions. The features of PDAC E-cadherin, β-catenin, CK7 and CK18 marker expression indicate a greater EMT process at the periphery of the tumor and its severity increases with tumor progression. The optimal markers to determine the mesenchymal phenotype of PDAC cells are α-SMA and vimentin.

Stemness properties of SSEA-4+ subpopulation isolated from heterogenous Wharton's jelly mesenchymal stem/stromal cells.

Background: High heterogeneity of mesenchymal stem/stromal cells (MSCs) due to different degrees of differentiation of cell subpopulations poses a considerable challenge in preclinical studies. The cells at a pluripotent-like stage represent a stem cell population of interest for many researchers worldwide, which is worthy of identification, isolation, and functional characterization. In the current study, we asked whether Wharton's jelly-derived MSCs (WJ-MSCs) which express stage-specific embryonic antigen-4 (SSEA-4) can be considered as a pluripotent-like stem cell population. Methods: SSEA-4 expression in different culture conditions was compared and the efficiency of two cell separation methods were assessed: Magnetic Activated Cell Sorting (MACS) and Fluorescence Activated Cell Sorting (FACS). After isolation, SSEA-4+ cells were analyzed for the following parameters: the maintenance of the SSEA-4 antigen expression after cell sorting, stem cell-related gene expression, proliferation potential, clonogenicity, secretome profiling, and the ability to form spheres under 3D culture conditions. Results: FACS allowed for the enrichment of SSEA-4+ cell content in the population that lasted for six passages after sorting. Despite the elevated expression of stemness-related genes, SSEA-4+ cells neither differed in their proliferation and clonogenicity potential from initial and negative populations nor exhibited pluripotent differentiation repertoire. SSEA-4+ cells were observed to form smaller spheroids and exhibited increased survival under 3D conditions. Conclusion: Despite the transient expression of stemness-related genes, our findings could not fully confirm the undifferentiated pluripotent-like nature of the SSEA-4+ WJ-MSC population cultured in vitro.

Lack of Dosage Balance and Incomplete Dosage Compensation in the ZZ/ZW Gila Monster (Heloderma suspectum) Revealed by De Novo Genome Assembly.

Reptiles exhibit a variety of modes of sex determination, including both temperature-dependent and genetic mechanisms. Among those species with genetic sex determination, sex chromosomes of varying heterogamety (XX/XY and ZZ/ZW) have been observed with different degrees of differentiation. Karyotype studies have demonstrated that Gila monsters (Heloderma suspectum) have ZZ/ZW sex determination and this system is likely homologous to the ZZ/ZW system in the Komodo dragon (Varanus komodoensis), but little else is known about their sex chromosomes. Here, we report the assembly and analysis of the Gila monster genome. We generated a de novo draft genome assembly for a male using 10X Genomics technology. We further generated and analyzed short-read whole genome sequencing and whole transcriptome sequencing data for three males and three females. By comparing female and male genomic data, we identified four putative Z chromosome scaffolds. These putative Z chromosome scaffolds are homologous to Z-linked scaffolds identified in the Komodo dragon. Further, by analyzing RNAseq data, we observed evidence of incomplete dosage compensation between the Gila monster Z chromosome and autosomes and a lack of balance in Z-linked expression between the sexes. In particular, we observe lower expression of the Z in females (ZW) than males (ZZ) on a global basis, though we find evidence suggesting local gene-by-gene compensation. This pattern has been observed in most other ZZ/ZW systems studied to date and may represent a general pattern for female heterogamety in vertebrates.

INSM1 expression in primary and metastatic neuroendocrine neoplasms at distinct locations

BackgroundInsulinoma-associated protein 1 (INSM1) has been reported as a valuable marker for neuroendocrine neoplasms (NENs). The aims of this study were to evaluate any change in INSM1 expression between primary and metastatic NENs in distinct locations, as well as the expression of INSM1 at different differentiation levels. Furthermore, we would also investigate the significance of INSM1 expression in non-neuroendocrine neoplasms (non-NENs). MethodsWe collected 78 cases with primary NENs and 16 cases with metastatic NENs. An addition 7 cases of non-NENs with neuroendocrine (NE) differentiation and 84 cases of other non-NENs, respectively, were included as controls. ResultsIn our cohort, 82% of primary NENs and 88% of metastatic NENs expressed INSM1 with no difference between them. There was no difference in the expression of INSM1 in the lung and digestive system, and its staining pattern was independent of tumor differentiation or location. The proportion of INSM1 -positive in non-NENs with NE differentiation was significantly higher than that in other non-NENs. INSM1 sensitivity for primary NENs (82%) was comparable to Chromogranin A (82%), less than that of Synaptophysin (96%) and CD56 (94%); specificity was higher (96% vs 94%, 82%, and 89%, respectively). The sensitivity of INSM1 for well differentiated NENs was significantly higher than that of poorly differentiated NENs (100% vs 79%). ConclusionsINSM1 is a useful neuroendocrine marker in primary and metastatic NENs, helping to identify primary NENs with different degrees of differentiation. The expression of INSM1 was independent of tumor location. It should be with caution to interpret the expression of INSM1 in non-NENs that morphologically resemble NENs.

Reflection of Chinese Cultural Realities in the Modern Russian Language in the Paradigm of Subject and Semantic Correspondences

The article deals with the importance of language and culture interaction, the linguistic and cultural characteristics as features of the languages belonging to various linguistic macrogroups (Russian as part of Indo-European, Chinese as part of Sino-Tibetan). The paper highlights the importance of translation in the interaction of linguistic cultures; the difficulties that can be encountered in interpreting the realities of another culture are indicated, which is due to both the peculiarities of the lexical and grammatical structure of the source and translating languages, and the peculiarities associated with the traditional culture of the language community.&#x0D; The component of the meaning of the real words of the Russian and Chinese languages with different semantic structures is part of the denotative macro component of the lexical meaning of the word. The national-cultural component of words with different degrees of differentiation of concepts in the Russian and Chinese languages is included in the significative macro component of their lexical meaning, and its content consists of differential semes of the significative macro component. The national-cultural component of the lexical meaning of words of corresponding languages with a mismatched internal form is the semes of the denotative macro component. Russian linguoculture should take into account the specifics of the Russian language, and in cases where the realities are completely alien to Russian national and cultural ideas, the necessary historical and other comments are tobe given. It should be noted that recently, due to the intensification of national-cultural and economic contacts, a great number of words (including national-specific realities) from the Chinese language have been penetrating into the Russian language, which requires separate linguistic research.

Differentiating mental models of self and others: A hierarchical framework for knowledge assessment.

Developing an accurate model of another agent's knowledge is central to communication and cooperation between agents. In this article, we propose a hierarchical framework of knowledge assessment that explains how people construct mental models of their own knowledge and the knowledge of others. Our framework posits that people integrate information about their own and others' knowledge via Bayesian inference. To evaluate this claim, we conduct an experiment in which participants repeatedly assess their own performance (a metacognitive task) and the performance of another person (a type of theory of mind task) on the same image classification tasks. We contrast the hierarchical framework with simpler alternatives that assume different degrees of differentiation between mental models of self and others. Our model accurately captures participants' assessment of their own performance and the performance of others in the task: Initially, people rely on their own self-assessment process to reason about the other person's performance, leading to similar self- and other-performance predictions. As more information about the other person's ability becomes available, the mental model for the other person becomes increasingly distinct from the mental model of self. Simulation studies also confirm that our framework explains a wide range of findings about human knowledge assessment of themselves and others. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Spectral CT - a new supplementary method for preoperative assessment of pathological grades of esophageal squamous cell carcinoma

BackgroundSpectral CT imaging parameters have been reported to be useful in the differentiation of pathological grades in different malignancies. This study aims to investigate the value of spectral CT in the quantitative assessment of esophageal squamous cell carcinoma (ESCC) with different degrees of differentiation.MethodsThere were 191 patients with proven ESCC who underwent enhanced spectral CT from June 2018 to March 2020 retrospectively enrolled. These patients were divided into three groups based on pathological results: well differentiated ESCC, moderately differentiated ESCC, and poorly differentiated ESCC. Virtual monoenergetic 40 keV-equivalent image (VMI40keV), iodine concentration (IC), water concentration (WC), effective atomic number (Eff-Z), and the slope of the spectral curve(λHU) of the arterial phase (AP) and venous phase (VP) were measured or calculated. The quantitative parameters of the three groups were compared by using one-way ANOVA and pairwise comparisons were performed with LSD. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of these parameters in poorly differentiated groups and non-poorly differentiated groups.ResultsThere were significant differences in VMI40keV, IC, Eff-Z, and λHU in AP and VP among the three groups (all p < 0.05) except for WC (p > 0.05). The VMI40keV, IC, Eff-Z, and λHU in the poorly differentiated group were significantly higher than those in the other groups both in AP and VP (all p < 0.05). In the ROC analysis, IC performed the best in the identification of the poorly differentiated group and non-poorly differentiated group in VP (AUC = 0.729, Sensitivity = 0.829, and Specificity = 0.569 under the threshold of 21.08 mg/ml).ConclusionsQuantitative parameters of spectral CT could offer supplemental information for the preoperative differential diagnosis of ESCC with different degrees of differentiation.

EXTENSIVE MANDIBULAR LESION AS A PRIMARY SIGN OF NEOPLASM OF PLASMA CELL ORIGIN: A CASE REPORT

A 57-year-old woman complained of jaw pain and presented no swelling on intraoral examination. Imaging examinations showed extensive osteolytic lesions throughout the mandible with signs of manifestation in the maxilla, including the involvement of other bones. Computed tomography revealed several hypodense osteolytic areas with cortical disruption in the left lingual posterior region of the mandible. Moreover, the incisional biopsy showed diffuse and monotonous layers of plasmacytoid cells with different degrees of differentiation. Immunohistochemical analysis showed positivity in plasmacytoid cells for anti-kappa, CD138, MUM1, and CD79a antibodies, and negative results for anti-lambda and CD20. The diagnosis of multiple myeloma was confirmed based on the histopathological and immunohistochemical data along with the imaging finding of diffuse lytic lesions. The patient was referred for further examinations and treatment. She remained under follow-up for six months after the biopsy and manifested a pathological fracture of the left clavicle, probably related to the underlying disease. A 57-year-old woman complained of jaw pain and presented no swelling on intraoral examination. Imaging examinations showed extensive osteolytic lesions throughout the mandible with signs of manifestation in the maxilla, including the involvement of other bones. Computed tomography revealed several hypodense osteolytic areas with cortical disruption in the left lingual posterior region of the mandible. Moreover, the incisional biopsy showed diffuse and monotonous layers of plasmacytoid cells with different degrees of differentiation. Immunohistochemical analysis showed positivity in plasmacytoid cells for anti-kappa, CD138, MUM1, and CD79a antibodies, and negative results for anti-lambda and CD20. The diagnosis of multiple myeloma was confirmed based on the histopathological and immunohistochemical data along with the imaging finding of diffuse lytic lesions. The patient was referred for further examinations and treatment. She remained under follow-up for six months after the biopsy and manifested a pathological fracture of the left clavicle, probably related to the underlying disease.

Geochemistry and Petrology of the Bellecombe Lava Sequence, Enclos Fouqué Caldera, Piton de la Fournaise Volcano (Réunion, France)

Piton de la Fournaise is an active shield volcano located in the eastern area of the Réunion Island (Indian Ocean) whose activity is characterized by effusive and explosive episodes with the emission of scarcely differentiated magmas with mostly tholeiitic affinity. The presently active edifice has grown within the Enclos Fouqué caldera, a polylobate plain bounded on its western side by the 80–200 m high Bellecombe vertical cliffs. This escarpment exposes a vertical sequence of 12 lava flows cut by a dike with an age &gt; 5.5 kyrs. In this work, the Bellecombe products were investigated by X-ray fluorescence, Inductively Coupled Plasma Mass Spectroscopy, a Scanning Electron Microscope and X-ray computed microtomography in order to characterize the evolution over time of the magmatic system feeding the eruptive activity prior to the Enclos Fouqué caldera collapse. The results indicate that lava flows share a geochemical affinity with the two main series documented at Piton de la Fournaise, namely, Steady State Basalts (SSB) at the bottom and top of the sequence and Abnormal basalt Group (AbG) with different degrees of differentiation in the central part. The emission of these two different products in both a restricted area and timespan testifies to the dynamic activity of the plumbing system, capable of shifting rapidly from central to eccentric activity in the recent past.

Cell renewal index in the differential diagnosis of atypical small acinar proliferation and adenocarcinoma of the prostate

Introduction Singling out such diagnostic category as atypical small acinar proliferation of the prostate (ASAP) determines the necessity of forming additional approaches to differential morphological diagnosis in order to determine adenocarcinoma in time. Cell renewal index (CRI) is actively used to study proliferation and apoptosis in the epithelial cells of hormone-dependent glands, but in prostate pathology this criterion has not been studied.The aim of the study was to characterize the cell renewal index in atypical small acinar proliferation and prostate adenocarcinoma of different degrees of differentiation in order to optimize differential diagnosis.Materials and methods We studied 720 prostate biopsy specimens from 60 patients: Group 1 — 15 patients with ASAP; Group 2 − 15 with adenocarcinoma of high-grade of differentiation; Group 3 − 15 with moderately differentiated adenocarcinoma; Group 4 − 15 with low differentiated adenocarcinoma. We used immunohistochemical method (Ki-67, CPP32) and non-parametric statistical methods of investigation.Results The CRI in ASAP was comparable to that in highly differentiated adenocarcinoma (p=0.5). In moderately differentiated adenocarcinoma the CRI was significantly higher than in ASAP and highly differentiated adenocarcinoma (p=0.004). The greatest increase in CRI was noted in the low-differentiated adenocarcinoma group, which was higher and significantly different from the ASAP (p=0.000), highly differentiated carcinoma (p=0.003) and moderately differentiated prostatic carcinoma (p=0.000) groups.Discussion On the basis of statistical analysis the present study helped to reveal the identity of CRI parameters in ASAP and highly differentiated adenocarcinoma of the prostat, which allows to add a number of morphological criteria for transferring patients from the group of undetermined diagnosis of ASAP to the group of adenocarcinoma. There is a need for further investigation of CRI with multiparametric analysis including investigation of the expression levels of hormones involved in the regulation of cell renewal in the prostate and growth factors associated with them.Conclusion The study allowed to reveal the identity of the CRI in ASAP and highly differentiated adenocarcinoma of the prostate, which can supplement a number of morphological criteria for transferring patients from the group of undeterminate diagnosis of ASAP to the group of adenocarcinoma.

TNFSF15 and MIA Variant Associated with Immunotherapy and Prognostic Evaluation in Esophageal Cancer.

Esophageal cancer (ESCA) is a common gastrointestinal tumor, and China is one of the regions with a high incidence. Tumor immune-related cells play important roles in the tumorigenesis and development of ESCA. However, the role of tumor immune-related genes in the development of ESCA has not been established. In this study, weighted gene coexpression network analysis (WGCNA) was used to analyze ESCA gene expression using data from The Cancer Genome Atlas (TCGA) database. Gene expression was associated with clinical traits, and modules related to CD8+T cells, dendritic cells, and regulatory T cells (Tregs) were obtained. The GO analysis showed that inflammatory chemotaxis networks were activated by cell chemotaxis, chemokine activity, and chemokine binding receptor. Three hub genes (IL17C, TNFSF15, and MIA) related to tumor immunity and metastasis were identified by WGCNA, and the abnormal expression of each hub gene in ESCA has a poor prognosis, especially in patients with high expression (P < 0.05). The risk assessment analysis also showed that tumor stage was positively correlated with tumor risk in ESCA (P < 0.05). Therefore, more than 50 pairs of tumor tissues from the T1-T3 stages with different degrees of differentiation and paracancerous tissues were selected to confirm the expression of the three genes using RT-qPCR and immunofluorescence (IF). The infiltration of CD8+ T cells in tumor tissues was lower than that in normal tissues. According to the RT-qPCR, the expressions of IL17 C, TNFSF15, and MIA in moderately and poorly differentiated tissues were significantly higher than those in normal tissues (P < 0.05). In contrast, their expressions were decreased in high differentiated tissues (P < 0.05). Furthermore, IL17C, TNFSF15, and MIA were all positively correlated with immune checkpoint PD-1; TNFSF15 and MIA were also positively correlated with CTLA4, TIGIT, and CD96. In summary, IL17C, TNFSF15, and MIA may act as biomarkers for prognosis in moderately and poorly differentiated ESCAs, and they may be used as predictive genes of immunotherapy associated with CD8+ T cell and Tregs invasion in ESCAs.

High-resolution integrated dynamic shimming diffusion-weighted imaging (DWI) in the assessment of rectal cancer.

To investigate the feasibility of high-resolution integrated dynamic shimming echo planar imaging (iEPI) applied to rectal cancer. A total of seventy-eight patients with non-mucinous rectum adenocarcinoma were enrolled in this study. Using a prototype high-resolution iEPI sequence, high-resolution single-shot EPI (sEPI) sequence, and sEPI sequence, subjective and objective assessment and apparent diffusion coefficient (ADC) value were measured for comparison. The spearman rank correlation analysis test and the receiver operating characteristic curve were performed to evaluate correlation between tumor ADC values, corresponding T stage, and differentiation degree of rectal cancer. The subjective assessment of the image quality (IQ) of high-resolution iEPI was rated superior to high-resolution sEPI and sEPI by both readers (p < 0.001). Signal-to-noise ratio, contrast-to-noise, and signal-intensity ratio were significantly higher in high-resolution iEPI than the other two sequences (p < 0.001). There was no significant difference of tumor ADC values among three EPI sequences in the group of low- to well-differentiated rectal cancer. An inverse correlation was noted between ADC values on three DWI sequences and pathological T stage of rectal cancer (r = - 0.693, - 0.689, - 0.640, p < 0.001). The AUC values of high-resolution iEPI, high-resolution sEPI, and sEPI in predicting well-differentiated rectal cancer were 0.910, 0.761, and 0.725 respectively. In conclusion, the high-resolution iEPI provided significantly higher IQ and stable ADC compared to another two sequences. High-resolution iEPI has the highest efficacy among three examined sequences in differentiation of rectal cancer with different degrees of differentiation. • High-resolution iEPI provided a significantly better IQ than high-resolution sEPI and sEPI when assessing rectal cancer. • The AUC of high-resolution sEPI was the highest among three EPI sequences in predicting well-differentiated rectal cancer.

The influence of asset specificity on farmers’ willingness to participate in fallow from the perspective of farmer differentiation

Fallow is an important institutional guarantee for green agricultural development and an important measure to promote rural revitalization. Asset specificity is a crucial factor that affects farmers’ willingness to participate in fallow. In order to improve farmers’ willingness of to fallow and promote the long-term promotion of fallow system, based on the perspective of farmer differentiation, a total of 1,240 micro survey data in four cities of Gansu province was used to quantify the asset specificity by the entropy method. A multivariate ordered Logit model and a double-hurdle model were established to explore the effects of asset specificity on the willingness of farmers with different degrees of differentiation. The results show that: 1) There are differences in fallow willingness among different types of farmers. The fallow willingness of non-farmers and II part-time farmers is generally stronger than that of pure farmers and I part-time farmers. 2) Geographical location specificity has a significant negative impact on the fallow willingness of the four types of non-fallow farmers, and has significant negative impacts on the subsequent fallow willingness and fallow degree of the four types of fallow farmers. 3) Physical asset specificity has a significant negative effect on the fallow willingness of pure farmers, I part-time and II part-time farmers among non-fallow farmers, but has little effect on the subsequent fallow willingness of fallow farmers. 4) Human capital specificity has a significant negative impact on the fallow willingness of the four types of non-fallow farmers, and has a significant negative impact on the subsequent fallow willingness and fallow degree of the four types of fallow farmers.

Реактивные изменения соединительнотканных структур в периферических нервах овец при патологии печени

Experimental studies were carried out on sheep using a tetramethane model of hepatosis. Ultrastructural data made it possible to characterize morphofunctional changes in peripheral nerves in sheep, in particular, in myelinated and non-myelinated fibers, neurolemmocytes, and connective tissue structures. The pathological process in the peripheral nervous system initiates a combined pathology of the abdominal organs. This is due to the commonality of their innervation with the dorsal and ventral vagus, celiac, phrenic nerves, and branches of the solar plexus. A decrease in the trophic function of the nerves leads to morphological changes in the pancreas, adrenal glands, kidneys, stomach, and small intestine, which were recorded at the ultrastructural level. As a result, hypoxia, energy and plastic insecurity occur, which leads to destructive processes that involve neurolemmocytes, nerve fibers, neurocytes, connective tissue cells and collagen fibers. Structural and functional changes in sheep, with experimental hepatosis, contribute to quantitative and qualitative changes in the nucleoplasm, cytoplasm, swelling and detachment of the karyolemma. Destruction of organelles depends on the intimate processes of cytolysis. At the same time, the connective tissue in the peripheral nerves suffers significantly, and its functional state largely determines the reactivity of the body. It accumulates various substances. An ultrastructural study of clinically healthy animals shows that in the peripheral nerves, in addition to the nerve components, bundles of collagen fibers form a large volume, where they form a dense tie, passing in different directions. Each of them consists of thinner fibrils, which in turn are bundles of subfibrils. Among the fibers are fibroblasts, which have a different degree of differentiation. Thus, mature fibroblasts have a welldeveloped granular endoplasmic reticulum and numerous ribosomes, with an actively functioning Golgi apparatus, mitochondria, and few microfilaments. In pathology, the qualitative composition of fibroblasts changes, lysis of collagen fibers occurs, and communication with neurolemmocytes is lost. At the same time, fibroblasts strengthen contacts with each other. Such contacts between two, three or more fibroblasts are often seen. Others are located next to vascular endothelial cells and pericytes. Apparently, in pathology, fibroblasts require an informative field for the overall coordination of adaptive processes. On the other hand, it is known that fibroblasts begin to produce IL-1, which affects many processes in the body, in particular, it changes the synthetic functions. This is probably why the connective tissue framework in peripheral nerves changes, and their decay, in turn, stimulates the production of IL-1 by fibroblasts. The latter not only destroys connective tissue elements, but also activates the secretion of collagenase, the processes of proliferation and differentiation of fibroblasts. Fibroblasts activated by IL1 produce PGE2.

Building an ensemble learning model for gastric cancer cell line classification via rapid raman spectroscopy

Cell misuse and cross-contamination can affect the accuracy of cell research results and result in wasted time, manpower and material resources. Thus, cell line identification is important and necessary. At present, the commonly used cell line identification methods need cell staining and culturing. There is therefore a need to develop a new method for the rapid and automated identification of cell lines. Raman spectroscopy has become one of the emerging techniques in the field of microbial identification, with the advantages of being rapid and noninvasive and providing molecular information for biological samples, which is beneficial in the identification of cell lines. In this study, we built a library of Raman spectra for gastric mucosal epithelial cell lines GES-1 and gastric cancer cell lines, such as AGS, BGC-823, HGC-27, MKN-45, MKN-74 and SNU-16. Five spectral datasets were constructed using spectral data and included the full spectrum, fingerprint region, high-wavelength number region and Raman background of Raman spectra. A stacking ensemble learning model, SL-Raman, was built for different datasets, and gastric cancer cell identification was achieved. For the gastric cancer cells we studied, the differentiation accuracy of SL-Raman was 100% for one of the gastric cancer cells and 100% for six of the gastric cancer cells. Additionally, the separation accuracy for two gastric cancer cells with different degrees of differentiation was 100%. These results demonstrate that Raman spectroscopy combined with SL-Raman may be a new method for the rapid and accurate identification of gastric cancer. In addition, the accuracy of 94.38% for classifying Raman spectral background data using machine learning demonstrates that the Raman spectral background contains some useful spectral features. These data have been overlooked in previous studies.

Single-Cell Transcriptomics Unveils the Dedifferentiation Mechanism of Lung Adenocarcinoma Stem Cells

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, and its prognosis is still poor due to therapy resistance, metastasis, and recurrence. In recent years, increasing evidence has shown that the existence of lung cancer stem cells is responsible for the propagation, metastasis, therapy resistance, and recurrence of the tumor. During their transition to cancer stem cells, tumor cells need to inhibit cell differentiation and acquire invasive characteristics. However, our understanding of the property and role of such lung cancer stem cells is still limited. In this study, lung adenocarcinoma cancer stem cells (LCSCs) were enriched from the PC-9 cell line in a serum-free condition. PC-9 cells grew into spheres and showed higher survival rates when exposed to gefitinib: the drug used for the treatment of LUAD. Additionally, we found that the canonical stemness marker protein CD44 was significantly increased in the enriched LCSCs. Then, LCSCs were inoculated into the groin of nude mice for 1.5 months, and tumors were detected in the animals, indicating the strong stemness of the cells. After that, we performed single-cell RNA sequencing (scRNA-seq) on 7320 LCSCs and explored the changes in their transcriptomic signatures. We identified cell populations with a heterogeneous expression of cancer stem marker genes in LCSCs and subsets with different degrees of differentiation. Further analyses revealed that the activation of the FOXM1 (oncoprotein) transcription factor is a key factor in cell dedifferentiation, which enables tumor cells to acquire an epithelial-mesenchymal transition phenotype and increases the LCSC surface marker CD44. Moreover, we found that the combination of CD44, ABCG2, and ALCAM was a specific marker for LCSCs. In summary, this study identified the potential factors and molecular mechanisms underlying the stemness properties of LUAD cancer cells; it could also provide insight into developing novel and effective therapeutic approaches.