Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans ; Ribosomes/physiology* ; Ribosomal Proteins/metabolism* ; Mutation ; Animals ; Cell Nucleolus/metabolism* ; Protein Biosynthesis ; Phase Separation

PBK is a cancer/testis antigen that exhibits absent expression in various normal human tissues,but undergoes aberrant overexpression upon cellular transformation,thereby promoting the initiation,metastasis and even drug resistance of cancer.Consequently,it represents a novel target for tumor immunotherapy.In this study,PBK-Nitrath,a protein vaccine specifically designed to target PBK by fusing nitrated T epitope with the PBK protein was developed,using the IFN-γ ELISpot method to evaluate the activation level of PBK antigen-specific T cells in the spleen of immunized mice,and conducting in vitro cytotoxicity T cell killing efficacy test to evaluate the killing ability against H22 hepatic carcinoma cells;the anti-tumor activity was evaluated using a H22 hepatic carcinoma subcutaneous transplantation tumor model,and the differentiation of peripheral blood and spleen T lymphocytes and tumor immune infiltration were analyzed by flow cytometry.Results showed that PBK-Nitrath could efficiently induce the activation of antigen-specific T cells against PBK while enhancing cytotoxic T lymphocyte-mediated killing capacity,significantly impede hepatic carcinoma progression in mice and increase the ratio of CD8+CD107a+T cells within peripheral blood and spleen,and facilitate tumor lymphocyte infiltration.Our findings reveal the potential utility of PBK-Nitrath as an effective candidate for tumor vaccine.

Objective:To explore the correlation between serum levels of interleukin-9 (IL-9), platelet activating factor (PAF), total immunoglobulin E (IgE), interferon γ (IFN-γ), and interleukin-4 (IL-4) in patients with chronic spontaneous urticaria (CSU).Methods:Sixty CSU active phase patients admitted to the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 were selected and included in the CSU active phase group. Based on the 7-day Urticaria Activity Score (UAS7), they were divided into three groups: 15 mild group, 25 moderate group, and 20 severe group; And 19 patients who entered the quiescent phase of the disease after 28 days of standardized antihistamine treatment were included in the CSU quiescent phase group. Another 30 healthy subjects who participated in the physical examination at the same time at our hospital′s physical examination center were selected to be included in the healthy control group. 5 ml of fasting elbow vein blood was collected from CSU active and stationary patients, as well as healthy subjects. The serum levels of IL-9, PAF, total IgE, IFN-γ, and IL-4 were detected using enzyme-linked immunosorbent assay. Pearson correlation test was used to analyze the correlation between serum IL-9, PAF levels and total IgE, IFN-γ, and IL-4 levels in CSU active patients.Results:The serum levels of IL-9, PAF, total IgE, and IL-4 in the CSU active phase group were higher than those in the CSU stationary phase group and healthy control group (all P<0.05), and the serum IFN-γ levels were lower than those in the CSU stationary phase group and healthy control group (all P<0.05). There was no statistically significant difference in the levels of the above indicators between the healthy control group and the CSU stationary group (all P>0.05). The serum levels of IL-9, PAF, total IgE, and IL-4 in the severe group were significantly higher than those in the mild and moderate groups (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild and moderate groups (all P<0.05); The serum levels of IL-9, PAF, total IgE, and IL-4 in the moderate group were significantly higher than those in the mild group (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild group ( P<0.05). Pearson correlation analysis showed that serum IL-9 and PAF levels were positively correlated with serum total IgE and IL-4 levels in CSU active phase patients (IL-9: r=0.726, 0.870, PAF: r=0.788, 0.795, all P<0.01), and negatively correlated with serum IFN-γ levels (IL-9: r=-0.831, PAF: r=-0.816, all P<0.01). Conclusions:The serum levels of IL-9 and PAF in patients with active CSU are elevated and correlated with total IgE, IFN-γ, and IL-4 levels, suggesting that IL-9 and PAF may be related to the occurrence and development of CSU.

Objective To investigate the role of RNA-binding motif protein X-linked(RBMX)in regulating the proliferation,migration,invasion and glycolysis in human bladder cancer cells.Methods A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown,respectively,and successful cell modeling was verified using RT-qPCR and Western blotting.Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay,and cell migration and invasion abilities were determined using Transwell experiment.The expressions of glycolysis-related proteins M1 pyruvate kinase(PKM1)and M2 pyruvate kinase(PKM2)were detected using Western blotting.The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits.Results RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown.RBMX overexpression significantly inhibited the proliferation,clone formation,migration and invasion of bladder cancer cells,while RBMX knockdown produced the opposite effects.Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2,while RBMX knockdown produced the opposite effects.Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression(P<0.05)but increased significantly following RBMX knockdown(P<0.05).Conclusion RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression,suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.

Objective To investigate the role of RNA-binding motif protein X-linked(RBMX)in regulating the proliferation,migration,invasion and glycolysis in human bladder cancer cells.Methods A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown,respectively,and successful cell modeling was verified using RT-qPCR and Western blotting.Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay,and cell migration and invasion abilities were determined using Transwell experiment.The expressions of glycolysis-related proteins M1 pyruvate kinase(PKM1)and M2 pyruvate kinase(PKM2)were detected using Western blotting.The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits.Results RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown.RBMX overexpression significantly inhibited the proliferation,clone formation,migration and invasion of bladder cancer cells,while RBMX knockdown produced the opposite effects.Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2,while RBMX knockdown produced the opposite effects.Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression(P<0.05)but increased significantly following RBMX knockdown(P<0.05).Conclusion RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression,suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.

Abstract Type 2 diabetes mellitus (T2DM) has become a worldwide epidemic, which poses a great threat to the global healthcare system. Based on review of publications pertaining to T2DM health management in urban communities, this article focuses on the health management models of T2DM in foreign urban communities, including insurance companies and medical institutions, self-management plans, community management, community and home hybrid services, artificial intelligence + big data management, social media and online community management, precision health management, and proposes suggestions for T2DM health management in Chinese urban communities based on currently available national management models, including increasing the standardization of the management level, improving the supporting facilities of professional talents, mobilizing social forces to support, improving the scientific and technological level of management tools, strengthening the advantages of traditional Chinese medicine and exploring novel personalized models, so as to provide insights into promoting the sustainable development of T2DM health management in Chinese urban communities.

The skeletal system, which contains bones, joints, tendons, ligaments and other elements, plays a wide variety of roles in body shaping, support and movement, protection of internal organs, production of blood cells and regulation of calcium and phosphate metabolism. The prevalence of skeletal diseases and disorders, such as osteoporosis and bone fracture, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, increases with age, causing pain and loss of mobility and creating a huge social and economic burden globally. Focal adhesions (FAs) are macromolecular assemblies that are composed of the extracellular matrix (ECM), integrins, intracellular cytoskeleton and other proteins, including kindlin, talin, vinculin, paxillin, pinch, Src, focal adhesion kinase (FAK) and integrin-linked protein kinase (ILK) and other proteins. FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell-environment communications and modulates important processes, such as cell attachment, spreading, migration, differentiation and mechanotransduction, in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways. This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.

Objective:To explore the relationship of serum interleukin (IL) -9 and platelet-activating factor (PAF) levels with serum total immunoglobulin E (IgE) levels, disease severity and disease course in patients with chronic spontaneous urticaria (CSU) .Methods:A total of 60 patients with active CSU were collected from Department of Dermatology, the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 (active CSU group), and divided into mild group, moderate group and severe group according to 7-day urticaria activity score (UAS7). After 28-day standard antihistamine therapy, the patients whose condition became stable were included in the stable CSU group. During the same period, 30 health examinees were included in the healthy control group. Peripheral venous blood samples were collected from the subjects in each group, enzyme-linked immunosorbent assay (ELISA) was performed to detect serum levels of IL-9 and PAF, and immunoturbidimetric assay to detect the serum total IgE level. Correlations of serum IL-9 and PAF levels with serum total IgE levels, UAS7 scores and disease courses were analyzed in patients with CSU. One-way analysis of variance was used for comparisons among multiple groups, least significant difference- t test for multiple comparisons, and Pearson correlation analysis for correlation analysis. Results:Totally, 28 males and 32 females were included in the active CSU group, their age ranged from 11 to 68 years (34.68 ± 8.62 years), and the disease duration ranged from 2 months to 7 years (1.42 ± 0.41 years). In the healthy control group, 14 were males and 16 were females, and their age ranged from 10 to 70 years (35.06 ± 7.89 years). According to UAS7, 12, 26, and 22 patients were diagnosed with mild, moderate and severe CSU respectively, and 22 were included in the stable CSU group after standard treatment. The levels of serum IL-9, PAF and total IgE significantly differed among the active CSU group, stable CSU group and healthy control group (IL-9: 144.34 ± 23.19 vs. 109.25 ± 20.77 vs. 107.23 ± 19.23 pg/ml; PAF: 362.45 ± 51.45 vs. 223.18 ± 32.46 vs. 221.23 ± 28.38 pg/ml; total IgE: 168.12 ± 32.48 vs. 24.04 ± 7.04 vs. 21.76 ± 5.95 IU/ml; F = 38.80, 148.38, 499.12, respectively, all P < 0.001), and were significantly higher in the active CSU group than in the stable CSU group and healthy control group (all P < 0.05), while there was no significant difference between the stable CSU group and healthy control group (all P > 0.05). Pearson correlation analysis showed that the serum IL-9 and PAF levels were positively correlated with serum total IgE levels and UAS7 scores (all P < 0.05), but not correlated with the disease course (both P > 0.05) . Conclusion:Serum IL-9 and PAF levels in patients with active CSU were markedly elevated along with the increase in disease severity, and closely correlated with serum total IgE levels.

Objective:To analyze the effect of perioperative SEPT9 level in peripheral blood on long-term prognosis of patients with colorectal tumors. Methods:Retrospectively analyzed the data of 334 patients with colorectal cancer admitted to the Department of Anus & Intestine Surgery from January 2017 to December 2022, including 197 male patients and 137 female patients, aged 29 to 83 (62.8±10.7) years. Positive group was consisted of 241 patients with positive SEPT9 before surgery, while negative group was consisted of 93 patients with negative SEPT9 before surgery. Among the positive group, 169 cases turned negative for SEPT9 on the one week after surgery (transnegative group), and another 72 cases did not turn negative (non negative group). Univariate and multivariate analysis of clinical general data were carried out to screen out the risk factors affecting the long-term prognosis of colorectal cancer patients after surgery. The survival curve was calculated by Kaplan-Meier method, and the Log-rank test was used to compare the difference in survival rate between groups. Results:All patients′ overall median survival time was 67 months, and the 1, 3 and 5 years overall survival rate was 91.9%, 70.9% and 57.1%. The results of multi-factor analysis showed that whether the tumor had lymph node metastasis, TNM stage, and preoperative SEPT9 methylation status were independent risk factors affecting the long-term prognosis of colorectal cancer ( P=0.004, <0.001, 0.041), while for patients with preoperative SEPT9 positive, TNM stage of tumor and whether SEPT9 turned negative after surgery were independent risk factors for prognosis ( P=0.026, 0.001). The median survival time of patients in positive group and negative group was 63 months and 71 months, respectively. The 1, 3 and 5 year survival rates after surgery were 90.4%, 67.0%, 55.0% and 95.7%, 79.1% and 64.6%, respectively( P=0.007). The median survival time of the patients in the transnegative group and nonnegative group was 45 months and 62 months, respectively. The 1, 3 and 5-year survival rates were 83.2%, 60.5%, 48.1% and 93.5%, 72.9%, 63.5%( P<0.001). Conclusions:Perioperative SEPT9 level is correlated with long-term prognosis of CRC patients, and patients with negative SEPT9 before surgery have better prognosis than those with positive SEPT9. Preoperative positive patients who do not turn negative after surgery often indicate poor prognosis of tumor.

Colorectal cancer is a common tumor of the digestive system with a high degree of malignancy. Most patients are in the advanced stages of the disease when they develop symptoms. Although the detection rate of traditional screening methods is improving with advances in imaging and the popularity of colonoscopy, the diagnosis of early, asymptomatic colon cancer is still unsatisfactory. Therefore, it is particularly important to further study the occurrence and development mechanism of colorectal cancer and obtain new ideas for the diagnosis and treatment.? In recent years, with the deepening of epigenetics research, the role of DNA methylation in the pathogenesis of colorectal cancer has gradually attracted attention. This paper will review the research progress of DNA methylation in colorectal cancer′s diagnosis and treatment.