Objective:To construct A novel scoring model of immune signatures for colon cancer based on machine learning,which improve the survival prediction and immune therapy.Methods:Screening immune signatures from 1 301 immune-related genes(IRG)by the combined strategy of Lasso+bootstrap+multi Cox to calculate IRG scores of colon cancer patients from TCGA databases,and comprehensive the differences on function,prognostic status and immune therapy between high IRG scores group and IRG scores group.Results:Groups based on IRG scores were significantly different on the prognostic status of colon cancer patients,which were validated by other independent datasets.The IRG scores also could assess the effect of immune therapy of colon cancer.Conclusion:This study provides ideas for immune therapy and researches of colon cancer based on immune genes,and IRG scores can be used to assess the prognosis of colon cancer patients.

Colorectal cancer is a common malignant tumor.Revealing the interaction between tumor cells and tu-mor microenvironment(TME)can provide new targets for the prevention or therapy of colorectal cancer.Three-dimensional models such as cell spheroids,organoids,organ chips,and three-dimensional printing have been widely used to simulate TME in colorectal cancer,which can better reproduce the structure and heterogeneity of TME.This paper reviews the progress in the application of three-dimensional models in TME research of colorectal cancer to provide references for future research.

Metabolic diseases refer to metabolic disorders caused by abnormal material metabolism or energy metabolism of the body such as diabetes,hyperlipidemia,hyperuricemia and liver disease.In recent years,with the change of national diet structure,its incidence has increased year by year,which seriously endangers national physical and mental health.In modern medicine,long-term treatment of metabolic diseases is often used in the treatment of chemical drugs,which is easy to produce drug resistance and liver and kidney damage.Tannin is a class of polyphenolic compounds composed of glucose,gallic acid,flavanols,etc.,which has antibacterial,anti-tumor,anti-oxidation,hypoglycemic,antiviral,anti-inflammatory and analgesic effects,and has a clear easing effect on metabolic diseases.Tannin in the treatment of metabolic diseases has the advantages of less toxic side effects,significant curative effect,low cost,easy to popularize,etc.,which provides a better choice for the treatment of metabolic diseases.

Objective:To investigate the effect and mechanism of lactoferrin (LF) on biological behaviors of brain glioma cells.Methods:The effect of LF at different concentrations (0, 100, 200 and 300 μg/mL) on the proliferative ability of human glioma cell line U87MG was analyzed by MTT assay to screen the optimal drug concentration. U87MG cells were divided into blank control group and LF (200 μg/mL) treatment group. Edu staining, Transwell assay, Mito-Tracker staining and DCFH-DA staining were used to detect the cell proliferation, migration, mitochondrial activity and reactive oxygen level. Autophagy marker protein microtubule associated protein 1 light chain 3B (LC3B) expression was detected by immunofluorescent chemical staining; contents of superoxide dismutase (SOD) and malonaldehyde (MDA) were detected by colorimetric chemical sensors; expressions of genes related to epithel-to-mesenchymal transformation (E-cadherin, fibronectin, N-cadherin, vimentin and Snail) were detected by reverse transcription (RT)-PCR; expressions of apoptosis-related proteins (Bax and Bcl-2) were detected by Western blotting.Results:Compared with blank control group, the LF treatment group had significantly decreased proportions of Edu positive cells and Mito-Tracker positive cells, number of cell migration and SOD content, and statistically increased proportion of DCFH-DA positive cells, MDA content and LC3B immunofluorescent staining intensity in cytoplasm ( P<0.05). Compared with blank control group, the LF treatment group had significantly decreased E-cadherin mRNA expression and Bcl-2 protein expression, and statistically increased fibronectin, N-cadherin, vimentin and Snail mRNA expressions and Bax protein expression ( P<0.05). Conclusion:LF can effectively inhibit the proliferation, migration, invasion and other biological behaviors of glioma cells, whose mechanism is closely related to mitochondrial activity.

As a newly discovered posttranslational modification (PTM), crotonylation has been identified in histone and nonhistone proteins and has important roles in the regulation of various diseases and biological processes. With the development of high-resolution mass spectrometry approaches, an increasing number of endogenous crotonylation has been detected and identified. The discovery of crotonylation regulatory enzymes paved the way for the study of crotonylation mechanism. In this review, we summarize the biological functions and regulatory mechanism of crotonylation in eukaryotes and introduce the recent progress on crotonylation in malignant tumor.

BACKGROUND: MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms. METHODS: We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 ( RUNX3 ) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC. RESULTS: MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion. CONCLUSIONS Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.
Humans ; Carcinoma, Hepatocellular/pathology* ; Epithelial-Mesenchymal Transition/genetics* ; Liver Neoplasms/pathology* ; Gene Expression Regulation, Neoplastic/genetics* ; MicroRNAs/metabolism* ; Cell Movement/genetics* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Core Binding Factor Alpha 3 Subunit/metabolism*

Objective:To analyze the value of folate receptor-positive circulating tumor cells (FR +-CTC) in the diagnosis and efficacy evaluation of patients with small cell lung cancer (SCLC). Methods:The data of 59 patients with SCLC and 14 patients with benign pulmonary diseases treated in China-Japan Friendship Hospital from May 2017 to October 2019 were retrospectively analyzed. Folate receptor targeted detection was used to detect the level of FR +-CTC in the blood of SCLC patients. The levels of serum progastrin-releasing peptide (Pro-GRP), neuron-specific enolase (NSE), cytokeratin 19 fragment 21-1 (Cyfra21-1) , and carcinoembryonic antigen (CEA) were detected by using chemiluminescence. The median ( P25, P75) was used as all the detection indexes. Mann-Whitney U test was used for pairwise comparison, Spearman correlation test was used to analyze the correlation between two variables, and receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy. Results:The level of FR +-CTC in 59 patients with SCLC was 11.00 FU/3 ml (7.10 FU/3 ml, 14.50 FU/3 ml), and the positive rate of FR +-CTC in patients with SCLC was 66.10% (30/59); the level of FR +-CTC in 14 patients with benign pulmonary diseases was 6.75 FU/3 ml (5.03 FU/3 ml, 7.85 FU/3 ml), and the positive rate of FR +-CTC in 14 patients with benign pulmonary diseases was 14.29% (2/14). The level of FR +-CTC in patients with SCLC was higher than that in patients with benign pulmonary diseases, and the difference was statistically different ( U = 33.50, P < 0.01). The expression level of FR +-CTC was not related to age, gender and smoking history in SCLC patients (all P>0.05). The expression level of FR +-CTC in patients with extensive-stage was higher than that in patients with limited-stage, and the difference was statistically significant ( P < 0.05). Tumor markers Pro-GRP, NSE, Cyfra21-1 and CEA were compared with FR +-CTC, and the ROC curve was drawn; the results showed that FR +-CTC had better sensitivity (71.2%) and specificity (92.90%) in the diagnosis of SCLC. For SCLC patients who received chemotherapy, the decrease range of FR +-CTC in patients with partial remission and stable disease was greater than that in patients with the progression of disease, and the differences were statistically significant (all P < 0.05). Conclusion:FR +-CTC can assist the diagnosis and disease staging of SCLC. For patients receiving chemotherapy, continuous detection of circulating tumor cells can help to evaluate the efficacy of chemotherapy and provide a reference for the choice of clinical treatment.

Objective:To investigate the clinical and genetic features, and treatment of X-linked hypophosphatemic rickets (XLH).Methods:In this retrospective study, we reviewed the medical records of 25 pediatric patients with XLH who were admitted to Department of Endocrinology Genetics and Metabolism,Beijing Children′s Hospital from January 2010 to January 2020. The clinical characteristics, PHEX gene variants, as well as clinical outcome of the patients were summarized. To analyze the correlation between genotype and phenotype, the patients were divided into different subgroups according to the location of the variants, including N-terminal-located vs. C-terminal-located variant, and Zn-binding domain exon 17 or 19 variant vs. non-exon 17 or 19 variant. The age at onset, height standard deviation score (HtSDS), intercondylar or intermalleolar distance, fasting serum phosphorus, and HtSDS and intercondylar or intermalleolar distance at the final follow-up were compared by rank sum test or t text. Results:Among the 25 children with XLH, 8 were boys and 17 were girls. The median age of onset was 1.2 (1.0, 1.8) years, and the median age of diagnosis was 2.5 (1.5, 4.3) years. The main clinical manifestations were abnormal gait and lower limb deformity. The HtSDS was -2.0(-3.2, -0.8), and the intercondylar or intermalleolar distance was 4.5 (3.0, 6.0) cm. The fasting serum phosphorus level was 0.8 (0.7, 0.9) mmol/L, while the serum alkaline phosphatase level was (721±41) U/L and the serum calcium level was (2.5±0.1) mmol/L. Three patients (12%) had parathyroid hormone levels above the upper limit of the normal range. Twenty-five patients (100%) showed radiographic changes of active rickets. Nephrocalcinosis was found in 2 cases (9%). Twenty-four different PHEX variations were detected in 25 patients, among whom 11 (44%) had not been reported previously. No hot spot variation was found. No statistical differences (all P>0.05) were identified in clinical features and outcomes either in comparing patients with N-terminal (21 cases) and C-terminal (4 cases) variants, or in comparing patients with variant located in exon 17 or 19 (4 cases) or not (21 cases). Twenty-four cases (96%) were treated regularly with phosphate supplements and active vitamin D. After 2.7 (1.6, 5.0) years of follow-up, clinical symptoms were relieved in 96% (24/25) of the patients. The HtSDS after treatment had no significant difference compared to that before treatment (-2.0(-3.2, -0.8) vs.-2.0(-2.8, -1.1), Z =-0.156, P>0.05), while the intercondylar or intermalleolar distance after treatment was significantly reduced compared to that before treatment (4.5(3.0, 6.0) vs. 1.5(0, 3.3) cm, Z =-3.043, P<0.05). Bone X-rays were reexamined in 17 cases after treatment, and radiographic signs of rickets were improved. Eighteen cases had secondary hyperparathyroidism and 7 cases had nephrocalcinosis. Conclusions:The main clinical manifestations of XLH are abnormal gait, lower limb deformity and short stature. A high proportion of novel variations of PHEX gene but no hot spot variation neither genotype-phenotype correlation are found. Regular treatment with phosphate supplements and active vitamin D can significantly improve the symptoms except for the height. However, the rate of adverse events including secondary hyperparathyroidism and nephrocalcinosis seems to be high.

Objective:To qualitatively analyze the elasticity characteristics of boundaries and surrounding liver tissue of focal liver lesions (FLL) by real-time shear wave elastography (SWE), and to analyze the relating influencing factors.Methods:One hundred and fifty-two patients with FLLs (152 lesions) from February 2012 to October 2013 in the First Affiliated Hospital of Sun Yat-Sen University were collected. SWE of FLLs and the surrounding liver tissue was performed and baseline clinical data were collected. The elastic boundary (clear or not clear) of FLLs and elasticity distributions of surrounding liver tissue and their influencing factors were analyzed.Results:A total of 26 benign lesions and 126 malignant lesions were included in this study. Twenty-five cases (96.2%) of benign lesions showed clear elastic boundaries and 1 case (3.8%) showed unclear elastic boundary while 82 cases (65.1%) of malignant lesions showed clear elastic boundaries and 44 cases (34.9%) showed unclear elastic boundaries. Multivariate analysis showed benign/malignant lesion was an independent influencing factor for elastic boundary ( P<0.05). Twenty cases (76.9%), 6 cases (23.1%) and 0 case of liver tissue around benign lesions showed type A, B and C elastic distribution respectively while 17 cases (13.5%), 60 cases (47.6%), and 49 cases (38.9%) of liver tissue around malignant lesions showed type A, B, and C elastic distribution. There were statistically significant differences of benign and malignant lesions, different viral hepatitis backgrounds, different gender, and different ALB, TBIL, ALT levels in elasticity distributions of surrounding liver tissue of FLLs among type A, B and C (all P<0.05) while there was no significant difference in different lesion size( P=0.036). Conclusions:The elasticity characteristics of boundaries and surrounding liver tissue of FLLs on SWE images can provide a reference for differential diagnosis of benign and malignant FLLs. The elastic characteristics of surrounding liver tissue of FLLs are influenced by the nature of lesions and the background of liver disease, but are not influenced by lesion size. Further quantitative studies of elasticity characteristics of boundaries and surrounding liver tissue are needed for the differential diagnosis of different types of FLLs.

Objective:To establish a model based on two-dimensional shear wave elastography (2D-SWE) for predicting post-hepatectomy liver failure (PHLF) among patients with hepatocellular carcinoma (HCC).Methods:One hundred and one consecutive patients with HCC undergoing hepatectomy from August 2018 to July 2019 were enrolled prospectively in the First Affiliated Hospital of Sun Yat-Sen University. Laboratory tests, shear wave elastography in liver parenchyma, and abdominal contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) were performed preoperatively. Liver functional reserve, liver stiffness (LS), and tumor-related imaging parameters were assessed. PHLF was defined according to the definition of International Study Group of Liver Surgery Recommendations (ISGLS). A predictive model was developed by logistic regression analysis and the performance thereof was evaluated by receiver operating characteristic (ROC) curve analysis and Hosmer-Lemeshow test.Results:PHLF occurred in 39 patients (38.9%). Logistic regression analysis identified that international normalized ratio ( OR=1.09, P=0.026), LS( OR=1.297, P=0.004) and the largest nodule diameter( OR=1.191, P=0.015) were independent risk factors of PHLF.The area under curve (AUC) of the model was 0.842(95% CI =0.763-0.921), which was significantly higher than those of ALBI score, MELD score and Child-Pugh score (AUC 0.626-0.688, P<0.05). The model also showed good calibration in Hosmer-Lemeshow test ( P=0.498). Conclusions:A model based on 2D-SWE provides good preoperative prediction of PHLF among patients with HCC, which might have the potential in better customizing treatment strategy in those patients.