Coiled-coil domain-containing 154 promotes colorectal cancer proliferation and metastasis via interacting with minichromosome maintenance complex component 2.

Coiled-Coil Domain-Containing (CCDC) is a large class of structural proteins containing left-handed supercoiled structure. The clinical value and the functional implication of CCDC in colorectal cancer (CRC) remain unknown. Based on the genetic, transcriptional, and clinical data from The Cancer Genome Atlas, five of thirty-six CCDC proteins were differentially expressed in the CRC and associated with the survival of patients with CRC. A CCDC-score model was established to evaluate the prognosis of patients. The potential function of Coiled-Coil Domain-Containing 154 (CCDC154) was investigated using bioinformatical methods, which unveiled that high expression of CCDC154 indicates poor survival for patients with CRC and correlates with low infiltration of CD8+ T cells and high infiltration of neutrophils, indicating that CCDC154 enhances tumor growth and metastasis. CCDC154 interacts with Minichromosome Maintenance Complex Component 2 (MCM2) protein and promotes malignant phenotype via MCM2. We validated the expression level and survival prediction value of CCDC154 in clinical samples, and analyzed its co-expression of MCM2, Ki-67 and p53. This work discloses the role of CCDC in clinical setting and CCDC154 functions in CRC.

Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

[Comparison between macroscopic identification and DNA barcoding identification of Amomi Fructus].

This study aims to explore the consistency between macroscopic identification and DNA barcoding identification of Amomi Fructus. With the DNA barcoding identification results, we evaluated the reliability of identifying Amomi Fructus quality by combining macroscopic traits with main volatile chemical components. Thirteen batches of Amomi Fructus samples were collected for identification. Firstly, the morphological and sensory characteristics of each sample were observed and recorded according to the standard in Chinese Pharmacopoeia(2020 edition). The 100-fruit weight, longitudinal diameter, transverse diameter, and longitudinal diameter-to-transverse diameter ratio were measured, which correspond to large, solid, and full kernel representing good quality in the sensory evaluation. The odor value detected by electronic nose and major volatile components(borneol, camphor, limonene, and borneol acetate) correspond to the sensory evaluation of strong odor representing good quality. Secondly, DNA barcoding was employed to identify the 13 batches of samples. Finally, clustering analysis was performed for the main volatile components and macroscopic traits, and the identification results were compared with those of DNA barcoding. Except two batches of samples(No.6 and No.10), the macroscopic identification showed the results consistent with those of DNA barcoding, with an identification rate of 84.62%. The clustering results of the content of four volatile chemical components and macroscopic traits were also consistent with the DNA barcoding identification results. DNA barcoding can verify the results of macroscopic identification and provide a scientific basis for the inheritance and development of macroscopic identification. Moreover, the combination of macroscopic traits and chemical components demonstrates higher accuracy in the quality evaluation of Chinese medicinal materials.

Molecular Characteristics of T Cell-Mediated Tumor Killing in Hepatocellular Carcinoma.

Background: Although checkpoint blockade is a promising approach for the treatment of hepatocellular carcinoma (HCC), subsets of patients expected to show a response have not been established. As T cell-mediated tumor killing (TTK) is the fundamental principle of immune checkpoint inhibitor therapy, we established subtypes based on genes related to the sensitivity to TKK and evaluated their prognostic value for HCC immunotherapies. Methods: Genes regulating the sensitivity of tumor cells to T cell-mediated killing (referred to as GSTTKs) showing differential expression in HCC and correlations with prognosis were identified by high-throughput screening assays. Unsupervised clustering was applied to classify patients with HCC into subtypes based on the GSTTKs. The tumor microenvironment, metabolic properties, and genetic variation were compared among the subgroups. A scoring algorithm based on the prognostic GSTTKs, referred to as the TCscore, was developed, and its clinical and predictive value for the response to immunotherapy were evaluated. Results: In total, 18 out of 641 GSTTKs simultaneously showed differential expression in HCC and were correlated with prognosis. Based on the 18 GSTTKs, patients were clustered into two subgroups, which reflected distinct TTK patterns in HCC. Tumor-infiltrating immune cells, immune-related gene expression, glycolipid metabolism, somatic mutations, and signaling pathways differed between the two subgroups. The TCscore effectively distinguished between populations with different responses to chemotherapeutics or immunotherapy and overall survival. Conclusions: TTK patterns played a nonnegligible role in formation of TME diversity and metabolic complexity. Evaluating the TTK patterns of individual tumor will contribute to enhancing our cognition of TME characterization, reflects differences in the functionality of T cells in HCC and guiding more effective therapy strategies.

An integrated bioinformatic investigation of mitochondrial solute carrier family 25 (SLC25) in colon cancer followed by preliminary validation of member 5 (SLC25A5) in tumorigenesis.

Solute carrier family 25 (SLC25) encodes transport proteins at the inner mitochondrial membrane and functions as carriers for metabolites. Although SLC25 genetic variants correlate with human metabolic diseases, their roles in colon cancer remain unknown. Cases of colon cancer were retrieved from The Cancer Genome Atlas, and the transcriptionally differentially expressed members (DEMs) of SLC25 were identified. DNA level alterations, clinicopathological characteristics, and clinical survival were also investigated. A risk score model based on the DEMs was constructed to further evaluate their prognostic values in a clinical setting. The results were preliminarily validated using bioinformatic analysis of datasets from the Gene Expression Omnibus, immunohistochemical evaluations in clinical specimens, and functional experiments in colon cancer-derived cell lines. Thirty-seven DEMs were identified among 53 members of SLC25. Eight of 37 DEMs were introduced into a risk score model using integrated LASSO regression and multivariate Cox regression. Validated by GSE395282 and GSE175356, DEMs with high-risk scores were associated with the phenotypes of increasing tumor immune infiltration and decreasing glycolysis and apoptosis contents. SLC25A5 was downregulated in cancer, and its upregulation was related to better overall survival in patients from public datasets and in clinical cases. High SLC25A5 expression was an independent prognostic factor for 79 patients after surgical treatment. A negative correlation between CD8 and SLC25A5 was determined in specimens from 106 patients with advanced colon cancer. SLC25A5 attenuated cell proliferation, upregulated the expression of programmed cell death-related signatures, and exerted its biological function by inhibiting the MAPK signaling pathway. Our study reveals that mitochondrial SLC25 has prognostic value in patients with colon cancer. The bioinformatic analyses by following verification in situ and in vitro provide direction for further functional and mechanistic studies on the identified member of SLC25.

[High-speed identification of odor changes and substance basis of Myristicae Semen mildew by electronic nose and HS-GC-MS].

This study adopted headspace-gas chromatography-mass spectrometry(HS-GC-MS) and electronic nose to detect volatile components from Myristicae Semen samples with varying degrees of mildew, aiming at rapidly identifying odor changes and substance basis of Myristicae Semen mildew. The experimental data were analyzed by electronic nose and principal component analysis(PCA). The results showed that Myristicae Semen samples were divided into the following three categories by electronic nose and PCA: mildew-free samples, slightly mildewy samples, and mildewy samples. Myristicae Semen samples with different degrees of mildew greatly varied in volatile components. The volatile components in the samples were qualitatively and quantitatively detected by HS-GC-MS, and 59 compounds were obtained. There were significant differences in the composition and content in Myristicae Semen samples with different degrees of mildew. The PCA results were the same as those by electronic nose. Among them, 3-crene, D-limonene, and other terpenes were important indicators for the identification of mildew. Bicyclo[3.1.0]hexane, 4-methylene-1-(1-methylethyl)-, terpinen-4-ol, and other alcohols were key substances to distinguish the degree of mildew. In the later stage of mildew, Myristicae Semen produced a small amount of hydroxyl and aldehyde compounds such as acetaldehyde, 2-methyl-propionaldehyde, 2-methyl-butyraldehyde, and formic acid, which were deduced as the material basis of the mildew. The results are expected to provide a basis for the rapid identification of Myristicae Semen with different degrees of mildew, odor changes, and the substance basis of mildew.

Integrative Characterization of Immune-relevant Genes in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Tumor microenvironment plays an essential role in cancer development and progression. Cancer immunotherapy has become a promising approach for the treatment of hepatocellular carcinoma (HCC). We aimed to analyze the HCC immune microenvironment characteristics to identify immune-related genetic changes. METHODS: Key immune-relevant genes (KIRGs) were obtained through integrating the differentially expressed genes of The Cancer Genome Atlas, immune genes from the Immunology Database and Analysis Portal, and immune differentially expressed genes determined by single-sample gene set enrichment analysis scores. Cox regression analysis was performed to mine therapeutic target genes. A regulatory network based on KIRGs, transcription factors, and immune-related long non-coding RNAs (IRLncRNAs) was also generated. The outcomes of risk score model were validated in a testing cohort and in clinical samples using tissue immunohistochemistry staining. Correlation analysis between risk score and immune checkpoint genes and immune cell infiltration were investigated. RESULTS: In total, we identified 21 KIRGs, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), and found IKBKE, IL2RG, EDNRA, and IGHA1 may be equally important to PD-1 or CTLA4. Meanwhile, KIRGs, various transcription factors, and IRLncRNAs were integrated to reveal that the NRF1-AC127024.5-IKBKE axis might be involved in tumor immunity regulation. Furthermore, the immune-related risk score model was established according to KIRGs and key IRLncRNAs, and verified more obvious discriminating power in the testing cohort. Correlation analysis indicated TNFSF4 , LGALS9 , KIAA1429 , IDO2, and CD276 were closely related to the risk score, and CD4 T cells, macrophages, and neutrophils were the primary immune infiltration cell types. CONCLUSIONS: Our results highlight the importance of immune genes in the HCC microenvironment and further unravel the underlying molecular mechanisms in the development of HCC.

Thoracic Intraspinal Ganglioneuroma with Cough as Its Main Symptom:Report of One Case / 中国医学科学院学报

The ganglioneuroma is a benign tumor originating from sympathetic ganglion cells.It often locates in the posterior mediastinum,retroperitoneum,and adrenal medulla.The intraspinal ganglioneuromas is relatively rare in clinical practice,which mainly locates in the cervical and thoracolumbar segments.A patient with main symptom of cough was examined by magnetic resonance imaging before operation in our center.Intraspinal ganglioneuromas was confirmed in the left intervertebral cavity area.Total resection of the tumor via the posterior median approach was performed.HE staining showed the mature ganglion cells were scattered.The patient was followed up for three months and no tumor recurrence occured.

Health literacy level and its influencing factors among residents in Ningbo City / 预防医学

Objective To analysis the health literacy status, trends and distribution characteristics of Ningbo residents during 2015-2016, and to provide basis for developing health policies and intervention strategies. Methods During 2015-2016, 9810 residents of 15-69 years old in Ningbo were investigated by face-to-face interviews using the unified national questionnaire and multistage PPS sampling method. Results Totally 9750 residents correctly filled out the questionnaire. The adjusted health literacy (AHL) of residents in 2016 was 21.73％, increased by 6.29 percentage points than 2015 (15.44％) .The monitoring results of two years both showed that there was no significant differences of AHL between men and women (P >0.05) . However, the AHL of residents with different age-groups, occupations and education levels all assumed significant differences (P<0.05) . The AHL was significantly higher in urban residents than rural residents (P<0.05) .Among the 6 health issues, the AHL of safety and first aid was the highest (2015: 56.98％, 2016: 61.32％), and the chronic disease prevention (2015:11.23％, 2016: 12.10％) and basic medical care (2015: 11.97％, 2016: 13.81％) were the lowest, also who had the smallest lifting range. Logistic regression analysis displayed that residents with higher level of education had higher AHL (OR=1.72, 95％CI: 1.61-1.83) . Comparison with civil servants, institutions, teachers and medical professionals, farmers (OR=0.74, 95％CI: 0.58-0.94), workers (OR=0.70, 95％CI: 0.57-0.86) and other occupational groups (OR=0.78, 95％CI: 0.64-0.96) had lower AHL. Conclusion The health literacy of Ningbo residents is on the rise, Knowledge of chronic disease prevention and basic medical care will be the main contents of health literacy enhancement program in the future, especially for people with less education.