The long noncoding RNA FOXCUT promotes proliferation and migration by targeting FOXC1 in nasopharyngeal carcinoma.

Long noncoding RNAs play an important role in various biological processes, including tumorigenesis. FOXC1 (Forkhead box C1) is a member of the Forkhead box family of transcription factors and plays a crucial role in nasopharyngeal carcinoma. In this study, a novel long noncoding RNA (FOXCUT) located upstream of FOXC1 was investigated in 42 nasopharyngeal carcinoma patients. Our analysis revealed that the expression levels of FOXCUT and FOXC1 in nasopharyngeal carcinoma tissues were significantly higher than those observed in chronic nasopharyngitis tissues and that FOXCUT expression was positively correlated with FOXC1 expression. Additionally, knockdown of FOXCUT significantly inhibited proliferation and migration of nasopharyngeal carcinoma cell lines and resulted in downregulated expression of the matrix metalloproteinase 7 and matrix metalloproteinase 9, as well as vascular endothelial growth factor A and ß-catenin. Our findings suggested that FOXCUT expression contributed to the development and progression of nasopharyngeal carcinoma by targeting FOXC1 and that FOXCUT might be useful as a potential nasopharyngeal carcinoma biomarker and therapeutic target.

The role of FERMT2 in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy.

BACKGROUND: To investigate the prediction value of preoperative serum alpha-fetoprotein (AFP) level for the prognosis of hepatocellular carcinoma (HCC), by comparing pathological characteristics, recurrence rate and survival rate after hepatectomy. METHODS: 108 cases of HCC patients who received liver resection in our hospital from 2005 to 2011 were enrolled in this study. According to preoperative serum AFP level, the patients were divided into AFP ≤ 20 ng/mL group, AFP 20 to 400 ng/mL group and AFP > 400 ng/mL group, and the clinicopathological and cytopathological features were compared. All the patients were followed up for 24 months, the postoperative recurrence rates and survival rates were compared and analyzed, and the risk factors for HCC postoperative survival rate were studied by multifactor regression analysis. RESULTS: Of the 108 cases of HCC patients, there were 42 cases in AFP ≤20 ng/mL group, 28 cases in AFP 20-400 ng/mL group and 39 cases in AFP > 400 ng/mL group. It was shown that cell differentiation degrees (χ² = 20.198, P = 0.000) and microvascular invasion rates (χ² = 20.358, P = 0.000) were significantly different among the three groups. The AFP ≤ 20 ng/mL group showed higher cell differentiation degrees and significantly lower microvascular invasion rates compared to the other groups (P < 0.05). The follow-up data showed that postoperative 2-year recurrence rate (χ² = 6.164, P = 0.046), 18-month survival rate (χ² = 7.647, P = 0.022) and 24-month survival rate (χ² = 6.725, P = 0.035) of the three groups were significantly different, and we found that the AFP ≤ 20 ng/mL group had lower postoperative 2-year recurrence rate, and higher 18-month survival rate and 24-month survival rate than the other two groups (P <0.05). Multiple logistic regression analysis indicated that tumor diameter (≥ 5 cm) and preoperative serum AFP level (> 400 ng/mL) were closely correlated with HCC postoperative survival rate (P <0.05). CONCLUSIONS: It is shown that preoperative serum AFP level has considerable predictive value for the malignant feature and prognosis of HCC. It is suggested that HCC patients with no contraindication of operation and serum AFP ≤ 20 ng/mL can benefit most from primary treatment of hepatectomy. While HCC patients with serum AFP higher than 20 ng/mL need comprehensive therapy besides surgical resection and close follow up.

Helsmoortel-van der Aa syndrome in a Chinese pediatric patient due to ADNP nonsense mutation: A case report.

Background: Helsmoortel-van der Aa syndrome, also known as ADNP syndrome, is a condition that causes developmental delay, language impairment, autism spectrum, and variable extraneurologic features. It is caused by heterozygous mutations in the ADNP gene on chromosome 20q13. Most of the genetic causes of Helsmoortel-van der Aa syndrome have been reported are as de novo nonsense or frameshift stop mutations in exon 5 of ADNP gene, while fewer truncating variants were discovered in exons 4 and the 5' end of exon 5. Methods: In our study, a 4-year-old female Chinese patient was reported with delayed psychomotor development, language impairment, ataxia, anxiety, aggressive behavior, and congenital heart defect. Trio whole exome sequencing and copy number variation sequencing were performed. Results: A novel de novo heterozygous pathogenic mutation c.568C > T (p.Gln190Ter) was identified in the ADNP gene of the proband. His unaffected parents did not have the variant. According to the American College of Medical Genetics (ACMG) guidelines, c.568C > T was classified as "pathogenic". Conclusion: Our report indicated that c.568C > T (p.Gln190Ter) in ADNP gene is the cause of abnormal development of the nervous system, congenital heart disease and strabismus, broadening the spectrum of ADNP gene mutations associated with Helsmoortel-van der Aa syndrome.

MiR-199a-3p promotes repair of myocardial infarction by targeting NACC2.

OBJECTIVE: Myocardial infarction (MI) has gained widespread interest due to its high death and disability rate worldwide. Some miRNAs are markers of heart disease. Therefore, it is necessary to understand the mechanism for repairing MI injury. METHODS: Here, we evaluated the relative expression levels of miR-199a-3p in mouse and human myocardial cell models of injury, and its effect on myocardial cells viability using Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridline (EdU) assay, and flow cytometry assay as well as western blot in vitro. Furthermore, we performed bioinformatic online analysis to investigate the role that miR-199a-3p plays in cardiomyocyte injury, measured by dual-luciferase reporter assay. RESULTS: The results showed that miR-199a-3p significantly increased the growth rate of cardiomyocytes after treating them with hydrogen peroxide (H2O2). miR-199a-3p also acted as an inhibitor that directly targeted NACC2, resulting in a higher NACC2 expression level in the injury model of cardiomyocytes than normal myocardial cells and thus preventing miR-199a-3p-induced proliferation promotion in model cardiomyocytes. CONCLUSION: Our results demonstrate that miR-199a-3p may be a prognostic biomarker in myocardial injury.

Malignant transformation of biliary adenofibroma combined with benign lymphadenopathy mimicking advanced liver carcinoma: A case report.

BACKGROUND: Biliary adenofibromas (BAFs) are rare primary hepatic neoplasms, some of which can potentially undergo malignant transformation. Here, we describe a rare case of malignant transformation of BAF. CASE SUMMARY: A 51-year-old female was referred to our hospital with epigastric pain. Computed tomography showed a solitary liver mass combined with the enlargement of multiple mediastinal and cervical lymph nodes, clinically mimicking a liver carcinoma with extensive lymph node metastasis. However, core needle biopsy suggested BAF with malignant transformation. Finally, the patient underwent curative resection of the neoplasm and was recurrence-free for 12 mo. CONCLUSION: Our case serves as an example of a rare manifestation of BAF. Our report and the previously published experience, reinforce that curative resection should be considered the primary treatment for BAFs with malignant transformation, leading to a favorable prognosis.

Recurrent retroperitoneal Schwannomas displaying different differentiation from primary tumor: case report and literature review.

BACKGROUND: Retroperitoneal Schwannomas are uncommonly found in the retroperitoneum and few of them show malignant transformation and invasion. Local recurrence are common in malignant Schwannomas with very few reports of tumor distinct differentiation at recurrences. CASE PRESENTATION: We report here a rare case of retroperitoneal schwannoma with multiple origins from retroperitoneum and pelvic wall. Pathological examination confirmed the case as a schwannoma with malignant transformation. Radical dissection of the tumors along with the sacrifice of adjacent sigmoid colon and left kidney failed to provide a cure for this patient. Due to tumor recurrence, a second and a third surgery of radical excision were performed 6 months and 17 months later after the first surgery, respectively. Histopathologic analysis identified that the recurrent tumors were different from the original schwannoma because of their smooth muscle-like differentiation. CONCLUSION: Malignant schwannomas are uncommon sarcomas with a high incidence of local recurrence. Distinct immunohistochemical staining results of the tumors at recurrence indicate their potential of smooth-muscle like differentiation. Radical excision of the tumors may provide benefit for their local recurrences.

Immune protection conferred by three commonly used commercial live attenuated vaccines against the prevalent local strains of avian infectious bronchitis virus in southern China.

Live attenuated vaccines are critical in the control of avian infectious bronchitis. It is necessary to know the protection conferred by commonly used commercial live vaccines. In this study, specific pathogen-free chicks were vaccinated with the commercial live vaccines H120, 4/91 and LDT3-A. Blood samples were collected at weekly intervals for the detection of IBV-specific antibodies and quantification of CD4+ and CD8+ T lymphocytes. At 21 days post-inoculation the vaccinated birds were challenged with the IBV prevalent local strains GX-YL5, GX-GL11079 and GX-NN09032, respectively. Trachea and kidney samples were collected at 5 days post-challenge for the detection of the virus. The results showed that the H120 group exhibited medium antibody levels, the lowest percentages of CD4+, CD8+ T lymphocytes and the highest viral loads. The 4/91 group showed the lowest antibody levels, but the highest percentages of CD4+, CD8+ T lymphocytes and the lowest viral loads. The LDT3-A group showed the highest antibody levels, the medium percentages of CD4+, CD8+ T lymphocytes and the medium viral loads. The protection rates of H120, 4/91 and LDT3-A groups were 41.7-58.3%, 75.0-83.7% and 66.7-75.0%, respectively. The present study demonstrated that the vaccines H120, 4/91 and LDT3-A could stimulate the immunized chicks to produce different levels of humoral and cellular immunity to resist the infection of IBV, but couldn't provide complete protection against the prevalent local strains of IBV in southern China. Also, the vaccine 4/91 offered the best immune protection among the three vaccines.

Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid arthritis using LC-MALDI-TOF/TOF.

The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens. A total of 182 citrullinated peptides and 200 citrullinated sites were identified in RA SFs, while 3 citrullinated peptides and 4 citrullinated sites were identified in OA SFs. The 182 citrullinated peptides from RA SFs and the 3 citrullinated peptides from OA SFs were derived from 83 and 3 autoantigens, respectively. Eighty-three autoantigens except protein-arginine deiminase type-2 (PADI2) and protein-arginine deiminase type-2 (PADI4) were over-citrullinated compared with controls, and the citrullinated sites of PADI2 and PADI4 were different in two groups. Interestingly, citrullinated histone H3.3 (H3F3A) was found in OA controls, but not in RA groups. The differential citrullinated proteins identified in RA SFs suggested potential autoantigens were targeted for ACPAs response and might contribute to the induction and perpetuation of complement activation and joint inflammation in RA.

Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis.

BACKGROUND: Long noncoding RNAs (lncRNAs) have recently received wide attention as key molecules that mediate a variety of physiological and pathological processes by regulating gene expression; however, knowledge of lncRNAs in rheumatoid arthritis (RA) is limited. Thus, we investigated the lncRNA expression profile in fibroblast-like synoviocytes (FLSs) from patients with RA and explored the function of abundantly expressed lncRNAs. METHODS: LncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs in RA FLSs compared with normal FLSs. Quantitative polymerase chain reaction (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship between these aberrantly expressed lncRNAs and clinical characteristics. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the lncRNAs identified. RESULTS: According to the gene expression profiles, 135 lncRNAs were differentially expressed between RA and normal FLSs. Furthermore, qPCR data showed that lncRNA ENST00000483588 was up-regulated and that three lncRNAs (ENST00000438399, uc004afb.1, and ENST00000452247) were down-regulated in RA FLSs. The expression level of ENST00000483588 was positively correlated with the level of C-reactive protein and the Simplified Disease Activity Index score. Moreover, the areas under the ROC curve were 0.85, 0.92, 0.97, and 0.92 for ENST00000483588, ENST00000438399, uc004afb.1, and ENST00000452247, respectively. CONCLUSIONS: The results indicate that the dysregulation of ENST00000483588, ENST00000438399, uc004afb.1, and ENST00000452247 may be involved in the pathological processes of RA and that these lncRNAs may have potential value for the diagnosis and assessment of the disease activity of RA.

The prognostic value of intermedin in patients with breast cancer.

This study aimed to evaluate the prognostic value of preoperative plasma intermedin levels in breast cancer patients. Plasma intermedin levels of 252 breast cancer women and 100 healthy women were determined using radioimmunoassay kit. Adverse event was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause during 5-year follow-up. Disease-free survival was defined as the time between surgery and the date of any adverse event whichever appeared first. Overall survival was defined from surgery to death for any cause. The relationships between plasma intermedin levels and clinical outcomes of breast cancer patients were evaluated using multivariate analysis. The results showed that preoperative plasma intermedin levels were substantially higher in patients than in healthy subjects using t-test. Intermedin was identified as an independent predictor for 5-year mortality, adverse event, disease-free survival, and overall survival using multivariate analysis. Based on receiver operating characteristic curve analysis, preoperative plasma intermedin levels had high predictive value for 5-year mortality and adverse event. In conclusion, preoperative plasma intermedin levels are highly associated with poor patient outcomes and intermedin may be a potential prognostic biomarker for patients with breast cancer.

Rabbit model of radiation-induced lung injury.

OBJECTIVE: To explore the feasibility of establishing an animal model of chronic radiation-induced lung injury. METHODS: Twenty-eight New Zealand white rabbits were randomly divided into 3 groups (the right lung irradiation group, the whole lung irradiation group and the control group). Animal model of radiation-induced lung injury was established by high-does radiotherapy in the irradiation groups, then all rabbits underwent CT and pathological examinations at 1, 2, 4, 8, 12, 16 weeks, respectively after radiation. RESULTS: Within 4 weeks of irradiation, some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis. At 8-12 weeks after irradiation, CT scanning showed ground glass samples signs, patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. CONCLUSIONS: The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

Prognostic role of C-reactive protein in gastric cancer: a meta-analysis.

BACKGROUND: A number of studies have investigated the association between increased pretreatment serum C-reactive protein (CRP) levels and the prognosis of gastric cancer. However, due to the inconsistent results, whether the serum CRP level can be a prognostic factor in primary gastric cancer remains controversial. METHODS: We searched Medline, PubMed, Embase and the Cochrane Central Register of Controlled Trials for relevant high-quality reports. A meta-analysis was carried out using the included studies to assess the association between pretreatment serum CRP level and overall survival (OS) in patients with gastric cancer. Correlation analyses were conducted to evaluate the relationship between serum CRP and tumor characteristics such as tumor node metastasis (TNM) stage and recurrence. RESULTS: Twelve reports involving 2,597 patients with gastric cancer were included. Primary meta-analysis indicated a significant association between elevated CRP level and poor OS (HR 1.77, 95% CI 1.56-2.00). Subgroup analyses showed no single factor could alter the primary results when we divided the included studies by "number of patients", "max follow-up period", "TNM stage", "treatment" and "cut-off value". Correlation analyses showed that serum CRP level was significantly related to TNM stage (OR 2.96, 95% CI 2.22-3.93) and tumor recurrence (OR 1.81, 95% CI 1.21-2.71). CONCLUSIONS: We demonstrated that increased pretreatment serum CRP level (≥10mg/L) was significantly associated with poor prognosis in gastric cancer patients, either in early or advanced stages.

Disseminated intravascular coagulopathy caused by intracardiac mesothelioma.

We report a case of intracardiac mesothelioma complicated by chronic disseminated intravascular coagulopathy in a 50-year-old woman. Her symptoms were completely relieved by emergency resection of the tumor. Primary resection of the intracardiac mesothelioma is adequate treatment for this complicated surgical problem.