Association between homologous recombination deficiency status and carboplatin treatment response in early triple-negative breast cancer.

BACKGROUND: The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients. METHODS: Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients. RESULTS: HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment. CONCLUSION: TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.

Interplay of chronic obstructive pulmonary disease and colorectal cancer development: unravelling the mediating role of fatty acids through a comprehensive multi-omics analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients often exhibit gastrointestinal symptoms, A potential association between COPD and Colorectal Cancer (CRC) has been indicated, warranting further examination. METHODS: In this study, we collected COPD and CRC data from the National Health and Nutrition Examination Survey, genome-wide association studies, and RNA sequence for a comprehensive analysis. We used weighted logistic regression to explore the association between COPD and CRC incidence risk. Mendelian randomization analysis was performed to assess the causal relationship between COPD and CRC, and cross-phenotype meta-analysis was conducted to pinpoint crucial loci. Multivariable mendelian randomization was used to uncover mediating factors connecting the two diseases. Our results were validated using both NHANES and GEO databases. RESULTS: In our analysis of the NHANES dataset, we identified COPD as a significant contributing factor to CRC development. MR analysis revealed that COPD increased the risk of CRC onset and progression (OR: 1.16, 95% CI 1.01-1.36). Cross-phenotype meta-analysis identified four critical genes associated with both CRC and COPD. Multivariable Mendelian randomization suggested body fat percentage, omega-3, omega-6, and the omega-3 to omega-6 ratio as potential mediating factors for both diseases, a finding consistent with the NHANES dataset. Further, the interrelation between fatty acid-related modules in COPD and CRC was demonstrated via weighted gene co-expression network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment results using RNA expression data. CONCLUSIONS: This study provides novel insights into the interplay between COPD and CRC, highlighting the potential impact of COPD on the development of CRC. The identification of shared genes and mediating factors related to fatty acid metabolism deepens our understanding of the underlying mechanisms connecting these two diseases.

[Preparation and release mechanism of tectorigenin intragastric floating sustained-release tablets].

To investigate the preparation technology and release mechanism of tectorigenin intragastric floating sustained-release tablets. The tablet was produced by wet granulation compression method, with hydroxypropyl methyl cellulose (HPMCK15M), cross-linked polyvinyl pyrrolidone (PVPP), octadecanol and sodium bicarbonate as excipient. The prescriptions were screened and optimized by orthogonal experimental design with in vitro floating capacity and drug release characteristics as the evaluation indexes. The optimization results were as follows: tectorigenin 33.3%, HPMCK15M 16.7%, PVPP 20.0%, octadecanol 13.3%, sodium bicarbonate 5%, and starch gel 10.7%. The prepared tablet can be floated within 10 s in the artificial gastric juice, lasting for 12 h in vitro, with a cumulative release rate of 70% in 10 h. The analysis of Rritger-Peppas equation showed that the sustained-release tablet had two advantages of both drug diffusion and skeleton dissolution. The tablet had good appearance and compressibility, as well as favorable floating capacity and drug release characteristics.

LncRNA DICER1-AS1 promotes colorectal cancer progression by activating the MAPK/ERK signaling pathway through sponging miR-650.

BACKGROUND: Colorectal cancer (CRC) is a disease with high morbidity and mortality rates globally. Long noncoding RNAs (lncRNAs) play a fundamental role in tumor progression, and increasing attention has been paid to their role in CRC. This study aimed to determine the function of lncRNA DICER1 antisense RNA 1 (DICER1-AS1) in CRC and confirm its potential regulatory mechanisms in CRC. METHODS: The publicly available dataset was used to assess DICER1-AS1 function and expression in CRC. RT-qPCR or western blot assays were performed to verify DICER1-AS1, miR-650, and mitogen-activated protein kinase 1 (MAPK1) expression in CRC cells or tissues. To determine the function of DICER1-AS1, we performed CCK-8, colony formation, transwell, cell cycle, and in vivo animal assays. Using RNA sequence analysis, luciferase reporter assays, and bioinformatics analysis, the connection between DICER1-AS1, MAPK1, and miR-650 was investigated. RESULTS: DICER1-AS1 was significantly upregulated in CRC tissue compared to normal colon tissue. High DICER1-AS1 expression suggested a poor prognosis in CRC patients. Functionally, upregulation of DICER1-AS1 effectively promoted CRC proliferation, migration, and invasion ex vivo and tumor progression in vivo. Mechanistically, DICER1-AS1 functions as a competitive endogenous RNA (ceRNA) that sponges miR-650 to upregulate MAPK1, promotes ERK1/2 phosphorylation, and sequentially activates the MAPK/ERK signaling pathway. CONCLUSION: Our investigations found that upregulation of DICER1-AS1 activates the MAPK/ERK signaling pathway by sponging miR-650 to promote CRC progression, revealing a possible clinically significant biomarker and therapeutic target.

[Value of anti-neutrophil cytoplasmic antibody in diagnosis of Kawasaki disease].

OBJECTIVE: To study the value of anti-neutrophil cytoplasmic antibody (ANCA) in diagnosis of Kawasaki disease (KD). METHODS: Serum ANCA was detected in 30 children with typical Kawasaki disease (TKD) and in 16 with incomplete Kawasaki disease (IKD) in the acute and the recovery phases respectively. Twenty-five healthy children were randomly selected as a control group. An ultrasonic cardiography (UCG) was performed on children with KD in the acute phase. RESULTS: The mean positive rate of serum ANCA in the acute phase in KD children was 65%, with 69% in IKD children and 63% in TKD children, which were obviously higher than that in the control group (P<0.01). The positive rate of serum ANCA in the recovery phase in KD children was significantly lower than that in the acute phase (33% vs 65%, P<0.05). The positive rate of serum ANCA in the acute phase in children with KD was significantly higher than that detected by UCG (P<0.01). The incidence rate of coronary artery lesions in children with positive ANCA was obviously higher than that in children with negative ANCA (43% vs 13%; P<0.05). CONCLUSIONS: Serum ANCA may be used as a reference index for early diagnosis of KD and secondary coronary artery lesions in children.

[Serum levels of 25-(OH)D3 and immunoglobulin in children with bronchiolitis].

OBJECTIVE: To study the changes in the serum levels of 25-(OH)D3 and immunoglobulins in children with bronchiolitis, and the clinical significance of these changes. METHODS: Serum levels of 25-(OH)D3 were measured using ELISA in 35 children with bronchiolitis in the acute and recovery phases and 20 healthy children. Serum levels of immunoglobulins were determined by rate nephelometry. RESULTS: Compared with the healthy children, serum 25-(OH)D3, IgG and IgA levels in children with bronchiolitis in the acute phase were significantly lower and, in contrast, serum IgE levels were significantly higher (P<0.05). Serum 25-(OH)D3 levels increased and serum IgE levels decreased significantly in the recovery phase compared with the acute phase in children with bronchiolitis (P<0.05). However, compared with the healthy children, serum 25-(OH)D3 and IgA levels were significantly lower and serum IgE levels were significantly higher in children with bronchiolitis in the recovery phase (P<0.05). Serum 25-(OH)D3 levels in children with bronchiolitis in the acute phase were positively correlated with serum IgG (r=0.36, P<0.05) and IgA levels (r=0.63, P<0.01), and negatively correlated with serum IgE levels (r=-0.72, P<0.01). A negative correlation was found between serum 25-(OH)D3 and IgE levels in children with bronchiolitis in the recovery phase (r=-0.34, P<0.05). CONCLUSIONS: Serum 25-(OH)D3 levels decrease and there is immunoglobulin level imbalance in children with bronchiolitis, suggesting that 25-(OH)D3 and immunoglobulins may play important roles in the pathogenesis of bronchiolitis.

Prediction of distant metastasis and survival prediction of gastric cancer patients with metastasis to the liver, lung, bone, and brain: research based on the SEER database.

BACKGROUND: Gastric cancer (GC) is a globally important disease. It is the 5th most common malignancy and the 4th most common cause of death from cancer in the world. Patients with GC are often at an advanced stage when they are first diagnosed, and their overall prognosis is poor due to locally advanced and distant metastasis. This study sought to establish a predictive model of GC distant metastasis and survival that can be used to guide individualized treatment. METHODS: Patients diagnosed with GC from the Surveillance, Epidemiology, and End Results database were enrolled in the study. Univariate and multivariate logistic regression analyses were used to identify risk and prognostic factors for GC patients with distant metastasis. The factors were then used to construct nomograms to predict the probability of distant metastasis and the survival time of GC patients. Receiver operating characteristic (ROC) curve and decision curve analyses were used to verify the prediction ability of the nomograms. RESULTS: We established a comprehensive nomogram to predict the survival time of GC patients and 4 nomograms to predict distant metastasis. Nomograms could help oncologists to formulate treatment strategies and provide hospice care under an overall management model. CONCLUSIONS: Establishing a prediction model for distant metastasis and the survival of GC patients is of great clinical significance. The prediction of distant metastasis could help clinicians to make individualized assessments of patients and formulate individualized examination measures. Survival prediction models could help oncologists to formulate good treatment strategies and provide hospice care.

Changes in progenitors and differentiated epithelial cells of neonatal piglets.

This study aimed to assess the changes of small intestinal morphology, progenitors, differentiated epithelial cells, and potential mechanisms in neonatal piglets. Hematoxylin and eosin staining of samples from 36 piglets suggested that dramatic changes were observed in the jejunum crypts depth and crypt fission index of neonatal piglets (P < 0.001). The number of intestinal stem cells (ISC) tended to increase (P < 0.10), and a decreased number of enteroendocrine cells appeared in the jejunal crypt on d 7 (P < 0.05). Furthermore, the mRNA expression of jejunal chromogranin A (ChgA) was down-regulated in d 7 piglets (P < 0.05). There was an up-regulation of the adult ISC marker gene of SPARC related modular calcium binding 2 (Smoc2), and Wnt/ß-catenin target genes on d 7 (P < 0.05). These results were further verified in vitro enteroid culture experiments. A mass of hollow spheroids was cultured from the fetal intestine of 0-d-old piglets (P < 0.001), whereas substantial organoids with budding and branching structures were cultured from the intestine of 7-d-old piglets (P < 0.001). The difference was reflected by the organoid budding efficiency, crypt domains per organoid, and the surface area of the organoid. Furthermore, spheroids on d 0 had more Ki67-positive cells and enteroendocrine cells (P < 0.05) and showed a decreasing trend in the ISC and goblet cells (P < 0.10). Moreover, the mRNA expression of spheroids differed markedly from that of organoids, with low expression of intestinal differentiation gene (Lysozyme; P < 0.05), epithelial-specific markers (Villin, E-cadherin; P < 0.05), and adult ISC markers (leucine-rich repeat-containing G protein-coupled receptor 5 [Lgr5], Smoc2; P < 0.001), and up-regulation of fetal marker (connexin 43 [Cnx43]; P < 0.05). The mRNA expression of relevant genes was up-regulated, and involved in Wnt/ß-catenin, epidermal growth factor (EGF), Notch, and bone morphogenetic protein (BMP) signaling on d 7 organoids (P < 0.05). Spheroids displayed low differentiated phenotype and high proliferation, while organoids exhibited strong differentiation potential. These results indicated that the conversion from the fetal progenitors (spheroids) to adult ISC (normal organoids) might largely be responsible for the fast development of intestinal epithelial cells in neonatal piglets.

The establishment of a hub differential gene model to predict prognosis in stage II and III right- and left-sided colon cancer patients.

BACKGROUND: It is now recognized that the symptoms of colon cancer differ according to whether the tumor is located on the left or right side of the patient. The results of the present study point to the differences in the tissue and embryonic origins of left- and right-sided colon cancer that cause the variations in molecular typing. The research purpose of this study is to establish a core differential gene scoring model and proved its effect. METHODS: We downloaded transcriptome data and clinical information from The Cancer Genome Atlas (TCGA). A total of 243 patients in stages II and III were grouped according to the colon cancer site. Then we screened for differential transcriptome products. The corresponding differential gene were performing a corresponding protein interaction analysis. We used 12 algorithms in Cytoscape to calculate the hub genes and a total of 37 hub genes were obtained finally. We extracted the first principal component value (PC1) of the hub genes to evaluate the effectiveness of screening. Cox regression analysis was performed for the differential genes. Finally, we performed a prognostic analysis on right-sided colon cancer patients using the BST2 gene, PC1 and relevant clinical information. RESULTS: After screening for differentially expressed genes, 37 hub genes were obtained with appropriate algorithms. PC1 showed differences in hub genes between left- and right-sided colon cancer patients. BST2 and 31 other genes were identified as significant by Cox regression analysis and were significantly mutated in patients with right-sided colon cancer. Finally, we selected the BST2 gene and relevant clinical information as the prognostic factors to build a scoring model. The prediction effect of the model was satisfied. CONCLUSIONS: We constructed a prognostic model based on BST2, PC1, and other relevant clinical information and proved its good effect.

[Effect of tectorigenin on MCP-1 and ICAM-1 mRNA expression in injured vascular endothelial cells].

OBJECTIVE: To observe the protective effect of tectorigenin on the vascular endothelial cells(VEC) injured by oxidant low density lipoprotein-cholesterol and the expression of MCP-1 and ICAM-1 mRNA, and explore the mechanism of anti-atherosclerosis. METHOD: The VEC of rat was cultured in vitro and the 100 mg x L(-1) ox-LDL inducing oxidant injured model was used in this study. Different dosage tectorigenin was added into VEC and the activity of VEC was observed by MTT colorimetry. The expression of MCP-1 and ICAM-1 mRNA in VEC was detected by RT-PCR. RESULT: Tectorigenin had significantly protective effect on the VEC injured by ox-LDL and obviously inhibited the excessive expression of MCP-1 and ICAM-1 mRNA in VEC. CONCLUSION: It was the critical mechanism of anti-atherosclerosis that tectorigenin prevented the VEC oxidant injured and inhibited the excessive expression of MCP-1 and ICAM-1.