The first case of Odoribacter splanchnicus bacteremia isolated from a patient in China.

Background: Odoribacter splanchnicus is an extremely rare pathogen of human infection. This case reports bacteremia infection of O. splanchnicus, which is highly likely to result in misdiagnosis if inappropriate diagnostic method are used. Case presentation: A 29-year-old Chinese male patient with no underlying disease was hospitalized twice for injuries caused by a car accident. During the second hospitalization, abdominal surgery was performed and high fever developed after the surgery. A strain of O. splanchnicus was isolated from the blood and confirmed by MALDI-TOF-MS and 16S rRNA gene analysis. Finally, the patient recovered successfully by using antibiotics, fluid replacement and albumin input. Conclusions: This is the first case of O. splanchnicus bacteremia in China. We present a brief review of the cases concerning O. splanchnicus infection in humans. O. splanchnicus, as part of the normal intestinal flora, is well known for its anti-tumor and immune regulating properties, it is rarely isolated from clinical samples. This case illustrates the potential of O. splanchnicus as a pathogen and suggests attention to the use of new and advanced methods like MALDI-TOF MS and 16S rRNA gene sequencing to identify rarely isolated species from clinical samples.

lncRNA MIAT promotes luminal B breast cancer cell proliferation, migration, and invasion in vitro.

Long noncoding RNAs (lncRNAs) play a role in the emergence and progression of several human tumors, including luminal B breast cancer (BC). The biological functions and potential mechanisms of lncRNA myocardial infarction-associated transcripts (MIAT) in luminal B BC, on the contrary, are unknown. In this work, we used UALCAN database analysis to find high expression of lncRNA MIAT in luminal BC tissues and also confirmed high levels of lncRNA MIAT expression in luminal B BC tissues and cells. In vitro knockdown of MIAT inhibited the proliferation, migration, and invasion of BT474 cells. In addition, we found that miR-150-5p levels were significantly reduced in luminal B BC specimens and cells, and miR-150-5p levels were significantly increased when MIAT was knocked down. And TIMER database analysis showed that MIAT was positively associated with PDL1. Through bioinformatic tools and in vitro experiments, lncRNA MIAT could function as a competitive endogenous RNA (CeRNA) to further regulate programmed cell death ligand 1 (PDL1) expression by directly sponging miR-150-5p. In conclusion, our data suggest that MIAT, an oncogene, may sponge miR-150-5p to regulate PDL1 expression and affect proliferation, migration, and invasion in luminal B BC in vitro.

FTO, PIK3CB serve as potential markers to complement CEA and CA15-3 for the diagnosis of breast cancer.

The diagnostic efficacy of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) is limited in breast cancer (BC), highlighting the necessity of exploring novel biomarkers to improve for BC diagnosis. Therefore, we assessed the diagnostic value of fat mass and obesity-associated protein (FTO), phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit ß (PIK3CB) as a potential complementary biomarker to CEA and CA153 in breast cancer by measuring serum FTO,PIK3CB levels. FTO, PIK3CB, CEA and CA15-3 levels were measured in 112 BC patients and 64 healthy controls using enzyme-linked immunosorbent assay or electrochemiluminescence immunoassay. Spearman's rank correlation analysis was conducted to assess the correlation between the levels of the 2 markers. The relationships between FTO, PIK3CB, CEA, CA15-3 and clinical characteristics were evaluated. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic value of FTO, PIK3CB, CEA and CA15-3 of BC. Serum FTO, PIK3CB, CEA and CA15-3 levels were significantly increased in BC. There was no correlation between FTO, PIK3CB and CEA, CA15-3. FTO and PIK3CB demonstrated significant diagnostic performance for breast cancer, with FTO achieving a specificity of 90.63%. The diagnostic performance of 2-four biomarker combinations was significantly superior to individual CEA or CA153, with a combined panel of 4 biomarkers yielding an area under the curve (AUC) of 0.918, sensitivity of 81.25% and specificity of 85.94%. In early-stage breast cancer (I + II), the combination of FTO, PIK3CB, CEA and CA153 yielded an AUC of 0.895, sensitivity of 77.22% and specificity of 85.71%. FTO and PIK3CB can be served as potential biomarkers to complement CEA and CA15-3 for BC diagnosis. Combining FTO, PIK3CB, CEA and CA15-3 improves the diagnostic efficiency of breast cancer.

Recent research and clinical progress of CTLA-4-based immunotherapy for breast cancer.

Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) is currently gaining momentum for the treatment of breast cancer. Substantial progress has been made in clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors for breast cancer, but the cure rates are relatively low. To improve the efficacy of CTLA-4-based therapy for breast cancer, further research is imperative to explore more effective immune-based treatment strategies. In addition to monotherapy, CTLA-4 inhibitors are also being investigated in combination with other ICIs or alternative medications. However, it should be noted that immune-based treatments may cause adverse events. This review focuses on the mechanisms of CTLA-4 inhibitor monotherapy or combination therapy in breast cancer. We systematically summarize the latest research and clinical advances in CTLA-4-based immunotherapy for breast cancer, providing new perspectives on the treatment of breast cancer. In addition, this review highlights the immune-related adverse events (irAEs) associated with CTLA-4 inhibitors, providing insights into the development of appropriate clinical tumor immunotherapy regimens and intervention strategies.

Uncovering potential new biomarkers and immune infiltration characteristics in primary Sjögren's syndrome by integrated bioinformatics analysis.

Primary Sjögren's syndrome (pSS) is known as autoimmune disease characterized by damage to endocrine glands, such as the salivary and lacrimal glands. This study aimed to identify potential biomarkers for pSS using integrated bioinformatics analysis and explore the relationship between differentially expressed genes (DEGs) and immune infiltration. Three pSS datasets (GSE7451, GSE23117, and GSE40611) from the gene expression omnibus database were integrated. All the datasets were processed in R (version 4.0.3). A total of 16 immune cells and 13 immune functions were obtained. The top immune cell and immune function were "activated" dendritic cells and major histocompatibility complex class I. Correlation analysis showed the top correlation among 16 immune cells were B cells and tumor infiltrating lymphocytes, check-point and T cell co-stimulation, respectively. In comparisons of immune score, "activated" dendritic cells (.657 vs 594, P < .001), B cells (.492 vs 434, P = .004), macrophages (.631 vs 601, P = .010), inflammation-promoting (.545 vs 478, P < .001), Type I interferon Reponse (.728 vs 625, P < .001) and so on were higher in pSS than control group. In correlation analysis, the up-regulation of interferon induced protein with tetratricopeptide repeats 1 gene was strongly correlated with Type I interferon response with a correlation coefficient of .87. The receiver operating characteristic curve of 5 genes showed that the area under curve was.891. In the verification model, the area under curve was.881. In addition, disease ontology analysis supported the association between DEGs and pSS. In summary, pSS has a variety of DEGs in immune infiltration, which is worthy of the attention from clinicians.

Identification of disulfidptosis-related subgroups and prognostic signatures in lung adenocarcinoma using machine learning and experimental validation.

Background: Disulfidptosis is a newly identified variant of cell death characterized by disulfide accumulation, which is independent of ATP depletion. Accordingly, the latent influence of disulfidptosis on the prognosis of lung adenocarcinoma (LUAD) patients and the progression of tumors remains poorly understood. Methods: We conducted a multifaceted analysis of the transcriptional and genetic modifications in disulfidptosis regulators (DRs) specific to LUAD, followed by an evaluation of their expression configurations to define DR clusters. Harnessing the differentially expressed genes (DEGs) identified from these clusters, we formulated an optimal predictive model by amalgamating 10 distinct machine learning algorithms across 101 unique combinations to compute the disulfidptosis score (DS). Patients were subsequently stratified into high and low DS cohorts based on median DS values. We then performed an exhaustive comparison between these cohorts, focusing on somatic mutations, clinical attributes, tumor microenvironment, and treatment responsiveness. Finally, we empirically validated the biological implications of a critical gene, KYNU, through assays in LUAD cell lines. Results: We identified two DR clusters and there were great differences in overall survival (OS) and tumor microenvironment. We selected the "Least Absolute Shrinkage and Selection Operator (LASSO) + Random Survival Forest (RFS)" algorithm to develop a DS based on the average C-index across different cohorts. Our model effectively stratified LUAD patients into high- and low-DS subgroups, with this latter demonstrating superior OS, a reduced mutational landscape, enhanced immune status, and increased sensitivity to immunotherapy. Notably, the predictive accuracy of DS outperformed the published LUAD signature and clinical features. Finally, we validated the DS expression using clinical samples and found that inhibiting KYNU suppressed LUAD cells proliferation, invasiveness, and migration in vitro. Conclusions: The DR-based scoring system that we developed enabled accurate prognostic stratification of LUAD patients and provides important insights into the molecular mechanisms and treatment strategies for LUAD.

Pretreatment Fibrinogen-Albumin Ratio (FAR) Associated with Treatment Response and Survival in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Anti-PD-1 Therapy Plus Platinum-Based Combination Chemotherapy.

PURPOSE: PD-1 inhibitors have been routinely used to treat advanced non-small cell lung cancer (NSCLC) and have significantly improved clinical outcomes. In this study, we aimed to explore the influence of pretreatment fibrinogen-albumin ratio (FAR) on treatment response and survival in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. PATIENTS AND METHODS: A total of 91 patients with advanced NSCLC were included in the study. All patients received at least two cycles of systemic first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. Receiver operating characteristics analysis was performed to determine the optimal cutoff values of FAR. Univariate and multivariate analyses were used to identify independent prognostic factors, and the Kaplan-Meier method was used to estimate survival curves. RESULTS: Multivariate logistic regression analysis showed that N stage (N2-3) and high FAR (≥0.175, optimal cutoff value) were independent predictors for objective response rate (P = 0.0002, P = 0.0005, respectively). Multivariate Cox regression analysis of progression-free survival and overall survival showed that high FAR (≥0.145) was independent prognostic factors (P = 0.0061, P = 0.0024, respectively). Progression-free survival and overall survival were significantly shorter in the high FAR (≥0.145) group than those in the low FAR (<0.145) group (P = 0.0024, P = 0.0024, respectively). CONCLUSION: Pretreatment FAR was an independent predictor for treatment response and independent prognostic factors in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy.

Eriocitrin, a dietary flavonoid suppressed cell proliferation, induced apoptosis through modulation of JAK2/STAT3 and JNK/p38 MAPKs signaling pathway in MCF-7 cells.

Eriocitrin, a lemons flavanone, exhibits several biological properties, antiproliferative, and proapoptotic effects. However, its molecular mechanical action is not entirely clarified. Oxidative stress causes abnormal stimulation of signal transducer and activator of transcription 3 (STAT3) and c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs) signaling has been strongly connected with the ruling of cell survival and apoptosis of cancer cells. Herein, we investigated an antiproliferative and proapoptotic effect that Eriocitrin modulates STAT3/MAPKs signaling activation in MCF-7 cells. We noticed that Eriocitrin strongly enhances reactive oxygen species (ROS) generation, alteration of mitochondrial outer membrane potential, and enhances apoptotic morphological changes. Furthermore, Eriocitrin suppressed STAT3 phosphorylation via inhibiting an upstream molecule of JAK2 and Src kinase activation, thereby blocking STAT3 nuclear translocation. Similarly, Eriocitrin causes oxidative stress-mediated JNK/p38 MAPK signaling activation. We confirmed that Eriocitrin induced ROS-mediated apoptosis inhibited by the antioxidant substance of N-acetylcysteine. Eriocitrin induced apoptosis via suppression of STAT3 signaling regulated proteins, activating proapoptotic factors Bax, caspase 7, 8, 9 and suppressing Bcl-2, Bcl-x expression in MCF-7 cells. Overall, these results evidenced that Eriocitrin can affect multiple signaling events associated with tumorigenesis. From this evidence, Eriocitrin, a novel chemotherapeutic agent, can be used to treat breast cancer.

Comparison of Different EGFR Gene Mutation Status in Patients with Metastatic Non-Small Lung Cancer After First-Line EGFR-TKIs Therapy and Analyzing Its Relationship with Efficacy and Prognosis.

PURPOSE: The purpose of this study is to compare the different EGFR mutation status in patients with metastatic non-small cell lung cancer (NSCLC) after first-line EGFR-TKIs therapy and analyze its relationship with efficacy and prognosis. PATIENTS AND METHODS: This study retrospectively analyzed the data of patients with metastatic NSCLC harboring EGFR mutation in the Affiliated Tumor Hospital of Guangxi Medical University from June 2016 to December 2020. Samples were collected before treatment and at the time of disease progression after first-line EGFR-TKIs therapy. Amplification refractory mutation system (ARMS) PCR and next-generation sequencing (NGS) were used to detect EGFR mutation. ORR, DCR, and PFS of different EGFR mutation groups were compared. RESULTS: The EGFR mutation rate of re-biopsy was 60.23%. The inconsistency rate of EGFR mutations in the same and different simple types was 72.22% (26/36) and 92.31% (48/52), respectively. Alterations in terms of EGFR mutations were divided into four groups: Group A: EGFR-sensitive mutation negative and T790M negative (39.77%); Group B: EGFR-sensitive mutation positive and T790M negative (18.19%); Group C: EGFR-sensitive mutation negative and T790M positive (36.36%); Group D: EGFR-sensitive mutation positive and T790M positive (5.68%). The differences between the four groups in ORR and DCR were not statistically significant (P>0.05). The median PFS of all patients was 10.65 months. PFS of Group A, B, C, and D was 12.26, 7.96, 10.55, and 13.81 months, respectively, with statistical significance (Log rank P = 0.014). CONCLUSION: EGFR mutation status in metastatic NSCLC patients receiving the first- and second-generation TKIs after disease progression show diversity. Monitoring the EGFR mutation changes is of great importance for subsequent clinical decision-making and exploring the underlying mechanisms of acquired resistance.

Identification of differentially expressed lncRNAs and mRNAs in luminal-B breast cancer by RNA-sequencing.

BACKGROUND: Luminal B cancers show much worse outcomes compared to luminal A. This present study aims to screen key lncRNAs and mRNAs correlated with luminal-B breast cancer. METHODS: Luminal-B breast cancer tissue samples and adjacent tissue samples were obtained from 4 patients with luminal-B breast cancer. To obtain differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between luminal-B breast cancer tumor tissues and adjacent tissues, RNA-sequencing and bioinformatics analysis were performed. Functional annotation of DEmRNAs and protein-protein interaction networks (PPI) construction were performed. DEmRNAs transcribed within a 100 kb window up- or down-stream of DElncRNAs were searched, which were defined as cis nearby-targeted DEmRNAs of DElncRNAs. DElncRNA-DEmRNA co-expression networks were performed. The mRNA and lncRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database to validate the expression patterns of selected DEmRNAs and DElncRNAs. RESULTS: A total of 1178 DEmRNAs and 273 DElncRNAs between luminal-B breast cancer tumor tissues and adjacent tissues were obtained. Hematopoietic cell lineage, Cytokine-cytokine receptor interaction, Cell adhesion molecules (CAMs) and Primary immunodeficiency were significantly enriched KEGG pathways in luminal-B breast cancer. FN1, EGFR, JAK3, TUBB3 and PTPRC were five hub proteins of the PPI networks. A total of 99 DElncRNAs-nearby-targeted DEmRNA pairs and 1878 DElncRNA-DEmRNA co-expression pairs were obtained. Gene expression results validated in TCGA database were consistent with our RNA-sequencing results, generally. CONCLUSION: This study determined key genes and lncRNAs involved in luminal-B breast cancer, which expected to present a new avenue for the diagnosis and treatment of luminal-B breast cancer.

Relationship between expression of CXCR7 and NF-κB in breast cancer tissue and occurrence of breast cancer and lymphatic metastasis.

It is designed to discuss the relationship between the expression of chemokine receptor 7 (chemokine receptor 7, CXCR7) and nuclear transcription factor-κB (nuclear factor kappa B, NF-κB) and the occurrence of the breast cancer and lymphatic metastasis. METHOD: 80 samples were excised and confirmed as breast cancer through our hospital pathology from January 2014 to December 2016 and tumor tissues and normal mammary tissues 2 cm from the tumor edges were taken as an experimental group and a control group, respectively. The method of immunohistochemical is utilized to test the expression of CXCR7 and NF-κB in the breast cancer tissue, compared with the para-carcinoma tissue, and analyze its relevance with the clinicopathologic features of the breast cancer tissue, such as tumor size, TNM staging, lymphatic metastasis and other conditions. RESULTS: both CXCR7 and NF-κB were highly expressed in the breast cancer tissue, the positive rate was significantly higher that that of paracancerous normal tissues, and the difference was statistically significant. And the expressions of CXCR7 and NF-κB were related to TNM staging of the breast cancer and lymphatic metastasis and unrelated to the tumor size, age, and expressions of ER, PR and HER2. CONCLUSION: both CXCR7 and NF-κB are related to the malignant grade of the breast cancer and lymphatic metastasis, which may be regarded as in important indicator to judge the prognosis of the breast cancer and be expected to be the new target of curing part of the breast cancer.

[Influence of IL-2 on proliferation of cultured human pituitary adenoma cells and its mechanism].

AIM: To investigate the effects of IL-2 on the proliferation, cell cycle, protein kinase C(PKC) and cAMP/cGMP of cultured human pituitary adenoma cells. METHODS: MTT colorimetry, (3)H-TdR and flow cytometry were used to detect the proliferation and radioimmunoassay was used to observe the effect of IL-2 on PKC activity and cAMP/cGMP levels of cultured human pituitary adenoma cells. RESULTS: (1) IL-2 (1 x 10(4), 1 x 10(5) and 5 x 10(5) U/L) stimulated the proliferation and DNA synthesis of cultured human pituitary adenoma cells in a dose-dependent manner. (2) IL-2 (1 x 10(4), 1 x 10(5) and 5 x 10(5) U/L) decreased the ratio of pituitary adenoma cells in G(1) phase and increased the ratio in S and G(2) phase markedly. (3) Compared with control, PMA, a PKC activator, increased the activity of membrane and total PKC in human pituitary adenoma cells. However, after treatment with IL-2 (1 x 10(5) U/L), a significant increase of the activity of cytoplasmic, membrane and total PKC in human pituitary adenoma cells was observed. (4) IL-2 (5 x 10(4), 1 x 10(5) U/L) decreased the amount of cAMP in the cytoplasm of human pituitary adenoma cells, but had no effect on that of cGMP. CONCLUSION: IL-2 can stimulate the proliferation of pituitary adenoma cells through PKC and cAMP/cGMP signaling pathways.