Identification and Validation of Novel Metastasis-Related Immune Gene Signature in Breast Cancer.

Background: Distant metastasis remains the leading cause of death among patients with breast cancer (BRCA). The process of cancer metastasis involves multiple mechanisms, including compromised immune system. However, not all genes involved in immune function have been comprehensively identified. Methods: Firstly 1623 BRCA samples, including transcriptome sequencing and clinical information, were acquired from Gene Expression Omnibus (GSE102818, GSE45255, GSE86166) and The Cancer Genome Atlas-BRCA (TCGA-BRCA) dataset. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed using the GSE102818 dataset to identify the most relevant module to the metastasis of BRCA. Besides, ConsensusClusterPlus was applied to divide TCGA-BRCA patients into two subgroups (G1 and G2). In the meantime, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a metastasis-related immune genes (MRIGs)_score to predict the metastasis and progression of cancer. Importantly, the expression of vital genes was validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Results: The expression pattern of 76 MRIGs screened by WGCNA divided TCGA-BRCA patients into two subgroups (G1 and G2), and the prognosis of G1 group was worse. Also, G1 exhibited a higher mRNA expression level based on stemness index score and Tumor Immune Dysfunction and Exclusion score. In addition, higher MRIGs_score represented the higher probability of progression in BRCA patients. It was worth mentioning that the patients in the G1 group had a high MRIGs_score than those in the G2 group. Importantly, the results of RT-qPCR and IHC demonstrated that fasciculation and elongation protein zeta 1 (FEZ1) and insulin-like growth factor 2 receptor (IGF2R) were risk factors, while interleukin (IL)-1 receptor antagonist (IL1RN) was a protective factor. Conclusion: Our study revealed a prognostic model composed of eight immune related genes that could predict the metastasis and progression of BRCA. Higher score represented higher metastasis probability. Besides, the consistency of key genes in BRCA tissue and bioinformatics analysis results from mRNA and protein levels was verified.

Prognostic factors and benefit populations of ovarian function suppression in premenopausal HR+/HER2+ early-stage breast cancer patients who received trastuzumab: Evidence from a real-world study with long-term follow-up.

BACKGROUND: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) breast cancer exhibits considerable heterogeneity, and it is of great interest whether patients with premenopausal HR+/HER2+ breast cancer treated with trastuzumab can benefit from ovarian function suppression (OFS) therapy similarly to HR+/HER2- breast cancer. Here, we conducted a real-world study in this population to identify both who would derive substantial benefits from the addition of OFS and clinicopathological factors with potential prognostic value. METHODS: Multicenter data from 253 premenopausal patients with HR+/HER2+ early-stage breast cancer who received trastuzumab from October 2009 to October 2018 were retrospectively included. The Kaplan-Meier method was used for survival analysis, while the log-rank test was used to compare the survival rates. Univariate and multifactor Cox regression analyses were performed to analyze the independent risk factors affecting invasive disease-free survival (IDFS). RESULTS: After a median follow-up of 98.50 months, compared with tamoxifen/toremifene alone, tamoxifen/toremifene/aromatase inhibitors plus OFS demonstrated significant benefits in the overall study population (HR = 0.289, 95% CI: 0.100-0.835, p = 0.022, 8-year IDFS rate: 90.78% vs. 95.54%), especially in the lymph node-positive subgroup and age ≤40 years subgroup. Age ≤40 years, histological grade >2, lymph node involvement, PR ≤50%, and tamoxifen alone were independent prognostic factors. CONCLUSIONS: For premenopausal HR+ breast cancer patients, HER2 positivity alone is an indication for the addition of OFS in adjuvant endocrine therapy. Age, histological grade, lymph node status, the expression of PR, and OFS treatment were independent prognostic factors in this population.

hsdSA regulated extracellular vesicle-associated PLY to protect Streptococcus pneumoniae from macrophage killing via LAPosomes.

IMPORTANCE: S. pneumoniae is a major human pathogen that undergoes a spontaneous and reversible phase variation that allows it to survive in different host environments. Interestingly, we found hsdSA , a gene that manipulated the phase variation, promoted the survival and replication of S. pneumoniae in macrophages by regulating EV production and EV-associated PLY. More importantly, here we provided the first evidence that higher EV-associated PLY (produced by D39) could form LAPosomes that were single membrane compartments containing S. pneumoniae, which are induced by integrin ß1/NOX2/ROS pathway. At the same time, EV-associated PLY increased the permeability of lysosome membrane and induced an insufficient acidification to escape the host killing, and ultimately prolonged the survival of S. pneumoniae in macrophages. In contrast, lower EV-associated PLY (produced by D39ΔhsdSA ) activated ULK1 recruitment to form double-layered autophagosomes to eliminate bacteria.

Landscape of young breast cancer under 35 years in China over the past decades: a multicentre retrospective cohort study (YBCC-Catts study).

Background: The proportion of young breast cancer patients in China is significantly higher than in Western countries, and the clinicopathological characteristics and clinical problems faced by patients in China are different from those in Western countries too, so there is an urgent need to conduct some studies for young breast cancer patients in Asia. Methods: This study consisted of two breast cancer cohorts in China. The population-based cohort involved breast cancer cases diagnosed in 2000-2017 via cancer registration system, and we describe the epidemiological characteristics of the young breast cancer in China. The hospital-based cohort, patients eligible for enrollment were breast cancer in young women (≤35 years old) from eight centres in different regions of China, diagnosed and treated for the first time in six time periods (i.e., 2000, 2003, 2006, 2009, 2012, and 2015). Patient demographic characteristics and clinical features were compared among the six time periods using a trend test. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was performed to compare OS and DFS. Univariate and multivariate analyses were carried out using Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs). Findings: In the population-based cohort, age-specific incidence and age-standardised percentages of breast cancer cases younger than 35 years were increased. The proportion of breast cancer under the age of 35 is increasing more rapidly in rural areas than in urban areas. In the hospital-based cohort, a total of 1308 young breast cancer patients (≤35 years old) were collected. Proportion of patients treated with adjuvant taxane or anthracycline combined with taxane is gradually increasing over the six time periods, and the proportion of patients undergoing breast-conserving surgery is gradually increasing too. Meanwhile, the patients treated with combined ovarian function suppression (OFS) endocrine therapy gradually increased, and the duration of endocrine therapy gradually longer. There is an increasing trend in 5-year disease-free survival (DFS) rate for the total population in the six time periods between 2000 and 2015, but no significant difference in overall survival (OS) rate was observed. Early staging and longer duration of endocrine therapy were factors associated with a favorable prognosis. Interpretation: The incidence of younger breast cancers under 35 years of age has gradually increased and the pattern of patient care has changed significantly over time, which may contribute to the improved prognosis of younger breast cancer patients. Funding: Beijing Medical Award Foundation (YXJL-2020-0941-0763), Beijing Hope Run Special Fund of Cancer Foundation of China (LC2021L04), Chinese Academy of Medical Sciences Clinical Translational and Medical Research Fund (2022-I2M-C&T-A-014).

Primary neuroendocrine neoplasms of the kidney: a case report and literature review.

Primary kidney neuroendocrine tumors (NETs) are rare renal malignancies. However, detecting and monitoring neuroendocrine neoplasms remains challenging because of their nonspecific nature. We herein present a case involving a 53-year-old woman who experienced episodes of intermittent abdominal pain, dizziness, and nausea for a period of 5 days. Computed tomography urography revealed a small (approximately 19- × 16-mm) nodular shadow in the left kidney. The nodular shadow exhibited slightly lower density than the surrounding tissue as well as enhancement, with a portion protruding into the renal sinus region. Histological and immunohistochemical analyses of the biopsy specimen from the mass indicated a well-differentiated NET. After analysis of this case, we performed a literature review and herein discuss various techniques for imaging and pathological diagnosis of renal NETs. Additionally, we provide insights into the treatment options and prognosis for affected patients. By combining this case study with the existing published literature, we aim to offer a valuable reference for clinicians treatment patients diagnosed with renal NETs.

Anxiety-associated factors among employees with different personality profiles: a cross-sectional study in China.

Introduction: Anxiety not only harms employees' work efficiency and satisfaction but also presents as a hazard to their mental health. This study aimed to investigate the prevalence of anxiety among Chinese employees, identify their personality profiles and explore the anxiety-related factors in different personality profiles. Methods: This national investigation adopted the multistage random sampling method to recruit employees. A total of 3,875 employees were enrolled in this study, and 39.1% (1,515/3,875) of them were experiencing anxiety at the time of the study. Latent profile analysis (LPA) was conducted to identify personality subgroups among Chinese employees based on their BFI-10 scores. Results: LPA identified a three-profile solution among Chinese employees: average, resilient, and introverted. Employees in the resilient profile had the lowest anxiety rate (16.1%, 132/822), and those in the average profile had the highest rate (46.8%, 1,166/2,494). Multivariate analysis results showed that for all personality profiles, self-efficacy was positively associated with anxiety, and work-family conflict was negatively associated with anxiety. High levels of perceived social support and self-efficacy reduced the risk of anxiety and higher work-family conflict and no partner increased the odds of anxiety in the average profile. For the introverted profile, female gender, and living in a city increased the chances of suffering from anxiety. Discussion: This study identified that each personality profile of Chinese employees had its own set of factors associated with anxiety, which could facilitate employers to provide targeted interventions to alleviate employees' anxiety.

Contribution of coping style to the association between illness uncertainty and demoralisation in patients with breast cancer: a cross-sectional mediation analysis.

OBJECTIVE: Demoralisation is a common psychological issue in patients with cancer and aggravates depression, reduces the quality of life and even causes suicidal ideation. There is a lack of knowledge about illness uncertainty, coping style and demoralisation in patients with breast cancer. The current study explored the relationship between illness uncertainty and demoralisation among those patients, as well as the potential mediating role of coping style. DESIGN: A cross-sectional study. SETTING: Participants were recruited from the Breast Tumor Center in a tertiary hospital in Shijiazhuang, Hebei province. PARTICIPANTS: A total of 211 patients with breast cancer completed the survey. OUTCOME MEASURES: A total of 211 patients with breast cancer completed the Mishel's Uncertainty in Illness Scale, Trait Coping Style Questionnaire and the Mandarin version of Demoralization Scale (DS-MV). RESULTS: Of the patients, 47.40% exhibited symptoms of demoralisation (DS-MV>30), and the mean of demoralisation score was (29.55±13.21). The results demonstrated that illness uncertainty and negative coping styles were positively related to demoralisation (p<0.001), while active coping styles were negatively related to demoralisation (p<0.001). Importantly, coping styles could partially mediate the relationship between illness uncertainty and demoralisation (p<0.01). CONCLUSION: Our study illustrated that illness uncertainty was associated with demoralisation in patients with breast cancer, and coping style acted as a mediator in this relationship. The findings highlighted the critical role of reducing negative coping styles to the early prevention and efficient treatment of demoralisation among those patients.

A novel feedback regulated loop of circRRM2-IGF2BP1-MYC promotes breast cancer metastasis.

BACKGROUND: Metastasis is the leading cause of mortality in patients with breast cancer (BC). Studies demonstrate that circular RNAs (circRNAs) were involved in BC progression, while the molecular mechanisms remain largely unclear. METHODS: The microArray circRNA profiles were used to explore the differential expression circRNAs in BC and paracancerous normal tissues, and the quantitative reverse transcription-polymerase chain reaction was used to validate their expression level in clinical samples and cell lines. Nuclear/cytosolic fractionation and fluorescence in situ hybridization (FISH) assays were performed to examine circRRM2 (hsa_circ_0052582) subcellular location. The scratch wound healing and transwell assays were conducted to evaluate the impact of circRRM2 on BC cell migration and invasion. We predicted miRNAs that might bind with cricRRM2 and the downstream target genes using bioinformatics analysis and explored their expression levels and prognostic value in BC. FISH, RNA immunoprecipitation, Co-immunoprecipitation, Western blot, and rescue experiments were implemented to figure out circRRM2 function and underlying mechanisms in BC. RESULTS: The present study revealed several aberrant circRNAs in BC tissues and observed that circRRM2 was upregulated in tumor tissues of 40 patients with BC. High circRRM2 was significantly associated with advanced N stage in patients with BC. Gain- and loss- of function experiments revealed that circRRM2 promoted the migration and invasion of cells and functioned as an oncogene in BC. Mechanism studies showed that circRRM2 competed with miR-31-5p/miR-27b-3p to upregulate the IGF2BP1 expression. Furthermore, IGF2BP1 upregulated the circRRM2 level via interacting with MYC, which functioned as the transcriptional factor of circRRM2. Thus, the positive feedback loop that was composed of circRRM2/IGF2BP1/MYC was identified. CONCLUSION: This study confirms that upregulated circRRM2 functions an oncogenic role in BC metastasis. The positive feedback loop of circRRM2/IGF2BP1/MYC enforces the circRRM2 expression, which might offer a potential target for BC treatment.

Diffusion NMR for Measuring Dynamic Ligand Exchange on Colloidal Nanocrystals.

Ligand exchange is fundamentally related to the surface chemistry of nanoparticles in solution and is also an essential procedure for their synthesis and solution processing. The solution of ligand-bearing nanoparticles can be regarded as a dynamic equilibrium of bound and free ligands depending on the concentration and temperature. The direct experimental calibration of the ligand exchange dynamics relies on the in situ and real-time quantification of bound and free ligands. However, existing analytical strategies are often with limited applicability considering the requirement of special functional groups or the indirect detection of photoluminescence or reaction heat. In this work, we explore diffusion-based methods of solution-state nuclear magnetic resonance (NMR) as a general strategy to probe ligand exchange. Using comprehensive numerical simulations, we show that diffusion NMR with designable time sequences can effectively distinguish bound and free ligands and measure the exchange rate constants from 0.5 to 200 s-1 under typical instrumental settings. These methods are demonstrated experimentally on colloidal CdSe nanocrystal systems with carboxylate or amine ligands whose exchange rates were previously undetectable. The kinetic rate constants, activation energies, and thermodynamic parameters of ligand exchange have been obtained under variable temperature conditions. We expect the diffusion NMR strategies to be generally applicable for calibrating the exchange of organic ligands on various nanoparticle systems.

The value of hsa_circ_0058514 in plasma extracellular vesicles for breast cancer.

The aim of this study was to investigate the diagnostic value of hsa_circ_0058514 in plasma extracellular vesicles (EVs) in BC patients and its predictive value for neoadjuvant chemotherapy. The expression of hsa_circ_0058514 in a large sample of BC plasma and healthy subjects' plasma was detected by qPCR, and the ROC curve was drawn to verify its diagnostic value as a plasma tumor marker. Furthermore, the association between the expression of hsa_circ_0058514 and clinicopathological characteristics before and after treatment was detected in the plasma of 40 pairs of BC patients undergoing neoadjuvant therapy. The expression level of hsa_circ_0058514 in the plasma of BC patients was significantly higher than that of healthy subjects. The ROC curve showed that plasma hsa_circ_0058514 ROC in differentiating non-metastatic BC and healthy people had better diagnostic efficiency than conventional tumor markers CA153, CA125, and CEA. In patients with neoadjuvant therapy, the decrease in plasma hsa_circ_0058514 value before and after treatment correlated with pathological MP grade (r = 0.444, p = 0.004) and imaging tumor regression value (r = 0.43, p = 0.005) positive correlation. The detection of hsa_circ_0058514 in both extracellular vesicles of BC cell culture medium and human plasma was demonstrated. Hsa_circ_0058514 is detected in the plasma from BC cells secreted in the form of vesicles. Hsa_circ_0058514 can be used as an early plasma biological indicator for the diagnosis of BC in clinical applications, with a higher risk of recurrence and metastasis, and as a predictor of the effect of neoadjuvant therapy to guide the clinical use of neoadjuvant therapy.

Quality assessment of clinical practice guidelines on psychological distress of cancer patients using the AGREE II instrument.

Objective: This study aimed to assess the quality of the clinical practice guidelines on psychological distress among cancer patients and provide users with recommendations for coping with psychological distress. Methods: A systematic search of relevant clinical practice guidelines was undertaken to identify and select the clinical practice guidelines related to psychological distress among cancer patients. Literature databases were searched in PubMed, Web of Science, Excerpta Medica Database, the Cumulative Index to Nursing & Allied Health Literature, China Biology Medicine, China National Knowledge Infrastructure, WanFang and Weipu Journal Database. The guideline databases include Yimaitong Guidelines Network, National Guideline Clearinghouse, National Institute for Health and Clinical Excellence, American Society of Clinical Oncology (ASCO), New Zealand Guidelines Group, Scottish Intercollegiate GuidelinesNetwork, American Psychological Association, Registered Nurses' Association of Ontario and Cancer Care Ontario (CCO). Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Results: Six clinical practice guidelines were included and assessed for critical evaluation. The median score for the scope and purpose domain was 71.5% (IQR 64%-77.25%), the stakeholder involvement domain was 65% (IQR 47.5%-74.5%), the rigour of the development domain was 61.5% (IQR 45.5%-85.25%), the clarity of the presentation domain was 91% (IQR 72.25%-94.5%), the applicability domain was 70% (IQR 33%-78.75%), and the editorial independence domain was 48.84% (IQR 61.75%-95%). Four guidelines (ASCO, 2014; Canadian Association of Psychosocial Oncology, 2015; NCCN, 2020, and CCO, 2016) were classified as "recommended," and the remaining (European Palliative Care Research Collaborative and Chinese Psychosocial Oncology Society) were "recommended with modifications," especially in the domains of Stakeholder involvement, rigour of development, and applicability. The inter-rater consistency of each domain showed moderate level (0.52-0.90) analyzing by intraclass correlation. Conclusions: The clinical practice guidelines on psychological distress among cancer patients varied in quality, and there were discrepancies in terms of the recommendations and recommendation grades. These findings could contribute to improving the quality of clinical practice guidelines on psychological distress, and enable the development and implementation of evidence-based guidelines for cancer patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42020209204.

Pegylated Liposomal Doxorubicin, Docetaxel, and Trastuzumab as Neoadjuvant Treatment for HER2-Positive Breast Cancer Patients: A Phase II and Biomarker Study.

Background: Combined neoadjuvant chemotherapy with trastuzumab and pertuzumab is the standard regimen for human epidermal growth receptor 2 (HER2)-positive breast cancer (BC). However, pertuzumab is not available because it is not on the market or covered by medicare in some regions or poor economy. Anthracyclines and taxanes are cornerstones in BC chemotherapy, and their combination contributes to satisfactory efficiency in neoadjuvant settings. Nonetheless, concomitant administration of trastuzumab and an anthracycline is generally avoided clinically due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is less cardiotoxic compared with traditional anthracyclines. Here, we conducted this prospective study to evaluate the efficacy, safety, and potential biomarkers for PLD plus trastuzumab and docetaxel as neoadjuvant treatment in HER2-positive BC. Patients and Methods: Patients with stage II or III HER2-positive BC were recruited in this multicenter, open-label, single-arm, phase II study. Eligible patients were given 6 cycles of PLD plus docetaxel and trastuzumab. Primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints were breast pathological complete response (bpCR, ypT0/is), objective response rate (ORR), operation rate, breast-conserving surgery rate, and safety. Metadherin (MTDH), glutaminyl-peptide cyclotransferase (QPCT), topoisomerase II alpha (TOP2A), programmed death ligand 1 (PD-L1), and tumor-infiltrating lymphocytes (TILs) were evaluated in BC tissues pre-neoadjuvant for potential biomarkers. Results: Between March 2019 and February 2021, 54 patients were enrolled, 50 were included in the analysis, and 35 (70.0%) completed 6 cycles of neoadjuvant treatment. Forty-nine (98.0%) patients underwent surgery with a breast-conserving rate of 44.0%. The tpCR rate, bpCR rate, and ORR were 48.0% (95% CI, 33.7%-62.6%), 60.0% (95% CI, 45.2%-73.6%), and 84.0% (95% CI, 70.9%-92.8%), respectively. tpCR was associated with MTDH (p = 0.002) and QPCT (p = 0.036) expression but not with TOP2A (p = 0.75), PD-L1 (p = 0.155), or TILs (p = 0.76). Patients with HR-negative status were more likely to achieve bpCR compared with those with HR-positive status (76.2% vs. 48.3%, p = 0.047). Grade ≥3 adverse events occurred in 38.0% of patients. Left ventricular ejection fraction decline by ≥10% was reported in 18.0% of patients, and no patient experienced congestive heart failure. Conclusions: PLD plus docetaxel and trastuzumab might be a potential neoadjuvant regimen for HER2-positive BC with a high tpCR rate and manageable tolerability. MTDH and QPCT are potential predictive markers for tpCR.

Epigenetic study of early breast cancer (EBC) based on DNA methylation and gene integration analysis.

Breast cancer (BC) is one of the leading causes of cancer-related deaths in women. The purpose of this study is to identify key molecular markers related to the diagnosis and prognosis of early breast cancer (EBC). The data of mRNA, lncRNA and DNA methylation were downloaded from The Cancer Genome Atlas (TCGA) dataset for identification of differentially expressed mRNAs (DEmRNAs), differentially expressed lncRNAs (DElncRNAs) and DNA methylation analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyzes were used to identify the biological functions of DEmRNAs. The correlation analysis between DNA methylation and DEmRNAs was carried out. Then, diagnostic analysis and prognostic analysis of identified DEmRNAs and DElncRNAs were also performed in the TCGA database. Subsequently, methylation state verification for identified DEmRNAs was performed in the GSE32393 dataset. In addition, real-time polymerase chain reaction (RT-PCR) in vitro verification of genes was performed. Finally, AC093110.1 was overexpressed in human BC cell line MCF-7 to verify cell proliferation and migration. In this study, a total of 1633 DEmRNAs, 750 DElncRNAs and 8042 differentially methylated sites were obtained, respectively. In the Venn analysis, 11 keys DEmRNAs (ALDH1L1, SPTBN1, MRGPRF, CAV2, HSPB6, PITX1, WDR86, PENK, CACNA1H, ALDH1A2 and MME) were we found. ALDH1A2, ALDH1L1, HSPB6, MME, MRGPRF, PENK, PITX1, SPTBN1, WDR86 and CAV2 may be considered as potential diagnostic gene biomarkers in EBC. Strikingly, CAV2, MME, AC093110.1 and AC120498.6 were significantly actively correlated with survival. Methylation state of identified DEmRNAs in GSE32393 dataset was consistent with the result in TCGA. AC093110.1 can affect the proliferation and migration of MCF-7. ALDH1A2, ALDH1L1, HSPB6, MME, MRGPRF, PENK, PITX1, SPTBN1, WDR86 and CAV2 may be potential diagnostic gene biomarkers of EBC. Strikingly, CAV2, MME, AC093110.1 and AC120498.6 were significantly actively correlated with survival. The identification of these genes can help in the early diagnosis and treatment of EBC. In addition, AC093110.1 can regulate SPTBN1 expression and play an important role in cell proliferation and migration, which provides clues to clarify the regulatory mechanism of EBC.

Optical coherence tomography angiography characteristics and correlated factors with visual acuity in retinal arterial occlusion.

PURPOSE: To reveal the characteristics of vascular changes in retinal arterial occlusion (RAO) using optical coherence tomography angiography (OCTA) and determine the correlated factors with best-corrected visual acuity (BCVA). METHODS: This retrospective study recruited 54 RAO patients and 27 healthy individuals. Ophthalmic examinations including BCVA and OCTA were performed in all the patients and individuals. The OCTA outcomes were analyzed using SPSS software, and the characteristics of vascular changes and BCVA-related factors were summarized. RESULTS: The vessel density in all areas except fovea of both superficial capillary plexus (SCP) and deep capillary plexus (DCP) was significantly reduced in RAO eyes compared with the fellow eyes and normal control eyes (P < 0.05). The vessel density of DCP in all areas except fovea was significantly reduced in the fellow eyes compared with that in the normal control eyes as well (P < 0.05). The retinal thickness in fovea was significantly increased in RAO eyes compared with that in the fellow eyes and normal control eyes (P < 0.05), without any differences in other areas between the RAO eyes and the other two groups (P > 0.05). The retinal thickness in whole area and retinal thickness in fovea were correlated with BCVA, respectively (whole area: r = 0.295, P = 0.030; fovea: r = 0.322, P = 0.018). CONCLUSIONS: OCTA is a fast, noninvasive, and effective examination means for RAO that can display the vascular density and retinal thickness quantitatively and distinctly. RAO patients had reduced vascular density in both eyes and increased foveal retinal thickness in RAO eyes, showing a correlation with BCVA.

Identification of sequence polymorphisms in the mitochondrial deoxyribonucleic acid displacement-loop region as risk factors for systemic lupus erythematosus.

OBJECTIVES: This study aims to evaluate the relationship between sequence polymorphisms (SNPs) in the displacement-loop (D-loop) region of mitochondrial deoxyribonucleic acid (mtDNA) and systemic lupus erythematosus (SLE) in Chinese female patients. PATIENTS AND METHODS: This cross-sectional study was conducted between May 2017 and October 2017. The mtDNA was extracted from the peripheral blood of 97 female SLE patients (mean age 40.8 years; range, 20 to 79 years) and 108 age-matched healthy controls (mean age 48.7 years; range, 22 to 78 years). The SNPs of mtDNA D-loop were verified by polymerase chain reaction amplification and sequence analysis. The allele frequencies of D-loop region were compared by the Chi-square test between SLE and control groups. RESULTS: The SNP accumulation in SLE patients was significantly higher than that in the controls (p=0.027, 95% confidence interval [CI]: 0.075, 1.210). The frequencies of the major alleles of the nucleotides 73G/A (p<0.001, odds ratio [OR]=1.241) and 195T/C (p=0.047, OR=4.318) as well as the minor allele of nucleotide 199T/C (p=0.048, OR=0.279) were significantly higher in the SLE patients than in the controls, which indicated that 73G, 195T and 199C allele in the D-loop of mtDNA were associated with the risk of SLE. Further analysis indicated that the reactive oxygen species level in the SLE patients was significantly higher than that of controls (mean fluorescence intensity ± standard deviation: 3054.333±256.099 vs. 2099.167±599.662, p=0.009, 95% CI: 321.243, 1589.091). CONCLUSION: This study indicated the SNPs in the mtDNA may associated with the risk of SLE. Analysis of SNPs in the mitochondrial D-loop may help identify individuals who are at high risk of developing SLE.

The Diagnostic Value of Serum Exosomal Has_circ_0000615 for Breast Cancer Patients.

BACKGROUND: To explore the expression level of has_circ_0000615 in peripheral blood samples and evaluate its diagnostic value for breast cancer patients. METHODS: The peripheral blood samples of 95 breast cancer patients who underwent curative surgical resection and 95 age-matched healthy volunteers in our institutions from September 2019 to November 2020 were systematically collected. The expression level of has_circ_0000615 in the plasma was amplified and detected by qRT-PCR, and its correlation to clinicopathological characteristics of breast cancer patients were analyzed. RESULTS: Breast cancer patients had a significantly higher expression level of has_circ_0000615 in the plasma than healthy controls (P < 0.01), and its high expression was closely associated with advanced tumor stage (P=0.010), lymph node metastasis (P = 0.001) and high grade of recurrence risk (P=0.012). The receiver operator characteristic (ROC) curves showed that the area under curve (AUC) value, sensitivity and specificity of has_circ_0000615 for the diagnosis of non-metastatic breast cancer was 0.904 (95% CI: 0.863-0.944), 76.8% and 88.4%, respectively. Serum has_circ_0000615 expression had a better diagnostic efficiency than routine tumor biomarkers such as CA153, CA125 and CEA for distinguishing breast cancer patients from healthy individuals. TEM revealed that isolated exosomes from the culture medium of breast cancer cells had a disk-like appearance with a diameter of 80-200 nm vesicles, and the expression of exosome markers CD9 and CD81 was markedly increased. More importantly, the expression of has_circ_0000615 was detected in the exosomes and its expression level was markedly upregulated in breast cancer cell lines compared with normal ductal epithelial cells. The stability assay showed that there was no difference between RNA extraction at 0 hour and 24 hours in terms of the expression of has_circ_0000615 (P =0.327). Has_circ_0000615 might as exosomes be secreted into the circulating blood of breast cancer patients, resulting in a high expression level in plasma samples. CONCLUSION: The detection of has_circ_0000615 might be a promising diagnostic method for breast cancer.

Clinicopathological and prognostic significance of circRNAs in lung cancer: A systematic review and meta-analysis.

BACKGROUND: Circular RNAs (circRNAs) regulate multiple pathways during lung cancer pathogenesis. Apart from functional significance, many circRNAs have been shown to be associated with clinicopathological characteristics and predict lung cancer prognosis. Our aim is to summarize the expanding knowledge of clinical roles of circRNAs in lung cancer. METHODS: A thorough search of literature was conducted to identify articles about the correlation between circRNA expression and its prognostic and clinicopathological values. Biological mechanisms were summarized. RESULTS: This study included 35 original articles and 32 circRNAs with prognostic roles for lung cancer. Increased expression of 25 circRNAs and decreased expression of 7 circRNAs predicted poor prognosis. For non-small cell lung cancer, changes of circRNAs were correlated with tumor size, lymph node metastasis, distant metastasis, tumor node metastasis (TNM) stage, and differentiation, indicating the major function of circRNAs is to promote lung cancer invasion and migration. Particularly, meta-analysis of ciRS-7, hsa_circ_0020123, hsa_circ_0067934 showed increase of the 3 circRNAs was associated with positive lymph node metastasis. Increase of ciRS-7 and hsa_circ_0067934 was also related with advanced TNM stage. The biological effects depend on the general function of circRNA as microRNA sponge. CONCLUSIONS: CircRNAs have the potential to function as prognostic markers and are associated with lung cancer progression and metastasis.