Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery.

BACKGROUND: Postoperative progression and chemotherapy resistance is the major cause of treatment failure in patients with triple-negative breast cancer (TNBC). Currently, there is a lack of an ideal predictive model for the progression and drug sensitivity of postoperative TNBC patients. Diverse programmed cell death (PCD) patterns play an important role in tumor progression, which has the potential to be a prognostic and drug sensitivity indicator for TNBC after surgery. MATERIALS AND METHODS: Twelve PCD patterns (apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, and oxeiptosis) were analyzed for model construction. Bulk transcriptome, single-cell transcriptome, genomics, and clinical information were collected from TCGA-BRCA, METABRIC, GSE58812, GSE21653, GSE176078, GSE75688, and KM-plotter cohorts to validate the model. RESULTS: The machine learning algorithm established a cell death index (CDI) with a 12-gene signature. Validated in five independent datasets, TNBC patients with high CDI had a worse prognosis after surgery. Two molecular subtypes of TNBC with distinct vital biological processes were identified by an unsupervised clustering model. A nomogram with high predictive performance was constructed by incorporating CDI with clinical features. Furthermore, CDI was associated with immune checkpoint genes and key tumor microenvironment components by integrated analysis of bulk and single-cell transcriptome. TNBC patients with high CDI are resistant to standard adjuvant chemotherapy regimens (docetaxel, oxaliplatin, etc.); however, they might be sensitive to palbociclib (an FDA-approved drug for luminal breast cancer). CONCLUSION: Generally, we established a novel CDI model by comprehensively analyzing diverse cell death patterns, which can accurately predict clinical prognosis and drug sensitivity of TNBC after surgery. A user-friendly website was created to facilitate the application of this prediction model (https://tnbc.shinyapps.io/CDI_Model/).

CircEPSTI1 Promotes the Proliferation of HER2-Positive Breast Cancer Cells via circEPSTI1/miR-145/ERBB3 Axis.

Breast cancer is the most common type of cancer worldwide. There are great challenges in the prevention and treatment of breast cancer. In this study, we explored the molecular and biological mechanisms of circular RNA circEPSTI1 (has_circ_0000479) in the regulation of HER2-positive breast cancer cells. The expression of CircEPSTI1, microRNA miR-145, and ERBB3 in HER2-positive breast cancer cells was evaluated by qRT-PCR and western blot assays. Cell proliferation was assessed by CCK-8. Wound-healing and transwell migration assays were performed to evaluate cell migration. A transwell invasion assay was performed to detect cell invasion. The interaction of miR-145, circEPSTI1, and ERBB3 was confirmed bydual-luciferase reporter and RIP assays. CircEPSTI1 was upregulated in the HER2-positive breast cancer tissues and cells. Knockdown of circEPSTI1 inhibited SKBR3 and BT474 cell proliferation, migration, and invasion. Mechanistically, circEPSTI1 directly targeted miR-145, and miR-145 was a downstream mediator of circEPSTI1 in modulating the proliferation, migration, and invasion of SKBR3 and BT474 cells. ERBB3 was identified as a direct and functional target of miR-145 in HER2-positive breast cancer cells. Our findings demonstrate that circEPSTI1, an overexpressed circRNA in HER2-positive breast cancer, promotes the proliferation, migration, and invasion of SKBR3 and BT474 cells through the miR-145/ERBB3 axis.

Therapeutic Landscape of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

Human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) is a common malignancy that is prone to recurrence and metastasis in the early stages, resulting in a poor prognosis for patients. Many studies have suggested that targeted therapy promotes clinical outcomes in HER2+BC. With the introduction of trastuzumab in 1998, the prognosis of patients with early HER2+BC has improved significantly. However, owing to obstinate drug resistance and adverse events, the addition of new agents in standardized treatment has become a research hotspot. These promising agents include antibodies, antibody-drug conjugates, tyrosine kinase inhibitors, and anti-HER2 combined therapies. This article provides a brief description of the biology of BC and the expression of HER2, with the aim to provide an overview of the therapeutic landscape of HER2+BC by reviewing research results and introducing the latest evidence to provide a reference for clinical treatment.

Treatment efficacy of Lianhua Qingwen capsules for eraly-stage COVID-19.

OBJECTIVE: To systematically determine the effect of Lianhua Qingwen Capsules on the early antiviral and anti-inflammatory action against COVID-19 (Coronavirus 2019) and its applicational value in the treatment of COVID-19. METHODS: The clinical data of 66 early-mid-stage COVID-19 patients admitted to hospitals in Guangzhou between January 2020 and April 2020 were retrospectively analyzed. The patients receiving Lianhua Qingwen Capsule treatment were assigned to the observation group (n=33) and those given conventional therapy were included in the control group (n=33). The two groups were compared in terms of clinical effects and main symptom (fever, cough and fatigue) disappearance rate. RESULTS: In comparison with the control group, 1) the total effective rate was significantly higher in the observation group (P<0.05); 2) the disappearance rates of fever, cough and fatigue were statistically higher in the observation group; 3) the treatment time was significantly shorter and patient recovery was significantly better in the observation group; 4) the laboratory index levels [white blood cell (WBC), interleukin-6 (IL-6), serum amyloid A (SAA)] were better in the observation group. CONCLUSION: Lianhua Qingwen Capsules can significantly improve the total effective rate for COVID-19 patients, as well as shorten the hospital stay and treatment time, which is worth of promotion in the clinic.

Association Between Environmental and Socioeconomic Risk Factors and Hepatocellular Carcinoma: A Meta-Analysis.

BACKGROUND: The association between environmental and socioeconomic risk factors and the occurrence of hepatocellular carcinoma (HCC) are still inconclusive. A meta-analysis was conducted to address this issue. METHODS: We systematically searched the databases including PubMed, Web of Science, and Google Scholar and collected the related risk factors of HCC before March 6, 2020. Statistical analysis was performed on the odds ratio (OR) value and 95% CI of the correlation between environmental and socioeconomic factors and HCC. Begg's rank correlation test, Egger's linear regression test, and the funnel plot were employed for identification of the publication bias. RESULTS: Out of 42 studies, a total of 57,892 participants were included. Environmental and socioeconomic risk factors including ever educated (illiteracy); race (Black, Hispanic, and Asian); medium and low incomes; occupations (farmer and labor); passive smoking; place of residence (rural); blood aflatoxin B1 (AFB1) adduct level; exposure of pesticide, etc., were statistically increased with the occurrence of HCC (P < 0.05) and OR values and 95% CIs were 1.37 (1.00, 1.89), 2.42 (1.10-5.31), 1.90 (0.87-4.17), 5.36 (0.72-40.14), 1.48 (1.11, 1.96), 1.74 (1.00-3.03), 1.49 (1.06-2.08), 1.52 (1.07-2.18), 1.43 (0.27, 7.51), 1.46 (1.09, 1.96), 2.58 (1.67-3.97), and 1.52 (0.95-2.42), respectively. We found 6-9, 9-12, and ≥12 years of education that statistically reduced the risk of the occurrence of HCC (P < 0.05) and OR values and 95% CIs were 0.70 (0.58, 0.86), 0.52 (0.40, 0.68), and 0.37 (0.23, 0.59), respectively. No significant associations (P > 0.05) were observed between race (Hispanic and Asian), passive smoking, marital status, place of birth, place of residence, and HCC. In stratified analysis, exposure of pesticide was statistically significant (P < 0.05), while race of black was on the contrary. CONCLUSION: Environmental and socioeconomic risk factors have great impacts on the incidence rate of HCC. Improving national education and income levels can significantly reduce the risk of HCC. PROSPERO REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020151710.

circEPSTI1 Acts as a ceRNA to Regulate the Progression of Osteosarcoma.

BACKGROUND: Recent studies have reported the vital roles of circular RNAs (circRNAs) in tumor progression. However, the function and expression profile of most circRNAs in osteosarcoma remain unclear. METHODS: We examined the expression of circEPSTI1, a circRNA, in 50 paired adjacent normal tissues and osteosarcoma tissues by qRT-PCR. Then, we further explored the function of circEPSTI1 in osteosarcoma progression in vitro and in vivo. For example, cell proliferation and migration were examined. Some experiments were performed to explore the regulatory function of circEPSTI1 in miRNA and to investigate the potential role of circEPSTI1 in osteosarcoma. RESULTS: We found that circEPSTI1 was significantly upregulated in osteosarcoma. Inhibition of circEPSTI1 suppressed the osteosarcoma cancer cell proliferation and migration in vitro. Dual luciferase reporter assay showed that circEPSTI1 and MCL1 (myeloid cell leukaemia 1) could bind to miR-892b and that MCL1 and circEPSTI1 were targets of miR-892b. CONCLUSION: Thus, the circEPSTI1-miR-892b-MCL1 axis affected osteosarcoma progression through the miRNA sponging mechanism. circEPSTI1 may serve as a target and biomarker for osteosarcoma treatment.

miR-150 contributes to the radioresistance in nasopharyngeal carcinoma cells by targeting glycogen synthase kinase-3ß.

INTRODUCTION: Radiotherapy has been the primary treatment for nasopharyngeal carcinoma (NPC), but the NPC radiocurability was severely limited with the radioresistance. The research suggested the important role of miRNAs in cancer therapeutic response. MATERIALS AND METHODS: A radioresistant NPC cell line CNE-2R, we exposed CNE-2 cells to a range of radiation doses. Levels of miR-150 were measured by quantitative reverse-transcriptase polymerase chain reaction in CNE-2R and CNE-2 cells. RESULTS: In this study, a cell line CNE-2R derived from parental CNE-2 was established via being exposed to stepwise escalated radiation dose. The expression of miR-150 was upregulated in CNE-2R cells. The radioresistance of CNE-2R cells was reversed after inhibiting miR-150 with specific inhibitor, while the radioresistance of CNE-2 cells was enhanced after the overexpression of miR-150. MiR-150b elicited these responses by directly targeting GSK3ß. Moreover, GSK3ß protein expression was downregulated in CNE-2R cells and restored GSK3ß expression increased radiosensitivity of CNE-2R cells. Importantly, the negative correlation between miR-150 expression and GSK3ß protein level was confirmed in the NPC tissues. High miR-150 expression and low GSK3ß protein level were associated with poor prognosis in NPC patients. CONCLUSION: Our findings suggested that miR-150-GSK3ß axis may be a novel candidate for developing rational therapeutic strategies for NPC treatment.

Unequal Distribution of Overweight Adolescents in Immigrant-Rich Areas: Analysis of Disparities among Public and Private School Students in Shanghai, China.

Accelerated urbanization and rising immigration to the big cities in China has resulted in education policies that produce disparate treatment of immigrant and non-immigrant students. The two types of students frequently wind up in different types of junior high schools. However, there is little research on whether disparities exist between students in public and private schools with regard to overweight. This study aims to address this gap through a comparison of the overweight status of junior high school students in public and private schools in Shanghai and explore the possible reasons for the observed differences. Students from two public and two private junior high schools were measured. In order to determine what factors might shape overweight among adolescents. Logistic regression analysis was used to assess associations between overweight and personal characteristics, birth-related factors, levels of physical activity, diet, family socioeconomic status and school environment. Students in private schools proved more likely to be overweight (15.20%, p < 0.05) than public school students (10.18%). Similarly, gender, breastfeeding, parental care and number of classes excluding physical education per day were found to be significant factors. However, private school students were also influenced by gestational age (yes/no: OR = 4.50, p < 0.001), frequency of snacks (sometimes/often: OR = 0.53, p < 0.01) and family income (¥6001-12,000/below ¥6000: OR = 3.27, p < 0.05). Time for lunch was the sole risk factor for public school students in the study (p < 0.05). To reduce the unequal distribution of overweight students between the two types of schools, interventions that consider different multiple risk factors should be implemented.

Advancing Implementation of Evidence-Based Public Health in China: An Assessment of the Current Situation and Suggestions for Developing Regions.

Objective. Existing research shows a serious scarcity of EBPH practice in China and other developing regions; as an exploratory study, this study aimed to assess the current EBPH implementation status in Shanghai of China qualitatively. Methods. Using semistructured key informant interviews, we examined the status of and impediments to the lagging EBPH in China. Data were analyzed based on the Consolidated Framework for Implementation Research (CFIR). Results. Chinese public health practitioners knew more about evidence-based medicine but less about EBPH. The situation was worse in community healthcare centers. Participants perceived that evidence sources were limited and the quality of evidence was low. Concerning the inner setting factors, the structural characteristics, networks and communications, implementation climate, and leadership engagement were confronted with many problems. Among the outer setting factors, external government policies and incentives and low patient compliance were the key problems. Additionally, public health practitioners in Shanghai lacked sufficient awareness of EBPH. Furthermore, the current project-based EBPH lacks a systematic implementation system. Conclusions. Existing practical perspectives on EBPH indicate a lag in the advocacy of this new ideology in China. It would be advisable for healthcare institutions to take the initiative to explore feasible and multiple methods of EBPH promotion.