Clinical characteristics and prognosis of primary small cell carcinoma of the breast: a propensity score-matched, population-based study.

OBJECTIVE: The purpose of this study was to describe the clinicopathological characteristics and prognosis of primary small cell carcinoma of the breast (PSCCB) and compare PSCCB with breast invasive ductal carcinoma (IDC). DESIGN: A retrospective cohort study. SETTING: Data of patients with PSCCB and breast IDC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. PARTICIPANTS: Eighty-three patients with PSCCB and 410 699 patients with breast IDC were enrolled in the present cohort study. MATERIALS AND METHODS: Patients with PSCCB and breast IDC were identified from the SEER database between 2004 and 2016. The clinicopathological characteristics and survival of patients with PSCCB and IDC were compared. Propensity score matching (PSM) analysis was performed to adjust for differences in baseline characteristics when comparing overall survival (OS) and cancer-specific survival (CSS). Moreover, OS-/CSS-specific nomograms were established to predict the prognosis of PSCCB. RESULTS: Compared with IDC, PSCCB was significantly correlated with older age, male, higher pathological grade, higher TNM (tumour, node, metastases) stage, a higher proportion of triple-negative breast cancer, a lower proportion of ER/PR positivity and significantly worse clinical outcome. The median OS and CSS of patients with PSCCB were 23.0 m (95%CI 13.0 to 56.0) and 28.0 m (95%CI 18.0 to 66.0), respectively. The 5-year OS and CSS rates in the PSCCB group were 36.1% and 42.4%, respectively. In the matched cohort after PSM analysis, patients with PSCCB had significantly worse OS and CSS than IDC patients. Multivariate Cox regression analysis demonstrated that T stage and administration of chemotherapy were independent prognostic factors for both OS and CSS in patients with PSCCB. The C-index for OS-/CSS-specific nomogram was 0.75 (95%CI 0.66 to 0.85)/0.79 (95%CI 0.69 to 0.89), respectively. The calibration curve in the ROC analysis indicated that the predicted value was consistent with the actual observation value. Decision curve analysis suggested that the nomogram model has a significant positive net benefit from the risk of death and are better than the traditional TNM staging system. CONCLUSION: PSCCB has distinct clinicopathological characteristics, and patients with PSCCB have significantly worse clinical outcomes than those with IDC.

Risk factors and survival prediction of young breast cancer patients with liver metastases: a population-based study.

Background: The risk and prognosis of young breast cancer (YBC) with liver metastases (YBCLM) remain unclear. Thus, this study aimed to determine the risk and prognostic factors in these patients and construct predictive nomogram models. Methods: This population-based retrospective study was conducted using data of YBCLM patients from the Surveillance, Epidemiology, and End Results database between 2010 and 2019. Multivariate logistic and Cox regression analyses were used to identify independent risk and prognostic factors, which were used to construct the diagnostic and prognostic nomograms. The concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the performances of the established nomogram models. Propensity score matching (PSM) analysis was used to balance the baseline characteristics between the YBCLM patients and non-young patients with BCLM when comparing overall survival (OS) and cancer-specific survival (CSS). Results: A total of 18,275 YBC were identified, of whom 400 had LM. T stage, N stage, molecular subtypes, and bone, lung, and brain metastases were independent risk factors for LM developing in YBC. The established diagnostic nomogram showed that bone metastases contributed the most risk of LM developing, with a C-index of 0.895 (95% confidence interval 0.877-0.913) for this nomogram model. YBCLM had better survival than non-young patients with BCLM in unmatched and matched cohorts after propensity score matching analysis. The multivariate Cox analysis demonstrated that molecular subtypes, surgery and bone, lung, and brain metastases were independently associated with OS and CSS, chemotherapy was an independent prognostic factor for OS, and marital status and T stage were independent prognostic factors for CSS. The C-indices for the OS- and CSS-specific nomograms were 0.728 (0.69-0.766) and 0.74 (0.696-0.778), respectively. The ROC analysis indicated that these models had excellent discriminatory power. The calibration curve also showed that the observed results were consistent with the predicted results. DCA showed that the developed nomogram models would be effective in clinical practice. Conclusion: The present study determined the risk and prognostic factors of YBCLM and further developed nomograms that can be used to effectively identify high-risk patients and predict survival outcomes.

Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a devastating stroke type with high mortality and disability. Inflammatory response induced by macrophages/microglia (M/Ms) activation is one of the leading causes of brain damage after ICH. The anti-inflammatory effects of resveratrol (RSV) have already been evaluated in several models of central nervous system disease. Therefore, we designed the current study to assess the role of RSV in ICH and explore its downstream mechanism related to Sirt3. The autologous artery blood injection was administrated to create an ICH mouse model. M/Ms-specific Sirt3 knockout Sirt3f/f; CX3CR1-Cre (Sirt3 cKO) mouse was used to evaluate the role of Sirt3 on RSV treatment. Neuronal function and hematoma volume were assessed to indicate brain damage. The pro-inflammatory marker (CD16) and cytokine (TNF) were measured to evaluate the inflammatory effects. Our results showed that RSV treatment alleviates neurological deficits, reduces cell death, and increases hematoma clearance on day 7 after ICH. In addition, RSV effectively suppressed CD16+ M/Ms activation and decreased TNF release. In Sirt3 cKO mice, the protective effects of RSV were abolished, indicating the potential mechanism of RSV was partially due to Sirt3 signaling activation. Therefore, RSV could be a promising candidate and therapeutic agent for ICH and Sirt3 could be a potential target to inhibit inflammation.

Clinical characteristics and prognostic nomogram for patients with insular thyroid carcinoma: a population-based analysis.

BACKGROUND: Insular thyroid carcinoma (ITC) is an uncommon poorly differentiated thyroid malignancy. Due to its rarity, its demographic and clinicopathological features and survival remains unclear. The present study aimed to describe the features and survival of ITC, determine its prognostic factors, and establish a prognostic nomogram. METHODS: Patients with ITC were identified in the Surveillance, Epidemiology, and End Results database from 2004 to 2019. The features and survival of patients with ITC and other thyroid carcinomas were compared after balancing the baseline characteristics using propensity score matching (PSM). Univariate and multivariate Cox analyses were used to identify the prognostic factors for ITC. Moreover, overall survival (OS)- or cancer-specific survival (CSS)-specific nomograms were established to predict ITC prognosis. RESULTS: A total of 206 patients with ITCs were identified. The 1-, 2-, 5-, and 10-year OS rates of 206 patients with ITC were 90.3%, 82.0%, 62.2%, and 42.5%, respectively. The median OS was 93 months (95% CI, 73.0-140.0), while the median CSS was 141 months (95% CI, 93.0-173.0). After PSM analysis, the survival analysis of the matched cohort revealed that ITC had a worse clinical outcome than papillary thyroid cancer and follicular thyroid cancer, and better survival than anaplastic thyroid carcinoma. Multivariate Cox regression analysis demonstrated that age, N stage, M stage, and surgery were independent prognostic factors for both OS and CSS in ITC patients. The C-indices for the OS- and CSS-specific nomograms were 0.778 (95% CI, 0.724-0.832) and 0.808 (95% CI, 0.754-0.862), respectively. The calibration curve and ROC analysis indicated that the nomogram models exhibited a good discriminative ability. Decision curve analysis suggested that the nomogram models had a significant positive net benefit and were better than the traditional TNM staging system at predicting survival. CONCLUSION: ITC has distinct clinicopathological characteristics and survival compared to other thyroid carcinomas, and the established nomogram could predict the survival probability of patients with ITC accurately with a higher net benefit.

Protective role of TLR9-induced macrophage/microglia phagocytosis after experimental intracerebral hemorrhage in mice.

INTRODUCTION: Intracerebral hemorrhage (ICH) causes devastating morbidity and mortality, and studies have shown that the toxic components of hematomas play key roles in brain damage after ICH. Recent studies have found that TLR9 participates in regulating the phagocytosis of peripheral macrophages. The current study examined the role of TLR9 in macrophage/microglial (M/M) function after ICH. METHODS: RAW264.7 (macrophage), BV2 (microglia), and HT22# (neurons) cell lines were transfected with lentivirus for TLR9 overexpression. Whole blood from C57BL/6 or EGFPTg/+ mice was infused for phagocytosis and injury experiments, and brusatol was used for the experiments. Intraperitoneal injection of the TLR9 agonist ODN1826 or control ODN2138 was performed on days 1, 3, 5, 7, and 28 after ICH to study the effects of TLR9 in mice. In addition, clodronate was coinjected in M/M elimination experiments. The brains were collected for histological and protein experiments at different time points after ICH induction. Cellular and histological methods were used to measure hematoma/iron residual, M/Ms variation, neural injury, and brain tissue loss. Behavioral tests were performed premodeling and on days 1, 3, 7, and 28 post-ICH. RESULTS: Overexpression of TLR9 facilitated M/M phagocytosis and protected neurons from blood-derived hazards in vitro. Furthermore, ODN1826 boosted M/M activation and phagocytic function, facilitated hematoma/iron resolution, reduced brain injury, and improved neurological function recovery in ICH mice, which were abolished by clodronate injection. The experimental results indicated that the Nrf2/CD204 pathway participated in TLR9-induced M/M phagocytosis after ICH. CONCLUSION: Our study suggests a protective role for TLR9-enhanced M/M phagocytosis via the Nrf2/CD204 pathway after ICH. Our findings may serve as potential targets for ICH treatment.

Effect of an educational intervention on HPV knowledge and attitudes towards HPV and its vaccines among junior middle school students in Chengdu, China.

BACKGROUND: Little is known about the knowledge and attitudes towards human papillomavirus (HPV) and its vaccines among adolescents in mainland China. Also, limited information has been available on how to improve their knowledge and willingness towards HPV and its vaccines to ensure a successful vaccination program in the future. METHODS: This was a school-based interventional follow-up study. One urban and one rural junior middle school in Chengdu were selected by convenience sampling. At baseline, half of the grade one students were randomly selected as controls and the rest were interventions. A set of self-administered questionnaires on HPV and its vaccines were completed by both groups at baseline. After that, only the intervention group received a PowerPoint-oriented health education and finished the post-education questionnaires. One year later, both groups completed the same questionnaires as the follow-up survey. RESULTS: In total, 1675 students finished the pre-intervention questionnaires; 751 were from the control group and 924 were from the intervention group. Among them, only 34.3% had heard of cervical cancer/genital warts, while only 15.1% of them had ever heard of HPV. However, 55.2% of students showed their willingness to be vaccinated even before any intervention. Seven variables were found to be associated with the willingness to be vaccinated at baseline. Immediately after the intervention, 88.4% of students were willing to vaccinate themselves. After 1 year, the effectiveness of intervention remained but decreased. Compared with the control group, the intervention group was more aware about cervical cancer, HPV and its vaccines with statistical significance. However, the level of HPV knowledge and willingness to be vaccinated among the intervention group had significantly decreased compared with that immediately after the intervention (P < 0.001). CONCLUSIONS: The baseline level of knowledge on HPV, its vaccines, and cervical cancer was very low among junior middle school students in Chengdu, China. However, the willingness to be vaccinated seemed positive. School-based health education is effective and appropriate in increasing the awareness of HPV and willingness towards its vaccines. Regular health education on HPV and cervical cancer prevention at a shorter interval should be guaranteed to ensure continuous effectiveness.

[The effect of 5-fluorouracil on enriching cancer stem cells of hepatoma cell line BEL-7402].

OBJECTIVE: To investigate the effect of 5-FU (5-fluorouracil) on enriching cancer stem cells of HCC cell line BEL-7402 and the biological characteristics of enriched cells. METHODS: The enriching concentration of 5-FU was determined by CCK-8 (cell counting kit-8). Flow Cytometry was used to determine the changes in cell cycle and positive expression ratio of surface marker CD56, CD54, EpCAM and CD133. The self-renewal and differentiation of positive cells were tested by colony formation assay, and were compared with the control group. RESULTS: Enriching concentration of 5-FU was determined as 10 µg/ml with 48 h incubation. After enrichment, G0/G1 phase cells increased from 57.50 %+/-0.98% to 68.70%+/-3.41% (P<0.05). Whereas S phase cells decreased from 40.26%+/-4.12% to 31.80%+/-4.15% (P<0.01); G2/M phase cells disappeared in experimental group, and was 5.80%+/-1.87% in control group (P<0.01). The proportion of the cell cycle changed with significant statistical differences. Meanwhile, positive rate of cell surface makers CD56, CD54, EpCAM and CD133 increased from 0.57%+/-0.12%, 8.10%+/-6.79%, 0.3%+/-0.01% and 3.20%+/-0.99% to 4.13%+/-0.06%, 50.08%+/-1.69%, 0.55%+/-0.07% and 10.51%+/-1.13%, respectively. The difference was significant (P<0.05). The colony forming ratio of CD56, CD54, EpCAM and CD133 negative cells and positive cells were 2.11%+/-0.21%, 3.32%+/-0.31%; 0.86%+/-0.101%, 2.40%+/-0.52 %; 7.19%+/-0.56%, 7.73%+/-0.71%; 2.70%+/-0.26%, 5.75%+/-0.81%, respectively, and significant differences were found between (P<0.05). CONCLUSION: 5-fluorouracil enriched the cancer stem cell population in HCC cell line BEL-7402. CD56 and CD54 can be used as important surface markers in research of liver cancer stem cells.