Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Calculated plasma volume status is associated with poor outcomes in acute ischemic stroke treated with endovascular treatment.

Background and purpose: The impact of calculated plasma volume status (PVS) on the prognosis of acute ischemic stroke treated with endovascular treatment (EVT) remains undetermined. This study aimed to investigate the association between PVS and 90 days functional outcomes after EVT. Methods: We enrolled patients treated with EVT in the anterior circulation from a prospective registry. The endpoint was a modified Rankin scale score of ≥3 points at 90 days after EVT. We used multivariable logistic regression models to investigate the association between PVS and poor outcomes. We used the restricted cubic spline to present the linearity between PVS and poor outcomes. Results: Among the 187 enrolled patients (median age, 65 years; 35.8% women), a total of 81 patients (43.3%) experienced poor outcomes at 90 days. In multivariable analyses, PVS was associated with poor outcomes despite increasing confounding factors (odds ratio, 3.157; 95% confidence interval, 1.942-5.534; P < 0.001). The restricted cubic spline revealed a positive correlation between PVS and the risk of poor outcomes after EVT (P for nonlinearity = 0.021). Conclusion: Our study found that an elevated PVS value was associated with poor outcomes after EVT. Further prospective cohorts were warranted to evaluate the utility of PVS in AIS treated with EVT.

Sesamol inhibits proliferation, migration and invasion of triple negative breast cancer via inactivating Wnt/ß-catenin signaling.

Triple negative breast cancer (TNBC), a particularly aggressive breast cancer subtype without estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) expression, possesses highly invasive capacity, uncontrolled proliferative phenotype and poor clinical prognosis. Sesamol enriched in sesame seeds has been widely reported as a metabolic modulator due to its anti-aging, anti-hepatotoxic and cardio-protective properties. In this study, we found that sesamol significantly inhibited proliferation, migration and invasion of TNBC cells via attenuating PCNA, CyclinD1 expression and reversion of epithelial-mesenchymal transition (EMT) characterized by increased epithelial marker E-cadherin and decreased mesenchymal marker N-cadherin, Vimentin, Snail expression. Moreover, sesamol inactivated Wnt/ß-catenin signaling and Wnt agonist 1 AMBMP application reversed the inhibition of proliferation, migration and invasion of TNBC by sesamol administration. Subsequently, our data showed that sesamol induced Wnt inhibitory factor 1 (WIF1), an endogenous inhibitor of Wnt/ß-catenin pathway, expression and WIF1 artificial knockdown abrogated the inactivation of Wnt/ß-catenin signaling by sesamol exposure in TNBC cells. And we found that promoter region de-methylation was responsible for WIF1 up-regulation by sesamol administration. Finally, with the xenograft assay using nude mice, we also found that sesamol inhibited proliferation and metastasis of TNBC via WIF1-induced inactivation of Wnt/ß-catenin signaling in vivo. Collectively, these data added novel understandings and evidences to the anti-cancer properties of sesamol.

Sesamol Epigenetically Induces Estrogen Receptor α Re-expression by Upregulating miR-370-3p in Estrogen Receptor α-Negative Breast Cancer.

Due to lack of estrogen receptor α (ERα, gene name: ESR1), ERα-negative breast carcinoma is insensitive to endocrine therapy, and restoration of ERα has become a promising strategy for ERα-negative breast cancer treatment. Sesamol, a naturally occurring phenolic compound, is usually extracted from sesame seeds. Previous investigations have unmasked its anti-oxidant and anti-inflammation properties. In this study, sesamol induced ERα functional re-expression followed by upregulation of its downstream pS2 and GREB1 genes in ERα-negative breast carcinoma. Moreover, it endowed responsiveness of ERα-negative breast carcinoma to the endocrine treatment drug 4-hydroxytamoxifen without influencing the viability of normal human umbilical vein endothelial cells. Mechanistically, sesamol induced ESR1 gene promoter demethylation by downregulating the expression of the DNA methyltransferases DNMT3A and DNMT3B, without affecting DNMT1. Moreover, the non-coding RNA miR-370-3p directly targeted DNMT3A and DNMT3B mRNA, and its expression increased upon treatment with sesamol. Artificial abrogation of miR-370-3p expression with an antagomir abolished the inhibition of DNMT3A and DNMT3B expression by sesamol, resulting in a fallback in ERα reactivation. In mice, sesamol significantly induced ERα re-expression via miR-370-3p-mediated downregulation of DNMT3A and DNMT3B. Sesamol may be a safe and effective option for clinical adjuvant therapy in patients with ERα-negative breast cancer.