Profilin 1, negatively regulated by microRNA-19a-3p,serves as a tumor suppressor in human hepatocellular carcinoma

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.     

SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters

Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface.     

Two new bisamides from the leaves of Aglaia perviridis

Two new bisamides, aglaiamides A (1) and B (2), along with three known ones (3–5), were isolated from the leaves of Aglaia perviridis. Their structures were established on the basis of detailed spectroscopic analyses.     

浅谈新型冠状病毒肺炎合并基础病的中医药防治策略＊

2019年12月始，新型冠状病毒肺炎（Corona Virus Disease 2019，COVID-19）以湖北武汉为中心向全国各地蔓延。目前数据显示，COVID-19合并糖尿病、高血压、肿瘤等基础病的患者病情较为严峻，病死率相对较高。该类患者的临床治疗策略有待进一步深入研究。在此次疫情防治过程中，中西医结合治疗手段于COVID-19的防治及患者基础疾病的兼顾治疗方面展现出了一定的特色及优势。本文结合中医“未病先防，既病防变，瘥后防复”思想，拟从COVID-19合并糖尿病、高血压、肿瘤三个方面，探讨COVID-19爆发形势下合并基础病患者的中医药防治策略。     

Comparison of auditory steady-state response and click-evoked auditory brain response in infants with different types and degrees of hearing loss

Abstract

Background: Auditory steady-state response (ASSR) and click-evoked auditory brain response (c-ABR) have been used for hearing assessment for decades years, the correlation of the two methods and the effects of type and degree of hearing loss (HL) to the correlation in infants younger than 6?months of age are unclear.

Objectives: To compare the correlation of ASSR and c-ABR and then to analyse the effects of type and degree of HL on the correlation in infants younger than 6?months of age.

Material and methods: Retrospective study comparing ASSR thresholds at various frequencies with c-ABR thresholds. 182 ears from 96 infants were assessed and classified according to types and degrees of HL.

Results: The correlation coefficients were: 0.823, 0.864, 0.891, 0.871, 0.908, 0.915 and 0.913 between ASSR thresholds at 0.5, 1, 2, 4, 2–4, 1–2–4, 0.5–1–2–4?kHz and c-ABR thresholds respectively. The correlation coefficients in the group of sensorineural HL (SHL) (r?=?0.763–0.900) were higher than conductive HL (r?=?0.309–0.619) across all frequencies. The coefficients of severe-profound SHL (r?=?0.595–0.790) were higher than mild-moderate SHL (r?=?0.434–0.687) across all frequencies.

Conclusions and significance: ASSR was one valuable cross-check measure by providing frequency specific information in auditory assessment.     

慕课在我国高等医学教育中应用的文献计量分析

目的　探讨慕课在我国高等医学教育领域的应用现状和发展趋势，为本领域今后的研究提供参考。方法　检索中国知网、万方数据服务平台、维普数据库、中国生物医学文献数据库建库以来至2020年3月1日收录的相关文献，运用文献计量学方法对年发文量、期刊分布、基金支持、著者分布、被引频次、文献类型和高频关键词进行统计分析。将导出的资料用Excel 2010建立数据库，借助频数分析法进行描述性统计。结果　纳入文献754篇，分别收录于262种期刊；以医学教育类期刊为主；基金资助率达50%；黄坪、张欣、李鑫辉等7人为核心作者；以人体解剖学为代表的基础医学类课程应用研究最多；慕课应用研究以理论课程为主；课程评价包括终末性评价、形成性评价、平台考核、综合能力和自主学习能力５大方面；研究热点为基于慕课的混合式教学模式及其在护理教育、中医教育及继续医学教育中的应用。结论　近5年，慕课在我国高等医学教育中发展迅速，核心作者已形成，但缺乏深度合作。未来应增加实验（训）类课程的应用研究，同时应进一步完善实验性研究的设计及课程评价体系。     

Apatinib Monotherapy or Combination Therapy for Non-Small Cell Lung Cancer Patients With Brain Metastases

Apatinib, an oral small molecular receptor tyrosine kinase inhibitor (TKI) developed first in China, exerts antiangiogenic and antineoplastic function through selectively binding and inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we aimed to explore the efficacy and safety profile of apatinib monotherapy, or combined with chemotherapy or endothelial growth factor receptor (EGFR)-TKI in heavily pretreated non-small cell lung cancer (NSCLC) patients with brain metastases. We performed a retrospective analysis for relapsed NSCLC patients with brain metastases from our institute, who received apatinib (250 mg or 500 mg p.o. qd) monotherapy, or combination with EGFR-TKI or chemotherapy as second or more line systemic therapy until disease progression or unacceptable toxicity occurred. The objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and safety were analyzed. A total of 26 eligible patients were included: 24 patients diagnosed with adenocarcinoma, 2 with squamous carcinoma, and 14 patients harboring EGFR sensitizing mutations. The mPFS and mOS were 4.93 (range, 0.27−32.91; 95% CI 3.64−6.22) and 14.70 (range, 0.27−32.91; 95% CI 0.27−43.60) months for the whole group. The ORR and DCR were 7.7% (2/26) and 69.2% (18/26) for the entire lesions, and 7.7% (2/26) and 79.6% (20/26) for brain metastases, respectively. Compared with patients who received apatinib monotherapy, patients who received apatinib combination treatment had more favorable mPFS (11.77 vs. 2.27 months, p<0.05) and mOS (24.03 vs. 6.07 months, p<0.05). Treatment-related toxicities were tolerable including grade 1/2 hypertension, hand-and-foot syndrome, fatigue, nausea, liver dysfunction, myelosuppression, skin rash, and palpitation. In conclusion, apatinib exhibited high activity and good tolerance for NSCLC patients with brain metastasis, and it might become a potential choice for metastatic brain tumors in NSCLC patients.     

脑脊液降钙素原及乳酸测定在早期诊断颅脑术后颅内感染的意义

目的研究降钙素原(PCT)及乳酸水平在早期诊断颅脑术后颅内感染的意义。方法颅脑术后颅内感染患者(n=20)和非颅内感染患者(n=20)的脑脊液和血液样本,检测脑脊液和血清PCT,脑脊液和血液乳酸水平等指标并进行统计分析。结果感染组脑脊液和血清PCT、乳酸水平较非感染组显著升高,差异有统计学意义(P0.05)。脑脊液PCT和乳酸水平诊断敏感性及特异性均较血清PCT和乳酸水平高。结论脑脊液PCT、乳酸在颅脑手术术后颅内感染的诊断中均有意义,其中脑脊液PCT较乳酸敏感性更高,临床应用价值更大。