朝鲜淫羊藿酸性多糖的理化特性及对HepG2细胞脂质堆积的改善作用＊

目的 对比研究朝鲜淫羊藿酸性多糖酯化还原前后的理化特性，并探讨其改善油酸诱导的肝癌HepG2细胞脂质堆积活性的差异。方法 采用高效凝胶渗透色谱法测定朝鲜淫羊藿酸性多糖（EFPA）的均一性和分子量，高效液相色谱法测定EFPA和酯化还原后朝鲜淫羊藿酸性多糖（EFPA-R）的单糖组成；采用油酸（OA）处理HepG2细胞诱导建立脂质蓄积模型，不同浓度EFPA与EFPA-R（10、30、100、300 μg·mL^-1）分别和OA共同作用于细胞24 h，采用CCK-8试剂盒测定细胞存活率，油红O染色观察细胞内脂滴蓄积情况，并采用试剂盒测定细胞内总胆固醇（TC）、甘油三酯（TG）含量。结果 EFPA为成分均一的多糖组分，分子量为125.8 kDa，由甘露糖、葡萄糖、半乳糖、葡萄糖醛酸和阿拉伯糖组成，摩尔比为1.7∶7.4∶1.4∶1.8∶1.0，葡萄糖占比最大，EFPA-R由甘露糖、葡萄糖、半乳糖和阿拉伯糖组成，摩尔比为0.8∶10.6∶2.1∶1.0；在10-300 μg·mL^-1范围内，EFPA和EFPA-R对HepG2细胞的抑制作用较弱，作为给药浓度；与空白组相比，模型组细胞中TC、TG含量显著升高（P < 0.01），细胞内红色脂滴显著增多，与模型组相比，EFPA可显著降低细胞中TC、TG含量（P < 0.01），明显减少细胞内红色脂滴（P < 0.05或P < 0.01），EFPA-R干预后细胞则无明显变化。结论 EFPA可明显改善HepG2细胞脂质堆积情况，且呈现剂量依赖性，而半乳糖醛酸（GalA）的存在可能是其抑制HepG2细胞脂质蓄积的关键因素。     

Study on the Value of Ultrasound Elastography Combined with Plasma miRNA Expression in the Early Detection of Breast Cancer

Background: Breast cancer (BC) is the most common malignant tumor in women, and its morbidity and mortality are increasing each year, due to the lack of specific clinical symptoms in the early stage of BC, and the lack of diagnostic methods for early breast cancer. Therefore, identifying an effective diagnostic method for early BC has become urgent. Materials and Methods: Breast lesions with a histological diagnosis that were examined by ultrasonic elastography (UE) in our department from June 2020 to December 2021 were reviewed. qRT-PCR was performed to measure the expression levels of miR-144-5p and miR-26b-5p in the plasma of patients with BC. The receiver operating characteristics (ROC) curve and area under the curve (AUC) were used to investigate the potential diagnostic value of miR- 144-5p, miR-26b-5p and the elastographic score in BC. Results: The ultrasonic elastography score(UES) was found to be significantly upregulated in BC compared with that in benign breast lesions, and the AUC, sensitivity and specificity were 0.809, 0.717 and 0.806 for distinguishing BC from benign breast lesions, respectively. miR-144-5p and miR-26b- 5p were found to be upregulated in the plasma of BC patients, and miR-144-5p+miR-26b-5p had 0.781 sensitivity and 0.780 specificity for the diagnosis of BC. Furthermore, we found that the diagnostic performance of miR-144-5p and miR-26b-5p combined with UES for BC had 0.913 sensitivity and 0.890 specificity. Conclusions: The combination of plasma miR-144-5p, miR-26b-5p and UES has a very high clinical application value for the early detection of BC.     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.     

滋肾育胎丸加减方预防ACA阳性者不良妊娠结局的效果及机制研究＊

目的 探讨滋肾育胎丸加减方预防抗磷脂抗体（ACA）阳性者不良妊娠结局的效果及机制研究。方法 选取2016年2月至2019年2月我院收治的89例ACA阳性，先兆性流产或有习惯性流产（RSA）史患者，将采用西医治疗的40例作为对照组，将采用西医联合滋肾育胎丸加减方治疗的49例作为观察组，比较两组中医证候疗效、中医证候积分、ACA-IgA、ACA-IgM、ACA-IgG、凝血指标［血小板聚集功能（PAF）、活化蛋白C（PC）、抗凝血酶（AT）、纤溶酶原激活抑制物-1（PAI-1）］、Th1/Th2细胞因子［干扰素γ（IFN-γ）、白介素-2（IL-2）、白介素-4（IL-4）、白介素-10（IL-10）］、妊娠结局、安全性。结果 治疗2周后检测ACA，观察组2例未降低，对照组11例未降低，观察组未降低患者占比低于对照组（P<0.05）；观察组总有效率100.00%高于对照组85.00%（P<0.05）；观察组治疗4周、7周后中医证候积分低于对照组（P<0.05）；观察组治疗4周、7周后ACA-IgA、ACA-IgM、ACA-IgG低于对照组（P<0.05）；观察组治疗4周、7周后PAF、PAI-1低于对照组，PC、AT高于对照组（P<0.05）；观察组治疗4周、7周后IFN-γ、IL-2低于对照组，IL-4、IL-10高于对照组（P<0.05）；观察组活产率95.92%高于对照组80.00%（P<0.05）；组间不良反应总发生率比较，差异无统计学意义（P>0.05）。结论 动态监测ACA对滋肾育胎丸加减方精准应用具有指导意义，指导滋肾育胎丸加减方通过调理脏腑、气血、经络功能，改善先兆性流产或有RSA史患者临床症状及凝血因子指标，降低ACA水平，并可改善患者免疫耐受功能，提高胎儿活产率，且安全性高。     

脑卒中患者急性应激障碍及影响因素研究

目的探讨脑卒中患者急性应激障碍发生现状及影响因素。方法采用斯坦福急性应激反应问卷对349例脑卒中住院患者进行调查。结果共163例(46.70%)患者发生急性应激障碍;Logistic回归分析结果显示,患者性格、是否存在偏瘫及是否吞咽功能障碍是脑卒中患者发生急性应激障碍的主要影响因素(P0.05,P0.01)。结论脑卒中患者急性应激障碍发生率较高,内向性格及存在偏瘫和吞咽功能障碍的患者更容易发生急性应激障碍。医护人员应及时为高危患者提供个体化治疗及预见性护理,防止脑卒中患者发生急性应激障碍。     

2013-2017年我国四种恶性肿瘤住院费用水平及结构变动度分析

背景　恶性肿瘤给家庭、社会带来了沉重的医疗、经济负担，极易导致部分家庭“因病致贫”或放弃治疗，目前相关研究多集中于单一病种、分散地域的研究，仍缺乏对于全国范围与多病种恶性肿瘤住院费用变化及结构构成的考量。目的　分析2013-2017年我国4种恶性肿瘤住院费用水平以及影响住院费用的主要项目和结构变动情况，为控制医疗费用上涨、深化新医改提供参考依据。方法　本研究数据来源于《2014中国卫生和计划生育统计年鉴》《2015中国卫生和计划生育统计年鉴》《2016中国卫生和计划生育统计年鉴》《2017中国卫生和计划生育统计年鉴》以及《2018中国卫生健康统计年鉴》，样本跨度为2013-2017年。统计“30种疾病人均住院费用”中的胃恶性肿瘤、肺恶性肿瘤、食管恶性肿瘤以及膀胱恶性肿瘤的数据，4种恶性肿瘤的人均住院费用包括药费、检查费、治疗费、手术费和手术材料费。2019年4-8月，采用结构变动度法分析我国2013-2017年4种恶性肿瘤的住院费用的结构变动情况〔结构变动值（VSV）、结构变动度（DSV）、结构变动贡献率〕。结果　2013-2017年，4种恶性肿瘤的人均住院费用逐年上升，其中胃恶性肿瘤的人均住院费用始终最高，且肺恶性肿瘤的人均住院费用上升幅度最大。2013-2017年，在4种恶性肿瘤住院各项费用的占比中，药费占比最高且总体逐年下降。从4种恶性肿瘤住院各项费用的实际变化来看，药费在2013-2014年有所上升，2014-2017年逐年下降；检查费在2013-2014年下降，2014-2017年缓慢上升；手术费与手术材料费在2013-2017年逐年上升。2013-2017年，在4种恶性肿瘤住院各项费用中均是药费的VSV最大；4种恶性肿瘤药费、检查费的VSV均呈负向变化，手术费和手术材料费的VSV均呈正向变化，治疗费的VSV增减均不明显。2013-2017年，4种恶性肿瘤住院费用的DSV从大到小依次为肺恶性肿瘤、胃恶性肿瘤、食管恶性肿瘤、膀胱恶性肿瘤。2013-2017年，4种恶性肿瘤住院各项费用中均是药费的结构变动贡献率最大，治疗费的结构变动贡献率最小；除药费外，胃恶性肿瘤、肺恶性肿瘤住院各项费用中均是手术材料费和手术费的结构变动贡献率次之，食管恶性肿瘤住院各项费用中手术费、检查费的结构变动贡献率次之，膀胱恶性肿瘤住院各项费用中检查费、手术材料费的结构变动贡献率次之。结论　2013-2017年我国4种恶性肿瘤手术费的结构变动贡献率虽然较为理想，但药费、治疗费仍是住院费用结构的重点调整对象；同时为有效降低恶性肿瘤的人均住院费用，应当加强控制手术材料费与检查费；而胃恶性肿瘤与肺恶性肿瘤患者的疾病经济负担严重，若要缓解应加强疾病的早期预防与住院费用管控。     

基于雨课堂的临床流行病学教学改革与实践

目的探讨雨课堂在临床流行病学教学中的作用和效果。方法采用随机对照法在本科阶段无流行病学学习经历的临床专业硕士研究生中,使用雨课堂线上课前预习及课后随堂练习的功能,用于评价雨课堂线上功能的辅助教学效果。结果应用雨课堂线上功能干预组与对照组在基线、阶段小测和末考卷面成绩均无统计学差异;但对于主动学习,雨课堂参与度较高的学生成绩提高明显。结论雨课堂有利于理论性较强课程的学习,但是仍不能忽略课堂教学师生互动过程。     

Optimal tracking control for non-zero-sum games of linear discrete-time systems via off-policy reinforcement learning

In this article, a model-free off-policy reinforcement learning algorithm is applied to address the optimal tracking problem based on multiplayer non-zero-sum games for discrete-time linear systems. In contrast to the traditional method and the policy iteration method for solving the optimal tracking problems, the proposed algorithm operates with the system data rather than the knowledge of the system dynamics. For performing the proposed algorithm, an auxiliary augmented system is constructed via assembling the original system and the reference trajectory while a discount factor is introduced into the performance indexes. It is analyzed that the solutions of the proposed algorithm converge to the Nash equilibrium and the result is not influenced by the probing noise. Two simulations are presented to verify the feasibility and effectiveness of the proposed algorithm.     

Investigation of Bimetallic Nickel Catalysts in Catalyst‐Transfer Polymerization of π‐Conjugated Polymers

A comparative study involving bimetallic nickel catalysts designed from disubstituted N,N,N′,N′‐tetra(diphenylphosphanylmethyl)benzene diamine bridging ligands is reported. Catalyst behavior is explored in the Kumada catalyst‐transfer polymerization (KCTP) using poly(3‐hexylthiophene) (P3HT) as the model system. The success of a controlled polymerization is monitored by analyzing monomer conversion, degree of polymerization, end‐group identity, and molecular weight distribution. The characterization of P3HT obtained from KCTP initiated with the bimetallic catalysts shows chain‐growth behavior; however, the presence of Br/Br end‐groups and broader molecular weight distribution reveals a reduced controlled polymerization compared to the commonly employed Ni(dppp)Cl₂. The observed increase in intermolecular chain transfer and termination processes in KCTP initiation with the bimetallic catalysts can be attributed to a weaker Ni(0)‐π‐aryl complex interaction, which is caused by increased steric crowding of the coordination sphere.