A Multi-Scale DNN Algorithm for Nonlinear Elliptic Equations with Multiple Scales

Algorithms based on deep neural networks (DNNs) have attracted increasing attention from the scientific computing community. DNN based algorithms are easy to implement, natural for nonlinear problems, and have shown great potential to overcome the curse of dimensionality. In this work, we utilize the multi-scale DNN-based algorithm (MscaleDNN) proposed by Liu, Cai and Xu (2020) to solve multi-scale elliptic problems with possible nonlinearity, for example, the p-Laplacian problem. We improve the MscaleDNN algorithm by a smooth and localized activation function. Several numerical examples of multi-scale elliptic problems with separable or non-separable scales in low-dimensional and high-dimensional Euclidean spaces are used to demonstrate the effectiveness and accuracy of the MscaleDNN numerical scheme.     

嘉兴市新居民儿童心理发育行为问题及影响因素分析

目的调查嘉兴市新居民儿童心理发育行为问题及影响因素，为改善新居民儿童心理健康提供理论依据。方法随机抽取新居民儿童548例，本地儿童1248例，采用自编量表评估儿童家庭影响因素，长处与困难问卷评估儿童心理发育行为问题，心理痛苦温度计评估主观心理痛苦程度，儿童心理虐待与忽视量表评估家庭教养方式，社会支持量表评估社会支持程度。结果新居民儿童主观评定心理痛苦程度高于本地儿童（P=0.002）。新居民儿童亲社会化行为低于本地儿童（P=0.000），多动/注意缺陷问题高于本地儿童（P=0.011）。儿童忽视虐待量表本地儿童5个因子得分低于新居民儿童：责骂因子（P=0.000）、恐吓因子（P=0.000）、情感忽视因子（P=0.000）、教育忽视因子（P=0.000）、身体忽视因子（P=0.000）。社会支持量表本地儿童3个因子得分均高于新居民儿童：客观支持（P=0.032）、主观支持（P=0.000）、对支持的利用度（P=0.000）。新居民儿童在新居民儿童学校、混合学校、本地儿童学校的3类学校中亲社会化行为、忽视因子、虐待因子、社会支持均有统计学差异（均P＜0.05）。结论新居民儿童较本地儿童心理发育行为明显落后，良好的家庭教养方式和有效的社会支持系统能够更快更好地促进其身心发育。     

Ki-67表达与原发性肝癌根治性切除术后行预防性肝动脉化疗栓塞患者预后的关系

目的:探讨Ki-67表达与原发性肝癌根治性切除术后行预防性TACE患者预后的关系。方法:采用回顾性队列研究,收集2014年12月—2016年1月福建医科大学孟超肝胆医院150例行原发性肝癌根治性切除术并在术后2个月内行预防性TACE患者的临床病理资料,根据术后肝癌组织病理Ki-67评分分为为低表达组(Ki-67评分≤20%,44例)和高表达组(Ki-67评分20%,106例);分析Ki-67表达量与患者临床病理因素及复发与生存的关系。结果:高表达组肿瘤多发、肿瘤包膜不完整及合并微血管癌栓患者比例明显高于低表达组(均P0.05)。Ki-67高表达与肿瘤多发、肿瘤直径大为影响无瘤生存期的独立危险因素(均P0.05);Ki-67高表达与肿瘤多发、肿瘤直径大、肿瘤包膜不完整、合并微血管癌栓为影响总生存期的独立危险因素(均P0.05);高表达组患者复发率明显高于低表达组(57.9%vs. 37.7%,χ~2=6.777,P0.05),总生存率明显低于低表达组(45.6%vs. 75.9%,χ~2=8.447,P0.05)。结论:Ki-67的表达量对肝癌根治性切除术后行预防性TACE患者的预后有显著影响,高表达者预后不良。     

健脾温肾软坚解毒方、康艾注射液联合低剂量化疗治疗老年脾肾两虚型晚期非小细胞肺癌的临床研究

目的观察健脾温肾软坚解毒方、康艾注射液联合低剂量化疗对老年脾肾两虚型晚期非小细胞肺癌患者瘤灶、免疫功能及无进展生存期的影响。方法将80例老年脾肾两虚型晚期非小细胞肺癌患者随机分为治疗组和对照组,每组40例。对照组予常规剂量化疗,治疗组予健脾温肾软坚解毒方、康艾注射液联合低剂量化疗。化疗2个周期后,观察两组患者瘤灶、免疫功能的变化情况,随访患者的无进展生存期。结果①试验期间,对照组脱落2例,试验组无脱落,最终完成试验者78例,其中治疗组40例,对照组38例。②两组实体瘤疗效比较,差异无统计学意义(P0.05)。③化疗1个周期与化疗前组内比较,两组血清NK、CD3~+、CD4~+、CD8~+水平差异无统计学意义(P0.05);化疗2个周期与化疗前组内比较,治疗组血清CD8~+水平升高(P0.05),对照组血清NK、CD3~+、CD4~+水平降低(P0.05)。化疗1个周期后组间比较,治疗组血清CD3~+、CD4~+水平高于对照组(P0.05);化疗2个周期后组间比较,治疗组血清NK、CD3~+、CD4~+水平高于对照组(P0.05)。④两组患者中位无进展生存时间均为4.5个月,差异无统计学意义(P0.05)。结论健脾温肾软坚解毒方、康艾注射液联合低剂量化疗能有效控制老年肺肾两虚型晚期非小细胞肺癌患者的瘤灶变化,并有利于稳定血清NK、CD3~+和CD4~+水平,保护患者的免疫功能。     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit skeletal muscle growth (for review, see ref. 1). Mice lacking MSTN exhibit dramatic increases in muscle mass throughout the body, with individual muscles growing to about twice the normal size (2). MSTN appears to play two distinct roles in regulating muscle size, one to regulate the number of muscle fibers that are formed during development and a second to regulate the growth of those fibers postnatally. The sequence of MSTN has been highly conserved through evolution, with the mature MSTN peptide being identical in species as divergent as humans and turkeys (3). The function of MSTN has also been conserved, and targeted or naturally occurring mutations in MSTN have been shown to cause increased muscling in numerous species, including cattle (3–5), sheep (6), dogs (7), rabbits (8), rats (9), swine (10), goats (11), and humans (12). Numerous pharmaceutical and biotechnology companies have developed biologic agents capable of blocking MSTN activity, and these have been tested in clinical trials for a wide range of indications, including Duchenne and facioscapulohumeral muscular dystrophy, inclusion body myositis, muscle atrophy following falls and hip fracture surgery, age-related sarcopenia, Charcot–Marie–Tooth disease, and cachexia due to chronic obstructive pulmonary disease, end-stage kidney disease, and cancer.The finding that certain inhibitors of MSTN signaling can increase muscle mass even in Mstn^−/− mice revealed that the function of MSTN as a negative regulator of muscle mass is partially redundant with at least one other TGF-β family member (13, 14), and subsequent studies have identified activin A as one of these cooperating ligands (15, 16). MSTN and activin A share many key regulatory and signaling components. For example, the activities of both MSTN and activin A can be modulated extracellularly by naturally occurring inhibitory binding proteins, including follistatin (17, 18) and the follistatin-related protein, FSTL-3 or FLRG (19, 20). Moreover, MSTN and activin A also appear to share receptor components. Based on in vitro studies, MSTN is capable of binding initially to the activin type II receptors, ACVR2 and ACVR2B (also called ActRIIA and ActRIIB) (18) followed by engagement of the type I receptors, ALK4 and ALK5 (21). In previous studies, we presented genetic evidence supporting a role for both ACVR2 and ACVR2B in mediating MSTN signaling and regulating muscle mass in vivo. Specifically, we showed that mice expressing a truncated, dominant-negative form of ACVR2B in skeletal muscle (18) or carrying deletion mutations in Acvr2 and/or Acvr2b (13) have significantly increased muscle mass. One limitation of the latter study, however, was that we could not examine the consequence of complete loss of both receptors using the deletion alleles, as double homozygous mutants die early during embryogenesis (22). Moreover, the roles that the two type I receptors, ALK4 and ALK5, play in regulating MSTN and activin A signaling in muscle in vivo have not yet been documented using genetic approaches. Here, we present the results of studies in which we used floxed alleles for each of the type II and type I receptor genes in order to target these receptors alone and in combination in muscle fibers. We show that these receptors are functionally redundant and that signaling through each of these receptors contributes to the overall control of muscle mass.     

煮炸鹿茸加工过程中晚期糖基化终产物生成规律及动力学分析

目的研究煮炸鹿茸加工过程中晚期糖基化终产物的生成规律及动力学参数。方法通过构建葡萄糖与赖氨酸模拟煮炸鹿茸加工过程美拉德(Maillard)反应体系,分别采用紫外-可见分光光度法和UPLC-MS/MS法测定体系褐变指数和典型晚期糖基化终产物(羧甲基赖氨酸和羧乙基赖氨酸)含量变化,探讨晚期糖基化终产物的生成规律和动力学参数。结果鹿茸加工过程中煮炸时发生褐变反应,生成羧甲基赖氨酸和羧乙基赖氨酸反应的活化能分别为5.07、40.44、78.47 kJ/mol,且均为零级反应;烘烤时相应反应的活化能分别为6.72、89.34、164.77 kJ/mol,也均为零级反应。相对于生成羧甲基赖氨酸而言,生成羧乙基赖氨酸所需能量更高,反应更难发生。结论烘烤过程温度变化对晚期糖基化终产物的动力学参数影响显著高于煮炸过程,长时间较高温度的烘烤使鹿茸中产生了较多的晚期糖基化终产物,这些结果为鹿茸加工过程中晚期糖基化终产物的阻断、抑制策略提供了理论基础,对生产绿色安全的鹿茸及加强中药安全具有重要意义。     

新型冠状病毒肺炎疫情期间肺癌患者的应对措施

新型冠状病毒肺炎(COVID-19)是近段时间我国面临的重大公卫事件，我国是肺癌大国，为了加强肺癌患者对这一疾病的认识，在疫情期间，使广大肺癌患者做好自身疾病的管理，做好对新型冠状病毒肺炎的预防。本文结合肺癌患者自身特点，对新型冠状病毒肺炎的易感性、鉴别诊断、防护、治疗，以及肺癌患者的随访、抗肿瘤用药、营养、手术等方面进行探讨，并结合两者的关系综合归纳，可以为广大肺癌患者更好地应对疫情提供参考。