Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

以医院登记为基础的20万例恶性肿瘤患者生存报告

背景与目的：恶性肿瘤是全球重大的公共健康问题，患者生存率是评价恶性肿瘤诊治水平的重要指标。通过描述以医院登记为基础的20万例恶性肿瘤患者的生存情况，以真实世界数据从一个侧面反映我国恶性肿瘤的治疗效果。方法：纳入2008年1月1日—2017年12月31日之间在复旦大学附属肿瘤医院确诊为恶性肿瘤并接受住院治疗的患者共计202 542例。通过患者复诊病史资料、电话随访及死因数据链接等方式收集生存随访信息，随访统计时间截至2019年11月30日。应用寿命表法估计各个病种1年、3年和5年总生存率（overall survival，OS），以性别、年龄组、首次治疗时间分层。采用Kaplan-Meier生存曲线绘制各病种的总体生存曲线。结果：患者总体的1年、3年、5年OS分别为89.8%、77.4%和71.0%；男性患者5年OS为58.8%，女性患者为78.7%。在常见的恶性肿瘤中，甲状腺癌患者的5年OS最高，为98.6%；胰腺癌患者最低，为11.4%。2013—2017年首次治疗的乳腺癌、肺癌和肾癌患者5年OS分别为90.0%、55.9%和80.7%，显著高于2008—2012年首次治疗患者，其他肿瘤未见显著上升。结论：大部分恶性肿瘤患者经规范诊治可以获得较为理想的预后，女性生存情况显著优于男性，乳腺癌和肺癌患者的生存改善可能归功于新的临床治疗和早诊手段。     

新生儿高胆红素血症的临床治疗分析

目的探讨布拉氏酵母菌散治疗对新生儿高胆红素血症的临床疗效。方法在2018年1月—2019年1月期间,将医院诊治的110例新生儿高胆红素血症患儿纳入研究对象,按照治疗方法的不同,将患儿分成两组,采用常规蓝光照射治疗的患儿定为对照组,55例,在蓝光治疗基础上增加布拉氏酵母菌散治疗的患儿定为观察组,55例,对比两组患儿治疗的临床效果。结果观察组和对照组治疗的有效率分别为98.18%和87.27%,有统计学意义(P<0.05);治疗后3 d和1周,两组患儿的胆红素水平明显下降,且观察组患儿下降更加明显,与对照组相比差异有统计学意义(P<0.05);观察组患儿黄疸消退时间为(5.12±1.21)d,对照组患儿黄疸消退时间为(7.21±1.22)d,有统计学意义(P<0.05);观察组不良反应发生率为5.45%,明显低于对照组的12.73%,有统计学意义(P<0.05)。结论对新生儿高胆红素血症患儿在常规蓝光治疗的基础上增加布拉氏酵母菌散进行治疗,可以显著提高临床治疗效果。     

Family Caregivers' Subjective Caregiving Burden,Quality of Life,and Depressive Symptoms Are Associated With Terminally Ill Cancer Patients' Distinct Patterns of Conjoint Symptom Distress and Functional Impairment in Their Last Six Months of Life

Context

Family caregivers constitute a critical component of the end-of-life care system with considerable cost to themselves. However, the joint association of terminally ill cancer patients' symptom distress and functional impairment with caregivers' subjective caregiving burden, quality of life (QOL), and depressive symptoms remains unknown.

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.     

经皮电刺激联合导乐镇痛对分娩结局的影响及安全性分析

目的 探讨经皮电刺激联合导乐分娩镇痛对分娩结局的影响及安全性。方法 选择160例在我院住院待产的产妇作为研究对象,随机将其分为观察组与对照组,每组各80例;其中对照组予导乐分娩镇痛,观察组给予经皮电刺激联合导乐分娩镇痛。观察比较两组的VAS评分、产程时间、产后出血、剖宫产率、产妇满意度、新生儿情况、不良反应发生情况等。结果 与镇痛前比较,观察组镇痛后各时间段VAS评分降低,P＜0.05;与对照组比较,观察组的产后2 h出血量、剖宫产率降低,产妇满意度提高,P＜0.05。结论 经皮电刺激联合导乐镇痛可减轻产妇痛苦,降低剖宫产率,减少产后出血,提高产妇满意度,且无明显不良反应,值得在临床上推广应用。