蒙药绿松石的质量标准研究＊

目的 建立蒙药绿松石的质量标准。方法 收集不同产地绿松石，共10批。观察绿松石样品和粉末的性状并进行理化鉴别；按2020年版《中国药典》（四部）通则方法测定绿松石样品中水分、浸出物含量；采用原子吸收光谱法测定绿松石样品铜元素含量。结果 绿松石为不规则、周围带有黑石的块状物，表面蓝绿色，体重，质硬脆，难砸碎，断面呈贝壳状，蜡样光泽，粉末呈灰绿色，无臭，味淡；理化鉴别结果显示，呈铜盐反应；10批次样品中水分含量为0.41%-3.94%（SD=1.37%），浸出物含量为0.21%-0.81%（SD=0.21%），铜元素含量为3.03%-4.63%（SD=0.63%）。结论 初步拟定绿松石中水分含量不得超多5.0%、浸出物含量不得低于0.10%，铜元素含量应为2.60%-4.84%，制定的标准可用于蒙药材绿松石的质量控制。     

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.     

优克龙治疗输尿管结石(附60例报告)

目的　观察优克龙 (Urocalun )治疗输尿管结石的疗效和安全性。　方法　对 6 0例输尿管结石直径 <1cm的患者予口服优克龙治疗 ,4 5 0mg/次 ,3次 /d ,服药 5周。　结果　 6 0例患者中结石排出 4 5例 (75 % ) ;10例 (17% )结石位置下降 ;5例 (8% )位置无变化。 4例患者服药后有轻度胃部不适、恶心或口干。　结论　优克龙治疗输尿管结石效果良好。     

Behavioural, physiological and immunological consequences of social status and aggression in chronically coexisting resident-intruder dyads of male rats

The behavioural and physiological consequences of social status and reciprocal fighting in resident-intruder dyads of Long Evans male rats were evaluated. Before a chronic cohabitation of 10 days, residents and intruders were individually housed for one month to increase their aggressiveness. Control animals included isolates, i.e., animals kept individually housed throughout the experiment and pair-housed rats, i.e., pairs of rats housed together from their rats in the laboratory. In 19 out of 20 dyads, a clear dominance relationship developed with an advantage to the resident in 68% of the cases. Dominants showed more exploratory activity than subordinates in a open-field test at the end of the cohabitation period; subordinates groomed longer than animals from other experimental groups. Dominants had lower pain thresholds than individually and pair-housed animals. Both dominants and subordinates had higher tyrosine hydroxylase enzymatic activities in the left adrenal than isolated and pair-housed rats. Subordinates lost body weight and had higher plasma corticosteroid concentrations than animals from the other experimental groups. In addition, they had smaller thymus glands and reduced spleen lymphocyte responses to mitogenic stimulation in vitro, in comparison to dominant animals. These results show that subordination in the dyadic resident-intruder paradigm leads to a complex syndrome of behavioural and physiological changes, some of which may be modulated by the intensity of aggressive interactions.     

Protein components specifically associated with prespliceosome and spliceosome complexes.

We have carried out a systematic analysis of the protein composition of highly purified mammalian spliceosomes. We show that > 30 distinct proteins, including 20 previously unidentified components [designated spliceosome-associated proteins (SAPs)], are specifically associated with the spliceosome in a salt-resistant complex. In contrast to these spliceosome-specific proteins, we show that hnRNP proteins are not tightly associated with purified prespliceosome and spliceosome complexes. The splicing factor U2AF65, U1 snRNP-specific proteins, and several SAPs are present in the earliest prespliceosome complex (E). A set of 10 proteins is then added to the first ATP-dependent prespliceosome complex (A), and concomitantly, a significant decrease in the level of U2AF65 is observed. The fully assembled spliceosome is formed by the addition of 12 proteins in a reaction that requires ATP and both the 5' and 3' splice sites.     

彩色多普勒超声心动图与核磁共振诊断主动脉夹层动脉瘤的对比研究

目的　通过彩色多普勒超声心动图 (CDUCG)和核磁共振成像 (MRI)诊断主动脉夹层动脉瘤 (AD)的影像学特征 ,比较两种无创检查技术诊断AD的临床价值。方法　对临床疑诊AD的患者行CDUCG心脏各切面探查 ,重点扫查并测量主动脉各节段异常超声征象 (夹层发生部位、内膜片跨度、管径宽度等 ) ,对相同患者行MRI检查时在扫描图像上辨认并确定夹层发生的部位、撕裂范围等。结果　CDUCG诊断Ⅰ型AD 4例 ,Ⅱ型 2例 ,Ⅲ型AD 1例。MRI对Ⅰ、Ⅱ、Ⅲ型AD均可明确诊断。本文 3例Ⅲ型AD经MRI确诊并检出附壁血栓 2例 ,1例Ⅰ型AD可疑 ,余结果同CDUCG。结论　两种技术诊断AD各有优缺点 ,CDUCG偏重于诊断Ⅰ、Ⅱ型 ,MRI适合各型AD的诊断。前者更为迅速、直观 ,重复性强 ,可了解心血管病变的全部信息 ;危急重症患者不宜或难以接受MRI检查。     

T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

AIDS education in Switzerland: implementing strategies to reach groups with high risk behaviours, particularly youth

In Switzerland the Federal Office of Public Health has developeda comprehensive set of AIDS care and prevention policies andactivities in recent years. For their actual implementation,the main responsibility lies with the health departments ofthe 26 Cantons. This paper originates from one of the largeCantons, Vaud. Major efforts have been made from the Federallevel to transmit relevant AIDS-related information to the generalpublic. Much remains to be done to assist people, especiallyhigh risk groups, to translate the vital prevention messagesinto behaviour changes. For youth in general, new attitudestowards sexual relations are called for, different from thoseof young people 10 or 15 years ago. In Vaud, a number of entrypoints are used to pass on this education: physicians and nursesinvolved in school health, teachers and, among the latter, twogroups with specific in-service training and part-time functions—mediators(who make themselves available to children in various risk situations)and health animators (promoting the inclusion of health educationtopics in the teaching). There is a special health programmefor 16–19 year olds. Also a substantial tradition of sexualeducation sessions in the school system offers valuable opportunitiesfor AIDS education. Further, innovative strategies are developedto reach and work with the male homosexuals and, to the extentpossible, intravenous drug addicts. In conclusion it is emphasizedthat, in many ways, AIDS education issues demand courage fromhealth and public leaders.