热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

Characterization of membrane occupation and recognition nexus repeat containing 3, meiosis expressed gene 1 binding partner,in mouse male germ cells

Mammalian spermatogenesis is a well-organized process of cell development and differentiation. Meiosis expressed gene 1 (MEIG1) plays an essential role in the regulation of spermiogenesis. To explore potential mechanisms of MEIG1''s action, a yeast two-hybrid screen was conducted, and several potential binding partners were identified; one of them was membrane occupation and recognition nexus repeat containing 3 (MORN3). MORN3 mRNA is only abundant in mouse testis. In the testis, Morn3 mRNA is highly expressed in the spermiogenesis stage. Specific anti-MORN3 polyclonal antibody was generated against N-terminus of the full-length MORN3 protein, and MORN3 expression and localization was examined in vitro and in vivo. In transfected Chinese hamster ovary cells, the antibody specifically crossed-reacted the full-length MORN3 protein, and immunofluorescence staining revealed that MORN3 was localized throughout the cytoplasm. Among multiple mouse tissues, about 25 kDa protein, was identified only in the testis. The protein was highly expressed after day 20 of birth. Immunofluorescence staining on mixed testicular cells isolated from adult wild-type mice demonstrated that MORN3 was expressed in the acrosome in germ cells throughout spermiogenesis. The protein was also present in the manchette of elongating spermatids. The total MORN3 expression and acrosome localization were not changed in the Meig 1-deficient mice. However, its expression in manchette was dramatically reduced in the mutant mice. Our studies suggest that MORN3 is another regulator for spermatogenesis, probably together with MEIG1.     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

产前超声诊断胎儿右房异构一例

本文报道产前超声诊断胎儿右房异构一例。孕妇孕24周产前超声检查发现胎儿左位心合并复杂心血管畸形(右心室双出口、房室间隔缺损、肺动脉发育不良、双侧上腔静脉、心下型完全型肺静脉异位引流)、胃泡位于腹腔右侧、中位肝、可疑无脾、腹主动脉与下腔静脉位于脊柱左侧、双侧支气管呈右侧支气管对称形态,综合考虑右房异构可能。引产后经尸体解剖证实脾脏发育不良、右房异构。右房异构常合并复杂心血管畸形,因此产前超声发现复杂心血管畸形时,应警惕右房异构的可能。右房异构病死率极高,产前诊断具有重要意义。     

A mechanism for gratitude development in a child

Most scholars consider gratitude as a moral emotion, with only few seeing it as a character trait. As a result, no systematic mechanism has ever been attempted to develop gratitude in children. Given the social issue of widespread lack of gratitude in the one-child generations of China, this article attempts to outline a mechanism of parental moral education for gratitude development. The mechanism is underpinned by love, induction and discipline; and theoretically justified in accordance with key psychological and sociological theories, such as Piaget's theory of moral development, Kohlberg's moral stages theory, attachment theory, Hoffman's internalisation theory, Rest's social justice theory and Baumrind's parenting styles theory. The benefits and potential risks of each strategy of the mechanism are addressed.     

针刺辅助治疗难治性肠易激综合征临床试验方案关键点设计的思考＊

肠易激综合征（Irritable bowel syndrome，IBS）是临床常见病、多发病，其治疗方法丰富，但部分患者疗效欠佳，发展成难治性IBS。目前国内外关于针灸治疗难治性IBS的临床随机对照试验尚不多见。本文立足试验方案设计的“PICOS”原则，从研究对象及诊断标准、干预措施、对照措施、结局指标四个方面入手，重点探讨针刺辅助治疗难治性肠易激综合征临床试验设计的关键要点。从选择特色优势病种、明确诊断标准、制定符合临床实际的干预方案、运用符合目标的安慰针刺、结合研究设计和目的选定结局指标几个角度，阐述试验相关环节设计的原因和思考。