非编码RNA(non-coding RNA,ncRNA)是一种调节生物学过程的因子,在肿瘤的生物学行为中起到重要的作用.NcRNA在肿瘤中可作为竞争内源性RNA及RNA结合蛋白发挥作用,并且可以参与细胞转录与翻译的调节.自噬作为一种自我吞噬多余内容物并产生新分子维持细胞稳态的过程,对卵巢癌具有双重作用,需深入探讨.NcRNA可以通过自噬相关蛋白及信号通路介导卵巢癌生物学行为的变化.同时自噬具有多种分类,本文主要聚焦于经典的巨自噬作用,综述了卵巢癌中 ncRNA(miRNA,lncRNA及circRNA)与自噬的串扰,有助于提供基于ncRNA与自噬的卵巢癌治疗策略.

"肝""脑""目"三者在生理及病理上相互联系,形成了"肝-脑-目"轴交互体系.其关系存在多向交互串扰,影响干眼的发生发展.应用脏腑辨证理论从生理和病理两个层面对"肝-脑-目"轴的内涵进行阐述,并提出"肝-脑-目"轴的 3 种失衡状态及其与干眼发病的关系,且肝、肾与目的关系为"肝-脑-目"轴理论之关键.提出清肝疏肝以畅"肝-脑-目"轴、益精生髓以充"肝-脑-目"轴、补肝肾阴以理"肝-脑-目"轴的中医药治疗干眼思路,以期为临床治疗干眼提供参考.

Introduction::Basal cell carcinoma (BCC) is the most common skin cancer which mainly affects the population over 50 years of age. In addition to surgical treatment, nonsurgical treatment is also an attractive option for some patients.Case presentation::An 82-year-old man presented with BCC on his left nose wing more than 2 years ago. Due to his unwillingness to accept treatment that may lead to pain, discomfort, or trauma, the patient was prescribed oral acitretin 25 mg twice daily [0.8 mg/(kg·d)] and was instructed to apply 2% fusidic acid cream topically once daily for trauma protection. The lesion progressively shrank in size after 4 weeks of treatment, and was almost completely resolved after 28 weeks of follow-up. The patient reported mild adverse effects, such as mild skin fragility and cheilitis, and apparent scaling skin, which caused minor discomfort but did not affect the continuation of treatment.Discussion::The pathogenesis of BCC is still unclear, but it has been demonstrated to be linked to overactive hedgehog signaling and its crosstalk with other pathways such as phosphoinositide 3-kinase and mammalian target of rapamycin. Acitretin could obviously inhibit cell growth and proliferation and down-regulate AMP-dependent protein kinases that plays critical role in the blocking of malignant progression of several tumors including BCC.Conclusion::We provide an effective alternative for the patients with BCC who are unwilling to receive surgical therapy.

侵袭和转移是乳腺癌死亡的主要原因，上皮-间质转化(EMT)可通过促进肿瘤恶性、重编程肿瘤代谢等方式诱导肿瘤转移。而有氧糖酵解作为糖代谢的重要组成部分，不仅为肿瘤细胞快速生长提供充足的能量，还通过促进肿瘤的EMT过程为肿瘤细胞提供转移优势。此外，有氧糖酵解与EMT之间的串扰网络可协同触发肿瘤转移。因此，异常的葡萄糖代谢与EMT在乳腺癌转移的发生、发展中起着关键作用，提示其在乳腺癌转移治疗中的临床应用前景。

Hippo信号通路在进化上高度保守，参与调节细胞增殖、分化和组织动态平衡，在调控组织、器官大小及细胞数量方面发挥重要作用。常染色体显性多囊肾病（autosomal dominant polycystic kidney disease，ADPKD）是最常见的遗传性肾病，也是引起终末期肾病最常见的病因之一。近年的研究发现，Hippo信号通路与ADPKD的发生发展密切相关，通路主要成员的活性和表达异常对肾小管上皮细胞的纤毛和细胞极性等产生影响，诱发肾囊肿的形成。该综述总结了Hippo信号通路在ADPKD发病中的潜在机制，与其他信号通路的串扰，以及在不同物种中的差异，讨论针对Hippo信号通路治疗ADPKD的策略，以期为ADPKD的治疗提供新的思路。

Objective::The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus. The interaction between decidual γδ T cells and trophoblasts plays a pivotal role during successful pregnancy; however, their physiological functions in early-term human pregnancy are still not completely illustrated. This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidual γδ T cells and HTR8/SVneo trophoblast cells.Methods::The percentile of CXCR6 + γδ T cells in the peripheral blood from normal female and recurrent spontaneous abortion (RSA) patients was analyzed by flow cytometry. The expression of CXCR6 was detected in decidual immune cells via flow cytometry, and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus (LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells. Expression of granzyme B and cytokines and proliferation of decidual γδ T cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry. Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay. Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss. Results::The percentile of CXCR6 + γδ T cells in the peripheral blood from RSA patients was lower than normal pregnancies. The expression of CXCR6 was highest in the decidual γδ T cells among decidual immune cells, and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased. Expression of granzyme B in the decidual γδ T cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16, and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidual γδ T cells. Both the expression of CXCR6 in the decidual γδ T cells and proliferation of the decidual γδ T cells were promoted by HTR8/SVneo trophoblast cells. On the other hand, decidual γδ T cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation. In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidual γδ T cells and trophoblasts. Conclusions::Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidual γδ T cells and trophoblasts, and it showed a light on the effective strategy of adoptive transfer of CXCR6 + γδ T cells on the treatment of RSA. This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.

Background::Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys.Methods::In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining.Results::15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47, RASSF4, EBAG9, IER3, SASH1, SEPTIN7, and NUB1, which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL) -12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. Conclusion::Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.

外泌体(exos)作为一种直径在40～150 nm之间的细胞外囊泡，在介导细胞间通讯中扮演着重要角色。新的证据表明，肿瘤细胞分泌的exos(TEXs)可通过传递微小RNAs对肿瘤微环境中的免疫细胞进行驯化，使其处于免疫抑制状态，从而为肿瘤的生长、进展和转移提供有利支持。本综述旨在对TEXs微小RNAs在介导肿瘤免疫抑制中的研究进展进行总结，从而为深入理解肿瘤微环境中TEXs介导的肿瘤细胞和免疫细胞的"crosstalk"提供参考。

Background::Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.Methods::In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-β (TGF-β), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student’s t test or analysis of variance were used for statistical analysis. Results::In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ± 0.02 vs. 0.07 ± 0.02, t = 8.66, P = 0.001), TGF-β (0.54 ± 0.05 vs. 0.09 ± 0.06, t= 10.00, P < 0.001), p-Smad2/3 (0.58 ± 0.06 vs. 0.07 ± 0.03, t= 12.86, P < 0.001) and α-collagen I (0.27 ± 0.02 vs. 0.16 ± 0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ± 7.32 vs. 9.56 ± 1.68, t= 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ± 0.15 vs. 1.00 ± 0.10, t = 4.32, P = 0.012), AT1R (4.05 ± 0.64 vs. 1.00 ± 0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ± 0.36 vs. 1.00 ± 0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production. Conclusions::Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.

目的:研究皮肤黑素瘤细胞与血管内皮细胞间VEGF-IL-6-STAT3信号交互作用机制。方法:将血管内皮细胞EC-304分成3组：对照组，常规培养；血管内皮生长因子（VEGF）组，在含VEGF 165（50 μg/L）的内皮细胞培养基中培养；A375共培养组，与黑素瘤细胞A375共培养。24 h、48 h、72 h后收集培养液，酶联免疫吸附实验检测白细胞介素6（IL-6）的分泌量。将A375细胞分为4组：对照组，常规培养；A375+ EC-304组，与EC-304共培养；A375+ EC-304+ IL-6组：与EC-304细胞在含STAT3通路激动剂IL-6（50 μg/L）的DMEM中共培养；A375+ EC-304+ JSI-124组：与EC-304在含STAT3通路抑制剂JSI-124（1 μmol/L）的DMEM中共培养。分别在24 h、48 h、72 h后收集细胞，用Western印迹、CCK-8、Transwell侵袭实验分别检测STAT3、p-STAT3蛋白表达、细胞增殖活性及侵袭活性。采用双因素方差分析及 t检验统计分析数据。 结果:与对照组比较，VEGF组、A375共培养组EC-304培养基中IL-6分泌量均升高（ FVEGF = 29.63， P < 0.001； FA375 = 11.09， P = 0.020）。与对照组比较，A375+ EC-304组A375细胞p-STAT3蛋白表达升高（ P < 0.001），细胞活性增强（ P < 0.001），侵袭细胞数从（86.13 ± 7.24）个增加到（152.66 ± 16.04）个（ t= 4.43， P < 0.001）；与A375+ EC-304组比较，A375+ EC-304+ IL-6组细胞p-STAT3蛋白表达升高（ P < 0.001），细胞活性增强（ P < 0.001），侵袭细胞数量增加至（187.34 ± 14.38）个（ t= 2.17， P < 0.001）；与A375+ EC-304组比较，A375+ EC-304+ JSI-124组细胞的p-STAT3蛋白表达降低（ P < 0.001），细胞活性减弱（ P < 0.001），侵袭细胞数减少至（124.92 ± 8.72）个（ t=-1.86， P < 0.001）。 结论:皮肤黑素瘤A375细胞与血管内皮细胞之间存在VEGF-IL-6-STAT3信号交互作用机制，这种机制可促进A375细胞的增殖和侵袭。