外泌体长链非编码RNA在急性心肌梗死中的研究进展

外泌体是细胞间通讯的方式,而长链非编码RNA(lncRNA)作为外泌体内的信息载体,近年来有多项研究报道其参与了包括急性心肌梗死在内的多种心血管疾病。本文对外泌体lncRNA在急性心肌梗死领域中的相关研究进行综述,总结外泌体lncRNA发挥的调节作用,分析外泌体lncRNA作为心肌梗死标志物和治疗策略的研究现状,并通过公共数据库中的测序信息,筛选具有潜力的生物标志物。     

肝癌外泌体源性miRNA表达及其临床价值

肝细胞癌(HCC)早期诊断和有效治疗,仍然是困扰医学界的难题。外泌体是直径为40~100 nm的微小囊泡,内含蛋白质、脂质和核酸,作为信息物质交换的转运载体,在调控生物分子功能、维持细胞内环境中起重要作用。HCC外泌体功能包括胞间信息交换、新血管生成、癌细胞转移与多药耐药等,可介导微小RNA(miRNA)转化以调控肿瘤进展的微环境,进而影响癌细胞的病理生理学行为。外泌体源性miRNA可用于HCC监测或为早期诊断潜在特异标志物,且可作为HCC治疗靶目标,具有开发应用前景。现综述HCC外泌体源性miRNA研究的新进展。     

长链非编码RNA在肝细胞癌发生中的作用及其应用

肝细胞癌(HCC)是一种常见的恶性肿瘤,其起病隐匿,早期诊断困难,目前缺乏有效的治疗方法,且患者的5年生存率较低,复发率较高。近年来研究发现,部分长链非编码RNA(lncRNA)在HCC中异常表达,且表达水平与患者的预后相关。这些lncRNA可通过调控表观遗传、作为竞争性内源RNA以及参与肿瘤细胞上皮间质转化等多种机制,促进或抑制HCC的发生发展,可能成为新型HCC诊断标志物及治疗靶点。该文就lncRNA在HCC的发病机制、诊断及治疗方面的研究进展作一综述。     

外泌体在慢性乙型肝炎和HBV相关肝细胞癌发生发展中的作用机制

外泌体是由细胞内多囊泡体形成,携带脂质、蛋白质、编码和非编码RNA以及线粒体DNA等多种生物大分子,在体内可由包括肝细胞、肝星状细胞和免疫细胞在内的不同细胞类型释放,起着细胞间通讯的作用。越来越多研究表明,外泌体参与了HBV感染导致的慢性乙型肝炎(CHB)及肝细胞癌(HCC)的发生、发展及转归,有望成为HBV感染相关性HCC的早期诊断及预后评估的潜在生物学标志物。本文综述了外泌体在HBV感染宿主过程中的作用及其在CHB和HCC的发生、发展及预后中的重要性,以期为该领域的基础和临床研究提供新思路。     

相关肿瘤标记物在早期肝细胞癌诊断中的应用研究进展

肝细胞癌（HCC）是最常见的恶性肿瘤之一。HCC的早期诊断较困难。早期HCC缺乏典型症状及影像学表现，肿瘤标志物对HCC的诊断效能较高。临床常用的标志物如甲胎蛋白、甲胎蛋白异质体、脱-γ-羧基凝血酶原、高尔基体蛋白73等诊断早期HCC的灵敏度较低但目前临床应用最广泛。外泌体来源的微小RNA、长链非编码RNA及环状RNA等潜在新型肿瘤标记物，诊断早期HCC的灵敏度、特异度均较高。此外，基于相关肿瘤标记物及算法得到的GALAD和APAC综合评分模型可能进一步提高早期HCC的检出率。     

动脉粥样硬化相关循环血长链非编码RNA研究进展

动脉粥样硬化(As)是最常见的心脑血管疾病病变,严重影响着现代社会人类的身体健康。在As复杂的病理变化过程中寻找潜在的生物标记物,对于预防和治疗As疾病的发生和发展有着重要意义。研究表明长链非编码RNA(lncRNA)能够广泛参与到多种细胞活性的调控过程中,在As发生发展的不同阶段发挥作用。lncRNA可经由外泌体、微囊泡以及凋亡小体的包被,分泌至胞外后,进入循环系统。近些年,陆续有关于循环血lncRNA与As发生发展相关性的研究,血液中的lncRNA有望成为监测As病情进展的新型非介入诊断标记物。     

长链非编码RNA MALAT1在肝细胞癌发生发展中的作用

肝细胞癌(HCC)具有发病率高、生存率低、治疗效果不良、发病机制复杂等特点。近年来,多项研究证实lncRNA MALAT1在HCC中表达上调,具有促进HCC细胞增殖、侵袭和转移的作用,并且在HCC的诊断、预后及治疗方面具有临床指导意义。总结了lncRNA MALAT1在HCC中的研究现状,探讨其表达模式、作用机制以及在预测和监测HCC发展中的临床意义,以期深入了解lncRNA MALAT1在介导HCC发展中的作用。lncRNA MALAT1将有望成为HCC诊断和预后的潜在生物标志物,并在将来应用于临床靶点治疗。     

肝细胞癌早期诊断中的生物标志物

晚期肝细胞癌(HCC)患者预后通常较差,如若能早期诊断,并采取行之有效的治疗措施则可显著提高患者生存率。目前,AFP是检测HCC应用最广泛的血清标志物。然而,在一些HCC患者中并未发现AFP的升高。分析了AFP、乙型肝炎核心相关抗原、液体活检技术、微小RNA、长链非编码RNA及外泌体在HCC早期诊断中的应用潜力,通过探讨其研究进展,为HCC早期诊断方法的探索提供依据。     

基于网络铁死亡相关的长非编码RNA预测肝细胞癌患者预后研究*

目的 探讨构建基于铁死亡相关长链非编码RNA(lncRNA)的预后风险模型预测肝细胞癌(HCC)患者预后的价值。方法 自癌症基因组图谱TCGA数据库下载HCC患者RNA测序数据。基于HCC差异水平的铁死亡相关lncRNAs构建预后风险模型。结果 鉴定了5个基于HCC差异水平的铁死亡相关lncRNAs;Kaplan-Meier分析显示,高风险lncRNAs与HCC预后不良相关,预测3 a生存率的ROC曲线下面积(AUC)为0.873;单样本基因集富集分析(ssGSEA)发现低风险组与高风险组细胞溶解活性、MHCI类分子、I型INF反应、II型INF反应存在显著性差异(P<0.05);免疫检查点显示,两组CD44、TNFRSF4和CD276等水平也存在显著性差异(P<0.05)。结论 通过生物信息学方法筛选出5个基于HCC差异水平的铁死亡相关lncRNAs构建的预后风险模型为HCC防治研究奠定了一定的基础。     

外泌体在肝细胞癌发生进展及诊断治疗中的作用

外泌体是一种介导细胞间信息交流的功能载体,通过传递功能活性物质(如蛋白质、脂质、RNA分子、循环DNA等)在细胞间发挥作用,主要集中在免疫监测和肿瘤发生进展中方面.最近,越来越多的研究关注于外泌体在肝细胞癌(hepatocellular carcinoma,HCC)中的作用,除了诊断HCC外,还与发生和发展的机制包括血管生成和免疫逃逸等密切相关.因此,我对外泌体在HCC发生发展、诊断和治疗中的最新实验和临床研究数据做一综述.外泌体通过调节肿瘤微环境的耐受状态来调节免疫反应和肿瘤抑制,说明其在治疗HCC中具有作为靶点和药物载体的实用性和潜在可行性.未来将进一步阐明外泌体作为肝癌患者筛查、诊断和治疗靶点的确切作用和可靠性.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.