理冲汤加减联合TC 方案治疗晚期卵巢癌临床研究

目的:观察理冲汤加减联合紫杉醇+卡铂(TC)方案治疗晚期卵巢癌的临床疗效及对患者血液流变学指标、免疫功能及肿瘤标志物水平的影响。方法:选取96例卵巢癌晚期患者,按随机数字表法分为对照组和观察组各48例。对照组给予TC方案治疗,观察组在对照组基础上给予理冲汤加减治疗,21 d为1个疗程,2组均治疗2个疗程。统计2组治疗前后的中医证候积分及治疗期间不良反应发生情况,检测血液流变学指标、T细胞亚群及肿瘤标志物水平,对比2组临床疗效。结果:治疗后,2组少腹包块、腹胀痛、面色无华及形体消瘦积分均较治疗前降低(P0.05),观察组上述4项中医证候积分均低于对照组(P0.05)。观察组疾病控制率77.08%,高于对照组的56.25%(P0.05)。观察组治疗有效率54.17%,对照组治疗有效率41.67%,2组比较,差异无统计学意义(P0.05)。治疗后,2组血液流变学指标(全血黏度高切、全血黏度中切、全血黏度低切、血浆黏度)水平均较治疗前降低(P0.05),观察组上述4项血液流变学指标水平均低于对照组(P0.05)。治疗后,观察组CD3+、CD4+、CD4+/CD8+水平均高于对照组(P0.05),CD8+水平低于对照组(P0.05)。治疗后,2组糖类抗原125 (CA125)、糖类抗原19-9 (CA19-9)、甲胎蛋白(AFP)含量均较治疗前降低(P0.05),观察组CA125、CA19-9、AFP含量均低于对照组(P0.05)。观察组白细胞减少发生率6.25%,低于对照组的27.08%(P0.05)。2组贫血、血小板减少、恶心呕吐、腹泻发生率比较,差异均无统计学意义(P0.05)。结论:理冲汤加减联合TC方案治疗晚期卵巢癌,可以有效改善患者的临床症状、血液流变学指标、免疫功能,降低肿瘤标志物水平,减少化疗产生的不良反应。     

肿瘤相关巨噬细胞相关性miR-99a对子宫内膜癌细胞生长和侵袭的调控作用

背景与目的：肿瘤相关巨噬细胞（tumor-associated macrophage，TAM）浸润与肿瘤进展密切相关，但作用机制尚不明确，因此，探索miR-99a对单核巨噬细胞极化的影响及其对子宫内膜癌（endometrial cancer，EC）细胞生长、侵袭的影响。方法：检测EC组织中巨噬唾液酸蛋白（macrosialin）CD68表达并分析其与临床病理学特征之间的关系；运用人EC细胞系HEC-1B、RL95-2培养上清液诱导人单核细胞U937向TAM（M2型巨噬细胞）分化；将人工合成的miR-99a模拟物片段转染至诱导后的巨噬细胞，转染后运用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）及流式细胞术检测巨噬细胞相关因子CD68、CD163以及巨噬细胞甘露糖受体（mcrophage mannose receptor）CD206表达量变化，并运用酶联免疫吸附法（enzyme-linked immunosorbent assay，ELISA）检测巨噬细胞分泌相关细胞因子IL-12、IL-4和IL-10分泌量变化；将转染miR-99a的诱导后巨噬细胞与EC细胞共培养，运用细胞计数试剂盒（cell counting kit-8，CCK-8）和transwell法检测其对EC细胞增殖和侵袭能力的影响，并初步分析其可能的作用机制。结果：EC组织CD68高表达并与肿瘤肌层浸润及血管生成呈正相关；肿瘤细胞培养上清液成功诱导单核细胞向M2型TAM极化。转染miR-99a后单核细胞组CD68及CD163表达较对照组下降（P＜0.01），而CD206表达差异无统计学意义（P＞0.05），流式细胞术进一步证实上述表达变化；ELISA结果发现，转染miR-99a诱导后巨噬细胞中IL-12分泌增多（P＜0.01），而IL-4、IL-10分泌减少（P＜0.01），提示巨噬细胞向M2型极化受抑制。将诱导后巨噬细胞与EC细胞共培养，共培养后EC细胞增殖侵袭能力较对照组增加，而转染miR-99a模拟片段至诱导后巨噬细胞能够抑制其对增殖（P＜0.01）及侵袭能力的促进作用（P＜0.05）。诱导后巨噬细胞中过表达miR-99a后细胞中mTOR及其通路受到抑制。结论：EC间质巨噬细胞浸润与肿瘤肌层浸润及血管新生相关，miR-99a能够逆转单核细胞向M2表型极化，并抑制EC细胞介导TAM的促EC细胞生长和侵袭作用，其作用可能通过调控mTOR通路产生。     

医用粘胶相关性皮肤损伤的文献计量学分析

目的: 应用文献计量学方法,分析国内外医用粘胶相关性皮肤损伤（Medical adhesive-related skin injuries,MARSI）文献的研究主题和热点。方法: 检索Cochrane Library、PubMed、EMbase、Web of science、sinoMed、CNKI、Wanfang、VIP等数据库MARSI相关文献,检索时限为建库至2019年5月。采用SPSS 22.0 软件进行文献计量分析,利用gCLUTO统计对国内外高频主题词进行聚类分析。结果: 共纳入论文103篇,其中外文文献占总文献量的27.18%,中文文献占总文献量的72.82%。聚类分析将国内外高频主题词聚为4大类,依次为皮肤损伤及损伤类型、相关危险因素、风险评估及风险管理、护理干预措施。结论: MARSI仍是国内外研究的热点,其发病机制研究仍处于探索阶段,目前尚缺乏有效的预防策略,研究领域较局限。在今后的研究中,应加强MARSI预防的研究、注重多学科合作。     

【开放获取】男性肢端肥大症合并乳腺癌1例

患者男，64岁，因头颅增大、面部变长，颧骨隆起、下颌增大、双手掌肥厚、双手指粗短30余年，乳房肿物1年余就诊。患者30余年前无明显诱因出现渐进性手足增大，双手掌肥厚，嘴唇变厚，下颌增大，眉弓及颧骨突出，皮肤增厚，无乳腺增大、泌乳，未诊治……     

Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood–Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats

Brain edema is a vital contributor to early brain injury after subarachnoid hemorrhage (SAH), which is responsible for prolonged hospitalization and poor outcomes. Pharmacological therapeutic targets on edema formation have been the focus of research for decades. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to participate in neural development and brain injury. Here, we used PACAP knockout CRISPR to demonstrate that endogenous PACAP plays an endogenous neuroprotective role against brain edema formation after SAH in rats. The exogenous PACAP treatment provided both short- and long-term neurological benefits by preserving the function of the blood–brain barrier and glymphatic system after SAH. Pretreatment of inhibitors of PACAP receptors showed that the PACAP-involved anti-edema effect and neuroprotection after SAH was facilitated by the selective PACAP receptor (PAC1). Further administration of adenylyl cyclase (AC) inhibitor and sulfonylurea receptor 1 (SUR1) CRISPR activator suggested that the AC–cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA) axis participated in PACAP signaling after SAH, which inhibited the expression of edema-related proteins, SUR1 and aquaporin-4 (AQP4), through SUR1 phosphorylation. Thus, PACAP may serve as a potential clinical treatment to alleviate brain edema in patients with SAH.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00925-3) contains supplementary material, which is available to authorized users.Key Words: Subarachnoid hemorrhage, brain edema, pituitary adenylate cyclase-activating polypeptide, blood–brain barrier, glymphatic system     

GPER-mediated,oestrogen-dependent visceral hypersensitivity in stressed rats is associated with mast cell tryptase and histamine expression

Visceral hypersensitivity (VH) is common in irritable bowel syndrome (IBS), and female patients are more likely to seek healthcare services for IBS-related abdominal pain. Oestrogen has been reported to mediate pain modulation via its receptor, and mast cells are known to participate in the development of visceral hypersensitivity. Our previous studies showed that the G-protein-coupled oestrogen receptor (GPER, also known as GPR30) was expressed by mast cells in human colonic tissues and was associated with IBS type and severity of visceral pain. However, whether GPER is involved in oestrogen-dependent visceral hypersensitivity via mast cell degranulation is still unknown. Rats were subjected to wrap partial restraint stress to induce visceral hypersensitivity and were ovariectomized (OVX) to eliminate the effects of oestrogen on visceral hypersensitivity. OVX rats were treated with oestrogen, an oestrogen receptor α and β antagonist (ICI 182.780), a GPER antagonist (G15) or a GPER agonist (G1), to evaluate the effects of oestrogen via its receptor. The colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were performed to evaluate GPER and mast cell tryptase co-expression. Mast cell number with degranulation was detected by specific staining. Mast cell tryptase expression in rat colon was also investigated by Western blot and immunohistochemistry. Substance P and histamine expression were examined by ELISA. GPER was expressed by the majority of tryptase-positive mast cells in the colonic mucosa. Stressed rats showed increased visceral sensitivity, increased mast cell degranulation, mast cell tryptase expression, and increased colon histamine levels. Ovariectomy reduced stress-induced VH in female rats and decreased mast cell degranulation, mast cell tryptase expression, and histamine levels, whereas oestrogen replacement reversed these effects. In OVX rats, the GPER antagonist G15 counteracted the enhancing effects of oestrogen on stress-induced VH, mast cell degranulation, mast cell tryptase, and histamine expression, whereas VH was preserved after treatment with ICI 182.780. On the other hand, pretreatment with the selective GPER agonist G1 at doses between 1 and 20 μg/kg significantly increased VH, mast cell tryptase, and histamine expression in OVX-stressed rats, mimicking the effects of oestrogen. GPER plays a pivotal role in the regulation of mast cell degranulation, mast cell tryptase expression, and histamine levels and contributes to the development of colonic hypersensitivity in a female rat model of IBS.