瑞芬太尼靶控输注对宫颈癌根治术患者麻醉苏醒质量、应激反应及Th1/Th2免疫平衡的影响

摘要 目的：观察瑞芬太尼靶控输注对宫颈癌根治术患者麻醉苏醒质量、应激反应及辅助T细胞（Th）1/Th2免疫平衡的影响。方法：按照随机数字表法将2023年1月到2023年6月期间我院接受的120例宫颈癌根治术患者分为舒芬太尼组（n=60,舒芬太尼麻醉）和瑞芬太尼组（n=60,瑞芬太尼麻醉）。对比两组的麻醉苏醒质量、应激反应指标[皮质醇（Cor）、去甲肾上腺素（NE）、血管紧张素1（Ang-1）、血管紧张素2（Ang-2）]、Th1/Th2免疫平衡指标[包括Th1、Th2及调节性T细胞（Treg）、Th1/Th2比值],术后记录不良反应发生情况。结果：与舒芬太尼组相比,瑞芬太尼组的应激呼吸恢复时间、睁眼时间、拔管时间更短（P<0.05）。术后1 d,两组Cor、NE、Ang-1、Ang-2升高,但瑞芬太尼组低于舒芬太尼组（P<0.05）。术后1 d,两组Th1、Treg、Th1/Th2升高,但瑞芬太尼组低于舒芬太尼组;Th2下降,但瑞芬太尼组高于舒芬太尼组（P<0.05）。两组不良反应发生率组间对比未见差异（P>0.05）。结论：瑞芬太尼靶控输注用于宫颈癌根治术患者,可改善麻醉苏醒质量,减轻应激反应,调节Th1/Th2免疫平衡,且不增加不良反应的发生率,效果较好。     

下调miR-223表达对脓毒症心肌病小鼠心肌的保护作用及机制研究

摘要 目的：探讨下调miR-223表达对脓毒症心肌病（SCM）小鼠心肌的保护作用及其机制。方法：按随机数字表法将27只8-10 周龄SPF级雄性C57BL/6小鼠分配至SCM模型（0 h,6 h,12 h,18 h,24 h）时相组、Normal组、SCM组、miR-223 antagomir NC组、miR-223 antagomir组,每组3只。腹腔注射脂多糖（lipopolysaccharide, LPS）15 mg/kg构建SCM小鼠模型。miR-223 antagomir NC组与miR-223 antagomir组分别于建模前连续3天鼠尾静脉注射miR-223 antagomir NC、miR-223 antagomir预处理。采用反转录-聚合酶链反应（RT-PCR）研究SCM模型各个时相组小鼠心肌组织miR-223的表达情况。采用苏木素伊红（HE）染色法观察Normal组、SCM组、miR-223 antagomir NC组和miR-223 antagomir组小鼠心肌病理形态变化。采用酶联免疫吸附实验（ELISA）测定Normal组、SCM组、miR-223 antagomir NC组和miR-223 antagomir组小鼠血清cTnI、BNP、CK-MB、IL-6、IL-1β、TNF-α的含量并进行相关性分析。结果：SCM模型时相组小鼠随刺激时间延长,心肌组织miR-223表达水平逐渐升高。与Normal组比较,SCM组、miR-223 antagomir NC组、miR-223 antagomir组小鼠心肌组织出现不同程度损伤;血清心肌损伤标记物cTnI、BNP、CK-MB及炎性因子IL-6、IL-1β、TNF-α的表达水平均上升,差异具有统计学意义（P<0.05）;与SCM组比较,miR-223 antagomir NC组各项指标相差不大,差异均无统计学意义（P>0.05）;miR-223 antagomir组小鼠心肌组织病理损伤程度有所减轻,心肌损伤标记物cTnI、BNP、CK-MB及炎性因子IL-6、IL-1β、TNF-α水平下降,差异具有统计学意义（P<0.05）。相关性分析结果显示小鼠miR-223表达与心肌损伤标记物cTnI、BNP、CK-MB及炎性因子IL-6、IL-1β、TNF-α的表达呈正相关。结论：下调miR-223表达可通过减轻炎症反应对SCM小鼠心肌产生保护作用。     

小剂量糖皮质激素联合持续性血液净化治疗儿童严重脓毒症的效果及安全性研究

摘要 目的：分析小剂量糖皮质激素联合持续性血液净化治疗儿童严重脓毒症的效果及安全性。方法：选择自2021年1月至2023年1月接诊的102例儿童严重脓毒症患儿作为研究对象,随机分为对照组和观察组,各51例;对照组予以经典治疗方案,观察组在对照组的基础上,予以小剂量糖皮质激素联合持续性血液净化治疗;记录两组治疗后各项信息,比较两组治疗前后外周血乳酸、中心静脉血氧饱和度（ScvO₂）、血清炎症指标、PCIS评分、APACHE Ⅱ评分,观察主要并发症发生情况。结果：与对照组相比,观察组机械通气、低血压持续及入住ICU等时间较短,7 d内停升压药率较高（P＜0.05）;两组28 d病死率比较无差异（P＞0.05）;观察组治疗后乳酸、降钙素原（PCT）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）水平均较对照组低,ScvO₂水平较对照组高（P＜0.05）;观察组治疗后PCIS评分较对照组高,APACHE Ⅱ评分较对照组低（P＜0.05）;观察组主要并发症发生率低于对照组（P＜0.05）。结论：小剂量糖皮质激素联合持续性血液净化治疗有利于儿童严重脓毒症患儿病情转归,减少主要并发症发生,可能与阻断炎症反应有关,值得进一步研究应用。     

Sensory cues for the gradual frequency fall responses of the gymnotiform electric fish, Rhamphichthys rostratus

The sensory cues for a less known form of frequency shifting behavior, gradual frequency falls, of electric organ discharges (EODs) in a pulse-type gymnotiform electric fish, Rhamphichthys rostratus, were identified. We found that the gradual frequency fall occurs independently of more commonly observed momentary phase shifting behavior, and is due to perturbation of sensory feedback of the fish's own EODs by EODs of neighboring fish. The following components were identified as essential features in the signal mixture of the fish's own and the neighbor's EOD pulses: (1) the neighbor's pulses must be placed within a few millisecond of the fish's own pulses, (2) the neighbor's pulses, presented singly at low frequencies (0.2–4 Hz), were sufficient, (3) the frequency of individual pulse presentation must be below 4 Hz, (4) amplitude modulation of the sensory feedback of the fish's own pulses induced by such insertions of the neighbor's pulses must contain a high frequency component: sinusoidal amplitude modulation of the fish's own EOD feedback at these low frequencies does not induce gradual frequency falls. Differential stimulation across body surfaces, which is required for the jamming avoidance response (JAR) of wave-type gymnotiform electric fish, was not necessary for this behavior. We propose a cascade of high-pass and low-pass frequency filters within the amplitude processing pathway in the central nervous system as the mechanism of the gradual frequency fall response.Abbreviations EOD electric organ discharge - f frequency of EOD or pacemaker command signal - JAR jamming avoidance response - S ₁ stimulus mimicking fish's own EOD - f ₁ frequency of S₁ - S ₂ stimulus mimicking neighbor's EOD - f ₂ frequency of S₂     

Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential component of cellular defense against a vast variety of endogenous and exogenous insults, including oxidative stress. Nrf2 acts as a master switch in the circuits upregulating the expression of various stress-response proteins, especially heme oxygenase-1 (HO-1). Paradoxically, however, recent studies have demonstrated oncogenic functions of Nrf2 and its major target protein HO-1. Levels of Nrf2 and HO-1 are elevated in many different types of human malignancies, which may facilitate the remodeling of the tumor microenvironment making it advantageous for the autonomic growth of cancer cells, metastasis, angiogenesis, and tolerance to chemotherapeutic agents and radiation and photodynamic therapy. In this context, the cellular stress response or cytoprotective signaling mediated via the Nrf2–HO-1 axis is hijacked by cancer cells for their growth advantage and survival of anticancer treatment. Therefore, Nrf2 and HO-1 may represent potential therapeutic targets in the management of cancer. This review highlights the roles of Nrf2 and HO-1 in proliferation of cancer cells, their tolerance/resistance to anticancer treatments, and metastasis or angiogenesis in tumor progression.     

New strategy for in vitro activation of primordial follicles with mTOR and PI3K stimulators

It had been known for decades that primordial follicles in mammalian ovaries are assembled with definite numbers and represent the ovarian reserve throughout the reproductive life. Intra-oocyte PI3K/mTOR pathways have been indicated to play a central role on the activation of primordial follicles. Genetic modified mouse models with chronic activation of PI3K/mTOR signals in primordial oocytes showed premature activation of all primordial follicles and eventually their exhaustion. On the other hand, this may suggest that, unlike chronic activation of PI3K/mTOR, its acute activation in infertility would activate primordial follicles, permitting fertility during the treatment. Previously, PI3K stimulators were reported as a temporary measure to accelerate primordial follicle activation and follicular development in both mouse and human, and were applied in the treatment of infertility in premature ovarian failure (POF) patients. To address whether mTOR stimulators could play similar role in the process, we transiently treated neonatal and aged mouse ovaries with mTOR stimulators-phosphatidic acid (PA) and propranolol. Our results demonstrated the stimulators increased activation of primordial follicles and the production of progeny. Human ovarian cortex cubes were also treated with mTOR or/and PI3K stimulators in vitro. When they were used separately, both of them showed similar promotive effects on primordial follicles. Surprisingly, after joint-treatment with the 2 kinds of stimulators together, synergistic effects on follicular development were observed. Based on increased efficiency of follicular activation in humans, here we propose in vitro transient treatment with mTOR and PI3K stimulators as an optimized protocol for the application in different clinical conditions with limited follicle reserve.     

A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice

HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) and vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.