Involvement of neuronal nitric oxide synthase in cognitive impairment in isoflurane-treated rats

The underlying causes of post-operative cognitive dysfunction (POCD) in elderly patients remain to be elucidated. In order to explore possible contributory mechanisms, we tested the effects of isoflurane anesthesia on (i) expression of hippocampal neuronal nitric oxide synthase (nNOS) and (ii) the relationship of changes in nNOS expression to cognitive dysfunction in isoflurane-treated aged rats. Our results indicate that isoflurane treatment leads to significant changes in correct reactions (F = 28.35, p < 0.001), initiative avoidances (F = 29.33, p < 0.001), and total reaction time (TRT) (F = 6.99, p < 0.05) of treated rats in the Y-maze test. Isoflurane-treated rats had fewer correct reactions and initiative avoidances in the Y-maze test 24 and 48 h after 2 h of isoflurane anesthesia compared with control group rats (p < 0.05). TRTs to complete 20 trials of the Y-maze test increased significantly 48 h after 2 h anesthesia. The number of nNOS-positive hippocampal neurons decreased 24 h after anesthesia, corresponding to an increased mean immunostaining grey-scale value. These data show that isoflurane causes a transient decrease in expression of hippocampal nNOS in aged rats during early post-anesthesia stages, and that the transient decrease of nNOS is closely correlated with cognitive impairment in isoflurane-treated aged rats.     

Reversion to virulence of a subtype B avian metapneumovirus vaccine: Is it time for regulators to require availability of vaccine progenitors?

Empirically derived live avian metapneumovirus (AMPV) vaccines developed during the late 80s and early 90s have generally performed well in controlling turkey rhinotracheitis. Nonetheless, unstable attenuation was previously demonstrated in an AMPV subtype A vaccine. Until now this had not been investigated in subtype B vaccines due to lack of any similar availability of a vaccine progenitor or its sequence. The publication of the full genome sequence for the VCO3 vaccine progenitor facilitated a conclusive investigation of two AMPVs isolated from poults on a farm which had been vaccinated with VCO3 derived vaccine. Full genome sequencing of the isolates and their comparison to sequences of the vaccine and its progenitor, confirmed their vaccine origin. After determining the absence of extraneous infectious agents, one of these virus isolates was inoculated into 1-day-old turkeys in disease secure isolators and shown to cause disease with a severity similar to that caused by virulent field virus. This suggests that instability in live AMPV vaccines may be generalized and highlights the need for availability of vaccine progenitor sequences for the field assessment of all live viral vaccines.     

小细胞肺癌的治疗进展与现状

肺癌为一种恶性程度较高的肿瘤性疾病,其病死率居各种恶性肿瘤之首,发病率逐年上升,近年随着禁烟教育力度的增强和普及,发病率已出现下降势头。小细胞肺癌(SCLC)是一种以生长迅速、早期转移、高度侵袭性为特点的肺癌类型。小细胞肺癌的肿瘤细胞对化疗和放疗都非常敏感,但几十年来多方案的临床试验并没能找到彻底治愈小细胞肺癌的有效方法,多数患者在一线治疗以后仍会复发或转移。局限期小细胞肺癌的一线治疗包括双药化疗(足量EP方案:依托泊甙 顺铂/卡铂)联合胸腔放射治疗(TRT)。当联合方案达完全缓解(CR)或疗效较好的部分缓解(PR)患者,应后续应用预防性脑照射(PCI),可明显降低未来复发性脑转移的风险。日本和德国的临床研究显示含有伊立替康的IP方案及IC方案(伊立替康 顺铂/卡铂)治疗广泛期小细胞肺癌效果可比标准EP方案。各种强化疗法并不能提高小细胞肺癌患者的生存率。胸腔放疗方案的研究显示局限期小细胞肺癌患者早期同步应用超分割放疗方案配合化疗可以改善预后,可能与放疗越早介入越能有效减少耐药克隆株的发生有关。对于小细胞肺癌复发患者,可依据是敏感复发或是难治复发相应选择再次应用首次化疗方案或用二线单药化疗方案。培美曲塞联合铂类方案已应用于SCLC的一线及二线治疗。PET-CT的应用对小细胞肺癌的精确分期非常重要。真正符合Ⅰ_A期及Ⅰ_B期(TNM分期)的小细胞肺癌患者可考虑手术治疗,术后应行正规化疗。生物靶向治疗小细胞肺癌的若干研究性试验正在进行之中,这些生物制剂及其衍生物有可能会为未来小细胞肺癌的治疗带来一线曙光。     

端粒酶反转录酶与CA125在卵巢上皮性肿瘤组织中的原位表达及临床意义

目的:探讨端粒酶反转录酶(TRT)与CA125在卵巢上皮性肿瘤组织中的原位表达及临床意义。方法:收集93例卵巢上皮性肿瘤(良性47例、交界性15例、恶性31例),应用免疫组织化学S蛳P法检测肿瘤组织中TRT及CA125的原位表达,将结果进行统计学分析。结果:TRT的表达在良性(17.02%,8/47)和交界性(46.67%,7/15)以及恶性(90.32%,28/31)间的差异均有显著性意义(P<0.01);CA125的表达在良性(23.40%,11/47)和恶性(67.74%,21/31)间的差异有显著性意义(P<0.01),TRT的表达在浆液性肿瘤与黏液性肿瘤之间差异无显著性意义(P>0.05);CA125在各组浆液性肿瘤均明显高于黏液性肿瘤组,相比较差异有显著性意义(P<0.05);TRT和CA125在浆液性肿瘤的表达有一致性,相关性分析有显著性相关(P<0.01),在黏液性肿瘤中表达不相关(P>0.05)。结论:TRT和CA125的表达与卵巢上皮组织肿瘤的良恶性有关,尤其在卵巢浆液性肿瘤中TRT酶的活性与CA125呈正相关,二者的共同检测对诊断卵巢上皮组织肿瘤的类型和恶性程度有重要的临床意义。     

Evaluation of tinnitus retraining therapy for patients with normal audiograms versus patients with hearing loss

Objective

A few chronic tinnitus patients show normal hearing thresholds in the pure tone audiometry from 125 Hz to 8000 Hz (≤20 dB). We report the characteristics of the course of those patients underwent tinnitus retraining therapy (TRT) compared with other patients suffering from chronic and severe tinnitus.

Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy

BackgroundPolycythemia (erythrocytosis) is a known side effect of testosterone (T) replacement therapy (TRT) and appears to correlate with maximum T levels. There is also a well-established association between obstructive sleep apnea (OSA) and the development of polycythemia, which confers additional long-term cardiovascular morbidity. Synergy between TRT and OSA in the development of polycythemia remains poorly understood.AimThe objective of this study was to retrospectively assess the relationship of OSA and secondary polycythemia in hypogonadal men receiving TRT.MethodsWe performed a retrospective chart review of all men treated by a single provider from 2015 to 2019 for the diagnosis of hypogonadism. Patients who developed a hematocrit of 52% or greater were classified as having polycythemia. OSA was identified via clinical documentation or use of nocturnal continuous positive airway pressure. Demographics, laboratory values, treatment details, and comorbidities were recorded. Data were reported as mean ± SD for parametric variables and median [interquartile range] for non-parametric values.OutcomeThe primary outcome of this study was the association between OSA and polycythemia in hypogonadal men on TRT.Results474 men were included in this study. 62/474 (13.1%) men met the criteria for the diagnosis of polycythemia with a median hematocrit of 53.6 [interquartile range 52.6, 55.5]. Univariate analysis demonstrated a strong positive association between polycythemia and the concomitant diagnosis of OSA in hypogonadal men (P = .002). Even after correcting for age, body mass index (BMI), and peak T levels in the multivariate analysis (P = .01), this relationship remained significant with an odds ratio of 2.09 [95% CI 1.17, 3.76]. 37 men on TRT with polycythemia and OSA were included in the final cohort with a mean age of 59.2 ± 11.4 years, mean BMI of 32.4 ± 6.0, and median time from TRT initiation to polycythemia diagnosis of 3 years. All patients diagnosed with OSA were prescribed continuous positive airway pressure with poor compliance noted in 52.8% of men. 37.8% were managed via phlebotomy and 59.5% were managed via dose de-escalation of TRT. In hypogonadal men on TRT with polycythemia, BMI was the only risk factor strongly associated with OSA (P = .013).Clinical TranslationIn hypogonadal men (particularly those with elevated BMI) on TRT who develop secondary polycythemia, a diagnosis of OSA should be strongly considered.Strengths & LimitationsThis is a single provider retrospective study and further studies are needed to assess generalizability.ConclusionsIn this retrospective single-center cohort, the development of polycythemia in hypogonadal men on TRT was associated with an increased prevalence of OSA.Lundy SD, Parekh NV, Shoskes DA. Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy. J Sex Med 2020;17:1297–1303.     

习服疗法与掩蔽疗法对慢性耳鸣疗效的Meta分析

目的 系统评价并比较习服疗法和掩蔽疗法对慢性耳鸣的疗效.方法 从万方数据库、中国期刊全文数据库(CNKI)、维普数据库(VIP)、中国生物医学文献数据库(CBM)、PubMed、Web of science和Cochrane li-brary等中英文数据库中检索自建库到2020年2月与慢性耳鸣治疗相关的文献,全面收集采...     

大分割同期放化疗对局限期SCLC临床价值的Meta分析

目的:应用Meta分析评估大分割同期放化疗在局限期小细胞肺癌(limited disease small-cell lung cancer,LD-SCLC)中的价值。方法:检索中国生物医学文献数据库、中国学术期刊全文数据库、Cochrane Library、PubMed、Medline、Web of science、Embase 国内外数据库有关局部局限期SCLC患者大分割同期放化疗与常规分割/超分割同期放化疗对比的文献,依据入选和排除标准收集各项研究的近期疗效及生存情况，应用Meta分析方法评价大分割同期放化疗的临床疗效。结果:纳入符合标准的国内外文献5篇，共包括837例患者。大分割放疗与常规或超分割放疗相比，无进展生存时间相似(P=0.95)；大分割放疗可延长局限期小细胞肺癌患者的总生存期(P=0.03)；同时，大分割放疗不增加急性放射性食管炎和肺炎的发生率（RR=0.95，95%CI:0.63~1.42，P=0.79；RR=0.77，95%CI:0.39~1.51，P=0.44）。结论:大分割较常规分割/超分割同步放化疗延长总生存时间，不增加毒性，可作为局限期小细胞肺癌治疗的选择模式。     

慢性主观性耳鸣的治疗方法及疗效探讨

目的：探讨不同治疗方法在慢性主观性耳鸣治疗中的作用并进行分析。方法将符合纳入标准的154例患者分为3组,A组给予前列腺素E1静脉推注治疗,B组给予声治疗,C组给予前列腺素E1静脉推注联合声治疗,其中B组和C组均有专业的耳鼻喉科医师对其进行耳鸣相关知识的辅导。结果治疗2周后有效率,A组为37．5％,B组为32．0％,C组为40．0％,3组间差异无统计学意义（ P＞0．05）;治疗4周后有效率,A组为54．2％,B组为74．0％,C组为78．0％,A组与B组、A组与C组间差异有统计学意义（P＜0．05）,但B、C组间差异无统计学意义（P＞0．05）。A组治疗2、4周后疗效比较,差异无统计学意义（P＞0．05）,B组和C组治疗2、4周后疗效比较,差异均有统计学意义（P＜0．05）。结论慢性主观性耳鸣治疗以习服治疗为主,习服治疗可作为慢性主观性耳鸣患者的首选治疗方法。