基于全基因组测序的耐碳青霉烯类抗生素鲍曼不动杆菌耐药基因、毒力因子及同源性分析

摘要：目的 通过应用全基因组测序(whole genome sequencing, WGS)技术分析某三级医疗机构耐碳青霉烯类抗生素鲍曼不 动杆菌(carbapenem-resistant Acinetobacter baumannii, CRAB)的耐药基因、毒力因子及同源性。方法 收集该院2020年1月至3月 重症监护病房(Intensive care unit, ICU)、神经外科分离的11株医院感染CRAB菌株，通过二代测序平台进行全基因组测序, 应用 基因组流行病学中心(Center for genomic epidemiology, CGE)ResFinder 4. 0软件分析其耐药基因型，并应用MORPHEUS在线制作 热图，应用毒力因子数据库(virulence factors of pathogenic bacteria, VFDB)VFanalyzer软件筛选毒力因子，应用MLST软件检测菌 株的ST型，应用Kaptive软件检测荚膜型，应用CSI Phylogeny 1. 4软件及FigTree v1. 4. 4软件构建最大似然树(maximum likelihood tree, MLT)以分析其同源性。结果 11株CRAB对亚胺培南、美罗培南、头孢菌素、环丙沙星均呈现耐药，而对阿米卡星、左氧 氟沙星耐药的菌株株数较少。11株CRAB共检测出18种耐药基因，11株同时携带碳青霉烯酶耐药基因blaOXA-23和blaOXA-66，β-内酰 胺酶耐药基因以blaTEM-1D和blaADC-25为主，大部分菌株携带多种外排泵相关耐药基因及抗菌药物修饰酶耐药基因。11株CRAB均携 带多种毒力因子，包括外膜孔蛋白、脂多糖、生物膜、外排泵、磷脂酶和效应蛋白等，如OmpA、Lps、Csu、Pga、Ade、Plc、 Bas、Bau、Ent、Hem、Aba、Bfm、Pbp和Kat等。11株CRAB均为ST2-K22型，同源性分析结果显示C组内同源性关系相近，存 在院内传播的可能。结论 该院CRAB的耐药性、毒力特征复杂多样，同源性分析显示该院存在1种优势克隆株，该克隆株有医 院内传播的风险。     

多功能套针浮刺疗法治疗神经根型颈椎病——一项随机对照观察研究＊

目的 评价多功能套针浮刺疗法对神经根型颈椎病的临床疗效。方法 选取256例神经根型颈椎病患者，按随机数字表法分为观察组与对照组各128例。观察组应用多功能套针浮刺疗法进行干预，对照组为常规针刺治疗。两组患者均治疗7天。分别于治疗前后观察两组患者的简化McGill疼痛问卷（SF-MPQ）、国际标准颈椎功能障碍指数（NDI）和田中靖久颈椎病症状20分法量表评分，并于治疗结束后3个月观察复发率。结果 两组患者治疗后的SF-MPQ量表评分、NDI量表评分及田中靖久颈椎病症状20分法评分与治疗前相比均有改善（P<0.05），且观察组优于对照组（P<0.05）；两组患者于治疗后3个月随访，SF-MPQ量表评分与治疗后相比均有改善，且观察组优于对照组（P<0.05）；观察组临床疗效总有效率为96.88%，愈显率为81.25%；对照组总有效率为78.13%，愈显率为46.88%，观察组优于对照组（P<0.05）。结论 应用多功能套针浮刺疗法治疗神经根型颈椎病临床疗效显著，见效较快，可有效降低其复发率，且作用稳定，效果持久，值得临床推广应用。     

Impact of the COVID-19 pandemic on the hospital attendance of patients with primary cervical cancer in Heilongjiang,China

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒² = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒² = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒² = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒² = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒² = 74.674, P < .001) and 12 days in July-December 2020 (𝜒² = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.     

超声引导下经皮肺穿刺活检术术后并发症分析

目的分析超声引导下经皮肺穿刺活检术术后并发症的相关影响因素。 方法收集2015年1月至2017年12月于西部战区总医院住院并在超声引导下行经皮肺穿刺活检术的205例患者临床资料，分析205例患者穿刺术后病理结果及并发症发生率，探讨超声引导下经皮肺穿刺活检术术后并发症的相关影响因素。 结果205例患者行超声引导下经皮肺穿刺活检术，术后并发出血8例，占3.9%(8/205)，术后发热3例，占1.46% (3/205)，为低热，且予以对症治疗后均恢复正常，无严重并发症发生。术后出血的发生率在不同性别、年龄、BMI及病灶类型的患者中无显著差异(P>0.05)，且吸烟对患者术后出血率也无显著影响(P>0.05)；但有基础疾病的患者其术后出血率更高(P＝0.005)，且病灶直径越小，术后越容易并发出血(P＝0.006)。不同性别、年龄及病灶类型对术后发热的发生率无显著影响(P>0.05)，且术后发热与吸烟史及基础疾病史无关(P>0.05)，但BMI≥24或3 cm ≤病灶直径(d)<6 cm的患者术后更易发热(P<0.05)。 结论超声引导下经皮肺穿刺活检术术后并发症发生率低(约为5.37%)，主要为出血及低热，其中术后出血主要与基础疾病史和病灶直径有关，术后发热主要与病灶直径及BMI有关。     

MCI的情志病机及疏肝法干预的可行性探讨＊

轻度认知障碍（Mild cognition impairment， MCI）是尚未达到阿尔兹海默病（Alzheimer’s disease， AD）的诊断标准且可逆转为正常脑老化状态的最佳窗口期。情志异常、肝失疏泄（肝失疏泄日久致肝郁）已被证实为MCI的重要情志病机，且“长期负性情绪积累肝失疏泄致衰加速脑老化”的科学假说已在本课题组前期研究中得到初步证实，疏肝法干预肝郁型MCI患者疗效显著，但以上作用机制尚未得到完全阐述。因此本研究系统总结了中医学对MCI的认识，长期情绪不调肝失疏泄对MCI的影响及可能机制，疏肝解郁方药及其成分改善肝郁型MCI的可行性，并提出使用无束缚性设计的眼动技术以探索疏肝法改善肝郁型MCI的可行性，为MCI的中医药干预及其神经机制探讨提供新思路，为中医情志衰老学说增添新内涵。     

菊花总黄酮含药血清对干眼细胞模型AR、NF-κB磷酸化蛋白及TGF-β1表达的影响＊

目的 观察菊花总黄酮在体外条件下对泪腺上皮细胞中雄激素受体（Androgen Receptor，AR）的调控作用及对下游的核因子κB（Nuclear Factor kappa B，NF-κB）、转化生长因子-β1（transforming growth factor-beta1，TGF-β1）的表达影响。方法 以过氧化氢（H₂O₂）诱导泪腺上皮细胞凋亡，建立细胞模型，设立无雄激素培养空白对照组、含雄激素培养对照组、无雄激素培养黄酮治疗组。以MTT法摸索含药血清最佳干预加入量；免疫印迹实验（Western Blot）以及实时荧光定量PCR法（Quantitative Real-Time PCR，qPCR）检测泪腺上皮细胞中AR、NF-κB及TGF-β1的表达情况；并应用雄激素受体阻断剂氟他胺进行AR阻断后再次检测上述指标 。结果 MTT法检测后计算得出含药血清干预细胞的最终浓度为13.2%；无雄激素培养黄酮治疗组及含雄激素培养对照组中AR、NF-κB及TGF-β1的表达增强，与空白对照组对比有显著差异（P<0.01）；无雄激素培养黄酮治疗组中NF-κB表达量比含雄激素培养对照组表达量低，两者间的差异有统计学意义。氟他胺及含药血清干预后，无雄激素培养黄酮治疗组及含雄激素培养对照组中AR及NF-κB的表达未见提高，无统计学意义。结论 菊花总黄酮对泪腺上皮细胞可能存在拟雄激素效应，从而使AR、NF-κB表达增加，并通过上调TGF-β1的表达，可能起到在泪腺局部的抗炎作用。     

发达国家医学生器官捐献意愿研究现状的范围综述

目的了解发达国家医学生器官捐献意愿研究的目的、结果、障碍因素和解决对策。 方法以主题词和自由词联合的方式对PubMed、Web of Science、Ovid MEDLINE、Ovid EMBASE(Excerpta Medica)、EBSCOhost Complete和Cochrane Library等已发表文献数据库，以及灰色文献数据库York Centre for Reviews and Dissemination、Open Grey、ProQuest Dissertation and Theses和Mednar进行系统、全面地检索，并采用Arksey和O′Malley提出的范围综述框架进行文献资料整合。 结果共纳入17项发达国家医学生器官捐献意愿研究。研究背景主要为医学生未来对于公众器官捐献有着重要影响。研究结果表明，大多数医学生器官捐献意愿性良好，但不同亚组的研究结果不一；其最主要的障碍因素为医学生器官捐献相关知识的缺乏；解决对策主要为施予系统化、结构化和可评价的教育课程。 结论21世纪以来发达国家医学生器官捐献意愿研究方兴未艾，其研究的多层面、多角度以及揭示的问题、寻求的解决对策，可对我国现阶段医学生器官捐献的研究提供一定参考。     

Female reproductive and hormonal factors and lung cancer mortality among never-smokers: A prospective cohort study of 287 408 Chinese women

There is growing, but inconsistent evidence suggesting oestrogen may play a key role in lung cancer development, especially among never-smoking women for whom lung cancer risk factors remain largely elusive. Using the China Kadoorie Biobank, a large-scale prospective cohort with 302 510 women aged 30 to 79 years recruited from 10 regions in China during 2004 to 2008, we assessed the risk of lung cancer death among self-reported never-smoking women who were cancer-free at baseline, in relation to age at menarche, age at menopause, time since menopause, prior use of oral contraceptives (OCP), number of livebirths, breastfeeding and age at first livebirth. Women were followed up to December 31, 2016 with linkage to mortality data. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression, adjusting for key confounders including several socio-demographic, environmental and lifestyle factors. Among 287 408 never-smoking women, 814 died from lung cancer with a median follow-up of 10.3 years. Women who had used OCP within 15 years prior to baseline had a significantly higher hazard of lung cancer death compared with never-users: HR = 1.85 (95% CI: 1.14-3.00) and risk increased by 6% with each additional year of use: HR = 1.06 (1.01-1.10). Among parous women, the hazard of lung cancer death increased by 13% with each single livebirth: HR = 1.13 (1.05-1.23); and among post-menopausal women, the risk increased by 2% with each year since menopause: HR = 1.02 (1.01-1.04). These results suggest that reproductive factors which were proxies for lower endogenous oestrogen level, for example, longer duration of OCP use, could play a role in lung cancer development.