简介：摘要目的探讨全反式视黄酸(ATRA)体外诱导人视网膜色素上皮(ARPE)-19细胞凋亡的信号途径。方法采用不同浓度的ATRA处理ARPE-19细胞24 h、48 h，采用细胞计数试剂盒-8(CCK-8)法检测其细胞活性；分别采用0、2.5、5、10、15和20 μmol/L ATRA处理ARPE-19细胞24 h，通过流式细胞术和Western blot法检测细胞凋亡水平和caspase相关蛋白相对表达量；分别采用0、2.5、5、10和20 μmol/L ATRA处理ARPE-19细胞24 h，通过流式细胞术检测其总活性氧簇(ROS)水平和多重半胱氨酸天冬氨酸蛋白酶(multicaspase)水平，通过实时荧光定量PCR法检测caspase相关基因mRNA相对表达量。其中0 μmol/L ATRA组作为空白对照。结果CCK-8检测结果显示，ATRA处理ARPE-19细胞24 h和48 h后的半数抑制浓度(IC50)分别为13.88 μmol/L和11.99 μmol/L，不同浓度ATRA处理ARPE-19细胞24 h和48 h后细胞存活率总体比较，差异均有统计学意义(F＝176.60、350.30，均P<0.01)。细胞培养24 h时，2 μmol/L、6 μmol/L ATRA组细胞存活率较空白对照组高，12、14、16、18、20 μmol/L ATRA组细胞存活率较空白对照组低，差异均有统计学意义(均P<0.05)。流式细胞术检测结果显示，不同浓度ATRA处理ARPE-19细胞后24 h，细胞凋亡、multicaspase及ROS水平总体比较差异均有统计学意义(F＝86.39、166.84、101.40，均P<0.01)，其中2.5 μmol/L和5 μmol/L ATRA组细胞凋亡率较空白对照组下降，10、15和20 μmol/L ATRA组较空白对照组升高，2.5、5、10、20 μmol/L ATRA组multicaspase和ROS相对表达量较空白对照组升高，差异均有统计学意义(均P<0.01)；Western blot检测结果显示，与空白对照组比较，2.5、5、10、15、20 μmol/L ATRA组caspase 9蛋白相对表达量升高，差异均有统计学意义(均P<0.05)；与空白对照组比较，2.5 μmol/L ATRA组caspase 12蛋白相对表达量升高，5、10、15、20 μmol/L ATRA组逐渐降低，2.5、15、20 μmol/L ATRA组与空白对照组比较差异均有统计学意义(均P<0.05)；与空白对照组比较，5、10、20 μmol/L ATRA组caspase 3蛋白相对表达量升高，差异均有统计学意义(均P<0.05)；与空白对照组比较，2.5、5、10、15、20 μmol/L ATRA组cleaved caspase 3蛋白相对表达量显著升高，差异均有统计学意义(均P<0.01)。实时荧光定量PCR结果显示，与空白对照组比较，2.5、5、10、20 μmol/L ATRA组caspase 9、caspase 12 mRNA及5 μmol/L、10 μmol/L ATRA组caspase 3 mRNA相对表达量明显升高，差异均有统计学意义(均P<0.01)。ATRA浓度小于10 μmol/L时，caspase 9和caspase 12 mRNA的相对表达量呈浓度依赖性升高，当浓度达20 μmol/L时，其相对表达量显著降低，但仍高于空白对照组。结论ATRA体外诱导ARPE-19细胞凋亡是通过激活ROS及内源性caspase依赖性凋亡途径导致的。

简介：［摘 要］目的 探讨19例新型冠状病毒肺炎（NCP）患者治疗期间的护理。方法 对19例NCP患者治疗期间实施的护理措施。结果 19例NCP患者平稳度过治疗期，无患者死亡，无医务人员感染。结论 通过严格执行消毒隔离制度、有效的护理措施、使患者能积极配合治疗，平稳度过治疗期,同时防止了院内交叉感染。

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简介：摘要 ：目的：总结方证对应使用柴胡加龙骨牡蛎汤治疗失眠的经验。方法：本人于2020年5月1号-7月30号在黔江普兴中医院予柴胡加龙骨牡蛎汤加减治疗失眠40例，并分析该方治疗失眠的舌像脉像，症状特点以及兼夹症。结果：柴胡加龙骨牡蛎汤治疗失眠症的特点是心烦不寐或眠差易惊；典型舌脉是舌尖偏红，苔薄黄，双脉弦滑，右寸偏亢。该方治疗失眠症可兼伴头昏蒙，痤疮，胁痛，腰痛，月经不调等症状。据以上舌脉及症状予柴胡加龙骨牡蛎汤治疗，患者服用4-8付药后失眠得到明显缓解。结论：柴胡加龙骨牡蛎汤治疗气郁痰扰型失眠有着典型的舌脉像及症状特点，值得临床推广。为改善预后，对于易焦虑的失眠患者建议配合情志疏导。

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简介：【摘要】目的：对急性脑卒中合并肺炎的临床并行研究并给予护理建议。方法：本次研究选取时间范围在2020年3月至2021年3月之间，选取对象为40例于我院进行治疗的急性脑卒中患者，分析肺炎与脑卒中类型的关系并对比急性脑卒中与急性脑卒中合并肺炎患者的病死率。结果：出血性脑卒中患者发生肺炎的发生率（59.09%）明显比缺血性患者发生肺炎的发生率（22.22%）更高，两组对比（P＜0.05）。急性脑卒中合并肺炎患者的病死率（58.82%）明显高于单纯急性脑卒中患者的病死率（26.09%），两组对比（P＜0.05）。结论：相对于缺血性脑卒中患者而言，出血性脑卒中患者并发肺炎的几率更高，并发肺炎会增加脑卒中患者的病死率，所以在急性脑卒中患者的日常护理中，护理人员应着重注意对呼吸道的护理工作，从而减少病发肺炎的发生率，避免患者因并发肺炎而导致死亡。

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简介：AbstractBackground:Around the world, controlling the COVID-19 pandemic requires national coordination of multiple intervention strategies. As vaccinations are globally introduced into the repertoire of available interventions, it is important to consider how changes in the local supply of vaccines, including delays in administration, may be addressed through existing policy levers. This study aims to identify the optimal level of interventions for COVID-19 from 2021 to 2022 in the Philippines, which as a developing country is particularly vulnerable to shifting assumptions around vaccine availability. Furthermore, we explore optimal strategies in scenarios featuring delays in vaccine administration, expansions of vaccine supply, and limited combinations of interventions.Methods:Embedding our work within the local policy landscape, we apply optimal control theory to the compartmental model of COVID-19 used by the Philippine government’s pandemic surveillance platform and introduce four controls: (a) precautionary measures like community quarantines, (b) detection of asymptomatic cases, (c) detection of symptomatic cases, and (d) vaccinations. The model is fitted to local data using an L-BFGS minimization procedure. Optimality conditions are identified using Pontryagin’s minimum principle and numerically solved using the forward-backward sweep method.Results:Simulation results indicate that early and effective implementation of both precautionary measures and symptomatic case detection is vital for averting the most infections at an efficient cost, resulting in > 99% reduction of infections compared to the no-control scenario. Expanding vaccine administration capacity to 440,000 full immunizations daily will reduce the overall cost of optimal strategy by 25%, while allowing for a faster relaxation of more resource-intensive interventions. Furthermore, delays in vaccine administration require compensatory increases in the remaining policy levers to maintain a minimal number of infections. For example, delaying the vaccines by 180 days (6 months) will result in an 18% increase in the cost of the optimal strategy.Conclusion:We conclude with practical insights regarding policy priorities particularly attuned to the Philippine context, but also applicable more broadly in similar resource-constrained settings. We emphasize three key takeaways of (a) sustaining efficient case detection, isolation, and treatment strategies; (b) expanding not only vaccine supply but also the capacity to administer them, and; (c) timeliness and consistency in adopting policy measures.

简介：AbstractImportance:The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians.Objective:This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China.Methods:This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed.Results:In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died.Interpretation:Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

简介：AbstractBackground:As one of the non-pharmacological interventions to control the transmission of COVID-19, determining the quarantine duration is mainly based on the accurate estimates of the incubation period. However, patients with coarse information of the exposure date, as well as infections other than the symptomatic, were not taken into account in previously published studies. Thus, by using the statistical method dealing with the interval-censored data, we assessed the quarantine duration for both common and uncommon infections. The latter type includes the presymptomatic, the asymptomatic and the recurrent test positive patients.Methods:As of 10 December 2020, information on cases have been collected from the English and Chinese databases, including Pubmed, Google scholar, CNKI (China National Knowledge Infrastructure) and Wanfang. Official websites and medias were also searched as data sources. All data were transformed into doubly interval-censored and the accelerated failure time model was applied. By estimating the incubation period and the time-to-event distribution of worldwide COVID-19 patients, we obtain the large percentiles for determining and suggesting the quarantine policies. For symptomatic and presymptomatic COVID-19 patients, the incubation time is the duration from exposure to symptom onset. For the asymptomatic, we substitute the date of first positive result of nucleic acid testing for that of symptom onset. Furthermore, the time from hospital discharge or getting negative test result to the positive recurrence has been calculated for recurrent positive patients.Results:A total of 1920 laboratory confirmed COVID-19 cases were included. Among all uncommon infections, 34.1% (n = 55) of them developed symptoms or were identified beyond fourteen days. Based on all collected cases, the 95th and 99th percentiles were estimated to be 16.2 days (95% CI 15.5-17.0) and 22.9 days (21.7-24.3) respectively. Besides, we got similar estimates based on merely symptomatic and presymptomatic infections as 15.1 days (14.4-15.7) and 21.1 days (20.0-22.2).Conclusions:There are a certain number of infected people who require longer quarantine duration. Our findings well support the current practice of the extended active monitoring. To further prevent possible transmissions induced and facilitated by such infectious outliers after the 14-days quarantine, properly prolonging the quarantine duration could be prudent for high-risk scenarios and in regions with insufficient test resources.

简介：摘要肿瘤微环境(tumor microenvironment，TME)与肿瘤的发生、转移及其所在组织的结构、功能密切相关。在体研究肿瘤细胞与TME之间的相互作用机制，是基础和临床研究癌症发生发展、研发肿瘤精准诊断新技术以及开发有效抑制肿瘤新策略的迫切需求。分子影像学(molecular imaging)着眼于生物过程的分子水平变化，对早期TME中分子改变及环境变化的研究具有重要意义。现已研制出多种针对TME响应的19F-MR纳米分子成像探针，这类探针可在复杂TME中的某些特定刺激下，使含氟小分子核团暴露，19F-MR信号明显增强。利用探针这一环境响应特性，结合19F-MR成像，可在分子水平早期可视化TME中的恶性生物学行为，为实现肿瘤早期诊断及精准治疗提供有利支持。该综述从基础及临床研究需求出发，对已研发的TME响应型纳米分子成像探针展开评述，以期为新型纳米探针的设计、制备及临床转化提供研究思路及理论依据。

简介：AbstractThe coronavirus disease 2019 (COVID-19) pandemic represents an enormous challenge to all countries, regardless of their development status. The manipulation of its etiologic agent SARS-CoV-2 requires a biosafety containment level 3 laboratories (BSL-3) to understand virus biology and in vivo pathogenesis as well as the translation of new knowledge into the preclinical development of vaccines and antivirals. As such, BSL-3 facilities should be considered an integral part of any public health response to emerging infectious disease prevention, control and management. Differently from BSL-2, BSL-3 units vary considerably along the range from industrialized to the least developed countries. Innovative Developing Countries (IDCs) such as Brazil, which excelled at controlling the 2015-2017 Zika epidemic, had to face a serious flaw in its disease control and prevention structure: the scarcity and uneven geographic distribution of its BSL-3 facilities, including those for preclinical animal experimentation.

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简介：摘要目的分析复发/难治性急性B淋巴细胞白血病（R/R B-ALL）自体CD19嵌合抗原受体T细胞（CAR-T细胞）制备过程中，培养体系中残留白血病细胞导致CD19 CAR转入白血病细胞的特征和体外杀伤研究。方法①收集30例接受CD19 CAR-T细胞治疗的R/R B-ALL患者及6例健康志愿者外周血单个核细胞（PBMC）；②流式细胞术分析R/R B-ALL患者PBMC经CD3磁珠分选后及体外培养过程中体系白血病细胞残留情况；③患者及健康志愿者PBMC CD3+ T细胞转染CD19 CAR及CD22 CAR慢病毒，制备CD19 CAR-T、CD22 CAR-T细胞；④复苏Nalm-6细胞株，CD19 CAR慢病毒转染Nalm-6细胞，制备CD19 CAR-Nalm-6细胞，同时转染患者原代ALL细胞；⑤流式细胞术检测转染率；⑥CCK-8法检测细胞增殖；⑦乳酸脱氢酶（LDH）法检测CD19 CAR-T、CD22 CAR-T细胞对Nalm-6细胞及CD19 CAR-Nalm-6细胞杀伤活性。结果①30例接受CD19 CAR-T细胞治疗的R/R B-ALL患者中，2例CD3+ T细胞中发现3.32%、2.04%的白血病细胞残留，随体外培养时间延长，在培养第4天，白血病细胞完全消失。②体外培养中CD19 CAR-Nalm-6细胞增殖率高于Nalm-6细胞。③效靶比为1∶1且共培养24、48、72 h，CD19 CAR-T细胞对Nalm-6细胞的杀伤活性高于CD19 CAR-Nalm-6细胞；与CD19 CAR-T细胞相比，CD22 CAR-T细胞对CD19 CAR-Nalm-6细胞的杀伤活性更高。④相同效靶比情况，单独应用CD22 CAR-T细胞对CD19 CAR-Nalm-6细胞的杀伤活性高于CD19 CAR-T联合CD22 CAR-T细胞。结论CD19 CAR-T细胞制备过程中培养体系残留白血病细胞可能会导致CD19 CAR被引入白血病细胞中而导致CD19 CAR-T细胞治疗失败，在细胞制备过程中需要检测培养体系中白血病细胞的残留情况。CD22 CAR-T细胞治疗可作为上述情况的挽救治疗措施之一。

简介：摘要目的分析复发/难治性急性B淋巴细胞白血病（R/R B-ALL）自体CD19嵌合抗原受体T细胞（CAR-T细胞）制备过程中，培养体系中残留白血病细胞导致CD19 CAR转入白血病细胞的特征和体外杀伤研究。方法①收集30例接受CD19 CAR-T细胞治疗的R/R B-ALL患者及6例健康志愿者外周血单个核细胞（PBMC）；②流式细胞术分析R/R B-ALL患者PBMC经CD3磁珠分选后及体外培养过程中体系白血病细胞残留情况；③患者及健康志愿者PBMC CD3+ T细胞转染CD19 CAR及CD22 CAR慢病毒，制备CD19 CAR-T、CD22 CAR-T细胞；④复苏Nalm-6细胞株，CD19 CAR慢病毒转染Nalm-6细胞，制备CD19 CAR-Nalm-6细胞，同时转染患者原代ALL细胞；⑤流式细胞术检测转染率；⑥CCK-8法检测细胞增殖；⑦乳酸脱氢酶（LDH）法检测CD19 CAR-T、CD22 CAR-T细胞对Nalm-6细胞及CD19 CAR-Nalm-6细胞杀伤活性。结果①30例接受CD19 CAR-T细胞治疗的R/R B-ALL患者中，2例CD3+ T细胞中发现3.32%、2.04%的白血病细胞残留，随体外培养时间延长，在培养第4天，白血病细胞完全消失。②体外培养中CD19 CAR-Nalm-6细胞增殖率高于Nalm-6细胞。③效靶比为1∶1且共培养24、48、72 h，CD19 CAR-T细胞对Nalm-6细胞的杀伤活性高于CD19 CAR-Nalm-6细胞；与CD19 CAR-T细胞相比，CD22 CAR-T细胞对CD19 CAR-Nalm-6细胞的杀伤活性更高。④相同效靶比情况，单独应用CD22 CAR-T细胞对CD19 CAR-Nalm-6细胞的杀伤活性高于CD19 CAR-T联合CD22 CAR-T细胞。结论CD19 CAR-T细胞制备过程中培养体系残留白血病细胞可能会导致CD19 CAR被引入白血病细胞中而导致CD19 CAR-T细胞治疗失败，在细胞制备过程中需要检测培养体系中白血病细胞的残留情况。CD22 CAR-T细胞治疗可作为上述情况的挽救治疗措施之一。

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简介：摘要目的探讨>40岁女性冻融周期囊胚移植数目的选择策略，为降低双胎率、提高围产期临床结局提供参考。方法回顾性分析2017年1月至2019年12月在广东省妇幼保健院生殖中心年龄>40岁、接受冻融囊胚移植的377个移植周期患者，根据囊胚移植数目分为单囊胚和双囊胚移植组。比较两组临床妊娠率、种植率、流产率、活产率、早产率、双胎率及单胎分娩率。结果⑴两组取卵年龄、移植年龄、BMI、基础窦卵泡数(AFC)、基础卵泡刺激素(FSH)、抗苗勒氏管激素(AMH)、移植日子宫内膜厚度、获卵数、Gn启动剂量、Gn天数、Gn用量、优质胚胎数、D3可利用胚胎数比较差异均无统计学意义(P>0.05)；⑵两组种植率、早期流产率、晚期流产率、活产率比较差异无统计学意义(P>0.05)；⑶双囊胚组早产率(31.71%)明显高于单囊胚组(12.5%)，但差异无统计学意义(P＝0.083)；⑷双囊胚组临床妊娠率、双胎妊娠率高于单囊胚组，差异有统计学意义(P<0.05)；⑸双囊胚组单胎分娩率(75.61%)低于单囊胚组(95.83%)，差异有统计学意义(P＝0.036)。结论>40岁女性囊胚冻融移植，可选择单囊胚移植，保证活产率相当的情况下明显降低双胎率、提高单胎分娩率等围产期结局。

简介：摘要目的探讨儿科重症患者高速铁路(高铁)转运的可行性和安全性。方法收集2016年6月至2019年6月中国人民解放军总医院第七医学中心儿科医学部重症医学科高铁转运案例的临床资料，并做总结、回顾分析。结果(1)共高铁转运40例，全部为婴幼儿，男性占57.5%。(2)转运的原因依次为改善救治条件(25例，62.5%)，急诊外科手术(8例，20.0%)，明确诊断(4例，10.0%)，脱机困难(3例，7.5%)。(3)先天性心脏病为主要转诊病例，占77.5%，其次为呼吸系统疾病占17.5%。(4)呼吸支持模式：机械通气最多，占45.0%。(5)均采用"救护车-高铁-救护车"模式转运，长春病例最多，占45.0%，转运距离最近205 km，最远2 610 km，平均947 km。(6)所有病例均安全抵达，无意外事件，未发生医疗纠纷。结论以高铁为平台进行长途转运儿科重症患者，能够缩短转运时间，是安全、可行的。

简介：摘要目的探讨>40岁女性冻融周期囊胚移植数目的选择策略，为降低双胎率、提高围产期临床结局提供参考。方法回顾性分析2017年1月至2019年12月在广东省妇幼保健院生殖中心年龄>40岁、接受冻融囊胚移植的377个移植周期患者，根据囊胚移植数目分为单囊胚和双囊胚移植组。比较两组临床妊娠率、种植率、流产率、活产率、早产率、双胎率及单胎分娩率。结果⑴两组取卵年龄、移植年龄、BMI、基础窦卵泡数(AFC)、基础卵泡刺激素(FSH)、抗苗勒氏管激素(AMH)、移植日子宫内膜厚度、获卵数、Gn启动剂量、Gn天数、Gn用量、优质胚胎数、D3可利用胚胎数比较差异均无统计学意义(P>0.05)；⑵两组种植率、早期流产率、晚期流产率、活产率比较差异无统计学意义(P>0.05)；⑶双囊胚组早产率(31.71%)明显高于单囊胚组(12.5%)，但差异无统计学意义(P＝0.083)；⑷双囊胚组临床妊娠率、双胎妊娠率高于单囊胚组，差异有统计学意义(P<0.05)；⑸双囊胚组单胎分娩率(75.61%)低于单囊胚组(95.83%)，差异有统计学意义(P＝0.036)。结论>40岁女性囊胚冻融移植，可选择单囊胚移植，保证活产率相当的情况下明显降低双胎率、提高单胎分娩率等围产期结局。