Volume 134 · Issue 24 · 2021

在儿科医务工作者的共同努力下，我国儿童健康水平和儿科疾病治疗标准大幅提高。婴儿和5岁以下儿童死亡率显著下降。包括新生儿护理和疑难危重病例管理在内的生命支持技术得到了突飞猛进的发展。儿科亚专科临床诊疗、科研水平已与发达国家相当。我们与国际同行合作撰写了多个儿科病症的指南和专家共识，进行全球推广。中国专业知识在国际儿科领域具有巨大影响力，已成为不可或缺的重要力量。国内排名靠前的医学期刊《中华医学杂志》发此专刊，汇集儿科热点、重点问题，刊发基础和临床研究文章9篇，对儿科发展具有重要意义。

Azithromycin mass drug administration (MDA) is a key part of the strategy for controlling trachoma. This systematic review aimed to comprehensively summarize the present studies of azithromycin MDA on trachoma; provide an overview of the impact of azithromycin MDA on trachoma in different districts; and explore the possible methods to enhance the effectiveness of azithromycin MDA in hyperendemic districts.

PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched up to February 2021 with no language restriction. Studies reporting the effect of azithromycin MDA on trachoma were included. Mathematical modeling studies, animal studies, case reports, and reviews were excluded. The trachomatous inflammation-follicular (TF) <5.0% was used to judge the effect of azithromycin MDA on eliminating trachoma as a public health problem. Two researchers independently conducted the selection process and risk of bias assessment.

A total of 1543 studies were screened, of which 67 studies including 13 cluster-randomized controlled trials and 54 non-randomized studies were included. The effect of azithromycin MDA on trachoma was closely related to the baseline prevalence in districts. For the districts with baseline prevalence between 5.0% and 9.9%, a single round of MDA achieved a TF <5.0%. For the districts with baseline between 10.0% and 29.9%, annual MDA for 3 to 5 years reduced TF <5.0%. However, for the districts with high level of baseline prevalence (TF >30.0%), especially with baseline TF >50.0%, annual MDA was unable to achieve the TF <5.0% even after 5 to 7 years of treatment. Quarterly MDA is more effective in controlling trachoma in these hyperendemic districts.

Azithromycin MDA for controlling trachoma depends on the baseline prevalence. The recommendation by the World Health Organization that annual MDA for 3 to 5 years in the districts with TF baseline >10.0% is not appropriate for all eligible districts.

Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.

A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I² ≥ 50%) or fixed-effects model (I² < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.

Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF) %pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I² = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I² = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I² = 72%; P < 0.001) compared with MFC.

SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.

CRD42019133156.

儿童健康是世界范围内日益受到关注的重大健康问题之一，也是衡量一个国家社会进步和经济发展的重要指标。^[1]但我国儿科的发展也面临着医疗卫生资源与医疗需求的巨大矛盾、各地区发展不平衡等诸多问题。^[2]尽管临床实践指南（CPGs）在解决医疗健康问题方面发挥着重要而积极的作用，^[3]先前的研究表明，一些CpG的方法学质量可能不足。调查中国儿科CpG的现状并系统评价其方法学质量是重要和必要的。本文调查和分析了中国儿科CPGs的现状，采用研究与评价指南评价II（AGREE II）工具对中国儿科循证指南的方法学质量进行了评价。本研究的目的是使用AGREE II工具评估2010年至2017年中国出版的儿科循证指南的方法学质量，为指南制定者和使用者提供参考和指导。

胃癌(GC)是世界范围内最常见的恶性肿瘤之一。在中国，GC是第二常见的恶性肿瘤，是癌症死亡的第二大原因。^[1]Correa模型显示肠型GC的发展是一个连续的癌变过程，依次包括正常胃粘膜、非萎缩性胃炎、萎缩性胃炎(AG)、肠上皮化生(IM)、异型增生和肠型GC。^[2]上皮样肠形态取代了胃粘膜，胃粘膜被定义为IM。^[3]在这些癌前疾病中，IM被证明是GC的重要危险因素，尤其是不完全IM和广泛IM。^[4,5]

Histidine-tryptophan-ketoglutarate (HTK) is a solution commonly used for organ transplantation. However, there is no certified fixed regimen for on-pump heart surgery in neonates. We aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage perfusion.

A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages: a standard-dose (SD) group (n = 63, 40 mL/kg < HTK ≤ 60 mL/kg) and a high-dose (HD) group (n = 83, HTK >60 mL/kg). Propensity score matching (PSM) was performed to control confounding bias.

The SD group had a higher weight (3.7 ± 0.4 vs. 3.4 ± 0.4 kg, P < 0.0001), a lower proportion of complete transposition of the great artery (69.8% vs. 85.5%, P = 0.022), a lower cardiopulmonary bypass (CPB) time (123.5 [108.0, 136.0] vs. 132.5 [114.8, 152.5] min, P = 0.034), and a lower aortic x-clamp time (82.9 ± 27.1 vs. 95.5 ± 26.0 min, P = 0.005). After PSM, 44 patients were assigned to each group; baseline characteristics and CPB parameters between the two groups were comparable. There were no significant differences in peri-CPB blood product consumption after PSM (P > 0.05). The incidences of post-operative complications were not significantly different between the two groups. There were no significant differences in ventilation time, intensive care unit stay, and post-operative hospital stay (P > 0.05). Follow-up echocardiography outcomes at 1 month, 3 to 6 months, and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two groups.

In neonatal on-pump cardiac surgery patients, single-shot HD (>60 mL/kg) HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/kg. Thus, this study provides supporting evidence of the safety of HD HTK perfusion.

Prospective analyses have yet to identify a consistent relationship between sleep duration and the incidence of gastrointestinal (GI) cancers. The effect of changes in sleep duration on GI cancer incidence has scarcely been studied. Therefore, we aimed to examine the association between baseline sleep duration and annual changes in sleep duration and GI cancer risk in a large population-based cohort study.

A total of 123,495 participants with baseline information and 83,511 participants with annual changes in sleep duration information were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and their confidence intervals (CIs) for GI cancers according to sleep duration and annual changes in sleep duration.

In baseline sleep duration analyses, short sleep duration (≤5 h) was significantly associated with a lower risk of GI cancer in females (HR: 0.31, 95% CI: 0.10-0.90), and a linear relationship between baseline sleep duration and GI cancer was observed (P = 0.010), especially in males and in the >50-year-old group. In the annual changes in sleep duration analyses, with stable category (0 to -15 min/year) as the control group, decreased sleep duration (≤-15 min/year) was significantly associated with the development of GI cancer (HR: 1.29; 95% CI: 1.04-1.61), especially in the >50-year-old group (HR: 1.32; 95% CI: 1.01-1.71), and increased sleep duration (>0 min/year) was significantly associated with GI cancer in females (HR: 2.89; 95% CI: 1.14-7.30).

Both sleep duration and annual changes in sleep duration were associated with the incidence of GI cancer.

The scale assessment was helpful in predicting the presence of antibodies to autoimmune encephalitis. This study aimed to evaluate the application of antibody prevalence in Chinese patients with epilepsy and encephalopathy (APE2-CHN) and response to immunotherapy in Chinese patients with epilepsy and encephalopathy (RITE2-CHN) for patients with different neuronal surface antibodies.

A total of 1365 patients with epileptic seizures as the prominent feature in Xuanwu Hospital, Capital Medical University, from June 2016 to June 2020 were enrolled in our study. Of these, 915 patients with epilepsy of unknown etiology whose serum and/or cerebrospinal fluid samples were examined for autoimmune antibodies were selected. All patients were scored with antibody prevalence in patients with epilepsy and encephalopathy (APE2), response to immunotherapy with epilepsy and encephalopathy (RITE2), APE2-CHN, and RITE2-CHN scores.

Of the 915 patients, 191 patients were positive for neural-surface specific antibodies (115 N-methyl-D-aspartate receptor (NMDAR) Ab, 47 leucine-rich glioma-inactivated protein 1 (LGI1) Ab, 8 contactin-associated protein 2 (CASPR2) Ab, 4 AMPA2RAb, and 11 GABAR-B-Ab; 3 CASPR2-Ab and LGI1-Ab, 2 NMDAR-Ab and CASPR2-Ab, and 1 NMDAR-Ab and myelinoligodendrocyte glycoprotein [MOG] Ab). The sensitivity and specificity of APE2 ≥4 in predicting the presence of neural-surface specific antibodies in our study were 74.35% and 81.77%, respectively, and the sensitivity and specificity of APE2-CHN ≥4 were 75.92% and 84.53%, respectively. Eight cases had an APE2 score <4 and APE2-CHN score ≥5; all these patients had memory decline as the prominent manifestation. We divided the patients into six groups according to the different antibodies. APE2-CHN scores showed higher sensitivity for the prediction of NMDAR-Ab, but lower sensitivity for LGI1-Ab. A total of 187/191 (97.91%) patients received immunotherapy and 142/191 (74.35%) patients benefited from the treatments. The patients who were positive for LGI1-Ab with RITE2-CHN ≥8 responded well to immunotherapy.

APE2-CHN had the highest value for predicting the positivity of NMDAR-Ab and RITE2-CHN evaluated the response of immunotherapy for anti-LGI1 encephalitis appropriately. However, RITE2 and RITE2-CHN do not appear to be good predictors of immunotherapy outcomes for patients with specific neuronal-surface antibodies and high APE2-CHN scores are often indicative of a poor response to immunotherapy.

Single subcortical infarction (SSI) is caused by two main etiological subtypes, which are branch atheromatous disease (BAD) and cerebral small vessel disease (CSVD)-related SSI. We applied the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ), the Shape Trail Test (STT), and the Stroop Color and Word Test (SCWT) to investigate the differences in cognitive performance between these two subtypes of SSI.

Patients with acute SSIs were prospectively enrolled. The differences of MoCA-BJ, STT, and SCWT between the BAD group and CSVD-related SSI group were analyzed. A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function. We investigated the correlations between MoCA-BJ, STT, and SCWT using Spearman’s correlation analysis and established cut-off scores for Shape Trail Test A (STT-A) and STT-B to identify cognitive impairment in patients with SSI.

This study enrolled a total of 106 patients, including 49 and 57 patients with BAD and CSVD-related SSI, respectively. The BAD group performances were worse than those of the CSVD-related SSI group for STT-A (83 [60.5-120.0] vs. 68 [49.0-86.5], P= 0.01), STT-B (204 [151.5-294.5] vs. 153 [126.5-212.5], P= 0.015), and the number of correct answers on Stroop-C (46 [41-49] vs. 49 [45-50], P = 0.035). After adjusting for age, years of education, National Institutes of Health Stroke Scale and lesion location, the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.

BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language, attention, executive function, and memory. The mechanism of cognitive impairment after BAD remains unclear.

The association between miR-532-3p and tongue squamous cell carcinoma (TSCC) has been examined in the literature to improve the survival rate of patients with this tumor. However, further studies are needed to confirm the regulatory roles of this microRNA (miRNA) in TSCC. The objective of this study was to investigate the roles played by and the underlying mechanism used by the miR-532-3p/podoplanin (PDPN) axis in TSCC development.

Western blotting and quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) were performed to evaluate the PDPN expression level in TSCC tissues and cells. The proliferative, adhesive, and migratory capabilities of TSCC cells (CAL-27 and CTSC-3) were examined using cell counting kit-8 (CCK-8), cell adhesion, and wound-healing assays, respectively. The dual-luciferase reporter (DLR) assay was later conducted to confirm the relationship between miR-532-3p and PDPN.

The results indicated that PDPN expression was enriched in TSCC tissues and cells, and that the expression of PDPN was associated with some clinicopathological parameters of TSCC, including lymph node metastasis (P = 0.001), tumor-node-metastasis (TNM) staging (P = 0.010), and grading (P = 0.010). Further analysis also showed that PDPN knockdown inhibited the viability, adhesive ability, and migratory capacity of CAL-27 and CTSC-3 cells, effects that could be reversed by the application of a miR-532-3p inhibitor. Additionally, PDPN was found to be a direct target of miR-532-3p.

This research suggested that by targeting PDPN, miR-532-3p could inhibit cell proliferation viability, adhesion, and migration in TSCC. Findings also revealed that the miR-532-3p/PDPN axis might provide more insights into the prognosis and treatment of TSCC.

慢性髓性白血病（CML）在儿童中相对罕见，儿童年平均发病率为0.6~1.0例/百万<15岁和15至19岁青少年每百万例2.2例，分别占这两个年龄组所有新诊断白血病病例的2%至3%和9%。^[1]甲磺酸伊马替尼（IM）于2003年获得美国食品药品监督管理局（FDA）批准上市，目前已逐渐取代造血干细胞移植（HSCT）成为儿童慢性期CML（CML-CP）患者的一线治疗药物。^[2]然而，25%至29%的CML-CP儿科患者因耐药性或不耐受而停止IM治疗。^[3]对于此类患者，包括达沙替尼和尼洛替尼在内的第二代酪氨酸激酶抑制剂（2G-TKIs）分别于2017年和2018年被FDA批准作为一线和二线疗法。^[2]然而，鉴于这种肿瘤的罕见性和临床试验数据的缺乏，儿童CML的治疗遵循推荐的成人方案，对这些治疗在儿童和青少年中的长期疗效和安全性知之甚少。^[2]此外，很少有报告详细说明在中国儿童CML患者中连续使用IM作为一线治疗，然后使用2G-TKIs作为二线治疗。因此，非常需要在中国儿科患者的大型队列中调查IM治疗的长期效果。在本报告中，我们回顾性分析了在单个华南中心接受IM作为一线治疗和2G-TKIs作为二线治疗的58例CML-CP儿科患者的长期随访结果。

致编辑：营养缺乏是中低收入国家的主要公共卫生问题之一。由于儿童和青少年的快速生长和发育需求，他们特别容易营养不良。2015年，营养缺乏是195个国家和地区儿童和青少年残疾寿命的十大全球原因之一。^[1]营养缺乏可能对儿童和青少年的身体和认知发育产生不可逆转的影响，这可能导致更高的发病率和死亡率以及晚年生产力下降。营养缺乏是中国儿童和青少年的主要健康问题之一。2010年，中国0至14岁儿童因营养缺乏导致的死亡约占中国居民因营养缺乏死亡总人数的11.46%。^[2]了解全国儿童和青少年营养缺乏的疾病负担有助于有效的疾病控制和预防，这可能会促进未来改善所有人的健康。

致编辑：随着2019冠状病毒病（COVID-19）大流行在许多国家继续扩大，以及更具传染性的变种出现，第二波疫情可能会更加严重，并导致更大的感染和死亡率高峰。迫切需要开发有效的疫苗，这仍然是控制疫情的关键工具。在疫情持续爆发的地区和控制良好的国家，接种疫苗同样重要。

致编辑：手足口病（HFMD）是公认的由一组全球分布的肠道病毒（EVs）引起的儿科传染病。目前，手足口病仍然是中国儿童健康的主要威胁之一，2018年估计有20,537,199例病例，导致3667人死亡。^[1]现有数据表明，大多数手足口病病例是由肠道病毒71（EV-71）和柯萨奇病毒A16（CV-A16）血清型引起的。发现EV-71在严重和致命病例中占主导地位。从2015年开始，三种EV-71单价灭活疫苗在中国获得许可，并被证明对EV-71引起的手足口病具有很高的保护效力，但对非EV-71血清型无交叉保护作用，^[2]EVs表现出高度的地理多样性和血清型多样性。最近，人们对具有严重病例的CV-A6和CV-A10的爆发以及罕见血清型如echo病毒11和echo病毒30的出现感到担忧。疫苗保护覆盖率不足、地理多样性和手足口病病因谱的变化仍然是中国手足口病综合防控的挑战。关于HFMD流行病学的广泛特征，以及随着EV-71疫苗接种的进展，病毒遗传多样性和进化动态的转变的信息仍然有限。因此，我们对2014年至2019年四川省引进EV-71疫苗前后手足口病的流行病学和病原学特征进行了全面的回顾性分析，以期有助于该地区更好地预防和控制手足口病。

致编辑：全球每年新发宫颈癌病例53万例，死亡27万例，其中85%发生在发展中国家。其中，中国每年约有15万宫颈癌新发病例，占全球患者总数的三分之一。^[1]疫苗是预防传染病最经济、最有效的方法。要从根本上阻断人乳头瘤病毒（HPV）的传播，最有效的措施就是接种安全有效的HPV疫苗。^[2,3]大量研究表明，基于HPV L1病毒样颗粒（VLPs）的疫苗具有良好的安全性和保护效力。^[4]HPV16、HPV18、HPV58病毒感染是中国女性宫颈癌的主要病因。通过预防HPV16、HPV18、HPV58病毒的感染，可以预防85.0%~93.7%的宫颈癌。^[5]

致编辑：尽管局部麻醉提供了延长的术后镇痛，但没有合适的方法可以促进阻断的早期逆转，直到局部麻醉剂的作用持续时间已经过去。大量生理盐水用于逆转中枢神经轴阻滞。^[1,2]然而，据我们所知，没有研究报道在周围神经阻滞，尤其是肋锁骨阻滞中逆转神经阻滞的方法。在此，我们报告了一例肩部手术后接受连续肋锁骨阻滞镇痛的患者在通过导管注射生理盐水后运动和感觉功能显著恢复的病例。