Volume 134 · Issue 03 · 2021

组织工程(TE)，代表通过以下方式重建或修复器官和组织的技术体外使用生物活性物质的培养或构建已经成为用于组织重建和再生的最常用方法之一。它是一种极好的、可用的生物材料，不仅具有生物相容性和可降解性，而且还可以有效地将细胞和生长因子转运到受损组织，并为新形成的组织提供支持，直到其成熟。

多发性硬化症(MS)是一种发生于中年的中枢神经系统(CNS)自身免疫性疾病，其引起显著的社会和经济问题。目前现代西医对MS的治疗效果有所提高。然而，有一些严重的副作用，如进行性多灶性白质脑病和严重感染，这可能是由普遍的免疫抑制引起的。^[1,2,3]

Conventional pressure support ventilation (PS_P) is triggered and cycled off by pneumatic signals such as flow. Patient-ventilator asynchrony is common during pressure support ventilation, thereby contributing to an increased inspiratory effort. Using diaphragm electrical activity, neurally controlled pressure support (PS_N) could hypothetically eliminate the asynchrony and reduce inspiratory effort. The purpose of this study was to compare the differences between PS_N and PS_P in terms of patient-ventilator synchrony, inspiratory effort, and breathing pattern.

Eight post-operative patients without respiratory system comorbidity, eight patients with acute respiratory distress syndrome (ARDS) and obvious restrictive acute respiratory failure (ARF), and eight patients with chronic obstructive pulmonary disease (COPD) and mixed restrictive and obstructive ARF were enrolled. Patient-ventilator interactions were analyzed with macro asynchronies (ineffective, double, and auto triggering), micro asynchronies (inspiratory trigger delay, premature, and late cycling), and the total asynchrony index (AI). Inspiratory efforts for triggering and total inspiration were analyzed.

Total AI of PS_N was consistently lower than that of PS_P in COPD (3% vs. 93%, P = 0.012 for 100% support level; 8% vs. 104%, P = 0.012 for 150% support level), ARDS (8% vs. 29%, P = 0.012 for 100% support level; 16% vs. 41%, P = 0.017 for 150% support level), and post-operative patients (21% vs. 35%, P = 0.012 for 100% support level; 15% vs. 50%, P = 0.017 for 150% support level). Improved support levels from 100% to 150% statistically increased total AI during PS_P but not during PS_N in patients with COPD or ARDS. Patients’ inspiratory efforts for triggering and total inspiration were significantly lower during PS_N than during PS_P in patients with COPD or ARDS under both support levels (P < 0.05). There was no difference in breathing patterns between PS_N and PS_P.

PS_N improves patient-ventilator synchrony and generates a respiratory pattern similar to PS_P independently of any level of support in patients with different respiratory system mechanical properties. PS_N, which reduces the trigger and total patient’s inspiratory effort in patients with COPD or ARDS, might be an alternative mode for PS_P.

ClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/record/NCT01979627.

Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs.

In a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs.

There were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was -7.9 mmHg (95% CI, -9.9 to -5.9) in the brand-name drug group and -7.1 mmHg (95% CI, -9.1 to -5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2-2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment.

Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.

The development of the technique has improved the success rate of percutaneous coronary intervention (PCI) for instent chronic total occlusion (IS-CTO). However, long-term outcomes remain unclear. The present study sought to investigate long-term outcomes of PCI for IS-CTO.

A total of 474 IS-CTO patients were enrolled at two cardiac centers from 2015 to 2018 retrospectively. These patients were allocated into either successful or failed IS-CTO PCI groups. The primary endpoint (major adverse cardiac events [MACE]) consisted of recurrent angina pectoris (RAP), target-vessel myocardial infarction (MI), heart failure, cardiac death, or ischemia-driven target-vessel revascularization (TVR) at follow-up. Multivariable Cox regression analysis was used to investigate the association between treatment appropriateness and clinical outcomes.

A total of 367 patients were successfully treated with IS-CTO PCI while 107 patients had failed recanalization. After a median follow-up of 30 months (interquartile range: 17-42 months), no significant difference was observed between the two groups for the following parameters: cardiac death (successful PCI vs. failed PCI: 0.9% vs. 2.7%; adjusted hazard ratio [HR]: 1.442; 95% confidence interval [CI]: 0.21-9.887; P = 0.709), RAP (successful PCI vs. failed PCI: 40.8% vs. 40.0%; adjusted HR: 1.025; 95% CI: 0.683-1.538; P = 0.905), heart failure (successful PCI vs. failed PCI: 6.1% vs. 2.7%; adjusted HR: 0.281; 95% CI: 0.065-1.206; P = 0.088), target-vessel related MI (successful PCI vs. failed PCI: 1.5% vs. 2.7%; adjusted HR: 1.150; 95% CI: 0.221-5.995; P = 0.868), MACE (successful PCI vs. failed PCI: 44.2% vs. 45.3%; adjusted HR: 1.052; 95% CI: 0.717-1.543; P = 0.797). More patients were free of angina in the successful IS-CTO PCI group compared with failed PCI in the first (80.4% vs. 60%, P < 0.01) and second years (73.3% vs. 60.0%, P = 0.02) following up. Successful IS-CTO PCI had a lower incidence of MACE in the first and second years (20.2% vs. 40.0%, P < 0.01; 27.9% vs. 41.3%, P = 0.023) compared with failed PCI. After a median follow-up of 30 months, the reocclusion rate was 28.5% and TVR was 26.1% in the successful IS-CTO PCI group. Receiving >18 months of dual antiplatelet therapy (DAPT) was an independent predictor of decreased risk of TVR (HR: 2.682; 95% CI: 1.295-5.578; P = 0.008) or MACE (without TVR) (HR: 1.898; 95% CI: 1.036-3.479; P = 0.038) in successful IS-CTO PCI.

After a median follow-up of 30 months, the successful IS-CTO PCI group had MACE similar to that of the failed PCI group. However, the successful IS-CTO PCI group had improved angina symptoms and were free from requiring coronary artery bypass grafting in the first or second years. To decrease MACE, DAPT was found to be essential and recommended for at least 18 months for IS-CTO PCI.

Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study.

Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up.

Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6 ± 77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group.

Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in "real-world" patients with NVAF.

Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses.

We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves.

Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ² = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ² = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ² = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224-0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006).

Our single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.

Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.

Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.

ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3′,5′-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).

ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

High agglomeration of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin (DOX) to enhance immune efficacy in NB.

Bagg albino (BALB/c) mice were used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control groups (n = 20). The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition. NB antigen-specific cytotoxic T cells (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following low-dose DOX administration, immunotherapy was applied. The levels of human leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-γ in peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and tumor growth were compared among the groups. The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results.

The slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 (F = 271.686), Thl/Th2 cytokines, CD4⁺ and CD8⁺ lymphocytes, granzyme (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-γ (F = 240.709) in peripheral blood of each immunotherapy group were all higher compared with the control group (all of P values < 0.05). The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups.

Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.

Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for the study of brain function. Typically, rs-fMRI is performed on anesthetized animals. Although different functional connectivity (FC) in various anesthetics on whole brain have been studied, few studies have focused on different FC in the aged brain. Here, we measured FC under three commonly used anesthesia methods and analyzed data to determine if the FC in whole brain analysis were similar among groups.

Twenty-four male aged Wistar rats were randomly divided into three groups (n = 8 in each group). Anesthesia was performed under either isoflurane (ISO), combined ISO + dexmedetomidine (DEX) or α-chloralose (AC) according to the groups. Data of rs-fMRI was analyzed by FC in a voxel-wise way. Differences in the FC maps between the groups were analyzed by one-way analysis of variance and post hoc two-sample t tests.

Compared with ISO + DEX anesthesia, ISO anesthesia caused increased FC in posterior brain and decreased FC in the middle brain of the aged rat. AC anesthesia caused global suppression as no increase in FC was observed.

ISO could be used as a substitute for ISO + DEX in rat default mode network studies if the left temporal association cortex is not considered important.

鹦鹉热是一种人畜共患病鹦鹉热衣原体一种革兰氏阴性细胞内细菌。这种情况是由摄入受感染鸟类受污染的粪便和鼻腔分泌物引起的。人类鹦鹉热的严重程度从轻微的流感样症状到危及生命的严重肺炎不等。^[1]鉴于此鹦鹉热不是传统微生物学诊断的一部分。人类鹦鹉热经常被漏报、误诊和诊断不足。在本研究中，鹦鹉热对肺炎患者进行回顾性分析。

慢性液体超负荷（FO）是导致接受血液透析（HD）的患者高发病率和死亡率的众所周知的因素。^[1]高血压（BP）通常与超负荷容量有关。^[1,2,3,4]因此，测量时间点（例如，透析前和透析后）和容量状态可能影响HD患者BP的预后价值。本研究旨在检查液体容量和血压之间的相关性，以及它们对无冠状动脉疾病（CAD）的HD患者的预后影响。

肺栓塞（PE）患者静脉血栓栓塞（VTE）的复发率很高，复发通常是致命的。长期抗凝治疗可有效预防复发，但出血风险也随之增加。因此，VTE复发的风险评估在PE患者中很重要，因为高风险患者将受益于长期抗凝治疗，而低风险患者将不必要地暴露于增加的出血风险。在非亚洲人群中已经确定了VTE复发的几个危险因素，包括男性、高龄、血栓形成倾向、肥胖、停用抗凝治疗一个月后D-二聚体持续升高和残留血栓形成。然而，尚未在中国和亚洲人群中明确评估VTE复发的危险因素。最近的一项研究发现，用于评估急性PE患者疾病严重程度的欧洲心脏病学会（ESC）PE患者风险分层（2008年版）与VTE复发相关。^[1]简化肺栓塞严重程度指数（sPESI）也被广泛验证用于评估PE的疾病严重程度，对早期甚至长期死亡率具有良好的预后价值。尚不清楚该模型是否能预测VTE复发。本前瞻性研究的目的是调查急性PE首次发作后复发性VTE的短期和长期发生率以及复发性VTE的相关危险因素。还评估了VTE复发与sPESI评估的疾病严重程度之间的相关性。

致编辑：下呼吸道感染（LRTIs）是最致命的疾病之一，并且在过去15年中仍然是死亡的主要原因之一，特别是在低收入国家，并且是免疫抑制个体非常关注的问题。在计算机断层扫描（CT）上，位于外周肺野（PLF）的感染位于肺门周围的外三分之一椭圆形区域内。^[1]它们被正常肺实质包围，不太可能通过支气管镜观察和准确诊断。最近的研究已经证明了虚拟支气管镜导航（VBN）辅助支气管镜作为小周围性肺部病变的诊断工具的价值。宏基因组学下一代测序（mNGS）是一种可与第一代DNA测序技术相媲美的新测序方法。使用mNGS，我们可以对临床样本进行高通量测序，以分析微生物群落。为了筛选病原体，mNGS只需要直接从样品中提取少量DNA，以及生物信息学工具，该工具通过将测序读数与准确的参考基因组（或标记）数据库联系起来来识别病原体。本研究的目的是探索VBN联合mNGS作为成人LRTIs住院的潜在诊断工具的价值。

致编辑：中国胸科学会（CTS）于2016年更新了中国成人社区获得性肺炎（CAP）临床实践指南，^[1]并于2016年至2017年在全国范围内开展了一系列指南培训项目。为了衡量指南培训计划的成就并识别CAP管理的问题，我们在2018年3月至7月期间对负责CAP管理的医生进行了一次全国性的电子问卷调查。

致编辑：肥厚型心肌病（HCM）发生缺血性卒中的风险增加（在未选择的HCM患者中为5%-10%），而出血性卒中仅占HCM患者的不超过0.6%。^[1]我们报告了一例罕见的HCM并发出血性中风的病例，由潜在的烟雾病引起。

致编辑：伴有远处转移的鼻翼肺泡横纹肌肉瘤（ARMS）预后极差。由于鼻翼原发部位手术难以完全切除，远处转移不易控制。在此，我们提出一个不寻常的病例，一个29个月大的男孩，手臂在左鼻翼伴有骨转移，他接受了全身化疗以及¹²⁵I间质近距离放射治疗，这种特殊的多学科管理导致了完美的预后和轻微的长期副作用。

致编辑：一名59岁的中国男性，表现为严重咳嗽和呼吸急促，于2018年10月入院。计算机断层扫描显示一个4.0 cm × 2.0 cm的肿瘤位于右肺下叶[图1A]和多发性骨病变，进行芯针活检并经病理学家证实为腺癌。肿瘤学家和病理学家诊断为IVB期T4N3M1c的转移性肺腺癌。对活检肿瘤进行下一代测序（NGS），并对表皮生长因子受体（EGFR）发现外显子21 L858R突变，突变等位基因分数（MAF）为24.8%。埃克替尼（贝达制药有限公司，中国杭州），第一代EGFR酪氨酸激酶抑制剂（TKI），口服剂量为125 mg，每日三次。根据实体瘤缓解评估标准1.1，患者在5个月后获得部分缓解（PR）[图1B].磁共振发现多发性脑转移，右肺肿瘤增大[图1C]埃克替尼治疗9个月后。对新活检的进展肺组织进行NGS，表明T790M突变为阴性，MAFEGFR外显子21 L858R从24.8%降至1.83%。考虑到患者拒绝推荐的化疗，给予患者奥希替尼（80 mg，每日一次）。1个月后肺部肿瘤进展[图1D].采用卡铂和培美曲塞进行全身治疗，治疗2个月后病情稳定。然而，疾病在4个月后进展[图1E]，且患者的东部肿瘤协作组（ECOG）体能状态（PS）降至4级。用血清进行NGS和MAFEGFR外显子21 L858R突变增加至5.5%；MET还发现了拷贝数为3.1的扩增。考虑到患者病情危重，无法进行再活检MET未通过免疫组织化学或荧光再次证实扩增原地杂交。一种组合治疗，由克唑替尼（250 mg，每日两次）和第一代EGFR-给予TKI厄洛替尼（150 mg，每日一次）。患者ECOG评分改善至2分；原发性肺肿瘤长度减少51%[图1F].患者在咳嗽、呼吸困难和食欲等症状方面也获得了显著改善。在最后一次随访时，他的疾病控制了2个月。副作用是轻度痤疮和厌食。未发生腹泻、肺炎或转氨酶炎。

致编辑：随着腹腔镜技术的进步，微创手术在各种情况下得到了更广泛的应用。该指南由美国胃肠内窥镜外科医生协会（SAGES）于2017年发布，认为腹腔镜手术可以在怀孕的任何阶段安全地进行，尽管最好是在中期。^[1]自2004年以来，我们的团队已经为希望保留妊娠的怀孕患者进行了150多次腹腔镜手术。然而，这些病例中只有6例处于晚期。在此，我们报告一例妊娠35周时通过腹腔镜卵巢囊肿切除术成功治疗右侧卵巢囊肿扭转的病例。手术后，40岁时分娩了一名体重3000克的健康女性⁺²怀孕几周。

在最初的文章发表之后，^[1]作者告诉我们以下错误。