Volume 135 · Issue 08 · 2022

慢性淋巴细胞白血病（CLL）在中国汉族人中的发病率比主要为欧洲血统的人低10至20倍，相当于每10E+5人口/年的发病率为0.2至0.6vs.4.6每10E+5人口/年。^[1,2,3]这种显著较低的发病率以及因此在中国的患病率的原因尚不清楚，但与其他亚洲国家（包括日本人、韩国人和其他国家）有共同之处。^[4,5,6]对中国CLL患者的大型队列研究相对罕见，在中国大陆也没有基于人群的研究。报道了中国人和以欧洲血统为主的人之间的几个表面上的差异，如诊断年龄更小、背景基因型不同、IGHV突变，不同的刻板印象使用和不同的突变地形。^[7]然而，一般来说，汉族人中的大多数CLL病例与以欧洲血统为主的人中的CLL相似。

免疫性血小板减少症（ITP）是一种以孤立性血小板减少为特征的获得性疾病，是妊娠期血小板减少最常见的原因之一。患有严重血小板减少症的ITP妇女发生危及生命的产科并发症的风险增加。因此，我们就妊娠期ITP的诊断和管理建立了这一共识声明（详细信息可在补充文件http://links.lww.com/CM9/A978中获得）。

Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).

A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool.

In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26, P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17, P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42, P < 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48-4.71, P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-α inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68, P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22, P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69, P = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91, P < 0.001); higher risk of URTI for TNF-α inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78, P= 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36, P = 0.018); higher risk of nasopharyngitis for TNF-α inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84, P= 0.006).

This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

NOTCH1 mutation is an essential molecular biologic aberration in chronic lymphocytic leukemia (CLL). CLL patients with NOTCH1 mutation have shown an unfavorable survival and a poor response to chemoimmunotherapy. This study aims to present the mechanisms of adverse prognosis caused by NOTCH1 mutation from the perspective of the splicing factor heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1).

The microarray data in Gene Expression Omnibus datasets were analyzed by bioinformatics and the function of hnRNPA1 was checked by testing the proliferation and apoptosis of CLL-like cell lines. Afterward, quantitative reverse transcription-polymerase chain reaction and Western blotting were applied to explore the relationship among NOTCH1, c-Myc, and hnRNPA1.

RNA splicing was found to play a vital part in NOTCH1-mutated CLL cells; hence, hnRNPA1 was selected as the focus of this study. Higher expression of hnRNPA1 validated in primary NOTCH1-mutated CLL samples could promote proliferation and inhibit apoptosis in CLL. The expression of hnRNPA1 increased when NOTCH1 signaling was activated by transfection with NOTCH1 intracellular domain (NICD)-overexpressed adenovirus vector and declined after NOTCH1 signaling was inhibited by NOTCH1-shRNA. Higher expression of c-Myc was observed in NICD-overexpressed cells and hnRNPA1 expression was downregulated after applying c-Myc inhibitor 10058-F4. Moreover, in NICD-overexpressed cells, hnRNPA1 expression decreased through c-Myc inhibition.

Overexpression of c-Myc-dependent hnRNPA1 could promote proliferation and inhibit apoptosis in NOTCH1- mutated CLL cells, which might partly account for the poor prognosis of patients with NOTCH1 mutation.

Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.

This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.

A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups.

HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.

ClinicalTrials.gov: NCT01883180, NCT02673008.

The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.

A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed.

Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5-year overall survival [OS]: 58.5% vs. 100%, P = 0.003; 5-year event-free survival [EFS]: 54.1% vs. 83.4%, P = 0.010; 5-year cumulative incidence of relapse [CIR]: 45.2% vs. 6.3%, P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1% vs. 54.1%, P = 0.041; 5-year CIR: 11.6% vs. 45.2%, P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0% vs. 58.5%, P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR; age ≥10 years was an independent risk factor for OS and EFS; and high white blood cell count was an independent risk factor for EFS and CIR.

Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.

Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.

The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).

A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DM vs. 19.3% in non-DM, P = 0.026) and N3b status (18.8% in DM vs. 12.8% in non-DM, P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771, P= 0.011) and N3b status (OR= 1.752, P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424, P = 0.047). The preponderance of N3 stations metastasis (DM vs. non-DM, T1-2: 2.2% vs. 4.9%, T3: 29.0% vs. 20.3%, T4a: 38.9% vs. 25.8%, T4b: 50.0% vs. 36.6%; ELN16-29: 8.6% vs. 10.4%, ELN30-44: 27.9% vs. 20.5%, ELN ≥ 45: 37.7% vs. 25.3%), N3b status (DM vs. non-DM, T1-2: 0% vs. 1.7%, T3: 16.1% vs. 5.1%, T4a: 27.8% vs. 19.1%, T4b: 44.0% vs. 28.0%; ELN16-29: 8.6% vs. 7.9%, ELN30-44: 18.0% vs. 11.8%, ELN ≥ 45: 26.4% vs. 17.3%), and the number of MLN (DM vs. non-DM, T1-2: 0.4 vs. 1.1, T3: 8.6 vs. 5.2, T4a: 9.7 vs. 8.6, T4b: 17.0 vs. 12.8; ELN16-29: 3.6 vs. 4.6, ELN30-44: 5.8 vs. 5.5, ELN ≥ 45: 12.0 vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN.

DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients.

This was a retrospective study based on a consecutive cohort of 1191 SLE patients; 273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, ie, with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions; type B, subcortical hyperintense WM lesions; and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis.

Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002, P = 0.018, P = 0.045, and P = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 and P = 0.027, respectively), and these patients were more likely to present with disease damage (P < 0.001). In addition, the patients with hyperintense WM lesions exhibited a higher frequency of proteinuria (P = 0.009) and higher levels of CD8⁺ T cells (P = 0.005). In the multivariate logistic analysis, hyperuricemia and higher CD8+ T cells percentages were significantly correlated with hyperintense WM lesions in SLE patients (P= 0.019; OR 2.129, 95% confidence interval [CI] 1.313-4.006 and P < 0.001; OR 1.056, 95% CI 1.023-1.098, respectively).

Hyperintense WM lesions are common in SLE patients and significantly associated with systemic involvement, including NPSLE, LN, polyserous effusions, cardiac involvement, and disease damage. Hyperuricemia and a higher number of CD8+ T cells were independent factors associated with hyperintense WM lesions in SLE.

Hemifacial microsomia (HFM), which involves multiple sites with different levels of severity, is the second most common congenital craniofacial deformity after cleft lip and palate. However, three-dimensional (3D) measurements of mandibular deformities have not yet been studied in detail. The objective of this study is to investigate the method of 3D measurements of mandibular deformities in HFM patients.

A total of 48 HFM patients were included in this study. All clinical treatment for patients was performed in the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences at Peking Union Medical College from June 2006 to June 2020. The patients’ 3D computerized tomography scan data were processed using medical imaging software, following four iterative steps: 3D reconstruction, mirroring, differential analysis, and partition.

The characteristics of the mandibular bone in HFM patients are mainly presented as follows: (1) compared to the normal side, the part of the bone body that extends from the ascending ramus to the pogonion (Po-NB) is analyzed using a dynamic process: less fullness-fullness-more fullness; (2) absences were frequently observed among the angular zones, that is, the height of the ascending ramus is deficient.

HFM is a complicated condition with numerous variations in clinical presentation. We employed both 3D image reconstruction and computerization image processing techniques to investigate asymmetrical mandibular deformity in HFM patients in detail and with great accuracy. This will be of great use to clinicians for disease management.

重症监护超声（CCUS）在评估休克、呼吸衰竭和指导中心静脉通路方面至关重要。^[1]护士还使用超声波进行护理实践，如血栓筛查、超声引导血管穿刺、饲管放置和肺部物理治疗。^[2]CCUS的优势是无辐射、便携性和低成本。因此，CCUS在重症监护中具有相当大的临床用途。然而，超声图像的获取是准确评估的基础，超声的准确性与操作者技能水平有关。此外，CCUS在护理中的应用取决于护士的知识和培训。尽管已经对CCUS进行了许多临床研究，但关于重症监护室（ICU）护士超声培训计划的证据很少。^[3]在这项研究中，我们为ICU护士设计并实施了一个新的CCUS培训计划。我们的目的是评估短期教学培训对学员CCUS知识和技能的影响。

由于神经外科操作、出血、感染或肿瘤引起的多房性脑积水（MLH）在成人中并不常见，不能通过内窥镜开窗术或单侧脑室—腹膜分流术（VPS）轻松解决，目前还没有关于MLH手术策略的共识报道。治疗的目标是恢复被困心室间室之间的连通，^[1]目前的治疗方法包括通过内窥镜检查或开颅手术对分离的截留进行显微外科开窗，将多个导管放置在截留隔室中的分流手术，或这些方式的组合。^[2]现有证据似乎支持神经内窥镜作为一线治疗，而不是传统的分流术。然而，由于个体解剖复杂性和脑脊液流体力学，每个MLH病例必须单独评估。应用哪种治疗的决定基于个体解剖结构、潜在病理学、可用技术和治疗外科医生的经验。因此，不应排除文献中提出的任何程序先验的.^[1]Y型分支VPS与内镜开窗术治疗复杂性MLH具有优势互补，仍是交通性脑积水和内镜开窗术失败后的首选治疗方法。

食管裂孔疝（HH）通常与胃食管反流病（GERD）有关。HH会增加GERD的发病率。^[1]这些疾病的共存增加了治疗的难度，并且对于内镜治疗来说可能具有挑战性。最近出现了小HHs（≤2 cm）合并难治性GERD的治疗方法。然而，在内镜下治疗大型HHs（≥3 cm）合并难治性GERD方面仍存在知识空白。我们开发了一种新的内镜方法，称为食管裂孔疝—内镜粘膜下剥离术（HH-ESD），并进行了本研究，以阐明HH-ESD的有效性和安全性。

致编辑：自2019年12月爆发以来，严重急性呼吸综合征冠状病毒2（新型冠状病毒）已在全球范围内感染了>24亿人，导致>490万人死亡。为了了解新型冠状病毒感染的发病机制，已经在不同疾病阶段的冠状病毒疾病-2019（新冠肺炎）患者中构建了外周血单核细胞（PBMCs）的单细胞RNA测序（scRNA-seq）图谱。^[1]这些数据显示了中度患者中典型的干扰素应答和细胞毒性效应T细胞亚群的扩增。^[1]急性呼吸窘迫综合征患者进展为重型后，浆母细胞和非典型中性粒细胞亚群升高。^[1]相反，处于恢复期的患者浆细胞增加，并伴有新的B细胞受体变化。^[2]

致编辑：失血性休克是一种以微循环功能障碍和低灌注为特征的临界病理过程，严重后果是细胞损伤和器官功能障碍。肠屏障功能障碍是失血性休克引起远处器官损伤的关键环节。星状神经节阻滞（SGB）预防性治疗可显著减少失血性休克诱导的肠屏障损伤。^[1]然而，目前尚不清楚SGB后处理是否也能减轻失血性休克后的肠屏障损伤，这对于扩大SGB的临床应用至关重要。自噬是一种高度保守的分解代谢过程，通过细胞内溶酶体发生，在维持细胞稳态和存活中起着独特而重要的作用。既往研究表明，自噬的过度激活会加重缺血性肠损伤，而自噬抑制则会减轻肠粘膜屏障损伤。^[2,3]因此，自噬在SGB保护肠屏障中的作用尚不清楚。因此，我们推测SGB后处理通过抑制自噬激活来抑制失血性休克引起的肠屏障损伤。为了验证这一假设，我们研究了SGB后处理对失血性休克大鼠存活率、肠血流量、肠组织形态、肠屏障功能和自噬相关机制的影响。

致编辑：自发性脑出血（sICH）是我国老年人急性脑血管病中发病率较高的一种，死亡率高，存活者有远期功能损害。然而，ICH后住院期间继发感染是否对远期功能产生负面影响仍存在争议。阿里等人^[1]说明感染与ICH后90天患者的功能预后无关。相比之下，主啊等人^[2]发现脑出血后并发感染与不良预后有显著相关性。既往研究表明脓毒症相关脑病是ICH后院内昏迷的独立危险因素，^[3,4]但是关于脓毒症对sICH术后长期结局的比例和影响的临床研究仍然缺乏。

致编辑：恶性血液病治疗过程中胸部病变的发病率很高，除感染外，肿瘤复发或侵犯也很常见。由于血小板低和免疫力低下，经皮肺活检或支气管镜检查可能导致严重的咯血、气胸或感染，并且由于诊断不明确，治疗通常无效。即使当患者被诊断患有真菌疾病时，仅使用抗真菌药物也很难消除病变。电视辅助胸外科（VATS）是一种重要的外科手术，用于在微创环境中进行充分的疼痛缓解和镇静，允许在自主呼吸下进行胸部手术。^[1,2]我们在此报告一系列病例，以评估VATS在血液科通过肺活检或肺切除术进行诊断的可行性和安全性。

致编辑：胃肠道（GI）癌是中国最常见的恶性肿瘤。^[1]几十年来，胃肠道癌症的治疗选择仅限于手术、放疗和化疗。近年来，靶向程序性细胞死亡1（PD-1）或其程序性死亡配体1（PD-L1）的免疫检查点抑制剂（ICIs）已经显示出有希望的功效，并改变了胃肠道癌症的治疗前景。^[2]然而，在ICI治疗期间可能发生免疫相关不良事件（irAE）。此外，ICI相关的心脏毒性是一种罕见但潜在致命的毒性作用。

致编辑：扩张型心肌病（DCM）是一种病因不明的原发性心肌病。^[1]它是一种以左心室扩张和收缩功能障碍为主要特征的心肌疾病，由心肌对遗传和环境损伤的反应引起。临床表现为进行性心力衰竭、心律失常、血栓栓塞，甚至猝死。DCM的发病率和死亡率一直稳步上升，已成为心肌病的主要死亡原因之一。DCM可能涉及传导系统，并且通常与各种类型的心律失常相关，例如心房颤动（AF）。^[2]房颤会增加血管栓塞的风险。研究表明，房颤患者卒中发病率增加5倍，死亡率增加2倍。大约15%-20%的缺血性卒中是由AF引起的。DCM患者AF引起的血流动力学变化和血栓栓塞事件风险增加增加了其致残率和死亡率。因此，早期预测和干预DCM患者的房颤可有效改善预后和生活质量。DCM患者房颤的准确风险分类对于指导干预非常重要。诺模图基于多元逻辑回归分析的结果。它整合了多个预测指标，并以图表的形式将结果预测的各种变量之间的相关性可视化。^[3]在这项研究中，我们旨在通过开发列线图来识别可能发生房颤的扩张型心肌病患者。

致编辑：肺癌仍然是全球肿瘤相关死亡的最常见原因。低剂量计算机断层扫描（CT）筛查已被证明可以大大降低肺癌患者的死亡率。尽管不同指南推荐的筛查人群有所不同，但老年吸烟者始终是最重要的受试者。然而，已经发现相当一部分肺癌患者是年轻的，没有烟草消费。^[1]非吸烟肺癌甚至被认为是一种独立的疾病，是癌症死亡的第七大原因。从常规角度来看，这些年轻的不吸烟者患肺癌的风险并不高，一般被排除在筛查或管理之外。^[2]是否应该关注非高风险个体尚不清楚。

致编辑：面对世界范围内日益增加的不孕症，这十年见证了人工生殖技术（ART）的利用急剧上升。^[1]然而，体外受精（IVF）/卵胞浆内单精子注射（ICSI）取决于许多因素。此外，接受ART的患者不仅产生高额费用，而且增加了严重副作用的风险，如卵巢过度刺激综合征、感染和多胎妊娠。^[2]因此，ART结果的准确预测引起了极大的兴趣。

杨等人在2022年3月20日出版的文章中出现了出版商在排版过程中引入的印刷错误。^[1]