Volume 135 · Issue 18 · 2022

皮肌炎（DM）是一种特发性炎性肌病，有典型的皮肤表现和肌肉病变，通常累及多个器官。抗黑色素瘤分化相关基因-5（MDA5）DM通常表现为临床无肌病性DM（CADM），其特征是一系列独特的皮肤和全身表现，包括皮肤溃疡和间质性肺病（ILD）。其中，ILD是抗MDA5 DM最常见的并发症，在某些情况下可发展为快速进行性ILD（RP-ILD）。^[1,2]

The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort.

Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex.

In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P= 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P = 0.002), musculoskeletal damage (P = 0.023), cardiovascular impairment (P = 0.009), and CYC use (P = 0.001); while leukopenia (P = 0.017), arthritis (P = 0.014), and mycophenolate usage (P = 0.013) rates were lower.

Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.

Biological agents, such as tumor necrosis factor inhibitors (TNFi), have been widely used in rheumatoid arthritis (RA) patients and greatly improved goal achievement. The aim of this study was to investigate whether conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) combination was better in reducing relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi plus MTX in RA patients who achieved low disease activity (LDA) with TNFi and MTX therapy.

RA patients who failed to csDMARDs received an induction therapy of MTX plus TNFi for maximally 12 weeks. Those achieving LDA in 12 weeks were randomly assigned at a 1:1:1 ratio into three groups: (A) adding hydroxychloroquine and sulfasalazine for the first 12 weeks and then discontinuing TNFi for the following 48 weeks; (B) maintaining TNFi and MTX for 60 weeks; and (C) maintaining TNFi and MTX for the first 12 weeks and then discontinuing TNFi for the following 48 weeks. The primary outcome was relapse.

A total of 117 patients were enrolled for induction therapy and 67 patients who achieved LDA within 12 weeks were randomized, with 24, 21, and 22 patients in groups A, B, and C, respectively. The relapse rates of groups A and B during the entire 60 weeks were comparable [10/22 (45.5%) vs. 7/20 (35.0%), χ² = 0.475, P = 0.491], however, significantly lower than that of group C [10/22 (45.5%) vs. 17/20 (85.0%), χ² = 5.517, P = 0.019; 7/20 (35.0%) vs. 17/20 (85.0%), χ² = 11.035, P = 0.004, respectively]. Taking RMB 100,000 Yuan as the threshold of willingness to pay, compared to MTX monotherapy (group C), both TNFi maintenance and triple csDMARDs therapies were cost-effective, but triple csDMARDs therapy was better.

For RA patients who have achieved LDA with TNFi and MTX, csDMARDs triple therapy was a cost-effective option in favor of reducing relapse.

ClinicalTrials.gov, NCT02320630.

The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients.

Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits.

A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0 vs. 6.7 mg/L), pain visual analogue scale (4.8 vs. 4.5), patient’s and physician’s global assessment (4.9 vs. 4.5 and 4.9 vs. 4.5), 28-joint disease activity score using DAS28-CRP (4.3 vs. 4.0) simplified disease activity index (21.9 vs. 19.9), and clinical disease activity index (19.3 vs. 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4% vs. 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women.

In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.

Aurora kinases (AURKs) family plays a vital role not only in cell division but also in tumorigenesis. However, there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer (BC). Systematic bioinformatics analysis was conducted to explore the biological role, prognostic value, and immunologic function of AURKs family in BC.

The expression, prognostic value, and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals: ONCOMINE Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, Metascape, GeneMANIA, and LinkedOmics; and the result was verified using human tissues.

The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage (all P < 0.05). BC patients with high AURKA and AURKB expression had a worse overall survival, relapse-free survival, and distant metastasis-free survival (all P < 0.05). Verification experiment revealed that AURKA and AURKB were upregulated in BC (P < 0.05). AURKA and AURKB were specifically associated with several tumor-associated kinases (polo-like kinase 1 and cyclin-dependent kinase 1), miRNAs (miR-507 and miR-381), and E2F transcription factor 1. Moreover, AURKA and AURKB were correlated with immune cell infiltration. Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway, platinum drug resistance signaling pathway, ErbB signaling pathway, Hippo signaling pathway, and nucleotide-binding and oligomerization domain-like receptor signaling pathway.

Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.

Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis.

Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer Operetta^TM was used to obtain high-resolution images of three-dimensional organoids.

An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h.

This study provides the primary intestinal in vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.

减肥代谢手术已被证实是实现体重减轻、治疗肥胖相关疾病、提高生活质量的有效、安全、可行的方法。由于其简单性，袖状胃切除术（SG）在过去十年中比Roux-en-Y胃旁路术（RYGB）更常用。^[1]然而，在5年的随访期内，RYGB在过度减肥效果和2型糖尿病（T2DM）缓解方面优于SG。另一方面，RYGB后的微量营养缺乏和胃肠道疾病几乎是普遍的。Munir Alamo于2003年首次描述了袖状胃切除术伴空肠旁路（SGJB）。^[2]他们随后的研究揭示了该程序在实现体重减轻和改善T2DM缓解方面的有效性。^[3]林最近报告了类似的结果等人^[4]在中国患者中。后一作者还发现SG伴空肠空肠旁路（SG+JJB）[图1A]导致术后营养缺乏不太明显，并发症也比RYGB少。在这里，我们提出了一种新技术：袖状胃切除术加未切割空肠空肠旁路术（SG未切割JJB）。我们试图进一步简化旁路手术，并了解其短期安全性和有效性。

多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其中浆细胞在骨髓中增殖，导致溶骨性骨破坏。高达90%的MM患者存在骨受累，并与疼痛和骨骼相关并发症相关，如病理性椎体压缩性骨折（VCFs）。^[1]MM相关的VCFs导致脊柱不稳定、背痛、脊柱后凸、神经功能障碍和随后的呼吸系统并发症，这显著降低了受影响患者的生活质量。

致编辑：系统性红斑狼疮（SLE）是一种累及多系统的自身免疫性疾病。近年来，治疗性靶向治疗（T2T）策略被推荐用于SLE。^[1]免疫抑制药物是SLE治疗的标准护理。他克莫司是2019年更新的欧洲抗风湿病联盟和欧洲肾脏协会-欧洲透析和移植协会狼疮肾炎（LN）管理建议中推荐的钙调磷酸酶抑制剂之一。^[2]然而，很少有研究关注他克莫司治疗各种肾外SLE表现【补充表1，http：//links.lww.com/CM9/B122】。也没有关于他克莫司治疗SLE的T2T数据。因此，我们进行了这项单中心、前瞻性、真实世界研究，以更好地阐明他克莫司在各种SLE表现中的疗效和安全性，并为他克莫司提供T2T证据。

致编辑：银屑病通常与心血管疾病、肥胖和代谢综合征（MS）等合并症相关。然而，上述疾病在中国斑块型银屑病患者中的患病率仍然未知。最近，肿瘤坏死α抑制剂、白细胞介素-17A抑制剂等生物制剂已成功用于斑块型银屑病的治疗。然而，生物治疗对代谢相关合并症的影响仍有争议。有必要研究代谢相关合并症和斑块型银屑病与生物制剂作用之间的关系。

致编辑：抗磷脂综合征（APS）是一种以持续阳性抗磷脂抗体（aPL）（包括狼疮抗凝剂（LA）、抗心磷脂抗体（aCL）和抗β 2糖蛋白-I抗体（抗β 2GPI））患者发生血栓和产科事件为特征的疾病。APS的临床症状包括许多非血栓性表现，也称为标准外表现，包括血小板减少症、aPL肾病、网状青斑、瓣膜性心脏病和神经系统表现。^[1]先前的研究发现，具有标准外表现的原发性产科APS患者可能有发生血栓形成的风险，^[2]某些aPL类型与非标准表现相关。^[3]我们进行了一项回顾性研究，分析aPL相关的临床表型，尤其是标准外表现。本研究经北京协和医院医学伦理委员会批准。所有患者均签署了知情同意书。

到编辑：冠状动脉瘤（CAAs）是川崎病（KD）的并发症之一，可引起心肌缺血、梗死，甚至猝死。^[1]对伴有CAAs的KD患者进行准确的血栓风险分层对于确定患者是否需要积极的抗凝治疗至关重要。

致编辑：强直性脊柱炎（AS）是中轴性脊柱关节炎（ax-SpA）的代表性表型，延迟诊断是一个挑战。这种延迟可能正在改善，^[1]由于AS和ax-SpA的诊断标准已有数次更新，尤其是国际脊椎关节炎学会（ASAS）2009年的评估，^[2]认识到MRI是检测早期病变的有力方法。然而，关于诊断延迟在中国是否得到改善的知识仍然有限。因此，我们对14年来从同一家医院收集的两个数据集进行了比较研究。

致编辑：产后出血（PPH）是分娩的严重并发症，也是全世界孕产妇发病率和死亡率的主要原因。因此，正确和积极的PPH治疗是降低孕产妇死亡率的关键。Bakri球囊是PPH的一种治疗方法。在这里，我们研究了Bakri球囊的治疗效果、优点和缺点，为寻求合适的病理场合和放置Bakri球囊（美国印第安纳州斯潘塞库克公司）的最佳时机提供理论基础，并开发一种更合理有效的治疗PPH的方法。

致编辑：胃癌（GC）是全球第五大常见恶性肿瘤和第三大癌症相关死亡原因，超过70%的病例发生在亚洲人群中。^[1]绝大多数GC患者确诊时已是晚期，晚期GC患者预后较差，死亡率较高。手术切除是GC治疗的基石。化疗、放疗、靶向治疗、姑息性手术和最佳支持治疗已被用于晚期GC的治疗。转换疗法可能是延长总生存期的可行方法。由于GC是一种高度异质性的肿瘤，应根据其亚型进行治疗。人表皮生长因子受体2型（HER2）阳性GC是该病的独特亚型，其诊断和治疗策略不同于HER2阴性GC。HER2阳性晚期GC患者可受益于抗HER2治疗；然而，对于HER2阴性的晚期GC患者，目前尚无有效且规范的化疗方案。

致编辑：剖宫产（CS）是产科最重要和最安全的手术之一。当有医学指征时，CS可以是一种挽救生命的干预措施。在中国独生子女政策期间，出于各种原因，夫妇倾向于选择CS。2010年，中国的CS率上升至世界最高水平。^[1]然而，CS也可能对母体和新生儿产生各种不良后果。与阴道分娩相比，CS的孕产妇死亡率和母婴并发症更高。^[2]在过去的几十年里，CS发生率在世界范围内急剧增加，控制这些发生率已成为最突出的产科问题之一。

致编辑：我们饶有兴趣地读了孙的文章等人^[1]“保留十二指肠头部切除术和胰十二指肠切除术的对比分析。文章最有趣的结果是，保留十二指肠胰头部切除术（DPPHR）在围手术期和长期结果上有几个优势。不幸的是，在描述了所有“DPPHR的修改（Beger、Frey和Gloor）”后，他们没有具体说明哪种修改适用于接受DPPHR的28名患者中的每一位。