2024年 · 第137卷第14期

1型神经纤维瘤病(NF1）是一种常染色体显性遗传性疾病，由NF1基因。其特征是咖啡乳斑（CALMs）、皮肤神经纤维瘤（CNF）、丛状神经纤维瘤（PNF）、Lisch结节、视神经通路胶质瘤（OPG）、潜在的骨骼异常和其他涉及多个器官和系统的并发症。^[1]此外，大约10%的NF1患者可能进展为恶性周围神经鞘瘤(MPNST)。^[1]TheNF1基因编码神经纤维蛋白，调节Ras及其下游信号通路，如丝裂原活化蛋白激酶（MEK）/细胞外信号调节激酶（ERK）和磷脂酰肌醇-3-激酶（PI3K）/Akt/哺乳动物雷帕霉素靶标（mTOR）通路，从而抑制异常细胞分化和增殖。^[2,3]

中国专家共识在规范和完善炎症性肠病（IBD）临床诊疗方面的作用不言而喻。随着中国的临床和基础研究在对IBD的更好理解下变得标准化，更多关于中国患者的数据变得可用于制定共识和指南。该指南由中国消化内科学会IBD学组合作制定，纳入了最新的国际共识声明，^{[1,2,3,4,5,6,7]}国内研究成果和实际考虑，作为基于2018年中国IBD管理共识的更新。^[8]IBD指南由两部分组成：溃疡性结肠炎（UC）和克罗恩病，本手稿介绍了UC部分。本指南中使用的证据是按照指南的标准收集和分析的，为了清楚起见，内容被组织为问题陈述。本指南的制定旨在反映IBD的最新进展，为IBD的临床管理提供全面而有价值的指导。

炎症性肠病（IBD）是一种复杂的疾病，标准化的诊断和治疗对于提高医疗疗效至关重要。中国IBD管理共识/指南于1978年、1993年、2001年、2007年、2012年和2018年制定，显著规范和改善了中国IBD的临床管理。近期，鉴于我国IBD发病率不断上升，^[1]相关的临床和基础研究备受关注。证据的深度在增加，这为更新共识指南奠定了坚实的基础。此外，新的诊断方法和治疗模式正在快速开发和更新。在这方面，通过纳入最新的国际共识声明^[2,3,4,5,6]并结合我国研究成果和临床实践途径，中华医学会中华消化病学会炎症性肠病学组修订了2018炎症性肠病管理共识。^[7]本次修订与以往指南的不同之处在于，溃疡性结肠炎管理指南和克罗恩病（CD）管理指南分别制定和完成。这使得新指南能够充分反映各领域的研究进展，并为临床实践提供规范、全面、可行的指导。本文包含CD管理指南。

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily. As an amplifier of the inflammatory response, TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival. TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders. More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases. There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease. This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury, renal fibrosis, diabetic nephropathy, immune nephropathy, and renal cell carcinoma.

Gallbladder polypoid lesions (GPLs) refer to any elevated lesion of the mucosal surface of the gallbladder wall, and the prevalence is estimated to be between 0.9% and 12.1%. GPLs include benign polyps and malignant polyps. Benign polyps are further classified as non-neoplastic polyps and neoplastic polyps. Cholesterol polyps are the most common benign polyps and adenocarcinoma is the main type of malignant polyp. Hepatitis B virus infection, liver function abnormalities, dyslipidemia, and obesity are the main risk factors for GPLs. Studies of biological mechanisms have focused on malignant gallbladder polyps, the development of which is regulated by hormone levels in vivo, gut microbiota, inflammation, oxidative stress, Salmonella typhimurium, and related molecules. Diagnostic modalities include chemical examination and imaging examination, with imaging examination currently being the mainstay. Treatment of patients with GPLs is based on the presence or absence of symptoms, age, size of the polyps, tendency of the polyp to increase, and risk factors for symptomatic malignancy to determine whether surgery should be performed.

Given the established genetic linkage between triggering receptors expressed on myeloid cells 2 (TREM2) and Alzheimer’s disease (AD), an expanding research body has delved into the intricate role of TREM2 within the AD context. However, a conflicting landscape of outcomes has emerged from both in vivo and in vitro investigations. This study aimed to elucidate the multifaceted nuances and gain a clearer comprehension of the role of TREM2.

PubMed database was searched spanning from its inception to January 2022. The search criteria took the form of ( "Alzheimer’s disease" OR "AD" ) AND ( "transgenic mice model" OR "transgenic mouse model" ) AND ( "Triggering receptor expressed on myeloid cells" OR "TREM2" ). Inclusion criteria consisted of the following: (1) publication of original studies in English; (2) utilization of transgenic mouse models for AD research; and (3) reports addressing the subject of TREM2.

A total of 43 eligible articles were identified. Our analysis addresses four pivotal queries concerning the interrelation of TREM2 with microglial function, Aβ accumulation, tau pathology, and inflammatory processes. However, the diverse inquiries posed yielded inconsistent responses. Nevertheless, the inconsistent roles of TREM2 within these AD mouse models potentially hinge upon factors such as age, sex, brain region, model type, and detection methodologies.

This review substantiates the evolving understanding of TREM2’s disease progression-dependent impacts. Furthermore, it reviews the interplay between TREM2 and its effects across diverse tissues and temporal stages.

Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs.

We collected data from participants in the "Happy Breathing Program" in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs.

A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility (n = 3304, 43.1%) and a lack of trust in primary healthcare institutions (n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half (n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation "COPD" were more willing to undergo PFTs.

Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort.

Participants from the United Kingdom Biobank cohort (https://biobank.ndph.ox.ac.uk/) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn’s disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years’ follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HR_{Q4 vs. Q1} =1.36, 95% CI: 1.19-1.55, P_trend <0.001), UC (HR_{Q4 vs. Q1} =1.25, 95% CI: 1.07-1.46, P_trend=0.047), and CD (HR_{Q4 vs. Q1} =1.58, 95% CI: 1.26-1.97, P_trend <0.001) after multivariable adjustment. Compared with non-NAFLD, NAFLD participants had a significantly higher risk of incident IBD (HR=1.13, 95% CI: 1.04-1.24) and CD (HR =1.36, 95% CI: 1.17-1.58).

Higher degree of non-alcoholic fatty liver is associated with increased risk of incident IBD. Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatment of IBD.

Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM.

Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients (n = 34) hospitalized in the Peking University People’s Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics.

The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage.

The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.

Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.

We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts.

The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC.

The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.

A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.

Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis.

A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

上海妇科肿瘤集团（SGOG，www.shanghaigog.org），^[1]成立于2009年，是一个非营利性的临床研究组织，自2012年起成为妇科癌症Intergroup（GCIG）的正式成员。它由郎景河博士（中国）、加文·斯图尔特博士（加拿大）（2009-2020）指导；郎景河博士（中国）、马丁博士（中国）（2021-），并得到曹泽一博士（2009-2012）的支持。SGOG的使命是积极推动妇科癌症的研究者发起试验（IIT），特别是创新的II期临床试验。其次是在研究者培训、试验开发、人力资源和研究资助方面的高质量管理，SGOG已经启动了III期临床试验，以改善未来的临床实践。SGOG旨在通过开展系统、规范、高质量的临床试验获得可靠数据，指导中国卵巢癌、子宫内膜癌和宫颈癌的临床实践。SGOG每年召开两次小组会议，并积极参与GCIG国际交流与合作，扩大了其在妇科肿瘤临床研究领域的国际和国内影响力。这种协调不仅在学术团体之间特别相关，而且与国家和/或国际行业伙伴也特别相关。

致编辑：肺静脉窦隔离（PVAI）是用于治疗心房颤动（AF）患者的导管消融技术的基石。然而，仅PVAI策略治疗持续性房颤的结果已被证明是次优的。大多数持续性房颤患者可能需要PVAI以外的进一步心房消融。房颤驱动消融是一种针对持续性房颤的患者定制的消融策略，手术终点为房颤终止，近年来越来越受到关注。^[1]我们的目的是确定可以预测房颤终止的房颤驱动因素的电描记图（EGM）特征。

致编辑：当有主动脉修复指征时，胸主动脉腔内修复术（TEVAR）已被广泛接受为一线治疗。然而，在许多情况下，TEVAR仍然受到解剖条件的限制，最常见的排除情况是当涉及重要分支血管时，近端和/或远端着陆区不足。下行TEVAR中远端着陆区不足的发生率范围为2.5%至15.2%，并描述了延长其的不同方法。^[1]结合TEVAR和内脏血管开放血运重建的混合手术从血管内主动脉修复的早期阶段就已被采用，但其结果较差。血管内内脏动脉血运重建，如分支和开窗腔内移植物，最近已被使用。几项研究探讨了开窗/分支主动脉修复术中内脏动脉支架置入的结果，并显示了有希望的结果。^[2]然而，这些技术对可用的设备和技术技能要求很高。目前，没有食品药品监督管理局（FDA）批准的用于内脏动脉保存的分支TEVAR覆膜支架。烟囱或通气管手术相对更容易进行，但与较高的内漏发生率相关。^[3]

致编辑：囊性纤维化（CF）是一种由囊性纤维化跨膜电导调节因子突变引起的常染色体隐性疾病（CFTR）基因。迄今为止，超过2000年CFTR已经鉴定出突变。CF多发生于高加索人群，其发病率约为1/25,000~1/1800。然而，中国的CF病例数量较少。为探讨中国儿童CF的基因突变与临床特征，及其相关性，对10例CF或CFTR-在本研究中回顾性分析了相关疾病（CFTR-RD）。纳入2015年6月至2021年8月在首都儿科研究所附属儿童医院住院的新诊断为CF或CFTR-RD的儿童。本研究经首都儿科研究所伦理委员会批准（编号：SHERLL2021013），所有患者的父母或监护人均签署了知情同意书。

致编辑：减少导管癌的治疗原地（DCIS）近年来已被研究。5年辅助内分泌治疗（AET）方案是激素受体阳性DCIS的推荐治疗方法。选择性雌激素受体调节剂（如常用的他莫昔芬和托瑞米芬）和芳香酶抑制剂（AIs）是目前常用的AET药物。然而，长期AET伴随着严重的副作用，如更年期症状、子宫内膜癌、心血管事件、静脉血栓栓塞事件、骨质疏松症和关节疼痛，可显著降低患者的生活质量。据报道，只有50%的患者完成了推荐的5年AET，主要是因为副作用，而在持续时间较短的方案中观察到较高的依从率。^[1,2]因此，应考虑AET的降级，以减少AET的副作用并提高依从性。

致编辑：皮肤鳞状细胞癌（CSCC）起源于表皮层和（或）其相关附件的角质形成细胞，表现为一种快速增殖、高度破坏性的恶性肿瘤，2022年中国发生近2万例。^[1]CSCC的发病机制复杂，但近年来研究已取得重大进展。我们之前的研究确定了八种蛋白质，包括肌动蛋白α 1（ACTN1）、腱生蛋白C（TNC）、肌动蛋白捆绑蛋白1（FSCN1）、丝氨酸蛋白酶抑制剂家族B成员1（SERPINB1）、ras相关蛋白31（RAB31）、III型胶原α 1链（COL3A1）、I型胶原α 1链（COL1A1）和分化簇36（CD36），它们与CSCC的侵袭和转移显著相关。^[2]此外，我们随后的分析还揭示了CSCC患者血清ACTN1水平升高，这与肿瘤细胞分化、浸润深度和原发肿瘤直径相关。^[3]这强调了ACTN1在CSCC发病机制中的潜在关键作用。本研究旨在进一步探讨ACTN1在CSCC发病机制中的作用。

致编辑：绝经后骨质疏松症是一种典型的由雌激素缺乏引起的骨代谢紊乱疾病，以骨结构恶化、骨密度（BMD）降低、骨核变薄为特征，困扰着全球数百万绝经妇女。^[1]此外，雌激素缺乏伴随着氧化应激和炎症，从而导致骨质疏松症的发生和恶化。^[2]常规治疗方案疗效有限，不能满足长期治疗的要求。^[3]因此，为了缓解人类健康中的骨质疏松症问题，创新战略应探索当前战略的可能性和替代方案。在这项研究中，胶原肽（CP）被磷酸化，然后与镁离子螯合，以产生磷酸化胶原肽镁螯合物（PCP-Mg）。通过探索成骨细胞的成骨功能、对小鼠卵巢切除（OVX）诱导的骨丢失的预防作用以及其预防骨质疏松作用的潜在机制，研究了PCP-Mg的抗骨质疏松特性。该结果可为未来PCP-Mg在食品和医药领域防治骨质疏松症的研究和开发提供理论依据。