Volume 137 · Issue 09 · 2024

炎症性肠病（IBD），包括克罗恩病（CD）和溃疡性结肠炎（UC），是一种慢性、进行性疾病，严重程度波动，涉及复发和缓解的反复期。它已经成为一个全球公共卫生挑战。传统上，IBD主要在西方国家发现，北美和欧洲表现出最高的患病率和发病率。具体而言，UC的患病率和发病率分别为505/100,000和249/100,000，而CD的患病率和发病率分别为322/100,000和319/100,000。^[1]然而，在高患病率国家，IBD发病率最近趋于稳定，而亚洲和南美洲的新兴工业化国家的发病率和患病率都有所增加。^[2]

根据2019年全球疾病负担估计，钙化性主动脉瓣狭窄（AS）患者人数为940万，随着人口老龄化，这一数字将继续增加。^[1]对于有症状的重度AS的治疗，经导管主动脉瓣置换术（TAVR）已经发展成为所有风险谱中公认的选择，在全球范围内手术快速增长。TAVR的兴起开启了心脏瓣膜疾病管理的革命，从患者监测、疾病分期、多模态成像的使用、心脏团队的概念、设备的新设计和迭代到技术创新和未满足的临床需求的发现。由于全球采用TAVR，AS流行病学和患者特征的地理差异也被进一步确定。对不断变化的患者群体、当前的应用和突破以及剩余挑战的检查对于该技术的未来至关重要。在此，我们讨论了TAVR的时间利用、证据的积累和设备的进展、患者的选择以及一些关于TAVR改进的正在进行的主题。

具有致癌驱动突变的非小细胞肺癌（NSCLC）此前被认为是免疫治疗的“禁区”。^[1]随着证据的不断产生，免疫治疗有望为此类获得性酪氨酸激酶抑制剂（TKI）耐药后出现致癌驱动突变的NSCLC带来希望。然而，鉴于驱动突变、靶向治疗和免疫微环境之间复杂的相互作用，免疫治疗在具有不同致癌驱动突变的晚期非小细胞肺癌患者中的疗效仍然是一个持续争论的话题。在此背景下，《致癌驱动突变晚期非小细胞肺癌免疫治疗中国专家共识（2022版）》由中国抗癌协会肿瘤精准医学学会联合中华医学期刊肺癌专家组于2022年首次推出，旨在为临床提供规范化治疗指导。^[2]

Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.

Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene expression. The past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications, as prompted by the emergence of potent analytical approaches. The hematopoietic system provides a lifelong supply of blood cells, and gene expression is tightly controlled during the differentiation of hematopoietic stem cells (HSCs). The dysregulation of gene expression during hematopoiesis may lead to severe disorders, including acute myeloid leukemia (AML). Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis, which has led to the development of small-molecule inhibitors that target N6-methyladenosine (m⁶A) modification machinery as treatments. Here, we summarize the latest findings and our most up-to-date information on the roles of m⁶A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic system. Furthermore, we will discuss the therapeutic potential and limitations of cancer treatments targeting m⁶A.

Over the past decade, mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney disease. However, the precise molecular mechanisms linking mitochondrial damage to kidney disease remain elusive. The recent insights into the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthetase (cGAS)-stimulator of interferon gene (STING) signaling pathway have revealed its involvement in many renal diseases. One of these findings is that mitochondrial DNA (mtDNA) induces inflammatory responses via the cGAS-STING pathway. Herein, we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage, focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney diseases. Furthermore, we summarize the latest findings of cGAS-STING signaling pathway in cell, with a particular emphasis on its downstream signaling related to kidney diseases. This review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway, kidney diseases, and mitochondrial dysfunction.

Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals.

PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The potential publication bias for the variables was evaluated using Egger’s test.

A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (–0.24, 95% CI [–0.39, –0.08]; P = 0.002, I² = 87.7%), all regions of parafovea (–0.32, 95% CI [–0.54, –0.11]; P = 0.003; I² = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals.

Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes.

PROSPERO; http://www.crd.york.ac.uk/prospero/; No. CRD42021269885.

Patients who undergo coronary artery bypass grafting (CABG) are known to be at a significant risk of experiencing long-term adverse events, emphasizing the importance of regular assessments. Evaluating health-related quality of life (HRQoL) serves as a direct method to gauge prognosis. Our objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary (PCS) and Mental Component Summary (MCS) derived from the Short-Form 36 (SF-36) health survey in CABG patients.

The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and 2013. SF-36 assessments were conducted during both the hospitalization period and follow-up. The primary endpoint of the study was all-cause mortality, while the secondary outcome was a composite measure including death, myocardial infarction, stroke, and repeat revascularization. We assessed the relationships between the PCS and MCS at baseline, as well as their changes during the first 6 months after the surgery (referred to as ΔPCS and ΔMCS, respectively), and the observed outcomes.

The patients were followed for an average of 6.28 years, during which 35 individuals (35/433, 8.1%) died. After adjusting for clinical variables, it was observed that baseline MCS scores (hazard ratio [HR] for a 1-standard deviation [SD] decrease, 1.57; 95% confidence interval [CI], 1.07–2.30) and ΔMCS (HR for a 1-SD decrease, 1.67; 95% CI, 1.09–2.56) were associated with all-cause mortality. However, baseline PCS scores and ΔPCS did not exhibit a significant relationship with all-cause mortality. Notably, there was a dose-response relationship observed between ΔMCS and the likelihood of all-cause mortality (HRs for the 2nd, 3rd and 4th quartiles compared to the 1st quartile, 0.33, 0.45 and 0.11, respectively).

Baseline MCS and changes in MCS were independent predictors for long-term mortality of CABG. Better mental health status and recovery indicated better prognosis.

Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension.

The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60–80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes.

The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8–73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7–110.1 cm/s) in the standard treatment group (P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s^–1·year^–1vs. 36.7 cm·s^–1·year^-1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70–80 years or with SBP <140 mmHg.

Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension.

http://www.clinicaltrials.gov; No. NCT03015311.

Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.

About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health.

At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.

Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

Dual-energy computed tomography (DECT) is purported to accurately distinguish uric acid stones from non-uric acid stones. However, whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains unknown. Therefore, we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing them.

This research included two steps. For the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones, 178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were enrolled. For model construction, 93, 40, and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training, internal validation, and external validation sets, respectively. Radiomics features were extracted from non-contrast CT images, and the least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a radiomics signature. Then, a radiomics model incorporating the radiomics signature and clinical predictors was constructed. The performance of the model (discrimination, calibration, and clinical usefulness) was evaluated.

When patients with ammonium urate stones were included in the analysis, the accuracy of DECT in the diagnosis of uric acid stones was significantly decreased. Sixty-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT. A radiomics model incorporating the radiomics signature, urine pH value, and urine white blood cell count was constructed. The model achieved good calibration and discrimination {area under the receiver operating characteristic curve (AUC; 95% confidence interval [CI]), 0.944 (0.899–0.989)}, which was internally and externally validated with AUCs of 0.895 (95% CI, 0.796–0.995) and 0.870 (95% CI, 0.769–0.972), respectively. Decision curve analysis revealed the clinical usefulness of the model.

DECT cannot accurately differentiate ammonium urate stones from uric acid stones. Our proposed radiomics model can serve as a complementary diagnostic tool for distinguishing them in vivo.

Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.

Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.

A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain (COL1A1) and synaptotagmin like 2 (SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8⁺ T cells. In addition, single-cell analysis indicated that fibroblasts and CD8⁺ T cells in TAA were significantly higher than those in normal arterial wall tissue.

COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

致编辑：异基因造血干细胞移植（allo-HSCT）是骨髓增生异常综合征（MDS）和MDS/骨髓增生性肿瘤（MPN）患者唯一的长期生存治疗选择。不幸的是，造血干细胞移植(HSCT)后复发仍然是治疗失败的原因，挽救治疗的结果很差。迫切需要开发更好的调理方案。先前的研究显示地西他滨（DEC）和伊达比星（IDA）之间具有协同抗白血病作用。^[1]为了设计一种对高危MDS和MDS/MPN患者具有极低毒性但相当大的骨髓抑制活性和潜在免疫增强作用的调理策略，我们在这项前瞻性、多中心队列研究（以下简称“DEC/IDA研究”）中将DEC和IDA与白消安、环磷酰胺和氟达拉滨联合用于改良的清髓方案。

致编辑：肺栓塞（PE）是继中风和心脏病发作之后全球心血管相关死亡的第三大常见原因。由于血流动力学差异，PE患者表现出广泛的临床表现，从无症状到危及生命的情况。PE患者的复发率很高，尽管大多数患者在疾病的初始阶段后存活，但复发的风险贯穿一生。与首次PE发作的患者相似，复发性PE患者可能无症状。迄今为止，我们关于复发性PE的大部分知识来自临床试验或注册研究，其中有症状复发是主要终点，而无症状复发很少报道。此外，目前的指南建议治疗无症状PE患者与有症状PE患者相似，^[1,2]但不建议在PE诊断后通过影像学方法对无症状患者进行常规随访。^[3]

致编辑：冠状动脉粥样硬化性心脏病（CAD）源于冠状动脉粥样硬化（CAS）斑块堆积，导致冠状动脉狭窄（CS）和闭塞，最终引起心肌缺血、缺氧或坏死。研究表明，高级别CS可能是随后几个月ST段抬高心肌梗死的重要预测因素。^[1]

致编辑：颌骨囊肿是口腔颌面部最常见的良性肿瘤之一。^[1]迄今为止，根据世界卫生组织（WHO）头颈部肿瘤第四分类，几项研究报告了意大利、巴西、希腊和美国普通人群中的颌骨囊肿。^[2]然而，在大量中国人群中，没有与最新世卫组织分类相关的牙源性和非牙源性囊肿的临床病理学研究。此外，很少有流行病学研究分析颌骨囊肿的治疗方案和可能的术后并发症。因此，本研究旨在对中国西部大量人群中的颌骨囊肿进行详细和扩展的流行病学分析。

致编辑：越来越多的证据表明，阿尔茨海默病（AD）的临床前阶段（即无症状淀粉样变性）在认知症状出现前持续数十年，为早期干预提供了很大的窗口期。淀粉样蛋白病理学，与AD相关的最早病理变化，可以被检测到体内具有脑脊液（CSF）分析或正电子发射断层扫描（PET），其存在对于临床前AD（pre-AD）的诊断是必要的。然而，PET扫描和CSF分析都很昂贵，阻碍了它们在大规模筛查中的应用。因此，基于血液的生物标志物是理想的替代方案，因为它们具有成本效益并且是非侵入性的。血浆β-淀粉样蛋白(A β)生物标志物，特别是A β₄₂/A β₄₀比率，是合理的基于血液的候选者，因为最近的研究表明A β降低₄₂/A β₄₀沿AD连续体的比率。^[1]几项研究也证明了血浆A β与其他变量组合的预测价值。然而，基于磁共振成像（MRI）的灰质萎缩测量是一种神经退行性AD生物标志物，因为皮质萎缩可以预测随后的认知衰退和AD转化。^[2]最近的数据还证明了中枢淀粉样蛋白与主观认知衰退访谈（SCD-I）的记忆和语言领域之间的关联。^[3]因此，在本研究中，我们旨在（1）研究AD前期血浆A β的改变，并验证血浆A β用于检测外周AD前期脑淀粉样变性的诊断效率；（2）探索血浆A β模型中主观认知衰退（SCD）特征和灰质体积的叠加效应。

致编辑：数据适当性评估是一个回答来自常规医疗实践的电子健康记录（EHR）是否符合预期研究目的的过程，例如，可用于进行，具有足够的个人记录，能够从记录中提取相关信息等。^[1,2,3]这一点越来越被强调为将EHR（一种重要的真实世界数据[RWD]）用于科学目的的先决条件。^[4,5,6]尽管关于RWD适当性维度的定义、类型和评估方法仍存在争议，但最新的官方指南（即来自美国食品药品监督管理局[FDA]^[4]和中国国家药品监督管理局[NMPA]^[6]）建议评估从变量存在的初步阶段开始，随后深入到数据值问题（如缺失值、异常值等。），因为初步评估是整体RWD适当性的基础。^[7]人们对EHR在发展中地区的适当性知之甚少，这些地区的特点是就诊量高，医院数量多。因此，本研究旨在从核心变量比较的角度初步调查发展中地区医院RWD的适宜性。

致编辑：过敏性支气管肺曲霉病(ABPA)是一种由对抗原过敏引起的过敏性肺病曲霉属，最常见于哮喘或囊性纤维化患者。^[1]本病的主要临床特点是与血清免疫球蛋白（Ig）E水平升高有关，阳性烟曲霉(烟曲霉)特异性IgE/IgG、反复肺浸润和支气管扩张。但由于缺乏统一的诊断标准和筛查方法，ABPA总是诊断不足。2021年，日本人群过敏性支气管肺真菌病（ABPM）提出了新的诊断标准。该标准由Asano验证等人^[2]首次（所谓的浅野标准），并表明与现有的诊断标准（Rosenberg-Patterson标准、国际人类和动物真菌学学会[ISHAM]标准）相比，浅野标准对ABPM的诊断表现出更好的敏感性和特异性。在这项回顾性研究中，我们修改了浅野长晟标准，以验证其诊断ABPA的有效性。近年来，对于没有诊断金标准的疾病，潜在类别分析（LCA）已被用于评估诊断标准的性能。^[3]LCA是有限混合建模的一种形式，当真实结果未知时，它可以整合多个变量来定义一个子集。^[3]在诊断测试中，LCA可用于定义诊断组和非诊断组。以前的研究也使用“多学科团队（MDT）诊断”或“医生诊断”^[2]作为评价标准诊断效率的参考标准。我们比较了修改的浅野长晟标准[补充表1，http://links.lww.com/CM9/B940]与现有标准（Rosenberg-Patterson标准[补充表2，http://links.lww.com/CM9/B940]、ISHAM标准[补充表3，http://links.lww.com/CM9/B940]和修改的ISHAM标准[补充表4，http://links.lww.com/CM9/B940]的性能^[3]）分别以ABPA的LCA和MDT诊断为参考标准。

作者声明，在文章中^[1]发表于第135卷第24期中华医学杂志第2901页表2中关于“阿莫西林（≥3.0 g/天，1.0 t.i.d.或0.75 q.i.d.）和PPI（埃索美拉唑或雷贝拉唑，双倍剂量bid或标准剂量q.i.d.）给药14天”的定义应更正为“阿莫西林（3.0 g/天，1.0 t.i.d.，或0.75 q.i.d.）和PPI（埃索美拉唑或雷贝拉唑，双倍剂量bid或标准剂量q.i.d.）给药14天”。作者对由此造成的任何不便深表歉意。