2024年 · 第137卷第09期

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic, progressive illness that fluctuates in severity and involves recurring periods of relapse and remission. It has emerged as a global public health challenge. Traditionally, IBD has been predominantly found in Western countries, with North America and Europe exhibiting the highest rates of prevalence and incidence. Specifically, the prevalence and incidence rates for UC were 505/100,000 and 249/100,000, respectively, while for CD they were 322/100,000 and 319/100,000, respectively.^[1]However, there has been a recent stabilization of IBD incidence in countries with high prevalence rates, whereas newly industrialized countries in Asia and South America have experienced an increase in both incidence and prevalence.^[2]

The number of patients with calcific aortic stenosis (AS) is 9.4 million according to 2019 Global Disease Burden estimates, which will continue to increase as the population ages.^[1]For the treatment of symptomatic severe AS, transcatheter aortic valve replacement (TAVR) has evolved to be a well-established option across all risk spectra, with a rapid growth of procedures worldwide. The rise of TAVR initiates the revolution of the management of valvular heart diseases, from patient surveillance, the staging of disease, the use of multimodality imaging, the concept of the Heart Team, new designs and iterations of devices to technical innovations and the discovery of unmet clinical needs. As a consequence of the global adoption of TAVR, geographical differences in the epidemiology of AS and patient characteristics have also been further identified. An examination of the changing patient population, current applications and breakthroughs, and remaining challenges are crucial for the future of this technique. Herein, we discuss the temporal utilization of TAVR, the accumulation of evidence and progress of devices, the selection of patients, and some ongoing topics concerning the improvement of TAVR.

Non-small cell lung cancer (NSCLC) with oncogenic driver mutations was previously deemed "forbidden territory" for immunotherapy.^[1]With the continuous generation of evidence, immunotherapy is expected to bring hope for such NSCLC with oncogenic driver mutations after acquired tyrosine kinase inhibitor (TKI) resistance. However, given the intricate interplay between driven mutations, targeted therapy, and immune microenvironment, the efficacy of immunotherapy in advanced NSCLC patients with diverse oncogenic driver mutations remains a topic of ongoing debate. In this context, Chinese Expert Consensus on Immunotherapy for Advanced NSCLC with Oncogenic Driver Mutations (2022 edition) was first launched in 2022 by the Society of Cancer Precision Medicine of Chinese Anti-Cancer Association and the Lung Cancer Expert Group of Chinese Medical Journals, aiming to provide standardized treatment guidance for clinical practice.^[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.

To the Editor:Allogeneic hemopoietic stem cell transplantation (allo-HSCT) represents the only long-term survival treatment choice for patients with myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasm (MPN). Unfortunately, post-hemopoietic stem cell transplantation (HSCT) relapse remains a cause of treatment failure and the results of salvage treatments are poor. Developing better conditioning regimens is urgently needed. Previous studies have shown synergistic antileukemic effects between decitabine (DEC) and idarubicin (IDA).^[1]In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN, we combined DEC and IDA with busulfan, cyclophosphamide, and fludarabine for a modified myeloablative regimen in this prospective, multicenter cohort study (hereafter referred to as the "DEC/IDA study" ).

To the Editor:Pulmonary embolism (PE) is the third most common cause of cardiovascular-related death worldwide after stroke and heart attack. As a consequence of hemodynamic differences, patients with PE present a wide spectrum of clinical manifestations, ranging from asymptomatic to life-threatening conditions. There are high rates of recurrence in PE patients, and although most patients survive after the initial phase of the disease, the risk of recurrence remains throughout life. Similar to patients experiencing their first PE episodes, patients with recurrent PE may be asymptomatic. To date, much of our knowledge about recurrent PE has come from clinical trials or registry studies in which symptomatic recurrence was a major endpoint, while asymptomatic recurrence is rarely reported. Moreover, current guidelines suggest treating patients with asymptomatic PE similarly to those with symptomatic PE,^[1,2]but do not recommend routine follow-up of asymptomatic patients by imaging methods after PE diagnosis.^[3]

To the Editor: Coronary atherosclerotic heart disease (CAD) arises from coronary atherosclerosis (CAS) plaque buildup, resulting in coronary stenosis (CS) and occlusion, ultimately causing myocardial ischemia, hypoxia, or necrosis. Studies showed that the high-grade CS may be an important predictor of ST segment elevation myocardial infarction in subsequent months.^[1]

To the Editor:The jaw cyst is one of the most common benign tumors in the oral and maxillofacial region.^[1]To date, several studies have reported on jaw cysts in general populations from Italy, Brazil, Greece, and the United States in accordance with the 4th World Health Organization (WHO) classification of head and neck tumors.^[2]However, there are no clinicopathological studies of odontogenic and non-odontogenic cysts in a large Chinese population in relation to the latest WHO classification. Furthermore, few epidemiological studies have analyzed treatment plans and the possible postoperative complications of jaw cysts. Consequently, this study aimed to perform a detailed and extended epidemiological analysis of jaw cysts in a large population in West China.

To the Editor: Accumulating evidence has shown that the preclinical stage of Alzheimer’s disease (AD) (i.e., asymptomatic amyloidosis) lasts for decades before the onset of cognitive symptoms, providing a large window for early intervention. Amyloid pathology, the earliest pathological change associated with AD, can be detectedin vivowith cerebrospinal fluid (CSF) analysis or positron emission tomography (PET), and its presence is necessary for the diagnosis of preclinical AD (pre-AD). However, both PET scans and CSF analyses are expensive, hampering their use in large-scale screening. Thus, blood-based biomarkers are desirable alternatives, as they are cost-effective and not invasive. Plasma β-amyloid (Aβ) biomarkers, and particularly the Aβ₄₂/Aβ₄₀ratio, are logical blood-based candidates, as recent studies have shown decreased Aβ₄₂/Aβ₄₀ratios along the AD continuum.^[1]Several studies have also demonstrated the predictive value of plasma Aβ in combination with other variables. However, magnetic resonance imaging (MRI)-based measures of gray matter atrophy are a neurodegenerative AD biomarker, as cortical atrophy can predict subsequent cognitive decline and AD conversion.^[2]Recent data have also demonstrated an association between central amyloid and the memory and language domains of the subjective cognitive decline interview (SCD-I).^[3]Thus, in this study, we aimed to (1) investigate the plasma Aβ alterations in pre-AD and validate the diagnostic efficiency of plasma Aβ for detecting brain amyloidosis in peripheral pre-AD; and (2) explore the additive effects of subjective cognitive decline (SCD) features and gray matter volume in the plasma Aβ model.

To the Editor: Assessment of data appropriateness is a process to answer whether electronic health records (EHRs) from routine healthcare practices could fit intended study purposes, for example, available to be proceeded, with enough individual records, with relevant information able to be extracted from records, etc.^[1,2,3]This has been increasingly underscored as a prerequisite when using EHRs (one important type of real-world data [RWD]) for scientific purposes.^[4,5,6]Although controversies remain on the definitions, types and assessment methods of the dimensions of RWD appropriateness, the latest official guidelines (i.e., from the U.S. Food and Drug Administration [FDA]^[4]and China National Medical Products Administration [NMPA]^[6]) suggest that the assessment start from a preliminary stage on variable existence, and subsequently deepen into the issue of data value (such as missing value, outliers, etc.), as the preliminary assessment is the foundation of the overall RWD appropriateness.^[7]Little is known about the appropriateness of EHRs in developing regions, which feature high visit volumes and a great number of hospitals. Therefore, this study aimed to preliminarily investigate RWD appropriateness from hospitals in developing regions from the perspective of core variables’ comparison.

To the Editor:Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disease caused by hypersensitivity to antigens fromAspergillus, and it most commonly occurs in patients with asthma or cystic fibrosis.^[1]The main clinical characteristics of the disease are those related to elevated serum immunoglubulin (Ig) E level, positiveAspergillus fumigatus(A. fumigatus) specific IgE/IgG, repeated pulmonary infiltration, and bronchiectasis. However, due to the lack of unified diagnostic criteria and screening methods, ABPA is always underdiagnosed. In 2021, new diagnostic criteria were proposed for allergic bronchopulmonary mycosis (ABPM) in the Japanese population. The criteria were verified by Asanoet al^[2]for the first time (so-called Asano criteria), and showed that compared with the existing diagnostic criteria (Rosenberg-Patterson criteria, International Society for Human and Animal Mycology [ISHAM] criteria), the Asano criteria showed better sensitivity and specificity for the diagnosis of ABPM. In this retrospective study, we modified the Asano criteria to verify its effectiveness for diagnosing ABPA. In recent years, latent class analysis (LCA) has been used to evaluate the performance of diagnostic criteria for diseases without diagnostic gold standards.^[3]LCA is a form of finite mixture modeling which can integrate multiple variables to define a subset when the true outcome is unknown.^[3]In diagnostic tests, LCA can be used to define diagnostic and non-diagnostic groups. Previous studies also used "multidisciplinary team (MDT) diagnosis" or "physician diagnosis"^[2]as the reference standard to evaluate the diagnostic efficiency of the criteria. We compared the performance of the modified Asano criteria [Supplementary Table 1, http://links.lww.com/CM9/B940] with existing criteria (Rosenberg–Patterson criteria [Supplementary Table 2, http://links.lww.com/CM9/B940], ISHAM criteria [Supplementary Table 3, http://links.lww.com/CM9/B940], and modified ISHAM criteria [Supplementary Table 4, http://links.lww.com/CM9/B940]^[3]) using LCA and MDT diagnosis of ABPA as the reference standard, respectively.

The authors declare that in the article^[1]published in vol.135, issue 24 of theChinese Medical Journal, the definition about "The administration of both amoxicillin (≥3.0 g/day, 1.0 t.i.d., or 0.75 q.i.d.) and PPIs (esomeprazole or rabeprazole, double dose bid or standard dose q.i.d.) for 14 days" presented in the Table 2 on Page 2901 should be corrected to "The administration of both amoxicillin (3.0 g/day, 1.0 t.i.d., or 0.75 q.i.d.) and PPIs (esomeprazole or rabeprazole, double dose bid or standard dose q.i.d.) for 14 days". The authors deeply apologize for any inconvenience caused.