2024年 · 第137卷第04期

In recent years, the field of endoscopy has experienced significant technological advancements. These developments have facilitated the efficient use of endoscopy for precise examination and minimally invasive treatment of various lesions. A key parameter considered during both endoscopic diagnosis and treatment is the size of the lesion. In colon polypectomy, the size of the polyp is linked to the probability of malignancy and the likelihood of complications. Similarly, in the case of early gastric cancer, larger tumors are often associated with an increased likelihood of lymph node metastasis, and whether to perform endoscopic submucosal dissection (ESD) is partially dependent on the size of the lesion. Therefore, accurate measurement of lesion size may significantly impact the diagnosis and treatment plan for the patient. However, at present, there is no standardized method for quantitative measurement during endoscopy. This lack of a universal technique hinders the ability of clinical guidelines to provide precise recommendations for treatment.

Aging is a significant risk factor for various diseases, including asthma, and it often leads to poorer clinical outcomes, particularly in elderly individuals. It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage, resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases. The effects of aging affect not only the elderly but also those of younger ages, posing significant challenges to global healthcare. Thus, understanding the molecular mechanisms associated with aging in different diseases is essential. One intriguing factor is the aryl hydrocarbon receptor (AhR), which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process. Here, we review the literature on several major hallmarks of aging, including mitochondrial dysfunction, cellular senescence, autophagy, mitophagy, epigenetic alterations, and microbiome disturbances. Moreover, we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures, particularly in relation to the immune system. Furthermore, we explore how aging hallmarks affect clinical characteristics, inflammatory features, exacerbations, and the treatment of asthma. It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system. Compared with patients with other cancers, glioma patients often suffer from increased levels of psychological stress, such as anxiety and fear. Chronic stress (CS) is thought to impact glioma profoundly. However, because of the complex mechanisms underlying CS and variability in individual tolerance, the role of CS in glioma remains unclear. This review suggests a new proposal to redivide the stress system into two parts. Neuronal activity is dominant upstream. Stress-signaling molecules produced by the neuroendocrine system are dominant downstream. We discuss the underlying molecular mechanisms by which CS impacts glioma. Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.

As pancreatic cancer (PC) is highly malignant, its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies. First-line chemotherapies for PC, according to current guidelines, include fluoropyrimidine- and gemcitabine-based regimens. Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC, especially those involving glycolysis and glutamine metabolism, are highly associated with chemoresistance. Additionally, lipid metabolism is a major factor in chemoresistance. However, emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance. This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3⁺ and CD8⁺ T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3_CT (CD3⁺ T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology.

The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted.

The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3_CT and CD3-CD8 (the combination of CD3⁺ and CD8⁺ T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3_CT was confirmed as an independent prognostic factor, with high CD3_CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12–0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05–0.92, P = 0.037).

We quantify the spatial distribution of CD3⁺ and CD8⁺ T cells within tissue regions in WSIs using AI technology. The CD3_CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3_CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.

We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.

The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 (ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.

The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.

No. NCT00454519 (https://clinicaltrials.gov/)

Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.

This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups.

During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001).

LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.

Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.

We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD.

Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Hypertension and non-alcoholic fatty liver disease (NAFLD) share several pathophysiologic risk factors, and the exact relationship between the two remains unclear. Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and Mendelian randomization (MR) analyses.

Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017-2018. Subsequently, a two-sample MR study was performed using the genome-wide association study (GWAS) summary statistics to identify the causal association between hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and NAFLD. The primary inverse variance weighted (IVW) and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD. Sensitivity analyses were adopted to confirm the robustness of the results.

A total of 3144 participants were enrolled for our observational study in NHANES. Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk (odds ratio [OR] = 1.677; 95% confidence interval [CI], 1.159-2.423). SBP ≥130 mmHg and DBP ≥80 mmHg were also significantly positively correlated with NAFLD. Moreover, hypertension was independently connected with liver steatosis (β = 7.836 [95% CI, 2.334-13.338]). The results of MR analysis also supported a causal association between hypertension (OR = 7.203 [95% CI, 2.297-22.587]) and NAFLD. Similar results were observed for the causal exploration between SBP (OR = 1.024 [95% CI, 1.003-1.046]), DBP (OR = 1.047 [95% CI, 1.005-1.090]), and NAFLD. The sensitive analysis further confirmed the robustness and reliability of these findings (all P >0.05).

Hypertension was associated with an increased risk of NAFLD.

To perform anatomical anterior cruciate ligament reconstruction (ACLR), tunnels should be placed relatively higher in the femoral anterior cruciate ligament (ACL) footprint based on the findings of direct and indirect femoral insertion. But the clinical results of higher femoral tunnels (HFT) in double-bundle ACLR (DB-ACLR) remain unclear. The purpose was to investigate the clinical results of HFT and lower femoral tunnels (LFT) in DB-ACLR.

From September 2014 to February 2016, 83 patients who underwent DB-ACLR and met the inclusion and exclusion criteria were divided into HFT-ACLR (group 1, n = 37) and LFT-ACLR (group 2, n = 46) according to the position of femoral tunnels. Preoperatively and at the final follow-up, clinical scores were evaluated with International Knee Documentation Committee (IKDC), Tegner activity, and Lysholm score. The stability of the knee was evaluated with KT-2000, Lachman test, and pivot-shift test. Cartilage degeneration grades of the International Cartilage Repair Society (ICRS) were evaluated on magnetic resonance imaging (MRI). Graft tension, continuity, and synovialization were evaluated by second-look arthroscopy. Return-to-sports was assessed at the final follow-up.

Significantly better improvement were found for KT-2000, Lachman test, and pivot-shift test postoperatively in group 1 (P >0.05). Posterolateral bundles (PL) showed significantly better results in second-look arthroscopy regarding graft tension, continuity, and synovialization (P <0.05), but not in anteromedial bundles in group 1. At the final follow-up, cartilage worsening was observed in groups 1 and 2, but it did not reach a stastistically significant difference (P >0.05). No statistically significant differences were found in IKDC subjective score, Tegner activity, and Lysholm score between the two groups. Higher return-to-sports rate was found in group 1 with 86.8% (32/37) vs. 65.2% (30/46) in group 2 (P = 0.027).

The HFT-ACLR group showed better stability results, better PL, and higher return-to-sports rate compared to the LFT-ACLR group.

To the Editor: Psoriatic arthritis (PsA) is a highly heterogeneous inflammatory arthritis. It occurs in up to 30% of patients with psoriasis and can have severe impacts on peripheral joints, spine, tendon insertions, and fingers.^[1]Radiographic progression is currently the preferred method for assessing structural damage of PsA.^[2]Biologic treatment options for PsA include tumor necrosis factor-α inhibitors (TNFi), interleukin-12/23 inhibitors, and interleukin-17 (IL-17) inhibitors. The therapeutic effects of IL-17 inhibitors on structural damage were not consistent over multiple trials. Therefore, a systematic review and meta-analysis of the available randomized controlled trials (RCTs) was conducted to quantify the overall effect of IL-17 inhibitors on structural damage in PsA. This study was registered with PROSPERO (No. CRD42022301774).

To the Editor:Acne vulgaris (AV) is a common inflammatory skin condition. Population-based epidemiological studies have reported associations between dietary habits, lifestyle factors, family history, and the occurrence and development of acne.^[1,2,3,4]This study investigated the skincare behavior and cognition of patients with AV regarding predisposing factors using a designed electronic questionnaire.

To the Editor:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most effective options for hematological diseases. However, allo-HSCT treatment can cause serious complications. Post-transplant kidney damage is an important complication. In this study, we retrospectively analyzed the frequency of nephrotic syndrome (NS) after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor (HID) and matched donor (MD) HSCT (including matched sibling donors [MSD] and unrelated donors [URD]).

To the Editor: Glycemic control in individuals with type 1 diabetes (T1D) is challenging and requires multidimensional evaluation and precise management. Glycated hemoglobin (HbA1c) is currently the gold standard for assessing glucose control and predicting diabetes prognosis. However, it exhibits limitations in terms of accuracy, which is influenced by clinical factors,^[1]and its inability to reflect information about hypoglycemia and glycemic variability.^[2]Continuous glucose monitoring (CGM) has revolutionized glycemic profile evaluation by introducing novel glycemic variables that surpass conventional parameters and offer insights into critical areas for improving glycemic control.

To the Editor: Normal-tension glaucoma (NTG) is a progressive optic neuropathy characterized by irreversible blindness with statistically normal intraocular pressure (IOP) (≤21 mmHg),^[1,2]which makes early-stage diagnosis in the clinical practice difficult. Pathophysiological pathways underlying NTG include vascular dysregulation, toxic metabolite accumulation, and elevated translaminar cribrosa pressure difference (TLCPD).^[3]Although various small animal models have provided evidence of different pathophysiological mechanisms, the complicated clinical phenotype cannot be fully imitated by secondary disease models, and the gap between rodents and humans weakens their translational potential. Thus, the pathological changes associated with NTG remain unclear.

To the Editor: Tumor immune microenvironment plays a key role in breast cancer development and progression, which determines the long-term survival of breast cancer patients. Recent data have revealed that the application of cancer immunotherapy has some limitations, including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells.^[1]Thus, current clinical efforts are primarily focused on developing immune-based chemotherapy that can convert non-responders to responders.^[2]Immunogenic cell death (ICD) is a form of regulated cell death that is sufficient to activate an adaptive immune response. ICD can be usually triggered by certain chemotherapeutic drugs, oncolytic viruses, physicochemical therapies, and radiotherapy.^[3]Notably, a significant advantage of ICD, as a class of biomarkers, is that it integrates several immune-related pathways including danger signaling and T cell infiltration/activity. Some studies conducted to ascertain the prognostic value of ICD parameters have yielded contradictory results, which might be because of a limited number of patients and restricted ICD parameters. In this study, significant ICD-related biomarkers were identified and ICD-related signatures were derived to estimate the infiltration of immune cells, response to immunotherapy, and prognosis in breast cancer. Besides, a nomogram based on the independent clinicopathological factors and ICD risk scores was constructed for predicting the long-term survival of breast cancer patients, which may help in improving the clinical management of breast cancer patients.

To the Editor: It has been eighteen years since telocytes (TCs) were first categorized by Popescuet al^[1]in 2005. TCs were classified into interstitial cells of the Cajal (ICC) type based on their ultrastructure and immunohistochemical features, which are similar to mesenchymal cells.^[2]In the following ten years, TCs were found to have their own distinctive characteristics in terms of three-dimensional structure, immunological biomarkers, genomics, and multiple functions. Interestingly, TCs are definitely distinct from fibroblasts, mesenchymal stem cells, and endothelial cells in multiple organs of human beings and animals.^[3]They possess a particular cell body and a significantly different number of telopodes (Tps), which are considered as characteristic features compared to classical fibroblasts and endothelial cells.^[4]Tps form a moniliform pattern, consisting of thin segments (podomers) and small dilated regions (podsoms). The conbination of immunohistochemical biomarker analysis and transmission electron microscopy scanning, along with scanning electron microscopy (SEM) assay has become the "Gold Standard" protocol for distinguishing TCs from other interstitial cells.^[5]Under the SEM imaging, TCs with their interconnected Tps display a three-dimensional fabric that constructs an unabridged and convoluted network, indicating their ability to interact with parenchyma cells, immune cells, and cancer cells.^[6]

To the Editor: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has replaced other high-risk invasive methods and has become the primary method of tissue collection around the gastrointestinal tract.^[1]To further improve the effectiveness and safety of EUS-FNA, pathologists may perform rapid on-site cytology evaluation (ROSE), but this process requires the presence of pathologists. Macroscopic on-site evaluation (MOSE) has gained attention as it resolve the shortage of pathologist resources.^[2]Endoscopists can inspect the tissue core in real time and assess the adequacy of the punctured material. In this study, we conducted a single-center and single-arm exploratory study to explore the value of MOSE in assessing specimen quality during magnifier-based EUS-FNA and to confirm the cut-off length of visible tissue core (VTC) for EUS-FNA to help endosonographers independently predict the adequacy of punctured specimens. The VTC was defined as a white or incarnadine tissue core obtained from focal lesions with a relatively complete histological structure.

To the Editor:Air pollution can lead to respiratory and cardiovascular diseases (CVDs), and its impact on human health is very significant. Air particles less than 0.1 µm can pass through the blood brain barrier, reach the brain, and enter the central nervous system, causing physiological and pathological changes. A study shows that long-term exposure to fine particulate matter (PM_2.5) will increase the risk of CVDs among Chinese residents.^[1]Another study found that a short time exposure to low concentrations of air pollutants may also lead to the onset of acute coronary syndrome within one hour.^[2]A meta-analysis based on seven databases showed that environmental air pollution was positively correlated with elevated blood pressure and hypertension.^[3]Mounting evidence indicates that air pollution can cause cardiovascular and cerebrovascular diseases and affect human health furtherly.

To the Editor: Gestational diabetes mellitus (GDM) is a pathologic condition in which glucose intolerance and insulin resistance develop to different degrees during pregnancy. Women with GDM have higher odds of adverse maternal and fetal outcomes. Patients with a history of GDM were at a significantly increased risk for recurrence of GDM in subsequent pregnancies. Our previous and some other studies found an increased incidence of adverse perinatal outcomes in pregnant with recurrent GDM.^[1]So far, women with a prior history of GDM are not recommended to refrain from subsequent pregnancy in light of the limited available data. What about those women with a history of recurrent GDM? Should women with recurrent GDM be recommended to avoid further pregnancy? Currently, studies on perinatal outcomes of women with re-recurrent GDM and their prognostic factors are very rare. Therefore, this retrospective cohort study was performed to explore perinatal outcomes of pregnant woman with rerecurrent GDM and their prognostic factors.