2024年 · 第137卷第14期

Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disease caused by mutations in theNF1gene. It is characterized by cafe-au-lait macules (CALMs), cutaneous neurofibromas (CNF), plexiform neurofibromas (PNF), Lisch nodules, optic pathway gliomas (OPG), potential skeletal abnormalities, and other complications involving multiple organs and systems.^[1]Additionally, approximately 10% of individuals with NF1 may progress to develop malignant peripheral nerve sheath tumors (MPNST).^[1]TheNF1gene encodes neurofibromin, which regulates Ras and its downstream signaling pathways, such as the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways, thereby inhibiting abnormal cell differentiation and proliferation.^[2,3]

The role of Chinese expert consensus in standardization and improvement of the clinical diagnosis and treatment of inflammatory bowel disease (IBD) is self-evident. As clinical and basic research in China becomes standardized under a better understanding of IBD, more data on Chinese patients have become available to develop a consensus and guideline. This guideline, collaboratively developed by the IBD Group, Chinese Society of Gastroenterology, incorporates the latest international consensus statements,^{[1,2,3,4,5,6,7]}domestic research findings, and practical considerations, as an update based on the 2018 Chinese consensus on IBD management.^[8]The IBD guideline consists of two parts: ulcerative colitis (UC) and Crohn’s disease, and this manuscript presented the UC part. The evidence used in this guideline was collected and analyzed by the standard of guideline, and the contents were organized as problem statements, for clarity. The formulation of this guideline aimed to reflect the latest progress in IBD, providing comprehensive and valuable guidance for the clinical management of IBD.

Inflammatory bowel disease (IBD) is a complex condition, for which standardized diagnostics and treatment are paramount to enhance medical efficacy. Chinese consensus/guidelines for IBD management were formulated in 1978, 1993, 2001, 2007, 2012, and 2018, and markedly standardized and improved the clinical management of IBD in China. Recently, given the rising incidence of IBD in China,^[1]related clinical and basic research has received much attention. The depth of evidence is increasing, which has laid a solid foundation for updating the consensus guideline. Additionally, novel diagnostic methods and treatment modalities are being developed and updated rapidly. In this context, by incorporating the latest international consensus statements^[2,3,4,5,6]and integrating Chinese research findings and clinical practice approaches, the Inflammatory Bowel Disease Group of the Chinese Society of Gastroenterology, Chinese Medical Association, has revised the2018 Consensus on inflammatory bowel disease management.^[7]This revision differs from previous guidelines in that the guideline for ulcerative colitis management and that for Crohn’s disease (CD) management have been formulated and completed separately. This allows the new guidelines to fully reflect the research progress in each field, and to offer standardized, comprehensive, and feasible guidance for clinical practice. This text comprises the guideline for CD management.

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.

Shanghai Gynecologic Oncology Group (SGOG, www. ShanghaiGOG.org),^[1]established in 2009, is a non-profit organization of clinical research and the full member of Gynecology Cancer Intergroup (GCIG) since 2012. It was guided by Drs. Jinghe Lang (China), Gavin Stuart (Canada) (2009-2020); Drs. Jinghe Lang (China), Ding Ma (China) (2021-) and was supported by Dr. Zeyi Cao (2009-2012). The mission of SGOG is to actively promote the investigator-initiated trial (IIT) in gynecologic cancers, particularly the innovative phase II clinical trials. Followed by the high quality of management in investigators’ training, trial development, human resources, and research funding, SGOG has initiated phase III clinical trials to improve the future clinical practice. SGOG aims to obtain reliable data by conducting systematic, standardized, and high-quality clinical trials, to guide the clinical practice of ovarian cancer, endometrial cancer, and cervical cancer in China. SGOG holds group meetings twice a year, and actively participates in GCIG international communication and cooperation that expands its international and national influence in the field of clinical research in gynecologic cancers. This coordination is not only particularly relevant between academic groups but also with national and/or international industry partners.

To the Editor:Pulmonary vein antral isolation (PVAI) is the cornerstone of catheter ablation techniques used in the treatment of patients with atrial fibrillation (AF). However, the outcomes of a PVAI-only strategy for persistent AF have proven suboptimal. The majority of patients with persistent AF may require further atrial ablation beyond PVAI. Ablation of AF drivers, a patient-tailored ablation strategy for persistent AF with a procedural endpoint of AF termination, has garnered increasing attention in recent years.^[1]We aimed to determine the electrogram (EGM) characteristics of AF drivers that can predict AF termination.

To the Editor: Thoracic endovascular aortic repair (TEVAR) has been widely accepted as the first-line treatment when aortic repair is indicated. However, TEVAR is still limited by anatomic conditions in many circumstances, and the most common exclusion situations are inadequate proximal and/or distal landing zones when important branch vessels are involved. The incidence of insufficient distal landing zone in descending TEVAR ranges from 2.5% to 15.2%, and different approaches to extend it were described.^[1]Hybrid surgery with combined TEVAR and open revascularization of visceral vessels has been employed from the early stage of endovascular aortic repair but it is associated with poor outcomes. Endovascular visceral artery revascularization, such as branched and fenestrated endograft, has been used more recently. Outcomes of stenting visceral arteries during fenestrated/branched aortic repair were explored by several studies and promising results were exhibited.^[2]However, these techniques demand heavily on available device and technical skills. Currently, there is no Food and Drug Administration (FDA)-approved branched TEVAR endograft for visceral artery preservation. Chimney or snorkel procedures are relatively easier to perform, but it is associated with a higher incidence of endoleaks.^[3]

To the Editor: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To date, over 2000CFTRmutations have been identified. CF mostly occurs in the Caucasian population, and its incidence is approximately 1/25,000 to 1/1800. However, the number of CF cases in China is small. To discover the gene mutations and clinical characteristics of Chinese children with CF, as well as their correlation, the clinical data of 10 children with CF orCFTR-related disorders (CFTR-RD) were retrospectively analyzed in this study. Children with newly diagnosed CF or CFTR-RD were hospitalized at the Children’s Hospital Affiliated to the Capital Institute of Pediatrics from June 2015 to August 2021 were enrolled. This study was approved by the Ethics Committee of the Capital Institute of Pediatrics (No. SHERLL2021013), and all parents or guardian of patients have signed informed consent forms.

To the Editor:De-escalating the treatment of ductal carcinomain situ(DCIS) of the breast has been investigated in recent years. A 5-year adjuvant endocrine therapy (AET) regimen is the recommended treatment for hormone receptor-positive DCIS. Selective estrogen receptor modulators (such as the commonly used tamoxifen and toremifene) and aromatase inhibitors (AIs) are the currently used AET drugs. However, long-term AET is accompanied by severe side effects such as menopausal symptoms, endometrial carcinoma, cardiovascular events, venous thromboembolic events, osteoporosis, and joint pain that can significantly reduce patients’ quality of life. It was reported that only 50% of the patients completed the recommended 5-year AET mainly because of side effects, while higher adherence rates were observed with shorter-duration regimens.^[1,2]Therefore, de-escalation of AET should be considered to reduce the side effects of AET and improve adherence.

To the Editor:Cutaneous squamous cell carcinoma (CSCC) originates from the keratinocytes of the epidermal layer and (or) its associated appendages, manifesting as a rapidly proliferating, highly destructive malignancy, with almost 20,000 cases occurring in China in 2022.^[1]The pathogenesis of CSCC is complex, but recent studies have made significant progress. Our previous research identified eight proteins, including actinin alpha 1 (ACTN1), tenascin C (TNC), fascin actin-bundling protein 1 (FSCN1), serpin family B member 1 (SERPINB1), ras-related protein 31 (RAB31), collagen type III alpha 1 chain (COL3A1), collagen type I alpha 1 chain (COL1A1), and cluster of differentiation 36 (CD36), which are markedly linked to CSCC invasion and metastasis.^[2]Besides, our subsequent assays also revealed the elevated serum level of ACTN1 in CSCC patients, which correlated with tumor cell differentiation, invasion depth, and primary tumor diameter.^[3]This underscores the potentially pivotal role of ACTN1 in CSCC pathogenesis. This study aimed to further investigate the role of ACTN1 in the pathogenesis of CSCC.

To the Editor: Postmenopausal osteoporosis is a typical bone metabolic disruption disease caused by estrogen deficiency, characterized by deteriorated bone structure, reduced bone mineral density (BMD), and thinned sclerotin, which has troubled millions of menopausal women worldwide .^[1]Additionally, estrogen deficiency is accompanied by oxidative stress and inflammation, thus causing the occurrence and deterioration of osteoporosis.^[2]Conventional treatment options have limited efficacy and cannot meet the requirements of long-term treatment.^[3]Therefore, in order to alleviate the problem of osteoporosis in human health, innovative strategies should explore the possibilities and alternatives to current ones. In this study, collagen peptides (CP) were phosphorylated and then chelated with magnesium ions to produce phosphorylated collagen peptide magnesium chelates (PCP-Mg). The anti-osteoporosis properties of PCP-Mg were investigated by exploring the osteogenic function of osteoblasts, the preventive effect of ovariectomy (OVX)-induced bone loss in mice, and the potential mechanism underlying the effects on osteoporosis prevention. The results could provide a theoretical basis for the research and development of PCP-Mg in the food and pharmaceutical fields for the prevention and treatment of osteoporosis in the future.