2025年 · 第138卷第13期

Sepsis is a life-threatening condition, primarily triggered by infection, that can rapidly progress to multiple organ dysfunction syndrome (MODS) without timely intervention. The gut has long been recognized as a pivotal driver in the pathogenesis of sepsis and MODS.^[1]In severe sepsis and septic shock, the gut is often the first organ to be compromised and the last to recover, predisposing patients to intestinal dysbiosis and dysfunction, which further accelerates septic MODS.^[2]Growing evidence highlights the crucial role of the gut microbiota in sepsis pathophysiology, as sepsis-induced disruptions in microbial composition may contribute to organ failure.^[1]This interplay suggests a potential vicious cycle between gut microbiota dysregulation and sepsis progression.^[3]In this editorial, we explore the gut microbiota’s role in sepsis and potential therapeutic interventions.

Substantial progress has been made in the treatment of acute respiratory distress syndrome (ARDS), from its first description to the most recent updates in its definition and management guidelines.^[1,2]However, significant uncertainties persist regarding the optimal therapeutic strategies. These gaps highlight the need for a reevaluation of clinical practices and the initiation of innovative research to address the resolved challenges.

Sepsis is a significant global health burden, with substantial morbidity and mortality. The host immune response to infection appears to be a double-edged sword in the development of septic complications. Although an appropriate immune response is essential for pathogen clearance, an excessive or dysregulated response can lead to immune dissonance and subsequent organ injury. The immune response may vary depending on individual patient characteristics, pathogen type, infection site, and co-existing factors. This heterogeneity presents a substantial challenge for clinical evaluation of immune status.

Heart failure represents a growing pandemic as it affects ~64 million individuals globally,^[1]and it has an annual incidence of 2 million cases per year, one-third of which are in China.^[2,3]Of these, 10% progress to end-stage disease, for which cardiac transplantation remains the sole curative therapy. Despite this critical need, profound disparities persist: Only 6000 heart transplants are performed annually worldwide, with <500 pediatric cases, thus resulting in a staggering supply–demand gap of 1:100 (The International Society for Heart and Lung Transplantation, 2023 Registry).^[2]This critical disparity—which leads to >30% of waitlisted patients dying annually while <1% receive transplants—requires urgent innovations in donor optimization and recipient-specific therapeutic strategies.

Accessory cavitated uterine malformation (ACUM) is a rare obstructive uterine anomaly that remains poorly understood, posing challenges for clinical management. The aetiopathogenesis is hypothesised to involve the duplication and persistence of ductal Müllerian tissue usually near the round ligament attachment, potentially related to gubernaculum dysfunction. ACUM is specifically classified by Acién’s system, though rare variants necessitate continued international research to refine classification frameworks. This consensus aims to develop good clinical practice recommendations for the pathophysiology, terminology, clinical presentation, diagnosis, and treatment of ACUM. A working group consisted of Chinese and European experts, after approval from the European Society for Gynaecological Endoscopy, developed recommendations based on the best available evidence and experts’ opinion. Patients with ACUM present with typical symptoms such as dysmenorrhea and dyspareunia, and atypical symptoms, including gastrointestinal and generalized pelvic pain. Diagnostic criteria include isolated cavitated lesions in the anterolateral myometrium near the round ligament, lined by endometrial tissue and filled with haemorrhagic fluid, surrounded by a myometrial mantle with concentric orientation of myometrial fibres, and typically associated with a normal uterine cavity. Diagnosis is most accurately made through ultrasound and magnetic resonance imaging. Surgical excision of the ACUM is considered the definitive treatment offering near-complete symptom resolution, and a minimally invasive approach should be preferred when possible. The timing of surgery and the interval before attempting pregnancy remain unclear. The mode of delivery post-surgery is individualised based on the degree of myometrial involvement. The current consensus summarises the existing evidence on ACUM, providing good clinical practice recommendations for its management. Existing gaps in the understanding and management of ACUMs, highlight the need for further research to guide clinical decision-making.

Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promises, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.

In recent years, growing evidence indicates that the nervous system plays an indispensable role in tumor development and metastasis. Elucidating crosstalk between the nervous system and tumor progression has thrived as a hot topic and a new direction for understanding cancer pathogenesis. Notably, many novel discoveries have suggested that neurotransmitter receptors (NRs) are not only widely expressed in cancer cells, but also play key roles in regulating cancer initiation and progression by diverse approaches. In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention. The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, resistance to drugs, and participate in the formation of neural–cancer interactions. In addition, NRs also regulate cellular metabolic processes and tumor microenvironment (TME) remodeling. More importantly, numerous basic and clinical studies have suggested that NRs may be potential targets for cancer treatments, and corresponding agonists or antagonists have been identified effectively in controlling tumor growth and metastasis. In conclusion, NRs are emerging as novel targets for anti-cancer drug exploration and clinical cancer treatments, while trying to uncover deeper mechanisms and connections between NRs and cancer is of high clinical significance and translational value.

Definitive treatment of lung cancer with radiotherapy is challenging, as respiratory motion and anatomical changes can increase the risk of severe off-target effects during radiotherapy. Online adaptive radiotherapy (ART) is an evolving approach that enables timely modification of a treatment plan during the interfraction of radiotherapy, in response to physiologic or anatomic variations, aiming to improve the dose distribution for precise targeting and delivery in lung cancer patients. The effectiveness of online ART depends on the seamless integration of multiple components: sufficient quality of linear accelerator-integrated imaging guidance, deformable image registration, automatic recontouring, and efficient quality assurance and workflow. This review summarizes the present status of online ART for lung cancer, including key technologies, as well as the challenges and areas of active research in this field.

The choice of unicompartmental knee arthroplasty (UKA) vs. total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA.

PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards.

Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01–1.45; P <0.001), greater knee function (MD: 1.78; 95% CI: 0.34–3.22; P = 0.020), less pain (MD: 0.75; 95% CI: 0.43–1.06; P <0.001), and better health status (MD: 3.75; 95% CI: 0.81–6.69; P = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45–0.78; P <0.001) and shorter hospital stays (MD: –0.89; 95% CI: –1.57 to –0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction.

In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.

Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke.

This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes.

Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1–Q3: 20–88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12–0.49, P <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11–0.41, P <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08–0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06–0.50, P <0.01).

Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes.

Epidemiological data on chronic diarrhea in the Chinese population are lacking, and the association between obesity and chronic diarrhea in East Asian populations remains inconclusive. This study aimed to investigate the prevalence of chronic diarrhea and its association with obesity in a representative community-dwelling Chinese population.

This cross-sectional study was based on a multistage, randomized cluster sampling involving 3503 residents aged 20–69 years from representative urban and rural communities in Beijing. Chronic diarrhea was assessed using the Bristol Stool Form Scale (BSFS), and obesity was determined based on body mass index (BMI). Logistic regression analysis and restricted cubic splines were used to evaluate the relationship between obesity and chronic diarrhea.

The standardized prevalence of chronic diarrhea in the study population was 12.88%. The average BMI was 24.67 kg/m². Of all the participants, 35.17% (1232/3503) of participants were classified as overweight and 16.13% (565/3503) as obese. After adjustment for potential confounders, individuals with obesity had an increased risk of chronic diarrhea as compared to normal weight individuals (odds ratio = 1.58, 95% confidence interval: 1.20–2.06). A nonlinear association between BMI and the risk of chronic diarrhea was observed in community residents of males and the overall participant group (P = 0.026 and 0.017, respectively).

This study presents initial findings on the prevalence of chronic diarrhea among residents of Chinese communities while offering substantiated evidence regarding the significant association between obesity and chronic diarrhea. These findings offer a novel perspective on gastrointestinal health management.

Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process.

DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4⁺CD25^- T-cells or CD4⁺CD25⁺ T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice.

CD103⁺CD11b⁺ DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3⁺Treg percentages within a co-culture system of CD4⁺CD25^- T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3⁺ Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4⁺ T-cells or CD4⁺CD25⁺ T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice.

The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.

Immunosuppression is closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we aimed to examine the role of the Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis and elucidate its potential molecular mechanism in sepsis induced immunosuppression.

RNA sequencing databases were used to validate SAMSN1 expression in sepsis. The impact of SAMSN1 on sepsis was verified using gene knockout mice. Flow cytometry was employed to delineate how SAMSN1 affects immunity in sepsis, focusing on immune cell types and T cell functions. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing in RAW264.7 macrophages enabled interrogation of SAMSN1’s regulatory effects on essential macrophage functions, including cell proliferation and phagocytic capacity. The mechanism of SAMSN1 in the interaction between macrophages and T cells was investigated using the RAW264.7 cell line and primary cell lines.

SAMSN1 expression was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. Genetic deletion of Samsn1 in murine sepsis model improved T cell survival, elevated T cell cytolytic activity, and activated T cell signaling transduction. Concurrently, Samsn1 knockout augmented macrophage proliferation capacity and phagocytic efficiency. In macrophage, SAMSN1 binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), causing nuclear factor erythroid 2-related factor 2 (NRF2) to dissociate from the KEAP1–NRF2 complex and translocate into the nucleus. This promotes the transcription of the coinhibitory molecules CD48/CD86/carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), which bind to their corresponding receptors natural killer cell receptor 2B4/CD152/T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on the surface of T cells, inducing T-cell exhaustion.

SAMSN1 deletion augmented adaptive T cell immunity and macrophage phagocytic-proliferative dual function. Furthermore, it mediates the KEAP1–NRF2 axis, which affects the expression of coinhibitory molecules on macrophages, leading to T-cell exhaustion. This novel immunosuppression mechanism potentially provides a candidate molecular target for sepsis immunotherapy.

To the Editor: Ischemic heart disease (IHD) remains a major contributor to global mortality, with acute myocardial infarction (AMI) posing a significant public health issue. Although the majority of AMI cases involve obstructive coronary artery disease (MI-CAD), approximately 5–10% of patients present with myocardial infarction with non-obstructive coronary arteries (MINOCA).^[1]While percutaneous coronary intervention is effective for MI-CAD, patients with MINOCA, despite the lack of significant stenosis in major coronary vessels, often experience outcomes as poor as, or worse than, those of MI-CAD patients due to inadequate treatment approaches.

To the Editor: Endometrial cancer (EC) ranks as the second most common gynecologic malignancy in China, with rising incidence rates.^[1,2]In China, the 5-year survival rate for EC patients has improved from 55.1% in 2003–2005 to 72.8% in 2012–2015. However, due to sociodemographic, clinicopathological, and treatment-related factors, this remains lower than the 81% in the United States.^[3,4]EC is a complex disease with multiple risk factors, distinct histological subtypes, and a variety of available therapeutic options. However, we know very little about the real-world characteristics and treatment patterns of EC in China.^[5]Therefore, this large-scale, multicenter study aimed to investigate the demographic, histopathological, and molecular features of newly diagnosed EC patients in China, as well as to provide insights into current treatment patterns.

To the Editor: The cartilage–subchondral bone (SB) unit that comprises the articular cartilage (AC) layer and subchondral bone bears the most severe impact force of the knee joint. The mechanical integrity of cartilage and its resistance to injury depend not only on the biochemical composition of its extracellular matrix but also on its interaction with the underlying SB. Both structures act in concert with complementary mechanical functions, the former as a bearer and the latter as a structural girder and shock absorber.^[1]The SB absorbs most of the mechanical stimuli transmitted by joints.^[1]SB comprises two distinct anatomic entities: the subchondral bone plate (SP) and the subchondral trabecular (ST) bone, which differ greatly in compositional and mechanical properties. Bone is a nanocomposite material in which hard inorganic (hydroxyapatite crystallites) and organic (collagen fibrils) components are hierarchically arranged on the nanometer scale.^[2]Bone quality is dependent on the spatial distributions of the shape, size, and composition of bone constituents (minerals, collagen, and water).^[3,4]Previous studies have indicated that an initial decrease in the elastic modulus of SB occurred during the osteoarthritis (OA) pathological process.^[5]AC degeneration might be directly affected by the mechanical environmental changes induced by changes in the SB.^[5]However, to the best of our knowledge, the understanding of nanoscale mechanical properties across the osteochondral region is limited, which restricts the ability to understand the disease progression and to engineer replacement materials. Few studies have investigated the relationship between changes in the nanoscale surface topography and the mechanical properties of SB and those of AC. Therefore, one objective of our study was to evaluate changes in the topographical and mechanical properties of AC in Dunkin Hartley (DH) guinea pig knees relative to the stage of OA, with a specific focus on surface roughness—a key determinant of tissue lubrication. Another aim was to correlate observed changes in AC surface topography and mechanical properties with those of SB, which is crucial for understanding the functional interplay within the cartilage–subchondral bone unit in OA pathogenesis. We hypothesized that AC surface roughness and the indentation moduli of ST and SP increase with OA progression and play more significant roles in OA pathogenesis than their bone matrix topographical features.

To the Editor: Annular pustular psoriasis (APP), a rare variant of generalized pustular psoriasis (GPP), manifests as recurrent, ring-shaped erythematous lesions adorned with small, sterile pustules, following a subacute trajectory. The recurrent nature of APP substantially diminishes patient quality of life. Owing to its infrequency, unified treatment protocols remain elusive. Our study analyzes data from 4 original cases alongside 41 cases from existing literature, encapsulating demographic data, genetic profiles, clinical presentations, and responses to treatments. Also, we performed whole genome sequencing (WGS) to detect genetic features of APP. This study was approved by the Institutional Review Board of The University of Hong Kong–Shenzhen Hospital (No. [2024]151). Written informed consent was obtained from all the patients.

To the Editor: Upadacitinib, an oral janus kinase (JAK) inhibitor, exhibits a higher inhibitory potency for JAK1 compared to JAK2, JAK3, or tyrosine kinase 2, making it a promising candidate for the treatment of atopic dermatitis (AD). Global trials Measure Up 1, Measure Up 2, and AD Up have demonstrated efficacy and safety data for moderate-to-severe AD, both as monotherapy and in combination with topical corticosteroids (TCS).^[1,2]The updated 52-week results preliminarily reported sustained clinical benefits over 52 weeks,^[3,4]but data on long-term outcomes in Chinese patients remain limited. Ethnic differences in AD pathophysiology, including variations in immune signatures, underscore the need for region-specific evidence.^[5]Thispost hocanalysis of Measure Up 1 and AD Up trials evaluates the 140-week efficacy and safety of upadacitinib in Chinese patients.