Volume 138 · Issue 14 · 2025

免疫检查点疗法是一种不断发展的具有相当潜力的癌症治疗方法，通过调动机体免疫细胞对肿瘤细胞进行早期识别和清除，改变了传统的抗癌治疗策略，如手术、化疗和放疗。它是一种通过使用靶向免疫检查点的特异性抗体来防止肿瘤细胞免疫逃逸的治疗方法，这些免疫检查点抑制剂(ICI)的实例包括抗程序性细胞死亡-1(PD-1)/抗PD-配体1(PD-L1)和抗细胞毒性T淋巴细胞相关蛋白4(CTLA-4)。尽管ICI治疗在越来越多的肿瘤类型中具有无与伦比的疗效，但许多患者对治疗具有耐药性。患者间异质性可能与肠道微生物组的不同组成有关。

临床实践指南（以下简称“指南”）是指为向患者提供最佳医疗服务的循证建议，考虑各种干预措施的利弊。^[1]近年来，全球指南的制作大幅增加：1990年至2023年间，PubMed中索引的指南数量增加了近50倍。^[2]在过去的二十年里，由中国贡献者主导的指南数量也增加了近40倍。^[3,4,5,6]考虑到指南生产的这种不断升级的全球趋势，解决对其质量的担忧就更加重要了。高质量的指南增强了临床决策的科学基础，并在规范医疗保健专业人员的诊断和治疗实践方面发挥了关键作用。相反，规范不佳或不完整的指南，以及受实质性利益冲突影响的指南，会误导临床决策，浪费宝贵的医疗资源。最近的调查表明，准则的方法和报告质量普遍低于标准，^[7]这限制了它们在临床实践中的采用和实施。^[8,9,10]

Recent advances in large models demonstrate significant prospects for transforming the field of medical imaging. These models, including large language models, large visual models, and multimodal large models, offer unprecedented capabilities in processing and interpreting complex medical data across various imaging modalities. By leveraging self-supervised pretraining on vast unlabeled datasets, cross-modal representation learning, and domain-specific medical knowledge adaptation through fine-tuning, large models can achieve higher diagnostic accuracy and more efficient workflows for key clinical tasks. This review summarizes the concepts, methods, and progress of large models in medical imaging, highlighting their potential in precision medicine. The article first outlines the integration of multimodal data under large model technologies, approaches for training large models with medical datasets, and the need for robust evaluation metrics. It then explores how large models can revolutionize applications in critical tasks such as image segmentation, disease diagnosis, personalized treatment strategies, and real-time interactive systems, thus pushing the boundaries of traditional imaging analysis. Despite their potential, the practical implementation of large models in medical imaging faces notable challenges, including the scarcity of high-quality medical data, the need for optimized perception of imaging phenotypes, safety considerations, and seamless integration with existing clinical workflows and equipment. As research progresses, the development of more efficient, interpretable, and generalizable models will be critical to ensuring their reliable deployment across diverse clinical environments. This review aims to provide insights into the current state of the field and provide directions for future research to facilitate the broader adoption of large models in clinical practice.

Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients’ symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity—potentially attributed to underrecognition—and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.

Tuberculosis (TB) has one of the highest mortality rates among infectious diseases worldwide. The immune response in the host after infection is proposed to contribute significantly to the progression of TB, but the specific mechanisms involved remain to be elucidated. Single-cell RNA sequencing (scRNA-seq) provides unbiased transcriptome sequencing of large quantities of individual cells, thereby defining biological comprehension of cellular heterogeneity and dynamic transcriptome state of cell populations in the field of immunology and is therefore increasingly applied to lung disease research. Here, we first briefly introduce the concept of scRNA-seq, followed by a summarization on the application of scRNA-seq to TB. Furthermore, we underscore the potential of scRNA-seq for clinical biomarker exploration, host-directed therapy, and precision therapy research in TB and discuss the bottlenecks that need to be overcome for the broad application of scRNA-seq to TB-related research.

Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor (EGFR) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen.

We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints.

A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20–0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50–0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17–2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2–84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4–27.5 months) in integrated analysis.

For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy.

Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association.

This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results.

During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1–2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3–5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6–7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week (P_trend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD (P_trend = 0.011) and MCEs (P_trend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD (P_interaction = 0.037).

Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX.

This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10–15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10–15 mg weekly for MTX and 25 mg twice daily for IGU,n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52.

The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35–18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22–0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 (P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99–18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46–0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant.

IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA.

Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved.

A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro.

In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo. Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation.

Obstructive sleep apnoea–hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.

This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting.

This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III–IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan–Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate.

A total of 409 patients, 65.0% (n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% (n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573–0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3–5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054–2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10⁹/L (OR 3.772, 95% CI 1.377–10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10⁹/L (OR 2.006, 95% CI 1.219–3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs.

A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.

Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies.

The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted.

In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China’s CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging.

The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.

致编辑：当两个基因的同时扰动导致细胞死亡时，发生合成致死（SL），而单独扰动单个基因是相容的。结直肠癌（CRC）是主要的恶性肿瘤之一，在全球发病率中排名第三，在死亡率中排名第二。

致编辑：冠状动脉疾病（CAD）仍然是全世界发病率和死亡率的主要原因。^[1]动脉粥样硬化是一个缓慢进行的过程；因此，通常推荐有效的二级预防来阻止或延迟动脉粥样硬化向后续心血管事件的进展。^[2]然而，尽管最近在医疗和介入治疗方面取得了进展，冠状动脉粥样硬化性心脏病患者仍然处于心血管事件的高风险中，导致全球卫生支出不断增加。

致编辑：半椎体是一种不常见但并不罕见的脊柱畸形，可导致进行性先天性脊柱侧凸（CS）。由于其对支具治疗反应差，通常需要早期手术干预来矫正畸形和防止曲线进展。^[1]半椎体切除术已被证明是继发于半椎体的CS的有效手术治疗方法。最好的适应症是幼儿孤立性半椎体。^[2]不幸的是，一些CS患者，尤其是在农村地区，直到青春期才得到诊断和治疗。加重的脊柱畸形和相关的背痛促使他们寻求手术治疗。临床上，青少年病例通常表现为大的半椎骨，这意味着常规的半椎骨切除术会在椎骨之间留下大的残余间隙。因此，执行随后的机械压缩和缩短程序是一种高要求的技术，这可能导致失败的骨融合或其他神经并发症。^[3]众所周知，曲线的进展在青少年生长突增期间最快，并且在骨骼成熟时停止。对于接近成熟的脊柱，其导致进一步畸形的剩余生长潜力是有限的。青春期晚期患者真的需要完全半椎体切除术治疗CS吗？另一种合适的手术选择仍然值得研究。与传统的半椎体切除术相比，楔形截骨术（WO）可能是一些青少年患者的另一种可行选择。本研究旨在比较不同手术策略治疗青少年先天性半椎体患者的长期临床结果。

致编辑：亚低温诱发室颤停在微创手术中越来越受到重视。它不仅应用于微切口和胸腔镜手术，而且最近还应用于机器人手术。^[1,2,3,4]随着我们进行的全胸腔镜手术的数量和种类的增加，我们已经成功地将这种方法与中度低温诱导的心室颤动停搏相结合，用于心脏再手术。虽然有研究探索了亚低温诱发室颤停在微创手术中的应用，^[5,6,7]在比较全胸腔镜入路与传统胸骨正中切开入路方面，明显缺乏研究。本研究使用倾向评分匹配（PSM）回顾性检查和分析了这两种方法的围手术期结局。

自兴等人^[1]2019年，首次提出对通过多参数磁共振成像（mpMRI）和前列腺特异性膜抗原（PSMA）正电子发射断层扫描（PET）确定的高度可疑前列腺癌患者进行无术前活检的根治性前列腺切除术（RP），几篇原创文章报道了各种独立团队在这一方向上的尝试。尽管引发了广泛的争论，但这些文章和讨论为前列腺癌的诊断和治疗范式提供了新的见解。