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2026 Year 13 Volume 6 Issue
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Abstract：Artificial intelligence (AI) and big data are reshaping the healthcare landscape. However, clinical value depends on how well systems augment clinicians and fit into routine workflows. To this end, we introduce the TRIAD frame-work: trustworthy governance, real-world clinical value, and integrated adaptive deployment, to guide the develop-ment, validation, and deployment of clinical AI. TRIAD requires explicit data provenance and intended use, fairness auditing, and calibrated uncertainty. This framework evaluates the human-AI team in real workflows using teamlevel metrics, including accuracy, safety, workload, and patterns of acceptance, editing, and overriding. Deployment proceeds via staged rollouts with preregistered guardrails and continuous monitoring of performance and subgroup impact. TRIAD views intelligence as a property of the human-AI team rather than the AI model alone. Aligning gov-ernance, evaluation, and deployment around clinicians and patients enables durable gains in safety, equity, efficiency,and experience, thereby elevating clinical value.Keywords：TRIAD;Artificial intelligence (AI);Human-AI collaboration;Trust mechanisms;Clinical decision support60|35|0Updated：2026-08-20
PERSPECTIVE
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Abstract：BackgroundThe global increase in the incidence of early-onset cancers (defined as cancers diagnosed at 20–49 years old) is a serious public health problem. We investigated 1) whether the incidence trend of early-onset cancers differs from that of later-onset cancers and 2) whether both the incidence and mortality of early-onset can-cers have increased concurrently.MethodsWe utilized age-standardized incidence and mortality rates for early-onset and later-onset cancers diag-nosed between 2000 and 2017 from the Cancer Incidence in Five Continents and World Health Organization (WHO)mortality databases. The national obesity prevalence among adults aged 20–49 years was obtained from the National Clinical Database. Using joinpoint regression models, we calculated average annual percentage changes (AAPCs)for cancer incidence and mortality by cancer types and countries. We additionally conducted human development index (HDI)-stratified analyses and assessed the correlation between the obesity prevalence in younger populations and early-onset cancer incidence by country. To investigate the more recent trend of early-onset cancer mortality, we extended our mortality analysis after 2017 for cancer types and countries with statistically significant positive AAPCs in both incidence and mortality of early-onset cancers between 2000 and 2017.ResultsOur analysis showed that 10 early-onset cancer types (thyroid cancer, breast cancer, melanoma, uterine cancer, colorectal cancer, kidney cancer, cervical cancer, pancreatic cancer, multiple myeloma, Hodgkin lymphoma)in females and 7 early-onset cancer types (thyroid cancer, kidney cancer, testis cancer, prostate cancer, colorectal cancer, melanoma, leukemia) in males had statistically significant positive AAPCs in at least 10 countries. Among these, the following early-onset cancer types had significantly higher AAPCs than later-onset cancer types in females: colorectal cancer (6 countries; AAPC range: 1.8–3.8%), cervical cancer (6 countries; AAPC range: 1.2–3.3%), pancreatic cancer (5 countries; AAPC range: 2.3–13.0%), and multiple myeloma (5 countries; AAPC range: 3.1–9.8%); in males: prostate cancer (12 countries; AAPC range: 3.9–18.4%), colorectal cancer (8 countries; AAPC range: 1.8–3.2%), and kidney cancer (6 countries; AAPC range: 2.0–6.0%). We observed statistically significant positive AAPCs in both the incidence and mortality of the following early-onset cancer types: uterine cancer (5 countries) and colorectal cancer (3 countries in females and 5 countries in males). The steeper increases in early-onset cancers compared with later-onset cancers were mainly observed in the very high-HDI country group, including early-onset colorectal cancer (AAPC = 2.4%, 95% CI 2.1–2.6 in females; AAPC = 2.0%, 95% CI 1.7–2.4 in males) to later-onset colorectal cancer (AAPC= −0.1%, 95% CI −0.2 to 0 in females; AAPC = −0.2%, 95% CI −0.3 to 0 in males). We observed strong positive cor-relations between the increasing obesity prevalence and the rising incidence of early-onset obesity-related cancers in several countries, including Australia (7 cancer types), United Kingdom (7 cancer types), Canada (7 cancer types), Republic of Korea (7 cancer types), and USA (6 cancer types) in females and United Kingdom (7 cancer types), Canada (6 cancer types), Australia (5 cancer types), Sweden (5 cancer types), and Republic of Korea (4 cancer types) in males. Although we did not observe an apparent spike after 2017 in many countries, we observed continued increases in the mortality of certain cancer types, such as uterine cancer (Japan, Republic of Korea, United Kingdom, USA, and Ecuador) in females and colorectal cancer (Argentina, Canada, United Kingdom, and USA) in males.ConclusionsThe increase in many early-onset cancer types was significantly higher than that of later-onset cancers, and the incidence and mortality of certain early-onset cancer types (such as colorectal cancer) increased simultane-ously. Our study highlights global differences in cancer incidence and mortality trends of early-onset and later-onset cancers.Keywords：Neoplasms;epidemiology;risk factors;Global health;Young adults16|16|0Updated：2026-08-20 -
Abstract：BackgroundRisk-adapted colorectal cancer (CRC) screening has the potential to balance effectiveness with resource demands, yet evidence comparing it with established methods remains limited. This study aims to compare out-comes of risk-adapted CRC screening with colonoscopy and fecal immunochemical test (FIT) strategies.MethodsWe adopted a hybrid methodology combining real-world data from a population-based CRC screening randomized controlled trial (TARGET-C) with projections from a validated Markov-based microsimulation model (MIMIC-CRC). The TARGET-C trial enrolled 19, 582 participants aged 50–74 years from 6 centers in China, randomized in a 1: 2: 2 ratio into 3 groups. After applying the exclusion criteria, the final analysis included 3883 participants in the one-time colonoscopy group, 7793 in the annual FIT group, and 7697 in the risk-adapted screening group. In the latter group, screening allocation was determined by a composite risk score incorporating age, sex, family his-tory of CRC, smoking status, and body mass index, with high-risk participants referred for colonoscopy and low-risk participants for FIT. The primary outcome was detection rates of advanced neoplasm (CRC and advanced adenoma)over 4 rounds. Secondary outcomes included screening participation, colonoscopy demand, and costs from a societal perspective. Long-term effectiveness and cost-effectiveness were modeled over 15 years using MIMIC-CRC.ResultsAcross 4 rounds, overall participation rates (attending at least one screening round) were 42.3% (colonos-copy), 99.8% (FIT), and 92.5% (risk-adapted). Detection rates of advanced neoplasms were 2.8%, 2.3%, and 2.6%, respectively, with no significant differences (P > 0.05). Colonoscopies needed to detect 1 advanced neoplasm were 15.4, 7.9, and 9.3, respectively. From a societal perspective, the cost for detecting 1 advanced neoplasm was 15, 341, 21, 754, and 24, 300 Chinese Yuan, respectively. Over 15 years, risk-adapted screening reduced incidence by 16.7%and mortality by 21.5% compared with no screening, slightly less effective than colonoscopy (24.6% and 24.8%, respectively). Under observed real-world adherence, colonoscopy was the most cost-effective; under perfect full adherence, risk-adapted screening was the most cost-effective.ConclusionsIn this population-based CRC screening trial, risk-adapted screening, colonoscopy, and FIT demon-strated comparable effectiveness, but differed in participation rates, resource utilization, and cost-effectiveness. Risk-adapted screening could serve as a complementary approach to established strategies, particularly when health resources are limited.Trial registrationChinese Clinical Trial Registry (ChiCTR1800015506).Keywords：Colorectal cancer (CRC);screening;Risk-adapted screening;Randomized controlled trial;Cost-effectiveness34|27|0Updated：2026-08-20 -
Abstract：BackgroundPeritoneal fibrosis represents a major clinical challenge for end-stage renal disease (ESRD) patients when they are undergoing peritoneal dialysis (PD). Single-cell RNA sequencing identified that peritoneal mesothelial cells undergo a senescence fate transition in long-term PD patients. Whereas the existence of mesothelial cell senescence and the underlying mechanisms should be thoroughly explored.MethodsTo further investigate mesothelial cell senescence, we utilized a clinical cohort comprising dialysate effluents from PD patients and peritoneal biopsy specimens, peritoneal dialysis fluid (PDF)-induced mouse models,and cultured primary mesothelial cells. Single-cell RNA sequencing, transcriptome sequencing, immunofluorescence, Western blotting, and other analyses were administered. To validate the critical role of β-catenin in mesothelial cell senescence, β-catenin knockout mice were employed. Additionally, the senolytic drugs dasatinib plus quercetin were administered to PDF mice to assess the key role of mesothelial cell senescence in peritoneal fibrosis.ResultsSingle-cell RNA sequencing demonstrated that mesothelial cells derived from long-term PD patients are major trend to senescence fate. Moreover, β-catenin signaling was significantly upregulated, as well as trans-forming growth factor-β (TGF-β) pathways. We observed that senescent mesothelial cells were highly increased in both dialysate effluent and peritoneal biopsies of long-term PD patients. In dialysate effluent, matrix metalloproteinase-7 (MMP-7), an indicator of downstream targets of β-catenin, was positively correlated with TGF-β1. Both biomarkers were also positively associated with PD duration. Mechanistically, we found that β-catenin promotes dynamin-related protein 1 (Drp1) expression, a key mediator of mitochondrial fission, thereby inducing mesothelial cell senescence. Then, TGF-β1 was secreted to activate the Smad signaling pathway in fibroblasts, leading to myofibroblast activation and subsequent peritoneal fibrosis. Notably, administration of senolytic drugs, dasatinib plus quercetin, significantly alleviated peritoneal fibrosis regardless of treatment timing.ConclusionTargeting β-catenin signaling and mesothelial cell senescence may represent potential therapeutic interventions for preventing peritoneal fibrosis.Keywords：β-catenin;Mesothelial cell;Senescence;fibroblast;Peritoneal fibrosis;Peritoneal dialysis (PD)25|18|0Updated：2026-08-20 -
Abstract：BackgroundType 2 diabetes (T2D) is a global epidemic that reduces life expectancy. Evidence is limited on the benefits of achieving multiple guideline-recommended targets and cross-country differences. This study aimed to quantify the associations of risk factor control with mortality and life expectancy among individuals with T2D using nationwide cohorts from China, the USA, and the UK.MethodsWe included 46,351 adults with T2D at baseline from China Chronic Disease and Risk Factors Surveillance (CCDRFS; 2013, follow-up until 2021), USA National Health and Nutrition Examination Survey (USA NHANES;1999–2018, follow-up until 2019), and UK Biobank (2006–2010, follow-up until 2022). Patients with T2D were matched to controls without T2D using propensity score matching based on key demographic factors. Cox regression estimated mortality associated with lifestyle and metabolic factors outside target ranges [physical inactivity, smoking,unhealthy diet, elevated hemoglobin A1c (HbA1c), dyslipidemia, high blood pressure].ResultsOnly a small proportion of participants achieved ≥ 5 combined targets: 16.0% in CCDRFS, 9.9% in USA NHANES, and 6.8% in UK Biobank. During 470,369 person-years of follow-up, 7650 deaths (16.5%) occurred among individuals with T2D, and 9349 deaths (10.2%) occurred among controls over 965,249 person-years. At age 50, individuals with ≤ 1 risk factor outside the target lived 6–9 years longer than those with ≥ 5, and their life expectancy was comparable to that of controls without T2D. The association was independent of genetic predisposition to shorter lifespan in the UK Biobank. Additionally, individuals with T2D who failed to achieve optimal metabolic control but maintained a healthy lifestyle had a longer life expectancy compared with those who achieved optimal metabolic control but had an unhealthy lifestyle across all cohorts, with life expectancy gains ranging from 1.5 to 3.4 years depending on sex and cohort. Among individuals with T2D, healthy lifestyle behaviors (physical activity, non-smoking,a healthy diet) and HbA1c control contributed most to gains in life expectancy. Variations in multiple risk factor control and their associations with all-cause mortality were observed across different population subgroups.ConclusionsAchievement of guideline targets for multiple risk factors was low among individuals with T2D in China,the USA, and the UK. Comprehensive management of multiple risk factors, particularly lifestyle factors, was associated with a substantial reduction in the life expectancy gap between those with and without T2D, underscoring the importance of guideline-based care and individualized management.Keywords：Type 2 diabetes (T2D);risk factors;Mortality;Life expectancy;Prospective study22|23|0Updated：2026-08-20 -
Abstract：BackgroundIn 2022, China experienced an unprecedented heatwave event, raising concerns about the health impacts of heatwaves. This study aims to understand the devastating health risk of the exceptional heatwave in 2022 by comparing heatwave-related mortality burden in 2022 with that during 2000–2021.MethodsWe collected daily mortality and daily maximum temperature (DMT) during 2006–2017 in 364 locations(counties/districts) of China. Heatwave was defined as an event with 2 or more consecutive days of DMT exceeding the 92.5th percentile. We employed a distributed lag nonlinear model (DLNM) and a meta-analysis to examine the heatwave-mortality association based on the data from 364 counties/districts, and then this association was used to assess the mortality burden attributable to heatwaves during 2000–2022 in 368 cities in China. A percentage change (%) indicator, comparing the 2022 mortality burden to the average value from 2000 to 2021, was further calculated to highlight the severity of heatwaves in 2022.ResultsIn the past 2 decades, the frequency and intensity of heatwaves in China significantly increased,with the cumulative excessive degree-day increasing to 31,626 in 2022 compared with the annual average value of 13,772 during 2000–2021 across China. In 2022, we observed 62,961 [95% confidence internal (CI) 54,945–70,413]heatwave-related deaths in China, which was much higher than the annual average [35,987 (95% CI 31,252–40,471)]attributable to heatwaves during 2000–2021. The vulnerability groups of heatwave-related mortality in 2022 primarily included patients with cardiovascular diseases [40,567 (95% CI 35,313–45,404)], females [35,876 (95% CI 31,035–41,005)], and people aged over 65 years [56,208 (95% CI 49,023–62,864)]; and greater heatwave-related mortality was found in eastern-central China. The attributable fraction (AF) of heatwave-related deaths increased from an annual average of 11.01‰ (95% CI 9.56–12.38) during 2000–2021 to 18.11‰ (95% CI 15.80–20.25) in 2022 with 64.43% increment (95% CI 38.10–93.78), and the increase rates were greater in Xizang Autonomous Region(159.77%, 95% CI 12.84–477.87) and Sichuan Province (133.64%, 95% CI 3.84–416.61).ConclusionsThis study indicated that the frequency and intensity of heatwaves significantly increased in the past 2 decades in China, and the 2022 heatwaves were linked to a substantial mortality burden in China, with significant population and regional heterogeneity. Our findings underscore the need for developing comprehensive heat adaptation plans in the context of rapid aging and ongoing global warming.Keywords：Climate change;Heatwave;Mortality;Risk;Burden27|38|0Updated：2026-08-20
RESEARCH
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Abstract：Cancer neuroscience, an emerging convergent discipline, offers novel insights into the dynamic interplay between the nervous system and cancer progression. Bidirectional signaling between the nervous system and tumors, particularly within the innervated tumor microenvironment (TME), modulates key cancer hallmarks, including proliferation, immune evasion, angiogenesis, and metastasis. Neural ablation shows heterogeneous outcomes depending on nerve subtype and tumor context, underscoring the importance of nerve-type-specific and context-dependent therapeutic approaches. These mechanistic advances are catalyzing novel therapeutic strate-gies that target neural-TME interactions through the integration of neuroscience and oncology. Here, we highlight recent progress in cancer neuroscience and propose revised therapeutic frameworks aimed at the neuro-innervated TME. These strategies employ interdisciplinary approaches, such as drug repurposing [β-adrenergic receptor (β-AR)blockers, antipsychotics, antidepressants], and nanotechnology-enabled targeted delivery. Both preclinical and clini-cal data support the potential of neural-targeted therapies to improve precision, circumvent drug resistance, and enhance clinical outcomes. By bridging neuroscience and oncology, this framework delineates a translational pathway for harnessing neural-tumor crosstalk, presenting a promising avenue for advancing cancer therapeutics and improving patient care.Keywords：Bioelectricity;Cancer neuroscience;Drug repurposing;Neurotransmitters;Neurotrophic factors;Targeted therapy14|9|0Updated：2026-08-20 -
Abstract：Artificial intelligence (AI) offers transformative potential in pathology, where histopathological images remain the diagnostic gold standard due to their rich morphological and molecular information. While the rapid development of AI-driven computational pathology tools is revolutionizing disease interpretation, these technologies have not yet been systematically evaluated. Therefore, this review systematically evaluates AI applications across the diagnostic continuum, from image preprocessing and tumor classification to prognostic stratification and the discovery of predictive biomarkers. It presents a technical taxonomy of the algorithms and foundation models powering these applications, benchmarking their performance across diverse diagnostic tasks through rigorous comparative analyses. It also identifies critical challenges in clinical translation, including computational scaling, noisy annotations, interpretability gaps, and domain shifts. Finally, it proposes a roadmap for advancing AI applications in precision oncology and pathological research. By bridging technological innovation with clinical needs, this review aims to accelerate the integration of robust, unified, scalable AI solutions into diagnostic workflows.Keywords：Artificial intelligence (AI);Pathology images;Quantitative feature;Pathology foundation model30|44|0Updated：2026-08-20
REVIEW
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Keywords：G-quadruplex;RNA-DNA hybrids;Genome instability;DNA repair;Chromatin architecture46|36|0Updated：2026-08-20
COMMENTARY
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