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2026 Year 13 Volume 7 Issue
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Abstract：Target trial emulation (TTE) has demonstrated popularity because of its ability to improve the reliability of causal inference from observational data. Nevertheless, knowledge about the current use, potential challenges, and insights of target trials in oncology is scarce. A total of 90 TTE studies in cancer areas were identified through systematic reviews in PubMed and Embase. Among the 54 applications in cancer treatment, registry databases (44.4%) and overall survival (OS, 63.0%) were predominantly used as data sources and primary endpoints, respectively. Approximately 30 (55.6%) of the included TTE cases were associated with immortal time bias, and 21 (38.9%) were associated with prevalent user bias. Among the 21 trials from 13 studies that aimed to calibrate the results from preexisting randomized controlled trials (RCTs), only 42.9% met both statistical agreement and estimate agreement. The availability of fit-for-purpose data sources and uncertainty about result concordance were the main hurdles limiting the quantity and quality of TTE in oncology areas. Promoting regulatory acceptance by initiating special projects could be crucial for the expanded application of real-world data (RWD) using TTE. Potential solutions,such as the integration of electronic medical records at the regional or country level, linkage with insurance claims databases, the modernization of eligibility criteria, the use of OS as the primary endpoint, and other best practices,were recommended for improving the feasibility and quality of oncology TTE.Keywords：Target trial emulation (TTE);Oncology;Bias;Real-world database24|30|0Updated：2026-08-20
PERSPECTIVE
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Abstract：BackgroundAnemia is a major global health problem. There were 89% of all anemia-related disabilities in developing countries. We aim to analyze the burden of anemia and its underlying causes in China from 1990 to 2023.MethodsUtilizing the data of the 2023 Global Burden of Disease (GBD 2023) study, this study analyzed the burden of anemia in China between 1990 and 2023. Then we analyzed the number and rate of anemia attributed to 16 underlying causes for all genders and ages. Drivers of change in prevalence and years lived with disability (YLD) numbers due to anemia were explored by decomposition analysis. And locally weighted regression was used to estimate the relationship between socio-demographic index (SDI) and age-standardized prevalence rate (ASPR) and age-standardized YLD rate due to anemia.ResultsFrom 1990 to 2023, the ASPR and age-standardized YLD rate showed a downward trend among all anemia types (P < 0.05), and the ASPR and age-standardized YLD rate of anemia in females were higher than those in males. The highest number and rate of prevalence were found in mild anemia, and the highest number and rate of YLD were found in moderate anemia. As age increased, the prevalence and YLD rate of anemia increased, with a significant increase in females aged 20−54, in particular of moderate anemia. In 2023, the highest ASPR and age-standardized YLD rate among all anemia types were in the Northwestern regions. Compared to 1990, 31 provinces, Hong Kong,and Macao exhibited declines in both the ASPR and the age-standardized YLD rate for anemia. In China, most of the prevalent cases and YLD were attributable to dietary iron deficiency in 2023. The total prevalence of anemia decreased by 46.14% [95% uncertainty interval (UI) 27.54−61.02], of which age-specific rate, population growth,and population aging accounted for -77.32%, 21.33%, and 9.84%, respectively. A negative association between SDI and the ASPR and age-standardized YLD rate of anemia was shown in China.ConclusionsFrom 1990 to 2023, the burden of anemia in China has decreased but remained heavy among women of childbearing age, the elderly, and in the Northwestern region. Tailored prevention and control strategies should be strengthened to reduce the burden of anemia in high-risk areas.Keywords：Anemia;Prevalence;Years lived with disability (YLD);Burden of disease;Trend29|35|0Updated：2026-08-20 -
Abstract：BackgroundSepsis and rheumatoid arthritis (RA) are distinct yet mechanistically related conditions commonly driven by dysregulated inflammatory responses. Here, we explored the counterintuitive hypothesis that an epitope from a deleterious anti-tetranectin (TN) antibody (mAb9) could hold unforeseen therapeutic potential.MethodsBy mapping mAb9’s epitope to P2 (residues 55–70), a region crucial for TN’s protective functions, we developed P2-1, a water-soluble derivative as a targeted therapy. We then employed animal models of sepsis (cecal ligation and puncture) and arthritis (collagen antibody-induced arthritis) to evaluate the therapeutic effects of P2, P2-1, and a procathepsin L (pCTS-L)-neutralizing antibody by assessing septic survival, arthritis severity, pain sensi-tivity, and joint tissue histology. In parallel, we utilized a surface plasmon resonance (SPR) assay and computational modeling to examine the P2-1/high mobility group box 1 (HMGB1) interaction. Finally, we elucidate the effect of P2-1 on the HMGB1-induced release of pCTS-L and other cytokines and chemokines using primary human peripheral blood mononuclear cells (PBMCs).ResultsP2-1 significantly improved survival and reduced systemic inflammation in a sepsis model, and attenuated arthritis severity and pain sensitivity in an RA model, even with therapeutic administration after disease onset. Mecha-nistically, P2-1 exhibited high-affinity binding to HMGB1 and selectively suppressed HMGB1-induced cathepsin L (Ctsl) mRNA upregulation and pCTS-L secretion from human immune cells, crucially without perturbing other HMGB1-induced cytokines and chemokines. We further validated pCTS-L as a therapeutic target by demonstrating that a neu-tralizing antibody conferred potent antiarthritic effects, reducing joint inflammation, pain, and structural damage.ConclusionsOur findings introduce a paradigm-shifting drug discovery strategy that transforms insights from harm-ful antibody action into targeted therapeutics for the HMGB1-pCTS-L axis. This approach not only delivers P2-1 as a potent therapy but also establishes pCTS-L as a crucial mediator in inflammatory diseases such as sepsis and RA.Keywords：High mobility group box 1 (HMGB1);Procathepsin L;Tetranectin;sepsis;Rheumatoid arthritis (RA);antibody;Mimetic peptide;Epitope;Innate immune cells19|39|0Updated：2026-08-20 -
Abstract：Background:Antimicrobial resistance (AMR) constitutes a critical global health challenge with major implications for public health and economic stability, increasing infection- and sepsis-related mortality. Despite growing evidence on its contribution to disease burden, comprehensive assessments of long-term trends at the regional level remain limited in the World Health Organization (WHO) Southeast Asia Region (SEAR) and Western Pacific Region (WPR).Methods:We used data from the Global Research on Antimicrobial Resistance (GRAM) Project to evaluate sepsis-and AMR-related deaths and disability-adjusted life-years (DALYs) for 11 infectious syndromes, 22 pathogens, and 84 pathogen-drug combinations across 42 countries and territories in the WHO SEAR and WPR from 1990 to 2021. AMR burden was estimated under two counterfactual scenarios: deaths and DALYs attributable to AMR (representing the burden if drug-resistant infections were replaced by drug-susceptible infections), and deaths and DALYs associated with AMR (representing the burden if infections did not occur at all). We reported numbers, crude rates, and age-standardized rates, and generated forecasts of AMR burden to 2050 using an autoregressive integrated moving average model.Results:In SEAR and WPR, there were 8.36×106 [95% uncertainty interval (UI) 7.93–8.79] sepsis-related deaths in 1990, which decreased to 6.03×106 (95% UI 5.68–6.39) in 2019 before increasing to 8.31×106 (95% UI 7.86–8.76) in 2021. The number of deaths associated with AMR ranged from 2,445,875 (95% UI 2,221,769–2,670,192) in 1990 to 2,358,190 (95% UI 2,173,521–2,545,190) in 2021, while deaths attributable to AMR ranged from 546,479 (95% UI 487,669–605,277) to 587,103 (95% UI 534,165–639,903) over the same period. From 1990 to 2021, deaths attributable to AMR decreased among people <25 years, with a 76.1% [95% confidence interval (CI) 70.6–81.6] reduction occurring among children <5 years, while those among adults aged ≥70 years more than doubled, increasing from 133,013 (95% UI 124,066–141,922) to 298,366 (95% UI 284,023–312,475). The largest increase in the number of deaths attributable to AMR was caused by methicillin-resistant Staphylococcus aureus [from 30,168 (95% UI 24,956–35,351) in 1990 to 66,946 (95% UI 57,544–76,479) in 2021]. In 2021, Kiribati had the highest age-standardized mortality rate (per 100,000 person-years) attributable to AMR [30.9 (95% UI 24.1–37.8)], whereas New Zealand had the lowest [3.2 (95% UI 2.6–3.8)] among the two regions. By 2050, the number of deaths associated with AMR is predicted to reach 3,875,753 (95% UI 1,502,402–9,998,297) in these two regions, of which 952,592 (95% UI 766,353–1,184,090) deaths are attributable to AMR.Conclusions:This study highlights the escalating burden of AMR in SEAR and WPR, emphasizing the urgent need for attention to this persistent and growing crisis. Our analyses underscore the dual challenge of sustaining gains among people <25 years while addressing the alarming increase of AMR in elderly populations. Given the high variability of AMR burden by pathogen, age group, and country, strengthened surveillance and improved laboratory capacity are essential to accurately characterize resistance patterns and guide clinical decision-making.Keywords：Antimicrobial resistance;Burden;Southeast Asia Region (SEAR);Western Pacific Region (WPR)29|38|0Updated：2026-08-20 -
Abstract：Background:Mitochondrial quality control is essential for limiting myocardial injury induced by ischemia/reperfusion(I/R), a major contributor to adverse outcomes after reperfusion therapy. This study aimed to determine whether the deubiquitinase ubiquitin-specific protease 18 (USP18) regulates mitophagy during cardiac I/R injury and thereby represents a potential therapeutic target to attenuate myocardial I/R injury.Methods:Cardiac-specific USP18 knockout mice were subjected to cardiac I/R injury. To elucidate the role of USP18 in mitophagy regulation and cardiac I/R injury, we performed RNA sequencing, proteomic mass spectrometry, transmission electron microscopy, and mitophagy assays. In parallel, adeno-associated virus serotype 9 (AAV9)-mediated overexpression of USP18, knockdown of Parkin and phosphatase and tensin homolog-long (PTEN-L), and administration of an anti-PTEN-L neutralizing antibody were used to elucidate the underlying mechanisms. Additionally, serum samples from patients with ST-segment elevation myocardial infarction (STEMI) were collected to assess clinical relevance.Results:USP18 expression was upregulated in mouse hearts following I/R injury and in ischemic human heart tissue. Cardiac-specific USP18 deficiency mitigated I/R-induced acute myocardial injury, mitochondrial dysfunction, and adverse cardiac remodeling, whereas USP18 overexpression exacerbated these pathological changes. Mechanistically, USP18 interacted with PTEN-L, which in turn bound to and inhibited the phosphorylation and translocation of Parkin to mitochondria, thereby suppressing mitophagy. Parkin knockdown abolished the cardioprotective effects conferred by USP18 deficiency, whereas PTEN-L knockdown reversed the detrimental effect of USP18 overexpression. Moreover, PTEN-L also exerted pathogenic effects via a paracrine mechanism, as neutralizing PTEN-L with an antibody attenuated cardiac I/R injury. Serum PTEN-L levels were elevated in STEMI patients, particularly postintervention.Conclusions:USP18 impairs mitophagy and exacerbates cardiac I/R injury through a PTEN-L-Parkin axis, involving both intracellular and paracrine mechanisms. Targeting the USP18-PTEN-L pathway may represent a novel therapeutic strategy to alleviate myocardial I/R injury.Keywords：Myocardial ischemia/reperfusion (I/R) injury;Ubiquitin-specific protease 18 (USP18);Mitophagy;Phosphatase and tensin homolog-long (PTEN-L);Parkin26|42|0Updated：2026-08-20
RESEARCH
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Abstract：Disruptions in lipid metabolism cause numerous metabolic diseases, including obesity, diabetes, cardiovascular diseases, and liver disorders. Consequently, lipid metabolism serves as a potential therapeutic target, influencing the progression of various non-metabolic diseases such as kidney diseases, cancer, neurodegenerative disorders, aging, and bone-related diseases. The metabolic pathways involved in lipid metabolism are complex and highly interconnected. Although the abundance of metabolic targets presents opportunities for lipid metabolism regulation, the limited precision and safety of traditional therapeutic approaches remain significant challenges. These limitations have catalyzed the development of multifunctional nano-delivery platforms aimed at targeted intervention in lipid metabolic processes, further enhancing the flexibility of lipid metabolism regulation. This review outlines the latest advancements and representative applications of these multifunctional nano-delivery platforms. Notably, extensive research has been conducted on nanoparticles and liposomes, with these technologies being relatively mature. Furthermore, numerous novel biomaterials, including engineered adipocytes, exosome vesicles secreted by natural cells, smart-responsive nanomicelles, composite hydrogels, and engineered lipid droplets, are being increasingly explored. Finally, the review discusses the advantages of drug delivery strategies based on the targeted intervention of lipid metabolic processes, the limitations of current technologies, promising future research directions, and treatment challenges.Keywords：Multifunctional nano-delivery system;Lipid metabolism;Lipid metabolism reprogramming;Lipid metabolism-related diseases33|18|0Updated：2026-08-20 -
Abstract：Polytrauma with predominant musculoskeletal (MSK) injury, resulting from blast, blunt, and crush mechanisms, remains a leading and complex challenge in both military and civilian medicine. These injuries not only disrupt tissues structurally but also trigger systemic cascades involving immune imbalance, endothelial dysfunction, mitochondrial stress, and premature cellular senescence. Such pathological processes contribute to both immediate clinical instability and long-term complications such as fibrosis, aberrant bone formation, neuroinflammation, and chronic disability. Conventional injury assessments, which rely heavily on anatomical scoring and nonspecific blood markers, fail to capture the dynamic molecular landscape underlying these conditions. To address this critical gap, we performed a comprehensive scoping review integrating evidence from basic science, translational studies, and clinical research published between January 2000 to June 2025, with particular emphasis on recent advances. The review highlights the discovery and validation of emerging blood-based and molecular biomarkers, including fatty acid-binding protein 3, syndecan-1, galectin-3, and trauma-associated microRNAs, as well as innovative diagnostic paradigms such as wearable biosensors, minimally invasive liquid biopsy platforms, and artificial intelligence (AI)-driven analytics. Unlike prior reviews, our analysis uniquely integrates findings across both military and civilian trauma contexts, providing actionable frameworks for clinical application. Building on these insights, we outline a practical roadmap: 1) deploys integrated multi-marker panels for early risk stratification, 2) expands inclusive trauma biobanking to capture diverse injury phenotypes, and 3) uses adaptive, data-driven tools for real-time triage and personalized intervention. This approach links acute systemic responses to downstream recovery and rehabilitation, offering actionable guidance for both military and civilian trauma systems.Keywords：Musculoskeletal (MSK) injury;Polytrauma;Biomarkers;Endothelial dysfunction;Biosensors;Artificial intelligence (AI)19|19|0Updated：2026-08-20
REVIEW
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Keywords：Chitosan hydrogel;Epsilon poly-L-lysine;Extracellular vesicles;Polymicrobial-infected extremity soft tissue injury;Acinetobacter baumannii;Escherichia coli;Staphylococcus epidermidis;Porcine polytrauma model;Pulmonary contusion;Hemorrhage10|15|0Updated：2026-08-20
LETTER TO THE EDITOR
- Keywords：Burn injury;sepsis;epidemiology;Biomarkers;Artificial intelligence;antibiotics20|31|0Updated：2026-08-20
COMMENTARY
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