Military Medical Research最新文献

Background: The level of premature deaths (deaths among those aged 30-69 years) caused by cancer is an important indicator of evaluating the level of cancer prevention and control. However, the current burden and temporal trends in cancer-related premature deaths, and their impact on life expectancy at the global, regional, and national levels are not clear.

Methods: Cancer mortality data for 185 countries were obtained from the GLOBOCAN 2022 database. High-quality cancer mortality data and national population statistics for 47 countries were extracted from the United Nations and national cancer registry databases, covering the period 2003-2022. Countries were classified based on the human development index (HDI). The death probability, the year of life lost (YLL), and the potential gain in life expectancy (PGLE) attributable to premature deaths from site-specific and all-cancers combined were calculated.

Results: Globally, the probability of premature cancer deaths was 6.49% (95% UI 6.49-6.50). The YLLs caused by cancer-related premature death were 163.86 million (95% UI 163.70-164.03), constituting 65.58% of the total cancer-related YLLs. The PGLEs were 1.16 years (95% UI 1.16-1.16). The premature death probability increased with higher HDI levels in men, but decreased in women. Cancer-related premature deaths as a proportion of total cancer deaths varied from 18.31% (95% UI 18.20-18.43) in Japan to 84.44% (95% UI 76.10-91.16) in São Tomé and Príncipe. Lung cancer was the leading cause of cancer-related premature deaths in men, and breast cancer ranked first in women. By eradicating premature deaths attributable to lung, liver, colorectal, and stomach cancer in men, and to breast, cervical, and lung cancer in women, 0.55 years (95% UI 0.55-0.55) and 0.49 years (95% UI 0.49-0.49) of PGLEs could be achieved, accounting for 48.67% and 42.24% of the total PGLEs, respectively. Cancer-related premature deaths decreased significantly in 38 countries during 2003-2022 (P < 0.05). The probability of premature cancer-related deaths decreased by more than 15.50% from 2015 to 2022 in 16 countries.

Conclusions: Cancer-related premature deaths declined in many countries, with 16 of them having achieved the expected reduction by 2022. The current burden of cancer-related premature deaths is profound but varies around the world. Eliminating premature deaths from major cancer types could substantially increase life expectancy, underscoring the importance of prevention and treatment efforts for these cancers.

Background: Although sepsis is known to be the leading cause of morbidity and mortality in adult burn patients, its epidemiology and impact are poorly understood. This study aims to address these gaps by further characterizing predictors of sepsis and comparing outcomes between septic and non-septic burn patients in different age groups.

Methods: We included patients (≥ 18 years) with thermal burn injuries ≥ 5% total body surface area (TBSA) admitted to two burn centers between 1 January 2006 and 30 June 2021, and 1 January 2023 and 6 April 2025. Patients were stratified by age into adults (18-59 years) and older adults (≥ 60 years), and by diagnosis of sepsis during hospitalization (sepsis vs. control). Demographics, injury characteristics, mortality, and in-hospital complications were assessed. Multivariate logistic regression models were used to identify predictors of sepsis and mortality among septic patients.

Results: This study included a total of 1465 patients, including 1094 adults and 371 older adults. Sepsis was diagnosed in 20.1% of adult burn patients, with a median onset at 10 d following injury. Increasing age, greater TBSA, and inhalation injury were identified as significant risk factors for sepsis. Among patients who developed sepsis, earlier onset and female sex were associated with an elevated risk of mortality. In older adults, the incidence of sepsis was 22.9%, with a median onset at 11 d post-burn. The odds of sepsis diagnosis increased with higher TBSA and the presence of inhalation injury. Earlier sepsis onset was associated with increased mortality in older adults.

Conclusions: Sepsis represents a significant clinical challenge in burn patients, with age, TBSA, inhalation injury, and comorbidities significantly influencing its incidence and outcomes. Notably, early sepsis onset and female sex are associated with increased mortality, highlighting the need for advanced monitoring, prompt interventions, and the exploration of innovative sex-specific strategies to optimize outcomes in this high-risk population.

Background: Lumbar disc degeneration (LDD) displays considerable heterogeneity in terms of clinical features and pathological changes. However, researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features. This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.

Methods: One hundred and twenty-two nucleus pulposus (NP) tissues from 108 patients were consecutively collected for bulk RNA sequencing (RNA-seq). An unsupervised clustering method was employed to analyze the bulk RNA matrix. Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix (ECM) dysregulation. The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets. Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved. Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.

Results: LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling: C1 with collagenesis, C2 with ossification, C3 with low chondrogenesis, and C4 with fibrogenesis. Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1; NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes; Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis; Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α (TNF-α). Furthermore, the random forest diagnostic prediction model was proven to have a robust performance [area under the receiver operating characteristic (ROC) curve: 0.9312; accuracy: 0.84] in stratifying the molecular subtypes of LDD based on 12 clinical features.

Conclusions: Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features. The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.

Background: Most sepsis patients develop sepsis-associated acute kidney injury (SA-AKI), which poses a significant threat to survival and lacks specific treatment. To date, there are no published randomized controlled trials that have established a link between albumin use and SA-AKI development in sepsis. Therefore, it is unclear whether albumin use may influence the risk of SA-AKI.

Methods: The present study employed a target trial emulation using observational data to track adult sepsis patients initially admitted to the intensive care unit at Beth Israel Deaconess Medical Center, Boston, Massachusetts, for a period of 7 d from 2008 to 2022. Immortal time bias was controlled using the clone-censor-weight (CCW) method, along with a new-user design to address current user bias. The exposure variable was the early administration of albumin following the onset of sepsis. Based on albumin use, patients were classified into two groups: the albumin group (n = 27,088) and the no albumin group (n = 27,088). The primary outcome was the development of SA-AKI, and the secondary outcome was 7-day all-cause mortality. The primary outcome was analyzed using competing risk analyses. Furthermore, sensitivity and subgroup analyses were also performed.

Results: Among the 27,088 patients analyzed, albumin administration was associated with a significantly higher SA-AKI risk (relative difference = 3.47%, 95% CI 1.76-5.23) compared to non-administration. There was no clinically meaningful difference in 7-day survival (relative difference = 0.05%, 95% CI -2.30 to 2.45). Sensitivity analyses consistently supported these results. All these analyses were conducted on data that were collected after CCW.

Conclusions: Early albumin administration may increase the risk of SA-AKI in sepsis patients without conferring a short-term survival benefit. These results underscore the need for a rigorous risk-benefit assessment when incorporating albumin into sepsis resuscitation protocols and highlight the need for further clinical validation. However, it is important to exercise caution when interpreting the conclusions of this study, given its exploratory and preliminary nature.

Background: Antipsychotic-induced movement disorders (AIMDs) are prevalent side effects of antipsychotics, particularly during the acute phase of treatment. This study aimed to elucidate the genetic mechanisms underlying AIMDs using a genome-wide association study (GWAS).

Methods: GWASs on AIMDs were conducted in 3 independent cohorts: a discovery cohort of 3067 patients (2016 subjects were reserved after quality control), a validation cohort of 277 patients, and a multi-ancestry validation cohort of 766 patients. Subsequent post-GWAS analyses included gene-based analyses, transcriptome-wide association studies (TWASs), and polygenic risk score (PRS) profiling.

Results: Our study identified 2 loci located in RAB44 gene (rs116249243, P = 5.98 × 10^-9; rs117097482, P = 1.17 × 10^-8) associated with extrapyramidal symptoms (EPSs), 1 locus (rs6826172, P = 5.56 × 10^-9) related to akathisia, and 76 loci linked to involuntary movements (11 genes were mapped). Risk loci located in CNTNAP2, LUZP2, TMEM167A, and RAB44 genes were successfully replicated in the validation cohort, whereas the locus located in RAB44 was also replicated in the multi-ancestry cohort. Gene-based analyses indicated that XRCC4 and PAIP2B reached significance at the genome-wide level in involuntary movements. Tissue expression analysis revealed that involuntary movement-related genes are predominantly expressed in the substantia nigra. Additionally, the TWAS suggested a causal relationship between XRCC4 and involuntary movement. The PRSs derived from the discovery cohort significantly predicted AIMDs in the validation cohort, with area under the receiver operating characteristic curve (AUC) values from 0.60 to 0.80.

Conclusions: Our findings highlight the role of substantia nigra related gene polymorphisms in AIMDs. This study provides novel insights into the pathogenesis of AIMDs and supports the potential for personalized treatment approaches for schizophrenia.

Trial registration: ChiCTR ( https://www.chictr.org.cn/showproj.html?proj=8604 ), No. ChiCTR-TRC-10000934; ChiCTR ( https://www.chictr.org.cn/showproj.html?proj=129668 ), No. ChiCTR2100048320.

Background: Sudden cardiac death (SCD) accounts for more than half of all sudden death cases, posing a significant health burden in China. However, epidemiological data on SCD are scarce due to the lack of a central data registry and the heterogeneity of case definitions. This study aims to provide reliable estimates of the incidence and risk factors of SCD in China at the national and regional levels from 2013 to 2021, as well as the current status of prevention.

Methods: The multi-cause mortality data from 2013 to 2021 were obtained from the National Mortality Surveillance System of China. Deaths related to cardiac arrest were identified. Crude and age-standardized mortality rates were calculated by time, and region. Joint point regression was applied to identify significant changes during the study period. Subgroup analyses and multilevel negative binomial analysis were performed to understand the SCD risk factors. The first-line prevention measures and their current implementation in China and developed countries were also determined from published articles.

Results: From 2013 to 2021, the crude mortality rate of sudden cardiac arrest increased markedly from 8.36 deaths per 100,000 population in 2013 to 18.59 deaths per 100,000 population in 2021. There were considerable differences among regions. Subgroup analysis and negative binomial regression results indicated that males and the elderly were at higher risk of SCD. SCD may be associated with poor medical conditions. More than half of SCDs occurred outside hospitals, and approximately 60% of SCDs were related to ischemic heart disease as the underlying cause. Currently, developed countries have widely adopted primary prevention and emergency treatment measures; however, the utilization rate of such measures in China is relatively low and should be improved.

Conclusions: With the continuous rise in the prevalence of cardiovascular diseases and their related risk factors in China, the burden of SCD is expected to increase. In addition to strengthening the clinical pathways for sudden cardiac arrest cases in pre-hospital and hospital settings, it is also necessary to enhance public awareness, knowledge and first-line practical training through large-scale policies for governmental and community-based projects.

Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance. The most effective preventive strategies currently recommended include environmental acclimatization (slow ascent and/or pre-acclimatization) or pharmacological support of acclimatization using acetazolamide. However, these strategies are not practical for high-altitude exposures that require rapid and unplanned ascent, high physical and mental performance, such as rescue missions or military operations. Dexamethasone and other modulators of the glucocorticoid system take effect quickly and are effective alternatives for preventing acute altitude illnesses when rapidly ascending to high altitudes. As the efficacy of dexamethasone in preventing acute mountain illnesses remains controversial, a review of existing studies on the use of dexamethasone for the prevention of acute mountain sickness was conducted, aiming to determine the best strategy. Possible mechanisms of protection against acute altitude illnesses are discussed based on the results of clinical trials. The data indicate that dexamethasone is most effective at altitudes above 4000 m at doses of 8-16 mg/d. Appropriately designed and powered trials are needed to obtain more evidence-based results on the dosage and timing of dexamethasone administration, and to provide optimized recommendations for the application of this powerful pharmacological tool.

Background: Brain volume measurement serves as a critical approach for assessing brain health status. Considering the close biological connection between the eyes and brain, this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata, and to offer a cost-effective approach for assessing brain health.

Methods: Based on clinical information, retinal fundus images, and neuroimaging data derived from a multicenter, population-based cohort study, the KaiLuan Study, we proposed a cross-modal correlation representation (CMCR) network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects. Specifically, individual clinical information, which has been followed up for as long as 12 years, was encoded as a prompt to enhance the accuracy of brain volume estimation. Independent internal validation and external validation were performed to assess the robustness of the proposed model. Root mean square error (RMSE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM) metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.

Results: The proposed framework yielded average RMSE, PSNR, and SSIM values of 98.23, 35.78 dB, and 0.64, respectively, which significantly outperformed 5 other methods: multi-channel Variational Autoencoder (mcVAE), Pixel-to-Pixel (Pixel2pixel), transformer-based U-Net (TransUNet), multi-scale transformer network (MT-Net), and residual vision transformer (ResViT). The two- (2D) and three-dimensional (3D) visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images. Thus, the CMCR framework accurately captured the latent structural correlations between the fundus and the brain. The average difference between predicted and actual brain volumes was 61.36 cm³, with a relative error of 4.54%. When all of the clinical information (including age and sex, daily habits, cardiovascular factors, metabolic factors, and inflammatory factors) was encoded, the difference was decreased to 53.89 cm³, with a relative error of 3.98%. Based on the synthesized brain MR images from retinal fundus images, the volumes of brain tissues could be estimated with high accuracy.

Conclusions: This study provides an innovative, accurate, and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.

Trial registration no: NCT05453877 ( https://clinicaltrials.gov/ ).