Immune-resistant colorectal cancer (irCRC), represented by microsatellite stable/proficient mismatch repair (MSS/pMMR) tumors, responds poorly to immune checkpoint blockade (ICB). Here, we developed an ultrasound-targeted nanodroplet destruction (UTND) strategy combined with surface anti-PD-L1-decorated nanodroplets (PPP@P@map) to enhance ICB responsiveness in MSS colorectal cancer. In CT26 and CMT93 murine subcutaneous MSS colorectal cancer models, PPP@P@map combined with UTND markedly suppressed tumor growth compared with control treatments. Single-cell RNA sequencing identified CAF_Pi16 as a candidate therapy-associated cancer-associated fibroblast subset that showed a treatment-related increase after PPP@P@map + UTND, which was further supported by flow cytometry and multiplex immunofluorescence validation. Mechanistically, UTND induced oxidative stress in tumor cells and promoted the generation of advanced glycation end products (AGEs), which activated the AGE-RAGE/PKCα/NF-κB pathway in CAF_Pi16 and increased CCL7 secretion. CAF_Pi16-derived CCL7 provided a CCR2-dependent functional cue to CD8+ T cells. In purified CD8+ T cells, CCL7 activated NF-κB-related signalling, enhanced activation and cytotoxic effector features, and promoted NKG2D expression; these effects were attenuated by CCR2 blockade or NF-κB inhibition. Functionally, CCL7 enhanced CD8+ T cell-mediated tumor-cell killing, whereas NKG2D blockade reduced this effect and weakened the antitumor efficacy of PPP@P@map + UTND in vivo. Together, these findings reveal a UTND-induced tumor cell-CAF_Pi16-CCL7-CD8+ T-cell signalling axis that enhances NKG2D-associated antitumor immunity and provides a mechanistic basis for further investigation of UTND-based strategies to improve ICB responsiveness in MSS/pMMR colorectal cancer.

The Waist-adjusted Weight Index (WWI) is a novel anthropometric marker, its association with dyslipidemia in Asian populations remains unclear. This study examines the relationship between WWI and dyslipidemia in Japanese adults. Grounded in adipose tissue dysfunction and metabolic syndrome mechanisms, WWI, an index of central adiposity independent of body weight, serves as a biologically plausible predictor of dyslipidemia. We retrospectively analyzed 15,453 adults, undergoing health examination from Gifu Murakami Memorial Hospital (1994-2016). Logistic regression and fitted smooth curve analysis assessed WWI and dyslipidemia associations. Stratified analyses were performed based on sex, age, exercise, alcohol consumption, and smoking. WWI was positively associated with dyslipidemia (Adjusted OR = 1.30, 95% CI: 1.21-1.39). Risk increased across quartiles: Q2 (OR = 1.20), Q3 (OR = 1.36), Q4 (OR = 1.44). Smooth curve analysis indicated a nonlinear, accelerating increase. Associations were stronger in men, adults >60, smokers, drinkers, and those with insufficient exercise (P < 0.05). The findings support mechanistic links proposed by the adipose tissue disease theory and metabolic syndrome model, highlighting WWI as a simple, effective early screening tool for dyslipidemia. Prospective studies are needed to validate its predictive value in clinical and public health practice.

Risk prediction in dilated cardiomyopathy (DCM) remains suboptimal, and there is uncertainty about how newer machine-learning (ML) methods compare with conventional regression for clinically useful prognostic modelling. Advanced three-dimensional (3D) echocardiographic measures, particularly of right ventricular function, may improve model performance when combined with routinely collected clinical data. We aimed to compare conventional Cox regression, penalised Cox regression, and ML approaches for prognostic modelling in DCM and to identify models that offer the best balance of discrimination, calibration, and interpretability for risk stratification. We conducted a retrospective cohort study including 196 adults with DCM attending a tertiary cardiology centre between 2021 and 2023. Participants were followed for a composite outcome of all-cause mortality, heart failure rehospitalisation, or left ventricular assist device (LVAD) implantation. We considered 41 candidate predictors, including demographic and clinical variables and 3D echocardiographic parameters (e.g. 4D right ventricular ejection fraction [4D-RVEF], tricuspid annular plane systolic excursion [TAPSE], right ventricular global longitudinal strain [RVGLS], left atrial volume index [LAVI], and pulmonary artery systolic pressure [PASP]). Twelve prognostic models were developed including conventional Cox regression, penalised Cox regression (Lasso-Cox), and several ML models—and evaluated using internal and performance assessment at different prediction horizons (up to 24 months). Performance was assessed using area under the receiver operating characteristic curve (AUC), calibration plots, and SHAP-based feature importance. At 12 months, he best-performing ML model achieved the highest discrimination (AUC 0.990),followed by GBDT and Lasso-Cox (AUC 0.825). Model discrimination attenuated at longer prediction horizons, with the Lasso-Cox model maintaining acceptable performance at 24 months (AUC 0.729). Although RF and GBDT demonstrated excellent discrimination, calibration analyses revealed systematic under- and over-prediction at the extremes of risk. By contrast, Lasso-Cox showed more stable and favourable calibration across risk deciles. Across models, key predictors consistently included 4D-RVEF, LAVI, PASP, and TAPSE. In this DCM cohort, ML models, particularly RF, maximised discrimination but exhibited calibration issues. A penalised regression model (Lasso-Cox) provided the best overall trade-off between discrimination, calibration, and interpretability, and is therefore recommended as the preferred approach for clinical risk stratification and future public health–oriented implementation studies in DCM.

Microsatellite stable (MSS) colorectal cancer (CRC) is largely resistant to immune checkpoint blockade due to its immunosuppressive tumor microenvironment (TME). Ultrasound-targeted nanobubble destruction (UTND) offers a localized physical delivery method, but its active immunomodulatory mechanisms remain underexplored. Ultrasound-responsive NBs loaded with CTLA-4 antibody (PF4) were fabricated and characterized. A CT26 mouse CRC model was used to evaluate anti-tumor effects across four treatment groups. Single-cell RNA sequencing (scRNA-seq) analyzed cellular changes in the TME. The activation of the NF-κB pathway was verified through western blot analysis, qPCR, and immunofluorescence staining. Intracellular ROS production was assessed using flow cytometry, confocal microscopy, and an enzyme immunoassay. Furthermore, the effects of Ccl8 on regulatory T (Treg) cells were examined by flow cytometry, qPCR and western blot. Combination treatment with UTND and anti-CTLA-4 suppressed tumor growth relative to single-agent treatments. ScRNA-seq identified a CCL8-expressing macrophage subpopulation (Macro Ccl8) that was more abundant in the combination group. UTND promoted ROS production, which activated NF-κB signaling and increased Ccl8 transcription. CCL8 secreted by Macro Ccl8 modulated Treg function through the Ccl8-Ccr2 axis. Together with direct CTLA-4 checkpoint inhibition, this cascade contributed to elevated CD8 + T cell activity. In the CT26 mouse model, UTND combined with CTLA-4 antibody modulates the immunosuppressive TME partially through inducing Macro Ccl8 via the ROS–NF-κB–Ccl8 axis, in addition to direct CTLA-4 blockade. This dual mechanism attenuates Treg function and enhances antitumor immunity, providing a preclinical rationale for combining ultrasound-based physical intervention with immunotherapy in MSS CRC.

The most severe side effect of chemotherapy is cardiotoxicity, frequently causing myocardial injury characterized by excessive oxidative stress and fibrosis for which effective treatments are lacking. To address this, a hydrogen delivery system, hydrogen nanobubbles (HNBs), was constructed, leveraging hydrogen's selective antioxidant and antifibrotic properties to counteract doxorubicin (Dox)-induced myocardial injury and explore its mechanism. HNBs were constructed via polymer self-assembly. Nanoparticle tracking analysis indicated a size of 265.1 ± 26 nm. The average hydrogen content of HNBs measured by chemical titration was about 1.9 mg/L. TEM revealed spherical HNBs with a dense outer lipid polymer layer encapsulating hydrogen. CCK-8 assays confirmed over 90% cell viability, demonstrating good biosafety. ROS fluorescence staining and flow cytometry showed that HNBs significantly reduced Dox-induced ROS increases. RT-qPCR revealed the upregulation of antioxidant genes (NRF2, SOD2, and GPX-1). Flow cytometry and JC-1 staining indicated that HNBs mitigated apoptosis and restored mitochondrial membrane potential. TEM displayed reduced mitochondrial damage and intracellular vacuolation. In a Dox-induced cardiomyopathy mouse model, HNBs improved cardiac function, normalized echocardiographic parameters (EF, FS, LVIDs, and LVIDd), and lowered myocardial ROS levels. Ultrasonic enhanced images showed that HNBs have good myocardial differential targeting. In vivo fluorescence imaging of mice showed that HNBs could accumulate in the myocardium in large quantities at 1 h. mRNA-seq and network pharmacology suggested that HNBs inhibit myocardial fibrosis. Masson staining results showed that HNBs could improve Dox-induced myocardial fibrosis. RT-qPCR and Western blotting confirmed the reduced expression of fibrosis markers (ACTA2, COL1, and FN1), preliminarily linking the mechanism to suppression of both PI3K/AKT and TGF-β/SMAD pathways. In summary, HNBs inhibit oxidative stress and myocardial fibrosis, reversing Dox-induced cardiac injury primarily through the dual suppression of the PI3K/AKT and TGF-β/SMAD pathways.

Background:While the aging global population faces a rising chronic obstructive pulmonary disease (COPD) mortality burden, comprehensive assessments of this burden concerning multiple environmental risks and socioeconomic inequalities among the oldest-old (aged ≥80 years) remain limited. This study aims to comprehensively assess the burden of environmental risk-attributable COPD mortality, its temporal trends, and socioeconomic inequalities among the global population aged ≥80 years. Methods:Data from the Global Burden of Disease (GBD) Study 2021 were used to analyse COPD deaths and age-specific mortality rates attributable to eight environmental risk factors among adults aged 80 years and older from 1990 to 2021. Mortality estimates were derived from multiple GBD data sources, including household surveys, censuses, and vital registration systems. We examined mortality patterns and trends at the global, regional, and national levels. Temporal trends in age-specific mortality rates were assessed using Joinpoint regression, and Socio-demographic Index (SDI) related inequalities across 204 countries were evaluated using the slope index of inequality (SII) and relative concentration index (RCI). Results:In 2021, the leading environmental risk factors for age-specific COPD mortality rates were smoking {351.85 per 100,000 population [95% uncertainty interval (UI): 268.79-433.10]}, ambient particulate matter pollution [241.60 (175.22-299.69) per 100,000 population], and household air pollution from solid fuels (HAP) [157.27 (83.42-292.74) per 100,000 population]. The leading contributor to male COPD mortality was smoking [717.70 (555.94-871.14) per 100,000] and ambient particulate matter pollution [335.99 (245.85-411.01) per 100,000 population], whereas female mortality was primarily driven by ambient particulate matter pollution [181.00 (123.04-234.92) per 100,000 population] and HAP [141.30 (76.19-250.28) per 100,000 population]. From 1990 to 2021, COPD mortality rates attributable to HAP showed the largest reduction [percentage change: -72% (-83% to -53%)]. Joinpoint regression revealed temporal patterns. Smoking attributable mortality increased until 1998, then sustained a decline. Ambient particulate matter pollution attributable mortality rose until 2014 before decreasing. Ambient ozone attributable mortality followed a fluctuating pattern. High temperature was the only factor among the eight assessed with a statistically significant, overall increasing trend throughout 1990-2021 {annual percent change: 1.49% [95% confidence interval (CI): 0.98-2.00]}. In terms of health inequalities, HAP demonstrated the highest degree of socio-demographic inequality in 2021 [RCI: -0.404 (-0.474 to -0.334); SII: -545.59 (-637.30 to -453.89) per 100,000 population], with the relative inequality increasingly concentrated in lower-SDI countries. For ambient particulate matter pollution, absolute inequality shifted increasingly toward disadvantaged settings. Notably, both absolute and relative inequalities in ozone-attributable COPD mortality increased from 1990 to 2021, with mortality disproportionately concentrated in lower-SDI countries. Conclusions:These findings provide a critical evidence base for formulating integrated public health strategies aimed at mitigating burdens of environmental risk-attributable COPD mortality among adults aged 80 years and older. Such strategies entail prioritizing clean energy, clean cooking technologies, and ozone control in lower-SDI regions, along with reinforcing tobacco and climate-related actions globally.

Pathological cardiac hypertrophy, often triggered by the excessive production and accumulation of reactive oxygen and nitrogen species (RONS), may ultimately lead to heart failure. The treatment of myocardial hypertrophy often involves antioxidant stress therapy. In this study, by coordinating curcumin with ferric ions during the synthesis of Prussian blue nanoparticles, a Prussian blue-curcumin (PB-Cur) nanozyme is successfully engineered with exceptional reactive oxygen and nitrogen species (RONS) elimination capabilities. Following PVP modification, the PB-Cur nanozyme exhibited favorable biocompatibility and stability in aqueous solutions. Furthermore, the PB-Cur nanozyme shows remarkable reversible treatment efficacy against myocardial hypertrophy in both in vitro and in vivo models. After one week of treatment, the PB-Cur group in the transverse aortic constriction (TAC)-induced cardiac hypertrophy models displayed a notable decrease in myocardial hypertrophy and fibrosis. Echocardiographic findings also revealed a substantial improvement in cardiac function among TAC mice following PB-Cur administration. Mechanistically, through reactive oxygen species (ROS) elimination, the PB-Cur effectively downregulated oxidative stress-related pathways, including MAPK and PI3K-Akt, which hold promise for treating oxidative stress-related cardiac diseases.

OBJECTIVES:With the intensification of aging, the proportion of people affected by multimorbidity is steadily increasing worldwide. In remote areas of China, where economic development is lagging and healthcare resources are limited, the older hypertensive population may experience a higher burden of multimorbidity. However, comprehensive evidence is still lacking on how specific combinations of lifestyle behaviours (LBs) impact particular multimorbidity health outcomes in older hypertensive individuals. STUDY DESIGN:A cross-sectional study was conducted among the older hypertensive population (aged ≥65 years) from 1 July to August 31, 2023 in Jia County, a remote area of China. METHODS:A total of 40 diseases were categorized into physical, psychological and cognitive disorders. Multivariable-adjusted logistic regression models were used to estimate ORs and 95 % CIs for the associations between LBs and multimorbidity. RESULTS:Among 17,728 participants, the prevalence of physical, psychological, cognitive, physical-psychological multimorbidity (PPsM), physical-cognitive multimorbidity (PCM), psychological-cognitive multimorbidity (PsCM), and physical-psychological-cognitive multimorbidity (PPsCM) were 63.55 %, 30.12 %, 64.55 %, 22.31 %, 42.03 %, 22.57 %, and 16.74 %, respectively. Compared to participants without any healthy LBs, those with five healthy LBs were associated with a lower risk of physical, psychological, cognitive, PPsM, PCM, PsCM, and PPsCM. Overall, the risk of adverse outcomes decreased with the number of healthy LBs (Ptrend<0.001). However, combinations of healthy LBs of the same quantity but from different categories exhibited varying impacts on the outcomes. CONCLUSIONS:Multimorbidity involving physical, psychological, and cognitive disorders poses a significant challenge for managing hypertention. Strengthening the capacity of primary healthcare workers to promote healthy lifestyle practices and identifying the optimal LB combinations should be prioritized in the management of hypertensive individuals in remote areas of China.

Lipid droplets are important cell energy storage sites and are involved in various cellular activities. Two-photon fluorescent molecules that exhibit aggregation-induced emission (AIE) characteristics are important for applications in bioimaging and therapeutics, to overcome the induced aggregation-caused quenching (ACQ) of conventional fluorescent materials due to undesirable aggregation in a relatively concentrated solution or solid state. This paper reports on 2-((2,3-bis(4-methoxyphenyl) quinoxalin-6-yl) (phenyl) methylene) malononitrile (BMQMM), a lipid droplet-targeted AIE photosensitizer (PS) with a simple structure, two-photon imaging, and the features of type I reactive oxygen species (ROS) formation. Designing molecules with donor-it-acceptor (D-it-A) architecture plays an important role in obtaining fluorescent dyes for biomedical applications. However, this is challenging due to very limited electronic acceptors and donors. On the other hand, to endow fluorescent dyes with combined therapeutic applications, trivial molecular design is indispensable. Herein, we propose a dicyano-based electronic acceptor with a strong electron affinity, which can be used to develop fluorescent dyes. By structurally attaching two classical methoxyphenyl electronic donors to quinoxaline it system, a basic D-it-A module, namely BMQMM, can be generated. BMQMM is characterized by good biocompatibility, a large Stokes shift, and high photostability. Owing to its exceptional ability to specifically target lipid droplets, it can accurately visualize the distribution of lipid droplets in both cells and animal tissues. Moreover, it outperforms commercially available lipid droplet dyes. The efficient generation of ROS in BMQMM under visible light, as well as with the irradiation of two-photon excitation at low power, makes it possible to promote apoptosis and ferroptosis in osteosarcoma cells, which is helpful for photodynamic therapy (PDT) of bone tumors. Our study not only demonstrates a simple method for synthesizing BMQMM but also investigates its potential application in imaging lipid droplets both in vitro and in vivo, with one-photon excitation as well as two-photon excitation and with efficient ROS generation to enhance the effect of type I PDT. This provides an opportunity for the synthesis and application of AIE luminogens using a novel approach.

ObjectiveThe objective of this study was to examine the relationship between sleep duration and prediabetes, as well as to evaluate the influence of inflammation in mediating this association.MethodsA total of 4632 participants from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study, comprising both baseline and 4-year follow-up data. The prospective relationship between sleep duration and the risk of prediabetes was examined using logistic regression models. We used multinomial logistic regression to evaluate the impact of prediabetes on sleep duration changes over follow-up, assessing the role of C-reactive protein in the association using mediation analysis.ResultsParticipants with short sleep duration (<5 hours) had a higher risk of prediabetes (odds ratios=1.381 [95% CI: 1.028-1.857]) compared to those with normal sleep durations (7-8 hours). However, excessive sleep durations (≥9 hours) did not show a statistically significant association with prediabetes risk. Moreover, individuals at least 60years old who experienced short sleep durations exhibited a higher risk of prediabetes. Individuals with prediabetes were more likely to have shorter sleep duration than excessive sleep duration (relative risk ratios=1.280 [95% CI: 1.059-1.547]). The mediation analysis revealed a mediating effect of C-reactive protein on the association between prediabetes and reduced sleep duration.ConclusionsShort sleep duration was identified as a risk factor for the incidence of prediabetes. Conversely, prediabetes was found to contribute to shorter sleep duration rather than excessive sleep duration. Moreover, elevated levels of C-reactive protein may serve as a potential underlying mechanism that links prediabetes with shorter sleep.

BackgroundTo date, the differentiated requirements for network performance in various health care service scenarios—within, outside, and between hospitals—remain a key challenge that restricts the development and implementation of digital medical services. ObjectiveThis study aims to construct and implement a private 5G (the 5th generation mobile communication technology) standalone (SA) medical network in a smart health environment to meet the diverse needs of various medical services. MethodsBased on an analysis of network differentiation requirements in medical applications, the system architecture and functional positioning of the proposed private 5G SA medical network are designed and implemented. The system architecture includes the development of exclusive and preferential channels for medical use, as well as an ordinary user channel. A 3-layer network function architecture is designed, encompassing resource, control, and intelligent operation layers to facilitate management arrangements and provide network open services. Core technologies, including edge cloud collaboration; service awareness; and slicing of access, bearer, and core networks, are employed in the construction and application of the 5G SA network. ResultsThe construction of the private 5G SA medical network primarily involves system architecture, standards, and security measures. The system, featuring exclusive, preferential, and common channels, supports a variety of medical applications. Relevant standards are adhered to in order to ensure the interaction and sharing of medical service information. Security is achieved through mechanisms such as authentication, abnormal behavior analysis, and dynamic access control. Three typical medical applications that rely on the 5G network in intrahospital, interhospital, and out-of-hospital scenarios—namely, mobile ward rounds, remote first aid, and remote ultrasound—were conducted. Testing of the 5G-enabled mobile ward rounds showed an average download rate of 790 Mbps and an average upload rate of 91 Mbps. Compared with 4G, the 5G network more effectively meets the diverse requirements of various business applications in prehospital emergency scenarios. For remote ultrasound, the average downlink rate of the 5G network is 4.82 Mbps, and the average uplink rate is 2 Mbps, with an average fluctuation of approximately 8 ms. The bandwidth, performance, and delay of the 5G SA network were also examined and confirmed to be effective. ConclusionsThe proposed 5G SA medical network demonstrates strong performance in typical medical applications. Its construction and application could lead to the development of new medical service models and provide valuable references for the further advancement and implementation of 5G networks in other industries, both in China and globally.

The extent to which type 2 diabetes (T2D) reduces life expectancy depends on the risk of complications. We aimed to characterise the relationship between risk factors for diabetes complications and life expectancy, in individuals with T2D, free from major chronic disease, in a regional database linked with national New Zealand health databases. A prospective cohort study design was employed, analysing data from individuals with T2D drawn from the comprehensive Diabetes Care Support Service database (1994–2018). Participants with known values for all five within-target risk factors (WTRF +) including blood pressure, glycaemia, and LDL cholesterol, alongside being non-smoking with normal renal function at baseline, were included. Life expectancy free from cardiovascular disease (CVD), cancer, and dementia at age 50 years was estimated using multistate life tables, adjusting for demographics and clinical metrics. Women and men with no WTRF + at enrolment had a life expectancy free from CVD, cancer, or dementia of 13.1 (95

Plenty of circRNAs have been reported to play an important role in colorectal cancer (CRC), while the reason of abnormal circRNA expression in cancer still keep elusive. Here, we found that m7G RNA modifications were enriched in some circRNAs, these m7G modifications in circRNAs were catalyzed by METTL1, and the GG motif was the main site preference for m7G modifications in circRNAs. We further confirmed that METTL1 played a cancer-promoting role in CRC. We then screened a highly expressed circRNA, called circKDM1A, and found that METTL1 prevented the degradation of circKDM1A by m7G modification. CircKDM1A was further verified to promote proliferation, invasion and migration of CRC in vivo and in vitro. Its cancer-promoting ability was weakened after the m7G site mutation. CircKDM1A was verified to activate AKT pathway by upregulating PDK1, consequently promoting CRC progression. These results suggest that m7G-modified circRNA promotes CRC progression via activating AKT pathway. Our study uncovers an essential physiological function and mechanism of METTL1-mediated m7G modification in the regulation of circRNA stability and cancer progression.

OBJECTIVES:To examine the effects of changes in individual/multiple social activities between 65 and 70 years of age on incident long-term care (LTC) needs between 70 and 80 in older adults with depressive symptoms.METHODS:Participants were recruited from the New Integrated Suburban Seniority Investigation Project, an ongoing prospective cohort study. A total of 525 older adults with depressive symptoms were included. The validated 15-item Geriatric Depression Scale was used to assess depressive symptoms. A self-report questionnaire was used to measure social activities (social-related, learning, and personal). LTC needs was defined according to Japan's Long-term Care Insurance System. A competing risk model and a Laplace regression model were used to estimate the hazard ratios of LTC needs incidence and the 25th percentile difference in LTC-needs-free survival time and their 95% confidence intervals.RESULTS:Out of 4314 person-years of mild LTC needs, 108 individuals developed it. Participants who increased their frequency of learning activities have a lower risk of developing mild LTC needs. Increasing the frequency could also prolong LTC-needs-free survival time by approximately 2.61 years. Out of 4535 person-years for severe LTC needs, 54 individuals developed it. Participants with a continuous regular frequency of learning activities had a lower risk of developing severe LTC needs. However, the association between this frequency and LTC-needs-free survival time for severe LTC needs was insignificant in the multivariable models.CONCLUSIONS:Increased frequency of learning activities reduced the risk of LTC needs among older adults with depressive symptoms and prolonged their LTC-needs-free survival time.

IntroductionTo evaluate the long-term risk of developing type 2 diabetes (T2D) among women with a history of gestational diabetes mellitus (GDM) compared with those with impaired glucose tolerance (IGT).Research design and methodsUsing data from a primary care dataset linked with multiple health registries, this longitudinal study analyzed demographics, clinical data, and lifestyle factors of women diagnosed with GDM or IGT, assessing T2D incidence over 25 years, using Cox regression models.ResultsWomen with GDM, especially those over 35 years of Māori ethnicity, or socioeconomic deprivation, exhibited an elevated risk of T2D compared with those with IGT. The first 5 years post partum emerged as a critical window for intervention.ConclusionsThis study underscores the importance of early, targeted post-GDM interventions to mitigate T2D risk. It highlights the necessity of personalized post-GDM interventions to reduce T2D incidence which consider age, ethnicity, and socioeconomic status to maximize effectiveness.

Big data and artificial intelligence technologies have played a positive role in the prevention and control of COVID-19 outbreaks.However,its application and future trends has not been comprehensively discussed.Starting from the problems faced by the prevention and control of COVID-19,this study provided an overview of the common big data and artificial intelligence technologies and their practical application cases in the prevention and control of COVID-19 based on the introduction of the advantages of big data and artificial intelligence technologies,then discussed the application of big data and artificial intelligence technologies focusing on three elements of infectious source,route of transmission and susceptible population from the three stages that before,during,and after the COVID-19 outbreak based on the Haddon model perspective.The results of the study are important for clarifying the positive role of big data and artificial intelligence technologies in each stage of COVID-19 epidemic as well as their directions of development and application,further improving the efficiency and quality of the prevention and control of COVID-19,and effectively responding to new infectious diseases in the future.

A pre-metastatic niche (PMN) is a protective microenvironment that facilitates the colonization of disseminating tumor cells in future metastatic organs. Extracellular vesicles (EVs) play a role in intercellular communication by delivering cargoes, such as noncoding RNAs (ncRNAs). The pivotal role of extracellular vesicle-derived noncoding RNAs (EV-ncRNAs) in the PMN has attracted increasing attention. In this review, we summarized the effects of EV-ncRNAs on the PMN in terms of immunosuppression, vascular permeability and angiogenesis, inflammation, metabolic reprogramming, and fibroblast alterations. In particular, we provided a comprehensive overview of the effects of EV-ncRNAs on the PMN in different cancers. Finally, we discussed the promising clinical applications of EV-ncRNAs, including their potential as diagnostic and prognostic markers and therapeutic targets.

BACKGROUND:The prevalence of combinations of comorbidities and their associations with inpatient service utilization and readmission among patients with chronic obstructive pulmonary disease (COPD) have not been extensively examined. To address this gap in knowledge, an observational prospective study was conducted using retrospective data. AIMS:To identify patterns of comorbidities linked to length of hospital stay, daily expenses, and one-year readmission. METHODS:The 30 most common comorbidities were identified in patients with secondary diagnoses using the association rule mining (ARM) method. Regression models were used to examine the relationships between combinations of comorbidities and service utilization, with adjustments for covariates. RESULTS:The five most prevalent comorbidities were pulmonary heart disease (40.99%), ischemic heart disease (38.97%), heart failure (36.77%), hypertension (34.11%), and respiratory disorders (19.12%). Most combinations of comorbidities identified by ARM showed significant associations with an extended length of stay (>13 days), increased daily expenses (>930 CNY), and reduced readmission rates. Among these combinations, glycoprotein metabolism disorder had the strongest association with prolonged length of stay (adjusted odds ratio [aOR]): 1.89, 95% confidence interval [CI]: 1.82-1.95). Conversely, the combination of other brain diseases and respiratory failure was linked to higher daily expenses (aOR: 11.34, 95% CI: 10.58-12.15), and the presence of pulmonary heart disease was associated with elevated one-year readmission rates (aOR: 1.41, 95% CI: 1.37-1.46). CONCLUSION:Common combinations of comorbidities among inpatients with COPD were identified from an extensive collection of discharge medical records. Furthermore, the associations between comorbidities, inpatient service usage, and readmission rates were determined.

Background As life expectancy increases, so does the risk of age-related diseases and functional disability, which significantly raises the risk of all-cause mortality in older adults. Individuals with disabilities may die up to 20 years earlier than those who are non-disabled. Objectives To develop a prediction model for functional disability using random survival forest analysis (RSF). Methods Data were drawn from 2,364 older adults without functional disability from the China Health and Retirement Longitudinal Study (CHARLS), conducted from 2011 to 2020. Functional disability was the primary outcome. Univariable and multivariable Cox regression analyses were used to identify significant factors, which were then screened using variable importance (VIMP) and minimal depth to construct the RSF model. The model's performance was evaluated using calibration curves and the area under the receiver operating characteristic (AUC) curve. Multimorbidity trajectories were also identified as potential risk factors through group-based multi-trajectory modeling. Results Four multimorbidity trajectories were identified: no multimorbidity, newly-developing, moderate-developing, and severe-developing. The RSF model outperformed the Cox regression model in predicting functional disability, with key factors including age, education, walking time, grip strength, CES-D score, and multimorbidity trajectories. Significant factors identified were CES-D score, grip strength, multimorbidity trajectory, age, and the use of antihypertensive medications. Conclusions The RSF model, based on CHARLS data, effectively predicts functional disability in older adults, with depressive symptoms, handgrip strength, multimorbidity trajectories, age, and antihypertensive medication use emerging as key predictors.

Background: To date, the differentiated requirements for network performance in various health care service scenarios-within,outside, and between hospitals-remain a key challenge that restricts the development and implementation of digital medicalservices. Objective: This study aims to construct and implement a private 5G (the 5th generation mobile communication technology)standalone (SA) medical network in a smart health environment to meet the diverse needs of various medical services. Methods: Based on an analysis of network differentiation requirements in medical applications, the system architecture andfunctional positioning of the proposed private 5G SA medical network are designed and implemented. The system architectureincludes the development of exclusive and preferential channels for medical use, as well as an ordinary user channel. A 3-layernetwork function architecture is designed, encompassing resource, control, and intelligent operation layers to facilitate managementarrangements and provide network open services. Core technologies, including edge cloud collaboration; service awareness; andslicing of access, bearer, and core networks, are employed in the construction and application of the 5G SA network. Results: The construction of the private 5G SA medical network primarily involves system architecture, standards, and securitymeasures. The system, featuring exclusive, preferential, and common channels, supports a variety of medical applications. Relevantstandards are adhered to in order to ensure the interaction and sharing of medical service information. Security is achieved throughmechanisms such as authentication, abnormal behavior analysis, and dynamic access control. Three typical medical applicationsthat rely on the 5G network in intrahospital, interhospital, and out-of-hospital scenarios-namely, mobile ward rounds, remotefirst aid, and remote ultrasound-were conducted. Testing of the 5G-enabled mobile ward rounds showed an average downloadrate of 790 Mbps and an average upload rate of 91 Mbps. Compared with 4G, the 5G network more effectively meets the diverserequirements of various business applications in prehospital emergency scenarios. For remote ultrasound, the average downlinkrate of the 5G network is 4.82 Mbps, and the average uplink rate is 2 Mbps, with an average fluctuation of approximately 8 ms.The bandwidth, performance, and delay of the 5G SA network were also examined and confirmed to be effective Conclusions: The proposed 5G SA medical network demonstrates strong performance in typical medical applications. Itsconstruction and application could lead to the development of new medical service models and provide valuable references forthe further advancement and implementation of 5G networks in other industries, both in China and globally