Circulating miRNA-21 as a diagnostic biomarker for acute coronary syndrome: a systematic review and meta-analysis of diagnostic test accuracy study.

Background: Both early detection and treatment for acute coronary syndrome (ACS) have positively affected prognosis. A microRNA, miRNA-21 (miR-21), may have additional diagnostic potential for ACS among the others. This systematic review and meta-analysis aimed to evaluate the potential role of miR-21 in identifying ACS. Methods: PubMed, EMBASE and CENTRAL databases were searched up to March 17, 2024, for case-control and cohort studies assessing the diagnostic value of circulating miR-21 in patients with ACS. The search was limited to studies published in either English or Chinese. The primary outcome was the discriminative ability to circulate miR-21 for ACS, represented by the area under the standard receiver operating characteristic curve (AUC) analysis. Meta-analyses combined the AUCs using a random-effects model. Heterogeneity among the studies was detected by the I2 and Q statistics. The quality of the studies included was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Publication bias analysis was assessed constructing by the Egger's test (PROSPERO: CRD42020209424). Results: Eleven case-control studies containing a total of 2,413 subjects with 1,236 ACS cases and 1,177 controls were included. The mean age of participants in these studies ranges between 51.0 and 69.0 years. The meta-analysis showed an overall pooled AUC of 0.779 [95% confidence interval (CI): 0.715-0.843], with high heterogeneity noted between the studies (Q statistic =190.64, I2=94.23%, P<0.001). In subgroup analyses according to the subtypes of ACS, a pooled AUC of 0.767 (95% CI: 0.648-0.887) was derived from the studies focused on acute myocardial infarction cases only. The pooled AUC for unstable angina was 0.770 (95% CI: 0.718-0.822). In subgroup analyses according to the types of control groups, pooled AUC for ACS versus healthy controls was 0.779 (95% CI: 0.715-0.843), whereas the pooled AUC for ACS versus unhealthy controls was 0.740 (95% CI: 0.645-0.836). The quality assessment showed that the studies' overall quality was moderate. No evidence of publication bias was noted (P=0.49). Conclusions: Circulating miR-21 shows abilities to differentiate between ACS and non-ACS, suggesting its potential as a novel diagnostic biomarker for ACS. However, the evidence is weakened by high heterogeneity observed among the studies. Further research is essential before it can be applied in clinical practice.

Coping with the concurrent heatwaves and ozone extremes in China under a warming climate.

Intensive human activity has brought about unprecedented climate and environmental crises, in which concurrent heatwaves and ozone extremes pose the most serious threats. However, a limited understanding of the comprehensive mechanism hinders our ability to mitigate such compound events, especially in densely populated regions like China. Here, based on field observations and climate-chemistry coupled modelling, we elucidate the linkage between human activities and the climate system in heat-related ozone pollution. In China, we have observed that both the frequency and intensity of heatwaves have almost tripled since the beginning of this century. Moreover, these heatwaves are becoming more common in urban clusters with serious ozone pollution. Persistent heatwaves during the extremely hot and dry summers of 2013 and 2022 accelerated photochemical ozone production by boosting anthropogenic and biogenic emissions, and aggravated ozone accumulation by suppressing dry deposition due to water-stressed vegetation, leading to a more than 30% increase in ozone pollution in China's urban areas. The sensitivity of ozone to heat is demonstrated to be substantially modulated by anthropogenic emissions, and China's clean air policy may have altered the relationship between ozone and temperature. Climate model projections further highlight that the high-emission climate-socioeconomic scenario tends to intensify the concurrent heat and ozone extremes in the next century. Our results underscore that the implementation of a strict emission strategy will significantly reduce the co-occurrence of heatwaves and ozone extremes, achieving climate and environmental co-benefits.

Research on Evolution of Relevant Defects in Heavily Mg-Doped GaN by H Ion Implantation Followed by Thermal Annealing.

This study focuses on the heavily Mg-doped GaN in which the passivation effect of hydrogen and the compensation effect of nitrogen vacancies (VN) impede its further development. To investigate those two factors, H ion implantation followed by thermal annealing was performed on the material. The evolution of relevant defects (H and VN) was revealed, and their distinct behaviors during thermal annealing were compared between different atmospheres (N2/NH3). The concentration of H and its associated yellow luminescence (YL) band intensity decrease as the thermal annealing temperature rises, regardless of the atmosphere being N2 or NH3. However, during thermal annealing in NH3, the decrease in H concentration is notably faster compared to N2. Furthermore, a distinct trend is observed in the behavior of the blue luminescence (BL) band under N2 and NH3. Through a comprehensive analysis of surface properties, we deduce that the decomposition of NH3 during thermal annealing not only promotes the out-diffusion of H ions from the material, but also facilitates the repair of VN on the surface of heavily Mg-doped GaN. This research could provide crucial insights into the post-growth process of heavily Mg-doped GaN.

Carbon nanotube fibers with dynamic strength up to 14 GPa.

High dynamic strength is of fundamental importance for fibrous materials that are used in high-strain rate environments. Carbon nanotube fibers are one of the most promising candidates. Using a strategy to optimize hierarchical structures, we fabricated carbon nanotube fibers with a dynamic strength of 14 gigapascals (GPa) and excellent energy absorption. The dynamic performance of the fibers is attributed to the simultaneous breakage of individual nanotubes and delocalization of impact energy that occurs during the high-strain rate loading process; these behaviors are due to improvements in interfacial interactions, nanotube alignment, and densification therein. This work presents an effective strategy to utilize the strength of individual carbon nanotubes at the macroscale and provides fresh mechanism insights.

Synthesis and Characterization of Emulsifiers Based on the Maillard Reaction and Its Application in Stabilized DHA Algal Oil Nanoemulsions.

The aim of this study was to optimize the formation of sodium caseinate (CS) and gum arabic (GA) complexes through the Maillard reaction and to evaluate their effectiveness in improving the emulsification properties and stability of docosahexaenoic acid (DHA) nanoemulsions. First, the best target polysaccharides were selected, and the best modification conditions were determined using orthogonal experiments. Secondly, the response surface experiments were used to optimize the preparation process of the emulsion. The stability, in vitro digestion characteristics, and rheological characteristics of the emulsion prepared by means of CS-GA were compared with the emulsion prepared using a whey protein isolate (WPI). After the orthogonal test, the optimal modification conditions were determined to be a reaction time of 96 h, a CS-GA mass ratio of 1:2, a reaction temperature of 60 °C, and a degree of grafting of 44.91%. Changes in the infrared (IR), Raman, ultraviolet (UV), and endogenous fluorescence spectra also indicated that the complex structure was modified. The response surface test identified the optimal preparation process as follows: an emulsifier concentration of 5 g/L, an oil-phase concentration of 5 g/L, and a homogenization frequency of five, and the emulsion showed good stability. Therefore, the use of a nanoemulsion as a nanoscale DHA algal oil delivery system is very promising for extending the shelf life and improving the stability of food.

Multidisciplinary Management Strategies for Long COVID: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions.

3D spheroid HepaRG and fluorescent biphasic tracer for CYP3A4-mediated antibiotic interaction monitoring in sepsis.

Cytochrome P450 3A4 (CYP3A4) is a crucial enzyme in the metabolism of xenobiotics, particularly in drug metabolism interactions (DDIs), making it a significant factor in clinical drug use. However, current assay techniques are both laborious and costly, making it difficult to construct a high-throughput monitoring method that can be used in conjunction with the clinic. This poses certain safety hazards for drug combination. Therefore, it is crucial to develop a synchronized monitoring method for the inhibition and induction of CYP3A4. In this study, we utilized 3D culture technology to develop a HepaRG cells spheroid model. The CYP450 and transporter expression, the albumin secretion, and urea synthesis capacity characteristics were analyzed. The NEN probe was utilized as a tracer molecule for CYP3A4. The fluorescence intensity of metabolites was characterized by laser confocal technique to determine the inhibition and expression of CYP3A4 in the HepaRG cell spheroid model by the antibiotics for sepsis. The results indicate that the HepaRG sphere model successfully possessed the physiological phenotype of the liver, which could be used for drug interaction monitoring. Through positive drug testing, NEN probe was able to achieve bidirectional characterization of CYP3A4 induction and inhibition. The monitoring method described in this paper was successfully applied to drug interaction monitoring of commonly used antibiotics in sepsis patients, which is a convenient and rapid monitoring method. The proposed method offers a new strategy for monitoring CYP3A4-mediated drug-drug interactions with a high-throughput assay, which will help to improve the safety of clinical drug combination.

Structural characterization of Astragalus polysaccharide-D1 and its improvement of low-dose metformin effect by enriching Staphylococcus lentus.

To explore the adjuvant therapy drugs of low-dose metformin, one homogeneous polysaccharide named APS-D1 was purified from Astragalus membranaceus by DEAE-52 cellulose and Sephadex G-100 column chromatography. Its chemical structure was characterized by molecular weight distribution, monosaccharide composition, infrared spectrum, methylation analysis, and NMR. The results revealed that APS-D1 (7.36 kDa) consisted of glucose, galactose, and arabinose (97.51 %:1.56 %:0.93 %). It consisted of →4)-α-D-Glcp-(1→ residue backbone with →3)-ß-D-Galp-(1→ residue and terminal-α/ß-D-Glcp-(1→ side chains. APS-D1 could significantly improve inflammation (TNF-α, LPS, and IL-10) in vivo. Moreover, APS-D1 improved the curative effect of low-dose metformin without adverse events. APS-D1 combined with low-dose metformin regulated several gut bacteria, in which APS-D1 enriched Staphylococcus lentus to produce l-carnitine (one of 136 metabolites of S. lentus). S. lentus and l-carnitine could improve diabetes, and reduction of S. lentusl-carnitine production impaired diabetes improvement. The combination, S. lentus, and l-carnitine could promote fatty acid oxidation (CPT1) and inhibit gluconeogenesis (PCK and G6Pase). The results indicated that APS-D1 enhanced the curative effect of low-dose metformin to improve diabetes by enriching S. lentus, in which the effect of S. lentus was mediated by l-carnitine. Collectively, these findings support that low-dose metformin supplemented with APS-D1 may be a favorable therapeutic strategy for type 2 diabetes.

Integrated biomarker profiling for predicting the response of type 2 diabetes to metformin.

AIM: To explore biomarkers that can predict the response of type 2 diabetes (T2D) patients to metformin at an early stage to provide better treatment for T2D. METHODS: T2D patients with (responders) or without response (non-responders) to metformin were recruited, and their serum samples were used for metabolomic analysis to identify candidate biomarkers. Moreover, the efficacy of metformin was verified by insulin-resistant mice, and the candidate biomarkers were verified to determine the biomarkers. Five different machine learning methods were used to construct the integrated biomarker profiling (IBP) with the biomarkers to predict the response of T2D patients to metformin. RESULTS: A total of 73 responders and 63 non-responders were recruited, and 88 differential metabolites were identified in the serum samples. After being verified in mice, 19 of the 88 were considered as candidate biomarkers. Next, after metformin regulation, nine candidate biomarkers were confirmed as the biomarkers. After comparing five machine learning models, the nine biomarkers were constructed into the IBP for predicting the response of T2D patients to metformin based on the Naïve Bayes classifier, which was verified with an accuracy of 89.70%. CONCLUSIONS: The IBP composed of nine biomarkers can be used to predict the response of T2D patients to metformin, enabling clinicians to start a combined medication strategy as soon as possible if T2D patients do not respond to metformin.

Effects of chopping temperature on the gel quality of silver carp (Hypophthalmichthys molitrix) surimi: insight from gel-based proteomics.

BACKGROUND: Morden advanced analytical tools offer valuable information into the understanding of molecular mechanism of traditional food processing. Chopping temperature is well-known to affect the surimi gel quality of silver carp, but the detailed molecular mechanism is not very clear. In this study, a gel-based proteomics was performed on the extracted surimi proteins under different chopping temperatures (0, 5, 10, and 25 °C) along with other physicochemical characterization of surimi proteins and gels. RESULTS: With increased chopping temperature, protein extractability (in 3% sodium chloride) generally decreased, while the extracted protein generally exhibited larger surface hydrophobicity, reduced intrinsic fluorescence intensity, lower sulfhydryl content. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) profile of extracted protein showed a clear difference at 25 °C when compared with the other three temperatures, and more protein fragmentation occurred. Proteomic analysis of selected bands indicated that major myofibrillar proteins react differently with chopping temperatures, especially at 25 °C. The selected bands contained a variety of other proteins or their fragments, including adenosine triphosphate (ATP) synthase, glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate isomerase, heat shock protein, parvalbumin, collagen, and so forth. For the surimi gel, water-holding capacity and gel strength generally decreased with increased chopping temperature. CONCLUSION: Our results suggested that chopping at 0-10 °C is acceptable for the production of silver carp surimi in terms of gel strength and water-holding capacity. However, a chopping temperature near 0 °C led to less protein oxidation and denaturation. The inferior gel quality at 25 °C is linked to a decreased concentration of extracted protein and degradation of major myofibrillar protein, the latter is likely crosslinked with sarcoplasmic proteins. © 2024 Society of Chemical Industry.

Iron deficiency anemia and platelet dysfunction: A comprehensive analysis of the underlying mechanisms.

AIMS: This research aimed to study the changes in platelet function and their underlying mechanisms in iron deficiency anemia. MAIN METHODS: Initially, we evaluated platelet function in an IDA mice model. Due to the inability to accurately reduce intracellular Fe2+ concentrations, we investigated the impact of Fe2+ on platelet function by introducing varying concentrations of Fe2+. To probe the underlying mechanism, we simultaneously examined the dynamics of calcium in the cytosol, and integrin αIIbß3 activation in Fe2+-treated platelets. Ferroptosis inhibitors Lip-1 and Fer-1 were applied to determine whether ferroptosis was involved in this process. KEY FINDINGS: Our study revealed that platelet function was suppressed in IDA mice. Fe2+ concentration-dependently facilitated platelet activation and function in vitro. Mechanistically, Fe2+ promoted calcium mobilization, integrin αIIbß3 activation, and its downstream outside-in signaling. Additionally, we also demonstrated that ferroptosis might play a role in this process. SIGNIFICANCE: Our data suggest an association between iron and platelet activation, with iron deficiency resulting in impaired platelet function, while high concentrations of Fe2+ contribute to platelet activation and function by promoting calcium mobilization, αIIbß3 activation, and ferroptosis.

The effect of fine particulate matter (PM2.5) pollution on health inequality: an intergenerational perspective.

Air pollution poses a serious challenge to public health and simultaneously exacerbating regional & intergenerational health inequality. This research introduces PM2.5 pollution into the intergenerational health transmission model, and estimates its impact on health inequality in China using Ordered Logit Regression (OLR) and Multi-scale Geographically Weighted Regression (MGWR) model. The results indicate that PM2.5 pollution exacerbate the intergenerational health inequality, and its impacts show inconsistency across family income levels, parental health insurance status, and area of residence. Specifically, it is more difficult for offspring in low-income families to escape from the influence of unhealthy family to become upwardly mobile. Additionally, this health inequality is more significant in households in which at least one parent does not have health insurance. Moreover, the intergenerational solidification caused by PM2.5 pollution is higher in the east and lower in the west. Both the PM2.5 level and solidification effect are high in Beijing-Tianjin-Hebei region, Yangtze River Delta region and central areas of China, which is the focus of air pollution management. These findings suggest that more emphasis should be placed on family-based health promotion. In areas with high PM2.5 pollution levels, resources, subsidies and air pollution protection should be provided for less healthy families with lower incomes and no health insurance.

A systematic review on the appropriate discounting rates for the economic evaluation of gene therapies: whether a specific approach is justified to tackle the challenges?

OBJECTIVES: Discounting the cost and effect for health intervention is a controversial topic over the last two decades. In particular, the cost-effectiveness of gene therapies is especially sensitive to the discount rate because of the substantial delay between the upfront cost incurred and long-lasing clinical benefits received. This study aims to investigate the influence of employing alternative discount rates on the incremental cost-effectiveness ratio (ICER) of gene therapies. METHODS: A systematic review was conducted to include health economic evaluations of gene therapies that were published until April 2023. RESULTS: Sensitivity or scenario analysis indicated that discount rate represented one of the most influential factors for the ICERs of gene therapies. Discount rate for cost and benefit was positively correlated with the cost-effectiveness of gene therapies, that is, a lower discount rate significantly improves the ICERs. The alternative discount rate employed in some cases could be powerful to alter the conclusion on whether gene therapies are cost-effective and acceptable for reimbursement. CONCLUSIONS: Although discount rate will have substantial influence on the ICERs of gene therapies, there lacks solid evidence to justify a different discounting rule for gene therapies. However, it is proposed that the discount rate in the reference case should be updated to reflect the real-time preference, which in turn will affect the ICERs and reimbursement of gene therapies more profoundly than conventional therapies.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: : The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Discovery of Novel Macrocyclic MERTK/AXL Dual Inhibitors.

MERTK and AXL are members of the TAM (TYRO3, AXL, MERTK) family of receptor tyrosine kinases that are aberrantly expressed and have been implicated as therapeutic targets in a wide variety of human tumors. Dual MERTK and AXL inhibition could provide antitumor action mediated by both direct tumor cell killing and modulation of the innate immune response in some tumors such as nonsmall cell lung cancer. We utilized our knowledge of MERTK inhibitors and a structure-based drug design approach to discover a novel class of macrocyclic dual MERTK/AXL inhibitors. The lead compound 43 had low-nanomolar activity against both MERTK and AXL and good selectivity over TYRO3 and FLT3. Its target engagement and selectivity were also confirmed by NanoBRET and cell-based MERTK and AXL phosphorylation assays. Compound 43 had excellent pharmacokinetic properties (large AUC and long half-life) and mediated antitumor activity against lung cancer cell lines, indicating its potential as a therapeutic agent.

Pre-rigor salting improves gel strength and water-holding of surimi gel made from snakehead fish (Channa argus): The role of protein oxidation.

The purpose of this study was to determine the effect of pre-rigor salting on the quality characteristics of surimi gels prepared from snakehead fish muscle. Pre-rigor and post-rigor muscle were mixed with 0.3% or 3% NaCl (w/w) and made into surimi gels, respectively. Results showed that pre-rigor muscle had a higher content of ATP, longer sarcomere, higher pH and greater protein solubility. Metabolic profile suggested that pre-rigor muscle had higher content (a 28-fold increase) of antioxidants such as butyryl-l-carnitine. Transmission electron microscopy showed more damage of mitochondria in post-rigor muscle. Surimi paste from pre-rigor meat chopped with 3% NaCl generally showed greater radical scavenging ability and had higher content of free sulfhydryl. Surimi gel made from pre-rigor muscle salted with 3% NaCl showed a larger gel strength (3.18 kg*mm vs. 2.22 kg*mm) and better water-holding (86% vs. 80%) than that of post-rigor group. Based on these findings, we hypothesized that: In addition to other factors such as pH, degree of denaturation, etc., less protein oxidation in pre-rigor salted surimi also contributes to the improved gel properties.

Mechanism Exploration on the Immunoregulation of Allogeneic Heart Transplantation Rejection in Rats With Exosome miRNA and Proteins From Overexpressed IDO1 BMSCs.

Immunoregulation and indoleamine 2,3-dioxygenase 1 (IDO1) play pivotal roles in the rejection of allogeneic organ transplantation. This study aims to elucidate the immune-related functional mechanisms of exosomes (Exos) derived from bone marrow-derived mesenchymal stem cells (BMSCs) overexpressing IDO1 in the context of allogeneic heart transplantation (HTx) rejection. A rat model of allogeneic HTx was established. Exos were extracted after transfection with oe-IDO1 and oe-NC from rat BMSCs. Exos were administered via the caudal vein for treatment. The survival of rats was analyzed, and reverse transcription qualitative PCR (RT-qPCR) and immunohistochemistry (IHC) were employed to detect the expression of related genes. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, and flow cytometry was utilized to analyze T-cell apoptosis. Proteomics and RNA-seq analyses were performed on Exos. The data were subjected to functional enrichment analysis using the R language. A protein interaction network was constructed using the STRING database, and miRWalk, TargetScan, and miRDB databases predicted the target genes, differentially expressed miRNAs, and transcription factors (TFs). Exos from BMSCs overexpressing IDO1 prolonged the survival time of rats undergoing allogeneic HTx. These Exos reduced inflammatory cell infiltration, mitigated myocardial damage, induced CD4 T-cell apoptosis, and alleviated transplantation rejection. The correlation between Exos from BMSCs overexpressing IDO1 and immune regulation was profound. Notably, 13 immune-related differential proteins (Anxa1, Anxa2, C3, Ctsb, Hp, Il1rap, Ntn1, Ptx3, Thbs1, Hspa1b, Vegfc, Dcn, and Ptpn11) and 10 significantly different miRNAs were identified. Finally, six key immune proteins related to IDO1 were identified through common enrichment pathways, including Thbs1, Dcn, Ptpn11, Hspa1b, Il1rap, and Vegfc. Thirteen TFs of IDO1-related key miRNAs were obtained, and a TF-miRNA-mRNA-proteins regulatory network was constructed. Exosome miRNA derived from BMSCs overexpressing IDO1 may influence T-cell activation and regulate HTx rejection by interacting with mRNA.

Antibiotic combinations prediction based on machine learning to multicentre clinical data and drug interaction correlation.

BACKGROUND: With increasing antibiotic resistance and regulation, the issue of antibiotic combination has been emphasised. However, antibiotic combination prescribing lacks a rapid identification of feasibility, while its risk of drug interactions is unclear. METHODS: We conducted statistical descriptions on 16 101 antibiotic coprescriptions for inpatients with bacterial infections from 2015 to 2023. By integrating the frequency and effectiveness of prescriptions, we formulated recommendations for the feasibility of antibiotic combinations. Initially, a machine learning algorithm was utilised to optimise grading thresholds and habits for antibiotic combinations. A feedforward neural network (FNN) algorithm was employed to develop antibiotic combination recommendation model (ACRM). To enhance interpretability, we combined sequential methods and DrugBank to explore the correlation between antibiotic combinations and drug interactions. RESULTS: A total of 55 antibiotics, covering 657 empirical clinical antibiotic combinations were used for ACRM construction. Model performance on the test dataset showed AUROCs of 0.589-0.895 for various antibiotic recommendation classes. The ACRM showed satisfactory clinical relevance with 61.54-73.33% prediction accuracy in a new independent retrospective cohort. Antibiotic interaction detection showed that the risk of drug interactions was 29.2% for strongly recommended and 43.5% for not recommended. A positive correlation was identified between the level of clinical recommendation and the risk of drug interactions. CONCLUSIONS: Machine learning modelling of retrospective antibiotic prescriptions habits has the potential to predict antibiotic combination recommendations. The ACRM plays a supporting role in reducing the incidence of drug interactions. Clinicians are encouraged to adopt such systems to improve the management of antibiotic usage and medication safety.