The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

BACKGROUND: Despite some studies identifying a potential association between obesity and chronic obstructive pulmonary disease (COPD) risk, previous research had overlooked the dynamic nature of body weight over time, leading to inconsistent findings. The purpose of this study is to elucidate the relationship between adult weight change and COPD risk by adjusting for potential confounding factors. METHODS: We conducted a retrospective analysis using data from ten NHANES cycles (1999-2018), including adults aged 40-74 years. Weight change patterns were assessed using BMI at three time points and classified into five categories per period. Absolute weight change was also grouped into five levels. Multivariate logistic regression models, incorporating sampling weights, were used to examine associations between weight change and COPD, adjusting for demographic and lifestyle covariates. RESULTS: Compared with participants who maintained normal weight, stable obesity participants had increased risk of COPD from age 25 years to 10 years before the survey (OR = 1.45, 95% CI = 1.15 to 1.83), in the 10 years period before the survey (OR = 1.75, 95% CI = 1.47 to 2.08), and from age 25 years to survey (OR = 1.84, 95% CI = 1.46 to 2.31). Three periods indicate that weight gain in adulthood was associated with risk of COPD. In addition, substantial weight gain of more than 20 kg was associated with a higher risk of COPD. In stratified analyses, we also observed a more significant association between weight change and the risk of COPD in never smokers compared to former smokers. CONCLUSIONS Our study suggested that stable obesity and weight gain in adulthood were associated with an increased risk of COPD compared to those who maintain a normal weight, and that the association between weight gain and the incidence of COPD appears closer in patients who have never smoked.
Humans ; Pulmonary Disease, Chronic Obstructive/etiology* ; Middle Aged ; Male ; Female ; Adult ; Aged ; Retrospective Studies ; Weight Gain ; Obesity/complications* ; Risk Factors ; United States/epidemiology* ; Nutrition Surveys ; Body Mass Index

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients' quality of life. Zhengqing Fengtongning (ZF) is a traditional Chinese medicine preparation used to treat RA. ZF may cause liver injury. In this study, we aimed to develop a prediction model for abnormal liver function caused by ZF. METHODS: This retrospective study collected data from multiple centers from January 2018 to April 2023. Abnormal liver function was set as the target variable according to the alanine transaminase (ALT) level. Features were screened through univariate analysis and sequential forward selection for modeling. Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data. RESULTS: This study included 1,913 eligible patients. The LightGBM model exhibited the best performance (accuracy = 0.96) out of the 10 learning models. The predictive metrics of the LightGBM model were as follows: precision = 0.99, recall rate = 0.97, F1_score = 0.98, area under the curve (AUC) = 0.98, sensitivity = 0.97 and specificity = 0.85 for predicting ALT < 40 U/L; precision = 0.60, recall rate = 0.83, F1_score = 0.70, AUC = 0.98, sensitivity = 0.83 and specificity = 0.97 for predicting 40 ≤ ALT < 80 U/L; and precision = 0.83, recall rate = 0.63, F1_score = 0.71, AUC = 0.97, sensitivity = 0.63 and specificity = 1.00 for predicting ALT ≥ 80 U/L. ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels, the combination of TNF-α inhibitors, JAK inhibitors, methotrexate + nonsteroidal anti-inflammatory drugs, leflunomide, smoking, older age, and females in middle-age (45-65 years old). CONCLUSION This study developed a model for predicting ZF-induced abnormal liver function, which may help improve the safety of integrated administration of ZF and Western medicine. Please cite this article as: Yu Z, Kou F, Gao Y, Lyu CM, Gao F, Wei H. A machine learning model for predicting abnormal liver function induced by a Chinese herbal medicine preparation (Zhengqing Fengtongning) in patients with rheumatoid arthritis based on real-world study. J Integr Med. 2025; 23(1): 25-35.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Middle Aged ; Male ; Retrospective Studies ; Machine Learning ; Adult ; Aged ; Liver/physiopathology* ; Alanine Transaminase/blood*

Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

The inflammatory status in patients with chronic kidney disease(CKD)is closely associated with cardiovascular events,infections,and other complications,and is a powerful indicator for prognosis assessment.The core view of the"gut-kidney axis"theory reveals the relationship among inflammatory state,microbiota dysbiosis,and deterioration of renal function.The microbiota alters the microenvironment through structural changes and metabolites with different properties,subsequently leading to microbiota translocation,inducing inflammatory lesions,and damaging the kidneys.Recent studies have proposed that targeted microbiota intervention strategies such as probiotics,prebiotics,and synbiotics can modulate the microbiota structure,regulate the microenvironment,relieve renal inflammation,and affect the progression of renal disease,representing a potentially promising research direction in the future.This review discusses the characteristics of how intestinal microbiota influence the inflammatory status in CKD,focusing on the research progress of targeted microbiota intervention,aiming to discuss the effectiveness and scientific basis of these strategies,providing a foundation for the treatment of CKD and the expansion of targeted microbiota research,as well as offering references for the clinical application of probiotics,prebiotics,and synbiotics.

Objective:To investigate the protective effects and underlying mechanisms of carbon monoxide-releasing molecule-3 (CORM-3) against hypoxia-reoxygenation-induced injury in Caco-2 cells.Methods:A hypoxia-reoxygenation injury model was established in Caco-2 cell monolayers by culturing cells under glucose-free, serum-free hypoxic conditions (1% O 2) for 8 hours, followed by reoxygenation with glucose and serum restoration for 4 hours. Experimental groups included: blank control (Control), hypoxia-reoxygenation model (HR), and HR with 300 μmol/L (HR_C1), 400 μmol/L (HR_C2), or 500 μmol/L CORM-3 (HR_C3), plus HR with 500 μmol/L inactive iCORM-3 (HR_iC). CORM-3/iCORM-3 was administered during the hypoxic phase. Assessments included: cell viability (CCK-8 assay), apoptosis/necrosis rates (flow cytometry), monolayer permeability (sodium fluorescein), tight junction protein distribution (ZO-1, Occludin, Claudin2 immunofluorescence), protein expression (Western blot), and transcriptomic analysis of differentially expressed genes. Results:Compared to controls, HR group showed significantly reduced cell viability ( P<0.05), increased apoptosis/necrosis rates, elevated sodium fluorescein permeability (both P<0.05), disrupted tight junction structure, decreased Occludin and increased Claudin2 expression (both P<0.05). CORM-3 treatment significantly improved viability ( P<0.05), reduced apoptosis/necrosis rates and permeability (both P<0.05, concentration-dependent), mitigated tight junction damage, showed a non-significant trend toward increased Occludin, and significantly decreased Claudin2 expression ( P<0.05). Transcriptomics identified 25 differentially expressed genes, with KEGG analysis revealing 14 significant pathways (including MAPK signaling, inflammatory bowel disease, and cellular senescence). GO analysis highlighted immune-inflammatory responses and cell membrane barrier components, with TGFB3 as the primary immune-related gene. Conclusions:CORM-3 effectively reduces apoptosis/necrosis, preserves tight junctions, and mitigates hypoxia-reoxygenation injury in Caco-2 cells, potentially through MAPK signaling regulation and immune-inflammatory response modulation.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Radioactive contamination can occur during nuclear accidents, loss of radioactive sources and the use of radiation for photography, disinfection and detection. When the human body is accidentally contaminated by radionuclides, radionuclides can cause harm to the human body through inhalation, ingestion, direct transdermal absorption and contaminated wounds into body tissues and organs. In the treatment of radionuclide contamination in vivo, the main way is decorporation therapy, which mainly uses specific decorporation agents to selectively bind radionuclides to form stable non-toxic complexes, thereby preventing their deposition in the body, accelerating excretion, and reducing the total accumulation of radionuclides in human tissues. At present, internal radionuclide decorporation agents promote the release of radionuclides from the body mainly by stopping the entry of radionuclides into the body, ion exchange, chelation, and binding of exportants to carriers. But recent studies have found that lysosomal exocytosis, the natural clearing function of activated cells, also has a significant exportation effect. In this paper, we first introduced and analyzed the mechanism and research status of radionuclide decorporation agents that have been used in clinical practice, such as the blocking effect of potassium iodide, the ion exchange effect of Prussian blue, the chelation effect of DTPA, and the urine alkalinization effect of sodium bicarbonate. The second part introduces the mechanism and research status of promising radionuclide decorporation agents. Among them, 3,4,3-LI (1,2-HOPO) and 5-LIO (Me-3,2-HOPO) are the most promising ones and have been approved for phase I clinical trials. Others such as catecholamines, polyethyleneimine and fullerenes are also being studied with great potential. Polyethyleneimine, as a biological macromolecular chelator, has more chelating sites and stronger targeting effects than small molecule chelators, and has achieved a real breakthrough in decorporation. Fullerenes are known as “free radical sponges” with good free radical scavenging ability and antioxidant properties. In recent years, biomaterials have been widely used in the field of radionuclide decorporation, which has greatly improved the decorporation efficiency. Chitosan and pectin have shown great advantages in promoting radionuclide decorporation, chitosan can adsorb metal ions through electrostatic interaction and chelation, and can also react with free radicals to remove free radicals generated after radionuclides enter the body. Pectin can promote uranium efflux, but the exact mechanism remains unclear. Liposomes and nanomaterials as carriers enhance the intracellular drug delivery, prolong the retention time of drugs in the body, reduce adverse reactions, and make the traditional efflux enhancers glow with new vitality and have good development prospects. The last part summarizes and looks forward to the future research direction of radionuclide decorporation agents. At present, the research on decorporation agents at home and abroad is mostly stuck in the stage of drug development and drug synthesis, and few have actually entered the clinical trial stage. Therefore, the optimization of existing decorporation agents and the development of new ligands are critical. The targeting, biological safety, oral availability, and treatment needs of large-scale contamination scenarios are still the focus of attention. In addition, from the point of view of the mechanism itself, it is a new idea to promote the emission of radionuclides by activating potential channels, which can be continuously explored.