Development of an interpretable machine learning model associated with heavy metals' exposure to identify coronary heart disease among US adults via SHAP: Findings of the US NHANES from 2003 to 2018.

Limited information is available on the links between heavy metals' exposure and coronary heart disease (CHD). We aim to establish an efficient and explainable machine learning (ML) model that associates heavy metals' exposure with CHD identification. Our datasets for investigating the associations between heavy metals and CHD were sourced from the US National Health and Nutrition Examination Survey (US NHANES, 2003-2018). Five ML models were established to identify CHD by heavy metals' exposure. Further, 11 discrimination characteristics were used to test the strength of the models. The optimally performing model was selected for identification. Finally, the SHapley Additive exPlanations (SHAP) tool was used for interpreting the features to visualize the selected model's decision-making capacity. In total, 12,554 participants were eligible for this study. The best performing random forest classifier (RF) based on 13 heavy metals to identify CHD was chosen (AUC: 0.827; 95%CI: 0.777-0.877; accuracy: 95.9%). SHAP values indicated that cesium (1.62), thallium (1.17), antimony (1.63), dimethylarsonic acid (0.91), barium (0.76), arsenous acid (0.79), total arsenic (0.01) in urine, and lead (3.58) and cadmium (4.66) in blood positively contributed to the model, while cobalt (-0.15), cadmium (-2.93), and uranium (-0.13) in urine negatively contributed to the model. The RF model was efficient, accurate, and robust in identifying an association between heavy metals' exposure and CHD among US NHANES 2003-2018 participants. Cesium, thallium, antimony, dimethylarsonic acid, barium, arsenous acid, and total arsenic in urine, and lead and cadmium in blood show positive relationships with CHD, while cobalt, cadmium, and uranium in urine show negative relationships with CHD.

Effect of Traditional Chinese Medicine on Treating Antibiotic-Associated Diarrhea in Children: A Systematic Review and Meta-Analysis.

Background: Due to the limited treatment options in antibiotic-associated diarrhea (AAD) in children, more effective treatments should be explored. Traditional Chinese medicine (TCM) has a long history in China, which has produced a pretty effect in clinical practice. Many randomized clinical trials (RCTs) have explored the effect of traditional Chinese medicine on treating AAD in children. However, there has been no systematic review or meta-analysis on the impact of TCM on AAD in children. The aim of this study was to systematically review RCTs on the effect of TCM in children with AAD. Methods: RCTs in the past ten years on TCM for AAD in children were included. We searched Electronic databases as much as possible. This paper was registered in PROSPERO (CRD42022301034). Results: 26 studies were included in this systematic review. 25 studies reported the effects of TCM interventions on the total effective rate (RR = 1.20, CI 1.16 to 1.24; p < 0.001). 7 studies reported the effects of TCM interventions on the time to change the shape of feces (MD = -1.37, CI -1.67 to -1.07; p < 0.001). 17 studies reported the effects of TCM interventions (MD = -1.43, CI -1.71 to -1.15; p < 0.001). The pooled results showed that there were no significant differences between the two groups in CD3+, CD4+, CD8+, CD4 : CD8, time for bowel sounds to return to normal, hs-CRP, and IgM. There was a significant difference between the two groups in frequency of diarrhea on the third day after TCM intervention, vomiting improvement time, diamine oxidase, IL-8, TNF, IgA, IgG, and average hospital stay. Conclusions: TCM interventions combined with conventional therapy can improve the therapeutic effect of AAD in children. However, future studies are still needed for the low methodological quality.

A new strategy for accurate targeted diagnosis and treatment of cutaneous malignant melanoma: dual-mode phase-change lipid nanodroplets as ultrasound contrast agents.

BACKGROUND: Currently, effective detection and treatment of cutaneous malignant melanoma (CMM) still face severe challenges. Ultrasound molecular imaging as a noninvasive and easy-to-operate method is expected to bring improvements for tumor detection. PURPOSE: The aim of this research is to prepare novel phase-change ultrasound contrast agents, Nds-IR780, which can perform not only dual-mode molecule-targeted imaging but also targeted photothermal therapy for CMM. METHODS: A double emulsion process was used to prepare the Nds-IR780. Then, the entrapment rate and drug loading of IR-780 iodide in Nds-IR780 were detected by high-performance liquid chromatography. The biocompatibility of Nds-IR780 was evaluated by a CCK-8 assay and the characteristics and stability of that were verified through the particle size analyzer, laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). The abilities of dual-mode molecule-targeted imaging and targeted photothermal therapy for Nds-IR780 were confirmed via the in vitro and in vivo experiments. RESULTS: Nds-IR780 had good size distribution, polydispersity index, stability and biosafety. The in vitro and in vivo experiments confirmed that Nds-IR780 were capable of targeting CMM cells with high affinity (22.4±3.2%) and facilitating dual-mode imaging to detect the primary lesion and sentinel lymph nodes (SLNs) of CMM. Furthermore, the photothermal ablation of CMM mediated by Nds-IR780 was very effective in vivo. CONCLUSION: The newly prepared Nds-IR780 were observed to be effective targeted theranostic probe for the precise detection and targeted treatment of CMM.

FA-NBs-IR780: Novel multifunctional nanobubbles as molecule-targeted ultrasound contrast agents for accurate diagnosis and photothermal therapy of cancer.

Early accurate diagnosis and targeted therapy for cancer are essential to improve the prognosis of patients. With the emergence of molecular imaging, molecule-targeted ultrasound imaging for the non-invasive and precise detection of cancer has attracted increased attention. The investigation of molecule-targeted ultrasound contrast agents (UCAs) with excellent performance is urgently needed. In this study, we synthetized folic acid and IR-780 on self-made nanobubbles and prepared novel UCAs, named FA-NBs-IR780. The results showed that the conjugates had a uniform size distribution (591 ±â€¯52 nm). In vitro and in vivo experiments demonstrated that FA-NBs-IR780 can target tumour cells via dual molecular targeting, perform enhanced-contrast ultrasound imaging and near-infrared fluorescence (NIRF) imaging for the precise detection of tumours, and induce targeted photothermal therapy in lesions irradiated at 808 nm. Ex vivo experiments further confirmed that FA-NBs-IR780 efficiently induced tumour cell apoptosis and inhibited tumour growth. The newly fabricated FA-NBs-IR780 were observed to be molecule-targeted dual-mode UCAs and may have potential applications in early accurate diagnosis and targeted therapy of cancer in the future.

Herbal medicine Gan­fu­kang downregulates Wnt/Ca2+ signaling to attenuate liver fibrogenesis in vitro and in vivo.

The present study was designed to verify the effect of the Chinese prescription Gan­fu­kang (GFK) on the treatment of liver fibrosis, and to investigate its underlying mechanisms. Liver fibrosis was established in rats by the subcutaneous administration of 0.5 mg/kg carbon tetrachloride (CCl4) twice a week for 8 weeks. Subsequently, the rats were divided into four CCl4 groups, which were treated daily with vehicle and GFK (31.25, 312.5 and 3,125 mg/kg/day) orally between weeks 9 and 20. The inhibitory action of GFK­medicated serum on platelet­derived growth factor (PDGF)­stimulated HSC­T6 cells was also investigated. Biochemical parameters, hydroxyproline (Hyp) content and histological changes to the liver were measured. Reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemistry were used to examine the expression of α­smooth muscle actin (α­SMA), PDGF­BB, PDGF receptor ß, collagen type I and II, and the Wnt/Ca2+ signaling pathway. The results showed that GFK significantly alleviated the histological changes, decreased the content of Hyp in the liver and improved liver function in rats. In addition, GFK and GFK­medicated serum effectively inhibited collagen deposition, reduced the expression of α­SMA and downregulated the Wnt/Ca2+ signaling pathway in vivo and in vitro, respectively, as well as cell viability (P<0.05). These results indicated that GFK was effective in attenuating liver injury and fibrosis through downregulation of the Wnt/Ca2+ signaling pathway.

Protective effect of the herbal medicine Gan­fu­kang against carbon tetrachloride­induced liver fibrosis in rats.

The aim of the present study was to investigate the effect of a herbal medicine formula, Gan-fu-kang (GFK), on the treatment of liver fibrosis in rats and the mechanisms via which it exerts its effect. Liver fibrosis was induced in rats by subcutaneous injection of carbon tetrachloride (CCl4) at 0.5 mg/kg body weight, twice a week for 8 weeks. The rats were randomly selected to receive saline or GFK at 31.25, 312.5 or 3,125 mg/kg body weight/day between weeks 9 and 20. An additional group of rats without CCl4 injection was used as the baseline. In the liver fibrosis model rats, an increase in plasma liver enzymes, fibrotic markers in serum and liver fibrosis, production of α-smooth muscle actin, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1, synthesis of collagen and activation of the Wnt/ß-catenin signaling pathway were observed. GFK administration was found to significantly reduce these changes. Results of this study demonstrate that GFK has a protective and therapeutic effect on liver fibrosis induced by CCl4, which may be associated with its inhibitory activity on HSC proliferation and collagen synthesis, effectively downregulating Wnt/ß-catenin signaling.