Injectable Hydrogel With Glycyrrhizic Acid and Asiaticoside-Loaded Liposomes for Wound Healing.

BACKGROUND: Open skin wounds increase the risk of infections and can compromise health. Therefore, applying medications to promote healing at the injury site is crucial. In practice, direct drug delivery is often difficult to maintain for a long time due to rapid absorption or wiping off, which reduces the efficiency of wound healing. Consequently, the development of bioactive materials with both antibacterial and wound-healing properties is highly desirable. METHODS: This study synthesized liposomes loaded with glycyrrhizic acid (GA) and asiaticoside (AS) by film dispersion-ultrasonication method, which were then incorporated into a GelMA solution and cross-linked by ultraviolet light to form a bioactive composite hydrogel for wound dressings. RESULTS: This hydrogel is conducive to the transport of nutrients and gas exchange. Compared with GelMA hydrogel (swelling rate 69.8% ± 5.7%), the swelling rate of GelMA/Lip@GA@AS is lower, at 52.1% ± 1.0%. GelMA/Lip@GA@AS also has better compression and rheological properties, and the in vitro biodegradability is not significantly different from that of the collagenase-treated group. In addition, the hydrogel polymer has a stable drug release rate, good biocompatibility, and an angiogenic promoting effect. In vitro experiments prove that, at concentrations of 0.5, 1, 2, and 3 mg/mL, GelMA/Lip@GA@AS can inhibit the growth of Staphylococcus aureus. CONCLUSION: We synthesized GelMA/Lip@GA@AS hydrogel and found it possesses advantageous mechanical properties, rheology, and biodegradability. Experimental results in vitro showed that the bioactive hydrogel could efficiently release drugs, exhibit biocompatibility, and enhance angiogenesis and antimicrobial effects. These results suggest the promising application of GelMA/Lip@GA@AS hydrogel in wound-dressing materials.

Classification of coronary artery disease using radial artery pulse wave analysis via machine learning.

BACKGROUND: Coronary artery disease (CAD) is a major global cardiovascular health threat and the leading cause of death in many countries. The disease has a significant impact in China, where it has become the leading cause of death. There is an urgent need to develop non-invasive, rapid, cost-effective, and reliable techniques for the early detection of CAD using machine learning (ML). METHODS: Six hundred eight participants were divided into three groups: healthy, hypertensive, and CAD. The raw data of pulse wave from those participants was collected. The data were de-noised, normalized, and analyzed using several applications. Seven ML classifiers were used to model the processed data, including Decision Tree (DT), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Extra Trees (ET), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting (LightGBM), and Unbiased Boosting with Categorical Features (CatBoost). RESULTS: The Extra Trees classifier demonstrated the best classification performance. After tunning, the results performance evaluation on test set are: 0.8579 accuracy, 0.9361 AUC, 0.8561 recall, 0.8581 precision, 0.8571 F1 score, 0.7859 kappa coefficient, and 0.7867 MCC. The top 10 feature importances of ET model are w/t1, t3/tmax, tmax, t3/t1, As, hf/3, tf/3/tmax, tf/5, w and tf/3/t1. CONCLUSION: Radial artery pulse wave can be used to identify healthy, hypertensive and CAD participants by using Extra Trees Classifier. This method provides a potential pathway to recognize CAD patients by using a simple, non-invasive, and cost-effective technique.

Epidemiological changes of scarlet fever before, during and after the COVID-19 pandemic in Chongqing, China: a 19-year surveillance and prediction study.

BACKGROUND: This study aimed to investigate the epidemiological changes in scarlet fever before, during and after the COVID-19 pandemic (2005-2023) and predict the incidence of the disease in 2024 and 2025 in Chongqing Municipality, Southwest China. METHODS: Descriptive analysis was used to summarize the characteristics of the scarlet fever epidemic. Spatial autocorrelation analysis was utilized to explore the distribution pattern of the disease, and the seasonal autoregressive integrated moving average (SARIMA) model was constructed to predict its incidence in 2024 and 2025. RESULTS: Between 2005 and 2023, 9,593 scarlet fever cases were reported in Chongqing, which resulted in an annual average incidence of 1.6694 per 100,000 people. Children aged 3-7 were the primary victims of this disease, with the highest average incidence found among children aged 6 (5.0002 per 100,000 people). Kindergarten children were the dominant infected population, accounting for as much as 54.32% of cases, followed by students (34.09%). The incidence for the male was 1.51 times greater than that for the female. The monthly distribution of the incidence showed a bimodal pattern, with one peak occurring between April and June and another in November or December. The spatial autocorrelation analysis revealed that scarlet fever cases were markedly clustered; the areas with higher incidence were mainly concentrated in Chongqing's urban areas and its adjacent districts, and gradually spreading to remote areas after 2020. The incidence of scarlet fever increased by 106.54% and 39.33% in the post-upsurge period (2015-2019) and the dynamic zero-COVID period (2020-2022), respectively, compared to the pre-upsurge period (2005-2014) (P < 0.001). During the dynamic zero-COVID period, the incidence of scarlet fever decreased by 68.61%, 25.66%, and 10.59% (P < 0.001) in 2020, 2021, and 2022, respectively, compared to the predicted incidence. In 2023, after the dynamic zero-COVID period, the reported cases decreased to 1.5168 per 100,000 people unexpectedly instead of increasing. The cases of scarlet fever are predicted to increase in 2024 (675 cases) and 2025 (705 cases). CONCLUSIONS: Children aged 3-7 years are the most affected population, particularly males, and kindergartens and primary schools serving as transmission hotspots. It is predicted that the high incidence of scarlet fever in Chongqing will persist in 2024 and 2025, and the outer districts (counties) beyond urban zone would bear the brunt of the impact. Therefore, imminent public health planning and resource allocation should be focused within those areas.

Unveiling the therapeutic promise of EphA2 in glioblastoma: a comprehensive review.

Glioblastoma (GBM), a primary brain tumor, exhibits remarkable invasiveness and is characterized by its intricate location, infiltrative behavior, the presence of both the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB), phenotypic diversity, an immunosuppressive microenvironment with limited development yet rich vascularity, as well as the resistant nature of glioblastoma stem cells (GSCs) towards traditional chemotherapy and radiotherapy. These formidable factors present substantial obstacles in the quest for effective GBM treatments. Following extensive research spanning three decades, the hepatocellular receptor A2 (EphA2) receptor tyrosine kinase has emerged as a promising molecular target with translational potential in the realm of cancer therapy. Numerous compounds aimed at targeting EphA2 have undergone rigorous evaluation and clinical investigation. This article provides a comprehensive account of the distinctive roles played by canonical and non-canonical EphA2 signaling in various contexts, while also exploring the involvement of the EphA2-ephrin A1 signaling axis in GBM pathogenesis. Additionally, the review offers an overview of completed clinical trials targeting EphA2 for GBM treatment, shedding light on both the prospects and challenges associated with EphA2-directed interventions in the domain of cancer therapeutics.

Beyond skin deep: Revealing the essence of iPS cell-generated skin organoids in regeneration.

Various methods have been used for in vivo and in vitro skin regeneration, including stem cell therapy, tissue engineering, 3D printing, and platelet-rich plasma (PRP) injection therapy. However, these approaches are rooted in the existing knowledge of skin structures, which overlook the normal physiological processes of skin development and fall short of replicating the skin's regenerative processes outside the body. This comprehensive review primarily focuses on skin organoids derived from human pluripotent stem cells, which have the capacity to regenerate human skin tissue by restoring the embryonic skin structure, thus offering a novel avenue for producing in vitro skin substitutes. Furthermore, they contribute to the repair of damaged skin lesions in patients with systemic sclerosis or severe burns. Particular emphasis will be placed on the origins, generations, and applications of skin organoids, especially in dermatology, and the challenges that must be addressed before clinical implementation.

A Long-Range Disordering RuO2 Catalyst for Highly Efficient Acidic Oxygen Evolution Electrocatalysis.

Non-iridium acid-stabilized electrocatalysts for oxygen evolution reaction (OER) are crucial to reducing the cost of proton exchange membrane water electrolyzers (PEMWEs). Here, we report a strategy to modulate the stability of RuO2 by doping boron (B) atoms, leading to the preparation of a RuO2 catalyst with long-range disorder (LD-B/RuO2). The structure of long-range disorder endowed LD-B/RuO2 with a low overpotential of 175 mV and an ultra-long stability, which can maintain OER for about 1.6 months at 10 mA cm-2 current density in 0.5 M H2SO4 with almost invariable performance. More importantly, a PEM electrolyzer using LD-B/RuO2 as the anode demonstrated excellent performance, reaching 1000 mA cm-2 at 1.63 V with durability exceeding 300 h at 250 mA cm-2 current density. The introduction of B atoms induced the formation of a long-range disordered structure and symmetry-breaking B-Ru-O motifs, which enabled the catalyst structure to a certain toughness while simultaneously inducing the redistribution of electrons on the active center Ru, which jointly promoted and guaranteed the activity and long-term stability of LD-B/RuO2. This study provides a strategy to prepare long-range disordered RuO2 acidic OER catalysts with high stability using B-doping to perturb crystallinity, which opens potential possibilities for non-iridium-based PEMWE applications.

Special-form radial collateral artery perforator flaps for the reconstruction of complex hand defects.

BACKGROUND: The reconstruction of complex wounds of the hand still has challenges in achieving aesthetic, functional and sensory recovery. We presented our experience of using the polyfoliate and chimeric radial collateral artery perforator flaps (RCAPF) to repair complex hand defects, aiming to explore the feasibility of special-form RCAPFs in hand coverage and enhance the comprehension of their respective indications. METHODS: From June 2014 to March 2021, 26 cases (19 males and 7 females, mean 44.4 years) underwent defect and sensation reconstruction of their hands with special-form RCAPFs, which manifested as multiple adjacent or irregular single wounds and composite tissue defects complicated with a degree of nerve injury. The clinical effects of the free RCAPFs were evaluated by integrating the postoperative and long-term follow-up outcomes of all cases. RESULTS: Altogether 8 polyfoliate flaps, 17 chimeric flaps and 1 polyfoliate-chimeric flap were harvested. Of them, 23 flaps survived uneventfully in one stage. Venous congestion occurred in 3 cases, two of which survived through vascular exploration and another one was finally repaired by the contralateral RCAPF. The follow-up results showed that the appearance of both the recipient and donor sites mostly recovered satisfactory. All the bone flaps properly healed. The BMRC sensory evaluation results of all skin flaps were S4 in 8 flaps, S3 in 18 flaps, and S2 in 9 flaps. CONCLUSIONS: The free RCAPFs can be designed in various forms with a reliable blood supply, contributing to reconstructing simple and multiple wounds of the hand with or without bone defects and dead space.

TARGET based m6A methylation-related genes predict prognosis relapsed B-cell acute lymphoblastic leukemia.

PURPOSE: The current study aims to investigate the significance of N6-methyladenosine (m6A) methylationrelated genes in the clinical prognosis of childhood relapsed B-cell acute lymphoblastic leukemia (B-ALLL) patient. METHODS: Transcriptome data and corresponding clinical data on m6A methylation-related genes (including 20 genes) were obtained from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) database. RESULTS: The bone marrow (BM) samples of 134 newly diagnosed (naive) and 116 relapsed B-ALL from TARGET were enrolled in the current study. Three genes (FTO, HNRNPC, RBM15B) showed significant up-regulation in relapsed B-ALL compared with that in naive B-ALL.The three genes had a significantly worse survival (P < 0.05). The LASSO Cox regression model was used to select the most predictive genes as prognostic indicators, and YTHDC1 and FTO were identified as prognostic factors for relapsed B-ALL. Finally, the results of multivariate regression analysis showed that the risk score of m6A methylation-related genes was an independent prognostic factor in relapsed B-ALL (P < 0.05). CONCLUSION: We found that the expression levels of m6A methylation-related genes were different in naive and relapsed patients with B-ALL and correlated with survival and prognosis.This implies that m6A methylation-related genes may be promising prognostic indicators or therapeutic targets for relapsed B-ALL.

Biofilm-camouflaged Prussian blue synergistic mitochondrial mass enhancement for Alzheimer's disease based on Cu2+ chelation and photothermal therapy.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive and memory impairment. Metal ion imbalance and Mitochondrial dysfunction, leading to abnormal aggregation of ß-amyloid protein (Aß), are key factors in the pathogenesis of AD. Therefore, we designed a composite nanometer system of red blood cell (RBC) membranes-encapsulated Prussian blue nanoparticles (PB/RBC). Prussian blue nanoparticles (PBNPs) can chelate Cu2+ and reduce reactive oxygen species (ROS). The RBC membranes are a kind of natural long-lasting circulating carrier. At the same time, through NIR irradiation, the excellent photothermal ability of PBNPs can also temporarily open the blood-brain barrier (BBB), enhance the transmission efficiency of PB/RBC across the BBB, and depolymerize the formed Aß deposits, thereby achieving the optimal therapeutic effect. In vitro and in vivo studies demonstrated that PB/RBC could inhibit Cu2+-induced Aß monomers aggregation, eliminate the deposition of Aß plaques, improve the quality of mitochondria, restore the phagocytic function of microglia, alleviate neuroinflammation in APP/PS1 mice, and repair memory damage. In conclusion, our biofilm-camouflaged nano-delivery system provides significant neuroprotection by inhibiting Cu2+-induced Aß monomers aggregation, photothermally depolymerizing Aß fibrils and reducing the level of ROS, thus effectively ameliorating and treating AD.

Case Report: A case of rapamycin-eluting stent for the treatment of refractory stenosis of arteriovenous fistula stenosis.

For patients with repeated stenosis of autologous arteriovenous fistula, percutaneous transluminal angioplasty (PTA) or bare metal stent placement had limited efficacy. Rapamycin was reported to inhibit neointimal hyperplasia and keep blood vessels patent. In this study, we reported a case with refractory stenosis, i.e., a short duration of patency maintenance after each repeated PTA, which was treated with a rapamycin-eluting stent (RES). The RES extended the patency duration from 4 to 5 months on average to 14 months. The stent was used to maintain dialysis for over 30 months. RES may be an effective way to treat refractory stenosis and salvage limited vascular resources.

Association of triglyceride-glucose index with helicobacter pylori infection and mortality among the US population.

BACKGROUND: Limited research has explored the potential association between the Triglyceride-Glucose (TyG) and mortality, especially in individuals with Helicobacter pylori (H. pylori) infection. This study seeks to investigate the correlation between the TyG index and H. pylori infection and investigate whether the associations between the TyG index exposure and all-cause mortality are mediated by H. pylori infection. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 2,187 participants. Both univariable and multivariable-adjusted logistic regression analyses were employed to examine the relationship between H. pylori infection and relevant covariates. To assess the association between TyG index, and all-cause mortality in individuals with or without H. pylori infection, Cox regression analysis, and restricted regression cubic spline analysis were implemented. RESULTS: A significant positive correlation was observed between the TyG index and an elevated risk of H. pylori infection [OR 1.157, 95% CI (1.383 ~ 1.664)]. This correlation persisted even after adjusting for confounding factors [OR 1.189, 95% CI (1.003, 1.411), P < 0.05]. Furthermore, in patients with positive H. pylori infection, a noteworthy nonlinear correlation between the TyG index and all-cause mortality was identified (P = 0.0361). With an increase in the TyG index, all-cause mortality exhibited a corresponding rise, particularly following adjustment for all potential confounding factors. Conversely, in patients with negative H. pylori infection, no significant association was observed between the TyG index and all-cause mortality after adjusting for potential confounding factors. CONCLUSION: A higher TyG index was linked to increased H. pylori infection risks. Participants in the higher quantile group of the TyG index are positively associated with higher all-cause mortality compared to the higher quantile group of the TyG index in H. pylori-positive participants instead of H. pylori-negative participants.

Association of frailty index with all-cause and cardiovascular mortality with different diabetic status: NHANES 1999-2018.

AIMS: The relationship between frailty and mortality among individuals with varying diabetic statuses represents a burgeoning area of concern and scholarly interest within the medical community. However, there are limited studies that explore the relationship between frailty and mortality, as well as cause-specific mortality among individuals with non-diabetes, prediabetes, and diabetes patients. Hence, this study aims to investigate the relationship between the frailty statues and all-cause mortality, as well as cause-specific mortality in individuals with varying diabetic statuses using the data in the NHANES database. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 57, 098 participants. Both univariable and multivariable-adjusted logistic regression analyses, as well as Cox regression analysis were employed to examine the relationship between frailty index (FI) and mortality. RESULTS: This study, found a significant positive correlation between the frailty and the increased risk of all-cause mortality non-diabetic [OR 4.277, 95%CI (3.982, 4.594), P < 0.001], prediabetic [OR 2.312, 95%CI (2.133, 2.506), P < 0.001], and diabetic patients [OR 3.947, 95%CI (3.378, 4.611), P < 0.001]. This correlation still existed even after adjusting for confounding factors including age, sex, BMI, poverty, fasting insulin, education, smoke, alcohol drink, waist, hypertension, hyperlipidemia, fasting glucose, HbA1c, eGFR, creatinine and total bilirubin. Our result also suggested a significant positive correlation between the frailty index and the increased risk of CVD mortality among non-diabetic [OR 3.095, 95%CI (2.858, 3.352), P < 0.001] and prediabetic [OR 5.985, 95%CI (5.188, 6.904), P < 0.001] individuals. However, in patients with diabetes, the correlation between frailty and CVD mortality lost significance after adjusting for possible confounding factors [OR 1.139, 95%CI (0.794, 1.634), P > 0.05]. CONCLUSION: A nonlinear relationship has been identified between the FI and all-cause mortality, as well as CVD mortality in non-diabetic and pre-diabetic population. In diabetic patients, there was a significant positive correlation between the frailty and the increased risk of all-cause mortality, but not with CVD mortality. Renal function and liver function might potentially acted as an intermediary factor that elevated the risk of CVD mortality in frail patients with diabetes.

Successful creation and long-term usage of radiocephalic fistula based on the recanalized completely occluded radial artery.

The total occlusion of radial artery is a contraindication for reintervention and further usage. In this study, we report successful revascularization with creation of radiocephalic fistula from post-procedural chronically-occluded radial artery. The completely occluded radial artery was recanalized through ultrasound guided balloon angioplasty. A traditional radiocephalic fistula was created subsequently by using the recanalized radial artery for hemodialysis therapy. Though the fistula was failed at the 6 weeks caused by the juxta anastomotic stenosis, the further ultrasound guided percutaneous transluminal angioplasty restored the blood, and the hemodialysis therapy lasts for more than 1 year so far. It's feasible to create radiocephalic fistula based on the recanalized radial artery and maintain long-term hemodialysis therapy.

Assessment of Sonographic Parameters for Predicting Primary Patency Rate in Hemodialysis Patients With Venous Valve-Related Stenosis.

OBJECTIVES: Ultrasonography is more frequently used in patients with arteriovenous fistula (AVF) stenosis. The aim of this study is to use sonographic parameters for predicting primary patency in hemodialysis patients with venous valve-related stenosis (VVRS) who are treated by ultrasound-guided percutaneous transluminal angioplasty (PTA). METHODS: A total of 229 VVRS patients who underwent PTA between January 2017 and December 2021 were enrolled. Clinical characteristics were retrospectively collected. Sonographic parameters were measured both before and after PTA. Univariate and multivariate Cox analyses were performed to identify independent factors associated with primary patency rate. RESULTS: All measured sonographic parameters improved after PTA compared to before PTA. Before PTA, the diameter of VVRS > 1.0 mm, age ≤ 57 years, and body mass index (BMI) > 21.57 kg/m2 were associated with better outcomes. While the diameter of radial artery, proximal radial artery close to the anastomosis, brachial artery, the flow volume of brachial artery, the length and peak velocity (PV) of the VVRS, and the diameter and PV after the VVRS had no association with the primary patency rate. After PTA, only patients with a diameter of VVRS > 4.0 mm had favorable outcome. In addition, patients with a gain of diameter of VVRS > 2.4 mm after PTA had a trend of better outcomes. CONCLUSIONS: The diameter of VVRS before and after PTA could be served as markers to predict primary patency rate and second patency rate in AVF patients with VVRS. The gain of diameter of VVRS could also be a potential marker. CLINICAL IMPACT: Using simple markers of sonographic parameters, we could quickly identify patients with a higher risk of restenosis. These patients should be followed more closely in case of restenosis at early. It is also beneficial to the prevention of thrombosis. These measures help to preserve more valuable vascular for a long-term dialysis. Additionally, the physician should pay more attention on the dialysis-related complications in these risky patients, such as hemodialysis-related hypotension.

Analysis of factors affecting pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound ablation: a retrospective study.

OBJECTIVES: To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis. RESULTS: After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05). CONCLUSIONS: HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.

Systemic inflammatory response index as a predictor of stroke-associated pneumonia in patients with acute ischemic stroke treated by thrombectomy: a retrospective study.

BACKGROUND: The predictive value of systemic inflammatory response index (SIRI) for stroke-associated pneumonia (SAP) risk in patients with acute ischemic stroke (AIS) treated by thrombectomy remains unclear. This study aimed to investigate the predictive value of SIRI for SAP in patients with AIS treated by thrombectomy. METHODS: We included AIS patients treated by thrombectomy between August 2018 and August 2022 at our institute. We used multivariate logistic regression to construct the prediction model and performed a receiver operating characteristic curve analysis to evaluate the ability of SIRI to predict SAP and constructed a calibration curve to evaluate the prediction accuracy of the model. We evaluated the clinical application value of the nomogram using decision curve analysis. RESULTS: We included 84 eligible patients with AIS in the analysis, among which 56 (66.7%) had SAP. In the univariate analysis, there were significant differences in sex (p = 0.035), National Institute of Health Stroke Scale score at admission ≥ 20 (p = 0.019) and SIRI (p < 0.001). The results of multivariable logistic analysis showed that the risk of SAP increased with the SIRI value (OR = 1.169, 95% CI = 1.049-1.344, p = 0.014). Age ≥ 60 (OR = 4.076, 95% CI = 1.251-14.841, p = 0.024) was also statistically significant. A nomogram with SIRI showed good prediction accuracy for SAP in AIS patients treated by thrombectomy (C-index value = 0.774). CONCLUSIONS: SIRI is an independent predictor for SAP in patients with AIS treated by thrombectomy. A high SIRI value may allow for the early identification of patients with AIS treated by thrombectomy at high risk for SAP.

Machine learning-based prediction model for the efficacy and safety of statins.

Objective: The appropriate use of statins plays a vital role in reducing the risk of atherosclerotic cardiovascular disease (ASCVD). However, due to changes in diet and lifestyle, there has been a significant increase in the number of individuals with high cholesterol levels. Therefore, it is crucial to ensure the rational use of statins. Adverse reactions associated with statins, including liver enzyme abnormalities and statin-associated muscle symptoms (SAMS), have impacted their widespread utilization. In this study, we aimed to develop a predictive model for statin efficacy and safety based on real-world clinical data using machine learning techniques. Methods: We employed various data preprocessing techniques, such as improved random forest imputation and Borderline SMOTE oversampling, to handle the dataset. Boruta method was utilized for feature selection, and the dataset was divided into training and testing sets in a 7:3 ratio. Five algorithms, including logistic regression, naive Bayes, decision tree, random forest, and gradient boosting decision tree, were used to construct the predictive models. Ten-fold cross-validation and bootstrapping sampling were performed for internal and external validation. Additionally, SHAP (SHapley Additive exPlanations) was employed for feature interpretability. Ultimately, an accessible web-based platform for predicting statin efficacy and safety was established based on the optimal predictive model. Results: The random forest algorithm exhibited the best performance among the five algorithms. The predictive models for LDL-C target attainment (AUC = 0.883, Accuracy = 0.868, Precision = 0.858, Recall = 0.863, F1 = 0.860, AUPRC = 0.906, MCC = 0.761), liver enzyme abnormalities (AUC = 0.964, Accuracy = 0.964, Precision = 0.967, Recall = 0.963, F1 = 0.965, AUPRC = 0.978, MCC = 0.938), and muscle pain/Creatine kinase (CK) abnormalities (AUC = 0.981, Accuracy = 0.980, Precision = 0.987, Recall = 0.975, F1 = 0.981, AUPRC = 0.987, MCC = 0.965) demonstrated favorable performance. The most important features of LDL-C target attainment prediction model was cerebral infarction, TG, PLT and HDL. The most important features of liver enzyme abnormalities model was CRP, CK and number of oral medications. Similarly, AST, ALT, PLT and number of oral medications were found to be important features for muscle pain/CK abnormalities. Based on the best-performing predictive model, a user-friendly web application was designed and implemented. Conclusion: This study presented a machine learning-based predictive model for statin efficacy and safety. The platform developed can assist in guiding statin therapy decisions and optimizing treatment strategies. Further research and application of the model are warranted to improve the utilization of statin therapy.

Protective effects of Nogo-B deficiency in NAFLD mice and its multiomics analysis of gut microbiology and metabolism.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver ailment that can lead to serious conditions such as cirrhosis and hepatocellular carcinoma. Hepatic Nogo-B regulates glucose and lipid metabolism, and its inhibition has been shown to be protective against metabolic syndrome. Increasing evidence suggests that imbalances in the gut microbiota (GM) and lipid metabolism disorders are significant contributors to NAFLD progression. Nevertheless, it is not yet known whether Nogo-B can affect NAFLD by influencing the gut microbiota and metabolites. Hence, the aim of the present study was to characterize this process and explore its possible underlying mechanisms. METHODS: A NAFLD model was constructed by administering a high-fat diet (HFD) to Nogo-B-/- and WT mice from the same litter, and body weight was measured weekly in each group. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to assess blood glucose levels. At the end of the 12-week period, samples of serum, liver, and intestinal contents were collected and used for serum biochemical marker and inflammatory factor detection; pathology evaluation; and gut microbiome and metabolomics analysis. Spearman's correlation analysis was performed to determine possible correlations between differential gut microbiota and differential serum metabolites between groups. RESULTS: Nogo-B deficiency attenuated the effects of the HFD, including weight gain, liver weight gain, impaired glucose tolerance, hepatic steatosis, elevated serum lipid biochemicals levels, and liver function. Nogo-B deficiency suppressed M1 polarization and promoted M2 polarization, thus inhibiting inflammatory responses. Furthermore, Nogo-B-/--HFD-fed mice presented increased gut microbiota richness and diversity, decreased Firmicutes/Bacteroidota (F/B) ratios, and altered serum metabolites compared with those of WT-HFD-fed mice. During analysis, several differential gut microbiota, including Lachnoclostridium, Harryflintia, Odoribacter, UCG-009, and unclassified_f_Butyricoccaceae, were screened between groups. These microbiota were found to be positively correlated with upregulated purine metabolism and bile acid metabolites in Nogo-B deficiency, while they were negatively correlated with downregulated corticosterone and tricarboxylic acid cyclic metabolites in Nogo-B deficiency. CONCLUSION: Nogo-B deficiency delayed NAFLD progression, as demonstrated by reduced hepatocellular lipid accumulation, attenuated inflammation and liver injury, and ameliorated gut microbiota dysbiosis and metabolic disorders. Importantly, Odoribacter was strongly positively correlated with ALB and taurodeoxycholic acid, suggesting that it played a considerable role in the influence of Nogo-B on the progression of NAFLD, a specific feature of NAFLD in Nogo-B-/- mice. The regulation of bile acid metabolism by the gut microbiota may be a potential target for Nogo-B deficiency to ameliorate NAFLD.

The genetic diversity and evolution analysis of the Hainan melioidosis outbreak strains.

Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon "Dianmu" from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak. Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections.