Safety analysis of Oseltamivir and Baloxavir Marboxil after market approval: a pharmacovigilance study based on the FDA adverse event reporting system.

BACKGROUND AND OBJECTIVES: Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references. METHODS: A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug. RESULTS: Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01-9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74-9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15-32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98-57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43-52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26]. CONCLUSION: Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir's potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.

Mfn2 regulates mitochondria and mitochondria-associated endoplasmic reticulum membrane function in neurodegeneration induced by repeated sevoflurane exposure.

Repeated sevoflurane exposure in neonatal mice can leads to neuronal apoptosis and mitochondrial dysfunction. The mitochondria are responsible for energy production to maintain homeostasis in the central nervous system. The mitochondria-associated endoplasmic reticulum membrane (MAM) is located between the mitochondria and endoplasmic reticulum (ER), and it is critical for mitochondrial function and cell survival. MAM malfunction contributes to neurodegeneration, however, whether it is involved in sevoflurane-induced neurotoxicity remains unknown. Our study demonstrated that repeated sevoflurane exposure induced mitochondrial dysfunction and dampened the MAM structure. The upregulated ER-mitochondria tethering enhanced Ca2+ transition from the cytosol to the mitochondria. Overload of mitochondrial Ca2+ contributed to opening of the mitochondrial permeability transition pore (mPTP), which caused neuronal apoptosis. Mitofusin 2(Mfn2), a key regulator of ER-mitochondria contacts, was found to be suppressed after repeated sevoflurane exposure, while restoration of Mfn2 expression alleviated cognitive dysfunction due to repeated sevoflurane exposure in the adult mice. These evidences suggest that sevoflurane-induced MAM malfunction is vulnerable to Mfn2 suppression, and the enhanced ER-mitochondria contacts promotes mitochondrial Ca2+ overload, contributing to mPTP opening and neuronal apoptosis. This paper sheds light on a novel mechanism of sevoflurane-induced neurotoxicity. Furthermore, targeting Mfn2-mediated regulation of the MAM structure and mitochondrial function may provide a therapeutic advantage in sevoflurane-induced neurodegeneration.

Chemical constituents with antioxidant activity from the branches and leaves of Hultholia mimosoides.

Four undescribed homoisoflavanoids (1-4), one homoflavonoid (5), ten dibenzoxocin derivatives (6a-10a and 6b-10b), one dibenzoxocin-derived phenolic compound (11), one diterpenoid (13), three aliphatic dicarboxylic acid derivatives (14-16), together with the known diterpenoid 12-O-ethylneocaesalpin B (12) were obtained from the branches and leaves of Hultholia mimosoides. Their structures were elucidated by extensive spectroscopic techniques. Notably, each of the dibenzoxocins 6-10 existed as a pair of interconvertible atropisomers and the conformation for these compounds was clarified by NMR and ECD analyses. Protosappanin F (11) was a previously undescribed dibenzoxocin-derived compound in which one of the benzene rings was hydrogenated to a polyoxygenated cyclohexane ring and an ether linkage was established between C-6 and C-12a. The isolated polyphenols were tested for induction of quinone reductase and compounds 3 and 8 showed potent QR-inducing activity in Hepa-1c1c7 cells.

Exploring machine learning strategies for predicting cardiovascular disease risk factors from multi-omic data.

BACKGROUND: Machine learning (ML) classifiers are increasingly used for predicting cardiovascular disease (CVD) and related risk factors using omics data, although these outcomes often exhibit categorical nature and class imbalances. However, little is known about which ML classifier, omics data, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate and compare different machine learning strategies to predict CVD risk factors under different scenarios. METHODS: We compared the use of six ML classifiers in predicting CVD risk factors using blood-derived metabolomics, epigenetics and transcriptomics data. Upstream omic dimension reduction was performed using either unsupervised or semi-supervised autoencoders, whose downstream ML classifier performance we compared. CVD risk factors included systolic and diastolic blood pressure measurements and ultrasound-based biomarkers of left ventricular diastolic dysfunction (LVDD; E/e' ratio, E/A ratio, LAVI) collected from 1,249 Finnish participants, of which 80% were used for model fitting. We predicted individuals with low, high or average levels of CVD risk factors, the latter class being the most common. We constructed multi-omic predictions using a meta-learner that weighted single-omic predictions. Model performance comparisons were based on the F1 score. Finally, we investigated whether learned omic representations from pre-trained semi-supervised autoencoders could improve outcome prediction in an external cohort using transfer learning. RESULTS: Depending on the ML classifier or omic used, the quality of single-omic predictions varied. Multi-omics predictions outperformed single-omics predictions in most cases, particularly in the prediction of individuals with high or low CVD risk factor levels. Semi-supervised autoencoders improved downstream predictions compared to the use of unsupervised autoencoders. In addition, median gains in Area Under the Curve by transfer learning compared to modelling from scratch ranged from 0.09 to 0.14 and 0.07 to 0.11 units for transcriptomic and metabolomic data, respectively. CONCLUSIONS: By illustrating the use of different machine learning strategies in different scenarios, our study provides a platform for researchers to evaluate how the choice of omics, ML classifiers, and dimension reduction can influence the quality of CVD risk factor predictions.

Tumor-derived extracellular vesicles regulate macrophage polarization: role and therapeutic perspectives.

Extracellular vesicles (EVs) are important cell-to-cell communication mediators. This paper focuses on the regulatory role of tumor-derived EVs on macrophages. It aims to investigate the causes of tumor progression and therapeutic directions. Tumor-derived EVs can cause macrophages to shift to M1 or M2 phenotypes. This indicates they can alter the M1/M2 cell ratio and have pro-tumor and anti-inflammatory effects. This paper discusses several key points: first, the factors that stimulate macrophage polarization and the cytokines released as a result; second, an overview of EVs and the methods used to isolate them; third, how EVs from various cancer cell sources, such as hepatocellular carcinoma, colorectal carcinoma, lung carcinoma, breast carcinoma, and glioblastoma cell sources carcinoma, promote tumor development by inducing M2 polarization in macrophages; and fourth, how EVs from breast carcinoma, pancreatic carcinoma, lungs carcinoma, and glioblastoma cell sources carcinoma also contribute to tumor development by promoting M2 polarization in macrophages. Modified or sourced EVs from breast, pancreatic, and colorectal cancer can repolarize M2 to M1 macrophages. This exhibits anti-tumor activities and offers novel approaches for tumor treatment. Therefore, we discovered that macrophage polarization to either M1 or M2 phenotypes can regulate tumor development. This is based on the description of altering macrophage phenotypes by vesicle contents.

The mechanism of biofilm detachment in porous medium under flow field.

Biofilms are communities formed by bacteria adhering to surfaces, widely present in porous medium, and their growth can lead to clogging. Our experiment finds that under certain flow conditions, biofilms detach in pores and form a dynamically changing flow path. We define detachment that occurs far from the boundary of the flow path (with a distance greater than 200 µm) as internal detachment and detachment that occurs at the boundary of the flow path as external detachment. To understand the mechanism of biofilm detachment, we study the detachment behaviors of the Bacillus subtilis biofilm in a porous medium in a microfluidic device, where Bacillus subtilis strain is triple fluorescent labeled, which can represent three main phenotypes during the biofilm formation: motile cells, matrix-producing cells, and spores. We find that slow small-scale internal detachment occurs in regions with very few motile cells and matrix-producing cells, and bacterial movement in these areas is disordered. The increase in the number of matrix-producing cells induces clogging, and after clogging, the rapid detachment of the bulk internal biofilm occurs due to the increased pressure difference at the inlet and outlet. When both internal and external detachments occur simultaneously, the number of matrix-producing cells in the internal detachment area is 2.5 times that in the external detachment area. The results indicate that biofilm detachment occurs in areas with fewer matrix-producing cells, as matrix-producing cells can help resist detachment by secreting extracellular polymeric substances (EPSs).

Prospective association between social isolation, loneliness and lung function among Chinese middle-aged and older adults.

OBJECTIVE: Previous research has highlighted a heightened occurrence of social isolation and loneliness in older adults diagnosed with chronic lung diseases. Nevertheless, there exists a dearth of studies that have explored the influence of impoverished social relationships on lung function. This study aimed to examine the longitudinal association between social isolation, loneliness and lung function over 4 years among middle-aged and older Chinese adults. METHODS: This study employed two waves (2011 and 2015) of data from the China Health and Retirement Longitudinal Study (CHARLS). The analysis was limited to participants aged 45 years and above and stratified based on gender (3325 men and 3794 women). The measurement of peak expiratory flow (PEF) served as an indicator for assessing lung function. Lagged dependent variable regression models, accounting for covariates, were employed to explore the relationship between baseline social isolation and loneliness and the subsequent PEF. RESULTS: For women, social isolation was significantly associated with the decline in PEF at follow-up (ß = -.06, p < .001) even after adjusting for all covariates; no significant correlation was observed between loneliness and PEF. Among men, there was no significant association found between either social isolation or loneliness and PEF. CONCLUSIONS: Social isolation is prospectively associated with worse lung function in middle-aged and older Chinese women but not men. The results highlight the importance of promoting social relationships in public health initiatives, especially in groups that are more vulnerable.

Synaptic vesicle glycoprotein 2 A in serum is an ideal biomarker for early diagnosis of Alzheimer's disease.

BACKGROUND: Previous studies have demonstrated that early intervention was the best plan to inhibit the progression of Alzheimer's disease (AD), which relied on the discovery of early diagnostic biomarkers. In this study, synaptic vesicle glycoprotein 2 A (SV2A) was examined to improve the early diagnostic efficiency in AD. METHODS: In this study, biomarker testing was performed through the single-molecule array (Simoa). A total of 121 subjects including cognitively unimpaired controls, amnestic mild cognitive impairment (aMCI), AD and other types of dementia underwent cerebrospinal fluid (CSF) SV2A testing; 430 subjects including health controls, aMCI, AD and other types of dementia underwent serum SV2A, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and p-tau217 testing; 92 subjects including aMCI and AD underwent both CSF SV2A and serum SV2A testing; 115 cognitively unimpaired subjects including APOE ε4 carriers and APOE ε4 non-carriers were tested for serum SV2A, GFAP, NfL and p-tau217. Then, the efficacy of SV2A for the early diagnosis of AD and its ability to identify those at high risk of AD from a cognitively unimpaired population were further analyzed. RESULTS: Both CSF and serum SV2A significantly and positively correlated with cognitive performance in patients with AD, and their levels gradually decreased with the progression of AD. Serum SV2A demonstrated excellent diagnostic efficacy for aMCI, with a sensitivity of 97.8%, which was significantly higher than those of NfL, GFAP, and p-tau217. The SV2A-positive rates ranged from 92.86 to 100% in aMCI cases that were negative for the above three biomarkers. Importantly, of all the biomarkers tested, serum SV2A had the highest positivity rate (81.82%) in individuals at risk for AD. CONCLUSIONS: Serum SV2A was demonstrated to be a novel and ideal biomarker for the early diagnosis of AD, which can effectively distinguish those at high risk of AD in cognitively unimpaired populations.

Association of two novel systemic inflammatory biomarkers and frailty based on NHANES 2007-2018.

Background: Frailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States. Methods: This study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot. Results: This study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24-1.54) and 1.69 (1.53-1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55-2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10-1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95-2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty. Conclusion: The results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

Virulence Factors and Carbapenem-Resistance Mechanisms in Hypervirulent Klebsiella Pneumoniae.

Hypervirulent Klebsiella pneumoniae (hvKP) has emerged as a novel variant of K. pneumoniae, exhibiting distinct phenotypic and genotypic characteristics that confer increased virulence and pathogenicity. It is not only responsible for nosocomial infections but also community-acquired infections, including liver abscesses, endophthalmitis, and meningitis, leading to significant morbidity and mortality. HvKP has been reported all over the world, but it is mainly prevalent in Asia Pacific, especially China. Moreover, hvKP can acquire carbapenemase genes resulting in the emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP), which possesses both high virulence and drug resistance capabilities. Consequently, CR-hvKP poses substantial challenges to infection control and presents serious threats to global public health. In this paper, we provide a comprehensive summary of the epidemiological characteristics, virulence factors, and mechanisms underlying carbapenem resistance in hvKP strains with the aim of offering valuable insights for practical prevention strategies as well as future research.

Failure probability analysis of high fill levee considering multiple uncertainties and correlated failure modes.

Such complex causative factors in current failure probability models are represented by simply random uncertainty and completely independent or correlation of failure modes, which can often limit the model utility. In this study, we developed a methodology to construct failure probability models for high fill levees, incorporating the identification of uncertainties and an analysis of failure modes. Based on quantification of stochastic-grey-fuzzy uncertainties, probability analysis involved with overtopping, instability and seepage failure modes was implemented combined with probability and non-probability methods. Given that the interaction among failure modes typically exhibits nonlinear behavior, rather than linear correlation or complete independence, a simple methodology for the binary Copula function was established and implemented in MATLAB. This methodology was applied to the high fill segments of a long-distance water transfer project characterized by high population density. It shows that the failure probability of a single failure mode is overestimated when uncertainties are not considered, because of the randomness and fuzziness of some parameters and the greyness of information. Meanwhile, it is found that the magnitude of failure probability related to levee breach is overestimated without respect to failure modes correlation, especially when the probabilities of seepage and instability are both significant and closely aligned.

Advances in tumor microenvironment and underlying molecular mechanisms of bladder cancer: a systematic review.

Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer-which are believed to be connected to the malfunction of multigene and multilevel cell signaling network-remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer.

The long-term cost-effectiveness of once-weekly semaglutide versus sitagliptin for the treatment of type 2 diabetes in China.

BACKGROUND: To estimate the long-term cost-effectiveness of once-weekly semaglutide versus sitagliptin as an add-on therapy for type 2 diabetes patients inadequately controlled on metformin in China, to better inform healthcare decision making. METHODS: The Cardiff diabetes model which is a Monte Carlo micro-simulation model was used to project short-term effects of once-weekly semaglutide versus sitagliptin into long-term outcomes. Short-term data of patient profiles and treatment effects were derived from the 30-week SUSTAIN China trial, in which 868 type 2 diabetes patients with a mean age of 53.1 years inadequately controlled on metformin were randomized to receive once-weekly semaglutide 0.5 mg, once-weekly semaglutide 1 mg, or sitagliptin 100 mg. Costs and quality-adjusted life years (QALYs) were estimated from a healthcare system perspective at a discount rate of 5%. Univariate sensitivity analysis, scenario analysis, and probabilistic sensitivity analysis were conducted to test the uncertainty. RESULTS: Over patients' lifetime projections, patients in both once-weekly semaglutide 0.5 mg and 1 mg arms predicted less incidences of most vascular complications, mortality, and hypoglycemia, and lower total costs compared with those in sitagliptin arm. For an individual patient, compared with sitagliptin, once-weekly semaglutide 0.5 mg conferred a small QALY improvement of 0.08 and a lower cost of $5173, while once-weekly semaglutide 1 mg generated an incremental QALY benefit of 0.12 and a lower cost of $7142, as an add-on to metformin. Therefore, both doses of once-weekly semaglutide were considered dominant versus sitagliptin with more QALY benefits at lower costs. CONCLUSION: Once-weekly semaglutide may represent a cost-effective add-on therapy alternative to sitagliptin for type 2 diabetes patients inadequately controlled on metformin in China.

Altered functional brain activity in first-episode major depressive disorder treated with electro-acupuncture: A resting-state functional magnetic resonance imaging study.

Background: Previous studies have found electroacupuncture could improve the clinical symptoms of first-episode major depressive disorder (MDD), but the exact neural mechanism of action needs to be further elucidated. Methods: Twenty-eight first-episode MDD patients were randomly divided into 14 electro-acupuncture stimulation (EAS) groups and 14 sham-acupuncture stimulation (SAS) groups, and clinical symptoms were assessed and functional magnetic resonance imaging (fMRI) scans were done in both groups. Amplitude of low-frequency fluctuations (ALFF) was used to observe the changes between the pre-treatment and post-treatment in the two groups, and the altered brain areas were selected as region of interest (ROI) to observe the FC changes. Meanwhile, the correlation between the altered clinical symptoms and the altered ALFF and FC of brain regions in the two groups was analyzed. Results: The EAS significantly decreased the HAMD-24 and HAMA-14 scores of MDD than SAS group. The imaging results revealed that both groups were able to increase the ALFF of the left middle temporal gyrus and the left cerebellar posterior lobe. When using the left middle temporal gyrus and the left posterior cerebellar lobe as ROIs, EAS group increased the FC between the left middle temporal gyrus with the left superior frontal gyrus, the left middle frontal gyrus, and the left hippocampus, and decreased the FC between the left posterior cerebellar lobe and the left calcarine gyrus, while SAS group only increased the FC between the left middle temporal gyrus with the left superior frontal gyrus. The alternations in clinical symptoms after EAS treatment were positively correlated with the altered ALFF values in the left middle temporal gyrus and the altered FC values in the left middle temporal gyrus and the left middle frontal gyrus. Conclusion: EA demonstrates modulation of functional activity in the default mode network (DMN), sensorimotor network (SMN), cognitive control network (CCN), limbic system, and visual network (VN) for the treatment of the first-episode MDD. Our findings contribute to the neuroimaging evidence for the efficacy of EAS.

Examining the interplay between cardiovascular disease and cancer incidence: Data from NHANES III and continuous.

Introduction: This study aimed to investigate the relationship between risk factors of cancer among individuals with existing cardiovascular disease (CVD). Methods: The analysis included 438 and 2100 CVD patients aged 65+ from NHANES-III and Continuous datasets, respectively. Competing risk models with subdistribution hazards ratio (aHR) were used to identify risk factors. Results: Females in NHANES-III had lower cancer risk (aHR 0.39, P = 0.001) compared to males. Poor physical activity was associated with increased cancer risk in both datasets (aHR 2.59 in NHANES-III, aHR 1.59 in Continuous). In NHANES-Continuous, age (aHR 1.07, P < 0.001) and current smoking (aHR 2.55, P = 0.001) also showed a significant association with developing cancer. No other factors investigated showed significant associations. Discussion: This study highlights the interplay between traditional risk factors and the elevated risk of cancer in CVD patients. Further research with larger samples and wider age ranges is needed to solidify these findings and inform intervention strategies.

A longitudinal study of blood pressure circadian rhythm from childhood to early adulthood.

Altered blood pressure (BP) circadian rhythmicity has been increasingly linked with cardiovascular risk. However, little is known about BP circadian rhythm change with age and its possible sociodemographic, anthropometric, and genetic moderators. Twenty-four-hour ambulatory BP was measured up to 16 times over a 23-year period in 339 European Americans (EAs) and 293 African Americans (AAs), with an average age of 15 years at the initial visit. BP circadian rhythms were indexed by amplitude and percent rhythm (a measure of rhythm integrity) and calculated using Fourier analysis. BP amplitude and percent rhythm increased with age and average BP (BP mesor). AAs were more likely to have lower BP amplitude and percent rhythm than their EA counterparts. BP amplitude and percent rhythm also decreased with adiposity (BMI and waist circumference). The summer season was associated with lower BP amplitude in AAs and lower percent rhythm in both AAs and EAs. Sex, height, socioeconomic status, physical activity, and family history of essential hypertension did not have an independent impact on BP amplitude or percent rhythm. The results of the present study suggest that BP circadian rhythm increases with age and BP mesor from childhood to young adulthood, decreases with adiposity, and that AAs are more likely to have lower circadian rhythm than EAs. Furthermore, we demonstrated that the summer season is associated with lower BP rhythmicity.

Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.

Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.

Effect of platelet-rich plasma on healing of lower extremity diabetic skin ulcers: A meta-analysis.

The aim of this research is to explore the therapeutic efficacy of platelet-rich plasma (PRP) on the cutaneous ulceration of diabetes mellitus (DM). From the beginning of the database until January 2024, we looked through several databases to obtain randomised, controlled PRP studies to treat the wound healing of DM in adult patients. The Cochrane Collaboration's Risk-Of-Bias Instrument was used to evaluate the risk of bias in randomised, controlled studies. Funnel plots, sensitivity analyses and Egger regression tests were employed to determine the reliability and effectiveness of the meta-analyses. Depending on the degree of heterogeneity, a fixed or random effect model has been used. The statistical significance was determined to be below 0.05. Altogether 281 trials were collected from the database and entered into Endnote Software for screening, and 15 trials were analysed. It was found that PRP was associated with a higher rate of wound healing (OR, 3.23; 95% CI, 2.42, 4.31 p < 0.0001). PRP was associated with a reduction in the risk of post-operative wound infection (OR, 0.46; 95% CI, 0.21, 0.99 p = 0.05). PRP was associated with a reduction in the risk of amputations amongst those with DM (OR, 0.50; 95% CI, 0.30, 0.84 p = 0.009). Overall, PRP treatment for DM is expected to improve the rate of wound healing, decrease the risk of wound infection and decrease the risk of amputations.

Optimization of Bear Oil Extraction Process and Hair Growth Activity.

According to ancient Chinese books, bear grease has the effects of strengthening muscles and bones, which is beneficial for weakness, but there is relatively little research on it. Thus, the extraction of it is beneficial for compensating for research in this area. In this study, a uniform experimental design method was used to optimize the extraction process of bear grease by enzymatic hydrolysis extraction, and the extraction rate can reach 81.89% under optimized extraction conditions. Furthermore, the components of bear grease obtained by this study were analyzed by GC-MS, and the results showed that ursolic oil was rich in unsaturated fatty acids (67.51%), which was higher than that of the traditional method (66.92%). The composition of bear grease extracted by the enzymatic method was also better than that extracted by the traditional method. In addition, bear grease obtained in this study had the obvious activity of promoting hair growth. The length, weight, and number of hair follicles in the depilation area of mice in the high-dose group were significantly different from those in the blank group (p < 0.01). This study optimized the extraction process of bear grease and conducted a preliminary analysis of its fatty acid composition, which is expected to provide some reference for the development of the medicinal value of bear grease.

Controllable editing via diffusion inversion on ultra-widefield fluorescein angiography for the comprehensive analysis of diabetic retinopathy.

By incorporating multiple indicators that facilitate clinical decision making and effective management of diabetic retinopathy (DR), a comprehensive understanding of the progression of the disease can be achieved. However, the diversity of DR complications poses challenges to the automatic analysis of various information within images. This study aims to establish a deep learning system designed to examine various metrics linked to DR in ultra-widefield fluorescein angiography (UWFA) images. We have developed a unified model based on image generation that transforms input images into corresponding disease-free versions. By incorporating an image-level supervised training process, the model significantly reduces the need for extensive manual involvement in clinical applications. Furthermore, compared to other comparative methods, the quality of our generated images is significantly superior.