Network Analysis of Dyadic Burdens, Psychological Disorders, Psychological Resilience, and Illness- or Caregiving-Related Beliefs in Patients With Chronic Heart Failure and Their Caregivers.

BACKGROUND: Previous research has examined the dyadic health components consisting of dyadic burdens, psychological disorders, psychological resilience, and illness- or caregiving-related beliefs independently from each other in patients with chronic heart failure (CHF) and their caregivers, but there is a need for further insights into their interconnections. OBJECTIVE: We aimed to explore the interconnections among dyadic health components in patients with CHF and their caregivers. METHODS: We conducted a cross-sectional study, recruiting in a total of 355 patients with CHF and their 355 respective caregivers, totaling 710 individuals across the dyads. Assessments were conducted on symptom burden, caregiver burden, anxiety, depression, psychological resilience, perceived control, and caregiver self-efficacy. Network analysis was used regarding these constructs as nodes and their associations as edges. RESULTS: The strongest edge weight was observed between patients' anxiety and depression, followed by caregivers' anxiety and depression. Patients' depression exhibited the strongest edge weight with dyadic burdens. Caregiver burden was independently correlated with all nodes. Patients' symptom burden had fewer associations with the nodes within the caregiver community. Patients' anxiety, depression, and psychological resilience demonstrated the strongest and most influential correlations with other nodes. CONCLUSIONS: The findings illustrated extensive interconnections among dyadic health components in CHF dyads. These findings underscored the significance of managing and intervening with patients and caregivers as a dyadic whole. Given the strong and frequent associations of patients' anxiety, depression, and psychological resilience with other nodes in the network, interventions targeting these nodes may enhance the overall network health of CHF dyads.

Antisolvent precipitation for the synergistic preparation of ultrafine particles of nobiletin under ultrasonication-homogenization and evaluation of the inhibitory effects of α-glucosidase and porcine pancreatic lipase in vitro.

To further enhance the application of nobiletin (an important active ingredient in Citrus fruits), we used ultrasonic homogenization-assisted antisolvent precipitation to create ultrafine particles of nobiletin (UPN). DMSO was used as the solvent, and deionized water was used as the antisolvent. When ultrasonication (670 W) and homogenization (16000 r/min) were synergistic, the solution concentration was 57 mg/mL, and the minimum particle size of UPN was 521.02 nm. The UPN samples outperformed the RN samples in terms of the inhibition of porcine pancreatic lipase, which was inhibited (by 500 mg/mL) by 68.41 % in the raw sample, 90.34 % in the ultrafine sample, and 83.59 % in the positive control, according to the data. Fourier transform infrared spectroscopy analysis revealed no chemical changes in the samples before or after preparation. However, the crystallinity of the processed ultrafine nobiletin particles decreased. Thus, this work offers significant relevance for applications in the realm of food chemistry and indirectly illustrates the expanded application potential of nobiletin.

The Association Between Impaired Dyadic Coping and Frailty in Elderly Patients With Hypertension: A Latent Profile Analysis.

BACKGROUND: Lifelong hypertension highlights the importance of dyadic engagement in coping with the disease. Although dyadic coping is heterogeneous in patients with other diseases, little is known about it in elderly patients with hypertension. In addition, whether impaired dyadic coping is associated with frailty has yet to be elucidated. OBJECTIVES: The aim of this study was to investigate the latent profiles and characteristics of dyadic coping and the potential association between impaired dyadic coping and frailty in elderly patients with hypertension. METHODS: We recruited a total of 741 elderly patients with hypertension. Latent profile analysis was then used to identify the best-fitting model. Then, we used regression analysis to determine profile predictors and identify the association between impaired dyadic coping and frailty. RESULTS: The 5-profile model was considered to be the best-fitting model, as follows: profile 1, severely impaired dyadic coping; profile 2, mildly impaired dyadic coping; profile 3, normal dyadic coping; profile 4, better dyadic coping; and profile 5, the highest dyadic coping. In the fully adjusted model, the probability of frailty was 1.94-fold higher in the mildly impaired dyadic coping group (odds ratio, 1.94; 95% confidence interval, 1.09-3.47) and 2.66-fold higher in the severely impaired dyadic coping group (odds ratio, 2.66; 95% confidence interval, 1.11-6.39). CONCLUSIONS: We identified heterogeneity in dyadic coping and demonstrated that impaired dyadic coping was associated with frailty. Those at risk of dyadic coping impairment need to be identified early, followed by dyadic coping-based interventions to prevent or delay frailty.

The Prognostic Value of Serum Calcium Levels in Elderly Dilated Cardiomyopathy Patients.

Background: It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. Methods: A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. Results: In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan-Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Conclusions: Serum calcium level could be served as a simple and affordable tool to evaluate patients' prognosis in DCM.

Synthesis of site-specific Fab-drug conjugates using ADP-ribosyl cyclases.

Targeted delivery of small-molecule drugs via covalent attachments to monoclonal antibodies has proved successful in clinic. For this purpose, full-length antibodies are mainly used as drug-carrying vehicles. Despite their flexible conjugation sites and versatile biological activities, intact immunoglobulins with conjugated drugs, which feature relatively large molecular weights, tend to have restricted tissue distribution and penetration and low fractions of payloads. Linking small-molecule therapeutics to other formats of antibody may lead to conjugates with optimal properties. Here, we designed and synthesized ADP-ribosyl cyclase-enabled fragment antigen-binding (Fab) drug conjugates (ARC-FDCs) by utilizing CD38 catalytic activity. Through rapidly forming a stable covalent bond with a nicotinamide adenine dinucleotide (NAD+ )-based drug linker at its active site, CD38 genetically fused with Fab mediates robust site-specific drug conjugations via enzymatic reactions. Generated ARC-FDCs with defined drug-to-Fab ratios display potent and antigen-dependent cytotoxicity against breast cancer cells. This work demonstrates a new strategy for developing site-specific FDCs. It may be applicable to different antibody scaffolds for therapeutic conjugations, leading to novel targeted agents.

Reservoir rock typing assessment in a coal-tight sand based heterogeneous geological formation through advanced AI methods.

Geoscientists now identify coal layers using conventional well logs. Coal layer identification is the main technical difficulty in coalbed methane exploration and development. This research uses advanced quantile-quantile plot, self-organizing maps (SOM), k-means clustering, t-distributed stochastic neighbor embedding (t-SNE) and qualitative log curve assessment through three wells (X4, X5, X6) in complex geological formation to distinguish coal from tight sand and shale. Also, we identify the reservoir rock typing (RRT), gas-bearing and non-gas bearing potential zones. Results showed gamma-ray and resistivity logs are not reliable tools for coal identification. Further, coal layers highlighted high acoustic (AC) and neutron porosity (CNL), low density (DEN), low photoelectric, and low porosity values as compared to tight sand and shale. While, tight sand highlighted 5-10% porosity values. The SOM and clustering assessment provided the evidence of good-quality RRT for tight sand facies, whereas other clusters related to shale and coal showed poor-quality RRT. A t-SNE algorithm accurately distinguished coal and was used to make CNL and DEN plot that showed the presence of low-rank bituminous coal rank in study area. The presented strategy through conventional logs shall provide help to comprehend coal-tight sand lithofacies units for future mining.

Increased GABA signaling in liver macrophage promotes HBV replication in HBV-carrier mice.

Gamma-aminobutyric acid (GABA) signals in various non-neuronal cells including hepatocytes and some immune cells. Studies, including ours, show that type A GABA receptors (GABAARs)-mediated signaling occurs in macrophages regulating tissue-specific functions. Our recent study reveals that activation of GABAARs in liver macrophages promotes their M2-like polarization and increases HBV replication in mice. This short article briefly summarizes the GABA signaling system in macrophages and discusses potential mechanisms by which GABA signaling promotes HBV replication.

Multi-Trajectories of Symptoms and their Associations with Unplanned 30-day Hospital Readmission among Patients with Heart Failure: A longitudinal study.

AIMS: This study aimed to uncover hidden patterns and predictors of symptom multi-trajectories within 30 days after discharge in patients with heart failure and assess the risk of unplanned 30-day hospital readmission in different patterns. METHODS AND RESULTS: The study was conducted from September 2022 to September 2023 in four third-class hospitals in Tianjin, China. A total of 301 patients with heart failure were enrolled in the cohort, and 248 patients completed a 30-day follow-up after discharge. Three multi-trajectory groups were identified: mild symptom status (24.19%), moderate symptom status (57.26%), and severe symptom status (18.55%). With the mild symptom status group as a reference, physical frailty, psychological frailty, and comorbid renal dysfunction were predictors of the moderate symptom status group. Physical frailty, psychological frailty, resilience, taking diuretics, and comorbid renal dysfunction were predictors of the severe symptom status group. Compared with the mild symptom status group, the severe symptom status group was significantly associated with high unplanned 30-day hospital readmission risks. CONCLUSIONS: This study identified three distinct multi-trajectory groups among patients with heart failure within 30 days after discharge. The severe symptom status group was associated with a significantly increased risk of unplanned 30-day hospital readmission. Common and different factors predicted different symptom multi-trajectories. Healthcare providers should assess the physical and psychological frailty and renal dysfunction of patients with heart failure before discharge. Inpatient care aimed at alleviating physical and psychological frailty and enhancing resilience may be important to improve patients' symptom development post-discharge.

Simulated drug disposition in critically ill patients to evaluate effective PK/PD targets for combating Pseudomonas aeruginosa resistance to meropenem.

Bacterial infections, including those caused by Pseudomonas aeruginosa, often lead to sepsis, necessitating effective antibiotic treatment like carbapenems. The key pharmacokinetic/pharmacodynamic (PK/PD) index correlated to carbapenem efficacy is the fraction time of unbound plasma concentration above the minimum inhibitory concentration (MIC) of the pathogen (%fT > MIC). While multiple targets exist, determining the most effective one for critically ill patients remains a matter of debate. This study evaluated meropenem's bactericidal potency and its ability to combat drug resistance in Pseudomonas aeruginosa under three representative PK/PD targets: 40% fT > MIC, 100% fT > MIC, and 100% fT > 4× MIC. The hollow fiber infection model (HFIM) was constructed, validated, and subsequently inoculated with a substantial Pseudomonas aeruginosa load (1 × 108 CFU/mL). Different meropenem regimens were administered to achieve the specified PK/PD targets. At specified intervals, samples were collected from the HFIM system and subjected to centrifugation. The resulting supernatant was utilized to determine drug concentrations, while the precipitates were used to track changes in both total and drug-resistant bacterial populations over time by the spread plate method. The HFIM accurately reproduced meropenem's pharmacokinetics in critically ill patients. All three PK/PD target groups exhibited a rapid bactericidal response within 6 h of the initial treatment. However, the 40% fT > MIC and 100% fT > MIC groups subsequently showed bacterial resurgence and resistance, whereas the 100% fT > 4× MIC group displayed sustained bactericidal activity with no evidence of drug resistance. The HFIM system revealed that maintaining 100% fT > 4× MIC offers a desirable microbiological response for critically ill patients, demonstrating strong bactericidal capacity and effective prevention of drug resistance.

Ethanolamine as a biomarker and biomarker-based therapy for diabetic retinopathy in glucose-well-controlled diabetic patients.

Diabetic retinopathy (DR) is the leading cause of blindness among the working-age population. Although controlling blood glucose levels effectively reduces the incidence and development of DR to less than 50%, there are currently no diagnostic biomarkers or effective treatments for DR development in glucose-well-controlled diabetic patients (GW-DR). In this study, we established a prospective GW-DR cohort by strictly adhering to glycemic control guidelines and maintaining regular retinal examinations over a median 2-year follow-up period. The discovery cohort encompassed 71 individuals selected from a pool of 292 recruited diabetic patients at baseline, all of whom consistently maintained hemoglobin A1c (HbA1c) levels below 7% without experiencing hypoglycemia. Within this cohort of 71 individuals, 21 subsequently experienced new-onset GW-DR, resulting in an incidence rate of 29.6%. In the validation cohort, we also observed a significant GW-DR incidence rate of 17.9%. Employing targeted metabolomics, we investigated the metabolic characteristics of serum in GW-DR, revealing a significant association between lower levels of ethanolamine and GW-DR risk. This association was corroborated in the validation cohort, exhibiting superior diagnostic performance in distinguishing GW-DR from diabetes compared to the conventional risk factor HbA1c, with AUCs of 0.954 versus 0.506 and 0.906 versus 0.521 in the discovery and validation cohorts, respectively. Furthermore, in a streptozotocin (STZ)-induced diabetic rat model, ethanolamine attenuated diabetic retinal inflammation, accompanied by suppression of microglial diacylglycerol (DAG)-dependent protein kinase C (PKC) pathway activation. In conclusion, we propose that ethanolamine is a potential biomarker and represents a viable biomarker-based therapeutic option for GW-DR.

Effects of the family customised online FOCUS programme on patients with heart failure and their informal caregivers: a multicentre, single-blind, randomised clinical trial.

Background: Living with heart failure can severely affect the physical and mental health of patients with heart failure and their caregivers. Available dyadic self-care interventions for heart failure are scarce, especially in China. We aimed to develop and test the family FOCUS programme. Methods: This single-blind, randomised, controlled study was conducted at four hospitals in Tianjin, China. Patients with heart failure (aged at least 18 years) and their caregiver (dyads) were randomly assigned to either the intervention (n = 71) or control (n = 71) group in a 1:1 ratio. The primary outcomes of this study were patient self-care, with three specific dimensions (self-care maintenance, symptom perception, and self-care management), and caregiver contribution to self-care, mirroring these three dimensions. The outcomes were assessed at baseline (T0) and 4 (T1), 12 (T2), and 24 (T3) weeks post-discharge, respectively. This work is registered on ChiCTR, ChiCTR2100053168. Findings: Between May 20, 2022, and September 30, 2022, 142 dyads with heart failure were enrolled. The intervention group exhibited dropout rates of 6%, 8.5%, and 18.3% at 4, 12, and 24 weeks after discharge, while the control group showed 9.9%, 12.3%, and 25.4%. Compared with the control group, patients in the intervention group reported improved self-care maintenance (ß: 8.5, 95% CI: 0.7, 16.4) and management (ß: 7.2, 95% CI: 0.1, 14.3) at T1, as well as improved symptom perception at both T1 (ß: 9.7, 95% CI: 1.5, 17.9) and T2 (ß: 9.6, 95% CI: 0.6, 18.6). Furthermore, caregiver contributions to self-care maintenance, self-care management, and symptom perception (excluding T3) exhibited significant improvements at all timepoints. Interpretation: Although the significant improvements in patients' self-care were not long-lasting, this study suggested that the family FOCUS programme consistently enhanced caregivers' contributions to self-care. Future work could explore the effect of the family FOCUS programme on families with multiple chronic conditions. Funding: The National Natural Science Foundation of China.

Molecular insights into the proteomic composition of porcine treated dentin matrix.

Background: Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated dentin matrix (pTDM) is a potential alternative scaffold due to limited availability. However, there is a dearth of information regarding the protein composition and underlying molecular mechanisms of pTDM.Methods: hTDM and pTDM were fabricated using human and porcine teeth, respectively, and their morphological characteristics were examined using scanning electron microscopy. Stem cells derived from human exfoliated deciduous teeth (SHEDs) were isolated and characterized using flow cytometry and multilineage differentiation assays. SHEDs were cultured in three-dimensional environments with hTDM, pTDM, or biphasic hydroxyapatite/tricalcium phosphate. The expression of odontogenesis markers in SHEDs were assessed using real-time polymerase chain reaction and immunochemical staining. Subsequently, SHEDs/TDM and SHEDs/HA/TCP complexes were transplanted subcutaneously into nude mice. The protein composition of pTDM was analyzed using proteomics and compared to previously published data on hTDM.Results: pTDM and hTDM elicited comparable upregulation of odontogenesis-related genes and proteins in SHEDs. Furthermore, both demonstrated the capacity to stimulate root-related tissue regeneration in vivo. Proteomic analysis revealed the presence of 278 protein groups in pTDM, with collagens being the most abundant. Additionally, pTDM and hTDM shared 58 identical proteins, which may contribute to their similar abilities to induce odontogenesis. Conclusions: Both hTDM and pTDM exhibit comparable capabilities in inducing odontogenesis, potentially owing to their distinctive bioactive molecular networks.

Network analysis of symptoms, physiological, psychological and environmental risk factors based on unpleasant symptom theory in patients with chronic heart failure.

BACKGROUND: Somatic symptoms and related factors in patients with chronic heart failure have been extensively researched. However, more insight into the complex interconnections among these constructs is needed, as most studies focus on them independently from each other. AIMS: The aim of this study is to gain a comprehensive understanding of how somatic symptoms and related factors are interconnected among patients with chronic heart failure. METHODS: A total of 379 patients were enrolled. Network analysis was used to explore the interconnections among the somatic symptoms and related risk factors. RESULTS: The four core symptoms of chronic heart failure were daytime dyspnea, dyspnea when lying down, fatigue and difficulty sleeping. Within the network, the edge weights of depression-anxiety, subjective social support-objective social support, and subjective social support-social support availability were more significant than others. Among physiological, psychological and environmental factors, the edge weights of NYHA-dyspnea, depression-difficulty sleeping, and social support availability-dyspnea when lying down were more significant than others. Depression and anxiety had the highest centrality, indicating stronger and closer connections with other nodes. CONCLUSIONS: Psychological and environmental factors stood out in the network, suggesting the potential value of interventions targeting these factors to improve overall health.

Neuropsychological insights into exercise addiction: the role of brain structure and self-efficacy in middle-older individuals.

This study aimed to investigate the relationship between exercise addiction and brain structure in middle-older individuals, and to examine the role of self-efficacy in mediating physiological changes associated with exercise addiction. A total of 133 patients exhibiting symptoms of exercise addiction were recruited for this study (male = 43, age 52.86 ± 11.78 years). Structural magnetic resonance imaging and behavioral assessments were administered to assess the study population. Voxel-based morphological analysis was conducted using SPM12 software. Mediation analysis was employed to explore the potential neuropsychological mechanism of self-efficacy in relation to exercise addiction. The findings revealed a positive correlation between exercise addiction and gray matter volume in the right inferior temporal region and the right hippocampus. Conversely, there was a negative correlation with gray matter volume in the left Rolandic operculum. Self-efficacy was found to indirectly influence exercise addiction by affecting right inferior temporal region gray matter volume and acted as a mediating variable in the relationship between the gray matter volume of right inferior temporal region and exercise addiction. In summary, this study elucidates the link between exercise addiction and brain structure among middle-older individuals. It uncovers the intricate interplay among exercise addiction, brain structure, and psychological factors. These findings enhance our comprehension of exercise addiction and offer valuable insights for the development of interventions and treatments.

A tablet-based multi-dimensional drawing system can effectively distinguish patients with amnestic MCI from healthy individuals.

The population with dementia is expected to rise to 152 million in 2050 due to the aging population worldwide. Therefore, it is significant to identify and intervene in the early stage of dementia. The Rey-Osterreth complex figure (ROCF) test is a visuospatial test scale. Its scoring methods are numerous, time-consuming, and inconsistent, which is unsuitable for wide application as required by the high number of people at risk. Therefore, there is an urgent need for a rapid, objective, and sensitive digital scoring method to detect cognitive dysfunction in the early stage accurately. This study aims to clarify the organizational strategy of aMCI patients to draw complex figures through a multi-dimensional digital evaluation system. At the same time, a rapid, objective, and sensitive digital scoring method is established to replace traditional scoring. The data of 64 subjects (38 aMCI patients and 26 NC individuals) were analyzed in this study. All subjects completed the tablet's Geriatric Complex Figure (GCF) test, including copying, 3-min recall, and 20-min delayed recall, and also underwent a standardized neuropsychological test battery and classic ROCF test. Digital GCF (dGCF) variables and conventional GCF (cGCF) scores were input into the forward stepwise logistic regression model to construct classification models. Finally, ROC curves were made to visualize the difference in the diagnostic value of dGCF variables vs. cGCF scores in categorizing the diagnostic groups. In 20-min delayed recall, aMCI patients' time in air and pause time were longer than NC individuals. Patients with aMCI had more short strokes and poorer ability of detail integration (all p < 0.05). The diagnostic sensitivity of dGCF variables for aMCI patients was 89.47%, slightly higher than cGCF scores (sensitivity: 84.21%). The diagnostic accuracy of both was comparable (dGCF: 70.3%; cGCF: 73.4%). Moreover, combining dGCF variables and cGCF scores could significantly improve the diagnostic accuracy and specificity (accuracy: 78.1%, specificity: 84.62%). At the same time, we construct the regression equations of the two models. Our study shows that dGCF equipment can quantitatively evaluate drawing performance, and its performance is comparable to the time-consuming cGCF score. The regression equation of the model we constructed can well identify patients with aMCI in clinical application. We believe this new technique can be a highly effective screening tool for patients with MCI.

Latent transition analysis of instrumental activities of daily living in Chinese elderly: based on the 2014-2018 wave of the Chinese Longitudinal Healthy Longevity Survey.

BACKGROUND: The instrumental activities of daily living (IADL) among the elderly have been found to be heterogeneous, with different trajectories. However, the transition of the IADL over time remains unclear. We aimed to explore the transition probabilities and the predictors of IADL among the elderly. METHODS: Longitudinal data from the 2014 (T1) and 2018 (T2) waves of the Chinese Longitudinal Healthy Longevity Survey were extracted. A sample of 2,944 participants aged 65 years or older, with complete responses to the IADL scale, was included. Latent profile analysis (LPA) and latent transition analysis (LTA) were employed to identify latent profiles of IADL and investigate the transition probabilities between profiles from T1 to T2. The predictors of latent profiles and transition probabilities were examined using multinomial regression analysis. RESULTS: The results of LPA at both T1 and T2 supported a 4-profile model solution. They were labeled as the "Normal function profile," "Mildly impaired profile," "Moderately impaired profile," and "Highly impaired profile". The Normal function profile and Highly impaired profile were characterized by maintaining stability rather than transitioning over time, with transition probabilities of 0.71 and 0.68, respectively, for maintaining stability. The Mildly impaired profile and Moderately impaired profile were characterized by a stronger tendency towards transition rather than stability, with transition probabilities of 0.29 and 0.45, respectively, of transitioning to the Highly impaired profile. The transition probabilities from the three impaired function profiles to the Normal function profile ranged from 0.05 to 0.19. Age, gender, place of residence, and social participation were significant predictors of profile attribution at T1 and transition probabilities over time. CONCLUSIONS: This study employed the LTA to examine the transition probability of IADL among the Chinese elderly. By recognizing the different profiles of IADL and understanding the factors associated with transitions among the elderly, interventions can be tailored to improve their functional independence and successful reintegration into families and society.

Two somatic mutations in the androgen receptor N-terminal domain are oncogenic drivers in hepatocellular carcinoma.

The androgen receptor (AR) plays an important role in male-dominant hepatocellular carcinoma, and specific acquired somatic mutations of AR have been observed in HCC patients. Our previous research have established the role of AR wild type as one of the key oncogenes in hepatocarcinogenesis. However, the role of hepatic acquired somatic mutations of AR remains unknown. In this study, we identify two crucial acquired somatic mutations, Q62L and E81Q, situated close to the N-terminal activation function domain-1 of AR. These mutations lead to constitutive activation of AR, both independently and synergistically with androgens, making them potent driver oncogene mutations. Mechanistically, these N-terminal AR somatic mutations enhance de novo lipogenesis by activating sterol regulatory element-binding protein-1 and promote glycogen accumulation through glycogen phosphorylase, brain form, thereby disrupting the AMPK pathway and contributing to tumorigenesis. Moreover, the AR mutations show sensitivity to the AMPK activator A769662. Overall, this study establishes the role of these N- terminal hepatic mutations of AR as highly malignant oncogenic drivers in hepatocarcinogenesis and highlights their potential as therapeutic targets for patients harboring these somatic mutations.

The therapeutic effects of marine sulfated polysaccharides on diabetic nephropathy.

Marine sulfated polysaccharide (MSP) is a natural high molecular polysaccharide containing sulfate groups, which widely exists in various marine organisms. The sources determine structural variabilities of MSPs which have high security and wide biological activities, such as anticoagulation, antitumor, antivirus, immune regulation, regulation of glucose and lipid metabolism, antioxidant, etc. Due to the structural similarities between MSP and endogenous heparan sulfate, a majority of studies have shown that MSP can be used to treat diabetic nephropathy (DN) in vivo and in vitro. In this paper, we reviewed the anti-DN activities, the dominant mechanisms and structure-activity relationship of MSPs in order to provide the overall scene of MSPs as a modality of treating DN.

Triglyceride-glucose index's link to cardiovascular outcomes post-percutaneous coronary intervention in China: a meta-analysis.

Percutaneous coronary intervention (PCI) addresses myocardial ischaemia, but a significant subset of patients encounter major adverse cardiovascular events (MACE) post-treatment. This meta-analysis investigated the relationship between the post-PCI triglyceride-glucose (TyG) index and MACE. Comprehensive searches of the Embase, PubMed, Cochrane Library, and Web of Science databases were conducted up to 3 March 2023, using relevant keywords. The effect size was determined based on I2 statistic using random-effects models. Cluster-robust standard errors crafted the dose-response curve, and the GRADE Evaluation Scale was employed to rate the quality of evidence. The group with the highest TyG index had significantly higher post-PCI MACE rates than the lowest index group, with hazard ratios (HRs) of 2.04 (95% CI 1.65-2.52; I2  = 77%). Each unit increase in TyG index corresponded to HRs of 1.82 for MACE (95% CI 1.34-2.46; I2  = 92%), 2.57 for non-fatal MI (95% CI 1.49-4.41; I2  = 63%), and 2.06 for revascularization (95% CI 1.23-3.50; I2  = 90%). A linear relationship between TyG index and MACE risk was established (R2  = 0.6114). For all-cause mortality, the HR was 1.93 (95% CI 1.35-2.75; I2  = 50%), indicating a higher mortality risk with elevated TyG index. The GRADE assessment yielded high certainty for non-fatal MI but low certainty for all-cause mortality, revascularization, and MACE. The TyG index may predict risks of post-PCI MACE, all-cause mortality, non-fatal MI, and revascularization, with varied levels of certainty. A potential linear association between the TyG index and MACE post-PCI was identified. Future research should validate these findings.

Vanin1 (VNN1) in chronic diseases: Future directions for targeted therapy.

Vanin1 (VNN1) is an exogenous enzyme with pantetheinase activity that mainly exerts physiological functions through enzyme catalysis products, including pantothenic acid and cysteamine. In recent years, the crosstalk between VNN1 and metabolism and oxidative stress has attracted much attention. As a result of the ability of VNN1 to affect multiple metabolic pathways and oxidative stress to exacerbate or alleviate pathological processes, it has become a key component of disease progression. This review discusses the functions of VNN1 in glucolipid metabolism, cysteamine metabolism, and glutathione metabolism to provide perspectives on VNN1-targeted therapy for chronic diseases.