Identification of GMFG as a novel biomarker in IgA nephropathy based on comprehensive bioinformatics analysis.

Background: IgA nephropathy (IgAN) stands as the most prevalent form of glomerulonephritis and ranks among the leading causes of end-stage renal disease worldwide. Regrettably, we continue to grapple with the absence of dependable diagnostic markers and specific therapeutic agents for IgAN. Therefore, this study endeavors to explore novel biomarkers and potential therapeutic targets in IgAN, while also considering their relevance in the context of tumors. Methods: We gathered IgAN datasets from the Gene Expression Omnibus (GEO) database. Subsequently, leveraging these datasets, we conducted an array of analyses, encompassing differential gene expression, weighted gene co-expression network analysis (WGCNA), machine learning, receiver operator characteristic (ROC) curve analysis, gene expression validation, clinical correlations, and immune infiltration. Finally, we carried out pan-cancer analysis based on hub gene. Results: We obtained 1391 differentially expressed genes (DEGs) in GSE93798 and 783 DGEs in GSE14795, respectively. identifying 69 common genes for further investigation. Subsequently, GMFG was identified the hub gene based on machine learning. In the verification set and the training set, the GMFG was higher in the IgAN group than in the healthy group and all of the GMFG area under the curve (AUC) was more 0.8. In addition, GMFG has a close relationship with the prognosis of malignancies and a range of immune cells. Conclusions: Our study suggests that GMFG could serve as a promising novel biomarker and potential therapeutic target for both IgAN and certain types of tumors.

Association between systemic immune-inflammation index and insulin resistance and mortality.

The role of inflammation in disease promotion is significant, yet the precise association between a newly identified inflammatory biomarker and insulin resistance (IR) and mortality remains uncertain. We aim to explore the potential correlation between systemic immune-inflammation index (SII) and these factors. We used data from 2011 to 2016 of National Health and Nutrition Examination Survey, and multivariate logistic regression and restricted cubic spline were employed. Subgroup and interaction analysis were conducted to recognize the consistency of the results. The association between SII and mortality was described by survival analysis. 6734 participants were enrolled, of whom 49.3% (3318) exhibited IR and 7.02% experienced mortality. Multivariate logistic regression revealed that individuals in the highest quartile (Q4) of SII had a significantly increased risk of IR compared to those in the lowest quartile (Q1). We then identified a linear association between SII and IR with an inflection point of 407, but may be influenced by gender. Similarly, compared to Q1, people whose SII at Q4 showed a higher all-cause and cardiovascular mortality. It showed a significant association between SII and both all-cause and cardiovascular mortality, but the results need to be interpreted with caution.

Physical activity can reduce the risk of blood cadmium and blood lead on stroke: Evidence from NHANES.

The detrimental impact of heavy metals on cardiovascular well-being is a global concern, and engaging in suitable physical activity has been shown to confer cardiovascular advantage. Nevertheless, the potential of exercise to mitigate the deleterious effects of heavy metals on stroke remains uncertain. We conducted a cross-sectional survey to assess the influence of blood cadmium and blood lead on stroke occurrence, while also examining the role of physical activity. Weighted multivariate regression analysis was employed to examine the potential correlation, while subgroup and interaction analyses were used to investigate the sensitivity and robustness of the results. After controlling risk factors, it revealed a positive correlation between blood cadmium and lead levels and the occurrence of stroke. Specifically, a 50% increase in blood cadmium was associated with a 28% increase in stroke incidence, while a 50% increase in blood lead was associated with a 47% increase in stroke incidence. To estimate the non-linear relationship, we employed restricted cubic models. The results demonstrate a gradual decrease in the slope of the model curve as the intensity of physical activity increases, implying that engaging in physical activity may contribute to a reduction in the occurrence of stroke caused by blood cadmium and lead. Our findings suggest that blood cadmium and lead could be considered an autonomous risk factor for stroke within the general population of the United States. Moreover, engaging in physical activity has the potential to mitigate the potential detrimental consequences associated with exposure to heavy metals.

P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain. 3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine (P7C3-A20) can be neuroprotective in various diseases, including ischemic stroke and neurodegenerative diseases. However, whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear. Therefore, in the present study, we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms. We established a traumatic brain injury rat model using a modified weight drop method. P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury. Severe neurological deficits were found in rats after traumatic brain injury, with deterioration in balance, walking function, and learning memory. Furthermore, hematoxylin and eosin staining showed significant neuronal cell damage, while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis. The presence of autolysosomes was observed using transmission electron microscope. P7C3-A20 treatment reversed these pathological features. Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-II (LC3-II) autophagy protein, apoptosis-related proteins (namely, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 [BNIP3], and Bcl-2 associated x protein [Bax]), and elevated ubiquitin-binding protein p62 (p62) autophagy protein expression. Thus, P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

Association between depression and stroke and the role of sociodemographic factors: A study among hypertensive populations.

OBJECTIVES: Studies have shown that depression increases the risk of stroke, and that this relationship can be modified by sex. However, few studies have explored this relationship in a hypertensive population, and an examination of sociodemographic factors may be useful in determining whether depression and stroke are related. MATERIALS AND METHODS: We used data from the National Health and Nutrition Examination Survey conducted between 2005-2018. The relationship between depression and stroke was investigated using a multivariate logistic regression. Effect modification by sex was examined using an interaction analysis model. RESULTS: Participants with mild or moderate depression had a 53 % (odds ratio, [OR] 1.53; 95 % confidence interval [CI], 1.15-2.04) higher risk of stroke than those without depression, with 1.76 times (95 % CI, 1.14-2.72) greater risk for major depression. Interaction analysis indicated that sex had no effect on this relationship (OR, 1.30; 95 % CI, 0.85-1.47, P=0.430). In comparison with Hispanics, non-Hispanic blacks and others/mixed-race individuals with depression had a greater risk of stroke (OR, 2.26; 95 % CI, 1.5-3.14; OR, 2.67, 95 % CI, 1.29-5.55). CONCLUSIONS: Our study found that the degree of depression was positively correlated with stroke in a hypertensive population, and that this relationship was not affected by sex.

Unravelling the relation between altruistic cooperativeness trait, smiles, and cooperation: a mediation analysis.

Introduction: Human cooperativeness is an important personality trait. However, the mechanism through which people cooperate remains unclear. Previous research suggests that one of the proposed functions of smiling is to advertise altruistic dispositions, leading to successful cooperation. In particular, studies have reported that Duchenne smiles are honest signals of cooperative intent because they are not easy to produce voluntarily. This study aimed to examine the predictive relationships among altruistic cooperativeness traits, Duchenne smiles, and cooperative behavior. Methods: A total of 90 people were randomly assigned to dyads and filmed while they participated in a ten-minute, unstructured conversation followed by a prisoner's dilemma game to measure their cooperative behaviors. Their smiles during conversations were classified as Duchenne or non-Duchenne. Participants' altruistic dispositions were measured before the conversation began using an anonymous prisoner's dilemma game. Results: The results of our linear regression analyses support previous findings that individual's Duchenne smiles and their own cooperative behavior are positively correlated. However, when we controlled for altruistic cooperativeness, Duchenne smiles no longer correlated with cooperative behavior. The results of the mediation analyses showed that Duchenne smiles and smile synchrony did not mediate the predictive relationship between altruistic cooperativeness and cooperative behavior. Discussion: Our results suggest that human cooperative behavior may be predetermined by altruistic cooperativeness. This calls for the reconsideration of the Duchenne smile as an underlying behavioral mechanism that is effective for signaling altruistic cooperative intent.

Exploring the pharmacological mechanisms of Tripterygium wilfordii against diabetic kidney disease using network pharmacology and molecular docking.

Background: Tripterygium wilfordii (TW), when formulated in traditional Chinese medicine (TCM), can effectively treat diabetic kidney disease (DKD). However, the pharmacological mechanism associated with its success has not yet been elucidated. The current work adopted network pharmacology and molecular docking for exploring TW-related mechanisms in treating DKD. Methods: In the present work, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was employed to obtain the effective components and candidate targets of TW. Additionally, this work utilized the UniProt protein database for screening and standardizing human-derived targets for effective components. The Cytoscape software was utilized to construct an effective component-target network for TW. Targets for DKD were acquired in the GEO, DisGeNET, GeneCards, and OMIM databases. Additionally, a Venn diagram was also plotted to select the possible targets of TW for treating DKD. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to explore the TW-related mechanism underlying DKD treatment. This work also built a protein-protein interaction (PPI) network based on the Cytoscape and String platform. Then, molecular docking was conducted in order to assess the affinity of key proteins for related compounds. Results: In total, 29 active components and 134 targets of TW were acquired, including 63 shared targets, which were identified as candidate therapeutic targets. Some key targets and important pathways were included in the effect of TW in treating DKD. Genes with higher degrees, including TNF and AKT1, were identified as hub genes of TW against DKD. Molecular docking showed that TNF and AKT1 bind well to the main components in TW (kaempferol, beta-sitosterol, triptolide, nobiletin, and stigmasterol). Conclusions: TW primarily treats DKD by acting on two targets (AKT1 and TNF) via the five active ingredients kaempferol, beta-sitosterol, triptolide, nobiletin, and stigmasterol.

Identification of the Genetic Influence of SARS-CoV-2 Infections on IgA Nephropathy Based on Bioinformatics Method.

INTRODUCTION: Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. It was initially detected in Wuhan, China, in December 2019. In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. Compared to healthy individuals, patients with IgA nephropathy (IgAN) are at a higher risk of SARS-CoV-2 infection. However, the potential mechanisms remain unclear. This study explores the underlying molecular mechanisms and therapeutic agents for the management of IgAN and COVID-19 using the bioinformatics and system biology way. METHODS: We first downloaded GSE73953 and GSE164805 from the Gene Expression Omnibus (GEO) database to obtain common differentially expressed genes (DEGs). Then, we performed the functional enrichment analysis, pathway analysis, protein-protein interaction (PPI) analysis, gene regulatory networks analysis, and potential drug analysis on these common DEGs. RESULTS: We acquired 312 common DEGs from the IgAN and COVID-19 datasets and used various bioinformatics tools and statistical analyses to construct the PPI network to extract hub genes. Besides, we performed gene ontology (GO) and pathway analyses to reveal the common correlation between IgAN and COVID-19. Finally, on the basis of common DEGs, we determined the interactions between DEGs-miRNAs, the transcription factor-genes (TFs-genes), protein-drug, and gene-disease networks. CONCLUSION: We successfully identified hub genes that may act as biomarkers of COVID-19 and IgAN and also screened out some potential drugs to provide new ideas for COVID-19 and IgAN treatment.

Predictors for short-term successful weaning from continuous renal replacement therapy: a systematic review and meta-analysis.

The systemic review and meta-analysis aimed to identify the predictors for short-term successful weaning from CRRT in severe AKI patients. PubMed, Embase, the Cochrane Library, and grey literature were searched for relevant studies investigating variables for short-term successful weaning from CRRT to August 2022. Our criteria included patients with AKI who required CRRT but excluded patients with kidney failure. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed-effect (I2≤50% and P-value of the Q statistic > 0.1) or random-effect models (I2>50% or p-value of the Q statistic ≤ 0.1) as appropriate. Our search yielded 11 studies and described 11 variables. The pooled analysis showed that chronic kidney disease (OR = 0.638, 95% CI: 0.491-0.829), CRRT duration (OR = 0.913, 95% CI: 0.882-0.946), and urine output at the cessation of CRRT (per 100 mL/day increase) (OR = 1.084, 95% CI: 1.061-1.108) were predictive factors for short-term successful weaning from CRRT. Male (OR = 0.827, 95% CI: 0.627-1.092), diabetes mellitus (OR = 0.970, 95% CI: 0.761-1.237), and sepsis (OR = 0.911, 95% CI: 0.717-1.158) were unrelated to the short-term weaning from CRRT. The relationship between hypertension, use of vasopressors or inotropes at the starting of CRRT, use of vasopressors or inotropes at the cessation of CRRT, use of diuretics at the cessation of CRRT, serum creatinine at the cessation of CRRT, and short-term weaning from CRRT remains unclear. Additional prospective studies are needed to evaluate this relationship further.

Unraveling the Mechanism of Zhibaidihuang Decoction against IgA Nephropathy Using Network Pharmacology and Molecular Docking Analyses.

Zhibaidihuang Decoction (ZBDHD) is a traditional Chinese medicine with immense potential to treat IgA nephropathy. However, its core ingredients and representative mechanism remain unclear. In this study, we uncovered the key component and underlying mechanisms of ZBDHD for IgA nephropathy by applying network pharmacology and molecular docking approaches. This was done by first identifying the active ingredients and, subsequently, their corresponding gene targets in ZBDHD with the help of the Traditional Chinese Medicine Systems Pharmacology and analysis platform (TCMSP) database, thereby constructing the drug-compound-target network. The IgA nephropathy-associated genes were then identified using GeneCards, Drugbank, and OMIM databases. The overlapped targets were later obtained to establish Protein-Protein Interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, we performed molecular docking among active compounds and hub genes, and thereby verified the key compound of ZBDHD. The drug-compound-gene network consisted of 289 nodes and 1,113 edges. The top four active ingredients were beta-sitosterol, kaempferol, quercetin and stigmasterol. The top five hub genes in the PPI network were AKT1, ILB1, IL-6, TNF, and TP53. Molecular docking results could demonstrate that there was high affinity among active compounds and the core targets, while quercetin may possibly be the key compound of ZBDHD. We first identified the positive compound and the candidate molecular mechanisms of ZBDHD in an IgA nephropathy treatment and discovered that quercetin might be the core compound of ZBDHD in the treatment of IgA nephropathy.

Early assessment of ventricular synchronization and function after left bundle-branch-area pacing with right bundle-branch block.

AIM: To evaluate ventricular synchronization and function in patients with right bundle-branch block after left bundle-branch-area pacing (LBBAP) by echocardiography. METHODS: Forty patients who successfully received LBBAP were selected and divided into the right bundle-branch block group (RBBB group) and the non-RBBB group by pre-operation ECG. Echocardiography and follow-up were performed 1 month after operation. Interventricular synchronization was evaluated by tissue Doppler (TDI), tissue mitral annular displacement (TMAD), and interventricular mechanical delay. The tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), tricuspid annulus sidewall systolic velocity (TV-s'), left ventricular global ventricular longitudinal strain (GLS), right ventricular free wall longitudinal strain (LS-RV), standard deviation of left ventricular 18 segments peak time difference (SDt-L) and standard deviation of right ventricular free wall 3 segments peak time difference (SDt-R) were applied to evaluate intraventricular synchronization and ventricular function. RESULTS: The difference of displacement peak time of the tricuspid and mitral valves, namely ΔPTTV-MV measured by TMAD, the difference of systolic time to peak of the tricuspid and mitral valves, namely ΔTsTV-MV measured by TDI, were statistically different between the two groups (P < 0.05). Compared with the non-RBBB group, there were no statistically significant differences in the GLS, RVFAC, LS-RV, TAPSE, TV-s', SDt-L, SDt-R (P > 0.05). CONCLUSION: Echocardiography technology including two-dimensional speckle tracking imaging (2D-STI), TDI, and TMAD can effectively analyze interventricular synchronization, intraventricular synchronization, and ventricular function. Although the movement of the right ventricular myocardium in the RBBB group was slightly later than that of the left ventricular myocardium after LBBAP, LBBAP could still be applied in RBBB patients with pacing indication.

Intracardiac versus transesophageal echocardiography for diagnosis of left atrial appendage thrombosis in atrial fibrillation: A meta-analysis.

INTRODUCTION: Left atrial appendage (LAA) thrombus in patients with atrial fibrillation is usually detected by transesophageal echocardiography (TEE). Intracardiac echocardiography (ICE) can be a suitable alternative to detect thrombosis. However, the effectiveness of the two methods for detecting LAA thrombus is still unclear, we performed a meta-analysis that compared ICE versus TEE for LAA thrombosis. METHODS: We searched PubMed, Cochrane Library, and Embase for published abstracts and manuscripts on June 1, 2020. The analysis was performed using RevMan 5.3, STATA 15, and Meta-Disc 1.4. RESULTS: Eight studies consists of 1108 patients (TEE = 558 vs. ICE = 550) were included. The average sensitivity of ICE and TEE to diagnose LAA thrombus is 1.0 (95% CI: 0.91-1.00) versus 0.68 (95% CI: 0.49-0.83), and specificity of ICE and TEE to diagnosis of LAA thrombus is 1.0 (95% CI: 0.99-1.00) versus 0.98 (95% CI: 0.96-0.99). The AUC of ICE and TEE is 0.9846 (SEAUC = 0.0196) and 0.9655 (SEAUC = 0.0401), and the Q* statistics is 0.9462 (SEQ* = 0.0406) and 0.9127 (SEQ * = 0.0616), respectively. Z test was performed on Q* statistics (Z = 0.45, p > .05). CONCLUSION: The ICE and TEE have similar diagnostic efficacy for LAA thrombosis, but the ICE has higher sensitivity. Compared with TEE, ICE may be more advantages and prospects for clinical application.

Transthoracic echocardiography-guided left bundle branch pacing without fluoroscopic guidance: A case report.

This case study demonstrates the feasibility of pacing the left bundle branch and atrial septum under transthoracic echocardiography (TTE) without fluoroscopic guidance. This technique could be useful to guide pacemaker implantation in some patients, especially pregnant women.

Delay optimization of multipoint pacing increases the cardiac index and narrows the QRS width.

INTRODUCTION: The benefits of MPP delay optimization on hemodynamics and ventricular contraction synchronicity can be quantified with cardiac index (CI) and QRS width. A delay with the maximum CI and minimum QRS width may be the optimized settings for multipoint pacing (MPP). METHODS: Twelve patients with advanced heart failure who received cardiac resynchronization therapy defibrillation with MPP at the Third People's Hospital of Chengdu from March 2016 to April 2019 were included. Interventricular and intraventricular delays were optimized through noninvasive cardiac output monitoring and a 12 lead ECG. RESULTS: According to CI, the optimized left ventricular- left ventricular - right ventricular delay setting was mainly 25 ms-25 ms and 40 ms-40 ms. And the delay with the minimum QRS width was mainly in 5 ms-5 ms, 25 ms-25 ms, and 40 ms-25 ms. The optimal MPP configuration increased CI compared to the MPP setting that produced the minimum CI (4.5 ± 1.3 vs. 2.8 ± 1.0 L/min/m2, P < 0.001). The QRS width of the optimized MPP was narrower than the MPP setting that produced the maximum QRS width (127 ± 20 vs. 160 ± 29 ms, P < 0.001). CONCLUSION: Delay optimization improves hemodynamic response and ventricular contraction synchronicity. The delay of 25 ms-25 ms may be the optimal setting for most MPP patients.

Head Movement Synchrony and Idea Generation Interference - Investigating Background Music Effects on Group Creativity.

Previous studies have indicated that divergent idea integration is an effective way to foster extraordinary creativity in groups. This study posits that background music (BGM) may aid in eliciting this phenomenon. Here to describe the effectiveness of BGM on group creativity, we hypothesized and suggested different mechanisms that genre and valence attributes of BGM would lead to extraordinary creativity. The temporal co-ordination of head movement synchrony (HMS) was investigated as a non-verbal cue and we found significant HMS response levels to idea generation. While the HMS as response did not depend on the quality of the prior ideas; it led to higher divergence and originality in the successively generated ideas. Results of this study showed the dominant contribution of upbeat positive valence (UP) music, relative to other genres, in HMS leading to divergent ideas. Following this, the potential role of upbeat music in enhancing participant sociability and positive valence in enhancing cooperation level was discussed. Upbeat positive music may decrease judgmental behavior during creative group tasks and inspire participants to share divergent perspectives. The use of such music can encourage participants to share new perspectives and integrate ideas. It may also provide a potential explanation for the enhancing effect of upbeat positive music on creative outcomes in groups.

[Safety and efficiency of pacing at right ventricular outflow versus at ventricular cardiac apex].

OBJECTIVE: To compare the safety and efficiency of pacing at right ventricular outflow versus right ventricular apex. METHOD: Patients were divided into two groups: pacing at ventricular cardiac apex (common pacing group, n = 22) and pacing at right ventricular outflow tract (uncommon pacing group, n = 18). RESULTS: Impedance and amplitude of R-wave were similar during implantation between the two groups (all P > 0.05). The pacing threshold and electric current were significant higher in uncommon group than those in common pacing group (all P < 0.05), however, these differences disappeared at 1 month post pacemaker implantation (all P > 0.05). The mean QRS duration tended to be shorter in uncommon pacing group compared to that in common pacing group (P > 0.05). There was no pacemaker associated adverse effect in both groups. CONCLUSION: The safety and efficiency of pacing at right ventricular outflow was similar as those of pacing at right ventricular apex.