Echinacoside ameliorates post-stroke depression by activating BDNF signaling through modulation of Nrf2 acetylation.

BACKGROUND: Post-stroke depression (PSD) affects approximately one-third of stroke survivors, leading to adverse outcomes in rehabilitation, reduced quality of life, and increased mortality rates. Despite these implications, the underlying causes of PSD remain unclear, posing challenges for prevention and treatment. Echinacoside (ECH), a natural compound with known neuroprotective and antidepressant properties, holds significant therapeutic potential for PSD. However, the precise mechanism of its action remains unknown. PURPOSE: To unravel the specific mechanism through which ECH alleviates PSD by exploring the intricate interplay between ECH and Nrf2, as well as its impact on the BDNF/TrkB signaling axis. STUDY DESIGN AND METHODS: A rat PSD model was established though middle cerebral artery occlusion coupled with chronic unpredictable mild stress, followed by ECH treatment. The rats' depressive state was evaluated using the sucrose preference test and force swimming test. Brain damage was assessed through TTC staining, Nissl staining, and TUNEL assay. The multifaceted mechanism of ECH in PSD was investigated using immunofluorescence, immunohistochemistry, RT-qPCR, dual-luciferase assay, and western blotting. Additionally, the interaction between ECH and Nrf2 was explored through molecular docking and microscale thermophoresis. RESULTS: Our findings unveiled a novel facet of ECH action, demonstrating its unique ability to upregulate Nrf2 through acetylation within the hippocampus of PSD-affected rats (p < 0.05). Moreover, ECH showcased its distinctive potential by enhancing BDNF transcriptional activity, activating the BDNF/TrkB signaling axis, and orchestrating a comprehensive response against oxidative stress and apoptosis, thereby alleviating PSD symptoms in rats (p < 0.05). CONCLUSIONS: This study not only provides insights into the pivotal role of Nrf2 in mediating the BDNF/TrkB axis activation by ECH but also highlights the novelty of ECH's mechanism in addressing PSD. The elucidation of these unique aspects positions ECH as a groundbreaking candidate for further exploration and development in the realm of PSD intervention.

Dehydroevodiamine ameliorates neurological dysfunction after traumatic brain injury in mice via regulating the SIRT1/FOXO3a/Bim pathway.

BACKGROUND: Traumatic Brain Injury (TBI) poses a considerable public health challenge, resulting in mortality, disability, and economic strain. Dehydroevodiamine (DEDM) is a natural compound derived from a traditional Chinese herbal medicine. Prior studies have substantiated the neuroprotective attributes of this compound in the context of TBI. Nevertheless, a comprehensive comprehension of the exact mechanisms responsible for its neuroprotective effects remains elusive. It is imperative to elucidate the precise intrinsic mechanisms underlying the neuroprotective actions of DEDM. PURPOSE: The aim of this investigation was to elucidate the mechanism underlying DEDM treatment in TBI utilizing both in vivo and in vitro models. Specifically, our focus was on comprehending the impact of DEDM on the Sirtuin1 (SIRT1) / Forkhead box O3 (FOXO3a) / Bcl-2-like protein 11 (Bim) pathway, a pivotal player in TBI-induced cell death attributed to oxidative stress. STUDY DESIGN AND METHODS: We established a TBI mouse model via the weight drop method. Following continuous intraperitoneal administration, we assessed the neurological dysfunction using the Modified Neurological Severity Score (mNSS) and behavioral assay, followed by sample collection. Secondary brain damage in mice was evaluated through Nissl staining, brain water content measurement, Evans blue detection, and Western blot assays. We scrutinized the expression levels of oxidative stress-related indicators and key proteins for apoptosis. The intricate mechanism of DEDM in TBI was further explored through immunofluorescence, Co-immunoprecipitation (Co-IP) assays, real-time quantitative PCR (RT-qPCR), dual-luciferase assays and western blotting. Additionally, we further investigated the specific therapeutic mechanism of DEDM in an oxidative stress cell model. RESULTS: The results indicated that DEDM effectively ameliorated oxidative stress and apoptosis post-TBI, mitigating neurological dysfunction and brain injury in mice. DEDM facilitated the deacetylation of FOXO3a by up-regulating the expression of the deacetylase SIRT1, consequently suppressing Bim expression. This mechanism contributed to the alleviation of neurological injury and symptom improvement in TBI-afflicted mice. Remarkably, SIRT1 emerged as a central mediator in the overall treatment mechanism. CONCLUSIONS: DEDM exerted significant neuroprotective effects on TBI mice by modulating the SIRT1/FOXO3a/Bim pathway. Our innovative research provides a basis for further exploration of the clinical therapeutic potential of DEDM in the context of TBI.

Antitumor Activity of Carboxymethyl Pachymaran with Different Molecular Weights Based on Immunomodulatory and Gut Microbiota.

Carboxymethyl pachymaran (CMP) was treated via high-temperature and cellulase hydrolysis to obtain HTCMP, HTEC-24, and HTEC-48. The chemical structure and in vivo antitumor activities of the four types of CMPs were investigated. Compared with CMP (787.9 kDa), the molecular weights of HTCMP, HTEC-24, and HTEC-48 were decreased to 429.8, 129.9, and 68.6 kDa, respectively. The viscosities and particle sizes of the CMPs could also decrease with the decline in the molecular weights. All the CMPs showed antitumor abilities, but HTEC-24 exhibited the best activity. In the animal study, when curing the spleen and thymus, CMPs displayed immunomodulatory effects by increasing the secretion of IFN-γ and IL2 in mice. The CMPs also exerted an antitumor ability by regulating the gut microbiota in tumor-bearing mice. Our results established a foundation to develop an antitumor drug with CMP.

Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.

Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future.

Genome-wide presence/absence variation discovery and its application in Peach (Prunus persica).

Gene presence/absence variation (PAV) is an important contributor to the studies of genetic diversity, gene identification, and molecular marker development in plants. In the present study, 100 peach (Prunus persica) accessions were used for genome resequencing to identify PAVs. Alignmentwith a reference genome yielded a total of 2.52 Mb non-reference sequences and 923 novel genes were identified. The dispensable PAVs were enriched in resistance, perhaps reflecting their roles in plant adaptation to various environments. Furthermore, selection sweeps associated with peach domestication and improvement were identified based on PAV data. Only 4.3% and 13.4% of domestication and improvement sweeps, respectively, were identified simultaneously using single nucleotide polymorphism (SNP) data, suggesting flexible identification between the different methods. To further verify the applicability of PAV identification, a genome-wide association study was conducted using 21 agronomic traits. Some of the identified loci were consistent with those reported in previous studies, while some were mapped for the first time; the latter included petiole length, petiole gland shape, and petiole gland number. Through tissue-specific expression analysis and gene transformation experiments, a novel gene, evm.model.Contig322_A94.1, was identified and found to be involved in chilling requirements. We speculated that this novel gene might regulate the trait by participating in the ABA signaling pathway. The PAVs identified in P. persica provide valuable resources for mapping the entire gene set and identifying optional markers for molecular selection in future studies.

Effects of degradation on the physicochemical and antioxidant properties of carboxymethyl pachymaran.

Poria cocos (Schw.) Wolf is a well-known edible and medicinal fungus. The polysaccharide in the sclerotium of P. cocos was extracted and prepared into carboxymethyl pachymaran (CMP). Three different degradation treatments including high temperature (HT), high pressure (HP) and gamma irradiation (GI) were used to process CMP. The changes in physicochemical properties and antioxidant activities of CMP were then comparatively investigated. We found that the molecular weights of HT-CMP, HP-CMP, and GI-CMP decreased from 787.9 kDa to 429.8, 569.5 and 6.0 kDa, respectively. Degradation treatments had no effect on the main chains of →3-ß-D-Glcp-(1 â†’ while changed the branched sugar residues. The polysaccharide chains of CMP were depolymerized after high pressure and gamma irradiation treatments. The three degradation methods improved the stability of CMP solution while decreased the thermal stability of CMP. In addition, we found that the GI-CMP with lowest molecular weight had the best antioxidant activity. Our results suggest that gamma irradiation treatment could degrade CMP as functional foods with strong antioxidant activity.

Discovery of a key gene associated with fruit maturity date and analysis of its regulatory pathway in peach.

Fruit maturity is an important agronomic trait of fruit crops. Although in previous studies, several molecular markers are developed for the trait, the knowledge about its candidate genes is particularly limited. In this study, a total of 357 peach accessions were re-sequenced to obtain 949,638 SNPs. Combing with 3-year fruit maturity dates, a genome-wide association analysis was performed, and 5, 8, and 9 association loci were identified. To screen the candidate genes for those year-stable loci on chromosomes 4 and 5, two maturity date mutants were used for transcriptome sequencing. Gene expression analysis indicated that Prupe.4G186800 and Prupe.4G187100 on chromosome 4 were essential to fruit ripening in peaches. However, the expression analysis of different tissues showed that the first gene has no tissue-specific character, but transgenic studies showed that the latter is more likely to be a key candidate gene than the first for the maturity date in peach. The yeast two-hybrid assay showed that the proteins encoded by the two genes interacted and then regulated fruit ripening. Moreover, the previously identified 9 bp insertion in Prupe.4G186800 may affect their interaction ability. This research is of great significance for understanding the molecular mechanism of peach fruit ripening and developing practical molecular markers in a breeding program.

Self-Stacked 3D Anisotropic BNNS Network Guided by Para-Aramid Nanofibers for Highly Thermal Conductive Dielectric Nanocomposites.

The enhancement of the heat-dissipation property of polymer-based composites is of great practical interest in modern electronics. Recently, the construction of a three-dimensional (3D) thermal pathway network structure for composites has become an attractive way. However, for most reported high thermal conductive composites, excellent properties are achieved at a high filler loading and the building of a 3D network structure usually requires complex steps, which greatly restrict the large-scale preparation and application of high thermal conductive polymer-based materials. Herein, utilizing the framework-forming characteristic of polymerization-induced para-aramid nanofibers (PANF) and the high thermal conductivity of hexagonal boron nitride nanosheets (BNNS), a 3D-laminated PANF-supported BNNS aerogel was successfully prepared via a simple vacuum-assisted self-stacking method, which could be used as a thermal conductive skeleton for epoxy resin (EP). The obtained PANF-BNNS/EP nanocomposite exhibits a high thermal conductivity of 3.66 W m-1 K-1 at only 13.2 vol % BNNS loading. The effectiveness of the heat conduction path was proved by finite element analysis. The PANF-BNNS/EP nanocomposite shows outstanding practical thermal management capability, excellent thermal stability, low dielectric constant, and dielectric loss, making it a reliable material for electronic packaging applications. This work also offers a potential and promotable strategy for the easy manufacture of 3D anisotropic high-efficiency thermal conductive network structures.

MADS-box protein PpDAM6 regulates chilling requirement-mediated dormancy and bud break in peach.

Bud dormancy is crucial for winter survival and is characterized by the inability of the bud meristem to respond to growth-promotive signals before the chilling requirement (CR) is met. However, our understanding of the genetic mechanism regulating CR and bud dormancy remains limited. This study identified PpDAM6 (DORMANCY-ASSOCIATED MADS-box) as a key gene for CR using a genome-wide association study analysis based on structural variations in 345 peach (Prunus persica (L.) Batsch) accessions. The function of PpDAM6 in CR regulation was demonstrated by transiently silencing the gene in peach buds and stably overexpressing the gene in transgenic apple (Malus × domestica) plants. The results showed an evolutionarily conserved function of PpDAM6 in regulating bud dormancy release, followed by vegetative growth and flowering, in peach and apple. The 30-bp deletion in the PpDAM6 promoter was substantially associated with reducing PpDAM6 expression in low-CR accessions. A PCR marker based on the 30-bp indel was developed to distinguish peach plants with non-low and low CR. Modification of the H3K27me3 marker at the PpDAM6 locus showed no apparent change across the dormancy process in low- and non-low- CR cultivars. Additionally, H3K27me3 modification occurred earlier in low-CR cultivars on a genome-wide scale. PpDAM6 could mediate cell-cell communication by inducing the expression of the downstream genes PpNCED1 (9-cis-epoxycarotenoid dioxygenase 1), encoding a key enzyme for ABA biosynthesis, and CALS (CALLOSE SYNTHASE), encoding callose synthase. We shed light on a gene regulatory network formed by PpDAM6-containing complexes that mediate CR underlying dormancy and bud break in peach. A better understanding of the genetic basis for natural variations of CR can help breeders develop cultivars with different CR for growing in different geographical regions.

Effects of Maturity and Processing on the Volatile Components, Phytochemical Profiles and Antioxidant Activity of Lotus (Nelumbo nucifera) Leaf.

In this study, fresh lotus leaves at two maturity stages were processed to tea products by different methods (white-tea process, green-tea process and black-tea process). The volatile compounds, phytochemical profiles and antioxidant activities of lotus-leaf tea were investigated. A total of 81 volatile components were identified with HS-GC-IMS. The mature lotus-leaf tea showed more volatile compounds than the tender lotus-leaf tea. The lotus leaf treated with the white-tea process had more aroma components than other processing methods. In addition, six types of phenolic compounds, including luteolin, catechin, quercetin, orientin, hyperoside and rutin were identified in the lotus-leaf tea. The mature leaves treated with the green-tea process had the highest levels of TPC (49.97 mg gallic acid/g tea) and TFC (73.43 mg rutin/g tea). The aqueous extract of lotus-leaf tea showed positive scavenging capacities of DPPH and ABTS radicals, and ferric ion reducing power, whereas tender lotus leaf treated with the green-tea process exhibited the strongest antioxidant activity. What is more, the antioxidant activities had a significant positive correlation with the levels of TPC and TFC in lotus-leaf tea. Our results provide a theoretical basis for the manufacture of lotus-leaf-tea products with desirable flavor and health benefits.

Assessing the impact of implementing multiple adherence measures to antiretroviral therapy from dispensing data: a short report.

Pharmacy dispensing data are useful for estimating adherence to therapy. Here, we implement multiple adherence measures to antiretroviral therapy (ART) and provide an online tool for visualising results. We conducted a cohort study for 2,042 people dispensed ART in Australia. We assessed adherence using the Proportion of Days Covered (PDC) within 360 days of follow-up as a continuous measure and dichotomised (PDC ≥80%). We defined a covered day as the 1) exposure to ≥3 antiretrovirals at the same time 2) exposure to any antiretroviral 3) lowest number of days covered per antiretroviral 4) average of days covered over all antiretrovirals 5) highest number of days covered per antiretroviral. For each method, we conducted sensitivity analyses. The median PDC ranged between 93.3%-98.3%. Between 67.0%-87.7% of individuals were classified as adherent, with higher values for measure 2 (85.5%-89.7%) and lower values for measure 3 (67.0%-70.9%). Censoring loss to follow-up had a higher impact on adherence estimates than considering a grace period. The variation in adherence estimates can be substantial, especially when dichotomising adherence. Researchers should consider operationalising multiple measures to estimate adherence bounds and identify a range of people at risk of non-adherence for targeted interventions.

Core-shell structured Co3O4@PPy composite for electrochemical determination of terbutylhydroquinone.

TBHQ is a significant synthetic antioxidant, but excessive use of TBHQ is harmful to human health. Therefore, the preparation of a high-efficiency TBHQ electrochemical sensor is of great significance. In this work, a core-shell structured Co3O4@PPy composite is synthesized for TBHQ determination and exhibits remarkable electrochemical properties. The core-shell structure of Co3O4@PPy composite shows the synergistic effects of fast charge transfer, rich active surface area and more active sites. Under optimal conditions, the linear range of the developed sensor is 0.2-600 µM, and the detection limit is 0.05 µM (S/N = 3). In addition, it also has good stability and reproducibility due to the stable protective role of the PPy shell. The proposed sensor can also be applied to practical sample detection.

SnTe thermoelectric materials with low lattice thermal conductivity synthesized by a self-propagating method under a high-gravity field.

The conventional fabrication methods (for example, melting and powder metallurgy) of bulk thermoelectric materials are time- and energy-consuming, which restrict their large-scale application. In this work, ultra-fast self-propagating synthesis under a high-gravity field was used to prepare SnTe bulks, which shortened the synthesis time from several days to a few seconds. The grain growth was suppressed and some small pores were reserved in the matrix during the ultra-fast solidification process. The increased grain boundaries and pores (nanoscale to micron scale) enhanced phonon scattering, which greatly decreased the lattice thermal conductivity. The obtained minimum lattice thermal conductivity is 0.81 W m-1 K-1, and the maximum zT value is 0.5 (873 K), which is comparable to the best reported results of the undoped SnTe alloy. The ultra-fast non-equilibrium synthesis technique opens up new possibilities to prepare high-efficiency bulk thermoelectric materials with reduced time and energy consumption.

Significance of CYP3A4∗1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities.

Objective: To investigate the association between CYP3A4∗1G and OPRM1A118G gene polymorphisms and postoperative analgesia with sufentanil in women of Zhuang ethnicity from western Guangxi, China. Methods: Forty-eight Chinese Zhuang women who underwent elective myomectomy under general anesthesia in our hospital from January 2019 to December 2020 were selected, and another 47 Chinese Han patients in the same period were selected as the control subjects. CYP3A4∗1G and OPRM1 A118G gene polymorphisms as well as sedation and pain scores at different time points after surgery were compared between the two groups of patients to analyze the relationship between the degree of pain and dosage of sufentanil and to analyze the effect of gene polymorphisms on the occurrence of adverse reactions. Results: The frequencies of ∗1/∗1G and ∗1G/∗1G genotypes, allele 1∗G of CYP3A4∗1G and genotypes AA, and allele A of OPRM1 A118G in Zhuang patients were lower than those in Han patients, while the frequencies of ∗1/∗1, allele ∗1 of CYP3A4∗1G and genotypes AG, genotypes GG, and allele G of OPRM1 A118G were higher in Zhuang women. There was no significant difference in the Ramsay and VAS scores between the two groups at different time points after surgery, but the sufentanil use in Zhuang patients was higher than in Han patients at different time points after surgery. In addition, sufentanil use was highest in Zhuang patients with the ∗1/∗1 genotype of the CYP3A4∗1G gene. No significant difference was found in the incidence of adverse reactions during analgesia between the two groups. Conclusion: CYP3A4∗1G could be associated with postoperative sufentanil analgesia in Zhuang patients in western Guangxi and should be considered when developing personalized analgesia regimens.

The Role of Glutamine and Glutaminase in Pulmonary Hypertension.

Pulmonary hypertension (PH) refers to a clinical and pathophysiological syndrome in which pulmonary vascular resistance and pulmonary arterial pressure are increased due to structural or functional changes in pulmonary vasculature caused by a variety of etiologies and different pathogenic mechanisms. It is followed by the development of right heart failure and even death. In recent years, most studies have found that PH and cancer shared a complex common pathological metabolic disturbance, such as the shift from oxidative phosphorylation to glycolysis. During the shifting process, there is an upregulation of glutamine decomposition driven by glutaminase. However, the relationship between PH and glutamine hydrolysis, especially by glutaminase is yet unclear. This review aims to explore the special linking among glutamine hydrolysis, glutaminase and PH, so as to provide theoretical basis for clinical precision treatment in PH.

Effects of drying on the structural characteristics and antioxidant activities of polysaccharides from Stropharia rugosoannulata.

We investigated the structural characteristics and antioxidant activities of two types of neutral polysaccharides and two types of acidic polysaccharides from Stropharia rugosoannulata under different drying methods. Fresh S. rugosoannulata were processed with freeze-vacuum drying (FVD) and hot-air drying (HAD). Polysaccharides from the dried S. rugosoannulata (SRP) were purified using a DEAE-52 cellulose column to obtain two types of neutral SRPs (FSRP-1 and HSRP-1) and two types of acidic SRPs (FSRP-2 and HSRP-2). We found that drying can affect the structural characteristics and antioxidant activities of SRPs. Varied monosaccharide compositions were found in FSRP-1, FSRP-2, HSRP-1 and HSRP-2, and HAD-treated SRP had more glucose and less galactose. The (1 → 6)-α-D-Galp linkage was the primary chain in FSRP-1 and HSRP-1, whereas the (1 → 3)-ß-D-Glcp was the backbone structure in FSRP-2 and HSRP-2. Our results thus suggest that hot air drying changed the ß-configuration in polysaccharides. FSRP-1, FSRP-2, HSRP-1 and HSRP-2 had positive ferric ion reducing antioxidant power and scavenging activities on ABTS+ and hydroxyl radicals, whereas HSRP exhibited a stronger antioxidant activity than that of FSRP. Hot-air dried S. rugosoannulata could therefore be recommended as a suitable candidate for use in the preparation of antioxidant polysaccharides as functional foods.

Comparative Effectiveness of Exercise Training for Patients With Chronic Thromboembolic Pulmonary Hypertension After Pulmonary Endarterectomy: A Systematic Review and Meta-Analysis.

Background: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) still experience reduced exercise capacity despite pulmonary endarterectomy (PEA). Exercise training improves the exercise capacity and quality of life (QoL) in patients with PH, but data on the effects of exercise training on these patients are scarce. The aim of this meta-analysis and systematic review was to evaluate the effectiveness and safety of exercise training in CTEPH after PEA. Methods: We searched the relevant literature published before January 2020 for the systematic review and meta-analysis using the PubMed, EMBASE, and Cochrane Library databases. The primary outcome was a change in the 6-min walking distance (6 MWD). We also assessed the effect of exercise on the peak oxygen uptake (VO2) or peak VO2/kg, oxygen uptake anaerobic threshold, workload, oxygen pulse, hemodynamics, arterial blood gases, oxygen saturation, N-terminal pro-brain-type natriuretic peptide (NT-proBNP), quality of life (QoL) and pulmonary function tests. Results: We included 4 studies with 208 exercise-training participants. In the pooled analysis, short-term exercise training can improve the 6 MWD of 58.89 m (95% CI: 46.26-71.52 m, P < 0.0001). There was a significant increase in the peak VO2/kg or peak VO2 after exercise training (3.15 ml/min/kg, 95% CI: 0.82-5.48, P = 0.008; 292.69 ml/min, 95% CI: 24.62-560.75, P = 0.032, respectively). After exercise training, the maximal workload and O2 pulse significantly improved. Three months of exercise training increased the right ventricular ejection fraction by 3.53% (95% CI: 6.31-11.94, P < 0.00001, I 2 = 0) independently of PEA surgery. In addition, NT-proBNP plasma levels significantly improved with exercise training after PEA [weighted mean difference (WMD): -524.79 ng/L, 95% CI: 705.16 to -344.42, P < 0.0001, I 2 = 0]. The partial pressure of oxygen and pH improved progressively over 12 weeks of exercise training (WMD: 4 mmHg, 95% CI: 1.01-8.33, P = 0.01; WMD: 0.03, 95% CI: 0.02-0.04, P < 0.0001, respectively). Subscales of the QoL measured by the SF-36 questionnaire had also improved. In addition, exercise training was well-tolerated with a low dropout rate, and no major adverse events occurred during exercise training. Conclusion: Exercise training may be associated with a significant improvement in the exercise capacity and QoL among CTEPH patients after PEA and was proven to be safe. However, more large-scale multicentre studies are needed to confirm the effectiveness and safety of exercise training in CTEPH patients after PEA. PROSPERO registration number: CRD42021235275.

Survival in severe pulmonary hypertension due to chronic lung disease: influence of in-hospital platelet distribution width.

Platelet distribution width has been recognized as risk predictors of idiopathic pulmonary arterial hypertension. This study aims to investigate whether in-hospital platelet distribution width would be useful to predict all-cause death in patients with severe pulmonary hypertension due to chronic lung diseases (CLD-PH). Early in-hospital platelet distribution width was measured in 67 severe CLD-PH patients who were confirmed by right heart catheterization and followed up. Event-free survival was estimated using the Kaplan-Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the association between the platelet distribution width level and all-cause death. During median of 2.4 (2.5, 3.7) years of follow-up, 44 patients died. A significant association was noted between in-hospital platelet distribution width level and the adjusted risk of all-cause mortality (hazard ratio: 1.245; 95% confidence interval: 1.117-1.386, P < 0.001). Compared with those with platelet distribution width <16.1%, the hazard ratio for all-cause death increased by 5.278 (95% confidence interval: 2.711-10.276, P < 0.0001) among patients with platelet distribution width ≥16.1%. Higher levels of platelet distribution width were also associated with increased risk of all-cause death. In-hospital platelet distribution width was independently associated with all-cause death in patients with severe CLD-PH. This potentially could be used to estimate the severity of severe CLD-PH.

Identification of Macrophage Polarization-Related Genes as Biomarkers of Chronic Obstructive Pulmonary Disease Based on Bioinformatics Analyses.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by lung inflammation and remodeling. Macrophage polarization is associated with inflammation and tissue remodeling, as well as immunity. Therefore, this study attempts to investigate the diagnostic value and regulatory mechanism of macrophage polarization-related genes for COPD by bioinformatics analysis and to provide a new theoretical basis for experimental research. METHODS: The raw gene expression profile dataset (GSE124180) was collected from the Gene Expression Omnibus (GEO) database. Next, a weighted gene coexpression network analysis (WGCNA) was conducted to screen macrophage polarization-related genes. The differentially expressed genes (DEGs) between the COPD and normal samples were generated using DESeq2 v3.11 and overlapped with the macrophage polarization-related genes. Moreover, functional annotations of overlapped genes were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resource. The immune-related genes were selected, and their correlation with the differential immune cells was analyzed by Pearson. Finally, receiver operating characteristic (ROC) curves were used to verify the diagnostic value of genes. RESULTS: A total of 4922 coexpressed genes related to macrophage polarization were overlapped with the 203 DEGs between the COPD and normal samples, obtaining 25 genes related to COPD and macrophage polarization. GEM, S100B, and GZMA of them participated in the immune response, which were considered the candidate biomarkers. GEM and S100B were significantly correlated with marker genes of B cells which had a significant difference between the COPD and normal samples. Moreover, GEM was highly associated with the genes in the PI3K/Akt/GSK3ß signaling pathway, regulation of actin cytoskeleton, and calcium signaling pathway based on a Pearson correlation analysis of the candidate genes and the genes in the B cell receptor signaling pathway. PPI network analysis also indicated that GEM might participate in the regulation of the PI3K/Akt/GSK3ß signaling pathway. The ROC curve showed that GEM possessed an excellent accuracy in distinguishing COPD from normal samples. CONCLUSIONS: The data provide a transcriptome-based evidence that GEM is related to COPD and macrophage polarization likely contributes to COPD diagnosis. At the same time, it is hoped that in-depth functional mining can provide new ideas for exploring the COPD pathogenesis.