Association between red blood cell distribution width and the all-cause mortality of patients with aortic stenosis: A retrospective study.

BACKGROUND: It is essential to assess the risk stratification of patients with aortic stenosis (AS). OBJECTIVE: To clarify the predictive value of red blood cell distribution width (RDW) in AS patients using a large cohort from the MIMIC-IV database. METHODS: Restricted cubic spline, the Kaplan-Meier method, and logistic and Cox regression analyses were used to explore the association between RDW and all-cause mortality in AS patients. Multivariate adjustments, propensity score matching and weighting, and subgroup analysis were conducted to exclude confounding factors. Receiver operating characteristic (ROC) and decision curve analysis (DCA) curves were drawn to evaluate the predictive performance of RDW. RESULTS: 1,148 patients with AS were included. Their death risks gradually increased with the elevation of RDW. Multivariate-adjusted 90-day (OR: 2.12; HR: 1.90; p = 0.001) and 1-year (OR: 2.07; HR: 1.97; p < 0.001) all-cause mortalities were significantly higher in patients with RDW≥14.7 %, which remained robust after propensity score matching and subgroup analysis. For AS patients with high RDW, those < 75 years old had higher death risks than those ≥ 75 years old. The area under the ROC curve of RDW were 0.741 and 0.75 at 90-day and 1-year follow-ups, respectively, exhibiting comparable performance to acute physiology score III and outperforming other critical illness scores in predicting the prognosis of AS patients. DCA curves also illustrated that RDW had a wide range of net benefits. CONCLUSIONS: High RDW was independently associated with increased 90-day and 1-year all-cause mortalities of AS patients, with strong predictive capability of prognosis.

Association of sarcopenia with the long-term risk of atrial fibrillation: A prospective cohort study.

The relationship between sarcopenia and the long-term risk of atrial fibrillation (AF) remains unclear. This study recruited a large prospective Caucasian cohort from the UK Biobank. Participants were assessed at baseline with handgrip strength and muscle mass and were categorized into groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia. Kaplan-Meier method and Cox proportional hazards model were used to explore the association between sarcopenia and the incidence of AF. The genetic predisposition of AF was assessed by polygenic risk score. Sensitivity analyses were performed to validate the results. A total of 384,433 participants with a median age of 58 years and 54.3% women were enrolled in this study. There were 24,007 cases of new-onset AF over a median follow-up of 12.56 years. The groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia accounted for 22,290 (6.1%), 1665 (9.2%), and 52 (11.9%) cases, respectively. Compared with the non-sarcopenia group, participants with probable sarcopenia or confirmed sarcopenia had an 8% (95% CI, 1.03-1.14) or 61% (95% CI, 1.23-2.12) higher risk of AF incidence. The findings remained robust in multiple sensitivity analyses, such as subgroup analysis and further adjustment of genetic predisposition. Notably, the association between sarcopenia and a high AF risk was more pronounced in younger participants, women, and those with valvular heart disease. In conclusion, sarcopenia was associated with a high long-term risk of AF in Caucasians, supporting sarcopenia as a new independent risk factor of AF.

Association of Cardiovascular Health with the Incidence of Venous Thromboembolism: A Prospective Study of 275,149 Participants from the UK Biobank.

BACKGROUND: The Life's Essential 8 (LE8) score, recently proposed by the American Heart Association, represents a new paradigm for evaluating cardiovascular health (CVH). We aimed to explore the association between CVH, estimated using LE8, and venous thromboembolism (VTE) incidence. METHODS: A total of 275,149 participants were recruited from the UK Biobank and divided into high (LE8 score ≥ 80), moderate (LE8 score < 80 but ≥ 50), and low (LE8 score < 50) CVH groups. Restricted cubic spline analysis, the Kaplan-Meier method, and the Cox proportional hazards model were used to explore the association between CVH and VTE. The genetic predisposition to VTE was assessed with a polygenic risk score. Sensitivity analyses were performed to validate the results. RESULTS: During a median follow-up of 12.56 years, VTE developed in 506 (4.09%), 6,069 (2.78%), and 720 (1.66%) participants with low, moderate, and high CVH levels, respectively. Compared with the low CVH group, participants in the moderate and high CVH groups had a 23% (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.71-0.85) and 41% (HR: 0.59; 95% CI: 0.52-0.66) lower risk of VTE, respectively, after adjusting for demographic characteristics, medical history, socioeconomic status, and genetic predisposition. This association remained robust in multiple sensitivity analyses. Higher CVH levels led to a more pronounced reduction in the risk of VTE in females and could appreciably offset the genetic risk of VTE. CONCLUSION: Higher CVH levels were significantly associated with a lower incidence of VTE, encouraging efforts to increase LE8 scores in individuals.

Integrated bioinformatics analysis and experimental animal models identify a robust biomarker and its correlation with the immune microenvironment in pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) represents a substantial global risk to human health. This study aims to identify diagnostic biomarkers for PAH and assess their association with the immune microenvironment through the utilization of sophisticated bioinformatics techniques. Methods: Based on two microarray datasets, differentially expressed genes (DEGs) were detected, and hub genes underwent a sequence of machine learning analyses. After pathways associated with PAH were assessed by gene enrichment analysis, the identified genes were validated using external datasets and confirmed in a monocrotaline (MCT)-induced rat model. In addition, three algorithms were employed to estimate the proportions of various immune cell types, and the link between hub genes and immune cells was substantiated. Results: Using SVM, LASSO, and WGCNA, we identified seven hub genes, including (BPIFA1, HBA2, HBB, LOC441081, PI15, S100A9, and WIF1), of which only BPIFA1 remained stable in the external datasets and was validated in an MCT-induced rat model. Furthermore, the results of the functional enrichment analysis established a link between PAH and both metabolism and the immune system. Correlation assessment showed that BPIFA1 expression in the MCP-counter algorithm was negatively associated with various immune cell types, positively correlated with macrophages in the ssGSEA algorithm, and correlated with M1 and M2 macrophages in the CIBERSORT algorithm. Conclusion: BPIFA1 serves as a modulator of PAH, with the potential to impact the immune microenvironment and disease progression, possibly through its regulatory influence on both M1 and M2 macrophages.

Transcriptome-Wide N6-Methyladenosine Alternations in Pulmonary Arteries of Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats and Novel Therapeutic Targets.

N6-methyladenosine (m6A) is a post-transcriptional epigenetic change with transcriptional stability and functionality regulated by specific m6A-modifying enzymes. However, the significance of genes modified by m6A and enzymes specific to m6A regulation in the context of pulmonary arterial hypertension (PAH) remains largely unexplored. MeRIP-seq and RNA-seq were applied to explore variances in m6A and RNA expression within the pulmonary artery tissues of control and monocrotaline-induced PAH rats. Functional enrichments were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To screen candidate m6A-related genes, the STRING and Metascape databases were used to construct a protein-protein interaction network followed by a real-time PCR validation of their expression. The expression level of an m6A regulator was further investigated using immunohistochemical staining, immunofluorescence, and Western blot techniques. Additionally, proliferation assays were conducted on primary rat pulmonary artery smooth muscle cells (PASMCs). We identified forty-two differentially expressed genes that exhibited either hypermethylated or hypomethylated m6A. These genes are predominantly related to the extracellular matrix structure, MAPK, and PI3K/AKT pathways. A candidate gene, centromere protein F (CENPF), was detected with increased expression in the PAH group. Additionally, we first identified an m6A reader, leucine rich pentatricopeptide repeat containing (LRPPRC), which was downregulated in the PAH rat model. The in vitro downregulation of Lrpprc mediated by siRNA resulted in the enhanced proliferation and elevated expression of Cenpf mRNA in primary rat PASMCs. Our study revealed a modified transcriptome-wide m6A landscape and associated regulatory mechanisms in the pulmonary arteries of PAH rats, potentially offering a novel target for therapeutic strategies in the future.

Evolutionarily conserved IL-22 participates in gut mucosal barrier through its receptors IL-22BP, IL-10R2 and IL-22RA1 during bacterial infection in teleost.

IL-22 is a critical cytokine of epithelial mucosal barrier. In humans, IL-22 signals through a heteroduplex receptor consisting of IL-22R and IL-10Rß. In fish, IL-22 and its receptors homologues have been cloned in a number of species, however, no studies have been reported how the receptors are involved in IL-22 transduction. For this purpose, in this study we identified IL-22 and its soluble receptor IL-22BP and transmembrane receptors IL-22RA1 and IL-10R2 in Carassius cuvieri × Carassius auratus red var. (named WR-IL-22, WR-IL-22BP, WR-IL10R2 and WR-IL22RA1, respectively). WR-IL-22, WR-IL-22BP, WR-IL10R2 and WR-IL22RA1 were relatively conserved in the evolutionary process, sharing the same conserved domains as their higher vertebrate homologues. When the fish were infected with the Aeromonas hydrophila, the expression of WR-IL-22, WR-IL-22BP, WR-IL10R2 and WR-IL22RA1 were significantly induced in the gut. The co-IP assay showed that WR-IL-22 not only interacted with WR-IL-22BP, but also with WR-IL10R2 and WR-IL22RA1. When introduced in vivo, WR-IL-22 activated the JAK1-STAT3 axis and protected the gut mucosa from A. hydrophila infection. However, overexpression of WR-IL-22BP or knockdown of transmembrane receptors WR-IL10R2 and WR-IL22RA1 significantly inhibited the activation of WR-IL-22-mediated JAK1-STAT3 axis and promoted bacterial colonization in the gut. These results provided new insights into the role of IL-22 and its receptors in the gut mucosa barrier and immune response in teleost.

Peripheral Nerve Block and Peri-operative Neurocognitive Disorders in Older Patients With Hip Fractures: A Systematic Review With Meta-analysis.

Background: Poor pain control and opioid use are risk factors for perioperative neurocognitive disorders (PND). The peripheral nerve block (PNB) can reduce pain and opioid consumption. This systematic review aimed to investigate the effects of PNB on PND in older patients with hip fractures. Methods: The PubMed, Cochrane Central Registers of Controlled Trial, Embase and ClinicalTrials.gov databases were searched from inception until November 19, 2021 for all randomized controlled trials (RCTs) comparing PNB with analgesics. The quality of the selected studies was assessed according to Version 2 of the Cochrane tool for assessing the risk of bias in RCTs. The primary outcome was the incidence of PND. Secondary outcomes included pain intensity and the incidence of postoperative nausea and vomiting. Subgroup analyses were based on population characteristics, type and infusion method of local anesthetics, and type of PNB. Results: Eight RCTs comprising 1015 older patients with hip fractures were included. Compared with analgesics, PNB did not reduce the incidence of PND in the elderly hip fracture population comprising patients with intact cognition and those with pre-existing dementia or cognitive impairment (risk ratio [RR] = .67; 95% confidence interval [CI] = .42 to 1.08; P = .10; I2 = 64%). However, PNB reduced the incidence of PND in older patients with intact cognition (RR = .61; 95% CI = .41 to .91; P = .02; I2 = 0%). Fascia iliaca compartment block, bupivacaine, and continuous infusion of local anesthetics were found to reduce the incidence of PND. Conclusions: PNB effectively reduced PND in older patients with hip fractures and intact cognition. When the study population included patients with intact cognition and those with pre-existing dementia or cognitive impairment, PNB showed no reduction in the incidence of PND. These conclusions should be confirmed with larger, higher-quality RCTs.

Identification of BRD7 by whole-exome sequencing as a predictor for intermediate-stage hepatocellular carcinoma in patients undergoing TACE.

OBJECTIVE: In the present study, we aimed to identify potential predictors of intermediate-stage hepatocellular carcinoma (HCC) using whole-exome sequencing (WES) in patients undergoing transarterial chemoembolization (TACE). MATERIALS AND METHODS: In A total of 51 patients, newly diagnosed with intermediate-stage HCC between January 2013 and December 2020, were enrolled. Prior to treatment, histological samples were collected for western blotting and immunohistochemistry. The predictive roles of clinical indicators and genes in patient prognosis were analyzed using univariate and multivariate analyses. Finally, the correlation between imaging features and gene signatures was examined. RESULTS: Using WES, we identified that bromodomain-containing protein 7 (BRD7) was significantly mutated in patients with different TACE responses. No significant difference in BRD7 expression was observed between patients with and without BRD7 mutations. HCC tumors exhibited higher BRD7 than normal liver tissues. Multivariate analysis revealed that alpha-fetoprotein (AFP), BRD7 expression, and BRD7 mutations were independent risk factors for progression-free survival (PFS). In addition, Child-Pugh class, BRD7 expression, and BRD7 mutations were independent risk factors for overall survival (OS). Patients with wild-type BRD7 and high BRD7 expression had worse PFS and OS, whereas those with mutated BRD7 and low BRD7 expression exhibited the best PFS and OS. The Kruskal-Wallis test revealed that wash-in enhancement on computed tomography might be an independent risk factor for high BRD7 expression. CONCLUSION: BRD7 expression may be an independent risk factor for prognosis in patients with HCC undergoing TACE. Imaging features such as wash-in enhancement are closely related to BRD7 expression.

FUT8-Mediated Core Fucosylation Promotes the Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease with unclear underlying molecular mechanisms and limited therapeutic options. This study aimed to explore the role of core fucosylation and the only glycosyltransferase FUT8 in PAH. We observed increased core fucosylation in a monocrotaline (MCT)-induced PAH rat model and isolated rat pulmonary artery smooth muscle cells (PASMCs) treated with platelet-derived growth factor-BB (PDGF-BB). We found that 2-fluorofucose (2FF), a drug used to inhibit core fucosylation, improved hemodynamics and pulmonary vascular remodeling in MCT-induced PAH rats. In vitro, 2FF effectively restrains the proliferation, migration, and phenotypic switching of PASMCs and promotes apoptosis. Compared with controls, serum FUT8 concentration in PAH patients and MCT-induced rats was significantly elevated. FUT8 expression appeared increased in the lung tissues of PAH rats, and the co-localization of FUT8 with α-SMA was also observed. SiRNA was used to knockdown FUT8 in PASMCs (siFUT8). After effectively silencing FUT8 expression, phenotypic changes induced in PASMCs by PDGF-BB stimulation were alleviated. FUT8 activated the AKT pathway, while the admission of AKT activator SC79 could partially counteract the negative effect of siFUT8 on the proliferation, apoptotic resistance, and phenotypic switching of PASMCs, which may be involved in the core fucosylation of vascular endothelial growth factor receptor (VEGFR). Our research confirmed the critical role of FUT8 and its mediated core fucosylation in pulmonary vascular remodeling in PAH, providing a potential novel therapeutic target for PAH.

miR-34a/DRP-1-mediated mitophagy participated in cisplatin-induced ototoxicity via increasing oxidative stress.

PURPOSE: Cisplatin is a widely used and effective chemotherapeutic agent for most solid malignant tumors. However, cisplatin-induced ototoxicity is a common adverse effect that limits the therapeutic efficacy of tumors in the clinic. To date, the specific mechanism of ototoxicity has not been fully elucidated, and the management of cisplatin-induced ototoxicity is also an urgent challenge. Recently, some authors believed that miR34a and mitophagy played a role in age-related and drug-induced hearing loss. Our study aimed to explore the involvement of miR-34a/DRP-1-mediated mitophagy in cisplatin-induced ototoxicity. METHODS: In this study, C57BL/6 mice and HEI-OC1 cells were treated with cisplatin. MiR-34a and DRP-1 levels were analyzed by qRT‒PCR and western blotting, and mitochondrial function was assessed via oxidative stress, JC-1 and ATP content. Subsequently, we detected DRP-1 levels and observed mitochondrial function by modulating miR-34a expression in HEI-OC1 cells to determine the effect of miR-34a on DRP-1-mediated mitophagy. RESULTS: MiR-34a expression increased and DRP-1 levels decreased in C57BL/6 mice and HEI-OC1 cells treated with cisplatin, and mitochondrial dysfunction was involved in this process. Furthermore, the miR-34a mimic decreased DRP-1 expression, enhanced cisplatin-induced ototoxicity and aggravated mitochondrial dysfunction. We further verified that the miR-34a inhibitor increased DRP-1 expression, partially protected against cisplatin-induced ototoxicity and improved mitochondrial function. CONCLUSION: MiR-34a/DRP-1-mediated mitophagy was related to cisplatin-induced ototoxicity and might be a novel target for investigating the treatment and protection of cisplatin-induced ototoxicity.

Association between prothrombin time-international normalized ratio and prognosis of post-cardiac arrest patients: A retrospective cohort study.

Background: Cardiac arrest (CA) can activate blood coagulation. This study aimed to explore the potential prognostic value of prothrombin time-international normalized ratio (INR) in post-CA patients. Methods: The clinical data of eligible subjects diagnosed with CA was extracted from the MIMIC-IV database as the training cohort. Restricted cubic spline (RCS), Kaplan-Meier (K-M) survival curve, and Cox regression analyses were conducted to elucidate the association between the INR and all-cause mortality of post-CA patients. Subgroup analysis, propensity score matching (PSM), and inverse probability of treatment (IPTW) were also conducted to improve stability and reliability. Data of the validation cohort were collected from the eICU database, and logistic-regression analyses were performed to verify the findings of the training cohort. Results: A total of 1,324 subjects were included in the training cohort. A linear correlation existed between INR and the risk of all-cause death of post-CA patients, as shown in RCS analysis, with a hazard ratio (HR) >1 when INR exceeded 1.2. K-M survival curve preliminarily indicated that subjects with INR ≥ 1.2 presented lower survival rate and shorter survival time, and the high level of INR was independently associated with 30-day, 90-day, 1-year, and in-hospital mortalities, with multivariate-adjusted HR of 1.44 (1.20, 1.73), 1.46 (1.23, 1.74), 1.44 (1.23, 1.69), and 1.37 (1.14, 1.64), respectively. These findings were consistent and robust across the subgroup analysis, PSM and IPTW analyses, and validation cohort. Conclusions: We systematically and comprehensively demonstrated that elevated INR was associated with increased short- and long-term all-cause mortality of post-CA patients. Therefore, elevated INR may be a promising biomarker with prognosis significance.

A retrospective study of audiological outcomes after endoscopic tympanoplasty and tympanomastoidectomy in patients with cholesteatoma.

OBJECTIVES: To investigated whether endoscopic tympanoplasty and tympanomastoidectomy could present satisfying audiological outcomes for cholesteatoma patients. METHODS: This was a retrospective study of 83 patients with cholesteatoma who underwent endoscopic tympanoplasty and tympanomastoidectomy between 2019 and 2021. The preoperative and postoperative audiological evaluations were performed. The evaluation methods included air conduction (AC), bone conduction (BC), and air-bone gap (ABG) procedures. RESULTS: Eighty-three patients were included in the study, all of whom underwent endoscopic tympanoplasty and tympanomastoidectomy. Forty-seven patients presented postoperative ABG≤20 dB (59.49%). The frequencies tested included low-frequency (LF), middle-frequency (MF), high-frequency (HF), and pure-tone average (PTA). All three audiological parameters significantly decreased after surgery (P < 0.05) at every frequency, except for BC-LF (P > 0.05). There were also significant differences between the preoperative and postoperative proportions of degree of hearing (P < 0.05). Additionally, shifts in AC, BC, and ABG were linearly related to preoperative AC, BC, and ABG. Lastly, postoperative ABG-PTA presented differently depending on preoperative stapes superstructure conditions (present: 15.81 ± 11.23 dB, absent: 22.94 ± 12.20 dB, P = 0.009). CONCLUSIONS: Our study of endoscopic tympanoplasty and tympanomastoidectomy presented complete audiological outcomes for cholesteatoma patients. It had a positive surgery success rate and improved AC, BC, and ABG at every frequency except BC-LF. Additionally, AC-LF and AC-MF improved to a greater degree than AC-HF due to these procedures. Moreover, the linear regression analyses demonstrated that preoperative ABG-PTA was the most efficient audiological indicator for surgery. Likewise, the preoperative condition of the stapes superstructure was proved to be the most efficient anatomical indicator for hearing outcomes.

Pulmonary veno-occlusive disease in Sjogren's syndrome: a case report.

BACKGROUND: Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) belongs to Group 1 pulmonary hypertension. Pulmonary veno-occlusive disease (PVOD), which is characterized by venous system aberrations, has been previously reported in CTD-PAH; however, it has rarely been observed in Sjogren's syndrome (SS). CASE PRESENTATION: Our 28-year-old female patient was admitted to the hospital with recurrent shortness of breath even after minimal physical activity. Her chest high-resolution CT scan demonstrated pulmonary artery dilatation and bilateral ground-glass nodules. A subsequent right heart catheterization confirmed pulmonary hypertension because her mean pulmonary arterial pressure was 62 mmHg. Our inquisitive genomic assessment identified a novel EIF2AK4 mutation at c.1021 C > T (p. Gln341*), the dominant causal gene of PVOD. Histological examination demonstrated stenosis and occlusions in the pulmonary veins. Because she presented with features such as dry eyes and Raynaud's phenomenon, we performed a biopsy on the labial salivary gland, which confirmed SS. Her treatment regimen included PAH-targeted therapies (tadalafil and macitentan) in combination with hydroxychloroquine. Although she was hospitalized several times due to acute exacerbation of PAH, her disease progression was under control, and she did not demonstrate any signs of pulmonary edema even after a three-year treatment period. CONCLUSION: Here, we report the case of an SS-PAH patient with PVOD who carried a novel biallelic EIF2AK4 mutation, and PAH-targeted therapies were well tolerated by our patient.

Idarubicin-Loaded DEB-TACE plus Lenvatinib versus Lenvatinib for patients with advanced hepatocellular carcinoma: A propensity score-matching analysis.

AIMS: To investigate the efficacy and safety of lenvatinib and idarubicin-loaded drug-eluting beads transarterial chemoembolization (IDADEB-TACE) in primary advanced hepatocellular carcinoma (HCC). METHODS: This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB-TACE as first-line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score-matching was used to reduce the influence of confounding factors on the outcomes. RESULTS: The study reviewed 118 patients who received lenvatinib plus IDADEB-TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score-matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post-treatment ORR (57.7% vs. 25.6%, p < 0.001, respectively), median OS and TTP (15.7 vs. 11.3 months, hazard ratio [HR] = 0.50, p < 0.001; 8.0 vs. 5.0 months, HR = 0.60, p = 0.003, respectively), 6- and 12-month OS rates (88.5% vs. 71.4%; 67.6% vs. 43.4%, respectively), and progression-free rates at 6 and 12 months (60.3% vs. 42.3%; 21.1% vs. 10.3%, respectively). Vascular invasion, α-fetoprotein level, and treatment type were independent OS predictors, and vascular invasion and treatment type were independent TTP predictors. Incidences of nausea/vomiting, fever, abdominal pain, and increased ALT/AST were higher in the LIDA group than in the LEN group. CONCLUSIONS: Lenvatinib plus IDADEB-TACE is well-tolerated and more effective than lenvatinib monotherapy in patients with advanced HCC.

Cationic metal-organic framework derived ruthenium-copper nano-alloys in porous carbon to catalytically boost the cycle life of Li-CO2 batteries.

Rechargeable Li-CO2 batteries are an innovative energy storage technology with broad application prospects owing to their superb energy density and ability to capture the greenhouse gas CO2. However, they are still suffering from severe challenges in the formation and decomposition of electrochemically sluggish Li2CO3 discharge products, resulting in poor battery performance. Development of an efficient cathodic electrocatalyst has the potential to address these issues by catalytically boosting the conversion of Li2CO3. Herein, we have designed a Ru-Cu nanoalloy decorated porous carbon (Ru-Cu@NPC) material derived from an anion-exchanged cationic MOF, and it can serve as an efficient cathode electrocatalyst for Li-CO2 batteries. Benefitting from the uniform distribution of ultrafine Ru-Cu nanoalloys with high catalytic performance, Ru-Cu@NPC displays excellent CO2 reduction and evolution activities. Impressively, the Li-CO2 battery with the Ru-Cu@NPC catalyst exhibits a remarkably low potential gap of 0.93 V at 100 mA g-1 and a stable discharge/charge cycling performance of more than 400 cycles at a high current density of 400 mA g-1 within a limiting capacity of 1000 mA h g-1. The study provides an opportunity for the research of cationic MOF derived bimetallic catalysts in the Li-CO2 battery field.

A retrospective cohort study on the association between early coagulation disorder and short-term all-cause mortality of critically ill patients with congestive heart failure.

Purpose: Coagulation disorder in congestive heart failure (CHF) has been well-documented. The prognostic value of a composite coagulation disorder score, which combines the absolute platelet count, international normalized ratio (INR), and activated partial thromboplastin time (APTT), has not been assessed in CHF. The present study endeavored to explore the association between the coagulation disorder score and adverse outcomes of critically ill patients with CHF. Methods: Patients diagnosed with CHF in the Medical Information Mart for Intensive Care III (MIMIC-III) database were included in the present retrospective cohort study. The coagulation disorder score was calculated according to the abnormalities of the absolute platelet count, INR, and APTT within 24 h after intensive care unit admission. The primary outcomes were the short-term all-cause mortality, including 30-, 90-day and in-hospital mortalities. The Kaplan-Meier (K-M) survival curve and the Cox proportional hazard model were performed to assess the correlation between coagulation disorder score and outcome events. Results: A total of 6,895 patients were enrolled in this study and divided into four groups according to the coagulation disorder score. K-M survival curve preliminarily indicated that subjects with higher coagulation disorder score presented lower survival rate and shorter survival time. After adjustment for potential confounders, the multivariate Cox analysis further illustrated that elevated coagulation disorder score as a quartile variable was significantly associated with increased all-cause mortality (quartile 4 vs. quartile 1, 30-day: HR [95% CI], 1.98 [1.50, 2.62], 90-day: HR [95% CI], 1.88 [1.49, 2.37], in-hospital: HR [95%CI], 1.93 [1.42, 2.61]). Conclusion: In critically ill patients with CHF, ones with high coagulation disorder score tend to be worse clinical prognosis, which would be a promising biomarker and helpful for the management of CHF patients.

Sensorineural damage in chronic suppurative otitis media with and without cholesteatoma: a comparative study.

Background: Chronic suppurative otitis media (CSOM) is a common otolaryngology disease, and cholesteatoma is the most aggressive type of CSOM. CSOM with and without cholesteatoma both result in a certain level of sensorineural damage, which can be categorized as air conduction (AC), bone conduction (BC), or air-bone gap (ABG), and AC, BC, and ABG are affected by many factors. Further analyses and comparisons of factors affecting sensorineural damage in CSOM with and without cholesteatoma were conducted in this study. Methods: A comparative study was conducted of 79 patients with CSOM (39 with cholesteatoma and 40 without cholesteatoma) whose diagnoses were mainly based on chronic middle ear infections and hearing loss (HL), typical computed tomography (CT) and surgical findings. Audiological evaluation included AC, BC and ABG, and sensorineural damage was defined as mixed and sensorineural HL (SNHL). Results: In relation to the types of HL, there were no significant differences between both groups. The CSOM with cholesteatoma group had significantly greater AC (P=0.000) and a significantly greater ABG (P>0.05) than the CSOM without cholesteatoma group, but BC did not differ significantly between both groups (P>0.05). The average AC-middle frequency (MF), AC-high frequency (HF), ABG-MF and ABG-HF of CSOM without cholesteatoma were smaller than these of CSOM with cholesteatoma (P<0.05). The degree of HL differed significantly between both groups (P=0.000). The CSOM with cholesteatoma group showed a higher level of HL than the CSOM without cholesteatoma group. The presence of cholesteatoma was presented a protective factor associated with sensorineural damage (P<0.05), while higher degrees of hearing and aging were risk factors (P<0.05), respectively. Conclusions: Our direct comparisons showed that HL progressed more rapidly in the CSOM with cholesteatoma group, which had higher frequencies in relation to AC, the ABG, and severity. However, in relation to BC, there were no significant differences between both groups, which was in line with the similar proportions of the types of HL in both groups. The logistic regression showed that the presence of cholesteatoma was a protective factor, and the degree of hearing and aging were risk factors associated with sensorineural damage.

Aeromonas hydrophila Ssp1: A secretory serine protease that disrupts tight junction integrity and is essential for host infection.

Aeromonas hydrophila is a Gram-negative bacterial pathogen with a broad host range, including fish and humans. In this study, we examined the function of a secretory serine protease (named Ssp1) identified in pathogenic A. hydrophila CCL1. Ssp1 possesses a trypsin-like serine protease domain and contains two conserved PDZ domains. Recombinant Ssp1 protein (rSsp1) treatment increased intestinal permeability by downregulating and redistributing tight junction protein Occludin in intestinal Caco-2 cells in vitro. Western blot demonstrated that rSsp1 treatment in Caco-2 cells resulted in marked increases in the expressions of myosin light chain kinase (MLCK) and phosphorylated myosin light chain (p-MLC). For virulence analysis, an isogenic CCL1 mutant ΔSsp1 was created. ΔSsp1 bears an in-frame deletion of the Ssp1 gene. A live infection study in crucian carps showed that, compared to CCL1, ΔSsp1 infection exhibited increased Occludin expression, reduced intestinal permeability and tissue dissemination capacity, and attenuated overall virulence in vivo. However, ΔSsp1 showed no differences in the biofilm formation, swimming motility, and resistance to environmental stress. These lost virulence capacities of ΔSsp1 were restored by complementation with the Ssp1 gene. Global transcriptome analysis and quantitative real-time RT-PCR showed that compared to CCL1 infection, ΔSsp1 promoted the expressions of antimicrobial molecules (MUC2, LEAP-2, Hepcidin-1, and IL-22). Finally, CCL1 infection caused significant dysbiosis of the gut microbiota, including increased Vibrio and Deefgea compared to ΔSsp1 infected fish. Taken together, these results indicate that Ssp1 is essential for the virulence of A. hydrophila and is required for the perturbation of intestinal tight junction barrier.

Integrated Bioinformatic Analysis Reveals TXNRD1 as a Novel Biomarker and Potential Therapeutic Target in Idiopathic Pulmonary Arterial Hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening cardiopulmonary disease lacking specific diagnostic markers and targeted therapy, and its mechanism of development remains to be elucidated. The present study aimed to explore novel diagnostic biomarkers and therapeutic targets in IPAH by integrated bioinformatics analysis. Four eligible datasets (GSE117261, GSE15197, GSE53408, GSE48149) was firstly downloaded from GEO database and subsequently integrated by Robust rank aggregation (RRA) method to screen robust differentially expressed genes (DEGs). Then functional annotation of robust DEGs was performed by GO and KEGG enrichment analysis. The protein-protein interaction (PPI) network was constructed followed by using MCODE and CytoHubba plug-in to identify hub genes. Finally, 10 hub genes were screened including ENO1, TALDO1, TXNRD1, SHMT2, IDH1, TKT, PGD, CXCL10, CXCL9, and CCL5. The GSE113439 dataset was used as a validation cohort to appraise these hub genes and TXNRD1 was selected for verification at the protein level. The experiment results confirmed that serum TXNRD1 concentration was lower in IPAH patients and the level of TXNRD1 had great predictive efficiency (AUC:0.795) as well as presents negative correlation with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). Consistently, the expression of TXNRD1 was proved to be inhibited in animal and cellular model of PAH. In addition, GSEA analysis was performed to explore the functions of TXNRD1 and the results revealed that TXNRD1 was closely correlated with mTOR signaling pathway, MYC targets, and unfolded protein response. Finally, knockdown of TXNRD1 was shown to exacerbate proliferative disorder, migration and apoptosis resistance in PASMCs. In conclusion, our study demonstrates that TXNRD1 is a promising candidate biomarker for diagnosis of IPAH and plays an important role in PAH pathogenesis, although further research is necessary.

A comparative study of changes in audiological characteristics when using endoscopic and microscopic stapes surgery in patients with otosclerosis.

Background: Endoscopic stapes surgery (ESS) is widely used to treat patients with otosclerosis, and accumulating evidence demonstrates that endoscopic stapedotomy is feasible and has similar, and often even better, audiological outcomes compared with microscopic stapedotomy. There is a lack of studies on comparisons of ESS and the audiological outcomes of ESS and microscopic stapes surgery (MSS). Therefore, in the present study, we investigated these to figure out if ESS could be a reasonable alternative treatment for otosclerosis patients. Methods: This was a cohort study of 65 patients with otosclerosis who underwent ESS (n=30) or MSS (n=35) between 2017 and 2021, whose diagnoses were mainly based on a history of progressive conductive or mixed deafness over 25 dB in the range of 0.25-4 kHz. Preoperative and postoperative audiological evaluation, including air-conduction (AC), bone-conduction (BC) and air-bone gap (ABG), was carried out using pure-tone audiometry and performed within 4 weeks before surgery and from 1-14 months after surgery. Results: Thirty ESS and 35 MSS patients were included. There were no significant differences in preoperative and postoperative pure-tone average AC (AC-PTA), BC-PTA, and ABG-PTA between the 2 groups. Postoperative ABG ≤10 dB was found in 8 ESS patients (60%) and 15 MSS patients (43%) (P=0.168). AC and ABG changes in the low-frequency (LF) and mid-frequency (MF) ranges were greater than those in the high-frequency (HF) range for both groups (P<0.05). Although auditory changes between the 2 groups were similar, MSS appeared to have a better BC-PTA compared with ESS (P=0.049). Shifts in ABG and BC were linearly related to preoperative ABG and BC in both groups, and shifts in AC were linearly related to preoperative AC in the ESS group (P<0.05). Conclusions: ESS had a similar audiological outcome compared with MSS, and LF and MF hearing improved to a greater degree than HF hearing in both groups in our study. Based on the linear regression analysis in our study, preoperative ABG-PTA was proved to be the most efficient surgical indicator for both types of stapes surgery for patients with otosclerosis.