Diagnostic Accuracy of Exosomal Long Noncoding RNAs in Diagnosis of NSCLC: A Meta-Analysis.

PURPOSE: Globally, non-small cell lung cancer (NSCLC) is the primary cause of cancer-related mortality, both early and accurate diagnosis are essential for effective treatment and improved patient outcomes. Exosomal noncoding RNAs (ncRNAs) have emerged as promising biomarkers for NSCLC diagnosis. This meta-analysis aims to assess the diagnostic accuracy of exosomal long noncoding RNAs (lncRNAs) for diagnosing NSCLC. METHODS: A comprehensive literature search was conducted to identify relevant studies that assessed the diagnostic performance of exosomal lncRNAs in NSCLC. Quality assessment and data extraction were performed independently by two reviewers. Pooled sensitivity, specificity, and other relevant diagnostic parameters were calculated using a bivariate random-effects model. Subgroup analyses and meta-regression were conducted to explore potential sources of heterogeneity. RESULTS: Sixteen studies, comprising 1843 NSCLC cases and 1298 controls, were included in this meta-analysis. The pooled sensitivity and specificity of nine exosomal lncRNAs for diagnosing NSCLC were 0.74 [95% confidence interval (CI) 0.69-0.79] and 0.78 (95% CI 0.68-0.85). The pooled area under the receiver operating characteristic curve (AUC) for fifteen lncRNAs was 0.80 (95% CI 0.768-0.831). Meta-regression could not find any source for interstudy heterogeneity. CONCLUSION: Exosomal lncRNAs, particularly AL139294.1, GAS5, LUCAT1, and SOX2-OT, have excellent diagnostic accuracy and promising diagnostic potential in NSCLC. Therefore, they can be used as diagnostic tools for early detection of NSCLC.

Impact of red blood cell transfusion and hemoglobin threshold on 1-year mortality among surgical sepsis survivors: A propensity score matching study.

BACKGROUND: Despite the fact that red blood cell (RBC) transfusion is commonly applied in surgical intensive care unit (ICU), the effect of RBC transfusion on long-term outcomes remains undetermined. We aimed to explore the association between RBC transfusion and the long-term prognosis of surgical sepsis survivors. METHODS: This retrospective study was conducted on adult sepsis patients admitted to a tertiary surgical ICU center in China. Patients were divided into transfusion and non-transfusion groups based on the presence of RBC transfusion. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW)were performed to balance the potential confounders. RESULTS: A total of 1421 surgical sepsis survivors were enrolled, including 403 transfused patients and 1018 non-transfused patients. There was a significant difference in 1-year mortality between the two groups (23.1 â€‹% vs 12.7 â€‹%, HR: 1.539, 95 â€‹% confidence interval [CI]: 1.030-2.299, P â€‹< â€‹0.001). After PSM and IPTW, transfused patients still showed significantly increased 1-year mortality risks compared to non-transfused individuals (PSM: 23.6 â€‹% vs 15.9 â€‹%, HR 1.606, 95 â€‹% CI 1.036-2.488 â€‹P â€‹= â€‹0.034; IPTW: 20.1 â€‹% vs 12.9 â€‹%, HR 1.600, 95 â€‹% CI 1.040-2.462 â€‹P â€‹= â€‹0.032). Among patients with nadir hemoglobin below 70 â€‹g/L, 1-year mortality risks in both groups were similar (HR 1.461, 95 â€‹% CI 0.909-2.348, P â€‹= â€‹0.118). However, among patients with nadir hemoglobin above 70 â€‹g/L, RBC transfusion was correlated with increased 1-year mortality risk (HR 1.556, 95 â€‹% CI 1.020-2.374, P â€‹= â€‹0.040). CONCLUSION: For surgical sepsis survivors, RBC transfusion during ICU stay was associated with increased 1-year mortality, especially when patients show hemoglobin levels above 70 â€‹g/L.

Exploring the optimal range of central venous pressure in sepsis and septic shock patients: A retrospective study in 208 hospitals.

BACKGROUND: The aim of this study was to investigate the optimal CVP range in sepsis and septic shock patients admitted to intensive care unit. METHODS: We performed a retrospective study with adult sepsis patients with CVP records based on the eICU Collaborative Research Database. Multivariable logistic regression was performed to explore the associations between CVP level and hospital mortality. Non-linear correlations and optimal CVP range were explored using restricted cubic splines (RCS). RESULTS: A total of 5302 sepsis patients were included in this study. Patients in 4-8 mmHg group owned the lowest odds ratio for raw hospital mortality (19.7%). The logistic regression analyses revealed that hospital death risk increased significantly when mean CVP level exceeds 12 mmHg compared to 4-8 mmHg level. U-shaped association of CVP with hospital mortality was revealed by RCS model in septic shock patients and the optimal range was 5.6-12 mmHg. While, there was a J-shaped trend for non-septic shock patients. For non-septic shock patients, patients had an increased risk of hospital death only if CVP exceeded 11 mmHg. CONCLUSIONS: We observed U-shaped association between mean CVP level and hospital mortality in septic shock patients and J-shaped association in non-septic shock patients. This may imply that patients with different severity of sepsis have different CVP requirements. We need to monitor and manage CVP according to the circulatory status of the sepsis patient.

Edaphic regulation of soil organic carbon fractions in the mattic layer across the Qinghai-Tibetan Plateau.

The mattic layer is a main ecological function bearer of alpine meadow soils in the Qinghai-Tibet Plateau. It has high soil organic carbon (SOC) content with a variety of SOC fractions, which are thought to have different sensitivities to climate change. The effects of soil properties and climate on the SOC fractions in the mattic layer are not well understood. To address this, we analyzed the effects of environmental factors on two SOC fractions: particulate organic carbon (POC) and mineral-associated organic carbon (MAOC). A random forest model (RFM), partial correlation analysis, and structural equation model (SEM) were used to quantify the relative effects of soil and climatic factors on SOC fractions. We found that SOC and its fractions are primarily regulated by soil properties rather than climate. Partial correlation analysis and SEM revealed that climate indirectly affects SOC by influencing soil properties. Silt+Clay and exchangeable calcium (Caex) were found to be the strongest contributing factors of MAOC and POC, respectively. A distinct shift occurs in the mechanism underlying SOC stabilization with varying soil pH. In acidic and neutral environments, amorphous Al/Fe-(hydr) oxides contribute to the stability of MAOC, whereas free Al/Fe-(hydr) oxides promote SOC mineralization. Conversely, Caex positively influences the stabilization of both POC and MAOC throughout the pH range. These results can be extrapolated to predict SOC dynamics in future soil conditions affected by environmental change, especially for use in Earth system models.

Realistic Nanoplastics Induced Pulmonary Damage via the Crosstalk of Ferritinophagy and Mitochondrial Dysfunction.

The smaller size fraction of plastics may be more substantially existing and detrimental than larger-sized particles. However, reports on nanoplastics (NPs), especially their airborne occurrences and potential health hazards to the respiratory system, are scarce. Previous studies limit the understanding of their real respiratory effects, since sphere-type polystyrene (PS) nanoparticles differ from NPs occurring in nature with respect to their physicochemical properties. Here, we employ a mechanical breakdown method, producing NPs directly from bulk plastic, preserving NP properties in nature. We report that among four relatively high abundance NP materials PS, polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polyethylene (PE) with a size of 100 nm, PVC induced slightly more severe lung toxicity profiles compared to the other plastics. The lung cytotoxicity of NPs is higher than that of commercial PS NPs and comparable to natural particles silicon dioxide (SiO2) and anatase titanium dioxide (TiO2). Mechanistically, BH3-interacting domain death agonist (Bid) transactivation-mediated mitochondrial dysfunction and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy or ferroptosis are likely common mechanisms of NPs regardless of their chemical composition. This study provides relatively comprehensive data for evaluating the risk of atmospheric NPs to lung health.

Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder.

BACKGROUND: It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. METHODS: 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. RESULTS: In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. CONCLUSIONS: Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

Sex-differential cognitive performance on MCCB of youth with BD-II depression.

BACKGROUND: Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression. METHOD: This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted. RESULT: ​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression. CONCLUSION: Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients.

Improving Intestinal Barrier Function in Sepsis by Partially Hydrolysed Guar Gum via the Suppression of the NF-κB/MLCK Pathway.

Partially hydrolyzed guar gum (PHGG) protects against intestinal barrier dysfunction and can ameliorate some intestinal diseases. However, whether PHGG has a role in protecting intestinal barrier function (IBF) during sepsis remains unclear. This study aimed to investigate the role and probable mechanism of PHGG in the intestinal mucosa in sepsis. A rat sepsis model was constructed using cecal ligation and puncture (CLP). FITC-dextran 4 (FD-4) flux, serum inflammatory mediator levels, tight junction (TJ) levels, jejunum mucosa pathology, and epithelial intercellular junction ultrastructure were monitored to evaluate the effect of PHGG on IBF. Caco-2 monolayers were used to study the impact and mechanism of PHGG on lipopolysaccharide (LPS)-induced barrier dysfunction in vitro. The expression of zonula occludens protein-1 and occludin and the location of P65 were studied by immunofluorescence. Nuclear factor kappa B (NF-κB) and myosin light chain kinase 3 (MLCK) pathway-related protein expression was verified by quantitative reverse transcriptase polymerase chain reaction or western blotting. The results indicated that the jejunal mucosa structure was destroyed, the villi were disrupted and shortened, and neutrophil infiltration was evident in the septic rats. Compared to Sham group, spetic rats had increased Chiu's score, serum inflammatory mediator levels, and FD-4 flux but decreased TJ and gap junction density. In addition, the expression of MLCK, p-MLC, and TJ proteins and the expression of P65 in the nucleus were increased in septic rats. Furthermore, compared to those in the Control group, LPS-treated Caco-2 cells showed lower cell viability and transepithelial electrical resistance, while had higher FD-4 flux and the expression of MLCK, p-MLC, TJ proteins and P65 in the nucleus. PHGG pretreatment reversed the above effects induced by CLP or LPS treatment. Moreover, SN50, an NF-κB inhibitor, attenuated the above effects of LPS on Caco-2 cells. Overall, PHGG reduced inflammation, increased TJ protein expression and localization, and relieved damage to the TJ structure and intestinal permeability through suppression of the NF-κB/MLCK pathway. This study provides new insights into the role of PHGG in sepsis therapy.

Study on the impact of COVID-19 pandemic on the mental health of Chinese college students: a cross-sectional analysis.

Background: The COVID-19 pandemic has significantly impacted the mental health of college students, prompting the need for universities to implement measures to mitigate these adverse effects. This study aims to assess the mental health status and mitigation measures of college students, identify the primary factors contributing to their mental health challenges, and provide suggestions for educational institutions to reduce negative psychological impacts. Methods: In February 2023, a questionnaire survey was conducted among 1,445 college students. Statistical analysis was performed on the survey results, and multiple regression models were used to identify significant influencing factors and optimize the model. Results: The study revealed correlations between factors affecting mental health during the pandemic, with interactions observed among some factors. Significant differences in mental health status were found among different groups of college students based on their information-sharing habits through apps and engagement in thesis research. Multiple regression analysis indicated that conducting academic research related to COVID-19 significantly increased the psychological stress of college students during the pandemic (p = 0.043). Among all mitigation measures, playing games demonstrated significant effectiveness in model analysis (p = 0.047). The optimization of the model showed that the multiple regression model considering the interaction of factors was more effective. Conclusion: Our research identifies crucial factors influencing the mental health of college students and investigates the mental health status of various student groups. We recommend that educational institutions adopt proactive strategies and a multifaceted approach to support the mental health of college students and address potential issues that may arise.

Causal associations of immune cells with benign prostatic hyperplasia: insights from a Mendelian randomization study.

BACKGROUND: Previous research has focused on the association between immune cells and the development of benign prostatic hyperplasia (BPH). Nevertheless, the causal relationships in this context remain uncertain. METHODS: This study employed a comprehensive and systematic two-sample Mendelian randomization (MR) analysis to determine the causal relationships between immunophenotypes and BPH. We examined the causal associations between 731 immunophenotypes and the risk of BPH by utilizing publicly available genetic data. Integrated sensitivity analyses were performed to validate the robustness, assess heterogeneity, and examine horizontal pleiotropy in the results. RESULTS: We discovered that 38 immunophenotypes have a causal effect on BPH. Subsequently, four of these immunophenotypes underwent verification using weighted median, weighted mode, and inverse variance weighted (IVW) algorithms, which included CD19 on CD24+ CD27+, CD19 on naive-mature B cell, HLA DR on CD14- CD16+ and HLA DR+ T cell%lymphocyte. Furthermore, BPH exhibited a significant association with three immunophenotypes: CD19 on IgD+ CD38dim (ß = -0.152, 95% CI = 0.746-0.989, P = 0.034), CD19 on IgD+ (ß = -0.167, 95% CI = 0.737-0.973, P = 0.019), and CD19 on naive-mature B cell (ß = -0.166, 95% CI = 0.737-0.972, P = 0.018). CONCLUSIONS: Our study provides valuable insights for future clinical investigations by establishing a significant association between immune cells and BPH.

Size, distribution, and vulnerability of the global soil inorganic carbon.

Global estimates of the size, distribution, and vulnerability of soil inorganic carbon (SIC) remain largely unquantified. By compiling 223,593 field-based measurements and developing machine-learning models, we report that global soils store 2305 ± 636 (±1 SD) billion tonnes of carbon as SIC over the top 2-meter depth. Under future scenarios, soil acidification associated with nitrogen additions to terrestrial ecosystems will reduce global SIC (0.3 meters) up to 23 billion tonnes of carbon over the next 30 years, with India and China being the most affected. Our synthesis of present-day land-water carbon inventories and inland-water carbonate chemistry reveals that at least 1.13 ± 0.33 billion tonnes of inorganic carbon is lost to inland-waters through soils annually, resulting in large but overlooked impacts on atmospheric and hydrospheric carbon dynamics.

Normalized circulating Tfh and Th17 associates with improvement in myasthenia gravis treated with ofatumumab.

Objective: To assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical improvement in patients with myasthenia gravis (MG). Methods: 28 anti-AchR positive MG patients treated with ofatumumab and 28 healthy controls (HCs) were included. Frequencies of cTfh and cTh17 cells were monitored by flow cytometry at baseline and 4, and 12 weeks after the initial dose ofatumumab. Serum cytokines associated with cTfh and cTh17, including IL-6, IL-21, and IL-17, were also analyzed. Results: The frequency of cTfh and cTh17 significantly increased in MG patients compared with HCs. Additionally, elevated levels of both T-cell subsets correlated with MG severity. During the follow-up, cTfh and cTh17 return to normal after BCDT. Furthermore, the decrease in cTfh and cTh17 was associated with MG scores improvement over time. Notably, cTfh- and cTh17-related cytokines, including IL-6, IL-21, and IL-17, exhibited a marked decrease following ofatumumab therapy. Conclusions: Abnormal expansion of cTfh and cTh17 cells may be key features in the immunopathology of MG. Their levels returned to normal after BCDT, which was closely correlated with clinical amelioration. This result suggests that these two T-cell subsets may be targets for BCDT treatment of MG.

Supershear triggering and cascading fault ruptures of the 2023 Kahramanmaras, Türkiye, earthquake doublet.

On 6 February 2023, two large earthquakes (moment magnitude 7.8 and 7.6) shocked a vast area of southeastern Türkiye and northern Syria, leading to heavy casualties and economic loss. To investigate the rupture process over multiple fault segments, we performed a comprehensive analysis of local seismic and geodetic data and determined supershear ruptures on the initial branch and the Pazarcik and Erkenek segments and subshear ruptures on the Amanos segment of event 1. The bilateral rupture of event 2 also presents distinct sub- and supershear velocities. The dynamic stress of the branch fault rupture triggered the Pazarcik segment initial rupture at a point 9 kilometers west of the junction of these two faults, boosting the supershear rupture of the Pazarcik segment of the main fault. The geometry and prestress level of multiple segments controlled the rupture behaviors and influenced the ground shaking intensity.

Pervasive soil phosphorus losses in terrestrial ecosystems in China.

Future phosphorus (P) shortages could seriously affect terrestrial productivity and food security. We investigated the changes in topsoil available P (AP) and total P (TP) in China's forests, grasslands, paddy fields, and upland croplands during the 1980s-2010s based on substantial repeated soil P measurements (63,220 samples in the 1980s, 2000s, and 2010s) and machine learning techniques. Between the 1980s and 2010s, total soil AP stock increased with a small but significant rate of 0.13 kg P ha-1 year-1 , but total soil TP stock declined substantially (4.5 kg P ha-1 year-1 ) in the four ecosystems. We quantified the P budgets of soil-plant systems by harmonizing P fluxes from various sources for this period. Matching trends of soil contents over the decades with P budgets and fluxes, we found that the P-surplus in cultivated soils (especially in upland croplands) might be overestimated due to the great soil TP pool compared to fertilization and the substantial soil P losses through plant uptake and water erosion that offset the P additions. Our findings of P-deficit in China raise the alarm on the sustainability of future biomass production (especially in forests), highlight the urgency of P recycling in croplands, and emphasize the critical role of country-level basic data in guiding sound policies to tackle the global P crises.

Personality traits as predictors for treatment response to sertraline among unmedicated obsessive-compulsive Disorder: A 12-weeks retrospective longitudinal study.

The effectiveness of selective serotonin reuptake inhibitors (SSRIs) as a primary treatment for obsessive-compulsive disorder (OCD) remains uncertain. Even after undergoing standard SSRIs treatment, 40%-60% of individuals with OCD persistently endure symptoms. Recent studies proposed that personality traits may influence the diversity of OCD treatment results. Thus, in this retrospective study, we evaluated the Eysenck Personality Questionnaire (EPQ) scores of 51 untreated patients with OCD and 35 healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed to assess OCD symptom severity at weeks 0, 2, 4, 8, and 12 of sertraline treatment. The primary outcome focused on the reduction rate of Y-BOCS scores (response: ≥25%; marked response: ≥50%). Our findings revealed that individuals with OCD demonstrated a significantly higher neuroticism score compared to healthy controls. Correlation analyses exposed a positive link between psychoticism and the duration of the disease. Moreover, family history strongly correlated with both obsessive thoughts and the total Y-BOCS score. Subsequent univariate Cox proportional analyses indicated that both low neuroticism and high extraversion traits could forecast the response to sertraline. Furthermore, only a high extraversion trait was linked to a marked response. Our results support the idea that personality traits may contribute to OCD vulnerability and predict sertraline treatment outcomes.

Aldehyde dehydrogenase 2 deficiency reinforces formaldehyde-potentiated pro-inflammatory responses and glycolysis in macrophages.

Aldehyde dehydrogenase 2 (ALDH2) deficiency caused by   genetic variant is present in more than 560 million people of East Asian descent, which can be identified by apparent facial flushing from acetaldehyde accumulation after consuming alcohol. Recent findings indicated that ALDH2 also played a critical role in detoxification of formaldehyde (FA). Our previous studies showed that FA could enhance macrophagic inflammatory responses through the induction of HIF-1α-dependent glycolysis. In the present study, pro-inflammatory responses and glycolysis promoted by 0.5 mg/m3 FA were found in mice with Aldh2 gene knockout, which was confirmed in the primary macrophages isolated from Aldh2 gene knockout mice treated with 50 µM FA. FA at 50 and 100 µM also induced stronger dose-dependent increases of pro-inflammatory responses and glycolysis in RAW264.7 murine macrophages with knock-down of ALDH2, and the enhanced effects induced by 50 µM FA was alleviated by inhibition of HIF-1α in RAW264.7 macrophages with ALDH2 knock-down. Collectively, these results clearly demonstrated that ALDH2 deficiency reinforced pro-inflammatory responses and glycolysis in macrophages potentiated by environmentally relevant concentration of FA, which may increase the susceptibility to inflammation and immunotoxicity induced by environmental FA exposure.

Structured postoperative handover protocol improves efficiency and quality of interdisciplinary communication and nursing care in surgical intensive care unit: a randomized controlled trial.

This study aimed to evaluate the effectiveness of a structured postoperative handover protocol for postoperative transfer to the SICU. This study was a randomized controlled trial conducted in a comprehensive teaching hospital in China. Patients who were transferred to the SICU after surgery were randomly divided into two groups. The intervention group underwent postoperative structured handover protocol, and the control group still applied conventional oral handover. A total of 101 postoperative patients and 50 clinicians were enrolled. Although the intervention group did not shorten the handover duration (6.18 ± 1.66 vs 5.94 ± 1.91; P = 0.505), the handover integrity was significantly improved, mainly reflected in fewer information omissions (1.44 ± 0.97 vs 0.67 ± 0.62; P < 0.001), fewer additional questions raised by ICU physicians (1.06 ± 1.04 vs 0.24 ± 0.43; P < 0.001) and fewer additional handovers via phone call (16% vs 3.9%; P = 0.042). The total score of satisfaction of the intervention group was significantly higher than that of the control group (76.44 ± 7.32 vs 81.24 ± 6.95; P = 0.001). With respect to critical care, the incidence of stage I pressure sore within 24 h was lower in the intervention group than in the control group (20% vs 3.9%, P = 0.029). Structured postoperative handover protocol improves the efficiency and quality of interdisciplinary communication and clinical care in SICU.Trial registration This study was registered in China on January 8th, 2022 at Chinese Clinical Trial Registry (ChiCTR2200055400).

circELP2 reverse-splicing biogenesis and function as a pro-fibrogenic factor by targeting mitochondrial quality control pathway.

Idiopathic pulmonary fibrosis (IPF) is considered as a chronic, fibrosing interstitial pneumonia with unknown mechanism. The present work aimed to explore the function, biogenesis and regulatory mechanism of circELP2 in pulmonary fibrosis and evaluate the value of blocking circELP2-medicated signal pathway for IPF treatment. The results showed that heterogeneous nuclear ribonucleoprotein L initiated reverse splicing of circELP2 resulting in the increase of circELP2 generation. The biogenetic circELP2 activated the abnormal proliferation and migration of fibroblast and extracellular matrix deposition to promote pulmonary fibrogenesis. Mechanistic studies demonstrated that cytoplasmic circELP2 sponged miR-630 to increase transcriptional co-activators Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ). Then, YAP1/TAZ bound to the promoter regions of their target genes, such as mTOR, Raptor and mLST8, which in turn activated or inhibited the genes expression in mitochondrial quality control pathway. Finally, the overexpressed circELP2 and miR-630 mimic were packaged into adenovirus vector for spraying into the mice lung to evaluate therapeutic effect of blocking circELP2-miR-630-YAP1/TAZ-mitochondrial quality control pathway in vivo. In conclusion, blocking circELP2-medicated pathway can alleviate pulmonary fibrosis, and circELP2 may be a potential target to treat lung fibrosis.

A nomogram based on psoas muscle index predicting long-term cirrhosis incidence in non-cirrhotic patients with HBV-related acute­on­chronic liver failure.

There is a lack of scoring system to predict the occurrence of cirrhosis in individuals with acute-on-chronic liver failure (ACLF) in the absence of cirrhosis. The goal of this study was to develop a psoas muscle index (PMI)-based nomogram for cirrhosis risk in non-cirrhotic patients with HBV-related ACLF. We included 274 non-cirrhotic HBV-ACLF patients who were randomly assigned to training and validation groups. Logistic analyses were performed to identify risk factors for cirrhosis. A nomogram was then constructed. The predictive performance of the nomogram was assessed using the area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA). During the 360-day follow-up, 44.5% (122/274) of non-cirrhotic HBV-ACLF patients developed cirrhosis. A higher PMI at the L3 level was correlated with a decreased risk of long-term cirrhosis occurrence (OR 0.677, 95% CI 0.518-0.885, P = 0.004). The nomogram incorporating PMI, age, neutrophil-to-lymphocyte ratio (NLR), and international normalized ratio (INR), indicated satisfactory predictive performance for cirrhosis risk stratification in ACLF population. The nomograms had an AUROC of 0.812 (95% CI 0.747-0.866) and 0.824 (95% CI 0.730-0.896) in the training and validation cohorts, respectively. The calibration curves displayed excellent predictive accuracy of the nomogram in both sets. In both cohorts, the DCA verified the nomogram's clinical efficacy. In non-cirrhotic HBV-ACLF patients, a greater PMI appears to protect against long-term cirrhosis occurrence. Strong predictive performance has been demonstrated by PMI-based nomograms in assessing the likelihood of 1-year cirrhosis in those with HBV-ACLF.