Toll-Like Receptor 9 Aggravates Pulmonary Fibrosis by Promoting NLRP3-Mediated Pyroptosis of Alveolar Epithelial Cells.

The apoptosis-prone property of alveolar epithelial cells plays a crucial role in pulmonary fibrosis(PF), but the role of pyroptosis in it is still unclear. Toll-like receptor 9(TLR9) has been reported to play a vital role in the pathogenesis of many diseases. However, the effect of TLR9 on alveolar epithelial cells in PF has not been fully elucidated. Gene expression microarray related to Idiopathic pulmonary fibrosis(IPF) was obtained from the Gene Expression Omnibus(GEO) database. In the mouse model of bleomycin-induced PF, adeno-associated virus(AAV6) was used to interfere with TLR9 to construct TLR9 knockdown mice to study the role of TLR9 in PF, and the specific mechanism was studied by intratracheal instillation of NLR family pyrin domain containing 3(NLRP3) activator. In vitro experiments were performed using A549 cells. Bleomycin-induced pyroptosis in the lung tissue of PF mice increased, and TLR9 protein levels also increased, especially in alveolar epithelial cells. The levels of fibrosis and pyroptosis in lung tissue of TLR9 knockdown mice were improved. We found that TLR9 can bind to the NLRP3, thereby increasing the activation of the NLRP3/caspase-1 inflammasome pathway. When we use the NLRP3 activator, the levels of fibrosis and pyroptosis in lung tissue of TLR9 knockout mice can be counteracted. Pyroptosis of alveolar epithelial cells plays a vital role in PF, and TLR9 can promote NLRP3-mediated pyroptosis of alveolar epithelial cells to aggravate the progression of PF and may become a feasible target for the prevention and treatment of PF.

Interferon regulatory factor 1 (IRF1) inhibits lung endothelial regeneration following inflammation-induced acute lung injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a respiratory condition caused by severe endothelial barrier dysfunction within the lung. In ARDS, excessive inflammation, tissue edema, and immune cell influx prevents endothelial cell regeneration that is crucial in repairing the endothelial barrier. However, little is known about the molecular mechanism that underpin endothelial cell regeneration in ARDS. METHODS: R-based bioinformatics tools were used to analyze microarray-derived transcription profiles in human lung microvascular endothelial cells (HLMVECs) subjected to non-treatment or lipopolysaccharide (LPS) exposure. We generated endothelial cell-specific interferon regulatory factor 1 (Irf1) knockout (Irf1EC-/-) and Irf1fl/fl control mice for use in an endotoxemic murine model of acute lung injury (ALI). In vitro studies (qPCR, immunoblotting, and ChIP-qPCR) were conducted in mouse lung endothelial cells (MLECs) and HLMVECs. Dual-luciferase promoter reporter assays were performed in HLMVECs. RESULTS: Bioinformatics analyses identified IRF1 as a key up-regulated gene in HLMVECs post-LPS exposure. Endothelial-specific knockout of Irf1 in ALI mice resulted in enhanced regeneration of lung endothelium, while liposomal delivery of endothelial-specific Irf1 to wild-type ALI mice inhibited lung endothelial regeneration in a leukemia inhibitory factor (Lif)-dependent manner. Mechanistically, we demonstrated that LPS-induced Stat1Ser727 phosphorylation promotes Irf1 transactivation, resulting in downstream up-regulation of Lif that inhibits endothelial cell proliferation. CONCLUSIONS: These results demonstrate the existence of a p-Stat1Ser727-Irf1-Lif axis that inhibits lung endothelial cell regeneration post-LPS injury. Thus, direct inhibition of IRF1 or LIF may be a promising strategy for enhancing endothelial cell regeneration and improving clinical outcomes in ARDS patients.

Academic performance in children with pectus excavatum: a real-world research with propensity score matching.

BACKGROUND: The optimal timing of surgery for pectus excavatum (PE) is controversial. A large proportion of children will not undergo surgery before puberty. However, untimely surgery may lead to a decline in the children's social adaptation and competitiveness because the children have already developed psychological and physiological impairments due to PE at an early age. The study retrospectively compared the academic performance in PE children undergoing the Nuss procedure versus nonsurgical observation. METHODS: This retrospective real-world research study included 480 PE patients with definite surgical indications, in whom it was first recommended that they undergo surgery between the ages of 6 and 12 years old. Academic performance was collected at baseline and 6 years later. A generalized linear regression was calculated to screen the factors affecting the performance. A propensity score matching (PSM) analysis was conducted to reduce the potential for confounding factors between surgical and nonsurgical PE patients. RESULTS: Haller index (HI) and pulmonary function were recognized as factors affecting baseline performance according to the generalized linear regression. For PE children with surgical indications, their academic performance significantly declined after 6 years of nonsurgical observation (52.1% ± 17.1% versus 58.3% ± 16.7%, p = 0.042). The academic performance in the surgery group was better than that in the nonsurgery group 6 years after PSM (60.7% ± 17.7% versus 52.1% ± 17.1%, p = 0.008). CONCLUSIONS: The severity of PE will affect the academic performance of children.For PE children with definite surgical indications between the ages of 6 and 12 years old, surgical intervention rather than nonsurgical observation is more conducive to the development of children's academic performance.

Adipose-Derived Circulating Exosomes Promote Protection of the Pulmonary Endothelial Barrier by Inhibiting EndMT and Oxidative Stress through Down-Regulation of the TGF-ß Pathway: A Potential Explanation for the Obesity Paradox in ARDS.

The "obesity paradox in acute respiratory distress syndrome" (ARDS) refers to the phenomenon in which obesity is associated with higher morbidity but lower mortality in patients with ARDS. Endothelial-to-mesenchymal transition (EndMT) represents a key link in the interaction between endothelial disruption and mesenchymal fibrosis under inflammatory and oxidative conditions, which represent the intersectional pathophysiology of ARDS. Adipose tissue is considered to constitute the major source of circulating exosomal microRNAs (miRNAs), which act as genetic forms of adipokines for cell-cell crosstalk. We aimed to demonstrate the regulation and mechanism of adipose-derived exosomes in the obesity paradox in ARDS. High-fat-induced obese mice and lean control mice were subjected to ARDS insult to investigate the effects of obesity on ARDS and microarray analysis was performed to screen for differences in circulating miRNAs. In addition, mice and pulmonary endothelial cells were administered with adipose-derived exosomal miR-122-5p to investigate the underlying molecular mechanisms. We found high-fat diet-induced obesity protected against ARDS in mice by reinforcing endothelial barrier and attenuating fibroproliferation. Circulating exosomes produced in the obese state mediated these protective effects by inhibiting EndMT and oxidative stress. Mechanistically, adipose-derived exosomal miR-122-5p promoted the integrity and function of pulmonary endothelial barrier and alleviated fibrogenesis by suppressing EndMT and oxidative stress through down-regulation of the transforming growth factor ß1 (TGF-ß1)/TGF-ß receptor 1 (TGF-ßR1)/Smad2 pathway in vivo and in vitro. In conclusion, adipose-derived circulating exosomal miR-122-5p protects against ARDS by reinforcing pulmonary endothelial barrier through inhibition of EndMT and oxidative stress via down-regulation of the TGF-ß pathway, which propose a potential explanation for the obesity paradox in ARDS and indicate promising prospects for adipose-derived exosomes in cell-free therapies for ARDS.

Protective effects of adipose-derived biogenic nanoparticles on the pulmonary microvascular endothelial barrier in mice with ventilator-induced lung injury via the TRPV4/ROCK1 signalling pathway.

PURPOSE: The "obesity paradox" phenomenon occurs in critically ill patients who receive mechanical ventilation. Our previous studies found that the adipose-derived exosomes secreted by obese mice have a protective effect on the pulmonary microvascular endothelial barrier. However, the extraction of exosomes is cumbersome, their yield is low, and their storage is difficult. After further research, we discovered a new type of adipose-derived bioactive material called: lipoaspirate nanoparticles (Lipo-NPs). METHODS: Lipo-NPs were extracted and identified using a tangential flow filtration system. The Lipo-NPs were used as an intervention in ventilator-induced lung injury (VILI) models in vivo and in vitro to investigate whether they have a protective effect on lung tissue damage (haematoxylin and eosin staining), lung barrier function (lung wet/dry [W/D] weight ratio, protein concentration in bronchoalveolar lavage fluid (BALF), and Vascular endothelial (VE)-expression), as well as their related mechanisms. RESULTS: In both in vivo and in vitro studies, Lipo-NPs can attenuate lung injury, reduce lung W/D ratio and protein concentration in BALF, and augment the expression of the adhesion link-protein VE-cadherin, thus playing a protective role in lung barrier function. This protective effect involves the activation of the transient receptor potential vanilloid 4 (TRPV4)/Rho-associated kinase1 (ROCK1) signalling pathway. We further verified the role of this signalling pathway via activation and inhibition of TRPV4 and ROCK1. Moreover, phosphorylation of myosin light chain 2 (MLC2) regulates F-actin and is a target of the ROCK pathway. CONCLUSION: Lipo-NPs can enhance the expression of VE-cadherin by inhibiting the TRPV4/ROCK1/pMLC2 signalling pathway in the mechanical ventilation model, thereby exerting a protective effect on the VILI pulmonary microvascular endothelial barrier.

The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China.

BACKGROUND: Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort. METHODS: Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months. RESULTS: Eight SNPs were not associated with clinical manifestations of PMN patients (Pc < 0.05). rs3828323 T allele was marginally significantly associated with hypertension (P = 0.008, Pc = 0.064, OR = 1.821). After treatment for PMN, the SR group (including CR and PR) had lower serum creatinine level (68.4 ± 18.8 µmol/L vs. 122.8 ± 126.6 µmol/L, P < 0.001), urea (5.5 ± 1.9 mmol/L vs. 8.0 ± 4.0 mmol/L, P < 0.001), uric acid (358.5 ± 95.1 µmol/L vs. 392.8 ± 118.1 µmol/L, P = 0.037) and urinary protein (0.23 (0.76,1.05) g/d vs. 3.01 (2.06,7.95) g/d, P < 0.001), higher eGFR (100.0 ± 20.1 ml/min/1.73m2 vs. 77.1 ± 35.3 ml/min/1.73m2, P < 0.001) and albumin (41.1 ± 5.1 g/L vs.30.4 ± 8.2 g/L, P < 0.001). We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype. CONCLUSIONS: Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association.

High Blood Eosinophil and YKL-40 Levels, as Well as Low CXCL9 Levels, are Associated with Increased Readmission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Readmission after hospital discharge is common among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Predictive biomarkers of readmission would facilitate stratification strategies and individualized prognosis. Therefore, this study aimed to investigate the utility of type 2 biomarkers (eosinophils, periostin, and YKL-40) and a type 1 biomarker (CXCL9) in predicting readmission events in patients with AECOPD. METHODS: This is a prospective observational study design. Blood levels of eosinophils, periostin, YKL-40, and CXCL9 were measured at admission. The clinical outcomes were 12-month COPD-related readmission, time to COPD-related readmission, and number of 12-month COPD-related readmissions. These outcomes were analyzed using logistic and Cox regression models and Spearman's rank test. RESULTS: A total of 123 patients were included, of whom 51 had experienced at least one readmission for AECOPD. High levels of eosinophils (≥200 cells/µL or 2% of the total white blood cell count, adjusted odds ratio [aOR] =3.138, P=0.009) and YKL-40 (≥14.5 ng/mL, aOR =2.840, P=0.015), as well as low CXCL9 levels (≤30.1 ng/mL, aOR =2.551, P=0.028), were associated with an increased COPD-related readmission. The highest relative readmission rate was observed in patients with both high eosinophil and YKL-40 levels. Moreover, high eosinophil and YKL-40 levels were associated with a shorter time to first COPD-related readmission and an increased number of 12-month COPD-related readmissions. CONCLUSION: High blood eosinophil and YKL-40 levels, as well as low CXCL9 levels, have predictive utility for the 12-month COPD-related readmission rate. Using eosinophils and YKL-40 together allows more precise identification of patients at high risk of COPD-related readmission.

Intermedin Reduces Oxidative Stress and Apoptosis in Ventilator-Induced Lung Injury via JAK2/STAT3.

Mechanical ventilation is an effective treatment for acute respiratory distress syndrome (ARDS), which can improve the prognosis of ARDS to a certain extent. However, it may further aggravate lung tissue injury, which is defined as ventilator-induced lung injury (VILI). Intermedin (IMD) belongs to the calcitonin gene-related peptide (CPRP) superfamily. Our previous studies have found that IMD reduces the expression proinflammatory cytokines, down-regulates nuclear translocation and improves the integrity of endothelial barrier in ARDS. However, the effect of IMD on VILI has not been clarified. Oxidative stress imbalance and apoptosis are the main pathophysiological characteristics of VILI. In the current study, we used C57B6/J mice and human pulmonary microvascular endothelial cells (HPMECs) to establish a VILI model to analyze the effects of IMD on VILI and explore its potential mechanism. We found that IMD alleviated lung injury and inflammatory response in VILI, mainly in reducing ROS levels, upregulating SOD content, downregulating MDA content, reducing the expression of Bax and caspase-3, and increasing the expression of Bcl-2. In addition, we also found that IMD played its anti-oxidative stress and anti-apoptotic effects via JAK2/STAT3 signaling. Our study may provide some help for the prevention and treatment of VILI.

Intermedin alleviates the inflammatory response and stabilizes the endothelial barrier in LPS-induced ARDS through the PI3K/Akt/eNOS signaling pathway.

Inflammatory storms and endothelial barrier dysfunction are the central pathophysiological features of acute respiratory distress syndrome (ARDS). Intermedin (IMD), a member of the calcitonin gene-related peptide (CGRP) family, has been reported to alleviate inflammation and protect endothelial cell (EC) integrity. However, the effects of IMD on ARDS have not been clearly elucidated. In the present study, clinical ARDS data were used to explore the relationship between serum IMD levels and disease severity and prognosis, and we then established a model to predict the possibility of hospital survival. Mouse models of ARDS and LPS-challenged endothelial cells were used to analyze the protective effect and underlying mechanism of IMD. We found that in patients with ARDS, increased serum IMD levels were associated with reduced disease severity and increased rates of hospital survival. IMD alleviated the LPS-induced inflammatory response by decreasing proinflammatory cytokines, NF-κB p65 expression and NF-κB p65 nuclear translocation. In addition, IMD stabilized the endothelial barrier by repairing adherens junctions (AJs), cytoskeleton and capillary leakage. IMD exerted protective effects against ARDS on pulmonary endothelial cells, at least partly, through PI3K/Akt/eNOS signaling, while IMD's anti-inflammation effect was mediated through an eNOS-independent mechanism. Our study may provide new therapeutic insight for ARDS treatment.

Hyperuricemia and its related histopathological features on renal biopsy.

BACKGROUND: Hyperuricemia (HUA) is very common in chronic kidney disease (CKD). HUA is associated with an increased risk of cardiovascular events and accelerates the progression of CKD. Our study aimed to explore the relationship between baseline serum uric acid levels and renal histopathological features. METHODS: One thousand seventy patients receiving renal biopsy in our center were involved in our study. The baseline characteristics at the time of the kidney biopsy were collected from Renal Treatment System (RTS) database, including age, gender, serum uric acid (UA), glomerular filtration rate (eGFR), serum creatinine (Cr), urea, albumin (Alb), 24 h urine protein quantitation (24 h-u-pro) and blood pressure (BP). Pathological morphological changes were evaluated by two pathologists independently. Statistical analysis was done using SPSS 21.0. RESULTS: Among 1070 patients, 429 had IgA nephropathy (IgAN), 641 had non-IgAN. The incidence of HUA was 38.8% (n = 415), 43.8% (n = 188), and 43.2% (n = 277) in all patients, patients with IgAN and non-IgAN patients, respectively. Serum uric acid was correlated with eGFR (r = - 0.418, p < 0.001), Cr (r = 0.391, p < 0.001), urea (r = 0.410, p < 0.001), 24-u-pro (r = 0.077, p = 0.022), systolic blood pressure (SBP) (r = 0.175, p < 0.001) and diastolic blood pressure (DBP) (r = 0.109, p = 0.001). Multivariate logistic regression analysis showed that after adjustment for Cr, age and blood pressure, HUA was a risk factor for segmental glomerulosclerosis (OR = 1.800, 95% CI:1.309-2.477) and tubular atrophy/interstitial fibrosis (OR = 1.802, 95% CI:1.005-3.232). HUA increased the area under curve (AUC) in diagnosis of segmental glomerulosclerosis. CONCLUSIONS: Hyperuricemia is prevalent in CKD. The serum uric acid level correlates not only with clinical renal injury indexes, but also with renal pathology. Hyperuricemia is an independent risk factor for segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis.

Behavioural disorders in children with pectus excavatum in China: a retrospective cohort study with propensity score matching and risk prediction model.

OBJECTIVES: Surgical repair of pectus excavatum is typically carried out immediately prior to puberty. However, at the time of surgery, some psychosocial issues, such as behavioural disorders may already have developed and the likelihood of these psychosocial disorders resolving after surgery is unclear. For this reason, some surgeons choose to perform surgical repair at an earlier age in some children. The study retrospectively compares the rate of behavioural disorders in children undergoing the Nuss procedure at 4 vs. 10 years of age. We also attempted to develop a model to predict the risk of behavioural disorders in 10 year-old patients. METHODS: The current study included children receiving Nuss procedure for pectus excavatum at either 4 or 10 years of age. The presence/absence of behavioural disorder was assessed preoperatively, and in the third year, after removal of the bar. A propensity score matching (PSM) analysis was conducted to reduce the potential for confounding by baseline factors. Multivariable logistic regression was conducted to establish a model to predict the risk of behavioural disorders in the third year after the removal of the bar. The model was accessed by discrimination and calibration. A formula and a nomogram were developed based on the results. RESULTS: The number of patients in each group was 45 after PSM. The rate of behavioural disorders at the baseline was significantly higher in the children undergoing Nuss procedure at 10 years of age [36% vs 20%, odds ratio (OR) 2.21, 95% confidence interval (CI) 0.85-5.72; P = 0.157]. The rate of behavioural disorders in the third year after the removal of the bar was 36% and 18% in children undergoing surgery at 10 and 4 years of age, respectively (OR 2.55, 95% CI 0.96-6.79; P = 0.094). The rate of persistent behavioural disorders, defined as continuing to have behavioural disorders in the third year after the removal of the bar in those with behavioural disorders at the baseline, was 88% vs 56% (OR 3.47, 95% CI 0.56-21.36; P = 0.204). Two patients (4%) relapsed in each group. A risk prediction model by variables of gender, Haller index, pulmonary function and score of Child Behaviour Checklist at the baseline was provided. CONCLUSIONS: The rate of behavioural disorders was considerably lower in children who underwent the Nuss procedure at 4 years of age than at 10 years of age. Behavioural disorders may not readily resolve after surgery. Performing surgery at an early age rather than just before puberty may be better for psychosocial development. Psychosocial aid is necessary in addition to surgery to address behavioural disorders.

Effects of four major brain protection strategies during proximal aortic surgery: A systematic review and network meta-analysis.

BACKGROUND: Reliable brain protection during proximal aortic surgery remains a formidable surgical challenge. Various cerebral protection techniques have been used in the clinic; however, there is no consensus regarding which strategy is best. In this network meta-analysis (NMA), we focused on permanent neurological deficits (PND) and perioperative mortality associated with four major brain protection strategies used during proximal aortic surgery. METHODS: We performed a literature search of the MEDLINE, Embase, Cochrane Library and PubMed databases. The primary outcomes of this analysis were PND and perioperative mortality. Network rank and surface under the cumulative ranking curve (SUCRA) analyses were performed to evaluate and identify the superiority of different brain protection techniques. RESULTS: Thirty-two studies involving 6772 participants were included in this review. The number of studies that involved DHCA, DHCA + ACP, DHCA + RCP and MHCA + ACP were 16, 19, 23 and 15, respectively. Based on SUCRA analyses, moderate hypothermic circulatory arrest with antegrade cerebral perfusion (MHCA + ACP) was the best choice in terms of PND (predictive probabilities: 77.5), and deep hypothermic circulatory arrest with retrograde cerebral perfusion (DHCA + RCP) was the best choice in terms of mortality (predictive probabilities: 65.4). Deep hypothermic circulatory arrest (DHCA) alone was inferior to the other techniques in terms of both PND and mortality. CONCLUSIONS: Effective cerebral perfusion should be actively considered. Retrograde perfusion (RCP) can reduce mortality and will not increase risks of PND compared with antegrade perfusion (ACP) when performing DHCA. Moderate hypothermia should be recommended when performing ACP. DHCA + RCP and MHCA + ACP seem to be appropriate brain protection strategies during proximal aortic surgery and more clinical studies involving pairwise comparisons between them are needed.

Interaction between PLA2R1 and HLA-DQA1 variants contributes to the increased genetic susceptibility to membranous nephropathy in Western China.

AIM: Recent studies showed that single nucleotide polymorphisms (SNP) within the phospholipase A2 receptor (PLA2R1) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) genes were associated with the susceptibility to patients with primary membranous nephropathy (PMN). However, the results of previous research have not been always consistent. METHODS: We performed a case-control study including 314 patients with PMN and 354 healthy subjects in Western China. Eight SNP in PLA2R1 and one SNP in HLA -DQA1 were genotyped and association between PLA2R1 and HLA-DQA1 was investigated. One hundred and twenty patients were detected anti-PLA2R antibodies to analyze the association between genotype and anti-PLA2R antibody. RESULTS: We found A allele of rs2715918 (odds ratio (OR) = 1.66, corrected P values (Pc) = 7.9 × 10-3 ), A allele of rs4665143 (OR = 1.76, Pc = 2.7 × 10-6 ) and A allele of rs2187668 (OR = 3.29, Pc = 8.0 × 10-11 ) were associated with PMN. Susceptibility of PMN was significantly increased with rs2715918 in dominant model (OR = 1.624, Pc = 5.0 × 10-2 ), rs4665143 in recessive model (OR = 2.134, Pc = 1.4 × 10-4 ) and rs2187668 in dominant model (OR = 3.961, Pc = 4.1 × 10-11 ). The haplotype ATAC of rs2715918, rs6757188, rs4665143, rs3749119 was associated with the high risk of PMN (OR = 1.453, P = 3.0 × 10-4 ). Interaction of rs2715918 GA/AA, rs4665143 GA/AA and rs2187668 GA/AA could significantly increase the 10.61-fold higher risk for the development of PMN (OR = 10.61, P = 4.0 × 10-10 ). Patients who carried with risk genotypes for both HLA-DQA1 and PLA2R1 (87.8%) had antibodies positivity. However, patients who carried low-risk genotypes (41.6%) had antibodies positivity (P = 0.001). CONCLUSION: There are some differences in PLA2R1 distributions in PMN patients between previous literature and our study. Our results showed that interactions between PLA2R1 and HLA-DQA1 alleles increased genetic susceptibility to PMN in Western China.

Potential association of long noncoding RNA HA117 with tetralogy of Fallot.

Tetralogy of Fallot (TOF) is a congenital heart disease characterized by abnormal cardiomyocyte differentiation in the right ventricular outflow tract (RVOT), and HA117 is a novel long noncoding RNA (lncRNA) with anti-differentiation roles. To investigate the potential association of HA117 with TOF, we collected 84 RVOT tissues from patients with TOF. We determined the expression of HA117 in RVOT samples from TOF patients and collected clinical data to conduct a cross-sectional and short-term follow-up study. McGoon ratio, Nakata index, and left ventricular end-diastolic volume index (LVEDVI) were negatively correlated with the expression of HA117 based on subgroup analysis, correlation analysis and logistic regression analysis. Additionally, cardiopulmonary bypass (CPB) time and ICU stay were longer in patients with higher expression of HA117 than in patients with lower expression of HA117. Furthermore, percentage improvement in SPO2 was significantly reduced in patients with increased HA117 expression at 6 months after surgery. Our results suggested that the increased expression of the novel lncRNA HA117 is a risk factor for unfavorable McGoon ratio, Nakata index and LVEDVI in TOF patients. Additionally, an increased expression of HA117 might lead to adverse short-term outcomes in TOF patients.

Effects of 4 major brain protection strategies during aortic arch surgery: A protocol for a systematic review and network meta-analysis using Stata.

BACKGROUND: Reliable brain protection during aortic arch surgery remains a formidable surgical challenge. Various cerebral protection techniques have been used in the clinic; however, there is no consensus regarding which strategy is best. We will perform a network meta-analysis (NMA) focusing on the permanent neurological deficits (PND) and perioperative mortality associated with 4 major brain protection strategies used during aortic arch surgery. METHODS: We will perform a literature search of MEDLINE, EMBASE, Cochrane Library, and PubMed databases. The primary outcomes of interest in this analysis will be PND and perioperative mortality. Inconsistencies in the NMA will be evaluated with global and local approaches. Network rank and surface under the cumulative ranking curve (SUCRA) analyses will be performed to evaluate and identify the superiority of different brain protection techniques. RESULTS: This study is ongoing and will be submitted to a peer-reviewed journal for consideration of publication. CONCLUSIONS: Our study will increase understanding of 4 major brain protection strategies during aortic arch surgery and be helpful to clinicians using NMA in their studies.

Changes in resting pulmonary function testing over time after the Nuss procedure: A systematic review and meta-analysis.

BACKGROUND: Pectus excavatum, the most common congenital chest wall deformity in pediatric patients, leads to pulmonary dysfunction. There is no consensus regarding the effectiveness of the Nuss procedure for recovering pulmonary function. In this meta- analysis, we focused on the changes that occur in pulmonary function after the Nuss procedure. METHODS: We performed a literature search in the MEDLINE, Embase, Cochrane library and PubMed databases. The included studies were required to contain pulmonary function tests with results adjusted to predicted values both before and after the Nuss procedure. The key outcomes of interest in this analysis were pulmonary function measured as forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC). Subgroup analyses were performed based on time since surgery and the mean ages of the patients when they underwent surgery by forest plots and meta-regressions. RESULTS: Thirteen studies involving 465 participants were included in this review. The standard mean difference (SMD) observed in FEV1 and FVC after surgery were 0.17 (95% CI, 0.01-0.33, p=0.04) and -0.18 (95% CI, -0.41-0.06, p=0.14), respectively. The overall meta-regression SMD of FEV1 and FVC by time since surgery were 1.21 (95% CI, 1.04-1.41, p=0.020) and 1.38 (95% CI, 1.05-1.83, p=0.027), respectively. We found evidence of a temporal relationship between time at which pulmonary function tests were performed after surgery and predicted FEV1 and FVC values. The SMD of FEV1 (0.26, p=0.012) was slightly higher in group evaluated more than 2year after initial surgery. CONCLUSIONS: Abnormal resting pulmonary functions tests performed prior to surgery showed an initial depression after surgery. The FEV1 of patients slightly increased at 2year post surgery compared with the baseline. Further studies with longer term follow-up are still needed to determine if pulmonary function could improve to normal after surgery. LEVELS OF EVIDENCE: Level of evidence: 4 (based on lowest level of article analyzed in meta-analysis/systematic review).

MhNCED3, a gene encoding 9-cis-epoxycarotenoid dioxygenase in Malus hupehensis Rehd., enhances plant tolerance to Cl- stress by reducing Cl- accumulation.

High Cl(-) concentrations in tissues can be toxic to crop plants and may lead to reduced growth rates and yields. 9-cis-epoxycarotenoid dioxygenase (NCED) is thought to be involved in the biosynthesis of abscisic acid (ABA), which is an important regulator of plant adaptive responses to stress. Here, the expression of MhNCED3 in Malus hupehensis Rehd. and the effects of MhNCED3 on plant tolerance to Cl(-) stress were explored. The results showed that MhNCED3 expression and ABA biosynthesis in M. hupehensis Rehd. were induced by Cl(-) stress. Ectopic expression of MhNCED3 in Arabidopsis complemented the phenotypic defects of the 129B08/nced3 mutant and enhanced WT tolerance to Cl(-) stress. The transgenic Arabidopsis showed improved growth and developmental status, increased ABA contents, and reduced transpiration rates and relative water content. Furthermore, ectopic expression of MhNCED3 decreased Cl(-) accumulation and oxidative damage, and up-regulated the expression levels of AtCLCc (chloride channel protein) and AtSLAH3 (slow anion channel 1 homolog 3) genes in Arabidopsis. These observations suggest that MhNCED3 has critical role in enhancing plant tolerance to Cl(-) stress by reducing Cl(-) accumulation.