Evaluation of CO2 removal rate of ECCO2R for a renal replacement therapy platform in an experimental setting.

BACKGROUND: A critical parameter of extracorporeal CO2 removal (ECCO2R) applications is the CO2 removal rate (VCO2). Low-flow venovenous extracorporeal support with large-size membrane lung remains undefined. This study aimed to evaluate the VCO2 of a low-flow ECCO2R with large-size membrane lung using a renal replacement therapy platform in an experimental animal model. METHODS: Twelve healthy pigs were placed under mechanical ventilation and connected to an ECCO2R-CRRT system (surface area = 1.8 m2; OMNIset®, BBraun, Germany). Respiratory settings were reduced to induce two degrees of hypercapnia. VCO2 was recorded under different combinations of PaCO2 (50-69 or 70-89 mm Hg), extracorporeal blood flow (ECBF; 200 or 350 mL/min), and gas flow (4, 6, or 10 L/min). RESULTS: VCO2 increased with ECBF at all three gas flow rates. In severe hypercapnia, the increase in sweep gas flow from 4 to 10 L/min increased VCO2 from 86.38 ± 7.08 to 96.50 ± 8.71 mL/min at an ECBF of 350 mL/min, whereas at ECBF of 200 mL/min, any increase was less effective. But in mild hypercapnia, the increase in sweep gas flow result in significantly increased VCO2 at two ECBF. VCO2 increased with PaCO2 from 50-69 to 70-89 mm Hg at an ECBF of 350 mL/min, but not at ECBF of 200 mL/min. Post-membrane lung PCO2 levels were similar for different levels of premembrane lung PCO2 (p = 0.08), highlighting the gas exchange diffusion efficacy of the membrane lung in gas exchange diffusion. In severe hypercapnia, the reduction of PaCO2 elevated from 11.5% to 19.6% with ECBF increase only at a high gas flow of 10 L/min (p < 0.05) and increase of gas flow significantly reduced PaCO2 only at a high ECBF of 350 mL/min (p < 0.05). CONCLUSIONS: Low-flow venovenous extracorporeal ECCO2R-CRRT with large-size membrane lung is more efficient with the increase of ECBF, sweep gas flow rate, and the degree of hypercapnia. The influence of sweep gas flow on VCO2 depends on the ECBF and degree of hypercapnia. Higher ECBF and gas flow should be chosen to reverse severe hypercapnia.

Effects of early versus delayed application of prone position on ventilation-perfusion mismatch in patients with acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: Prone position has been shown to improve oxygenation and survival in patients with early acute respiratory distress syndrome (ARDS). These beneficial effects are partly mediated by improved ventilation/perfusion (V/Q) distribution. Few studies have investigated the impact of early versus delayed proning on V/Q distribution in patients with ARDS. The aim of this study was to assess the regional ventilation and perfusion distribution in early versus persistent ARDS after prone position. METHODS: This is a prospective, observational study from June 30, 2021, to October 1, 2022 at the medical ICU in Zhongda Hospital, Southeast University. Fifty-seven consecutive adult patients with moderate-to-severe ARDS ventilated in supine and prone position. Electrical impedance tomography was used to study V/Q distribution in the supine position and 12 h after a prone session. RESULTS: Of the 57 patients, 33 were early ARDS (≤ 7 days) and 24 were persistent ARDS (> 7 days). Oxygenation significantly improved after proning in early ARDS (157 [121, 191] vs. 190 [164, 245] mm Hg, p < 0.001), whereas no significant change was found in persistent ARDS patients (168 [136, 232] vs.177 [155, 232] mm Hg, p = 0.10). Compared to supine position, prone reduced V/Q mismatch in early ARDS (28.7 [24.6, 35.4] vs. 22.8 [20.0, 26.8] %, p < 0.001), but increased V/Q mismatch in persistent ARDS (23.8 [19.8, 28.6] vs. 30.3 [24.5, 33.3] %, p = 0.006). In early ARDS, proning significantly reduced shunt in the dorsal region and dead space in the ventral region. In persistent ARDS, proning increased global shunt. A significant correlation was found between duration of ARDS onset to proning and the change in V/Q distribution (r = 0.54, p < 0.001). CONCLUSIONS: Prone position significantly reduced V/Q mismatch in patients with early ARDS, while it increased V/Q mismatch in persistent ARDS patients. Trial registration ClinicalTrials.gov (NCT05207267, principal investigator Ling Liu, date of registration 2021.08.20).

Neurally adjusted ventilatory assist as a weaning mode for adults with invasive mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Prolonged ventilatory support is associated with poor clinical outcomes. Partial support modes, especially pressure support ventilation, are frequently used in clinical practice but are associated with patient-ventilation asynchrony and deliver fixed levels of assist. Neurally adjusted ventilatory assist (NAVA), a mode of partial ventilatory assist that reduces patient-ventilator asynchrony, may be an alternative for weaning. However, the effects of NAVA on weaning outcomes in clinical practice are unclear. METHODS: We searched PubMed, Embase, Medline, and Cochrane Library from 2007 to December 2020. Randomized controlled trials and crossover trials that compared NAVA and other modes were identified in this study. The primary outcome was weaning success which was defined as the absence of ventilatory support for more than 48 h. Summary estimates of effect using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with accompanying 95% confidence interval (CI) were expressed. RESULTS: Seven studies (n = 693 patients) were included. Regarding the primary outcome, patients weaned with NAVA had a higher success rate compared with other partial support modes (OR = 1.93; 95% CI 1.12 to 3.32; P = 0.02). For the secondary outcomes, NAVA may reduce duration of mechanical ventilation (MD = - 2.63; 95% CI - 4.22 to - 1.03; P = 0.001) and hospital mortality (OR = 0.58; 95% CI 0.40 to 0.84; P = 0.004) and prolongs ventilator-free days (MD = 3.48; 95% CI 0.97 to 6.00; P = 0.007) when compared with other modes. CONCLUSIONS: Our study suggests that the NAVA mode may improve the rate of weaning success compared with other partial support modes for difficult to wean patients.

A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue development.

The tongue is one of the major structures involved in human food intake and speech. Tongue malformations such as aglossia, microglossia, and ankyloglossia are congenital birth defects, greatly affecting individuals' quality of life. However, the molecular basis of the tissue-tissue interactions that ensure tissue morphogenesis to form a functional tongue remains largely unknown. Here we show that ShhCre -mediated epithelial deletion of Wntless (Wls), the key regulator for intracellular Wnt trafficking, leads to lingual hypoplasia in mice. Disruption of epithelial Wnt production by Wls deletion in epithelial cells led to a failure in lingual epidermal stratification and loss of the lamina propria and the underlying superior longitudinal muscle in developing mouse tongues. These defective phenotypes resulted from a reduction in epithelial basal cells positive for the basal epidermal marker protein p63 and from impaired proliferation and differentiation in connective tissue and paired box 3 (Pax3)- and Pax7-positive muscle progenitor cells. We also found that epithelial Wnt production is required for activation of the Notch signaling pathway, which promotes proliferation of myogenic progenitor cells. Notch signaling in turn negatively regulated Wnt signaling during tongue morphogenesis. We further show that Pax7 is a direct Notch target gene in the embryonic tongue. In summary, our findings demonstrate a key role for the lingual epithelial signals in supporting the integrity of the lamina propria and muscular tissue during tongue development and that a Wnt/Notch/Pax7 genetic hierarchy is involved in this development.

Sequencing of Euscaphis konishii Endocarp Transcriptome Points to Molecular Mechanisms of Endocarp Coloration.

Flower and fruit colors are of vital importance to the ecology and economic market value of plants. The mechanisms of flower and fruit coloration have been well studied, especially among ornamental flower plants and cultivated fruits. As people pay more attention to exocarp coloration, the endocarp coloration in some species has often been ignored. Here, we report on the molecular mechanism of endocarp coloration in three development stages of Euscaphis konishii. The results show that endocarp reddening is closely related to anthocyanin accumulation, and a total of 86,120 unigenes were assembled, with a mean length of 893 bp (N50 length of 1642 bp). We identified a large number of differentially expressed genes associated with endocarp coloration, including anthocyanin biosynthesis, carotenoid biosynthesis, and chlorophyll breakdown. The genes participating in each step of the anthocyanin biosynthesis were found in the transcriptome dataset, but a few genes were found in the carotenoid biosynthesis and chlorophyll breakdown. In addition, the candidate R2R3-MYB transcription factors and candidate glutathione S-transferase transport genes, which likely regulate the anthocyanin biosynthesis, were identified. This study offers a platform for E. konishii functional genomic research and provides a reference for revealing the regulatory mechanisms of endocarp reddening.

Ectodermal Wnt controls nasal pit morphogenesis through modulation of the BMP/FGF/JNK signaling axis.

BACKGROUND: Mutations of WNT3, WNT5A, WNT9B, and WNT11 genes are associated with orofacial birth defects, including nonsyndromic cleft lip with cleft palate in humans. However, the source of Wnt ligands and their signaling effects on the orofacial morphogenetic process remain elusive. RESULTS: Using Foxg1-Cre to impair Wnt secretion through the inactivation of Gpr177/mWls, we investigate the relevant regulation of Wnt production and signaling in nasal-facial development. Ectodermal ablation of Gpr177 leads to severe facial deformities resulting from dramatically reduced cell proliferation and increased cell death due to a combined loss of WNT, FGF and BMP signaling in the developing facial prominence. In the invaginating nasal pit, the Gpr177 disruption also causes a detrimental effect on migration of the olfactory epithelial cells into the mesenchymal region. The blockage of Wnt secretion apparently impairs the olfactory epithelial cells through modulation of JNK signaling. CONCLUSIONS: Our study thus suggests the head ectoderm, including the facial ectoderm and the neuroectoderm, as the source of canonical as well as noncanonical Wnt ligands during early development of the nasal-facial prominence. Both ß-catenin-dependent and -independent signaling pathways are required for proper development of these morphogenetic processes.

An expanded definition of acute respiratory distress syndrome: Challenging the status quo.

Although the Berlin definition of acute respiratory distress syndrome (ARDS), 2012 has been widely used in clinical practice, issues have occasionally been raised regarding various criteria since it was proposed. High-flow nasal oxygen (HFNO) is widely used for effective respiratory support in acute respiratory failure. As patients who do not require ventilation but meet the Berlin criteria have similar characteristics to those with ARDS, the definition of ARDS may be broadened to include patients receiving HFNO. As the PaO2/FiO2 under-recognizes the diagnosis of ARDS, a SpO2/FiO2 value of ≤315 may be considered instead of a PaO2/FiO2 value of ≤300 for diagnosing the condition in resource-constrained settings. In this context, patients with severe COVID-19 always meet other criteria for ARDS except for 7-day acute onset. Therefore, the timeframe for the onset of ARDS may be extended to up to 14 days. An expanded definition of ARDS may allow early identification of patients with less severe diseases and facilitate testing and application of new therapies in patients with a high risk of poor outcomes. Here, we discuss the major controversies regarding the extension of the ARDS definition with a view to improving clinical implementation and patient outcomes.

Metabolite Fingerprinting for Identification of Panax ginseng Metabolites Using Internal Extractive Electrospray Ionization Mass Spectrometry.

Ginseng, a kind of functional food and medicine with high nutritional value, contains various pharmacological metabolites that influence human metabolic functions. Therefore, it is very important to analyze the composition and metabolites of ginseng. However, the analysis of active metabolites in ginseng samples usually involves various experimental steps, such as extraction, chromatographic separation, and characterization, which may be time-consuming and laborious. In this study, an internal extractive electrospray ionization mass spectrometry (iEESI-MS) method was developed to analyze active metabolites in ginseng samples with sequential sampling and no pretreatment. A total of 44 metabolites, with 32 ginsenosides, 6 sugars, and 6 organic acids, were identified in the ginseng samples. The orthogonal partial least-squares discriminant analysis (OPLS-DA) score plot showed a clear separation of ginseng samples from different origins, indicating that metabolic changes occurred under different growing conditions. This study demonstrated that different cultivation conditions of ginseng can be successfully discriminated when using iEESI-MS-based metabolite fingerprints, which provide an alternative solution for the quality identification of plant drugs.

Cell-specific clock-controlled gene expression program regulates rhythmic fiber cell growth in cotton.

BACKGROUND: The epidermis of cotton ovule produces fibers, the most important natural cellulose source for the global textile industry. However, the molecular mechanism of fiber cell growth is still poorly understood. RESULTS: Here, we develop an optimized protoplasting method, and integrate single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) to systematically characterize the cells of the outer integument of ovules from wild type and fuzzless/lintless (fl) cotton (Gossypium hirsutum). By jointly analyzing the scRNA-seq data from wildtype and fl, we identify five cell populations including the fiber cell type and construct the development trajectory for fiber lineage cells. Interestingly, by time-course diurnal transcriptomic analysis, we demonstrate that the primary growth of fiber cells is a highly regulated circadian rhythmic process. Moreover, we identify a small peptide GhRALF1 that circadian rhythmically controls fiber growth possibly through oscillating auxin signaling and proton pump activity in the plasma membrane. Combining with scATAC-seq, we further identify two cardinal cis-regulatory elements (CREs, TCP motif, and TCP-like motif) which are bound by the trans factors GhTCP14s to modulate the circadian rhythmic metabolism of mitochondria and protein translation through regulating approximately one third of genes that are highly expressed in fiber cells. CONCLUSIONS: We uncover a fiber-specific circadian clock-controlled gene expression program in regulating fiber growth. This study unprecedentedly reveals a new route to improve fiber traits by engineering the circadian clock of fiber cells.

Effect of EIT-guided PEEP titration on prognosis of patients with moderate to severe ARDS: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table. METHODS: This is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA). DISCUSSION: As a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date. TRIAL REGISTRATION: ClinicalTrial.gov NCT05207202. First published on January 26, 2022.

Neurally Adjusted Ventilatory Assist vs. Conventional Mechanical Ventilation in Adults and Children With Acute Respiratory Failure: A Systematic Review and Meta-Analysis.

Background: Patient-ventilator asynchrony is a common problem in mechanical ventilation (MV), resulting in increased complications of MV. Despite there being some pieces of evidence for the efficacy of improving the synchronization of neurally adjusted ventilatory assist (NAVA), controversy over its physiological and clinical outcomes remain. Herein, we conducted a systematic review and meta-analysis to determine the relative impact of NAVA or conventional mechanical ventilation (CMV) modes on the important outcomes of adults and children with acute respiratory failure (ARF). Methods: Qualified studies were searched in PubMed, EMBASE, Medline, Web of Science, Cochrane Library, and additional quality evaluations up to October 5, 2021. The primary outcome was asynchrony index (AI); secondary outcomes contained the duration of MV, intensive care unit (ICU) mortality, the incidence rate of ventilator-associated pneumonia, pH, and Partial Pressure of Carbon Dioxide in Arterial Blood (PaCO2). A statistical heterogeneity for the outcomes was assessed using the I 2 test. A data analysis of outcomes using odds ratio (OR) for ICU mortality and ventilator-associated pneumonia incidence and mean difference (MD) for AI, duration of MV, pH, and PaCO2, with 95% confidence interval (CI), was expressed. Results: Eighteen eligible studies (n = 926 patients) were eventually enrolled. For the primary outcome, NAVA may reduce the AI (MD = -18.31; 95% CI, -24.38 to -12.25; p < 0.001). For the secondary outcomes, the duration of MV in the NAVA mode was 2.64 days lower than other CMVs (MD = -2.64; 95% CI, -4.88 to -0.41; P = 0.02), and NAVA may decrease the ICU mortality (OR =0.60; 95% CI, 0.42 to 0.86; P = 0.006). There was no statistically significant difference in the incidence of ventilator-associated pneumonia, pH, and PaCO2 between NAVA and other MV modes. Conclusions: Our study suggests that NAVA ameliorates the synchronization of patient-ventilator and improves the important clinical outcomes of patients with ARF compared with CMV modes.

Diagnosis Accuracy of Lung Ultrasound for ARF in Critically Ill Patients: A Systematic Review and Meta-Analysis.

Background: Acute respiratory failure (ARF) is a commonly distressing condition in critically ill patients. Its early recognition and treatment may improve clinical outcomes. Mounting evidence suggests that lung ultrasound (LUS) could be an alternative to chest X-ray (CXR) or computed tomography (CT) for the diagnosis of ARF in critically ill patients. This meta-analysis aimed to determine whether LUS can be an alternative tool used to investigate the cause of ARF or thoracic pathologies associated with the diagnosis of ARF in critically ill patients. Method: A systematic literature search of the PubMed, Web of Science, Embase, and Cochrane Library databases was conducted from inception to March 2020. Two researchers independently screened studies investigating the accuracy of LUS with CXR or CT for adult critically ill patients with ARF. Data with baseline, true positives, false positives, false negatives, and true negatives were extracted. The study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The pooled sensitivity and specificity were obtained using a bivariate model. Results: Eleven studies, including 1,232 patients, were included in the meta-analysis. Most studies were of low quality. LUS had a pooled sensitivity of 92% (95% confidence interval [CI]: 85-96) and a pooled specificity of 98% (95% CI: 94-99). The area under the summary receiver operating characteristic curve was 98% (95% CI: 97-99). The sensitivity and specificity of LUS to identify different pathological types of ARF were investigated. For consolidation (1,040 patients), LUS had a sensitivity of 89% and a specificity of 97%. For pleural effusion (279 patients), LUS had a pooled sensitivity of 95% and a specificity of 99%. For acute interstitial syndrome (174 patients), LUS had a pooled sensitivity of 95% and a specificity of 91%. Conclusions: LUS is an adjuvant tool that has a moderate sensitivity and high specificity for the diagnosis of ARF in critically ill patients. Systematic Review Registration: The study protocol was registered with PROSPERO (CRD42020211493).

Evaluation of health-related quality of life and the related factors in a group of Chinese patients with interstitial lung diseases.

INTRODUCTION: Interstitial lung diseases (ILDs) include a wide variety of chronic progressive pulmonary diseases characterized by lung inflammation, fibrosis and hypoxemia and can progress to respiratory failure and even death. ILDs are associated with varying degrees of quality of life impairments in affected people. Studies on the quality of life in patients with ILDs are still limited, and there are few studies with long-term follow-up periods in these patients. METHODS: Data from patients who were clinically diagnosed with ILDs in the Respiratory Department, Beijing Chaoyang Hospital, Capital Medical University from January 2017 to February 2018 were collected. Clinical status and HRQoL were assessed at baseline and subsequently at 6- and 12-month intervals with the LCQ, mMRC, HADS, SF-36, and SGRQ. Multivariate linear regression was used to evaluate the determinants of the decline in HRQoL. RESULTS: A total of 139 patients with idiopathic interstitial pneumonia (IIP) and 30 with connective tissue disease-associated ILD (CTD-ILD) were enrolled, 140 of whom completed the follow-up. The mean age was 63.7 years, and 92 patients were men. At baseline, the decline in HRQoL assessed by the SF-36 and SGRQ was significantly associated with the mMRC, LCQ and HADS depression score. In the follow-up, changes in FVC%, DLco%, mMRC and LCQ were significantly associated with changes in HRQoL. CONCLUSIONS: HRQoL in both IIP and CTD-ILD patients deteriorates to varying degrees, and the trend suggests that poor HRQoL in these patients is associated with many determinants, primarily dyspnea, cough and depression. Improving HRQoL is the main aim when treating patients living with ILDs.

Comprehensive transcriptome analysis of reference genes for fruit development of Euscaphis konishii.

BACKGROUND: Quantitativereal-time reverse transcriptase polymerase chain reaction is the common method to quantify relative gene expression. Normalizating using reliable genes is critical in correctly interpreting expression data from qRT-PCR. Euscaphis konishii is a medicinal plant with a long history in China, which has various chemical compounds in fruit. However, there is no report describing the selection of reference genes in fruit development of Euscaphis konishii. METHODS: We selected eight candidate reference genes based on RNA-seq database analysis, and ranked expression stability using statistical algorithms GeNorm, NormFinder, BestKeeper and ReFinder. Finally, The nine genes related to the anthocyanin synthesis pathway of Euscaphis konishii were used to verify the suitability of reference gene. RESULTS: The results showed that the stability of EkUBC23, EkCYP38 and EkGAPDH2 was better, and the low expression reference genes (EkUBC23 and EkCYP38) were favourable for quantifying low expression target genes, while the high expression reference gene (EkGAPDH2) was beneficial for quantifying high expression genes. In this study, we present the suitable reference genes for fruit development of Euscaphis konishii based on transcriptome data, our study will contribute to further studies in molecular biology and gene function on Euscaphis konishii and other closely related species.

Multivariate analysis reveals phenotypic diversity of Euscaphis japonica population.

Fruit traits affect population genetic diversity by affecting seed protection and dispersal strategies, thereby comprising important components of phenotypic variation. Understanding of the phenotypic variation is an indispensable first step for developing breeding strategies. However, little information is known about the genetic variation in E. japonica-a monotypic species with abundant phenotypes that is mainly distributed in southern China. In this study, we evaluated the phenotypic diversity of 67 E. japonica using 23 phenotypic traits. Our results showed that the Shannon-Wiener (I) index of qualitative traits ranged from 0.55 to 1.26, and the color traits had a relatively high I. The average coefficient of variation of compound leaf traits (14.74%) was higher than that of fruit and seed traits (12.77% and 11.47%, respectively). Principal component analysis also showed that compound leaf and fruit traits were important components of total variation. Furthermore, correlation analysis revealed a significant difference in elevation and fruit color, irregular ribs, leaf margin and texture. The F value within populations was smaller than among populations, indicating the variation in phenotypic traits among populations was much greater than within populations. Dehua and Zunyi populations had the highest coefficients of variation, whereas Wenzhou population had the smallest-which may be attributed to habitat destruction. According to Q-type clustering, 67 samples clustered into four groups, with those having similar phenotypes clustering into the same group. In general, leaf and fruit traits had abundant phenotypic diversity, representing the main sources of phenotypic variation. Combined with clustering results and field surveys, this study suggests that the phenotypes of E. japonica are classified into two main categories: The deciduous E. japonica present at high altitudes; and the evergreen E. japonica present at low altitudes. Excavating E. japonica variations provides a theoretical reference for its classification and diversity, and is of great significance for planning genetic resources and establishing conservation strategies.