Development of a Prediction Score for Evaluation of Extubation Readiness in Neurosurgical Patients with Mechanical Ventilation.

BACKGROUND: There is no widely accepted consensus on the weaning and extubating protocols for neurosurgical patients, leading to heterogeneity in clinical practices and high rates of delayed extubation and extubation failure-related health complications. METHODS: In this single-center prospective observational diagnostic study, mechanically ventilated neurosurgical patients with extubation attempts were consecutively enrolled for 1 yr. Responsive physicians were surveyed for the reasons for delayed extubation and developed the Swallowing, Tongue protrusion, Airway protection reflected by spontaneous and suctioning cough, and Glasgow Coma Scale Evaluation (STAGE) score to predict the extubation success for neurosurgical patients already meeting other general extubation criteria. RESULTS: A total of 3,171 patients were screened consecutively, and 226 patients were enrolled in this study. The rates of delayed extubation and extubation failure were 25% (57 of 226) and 19% (43 of 226), respectively. The most common reasons for the extubation delay were weak airway-protecting function and poor consciousness. The area under the receiver operating characteristics curve of the total STAGE score associated with extubation success was 0.72 (95% CI, 0.64 to 0.79). Guided by the highest Youden index, the cutoff point for the STAGE score was set at 6 with 59% (95% CI, 51 to 66%) sensitivity, 74% (95% CI, 59 to 86%) specificity, 90% (95% CI, 84 to 95%) positive predictive value, and 30% (95% CI, 21 to 39%) negative predictive value. At STAGE scores of 9 or higher, the model exhibited a 100% (95% CI, 90 to 100%) specificity and 100% (95% CI, 72 to 100%) positive predictive value for predicting extubation success. CONCLUSIONS: After a survey of the reasons for delayed extubation, the STAGE scoring system was developed to better predict the extubation success rate. This scoring system has promising potential in predicting extubation readiness and may help clinicians avoid delayed extubation and failed extubation-related health complications in neurosurgical patients.

Comparative genomic analysis of carboxylesterase genes in Tenebrio molitor and other four tenebrionids.

Carboxylesterases (COEs) have various functions in wide taxons of organisms. In insects, COEs are important enzymes involved in the hydrolysis of a variety of ester-containing xenobiotics, neural signal transmission, pheromone degradation, and reproductive development. Understanding the diversity of COEs is basic to illustrate their functions. In this study, we identified 53, 105, 37, and 39 COEs from the genomes of Tenebrio molitor, Asbolus verucosus, Hycleus cichorii, and H. phaleratus in the superfamily of Tenebrionidea, respectively. Phylogenetic analysis showed that 234 COEs from these four species and those reported in Tribolium castaneum (63) could be divided into 12 clades and three major classes. The α-esterases significantly expanded in T. molitor, A. verucosus, and T. castaneum compared to dipteran and hymenopteran insects. In T. molitor, most COEs showed tissue and stage-specific but not a sex-biased expression. Our results provide insights into the diversity and evolutionary characteristics of COEs in tenebrionids, and lay a foundation for the functional characterization of COEs in the yellow mealworm.

Feasibility of low-dose dexmedetomidine for prevention of postoperative delirium after intracranial operations: a pilot randomized controlled trial.

BACKGROUND: Clinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors. METHODS: In this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 µg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented. RESULTS: Sixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (- 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation. CONCLUSIONS: The low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020.

A gap existed between physicians' perceptions and performance of pain, agitation-sedation and delirium assessments in Chinese intensive care units.

BACKGROUND: Pain, agitation-sedation and delirium management are crucial elements in the care of critically ill patients. In the present study, we aimed to present the current practice of pain, agitation-sedation and delirium assessments in Chinese intensive care units (ICUs) and investigate the gap between physicians' perception and actual clinical performance. METHODS: We sent invitations to the 33 members of the Neuro-Critical Care Committee affiliated with the Chinese Association of Critical Care Physicians. Finally, 24 ICUs (14 general-, 5 neuroscience-, 3 surgical-, and 2 emergency-ICUs) from 20 hospitals participated in this one-day point prevalence study combined with an on-site questionnaire survey. We enrolled adult ICU admitted patients with a length of stay ≥24 h, who were divided into the brain-injured group or non-brain-injured group. The hospital records and nursing records during the 24-h period prior to enrollment were reviewed. Actual evaluations of pain, agitation-sedation and delirium were documented. We invited physicians on-duty during the 24 h prior to the patients' enrollment to complete a survey questionnaire, which contained attitude for importance of pain, agitation-sedation and delirium assessments. RESULTS: We enrolled 387 patients including 261 (67.4%) brain-injured and 126 (32.6%) non-brain-injured patients. There were 19.9% (95% confidence interval [CI]: 15.9-23.9%) and 25.6% (95% CI: 21.2-29.9%) patients receiving the pain and agitation-sedation scale assessment, respectively. The rates of these two types of assessments were significantly lower in brain-injured patients than non-brain-injured patients (p = 0.003 and < 0.001). Delirium assessment was only performed in three patients (0.8, 95% CI: 0.1-1.7%). In questionnaires collected from 91 physicians, 70.3% (95% CI: 60.8-79.9%) and 82.4% (95% CI: 74.4-90.4%) reported routine use of pain and agitation-sedation scale assessments, respectively. More than half of the physicians (52.7, 95% CI: 42.3-63.2%) reported daily screening for delirium using an assessment scale. CONCLUSIONS: The actual prevalence of pain, agitation-sedation and delirium assessment, especially delirium screening, was suboptimal in Chinese ICUs. There is a gap between physicians' perceptions and actual clinical practice in pain, agitation-sedation and delirium assessments. Our results will prompt further quality improvement projects to optimize the practice of pain, agitation-sedation and delirium management in China. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03975751 . Retrospectively registered on 2 June 2019.

Use of Electrical Impedance Tomography (EIT) to Estimate Global and Regional Lung Recruitment Volume (VREC) Induced by Positive End-Expiratory Pressure (PEEP): An Experiment in Pigs with Lung Injury.

BACKGROUND Electrical impedance tomography (EIT) is a real-time tool used to monitor lung volume change at the bedside, which could be used to measure lung recruitment volume (VREC) for setting positive end-expiratory pressure (PEEP). We assessed and compared the agreement in VREC measurement with the EIT method versus the flow-derived method. MATERIAL AND METHODS In 12 Bama pigs, lung injury was induced by tracheal instillation of hydrochloric acid and verified by an arterial partial pressure of oxygen to inspired oxygen fraction ratio below 200 mmHg. During the end-expiratory occlusion, an airway release maneuver was conduct at 5 and 15 cmH2O of PEEP. VREC was measured by flow-integrated PEEP-induced lung volume change (flow-derived method) and end-expiratory lung impedance change (EIT-derived method). Linear regression and Bland-Altman analysis were used to test the correlation and agreement between these 2 measures. RESULTS Lung injury was successfully induced in all the animals. EIT-derived VREC was significantly correlated with flow-derived VREC (R²=0.650, p=0.002). The bias (the lower and upper limits of agreement) was -19 (-182 to 144) ml. The median (interquartile range) of EIT-derived VREC was 322 (218-469) ml, with 110 (59-142) ml and 194 (157-307) ml in dependent and nondependent lung regions, respectively. Global and regional respiratory system compliance increased significantly at high PEEP compared to those at low PEEP. CONCLUSIONS Close correlation and agreement were found between EIT-derived and flow-derived VREC measurements. The advantages of EIT-derived recruitability assessment included the avoidance of ventilation interruption and the ability to provide regional recruitment information.

Early growth response protein-1 upregulates long noncoding RNA Arid2-IR to promote extracellular matrix production in diabetic kidney disease.

Diabetic kidney disease (DKD) has surpassed chronic glomerulonephritis as the leading cause of end-stage renal disease. Previously, we showed that early growth response protein-1 (Egr1) plays a key role in DKD by enhancing mesangial cell proliferation and extracellular matrix (ECM) production. The long noncoding RNA (lncRNA) AT-rich interactive domain 2-IR (Arid2-IR) has been identified as a mothers against decapentaplegic homolog 3 (Smad3)-associated lncRNA in unilateral ureteral obstructive kidney disease. However, the effect of Egr1 on Arid2-IR in the development of DKD is still unknown. In this study, we found that Arid2-IR was increased in mice with high-fat diet and streptozotocin-induced type 2 diabetes and in mouse mesangial cells cultured with high glucose to mimic diabetes. Knockdown of Arid2-IR in mouse mesangial cells reduced the high expression levels of collagen-α1(I) (Col1a1) and α-smooth muscle actin (α-SMA) induced by high glucose. Furthermore, Arid2-IR expression changed the increased expression of Col1a1 and α-SMA caused by overexpression of Egr1. Overall, these data suggest that increased Arid2-IR likely contributes to ECM production in DKD and that Egr1 promotes ECM production in DKD partly by upregulating Arid2-IR. Thus, Arid2-IR may be a new target in the treatment of DKD.

Use of the Bispectral Index to Predict Recovery of Consciousness in Patients with Spontaneous Intracerebral Hemorrhage After Surgical Hematoma Evacuation: A Prospective Cohort Study.

BACKGROUND Our study aimed to test the predictive value of the bispectral index (BIS) for the post-operational consciousness recovery in patients undergone hematoma evacuation due to spontaneous intracerebral hemorrhage (ICH). MATERIAL AND METHODS In this prospective cohort study, we enrolled adult spontaneous ICH patients after surgical hematoma evacuation who did not recover consciousness on the first postoperative day. After patient enrollment, the BIS was continuously monitored for 12 hours, and the motor response on the Glasgow Coma Scale (GCS-M) was evaluated. The patients were followed up for 30 days and divided into a consciousness recovery group and a nonrecovery group. Receiver operating characteristic curve analysis was performed to investigate the predictive values of the BIS, GCS-M and ICH score on the consciousness recovery. The area under the curve (AUC) and 95% confidence interval (95%CI) were calculated. During the 12-hour monitoring period, the peak BIS value after GCS-M stimulation was used for ROC analysis. RESULTS Of the 55 enrolled patients, 19 patients recovered consciousness, and 36 patients did not. The BIS value of the consciousness recovery group was significantly higher than that of the nonrecovery group (P<0.001). For consciousness recovery prediction, the AUC (95%CI) of the BIS values after external stimulation was 0.97 (0.91-1.00), which was superior to the GCS-M (0.75 [0.59-0.91]) and ICH score (0.57 [0.41-0.73]). CONCLUSIONS Our study demonstrates that BIS might be a potential tool for predicting the consciousness recovery in ICH patients undergone surgical hematoma evacuation.

Role of p53/miR-155-5p/sirt1 loop in renal tubular injury of diabetic kidney disease.

BACKGROUND: Diabetic kidney disease is a renal microvascular disease caused by diabetes, known as one of the most serious and lethal complications of diabetes. Early renal hypertrophy is the main pathological feature, which gradually leads to the deposition of glomerular extracellular matrix and tubulointerstitial fibrosis, eventually developing irreversible structural damage to the kidneys. Autophagy is a cell self-homeostatic mechanism that is activated under stress conditions and may serve as a protective response to the survival of renal fibrogenic cells. MicroRNA (miRNA) network may be involved in the regulation of fibrosis. The purpose of this study is to assess how miRNAs regulate diabetic kidney disease and autophagy and fibrosis in renal proximal tubular cells under high glucose conditions. METHODS: Human renal proximal tubular (HK-2) cells were exposed to high glucose in vitro. Bioinformatic analysis was used to select the candidate gene for potential target regulation of miR-155, Sirt1. ATG5, ATG7 is the key to autophagosome formation, regulated by Sirt1. p53 regulates miR-155 expression as a transcription factor. MiR-155 overexpression and inhibition were achieved by transfection of miR-155 mimic and inhibit to evaluate its effect on Sirt1 and autophagy and fibrosis markers. Dual luciferase reporter assays were used to confirm the direct interaction of Sirt1 with miR-155. Overexpression and inhibition of Sirt1 gene were achieved by transfection of Sirt1 plasmid and Sirt1 si to observe its effect on P53. Chip assay experiments confirmed the direct regulation of P53 on miR-155. RESULTS: Under high glucose conditions, miR-155 was detected in HK-2 cells in concentration gradient, increased expression of p53 and down-regulated expression of sirt1 and autophagy-associated proteins LC3II, ATG5 and ATG7. Dual luciferase reporter assays indicate that miR-155 can target its binding to the Sirt1 3'UTR region to reduce its expression. Under high glucose conditions, over expression of miR-155 decreased the expression of LC3-II and ATG5 in HK-2 cells, while inhibition of miR-155 reversed this effect. Using chip assay testing in HK-2 cells, we demonstrated that p53 binds directly to miR-155. CONCLUSIONS: The signaling axis of p53, miR-155-5p, and sirt1 in autophagic process might be a critical adapting mechanism for diabetic kidney injury.

Use of esophageal balloon pressure-volume curve analysis to determine esophageal wall elastance and calibrate raw esophageal pressure: a bench experiment and clinical study.

BACKGROUND: Accurate measurement of esophageal pressure (Pes) depends on proper filling of the balloon. Esophageal wall elastance (Ees) may also influence the measurement. We examined the estimation of balloon-surrounding elastance in a bench model and investigated a simplified calibrating procedure of Pes in a balloon with relatively small volume. METHODS: The Cooper balloon catheter (geometric volume of 2.8 ml) was used in the present study. The balloon was progressively inflated in different gas-tight glass chambers with different inner volumes. Chamber elastance was measured by the fitting of chamber pressure and balloon volume. Balloon pressure-volume (P-V) curves were obtained, and the slope of the intermediate linear section was defined as the estimated chamber elastance. Balloon volume tests were also performed in 40 patients under controlled ventilation. The slope of the intermediate linear section on the end-expiratory esophageal P-V curve was calculated as the Ees. The balloon volume with the largest Pes tidal swing was defined as the best volume. Pressure generated by the esophageal wall during balloon inflation (Pew) was estimated as the product of Ees and best volume. Because the clinical intermediate linear section enclosed filling volume of 0.6 to 1.4 ml in each of the patient, we simplified the estimation of Ees by only using parameters at these two filling volumes. RESULTS: In the bench experiment, bias (lower and upper limits of agreement) was 0.5 (0.2 to 0.8) cmH2O/ml between the estimated and measured chamber elastance. The intermediate linear section on the clinical and bench P-V curves resembled each other. Median (interquartile range) Ees was 3.3 (2.5-4.1) cmH2O/ml. Clinical best volume was 1.0 (0.8-1.2) ml and ranged from 0.6 to 1.4 ml. Estimated Pew at the best volume was 2.8 (2.5-3.5) cmH2O with a maximum value of 5.2 cmH2O. Compared with the conventional method, bias (lower and upper limits of agreement) of Ees estimated by the simple method was - 0.1 (- 0.7 to 0.6) cmH2O/ml. CONCLUSIONS: The slope of the intermediate linear section on the balloon P-V curve correlated with the balloon-surrounding elastance. The estimation of Ees and calibration of Pes were feasible for a small-volume-balloon. TRIAL REGISTRATION: Identifier NCT02976844 . Retrospectively registered on 29 November 2016.

Bispectral Index Can Reliably Detect Deep Sedation in Mechanically Ventilated Patients: A Prospective Multicenter Validation Study.

BACKGROUND: Excessively deep sedation is prevalent in mechanically ventilated patients and often considered suboptimal. We hypothesized that the bispectral index (BIS), a quantified electroencephalogram instrument, would accurately detect deep levels of sedation. METHODS: We prospectively enrolled 90 critically ill mechanically ventilated patients who were receiving sedation. The BIS was monitored for 24 hours and compared with the Richmond Agitation Sedation Scale (RASS) evaluated every 4 hours. Deep sedation was defined as a RASS of -3 to -5. Threshold values of baseline BIS (the lowest value before RASS assessment) and stimulated BIS (the highest value after standardized assessment) for detecting deep sedation were determined in a training set (45 patients, 262 RASS assessments). Diagnostic accuracy was then analyzed in a validation set (45 patients, 264 RASS assessments). RESULTS: Deep sedation was only prescribed in 6 (6.7%) patients, but 76 patients (84.4%) had at least 1 episode of deep sedation. Thresholds for detecting deep sedation of 50 for baseline and 80 for stimulated BIS were identified, with respective areas under the receiver-operating characteristic curve of 0.771 (95% confidence interval, 0.714-0.828) and 0.805 (0.752-0.857). The sensitivity and specificity of baseline BIS were 94.0% and 66.5% and of stimulated BIS were 91.0% and 66.5%. When baseline and stimulated BIS were combined, the sensitivity, specificity, and clinical utility index were 85.0% (76.1%-91.1%), 85.9% (79.5%-90.7%), and 66.9% (57.8%-76.0%), respectively. CONCLUSIONS: Combining baseline and stimulated BIS may help detect deep sedation in mechanically ventilated patients.

Use of pressure muscle index to guide pressure support ventilation setting: a study protocol and statistical plan for a prospective randomised controlled proof-of-concept trial.

INTRODUCTION: Although pressure support ventilation is one of the most commonly used assisted ventilation modes in intensive care units, there is still a lack of precise strategies for setting pressure support. By performing an end-inspiratory airway occlusion, the difference between the peak and plateau airway pressure, which is defined as pressure muscle index (PMI), can be easily measured on the ventilator screen. Previous studies have shown that PMI is accurate in detecting high and low inspiratory effort. No study has been conducted to investigate the use of PMI as an indicator for setting inspiratory pressure support. METHOD AND ANALYSIS: This is a study protocol for a prospective, single-centre, randomised controlled, pilot trial. Sixty participants undergoing pressure support ventilation will be randomly assigned in a 1:1 ratio to the control group or intervention group, with pressure support adjusted according to standard care or guided by the PMI strategy for 48 hours, respectively. The feasibility of the PMI-guided strategy will be evaluated. The primary endpoint is the proportion of inspiratory effort measurements within a well-accepted 'normal' range, which is predefined as oesophageal pressure-time product per minute between 50 and 200 cmH2O⋅s/min, for each patient during 48 hours of pressure support adjustment. ETHICS AND DISSEMINATION: The study protocol has been approved by Beijing Tiantan Hospital (KY2023-005-02). The data generated in the present study will be available from the corresponding author on reasonable request. The results of the trial will be submitted to international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05963737; ClinicalTrials.org.

Use of pressure muscle index to predict the contribution of patient's inspiratory effort during pressure support ventilation: a prospective physiological study.

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support. Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort. Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort. Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

Characterization of three lamp genes from largemouth bass (Micropterus salmoides): molecular cloning, expression patterns, and their transcriptional levels in response to fast and refeeding strategy.

Lysosomes-associated membrane proteins (LAMPs), a family of glycosylated proteins and major constituents of the lysosomal membranes, play a dominant role in various cellular processes, including phagocytosis, autophagy and immunity in mammals. However, their roles in aquatic species remain poorly known. In the present study, three lamp genes were cloned and characterized from Micropterus salmoides. Subsequently, their transcriptional levels in response to different nutritional status were investigated. The full-length coding sequences of lamp1, lamp2 and lamp3 were 1251bp, 1224bp and 771bp, encoding 416, 407 and 256 amino acids, respectively. Multiple sequence alignment showed that LAMP1-3 were highly conserved among the different fish species, respectively. 3-D structure prediction, genomic survey, and phylogenetic analysis were further confirmed that these genes are widely existed in vertebrates. The mRNA expression of the three genes was ubiquitously expressed in all selected tissues, including liver, brain, gill, heart, muscle, spleen, kidney, stomach, adipose and intestine, lamp1 shows highly transcript levels in brain and muscle, lamp2 displays highly expression level in heart, muscle and spleen, but lamp3 shows highly transcript level in spleen, liver and kidney. To analyze the function of the three genes under starvation stress in largemouth bass, three experimental treatment groups (fasted group and refeeding group, control group) were established in the current study. The results indicated that the expression of lamp1 was significant induced after starvation, and then returned to normal levels after refeeding in the liver. The expression of lamp2 and lamp3 exhibited the same trend in the liver. In addition, in the spleen and the kidney, the transcript level of lamp1 and lamp2 was remarkably increased in the fasted treatment group and slightly decreased in the refed treatment group, respectively. Collectively, our findings suggest that three lamp genes may have differential function in the immune and energetic organism in largemouth bass, which is helpful in understanding roles of lamps in aquatic species.

Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis.

Objective: To investigate the pathogenesis of IBS-D by bioinformatics analysis of the differential microRNAs in rat colon tissue and to analyze and predict the function of their target genes. Methods: Twenty male Wistar rats of SPF class were randomly divided into two groups, the model group was manipulated using the colorectal dilatation method + chronic restraint stress method to establish the IBS-D model; while the blank group stroked the perineum at the same frequency. Screening of differential miRNAs after High-throughput sequencing of rat colon tissue. GO and KEGG analysis of target genes using the DAVID website, further mapping using RStudio software; the STRING database and the Cytoscape software were used to obtain the protein interaction network (PPI) of the target genes as well as the core genes. Finally, qPCR was used to detect the expression of target genes in the colon tissue of two groups of rats. Results: After the screening, miR-6324 was obtained as the key of this study. The GO analysis of target genes of miR-6324 is mainly involved in protein phosphorylation, positive regulation of cell proliferation, and intracellular signal transduction; it affects a variety of cellular components such as cytoplasm, nucleus, and organelles on the intracellular surface; it is also involved in molecular functions such as protein binding, ATP binding, and DNA binding. KEGG analysis showed that the intersecting target genes were mainly enriched in cancer pathways, proteoglycans in cancer, neurotrophic signaling pathway, etc. The protein-protein interaction network screened out the core genes mainly Ube2k, Rnf41, Cblb, Nek2, Nde1, Cep131, Tgfb2, Qsox1, and Tmsb4x. The qPCR results showed that the expression of miR-6324 decreased in the model group, but the decrease was not significant. Conclusion: miR-6324 may be involved in the pathogenesis of IBS-D as a potential biological target and provide further ideas for research on the pathogenesis of the disease or treatment options.

Corrigendum: Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis.

[This corrects the article DOI: 10.3389/fphar.2023.1044330.].

Use of airway pressure-based indices to detect high and low inspiratory effort during pressure support ventilation: a diagnostic accuracy study.

BACKGROUND: Assessment of the patient's respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (Paw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation. METHODS: In this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative Paw generated during the first 100 ms (P0.1) and the maximal negative swing of Paw (∆Pocc) were measured. After an end-inspiratory airway occlusion, Paw reached a plateau, and the magnitude of change in plateau from peak Paw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (Pmus) and Pmus-time product per minute (PTPmus/min) were used as the reference standard for the patient's effort. High and low effort was defined as Pmus > 10 and < 5 cmH2O, or PTPmus/min > 200 and < 50 cmH2O s min-1, respectively. RESULTS: A total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective Pmus and PTPmus/min criterion. The receiver operating characteristic area of the three Paw-based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83-0.96), specificity (0.74-0.88), and positive (0.80-0.91) and negative predictive values (0.78-0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using Pmus and PTPmus/min criterion, respectively. High receiver operating characteristic areas of the three Paw-based indices by the two criteria were found (0.93-0.95). A high sensitivity (0.80-1.00) and negative predictive value (0.97-1.00) were found with a low positive predictive value (0.23-0.64). CONCLUSIONS: By performing simple airway occlusion maneuvers, the Paw-based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort.

Ineffective Effort in Patients With Acute Brain Injury Undergoing Invasive Mechanical Ventilation.

BACKGROUND: Ineffective effort (IE) is a frequent patient-ventilator asynchrony in invasive mechanical ventilation. This study aimed to investigate the incidence of IE and to explore its relationship with respiratory drive in subjects with acute brain injury undergoing invasive mechanical ventilation. METHODS: We retrospectively analyzed a clinical database that assessed patient-ventilator asynchrony in subjects with acute brain injury. IE was identified based on airway pressure, flow, and esophageal pressure waveforms collected at 15-min intervals 4 times daily. At the end of each data set recording, airway-occlusion pressure (P0.1) was determined by the airway occlusion test. IE index was calculated to indicate the severity of IE. The incidence of IE in different types of brain injuries as well as its relationship with P0.1 was determined. RESULTS: We analyzed 852 data sets of 71 subjects with P0.1 measured and undergoing mechanical ventilation for at least 3 d after enrollment. IE was detected in 688 (80.8%) data sets, with a median index of 2.2% (interquartile range 0.4-13.1). Severe IE (IE index ≥ 10%) was detected in 246 (28.9%) data sets. The post craniotomy for brain tumor and the stroke groups had higher median IE index and lower P0.1 compared with the traumatic brain injury group (2.6% [0.7-9.7] vs 2.7% [0.3-21] vs 1.2% [0.1-8.5], P = .002; 1.4 [1-2] cm H2O vs 1.5 [1-2.2] cm H2O vs 1.8 [1.1-2.8] cm H2O, P = .001). Low respiratory drive (P0.1 < 1.14 cm H2O) was independently associated with severe IE in the expiratory phase (IEE) even after adjusting for confounding factors by logistic regression analysis (odds ratio 5.18 [95% CI 2.69-10], P < .001). CONCLUSIONS: IE was very common in subjects with acute brain injury. Low respiratory drive was independently associated with severe IEE.

A Highly Sensitive Urinary Exosomal miRNAs Biosensor Applied to Evaluation of Prostate Cancer Progression.

Prostate cancer is the most common cancer in the male population, carrying a significant disease burden. PSA is a widely available screening tools for this disease. Current screen-printed carbon electrode (SPCE)-based biosensors use a two-pronged probe approach to capture urinary miRNA. We were able to successfully detect specific exosomal miRNAs (exomiRs) in the urine of patients with prostate cancer, including exomiR-451 and exomiR-21, and used electrochemistry for measurement and analysis. Our results significantly reaffirmed the presence of exomiR-451 in urine and that a CV value higher than 220 nA is capable of identifying the presence of disease (p-value = 0.005). Similar results were further proven by a PAS greater than 4 (p-value = 0.001). Moreover, a higher urinary exomiR-21 was observed in the high-T3b stage; this significantly decreased following tumor removal (p-values were 0.016 and 0.907, respectively). According to analysis of the correlation with tumor metastasis, a higher exomiR-21 was associated with lymphatic metastasis (p-value 0.042), and higher exomiR-461 expression was correlated with tumor stage (p-value 0.031), demonstrating that the present exomiR biosensor can usefully predict tumor progression. In conclusion, this biosensor represents an easy-to-use, non-invasive screening tool that is both sensitive and specific. We strongly believe that this can be used in conjunction with PSA for the screening of prostate cancer.

A U-shaped association of tracheostomy timing with all-cause mortality in mechanically ventilated patients admitted to the intensive care unit: A retrospective cohort study.

Objectives: To evaluate the association of tracheostomy timing with all-cause mortality in patients with mechanical ventilation (MV). Method: It's a retrospective cohort study. Adult patients undergoing invasive MV who received tracheostomy during the same hospitalization based on the Medical Information Mart for Intensive Care-III (MIMIC-III) database, were selected. The primary outcome was the relationship between tracheostomy timing and 90-day all-cause mortality. A restricted cubic spline was used to analyze the potential non-linear correlation between tracheostomy timing and 90-day all-cause mortality. The secondary outcomes included free days of MV, incidence of ventilator-associated pneumonia (VAP), free days of analgesia/sedation in the intensive care unit (ICU), length of stay (LOS) in the ICU, LOS in hospital, in-ICU mortality, and 30-day all-cause mortality. Results: A total of 1,209 patients were included in this study, of these, 163 (13.5%) patients underwent tracheostomy within 4 days after intubation, while 647 (53.5%) patients underwent tracheostomy more than 11 days after intubation. The tracheotomy timing showed a U-shaped relationship with all-cause mortality, patients who underwent tracheostomy between 5 and 10 days had the lowest 90-day mortality rate compared with patients who underwent tracheostomy within 4 days and after 11 days [84 (21.1%) vs. 40 (24.5%) and 206 (31.8%), P < 0.001]. Conclusion: The tracheotomy timing showed a U-shaped relationship with all-cause mortality, and the risk of mortality was lowest on day 8, but a causal relationship has not been demonstrated.