New evidence for a role of DANCR in cancers: a comprehensive review.

Cancer remains a leading cause of mortality and poses a substantial threat to public health. Studies have revealed that Long noncoding RNA DANCR is a cytoplasmic lncRNA whose aberrant expression plays a pivotal role in various cancer types. Within tumour biology, DANCR exerts regulatory control over crucial processes such as proliferation, invasion, metastasis, angiogenesis, inflammatory responses, cellular energy metabolism reprogramming, and apoptosis. By acting as a competitive endogenous RNA for miRNAs and by interacting with proteins and mRNAs at the molecular level, DANCR contributes significantly to cancer progression. Elevated DANCR levels have also been linked to heightened resistance to anticancer drugs. Moreover, the detection of circulating DANCR holds promise as a valuable biomarker for aiding in the clinical differentiation of different cancer types. This article offers a comprehensive review and elucidation of the primary functions and molecular mechanisms through which DANCR influences tumours.

COVID-19 related acute necrotizing encephalopathy and acute myocarditis in an adult female: a novel case report of brain injury and myocarditis.

BACKGROUND: Acute necrotizing encephalopathy (ANE) and myocarditis are both acute, life-threatening conditions that can be triggered by COVID-19. We report a case of sequential ANE and myocarditis following a COVID-19 infection. CASE PRESENTATION: A 27-year-old female patient was brought to the emergency department due to episodes of fever for two days and a 9-h altered state of consciousness. Her condition rapidly developed into stuporous and hemodynamic instability within serval hours. Veno-arterial extracorporeal membrane oxygenation (ECMO) was rapidly initiated with other supportive treatments. The following-up MRI showed bilateral, symmetrically distributed lesions in the brainstem, bilateral hippocampal regions, and bilateral basal ganglia, consistent with ANE. The diagnosis was confirmed through the detection of SARS-CoV-2 and the exclusion of other potential causes. After weeks of medical treatment, her condition stabilized, and she was transferred for further rehabilitation treatment. CONCLUSIONS: This case study indicates that COVID-19 may simultaneously and rapidly affect the central nervous system and cardiovascular system, leading to poor outcomes. Accurate diagnosis and timely invasive bridging therapy, when necessary, can be lifesaving. Further exploration of potential mechanisms underlying COVID-19 central nervous system (CNS) and cardiovascular system manifestations will be important.

Variation in central venous oxygen saturation to evaluate fluid responsiveness: a systematic review and meta-analysis.

BACKGROUND: Since oxygen content and oxygen consumption typically remain unchanged within a short period, variation in central venous oxygen saturation (ΔScvO2) during fluid challenge can theoretically track the changes in cardiac output (CO). We conducted this meta-analysis to systematically assess the diagnostic performance of ΔScvO2 during a fluid challenge for fluid responsiveness in mechanically ventilated patients receiving volume expansion. METHODS: Electronic databases were systematically searched to identify relevant studies published before October 24, 2022. As the cutoff value of ΔScvO2 was expected to vary across the included studies, we estimated the area under the hierarchical summary receiver operating characteristic curve (AUHSROC) as the primary measure of diagnostic accuracy. The optimal threshold of ΔScvO2 and the corresponding 95% confidential interval (CI) were also estimated. RESULTS: This meta-analysis included 5 observational studies comprising 240 participants, of whom 133 (55%) were fluid responders. Overall, the ΔScvO2 during the fluid challenge exhibited excellent performance for defining fluid responsiveness in mechanically ventilated patients receiving volume expansion, with an AUHSROC of 0.86 (95% CI 0.83-0.89), a pooled sensitivity of 0.78 (95% CI 0.69-0.85), a pooled specificity of 0.84 (95% CI 0.72-0.91), and a pooled diagnostic odds ratio of 17.7 (95% CI 5.9-53.2). The distribution of the cutoff values was nearly conically symmetrical and concentered between 3 and 5%; the mean and median cutoff values were 4% (95% CI 3-5%) and 4% (95% CI not estimable), respectively. CONCLUSIONS: In mechanically ventilated patients receiving volume expansion, the ΔScvO2 during the fluid challenge is a reliable indicator of fluid responsiveness. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/ , registry number: CRD42022370192.

Prophylactic noninvasive respiratory support in the immediate postoperative period after cardiac surgery - a systematic review and network meta-analysis.

BACKGROUND: Noninvasive respiratory support has been increasingly applied in the immediate postoperative period to prevent postoperative pulmonary complications (PPCs). However, the optimal approach remains uncertain. We sought to evaluate the comparative effectiveness of various noninvasive respiratory strategies used in the immediate postoperative period after cardiac surgery. METHODS: We conducted a frequentist random-effect network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the prophylactic use of noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), high flow nasal cannula (HFNC), or postoperative usual care (PUC) in the immediate postoperative period after cardiac surgery. Databases were systematically searched through September 28, 2022. Study selection, data extraction, and quality assessment were performed in duplicate. The primary outcome was the incidence of PPCs. RESULTS: Sixteen RCTs enrolling 3011 patients were included. Compared with PUC, NIV significantly reduced the incidence of PPCs [relative risk (RR) 0.67, 95% confidence interval (CI): 0.49 to 0.93; absolute risk reduction (ARR) 7.6%, 95% CI: 1.6-11.8%; low certainty] and the incidence of atelectasis (RR 0.65, 95% CI: 0.45 to 0.93; ARR 19.3%, 95% CI: 3.9-30.4%; moderate certainty); however, prophylactic NIV was not associated with a decreased reintubation rate (RR 0.82, 95% CI: 0.29 to 2.34; low certainty) or reduced short-term mortality (RR 0.64, 95% CI: 0.16 to 2.52; very low certainty). As compared to PUC, the preventive use of CPAP (RR 0.85, 95% CI: 0.60 to 1.20; very low certainty) or HFNC (RR 0.74, 95% CI: 0.46 to 1.20; low certainty) had no significant beneficial effect on the incidence of PPCs, despite exhibiting a downward trend. Based on the surface under the cumulative ranking curve, the highest-ranked treatment for reducing the incidence of PPCs was NIV (83.0%), followed by HFNC (62.5%), CPAP (44.3%), and PUC (10.2%). CONCLUSIONS: Current evidence suggest that the prophylactic use of NIV in the immediate postoperative period is probably the most effective noninvasive respiratory approach to prevent PPCs in patients undergoing cardiac surgery. Given the overall low certainty of the evidence, further high-quality research is warranted to better understand the relative benefits of each noninvasive ventilatory support. CLINICAL TRIAL REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , registry number: CRD42022303904.

The ROX index as a predictor of high-flow nasal cannula outcome in pneumonia patients with acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: The respiratory rate-oxygenation (ROX) index has been increasingly applied to predict the outcome of high-flow nasal cannula (HFNC) in pneumonia patients with acute hypoxemic respiratory failure (AHRF). However, its diagnostic accuracy for the HFNC outcome has not yet been systematically assessed. This meta-analysis sought to evaluate the predictive performance of the ROC index for the successful weaning from HFNC in pneumonia patients with AHRF. METHODS: A literature search was conducted on electronic databases through February 12, 2022, to retrieve studies that investigated the diagnostic accuracy of the ROC index for the outcome of HFNC application in pneumonia patients with AHRF. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy due to the varied cutoff values of the index. We observed the distribution of the cutoff values and estimated the optimal threshold with corresponding 95% confidential interval (CI). RESULTS: Thirteen observational studies comprising 1751 patients were included, of whom 1003 (57.3%) successfully weaned from HFNC. The ROC index exhibits good performance for predicting the successful weaning from HFNC in pneumonia patients with AHRF, with an AUHSROC of 0.81 (95% CI 0.77-0.84), a pooled sensitivity of 0.71 (95% CI 0.64-0.78), and a pooled specificity of 0.78 (95% CI 0.70-0.84). The cutoff values of the ROX index were nearly conically symmetrically distributed; most data were centered between 4.5 and 6.0, and the mean and median values were 4.8 (95% CI 4.2-5.4) and 5.3 (95% CI 4.2-5.5), respectively. Moreover, the AUHSROC in the subgroup of measurement within 6 h after commencing HFNC was comparable to that in the subgroup of measurement during 6-12 h. The stratified analyses also suggested that the ROC index was a reliable predictor of HFNC success in pneumonia patients with coronavirus disease 2019. CONCLUSIONS: In pneumonia patients with AHRF, the ROX index measured within 12 h after HFNC initiation is a good predictor of successful weaning from HFNC. The range of 4.2-5.4 may represent the optimal confidence interval for the prediction of HFNC outcome.

Spinal cord infarction secondary to pulmonary embolism-induced cardiac arrest: a case report.

BACKGROUND: Pulmonary embolism is a common cause of cardiac arrest. Pulmonary embolism-induced cardiac arrest typically suffers from ischemic injuries to various organs, including the central nervous system. However, spinal cord infarction is a rare complication of pulmonary embolism-induced cardiac arrest. At present, there is no case report on the occurrence of spinal cord infarction secondary to pulmonary embolism-induced cardiac arrest without accompanied cerebral complications. CASE PRESENTATION: A 72-year-old woman with dyspnea and chest tightness was admitted to the emergency room. Cardiac arrest occurred within a short period after admission. Subsequent computed tomographic pulmonary angiography revealed multiple pulmonary thromboses, which were highly suspected to be the cause of cardiac arrest. Thrombolytic therapy with alteplase was given after the return of spontaneous circulation. Unfortunately, she was found to be paraplegic in both lower extremities after regaining consciousness. Spinal cord infarction was confirmed by thoracic magnetic resonance imaging. CONCLUSIONS: Despite receiving high-quality cardiopulmonary resuscitation, patients with cardiac arrest are at high risk of ischemic injury to the central nervous system. After the recovery of consciousness, clinicians should pay more attention to preclude the possibility of spinal cord infarction.

Optimizing left ventricular-arterial coupling during the initial resuscitation in septic shock - a pilot prospective randomized study.

BACKGROUND: Left ventricular-arterial coupling (VAC), defined as the ratio of effective arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), has been extensively described as a key determinant of cardiovascular work efficacy. Previous studies indicated that left ventricular-arterial uncoupling was associated with worse tissue perfusion and increased mortality in shock patients. Therefore, this study aims to investigate whether a resuscitation algorithm based on optimizing left VAC during the initial resuscitation can improve prognosis in patients with septic shock. METHODS: This pilot study was conducted in an intensive care unit (ICU) of a tertiary teaching hospital in China. A total of 83 septic shock patients with left ventricular-arterial uncoupling (i.e., the Ea/Ees ratio ≥ 1.36) were randomly assigned to receive usual care (usual care group, n = 42) or an algorithm-based resuscitation that attempt to reduce the Ea/Ees ratio to 1 within the first 6 h after randomization (VAC-optimized group, n = 41). The left VAC was evaluated by transthoracic echocardiography every 2 h during the study period. The primary endpoint was 28-days mortality. The secondary endpoints included lactate clearance rate, length of ICU stay, and duration of invasive mechanical ventilation (IMV). RESULTS: Eighty-two patients (98.8%) completed the study and were included in the final analysis. The Ea/Ees ratio was reduced in both groups, and the decrease in Ea/Ees ratio in the VAC-optimized group was significantly greater than that in the usual care group [median (interquartile range), 0.39 (0.26, 0.45) vs. 0.1 (0.06, 0.22); P < 0.001]. Compared with the usual care group, the VAC-optimized group likely exhibited the potential to reduce the 28-days mortality (33% vs. 50%; log-rank hazard ratio = 0.526, 95% confidence interval: 0.268 to 1.033). Moreover, the VAC-optimized group had a higher lactate clearance rate than the usual care group [27.7 (11.9, 45.7) % vs. 18.3 (- 5.7, 32.1) %; P = 0.038]. No significant difference was observed in terms of the length of ICU stay or duration of IMV. CONCLUSIONS: During the initial resuscitation of septic shock, optimizing left ventricular-arterial coupling was associated with improved lactate clearance, while likely having a beneficial effect on prognosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024031 . Registered 23 June 2019 - Retrospectively registered.

Left ventricular-arterial coupling as a predictor of stroke volume response to norepinephrine in septic shock - a prospective cohort study.

BACKGROUND: Left ventricular-arterial coupling (VAC), defined as the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), is a key determinant of cardiovascular performance. This study aims to evaluate whether left VAC can predict stroke volume (SV) response to norepinephrine (NE) in septic shock patients. METHODS: This was a prospective cohort study conducted in an intensive care unit of a tertiary teaching hospital in China. We recruited septic shock patients who had persistent hypotension despite fluid resuscitation and required NE to maintain mean arterial pressure (MAP) > 65 mmHg. Those patients in whom the target MAP was not reached after NE infusion were ineligible. Echocardiographic variables were measured before (baseline) and after NE infusion. SV responder was defined by a ≥ 15% increase in SV after NE infusion. RESULTS: Of 34 septic shock patients included, 19 (56%) were SV responders. Before NE infusion, SV responders had a lower Ees (1.13 ± 0.24 mmHg/mL versus 1.50 ± 0.46 mmHg/mL, P = 0.005) and a higher Ea/Ees ratio (1.47 ± 0.40 versus 1.02 ± 0.30, P = 0.001) than non-responders, and Ea in SV responders was comparable to that in non-responders (1.62 ± 0.36 mmHg/mL versus 1.43 ± 0.28 mmHg/mL, P = 0.092). NE significantly increased Ea and Ees in both groups. The Ea/Ees ratio was normalized by NE administration in SV responders but unchanged in non-responders. The baseline Ea/Ees ratio was positively correlated with NE-induced SV increases (r = 0.688, P < 0.001). Logistic regression analysis indicated that the baseline Ea/Ees ratio was a predictor of SV increases induced by NE (odd ratio 0.008, 95% confidence interval (CI): 0.000 to 0.293), with an area under the receiver operating characteristic curve of 0.816 (95% CI: 0.646 to 0.927). CONCLUSIONS: The left VAC has the ability to predict SV response to NE infusion in septic shock patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024031, Registered 23 June 2019 - Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=40359&htm=4 .

PSK1 coordinates glucose metabolism and utilization and regulates energy-metabolism oscillation in Saccharomyces cerevisiae.

Energy-metabolism oscillations (EMO) are ultradian biological rhythms observed in in aerobic chemostat cultures of Saccharomyces cerevisiae. EMO regulates energy metabolism such as glucose, carbohydrate storage, O2 uptake, and CO2 production. PSK1 is a nutrient responsive protein kinase involved in regulation of glucose metabolism, sensory response to light, oxygen, and redox state. The aim of this investigation was to assess the function of PSK1 in regulation of EMO. The mRNA levels of PSK1 fluctuated in concert with EMO, and deletion of PSK1 resulted in unstable EMO with disappearance of the fluctuations and reduced amplitude, compared with the wild type. Furthermore, the mutant PSK1Δ showed downregulation of the synthesis and breakdown of glycogen with resultant decrease in glucose concentrations. The redox state represented by NADH also decreased in PSK1Δ compared with the wild type. These data suggest that PSK1 plays an important role in the regulation of energy metabolism and stabilizes ultradian biological rhythms. These results enhance our understanding of the mechanisms of biorhythms in the budding yeast.

Preventive use of respiratory support after scheduled extubation in critically ill medical patients-a network meta-analysis of randomized controlled trials.

BACKGROUND: Respiratory support has been increasingly used after extubation for the prevention of re-intubation and improvement of prognosis in critically ill medical patients. However, the optimal respiratory support method is still under debate. This network meta-analysis (NMA) aims to evaluate the comparative effectiveness of various respiratory support methods used for preventive purposes after scheduled extubation in critically ill medical patients. METHODS: A systematic database search was performed from inception to December 19, 2019, for randomized controlled trials (RCTs) that compared a preventive use of different respiratory support methods, including conventional oxygen therapy (COT), noninvasive ventilation (NIV), high-flow oxygen therapy (HFOT), and combinational use of HFOT and NIV (HFOT+NIV), after planned extubation in adult critically ill medical patients. Study selection, data extraction, and quality assessments were performed in duplicate. The primary outcomes included re-intubation rate and short-term mortality. RESULTS: Seventeen RCTs comprising 3341 participants with 4 comparisons were included. Compared with COT, NIV significantly reduced the re-intubation rate [risk ratio (RR) 0.55, 95% confidence interval (CI) 0.39 to 0.77; moderate quality of evidence] and short-term mortality (RR 0.66, 95% CI 0.48 to 0.91; moderate quality of evidence). Compared to COT, HFOT had a beneficial effect on the re-intubation rate (RR 0.55, 95% CI 0.35 to 0.86; moderate quality of evidence) but no effect on short-term mortality (RR 0.79, 95% CI 0.56 to 1.12; low quality of evidence). No significant difference in the re-intubation rate or short-term mortality was found among NIV, HFOT, and HFOT+NIV. The treatment rankings based on the surface under the cumulative ranking curve (SUCRA) from best to worst for re-intubation rate were HFOT+NIV (95.1%), NIV (53.4%), HFOT (51.2%), and COT (0.3%), and the rankings for short-term mortality were NIV (91.0%), HFOT (54.3%), HFOT+NIV (43.7%), and COT (11.1%). Sensitivity analyses of trials with a high risk of extubation failure for the primary outcomes indicated that the SUCRA rankings were comparable to those of the primary analysis. CONCLUSIONS: After scheduled extubation, the preventive use of NIV is probably the most effective respiratory support method for comprehensively preventing re-intubation and short-term death in critically ill medical patients, especially those with a high risk of extubation failure.

Characterization of ciprofloxacin-resistant and ESBL-producing Salmonella enteric serotype Derby in Eastern China.

BACKGROUND: Fluoroquinolone resistance and ESBL-production are concurrently found in a limited number of Salmonella serotypes. The present study was aimed to characterize fluoroquinolone-resistant and ESBL-producing Salmonella enteric serotype Derby (S. Derby) isolates in terms of antimicrobial susceptibility, relevant genetic mechanisms, and PFGE. RESULTS: From 2013 to 2017 in Ningbo China, 52 S. Derby isolates were identified out of 826 non-typhoidal Salmonella isolates from patient feces, food, and environmental water samples. Three S. derby isolates were identified to be fluoroquinolone-resistant and ESBL-producing with cefotaxime MIC of 64 µg/mL and ciprofloxacin MIC of 4 µg/mL. The three isolates contained the same genetic structure of quinolone resistance, including a silent gyrA mutation S (TCC) 83S (TCT) and three PMQR genes qnrB, qnrS and aac(6')-Ib-cr. As withß-lactams resistance mechanisms, two isolates contained blaTEM, blaOXA, and blaCTX-M genes and one isolate contained blaOXA and blaCTX-M genes. Additionally, two isolates displayed more identical PFGE pattern than the third isolate, whereas three isolates showed the same plasmid profile of I1, W and P by PCR-based replicon typing. The conjugation experiment showed no dissemination of ß-lactam resistance by direct contact among isolates; the transformation experiment failed to transfer plasmid conferring ampicillin resistance to E. coli DH5a. CONCLUSION: The present study demonstrates the emerging fluoroquinolone-resistant and ESBL-producing S. Derby in both humans and the environment. Seeing that S. Derby has become one of the most common Salmonella serotypes, this situation gives rise to a new major risk of food-borne diseases.

Stress ulcer prophylaxis with proton pump inhibitors or histamine 2 receptor antagonists in critically ill adults - a meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: Proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) have been widely used as stress ulcer prophylaxis (SUP) in critically ill patients, however, its efficacy and safety remain unclear. This study aimed to assess the effect of SUP on clinical outcomes in critically ill adults. METHODS: Literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane database of clinical trials for randomized controlled trials (RCTs) that investigated SUP, with PPI or H2RA, versus placebo or no prophylaxis in critically ill patients from database inception through 1 June 2019. Study selection, data extraction and quality assessment were performed in duplicate. The primary outcomes were clinically important gastrointestinal (GI) bleeding and overt GI bleeding. Conventional meta-analysis with random-effects model and trial sequential analysis (TSA) were performed. RESULTS: Twenty-nine RCTs were identified, of which four RCTs were judged as low risk of bias. Overall, SUP could reduce the incident of clinically important GI bleeding [relative risk (RR) = 0.58; 95% confidence intervals (CI): 0.42-0.81] and overt GI bleeding (RR = 0.48; 95% CI: 0.36-0.63), these results were confirmed by the sub-analysis of trials with low risk of bias, TSA indicated a firm evidence on its beneficial effects on the overt GI bleeding (TSA-adjusted CI: 0.31-0.75), but lack of sufficient evidence on the clinically important GI bleeding (TSA-adjusted CI: 0.23-1.51). Among patients who received enteral nutrition (EN), SUP was associated with a decreased risk of clinically important GI bleeding (RR = 0.61; 95% CI: 0.44-0.85; TSA-adjusted CI: 0.16-2.38) and overt GI bleeding (RR = 0.64; 95% CI: 0.42-0.96; TSA-adjusted CI: 0.12-3.35), but these benefits disappeared after adjustment with TSA. Among patients who did not receive EN, SUP had only benefits in reducing the risk of overt GI bleeding (RR = 0.37; 95% CI: 0.25-0.55; TSA-adjusted CI: 0.22-0.63), but not the clinically important GI bleeding (RR = 0.27; 95% CI: 0.04-2.09). CONCLUSIONS: SUP has benefits on the overt GI bleeding in critically ill patients who did not receive EN, however, its benefits on clinically important GI bleeding still needs more evidence to confirm.

Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults.

UNLABELLED: Patients with acute-on-chronic liver failure (ACLF) represent a heterogeneous population. The aim of the study is to identify distinct groups according to the etiologies of precipitating events. A total of 405 ACLF patients were identified from 1,361 patients with cirrhosis with acute decompensation and categorized according to the types of acute insults. Clinical characteristics and prognosis between the hepatic group and extrahepatic group were compared, and the performance of prognostic models was tested in different groups. Two distinct groups (hepatic-ACLF and extrahepatic-ACLF) were identified among the ACLF population. Hepatic-ACLF was precipitated by hepatic insults and had relatively well-compensated cirrhosis with frequent liver and coagulation failure. In contrast, extrahepatic-ACLF was exclusively precipitated by extrahepatic insults, characterized by more severe underlying cirrhosis and high occurrence of extrahepatic organ failures (kidney, cerebral, circulation, and respiratory systems). Both groups had comparably high short-term mortality (28-day transplant-free mortality: 48.3% vs. 50.7%; P = 0.22); however, the extra-hepatic-ACLF group had significantly higher 90-day and 1-year mortality (90-day: 58.9% vs. 68.3%, P = 0.035; 1-year: 63.9% vs. 74.6%, P = 0.019). In hepatic-ACLF group, the integrated Model for End-Stage Liver Disease (iMELD) score had the highest area under the receiver operating characteristic curve (auROC = 0.787) among various prognostic models in predicting 28-day mortality, whereas CLIF-Consortium scores for ACLF patients (CLIF-C-ACLF) had the highest predictive value in the other group (auROC = 0.779). CONCLUSIONS: ACLF precipitated by hepatic insults is distinct from ACLF precipitated by extrahepatic insults in clinical presentation and prognosis. The iMELD score may be a better predictor for hepatic-ACLF short-term prognosis, whereas CLIF-C-ACLF may be better for extrahepatic-ACLF patients.

The microRNA miR-17 regulates lung FoxA1 expression during lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is a severe pulmonary disease that causes a high number of fatalities worldwide. Studies have shown that FoxA1 expression is upregulated during ALI and may play an important role in ALI by promoting the apoptosis of alveolar type II epithelial cells. However, the mechanism of FoxA1 overexpression in ALI is unclear. In this study, an in vivo murine model of ALI and alveolar type II epithelial cells injury was induced using lipopolysaccharide (LPS). LPS upregulated FoxA1 in the lung tissue of the in vivo ALI model and in LPS-challenged type II epithelial cells. In contrast, miR-17 was significantly downregulated in these models. After miR-17 antagomir injection, the expression of FoxA1 was significantly increased in ALI mice. MiR-17 mimics could significantly inhibit FoxA1 mRNA and protein expression, whereas the miR-17 inhibitor could significantly increase FoxA1 mRNA and protein expression in LPS-induced type II epithelial cells. Thus, our results suggest that the downregulation of miR-17 expression could lead to FoxA1 overexpression in ALI.

Correlation between catheter colonization of central venous catheters and clinical biochemical indicators: A retrospective analysis of the MIMIC­IV database.

BACKGROUND: Clinical studies have not fully assessed the potential impact of patients' biochemical indicators on the rate of positive for central venous catheter-tip microorganism culture (PCMC). METHODS: Data were obtained from an online Medical Information Mart for Intensive Care IV database. Patients who were ≥18 years old and had central venous catheter-tip culture results without continuous renal replacement therapy were included in the study. A comparison of patient characteristics and their biochemical indicators was made between negative and positive culture results. RESULTS: A total of 5,323 patients were included in the analysis, including 612 positive (PCMC group) and 4,711 negative culture results (negative for central venous catheter tip catheter-tip microorganism culture [NCMC] group). The only influence factor on PCMC in this study was the serum creatinine (Scr) (odds ratio: 1.312, 95% confidence interval: 1.084-1.590, P = .005), according to a binary logistic regression analysis. The cut-off value of Scr was 3.25 mg/dL. The prevalence of PCMC (27.1% vs 9.1%, P < .001) and Staphylococcus aureus (43.0% vs 18.6%, P < .001) for central venous catheter-tip culture results was much higher in patients with Scr ≥ 3.25 mg/dL than those Scr < 3.25 mg/dL. CONCLUSIONS: We used the large dataset collected from Medical Information Mart for Intensive Care IV to show that patients with Scr ≥ 3.25 mg/dL had an increased risk for PCMC.

[The mechanism of Xuebijing injection in preventing and treating lung injury induced by cardiopulmonary bypass by regulating the apoptosis of alveolar polymorphonuclear neutrophil].

OBJECTIVE: To investigate the protective effect of Xuebijing injection on acute lung injury (ALI) associated with cardiopulmonary bypass (CPB) by regulating the apoptosis of polymorphonuclear neutrophils (PMN). METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), CPB model group (CPB group) and Xuebijing pretreatment group (XBJ group) according to the random number table method, with 10 rats in each group. Rats in the CPB group and XBJ group undergoing CPB procedures for 60 minutes. Rats in the Sham group did not undergo CPB. Rats in the XBJ group received intraperitoneal injection of 4 mL/kg Xuebijing injection 2 hours before CPB. Rats in the Sham group and CPB group were injected with an equal amount of normal saline. 4 hours after CPB, arterial blood was collected for blood gas analysis to calculate respiratory index (RI), and lung tissue of rats was collected for determination of lung index (LI) and pulmonary water containing rate. PMN in bronchoalveolar lavage fluid (BALF) were collected and the activity of caspase-3 was detected. The apoptosis rate was detected by flow cytometry. The expressions of microRNA-142-3p (miR-142-3p) and FoxO1 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The protein expression of FoxO1 was detected by Western blotting. In addition, HL-60 cells were divided into control oligonucleotide transfection group, miR-142-3p mimics transfection group, and miR-142-3p inhibitor transfection group. After 48 hours of transfection, the activity of miR-142-3p binding to FoxO1 was detected using dual luciferase reporter genes. RESULTS: Compared with Sham group, RI, LI and pulmonary water containing rate were significantly increased in CPB group. The caspase-3 activity and apoptosis rate of PMN obtained from BALF were significantly decreased, the expression of miR-142-3p was decreased, and the expression of FoxO1 protein was increased. However, compared with CPB group, RI, LI and pulmonary water containing rate were significantly decreased in XBJ group [RI: 0.281±0.066 vs. 0.379±0.071, LI: 4.50±0.26 vs. 5.71±0.42, pulmonary water containing rate: (80.31±32.50)% vs. (84.59±3.41)%, all P < 0.01]. The caspase-3 activity and apoptosis rate of PMN obtained from BALF were significantly increased [caspase-3 activity: 0.350±0.021 vs. 0.210±0.014, apoptosis rate: (15.490±1.382)% vs. (8.700±0.701)%, both P < 0.01], the expression of miR-142-3p was significantly up-regulated (2-ΔΔCt: 2.61±0.17 vs. 0.62±0.05, P < 0.01), and the protein expression of FoxO1 was decreased [FoxO1/GAPDH (relative expression level): 0.81±0.04 vs. 1.22±0.06, P < 0.01]. However, there was no statistically significant difference in FoxO1 mRNA expression among the three groups. The bioinformatics analysis results showed that miR-142-3p can bind to the FoxO1 3'untranslated region (3'UTR). In HL-60 cells, compared with control oligonucleotide transfection group, the transfection of miR-142-3p mimics could reduce the expression of FoxO1 protein [FoxO1/GAPDH (relative expression level): 0.48±0.06 vs. 1.00±0.05, P < 0.01], however, the transfection of miR-142-3p inhibitor increased the expression of FoxO1 protein [FoxO1/GAPDH (relative expression level): 1.37±0.21 vs. 1.00±0.05, P < 0.05]. But, transfection with miR-142-3p mimics or inhibitor had no effect on FoxO1 mRNA expression. The luciferase reporter gene showed that miR-142-3p could bind to the FoxO1 3'UTR to inhibit FoxO1 expression. CONCLUSIONS: Xuebijing injection may promote the apoptosis of pulmonary alveolar PMN through the miR-142-3p/FoxO1 axis, and play a role in the prevention and treatment of CPB-induced ALI.

Dynamic arterial elastance as a predictor of arterial pressure response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome-a systematic review and meta-analysis.

Introduction: During the de-escalation phase of circulatory shock, norepinephrine weaning may induce diverse arterial pressure responses in patients with different vasomotor tones. Dynamic arterial elastance (Eadyn) has been extensively studied to predict the arterial pressure response to interventions. We conducted this meta-analysis to systematically assess the predictive performance of Eadyn for the mean arterial pressure (MAP) response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome. Materials and methods: A systematic literature search was conducted on May 29, 2023 (updated on January 21, 2024), to identify relevant studies from electronic databases. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy because of the varied thresholds reported. Additionally, we observed the distribution of the cutoff values of Eadyn, while computing the optimal value and its corresponding 95% confidential interval (CI). Results: A total of 5 prospective studies met eligibility, comprising 183 participants, of whom 67 (37%) were MAP responders. Eadyn possessed an excellent ability to predict the MAP response to norepinephrine weaning in patients with vasoplegic syndrome, with an AUHSROC of 0.93 (95% CI: 0.91-0.95), a pooled sensitivity of 0.94 (95% CI: 0.85-0.98), a pooled specificity of 0.73 (95% CI: 0.65-0.81), and a pooled diagnostic odds ratio of 32.4 (95% CI: 11.7-89.9). The cutoff values of Eadyn presented a nearly conically symmetrical distribution; the mean and median cutoff values were 0.89 (95% CI: 0.80-0.98) and 0.90 (95% CI: not estimable), respectively. Conclusions: This meta-analysis with limited evidences demonstrates that Eadyn may be a reliable predictor of the MAP response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome. Systematic Review Registration: PROSPERO CRD42023430362.

Axillary vein as an alternative venous access site for VV-ECMO cannulation: a case report.

BACKGROUND: Ultrasound-guided percutaneous axillary vein cannulation can reduce cannulation failure and mechanical complications, is as safe and effective as internal jugular vein cannulation, and is superior to subclavian vein cannulation using landmark technique. As far, reports of venovenous extracorporeal membrane oxygenation (VV-ECMO) with percutaneous axillary vein cannulation are rare. CASE PRESENTATION: A 64-year-old man presenting with dyspnea and chest tightness after aspirating sewage was admitted to the emergency department. Computed tomography (CT) showed diffuse exudation of both lungs and arterial blood gas analysis showed an oxygenation index of 86. He was diagnosed with aspiration pneumonia-induced acute respiratory distress syndrome (ARDS) and intubated for deteriorated oxygenation. Despite the combination therapy of protective mechanical ventilation and prone position, the patient's oxygenation deteriorated further, accompanied with multiple organ dysfunction syndrome, which indicated the requirement of support with VV-ECMO. However, vascular ultrasound detected multiple thrombus within bilateral internal jugular veins. As an alternative, right axillary vein was chosen as the access site of return cannula. Subsequently, femoral-axillary VV-ECMO was successfully implemented under the ultrasound guidance, and the patient's oxygenation was significantly improved. Unfortunately, the patient died of hyperkalemia-induced ventricular fibrillation after 36 h of VV-ECMO running. Despite the poor prognosis, the blood flow during ECMO run was stable, and we observed no bleeding complication, vascular injury, or venous return disorder. CONCLUSIONS: Axillary vein is a feasible alternative access site of return cannula for VV-ECMO if internal jugular vein access were unavailable.

3D-QSAR-Directed Synthesis of Halogenated Coumarin-3-Hydrazide Derivatives: Unveiling Their Potential as SDHI Antifungal Agents.

The pursuit of new succinate dehydrogenase (SDH) inhibitors is a leading edge in fungicide research and development. The use of 3D quantitative structure-activity relationship (3D-QSAR) models significantly enhances the development of compounds with potent antifungal properties. In this study, we leveraged the natural product coumarin as a molecular scaffold to synthesize 74 novel 3-coumarin hydrazide derivatives. Notably, compounds 4ap (0.28 µg/mL), 6ae (0.32 µg/mL), and 6ah (0.48 µg/mL) exhibited exceptional in vitro effectiveness against Rhizoctonia solani, outperforming the commonly used fungicide boscalid (0.52 µg/mL). Furthermore, compounds 4ak (0.88 µg/mL), 6ae (0.61 µg/mL), 6ah (0.65 µg/mL), and 6ak (1.11 µg/mL) showed significant activity against Colletotrichum orbiculare, surpassing both the SDHI fungicide boscalid (43.45 µg/mL) and the broad-spectrum fungicide carbendazim (2.15 µg/mL). Molecular docking studies and SDH enzyme assays indicate that compound 4ah may serve as a promising SDHI fungicide. Our ongoing research aims to refine this 3D-QSAR model further, enhance molecular design, and conduct additional bioactivity assays.