MR neurography showed brachial plexus abnormalities in syringomyelia with shoulder Charcot arthropathy: a case report.

Charcot shoulder is occasionally seen with syringomyelia. To the best of our knowledge this is the first report of brachial plexus abnormalities detected by magnetic resonance(MR) neurography in these patients. MR neurography is useful to evaluate small nerves and their disorders, and may contribute to the early diagnosis and differential diagnoses of such patients.

Effects of exercise interventions on cancer-related fatigue in breast cancer patients: an overview of systematic reviews.

OBJECTIVE: This overview of systematic reviews aims to critically appraise and consolidate evidence from current systematic reviews (SRs)/meta-analyses on the effects of exercise interventions on cancer-related fatigue (CRF) in breast cancer patients. METHODS: SRs/meta-analyses that explored the effects of exercise interventions on CRF in breast cancer patients compared with the routine methods of treatment and care were retrieved from nine databases. The methodological quality of the included SRs was appraised using A MeaSurement Tool to Assess systematic Reviews II (AMSTAR II). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to calculate the grading of outcomes in the included SRs. The exercise type, frequency, duration, and inclusion/absence of supervision were further evaluated with subgroup analyses. The Stata 16.0 software was utilized for data analysis. RESULTS: Twenty-nine reviews were included. The overall methodological quality and level of evidence of the included reviews were unsatisfactory, with only three reviews rated as high methodological quality and no review identified as high-quality evidence. Moderate certainty evidence indicated that exercise could improve fatigue in breast cancer patients (SMD = - 0.40 [95%CI - 0.58, - 0.22]; P = 0.0001). Subgroup analysis based on the types of exercise showed that yoga (SMD = - 0.30 [95%CI - 0.56, - 0.05]; I2 = 28.7%) and aerobic exercise (SMD = - 0.29 [95%CI - 0.56, - 0.02]; I2 = 16%) had a significantly better effect on CRF in breast cancer patients; exercising for over 6 months (SMD = - 0.88 [95%CI - 1.59, - 0.17]; I2 = 42.7%; P = 0.0001), three times per week (SMD = - 0.77 [95%CI - 1.04, - 0.05]; I2 = 0%; P = 0.0001), and for 30 to 60 min per session (SMD = - 0.81 [95%CI - 1.15, - 0.47]; I2 = 42.3%; P = 0.0001) can contribute to a moderate improvement of CRF. Supervised exercise (SMD = - 0.48 [95%CI - 0.77, - 0.18]; I2 = 87%; P = 0.001) was shown to relieve CRF. CONCLUSION: Exercise played a favorable role in alleviating CRF in breast cancer. Yoga was recommended as a promising exercise modality for CRF management in the majority of the included studies. Exercising for at least three times per week with 30 to 60 min per session could be recommended as a suitable dosage for achieving improvement in CRF. Supervised exercise was found to be more effective in alleviating CRF than unsupervised exercise. More rigorously designed clinical studies are needed to specify the exact exercise type, duration, frequency, and intensity to have an optimal effect on CRF in breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CRD42020219866.

Prevention of ulcerative colitis by Huangqin decoction: reducing the intestinal epithelial cell apoptosis rate through the IFN-γ/JAK/ETS signalling pathway.

CONTEXT: Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease that is closely related to inflammation and apoptosis. The traditional Chinese medicine compound preparation Huangqin decoction (HQD) has been widely used in the clinical treatment of UC, but the specific mechanism of its function is still inconclusive. OBJECTIVE: To explore the pathogenesis of UC based on the IFN-γ/JAK/ETS signalling pathway, and to clarify the biological mechanism of HQD. MATERIALS AND METHODS: Forty 8-week-old male C57BL/6 mice were randomly divided into four groups: normal control, model, model + salazosulfapyridine group (500 mg/kg, p.o., pd) and model + HQD (9.1 g/kg, p.o., pd). Using Dextran sulphate sodium (DSS) salt (2.5%, p.o.)+high-fat diet + hot and humid environment to build a mouse model of UC. One month later, the changes of colon morphology, serum inflammatory factors, intestinal epithelial cell apoptosis and IFN-γ/JAK/ETS signalling pathway related protein changes in mice were observed. RESULTS: Compared with the model group, HQD significantly reduced the pathological score of the model mice's colon (2.60 ± 0.25 vs. 4.80 ± 0.37), and reduced the serum IFN-γ (200.30 ± 8.45 vs. 413.80 ± 6.97) and other inflammatory factors, and reduced intestinal epithelial cell apoptosis (24.85 ± 4.87 vs. 214.90 ± 39.21). In terms of mechanism, HQD down-regulated IFN-γ/JAK/ETS signalling pathway related proteins in colon tissue of UC model mice. CONCLUSIONS: These data indicate that HQD can improve UC by reducing intestinal inflammation and apoptosis, providing experimental evidence for the wide application of HQD in clinical practice of UC.

Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis.

Na+ -taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case-control studies, its genotypic and phenotypic features remain open for in-depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682_683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25-hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age-dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients.

[The Clinical Value of the Pathophysiology Oriented Critical Care Ultrasound Exam (POCCUE) Protocol in Acute Respiratory and Circulatory Compromise of Critically Ill Patients].

OBJECTIVE: The aim of this study is to explore the diagnostic and therapeutic accuracy of pathophysiology and clinic oriented critical care ultrasound exam (POCCUE) protocol in acute respiratory and circulatory compromise of critically ill patients. METHODS: Prospectively included patients with acute respiratory and circulatory compromise from ICU of West China Hospital of Sichuan University from March to April 2018. The POCCUE protocol designed according to the pathophysiological changes of acute respiratory and circulatory disorders includes: the first part is the acquiring an ultrasound section and measuring corresponding indicators including pulmonary and echocardiographic indicators; the second part is a comprehensive analysis according to the former examination which evaluates the pathophysiological changes of acute respiratory and circulatory disorders, and then establish the initial etiology diagnosis and start treatment. The clinical value of the POCCUE protocol, including the accuracy of diagnosis, and the differences in treatment was verified by comparing the clinical outcome with the traditional treatment group. RESULTS: A total of 82 subjects were used for statistics. Compare with the traditional group, POCCUE can notably increase the diagnostic and therapeutic accuracy of clinic and pathophysiology (diagnostic accuracy: 93.90% vs. 68.29%, P < 0.01; therapeutic accuracy: 93.90% vs. 62.20%, P < 0.01). CONCLUSION: The POCCUE has a higher accuracy of diagnosis and treatment for patients with acute respiratory and circulatory compromise.

[The Correlation of Fast-track Extubation Ultrasound Score and Clinical Multi-organ Information Indicators of Postoperative of Cardiac Surgery].

OBJECTIVE: To evaluate the correlation of Fast-track extubation ultrasound score (FTEUS) and clinical multi-organ information indicators in post-cardiac surgery patients. METHODS: prospectively recruit post-cardiac surgery patients who were about to extubating from Febuary 2019 to September 2019. A fast-track extubation ultrasound score protocol (FTE-USP) was developed on the basis of the conventional fast-track extubation standard precisely and individualized. Cardiac, pulmonary and inferior vena cava ultrasound examinations were performed by specially trained observers, video data were saved, FTE-USP was used for scoring, Kendall consistency coefficient was used to meature the interobserver consistency. The correlation between the FTEUS and the patients' clinical indicators was evaluated. RESULTS: A total of 207 patients were recruited in the study, including 89 males and 118 females, aged (54.63±11.80) years. The FTEUS was performed at bedside with a mean time of (8.23±2.08) min, Kendall consistency coefficient is 0.941. With the increase of the total score of FTEUS, the incidence of clinical adverse events increased (especially the arrhythmia), and there were significant changes in liver, kidney, heart, lung and other organ function indicators, among which serum creatinine level, serum cystatin C level, serum NT-pro-brain natriuretic peptide, length of stay in intensive care unit, non-invasive mechanical ventilation time after extubation, and incidence of arrhythmia were positively correlated with FTEUS (P < 0.05).With FTEUS increased to 5 points, the incidence of arrhythmia (14/24, 58.3%), cardiopulmonary resuscitation (2/24, 8.3%) and weaning failure (2/24, 8.3%) increased. CONCLUSION: FTE-USP integrates multi-organ informations, can be performed quickly at the bedside and alerts adverse events. It has the potential to be applied to assist clinical decision-making in post-cardiac surgery patients before extubation.

Rapid and high-efficiency discrimination of different sialic acid species using dipeptide-based fluorescent sensors.

A series of dipeptide-based fluorescent sensors were developed that exhibit sensitive and distinct responses to six typical sialic acid (SA) species despite the interference of 300-fold d-glucose or other saccharides, thus contributing to a novel fluorescence sensing matrix allowing the rapid and high-efficiency discrimination of different SA species.

Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.

BACKGROUND: Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged length of hospital stay and increased healthcare costs in critically ill patients. Guidelines recommend a semi-recumbent position (30º to 45º) for preventing VAP among patients requiring mechanical ventilation. However, due to methodological limitations in existing systematic reviews, uncertainty remains regarding the benefits and harms of the semi-recumbent position for preventing VAP. OBJECTIVES: To assess the effectiveness and safety of semi-recumbent positioning versus supine positioning to prevent ventilator-associated pneumonia (VAP) in adults requiring mechanical ventilation. SEARCH METHODS: We searched CENTRAL (2015, Issue 10), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and the Chinese Biomedical Literature Database (CBM) (1978 to October 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing semi-recumbent versus supine positioning (0º to 10º), or RCTs comparing alternative degrees of positioning in mechanically ventilated patients. Our outcomes included clinically suspected VAP, microbiologically confirmed VAP, intensive care unit (ICU) mortality, hospital mortality, length of ICU stay, length of hospital stay, duration of ventilation, antibiotic use and any adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently and in duplicate screened titles, abstracts and full texts, assessed risk of bias and extracted data using standardised forms. We calculated the mean difference (MD) and 95% confidence interval (95% CI) for continuous data and the risk ratio (RR) and 95% CI for binary data. We performed meta-analysis using the random-effects model. We used the grading of recommendations, assessment, development and evaluation (GRADE) approach to grade the quality of evidence. MAIN RESULTS: We included 10 trials involving 878 participants, among which 28 participants in two trials did not provide complete data due to loss to follow-up. We judged all trials to be at high risk of bias. Semi-recumbent position (30º to 60º) versus supine position (0° to 10°) A semi-recumbent position (30º to 60º) significantly reduced the risk of clinically suspected VAP compared to a 0º to 10º supine position (eight trials, 759 participants, 14.3% versus 40.2%, RR 0.36; 95% CI 0.25 to 0.50; risk difference (RD) 25.7%; 95% CI 20.1% to 30.1%; GRADE: moderate quality evidence).There was no significant difference between the two positions in the following outcomes: microbiologically confirmed VAP (three trials, 419 participants, 12.6% versus 31.6%, RR 0.44; 95% CI 0.11 to 1.77; GRADE: very low quality evidence), ICU mortality (two trials, 307 participants, 29.8% versus 34.3%, RR 0.87; 95% CI 0.59 to 1.27; GRADE: low quality evidence), hospital mortality (three trials, 346 participants, 23.8% versus 27.6%, RR 0.84; 95% CI 0.59 to 1.20; GRADE: low quality evidence), length of ICU stay (three trials, 346 participants, MD -1.64 days; 95% CI -4.41 to 1.14 days; GRADE moderate quality evidence), length of hospital stay (two trials, 260 participants, MD -9.47 days; 95% CI -34.21 to 15.27 days; GRADE: very low quality evidence), duration of ventilation (four trials, 458 participants, MD -3.35 days; 95% CI -7.80 to 1.09 days), antibiotic use (three trials, 284 participants, 84.8% versus 84.2%, RR 1.00; 95% CI 0.97 to 1.03) and pressure ulcers (one trial, 221 participants, 28% versus 30%, RR 0.91; 95% CI 0.60 to 1.38; GRADE: low quality evidence). No other adverse events were reported. Semi-recumbent position (45°) versus 25° to 30° We found no statistically significant differences in the following prespecified outcomes: clinically suspected VAP (two trials, 91 participants, RR 0.74; 95% CI 0.35 to 1.56; GRADE: very low quality evidence), microbiologically confirmed VAP (one trial, 30 participants, RR 0.61; 95% CI 0.20 to 1.84: GRADE: very low quality evidence), ICU mortality (one trial, 30 participants, RR 0.57; 95% CI 0.15 to 2.13; GRADE: very low quality evidence), hospital mortality (two trials, 91 participants, RR 1.00; 95% CI 0.38 to 2.65; GRADE: very low quality evidence), length of ICU stay (one trial, 30 participants, MD 1.6 days; 95% CI -0.88 to 4.08 days; GRADE: very low quality evidence) and antibiotic use (two trials, 91 participants, RR 1.11; 95% CI 0.84 to 1.47). No adverse events were reported. AUTHORS' CONCLUSIONS: A semi-recumbent position (≧ 30º) may reduce clinically suspected VAP compared to a 0° to 10° supine position. However, the evidence is seriously limited with a high risk of bias. No adequate evidence is available to draw any definitive conclusion on other outcomes and the comparison of alternative semi-recumbent positions. Adverse events, particularly venous thromboembolism, were under-reported.

Postoperative intra-abdominal hypertension predicts worse hospital outcomes in children after cardiac surgery: a pilot study†.

OBJECTIVES: Our goal was to determine the incidence and characteristics of postoperative intra-abdominal hypertension (IAH) in paediatric patients undergoing open-heart surgery. METHODS: This single-centre study included consecutive children (aged <16 years) who underwent open-heart surgery between July 2020 and February 2021. Patients who entered the study were followed until in-hospital death or hospital discharge. The study consisted of 2 parts. Part I was a prospective observational cohort study that was designed to discover the association between exposures and IAH. Postoperative intra-abdominal pressure was measured immediately after admission to the intensive care unit and every 6 h thereafter. Part II was a cross-sectional study to compare the hospital-related adverse outcomes between the IAH and the no-IAH cohorts. RESULTS: Postoperatively, 24.7% (38/154) of the patients exhibited IAH, whereas 3.9% (6/154) developed abdominal compartment syndrome. The majority (29/38, 76.3%) of IAH cases occurred within the first 24 h in the intensive care unit. Multivariable analysis showed that the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score [odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.23-2.83, P = 0.004], right-sided heart lesion (OR = 5.60, 95% CI 2.34-13.43, P < 0.001), redo sternotomy (OR = 4.35, 95% CI 1.64-11.57, P = 0.003), high baseline intra-abdominal pressure (OR = 1.43, 95% CI 1.11-1.83, P = 0.005), prolonged cardiopulmonary bypass duration (OR = 1.01, 95% CI 1.00-1.01, P = 0.005) and deep hypothermic circulatory arrest (OR = 5.14, 95% CI 1.15-22.98, P = 0.032) were independent predictors of IAH occurrence. IAH was associated with greater inotropic support (P < 0.001), more gastrointestinal complications (P = 0.001), sepsis (P = 0.003), multiple organ dysfunction syndrome (P < 0.001) and prolonged intensive care unit stay (z = -4.916, P < 0.001) and hospitalization (z = -4.710, P < 0.001). The occurrence of a composite outcome (P = 0.009) was significantly increased in patients with IAH. CONCLUSIONS: IAH is common in children undergoing cardiac surgery and is associated with worse hospital outcomes. Several factors may be associated with the development of IAH, including basic cardiac physiology and perioperative factors. TRIAL INFORMATION: This study was registered in the Chinese Clinical Trial Registry (Trial number: ChiCTR2000034322)URL site: https://www.chictr.org.cn/hvshowproject.html?id=41363&v=1.4.

Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.

RAS guanyl releasing protein 1 (RASGRP1) is a guanine nucleotide exchange factor (GEF) characterized by the presence of a RAS superfamily GEF domain. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor, specifically activating RAS through the exchange of bound GDP for GTP. Activation of RAS by RASGRP1 has a wide range of downstream effects at the cellular level. Thus, it is not surprising that many diseases are associated with RASGRP1 disorders. Here, we present an overview of the structure and function of RASGRP1, its crucial role in the development, expression, and regulation of immune cells, and its involvement in various signaling pathways. This review comprehensively explores the relationship between RASGRP1 and various diseases, elucidates the underlying molecular mechanisms of RASGRP1 in each disease, and identifies potential therapeutic targets. This study provides novel insights into the role of RASGRP1 in insulin secretion and highlights its potential as a therapeutic target for diabetes. The limitations and challenges associated with studying RASGRP1 in disease are also discussed.

[The hot point and controversy of clinical measures in critical are medicine].

With its powerful ability to monitoring and support of organs, the survival rate of critically ill patients has been improved significantly by critical care medicine. Critical ill patients centralized in ICU accepted the treatments given by multidisciplinary team as a mode have played a very important role, especially during the rescue of victims in public health emergencies and natural disasters. Changings of the measures of monitoring and support are always along with the development of the critical care medicine. Fluid therapy is the most core measures in ICU, but there is a significant contradiction between positive fluid therapy and patient's impaired organ compensatory ability. The premise of appropriate fluid therapy is continuous and accurate evaluation of the hemodynamic status of critical ill patients. The variation of peak velocity of common carotid artery measured by bedside ultrasound can estimate the volume status of the SICU patients accurately. This method has high feasibility and accuracy and easy to be handled by the residents of ICU. The non-C. difficile associated nosocomial diarrhea even fatal enteritis in ICU can be caused by Klebsiella oxytoca and Clostridium perfringens. Although this kind of incidence occurs in a relatively low rate, it always associates with severe diseases and poor outcome. Analgesia and sedation had become routine measures in ICU. There is still great controversy in some of the sedation protocol, such as sedation level and wake up daily. More and more evidence-based data suggested taking appropriate sedation targeting to individuals, and the protocol should be integrated with the dealing of pain, anxiety and delirium.

Safety and feasibility of ultrasound-guided serratus anterior plane block and intercostal nerve block for management of post-sternotomy pain in pediatric cardiac patients: A prospective, randomized trial.

BACKGROUND: Postoperative analgesia in the cardiothoracic ICU has traditionally relied on intravenous opioids. Thoracic nerve blocks are attractive alternatives for analgesia that reduce the requirement for opioids, but their safety and feasibility remain unclear. METHODS: Sixty children were allocated randomly to three groups: group C received intravenous opioids alone, while group SAPB (deep serratus anterior plane block) and group ICNB (intercostal nerve block) received opioids combined with ultrasound-guided regional nerve blocks (0.2% ropivacaine 2.5 mg.kg-1) after patients were transferred to the ICU. The primary outcome was opioid requirement in the first 24 h after surgery. Other outcomes included the postoperative FLACC scale value, tracheal extubation time, and plasma ropivacaine concentrations after the block. RESULTS: The mean [sd] cumulative dose of opioids administered postoperatively within 24 h in the SAPB (168.6 [76.9] µg.kg-1) and ICNB groups (170.0 [86.8] µg.kg-1) were significantly lower by nearly 53% than those in group C (359.3 [125.3] µg.kg-1, p = 0.000). The tracheal extubation time was shorter in the regional block groups than that in the control group, but the difference was not statistically significant (p = 0.177). The FLACC scale values at 0, 1, 3, 6, 12, and 24 h post-extubation were similar in the three groups. The mean peak plasma ropivacaine concentrations in the SAP and ICNB groups were 2.1 [0.8] and 1.8 [0.7] mg.L-1, respectively, 10 min post-block and then slowly decreased. No noticeable complications associated with regional anesthesia were observed. CONCLUSIONS: Ultrasound-guided SAPB and ICNB provided safe and satisfactory early postoperative analgesia while reducing opioid consumption following sternotomy in pediatric patients. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiChiCTR2100046754.

Specific Clearance of Lipopolysaccharide from Blood Based on Peptide Bottlebrush Polymer for Sepsis Therapy.

Lipopolysaccharide (LPS) is the primary bacterial toxin that is vital to the pathogenesis and progression of sepsis associated with extremely high morbidity and mortality worldwide. However, specific clearance of LPS from circulating blood is highly challenging because of the structural complexity and its variation between/within bacterial species. Herein, a robust strategy based on phage display screening and hemocompatible peptide bottlebrush polymer design for specific clearance of targeted LPS from circulating blood is proposed. Using LPS extracted from Escherichia coli as an example, a novel peptide (HWKAVNWLKPWT) with high affinity (KD < 1.0 nм), specificity, and neutralization activity (95.9 ± 0.1%) against the targeted LPS is discovered via iterative affinity selection coupled with endotoxin detoxification screening. A hemocompatible bottlebrush polymer bearing the short peptide [poly(PEGMEA-co-PEP-1)] exhibits high LPS selectivity to reduce circulating LPS level from 2.63 ± 0.01 to 0.78 ± 0.05 EU mL-1 in sepsis rabbits via extracorporeal hemoperfusion (LPS clearance ratio > 70%), reversing the LPS-induced leukocytopenia and multiple organ damages significantly. This work provides a universal paradigm for developing a highly selective hemoadsorbent library fully covering the LPS family, which is promising to create a new era of precision medicine in sepsis therapy.

Association of IL-10-1082 G/G genotype with lower mortality of acute respiratory distress syndrome in a Chinese population.

We aimed to investigate whether interleukin-10 (IL-10) -1082 G/G genotype is associated with lower mortality of acute respiratory distress syndrome (ARDS) in a Chinese population. A hospital-based case-control study was conducted in 314 cases of ARDS and 210 controls who were admitted to an intensive care unit with sepsis, trauma, aspiration or massive transfusions. Cases were followed for 30-day mortality. The -1082G/G genotype was associated with lower development of ARDS (OR=0.51; 95% CI 0.34-0.76; P=0.001). Among patients with ARDS, the -1082G/G genotype was associated with lower 30-day mortality (OR=0.44; 95% CI 0.25-0.76; P=0.003). In conclusion, IL-10-1082 G/G genotype is associated with lower development and mortality of ARDS in a Chinese population.

Study protocol for a single-centre randomised controlled trial to investigate the effect of lung recruitment in paediatric patients after cardiac surgery.

INTRODUCTION: A number of published studies have revealed that lung recruitment can improve oxygenation, shorten the duration of mechanical ventilation (MV) and decrease mortality in adults with acute hypoxaemic respiratory failure, especially patients with acute respiratory distress syndrome. However, few articles have assessed lung recruitment in paediatric patients, especially after cardiac surgery. This clinical trial aimed to determine whether lung recruitment can reduce the duration of MV in paediatric patients with hypoxaemic respiratory failure after cardiac surgery. METHOD AND ANALYSIS: In this trial, we will randomly assign 234 paediatric patients (aged 28 days to 14 years) within 72 hours after cardiac surgery with an arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2) ratio (PaO2/FiO2) of <300 to either a lung recruitment group or a conventional group. The primary endpoint will be the duration of MV. The secondary endpoints will be ventilator-free days, PaO2/FiO2, respiratory system compliance, duration of non-invasive ventilation, reintubation rate, length of intensive care unit stay, length of hospital stay, occurrence of serious adverse events (barotrauma, persistent hypotension and arrhythmia), postoperative pulmonary complications. ETHICS AND DISSEMINATION: The ethics committee of West China Hospital of Sichuan University granted ethics approval for this study (20 August 2019). The results will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900025990.

Differentiation between glioma recurrence and treatment effects using amide proton transfer imaging: A mini-Bayesian bivariate meta-analysis.

Background: Amide proton transfer (APT) imaging as an emerging MRI approach has been used for distinguishing tumor recurrence (TR) and treatment effects (TEs) in glioma patients, but the initial results from recent studies are different. Aim: The aim of this study is to systematically review and quantify the diagnostic performance of APT in assessing treatment response in patients with post-treatment gliomas. Methods: A systematic search in PubMed, EMBASE, and the Web of Science was performed to retrieve related original studies. For the single and added value of APT imaging in distinguishing TR from TEs, we calculated pooled sensitivity and specificity by using Bayesian bivariate meta-analyses. Results: Six studies were included, five of which reported on single APT imaging parameters and four of which reported on multiparametric MRI combined with APT imaging parameters. For single APT imaging parameters, the pooled sensitivity and specificity were 0.85 (95% CI: 0.75-0.92) and 0.88 (95% CI: 0.74-0.97). For multiparametric MRI including APT, the pooled sensitivity and specificity were 0.92 (95% CI: 0.85-0.97) and 0.83 (95% CI: 0.55-0.97), respectively. In addition, in the three studies reported on both single and added value of APT imaging parameters, the combined imaging parameters further improved diagnostic performance, yielding pooled sensitivity and specificity of 0.91 (95% CI: 0.80-0.97) and 0.92 (95% CI: 0.79-0.98), respectively, but the pooled sensitivity was 0.81 (95% CI: 0.65-0.93) and specificity was 0.82 (95% CI: 0.61-0.94) for single APT imaging parameters. Conclusion: APT imaging showed high diagnostic performance in assessing treatment response in patients with post-treatment gliomas, and the addition of APT imaging to other advanced MRI techniques can improve the diagnostic accuracy for distinguishing TR from TE.

Aspartic Acid-Modified Phospholipids Regulate Cell Response and Rescue Memory Deficits in APP/PS1 Transgenic Mice.

Misfolding and accumulation of amyloid-ß (Aß) to form senile plaques are the main neuropathological signatures of Alzheimer's disease (AD). Decreasing Aß production, inhibiting Aß aggregation, and clearing Aß plaques are thus considered an important strategy for AD treatment. However, numerous drugs cannot enter the AD clinical trials due to unsatisfactory biocompatibility, poor blood-brain barrier penetration, little biomarker impact, and/or low therapeutic indicators. Here, a pair of chiral aspartic acid-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (l- and d-Asp-DPPE) are prepared to build stabilized chiral liposomes. We find that both l- and d-liposomes are able to rescue Aß aggregation-induced apoptosis, oxidative stress, and calcium homeostasis, in which the effect of d-liposomes is more obvious than that of l-ones. Furthermore, in AD model mice (APPswe/PS1d9 double-transgenic mice), chiral liposomes not only show biosafety but also strongly improve cognitive deficits and reduce Aß deposition in the brain. Our results suggest that chiral liposomes, particularly, d-liposomes, could be a potential therapeutic approach for AD treatment. This study opens new horizons by showing that liposomes will be used for drug development in addition to delivery and targeting functions.

Simotang Alleviates the Gastrointestinal Side Effects of Chemotherapy by Altering Gut Microbiota.

Simotang oral liquid (SMT) is a traditional Chinese medicine (TCM) consisting of four natural plants and is used to alleviate gastrointestinal side effects after chemotherapy and functional dyspepsia (FD). However, the mechanism by which SMT helps cure these gastrointestinal diseases is still unknown. Here, we discovered that SMT could alleviate gastrointestinal side effects after chemotherapy by altering gut microbiota. C57BL/6J mice were treated with cisplatin (DDP) and SMT, and biological samples were collected. Pathological changes in the small intestine were observed, and the intestinal injury score was assessed. The expression levels of the inflammatory factors IL-1ß and IL-6 and the adhesive factors Occludin and ZO-1 in mouse blood or small intestine tissue were also detected. Moreover, the gut microbiota was analyzed by high-throughput sequencing of 16S rRNA amplicons. SMT was found to effectively reduce gastrointestinal mucositis after DDP injection, which lowered inflammation and tightened the intestinal epithelial cells. Gut microbiota analysis showed that the abundance of the anti-inflammatory microbiota was downregulated and that the inflammatory microbiota was upregulated in DDP-treated mice. SMT upregulated anti-inflammatory and anticancer microbiota abundance, while the inflammatory microbiota was downregulated. An antibiotic cocktail (ABX) was also used to delete mice gut microbiota to test the importance of gut microbiota, and we found that SMT could not alleviate gastrointestinal mucositis after DDP injection, showing that gut microbiota might be an important mediator of SMT treatment. Our study provides evidence that SMT might moderate gastrointestinal mucositis after chemotherapy by altering gut microbiota.

Ferulic acid and feruloylated oligosaccharides alleviate anxiety and depression symptom via regulating gut microbiome and microbial metabolism.

Incidence of anxiety and depression has been surging in recent years, causing unignorable mental health crisis across the globe. Mounting studies demonstrated that overgrowth of detrimental gut microbes is driving the development of anxiety and depression. Our previous studies suggested that ferulic acid (FA) and feruloylated oligosaccharides (FOs) were potent in regulating gut microbiome and microbial metabolism in a variety of disease settings, including neuroinflammation. Given the increasing evidence solidifying the role of gut-brain axis in neurological disorders, we here investigated the therapeutic potential of FA and FOs in anxiety and depression. In present study we found that FA and FOs effectively alleviated anxiety and depression-like behavior in mice, while increasing the abundance of Firmicutes, Solibacillus, Acinetobacter and Arthrobacter, and decreasing the abundance of Parabacteroides, Oscollospira and Rummeliibacillus. In addition, FA and FOs were efficacious in enhancing phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine and caffeine metabolism in mice having depression. Our results validated FA and FOs as effective nutrition to prevent anxiety and depression, as well as provided mechanistic insight into their anti-anxiety and anti-depression function. We suggested that FOs mitigated the symptom of depression in mice potentially via changing gut microbiome structure and microbial metabolism.

Effects of single-nucleotide polymorphism on the pharmacokinetics and pharmacodynamics of metformin.

INTRODUCTION: Metformin has been recognized as the first-choice drug for type 2 diabetes mellitus (T2DM). The potency of metformin in the treatment of type 2 diabetes has always been in the spotlight and shown significant individual differences. Based on previous studies, the efficacy of metformin is related to the single-nucleotide polymorphisms of transporter genes carried by patients, amongst which a variety of gene polymorphisms of transporter and target protein genes affect the effectiveness and adverse repercussion of metformin. AREAS COVERED: Here, we reviewed the current knowledge about gene polymorphisms impacting metformin efficacy based on transporter and drug target proteins. EXPERT OPINION: The reason for the difference in clinical drug potency of metformin can be attributed to the gene polymorphism of drug transporters and drug target proteins in the human body. Substantial evidence shows that genetic polymorphisms in transporters such as organic cation transporter 1 (OCT1) and organic cation transporter 2 (OCT2) affect the glucose-lowering effectiveness of metformin. However, optimization of individualized dosing regimens of metformin is necessary to clarify the role of several polymorphisms.