Jialin Liu

The high prevalence and adverse impact of delirium in critically ill patients necessitate a deeper understanding of its mechanisms. This review explores the pivotal interplay between systemic inflammation and delirium, examining how insults like age, pain and surgery orchestrate neuroinflammation and delirium through microglial activation and blood-brain barrier disruption. Our synthesis identifies a spectrum of inflammatory and neuronal injury biomarkers with prognostic value and evaluates the burgeoning field of anti-inflammatory pharmacotherapy. We conclude that bridging this mechanistic knowledge to clinical practice via biomarker-driven trials is essential for developing effective interventions against delirium.

Introduction: Assessment of the V/Q ratio is crucial for understanding the pathophysiology of iNO therapy and prone position in ARDS patients. Recently, the concept of the absolute V/Q ratio measured by EIT has emerged. In this study, we first describe a case where a modified EIT parameter was employed to clinically monitor the absolute V/Q ratio in an ARDS patient during both prone positioning and iNO therapy.Case presentation: This report describes the case of a 69-year-old ARDS patient with refractory hypoxemia who underwent prone position and iNO therapy. The patient exhibited a positive response to the treatment, showing improved oxygenation and absolute V/Q. A modified EIT-derived parameter, the cardiac output (CO)-related V/Q match index, was utilized to evaluate the absolute V/Q ratio, demonstrating improved consistency with the oxygenation index compared to conventional indicators.Conclusion: This case elucidates the significance of the EIT-derived parameter—CO-related V/Q match index, revealing its benefits in evaluating the V/Q ratio under the various treatment strategies when compared to traditional ones.

Respiratory microbiome is extensively involved in human life activities and affects lung health and disease states through metabolism and immune regulation. Based on 16S rRNA gene sequencing and other methods, it is obvious that the diversity and the changes in the structure of respiratory microbiome and the dominant proliferation of pathogens are strongly related to the occurrence, development and clinical prognosis of ventilator-associated pneumonia (VAP). The mechanism by which respiratory microbiota promotes the clearance of pathogens may include the following aspects: (1) pre-stimulating innate immune system to increase the number of immune effector cells; (2) regulating pattern recognition receptor (PRR) to moderately promote the production of cytokines; (3) inducing the differentiation of neutrophils into specific subtypes and increasing the expression of antimicrobial genes; (4) producing free fatty acids and organic compounds that are capable of positively modulating the immune system. In conclusion, intervention of microbiome is beneficial to VAP patients. Therefore, this review illustrates the changes of respiratory flora in VAP and its effect on host immunity. At the same time, based on the review of the adjuvant treatment of VAP with probiotics, we put forward the prospect of respiratory commensal bacteria as a new clinical probiotic, in order to deepen the clinical understanding of the role of respiratory flora in VAP, and then provide new ideas for the evaluation of treatment and prognosis.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in patients admitted to the intensive care unit (ICU) patients with overwhelming inflammation considered to be an internal cause. The authors’ previous study indicated a potential correlation between phenylalanine levels and lung injury. Phenylalanine induces inflammation by enhancing the innate immune response and the release of pro-inflammatory cytokines. Alveolar macrophages (AMs) can respond to stimuli via synthesis and release of inflammatory mediators through pyroptosis, one form of programmed cell death acting through the nucleotide-binging oligomerization domain-like receptors protein 3 (NLRP3) signaling pathway, resulting in the cleavage of caspase-1 and gasdermin D (GSDMD) and the release of interleukin (IL) -1β and IL-18, aggravating lung inflammation and injury in ARDS. In this study, phenylalanine promoted pyroptosis of AMs, which exacerbated lung inflammation and ARDS lethality in mice. Furthermore, phenylalanine initiated the NLRP3 pathway by activating the calcium-sensing receptor (CaSR). These findings uncovered a critical mechanism of action of phenylalanine in the context of ARDS and may be a new treatment target for ARDS.

Introduction: Since the advent of 2019 novel coronavirus (COVID-19), the coexistence between social stigma and depression symptoms (depression hereafter) in COVID-19 patients has been mentioned, but the mechanisms involved remains unclear. This study aimed to explore how the stigma affects depression during the mid-pandemic period. Methods: A cross-sectional survey using non-probability sampling was conducted among asymptomatic COVID-19 carriers in Shanghai, China (April 2022). An online questionnaire was used to obtain information on demographic characteristics and psychological traits. Logistic regression and path analysis were performed to analyze the depression risk factors and examine the mediation model, respectively. Results: A total of 1283 participants (59.6% men) were involved in this study, in which 44.7% of carriers reported having depression. Univariate analyses found that education level (OR 0.575; 95% CI 0.448–0.737) and doses of vaccine (OR 1.693; 95% CI 1.042–2.750), were significantly associated with depression among asymptomatic carriers. The association between social stigma and depression was fully mediated by their feelings of entrapment and decadence (indirect effect = 0.204, p < 0.001; direct effect = −0.059, p = 0.058). The mediating role of entrapment between stigma and depression was moderated by age group (estimate = 0.116, p = 0.008). Conclusion: Mental health issues resulting from the COVID-19 pandemic are increasingly apparent in China and require urgent attention and responses. These findings provide new perspectives for the early prevention of depression in asymptomatic carriers.

Background: Since the outbreak of coronavirus disease (COVID-19) in December 2019 in Wuhan, it has spread rapidly worldwide. We aimed to establish and validate a nomogram that predicts the probability of coronavirus-associated acute respiratory distress syndrome (CARDS). Methods: In this single-centre, retrospective study, 261 patients with COVID-19 were recruited using positive reverse transcription–polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 in Tongji Hospital at Huazhong University of Science and Technology (Wuhan, China). These patients were randomly distributed into the training cohort (75%) and the validation cohort (25%). The factors included in the nomogram were determined using univariate and multivariate logistic regression analyses based on the training cohort. The area under the receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in the training and validation cohorts. Results: Independent predictive factors, including fasting plasma glucose, platelet, D-dimer, and cTnI, were determined using the nomogram. In the training cohort, the AUC and concordance index were 0.93. Similarly, in the validation cohort, the nomogram still showed great distinction (AUC: 0.92) and better calibration. The calibration plot also showed a high degree of agreement between the predicted and actual probabilities of CARDS. In addition, the DCA proved that the nomogram was clinically beneficial. Conclusion: Based on the results of laboratory tests, we established a predictive model for acute respiratory distress syndrome in patients with COVID-19. This model shows good performance and can be used clinically to identify CARDS early. Trial Registration: Ethics committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (No.:(2020) Linlun-34th).

Background: Effective removal of pathogenic bacteria is key to improving the prognosis of sepsis. Polymorphonuclear neutrophils (PMNs) are the most important components of innate cellular immunity and play vital roles in clearing pathogenic bacteria. However, the metabolic characteristics and immunomodulatory pathways of PMNs during sepsis have not been investigated. In the present study, we explored the immune metabolism characteristics of PMNs and the mechanism by which neutrophilic glycolysis is regulated during sepsis. Methods: Metabolomics analysis was performed on PMNs isolated from 14 septic patients, 26 patients with acute appendicitis, and 19 healthy volunteers. Transcriptome analysis was performed on the PMNs isolated from the healthy volunteers and the patients with sepsis to assess glycolysis and investigate its mechanism. Lipopolysaccharide (LPS) was used to stimulate the neutrophils isolated from the healthy volunteers at different time intervals to build an LPS-tolerant model. Chemotaxis, phagocytosis, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were evaluated. Results: Transcriptomics showed significant changes in glycolysis and the mTOR/HIF-1α signaling pathway during sepsis. Metabolomics revealed that the Warburg effect was significantly altered in the patients with sepsis. We discovered that glycolysis regulated PMNs’ chemotaxis and phagocytosis functions during sepsis. Lactate dehydrogenase A (LDHA) downregulation was a key factor in the inhibition of glycolysis in PMNs. This study confirmed that the PI3K/Akt-HIF-1α pathway was involved in the LDHA expression level and also influenced PMNs’ chemotaxis and phagocytosis functions. Conclusions: The inhibition of glycolysis contributed to neutrophil immunosuppression during sepsis and might be controlled by PI3K/Akt-HIF-1α pathway-mediated LDHA downregulation. Our study provides a scientific theoretical basis for the management and treatment of patients with sepsis and promotes to identify therapeutic target for the improvement of immune function in sepsis.

The current global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown limited responses to medical treatments. To observe the effect of combination treatment of giammonium glycyrrhizinate and vitamin C (DV) on the prognoses of patients with COVID-19. This retrospective observational study recruited 207 COVID-19 patients from Tongji Hospital, patients were assigned to DV and non-DV groups on the basis of the DV treatment. To make the results more credible, a propensity score matching (PSM) approach was adopted at a 1:3 ratio to determine the participants. Logistic analysis was used to assess the effect of DV therapy in the progress of COVID-19. In the DV group, the new-onset incidence rate of acute respiratory distress syndrome (ARDS) after admission was clearly lower than that in the non-DV group (DV vs. non-DV groups, 15.2% vs. 35.7%; P = 0.002). Compared with the non-DV group, the DV group showed fewer new onset of complications (such as ARDS, acute liver injury and acute myocardial injury) (DV vs. non-DV groups, 19.6% vs. 46.1%; P = 0.000). Moreover, DG+VC may help to recover the count of NK cells and decrease the level of sIL-2R. DG+VC might be a promising candidate for preventing the deterioration of COVID-19 patients, which is worthy to be studied in large and perspective cohort.

Background: We previously found that microbial disruption in Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) patients are long-lasting. Long-term microbial dysbiosis may lead to changes in metabolites. Short-chain fatty acids (SCFAs) are microbial fermentation products and show beneficial effects in patients with pneumonia. In this study, we aimed to explore the association between circulating SCFA levels and clinical outcomes in patients with PA-VAP.Methods: In this study, we analyzed SCFAs in the serum of 49 patients with PA-VAP by gas chromatography-mass spectrometry analysis. Twenty of these patients died, and 29 survived. The correlation between serum SCFAs and patient survival and immune parameters was analyzed.Results: We developed a partial least squares discriminant analysis (PLS-DA) model to examine differential SCFAs in 49 patients with PA-VAP. Among the seven SCFAs, only acetic acid was increased in non-survivors (P = 0.031, VIP > 1). Furthermore, high levels of acetic acid (>1.96ug/ml) showed increased 90-day mortality compared to low levels of acetic acid (<1.96ug/ml) in Kaplan-Meier survival analyses (P = 0.027). Increased acetic acid also correlated with reduced circulating lymphocyte and monocyte counts.Conclusion: Our study showed that increased circulating acetic acid is associated with 90-day mortality in PA-VAP patients. The decrease in lymphocytes and monocytes might be affected by acetic acid and involved in the poor prognosis.