Liao Pinhu

Introduction: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) and life-threatening multi-organ failure with increased levels of inflammatory mediators and viral load; however, little is known about its pathophysiology.Methods: To better understand the cellular status of COVID-19-induced ARDS, we performed single-cell RNA sequencing on peripheral blood samples from patients with COVID-19-induced ARDS. Single-cell RNA sequencing combined with bioinformatics analysis was used to study dynamic changes in cell composition and transcriptional profiles.Results: The single-cell RNA sequencing data revealed significant phenotypic differences between patients with COVID-19-induced ARDS and controls, mainly in monocytes, and CD8⁺ T and B cells. B-cell and monocyte abundances were significant in COVID-19-induced ARDS patients compared to controls, while CD8⁺ T cells were depleted. These data suggest that there is an imbalance between lymphocytes and monocytes in the blood of COVID-19-induced ARDS patients. In addition, cytokine interactions between T cells, monocytes and B cells are enhanced as evidenced by the intercellular communication analysis. In particular, T cell subsets target receptors on other cells via CCL5 and may play an important role in patients with COVID-19-induced ARDS.Conclusion: Our analysis suggested that a dysregulated adaptive immune response exists in patients with COVID-19-induced ARDS. Overall, we provided a cellular picture of the peripheral immune response in patients with COVID-19-induced ARDS.

Background: This study aims to assess the prognostic value of red blood cell distribution width–to–platelet ratio (RPR) in acute respiratory distress syndrome (ARDS) patients. Methods: The data collected from 540 ARDS patients from 2001 to 2012 were obtained from the Medical Information Mart for Intensive Care III Database. The 28-day all-cause mortality risk was considered as the primary outcome parameter, and the secondary outcomes were 60- and 90-day all-cause mortality. The association between RPR (≥0.19 vs. Results: The 28-day all-cause mortality was 22.4%. Among the 121 deaths, 92 (20.0%) presented with an RPR P < 0.001). The 60- and 90-day all-cause mortality was 27% and 28.7%, respectively. After adjusting for the relevant factors in the multivariate model, RPR ≥0.19 was independently correlated with the 28-day all-cause mortality (hazard ratio, 2.74; 95% confidence interval, 1.46–5.15; P = 0.002). There was no nonlinear relationship between RPR and the risk of 28-day all-cause mortality (P for overall association P for nonlinear = 0.635). Similar results were observed for both the pneumonia and nonpneumonia subgroups and sensitivity analyses. Conclusions: The data promote the use of RPR as a valuable prognostic indicator for ARDS patients.

Background Sepsis is a common inflammatory syndrome, and its mortality is associated with obesity. Body surface area (BSA) and body mass index (BMI) are closely related to body weight, height but BSA is more closely related to physiological parameters. The relationship between BSA and sepsis mortality has not been well known. This study aimed to assess the association between BSA and 28-day mortality among patients with sepsis hospitalized in the intensive care unit. Methods Information of sepsis patients were collected from the Medical Information Market in Intensive Care (MIMIC)-III database. BSA was calculated by using the Mosteller formula and grouped by gender and BSA tertiles. Kaplan-Meier curves and Cox proportional hazards analyses were the main statistical methods used. Restricted cubic splines were utilized to visualize the associations between continuous BSA and 28-day all-cause mortality. Results Sepsis patients (N = 2507) involved in the study included 1491 males (59.47%) and 1,016 females (40.53%). A linear negative association was found between the BSA and 28-day all-cause mortality in male patients. A higher BSA was independently associated with a lower death risk [hazard ratio (HR) 0.487, 95% confidence intervals (CI) 0.271–0.873; P = 0.016], but no association was found in females (HR 0.559, 95% CI 0.289–1.082; P = 0.840). Cox proportional hazards analysis showed that the BSA was an independent protective factor for 28-day outcomes in males with sepsis. Conclusions A linear inverse association was observed between the BSA and 28-day mortality risk in male sepsis patients.

Background: Feeding intolerance in patients with sepsis is associated with a lower enteral nutrition (EN) intake and worse clinical outcomes. The aim of this study was to develop and validate a predictive model for enteral feeding intolerance in the intensive care unit patients with sepsis. Methods: In this dual-center, retrospective, case-control study, a total of 195 intensive care unit patients with sepsis were enrolled from June 2018 to June 2020. Data of 124 patients for 27 clinical indicators from one hospital were used to train the model, and data from 71 patients from another hospital were used to assess the external predictive performance. The predictive models included logistic regression, naive Bayesian, random forest, gradient boosting tree, and deep learning (multilayer artificial neural network) models. Results: Eighty-six (44.1%) patients were diagnosed with enteral feeding intolerance. The deep learning model achieved the best performance, with areas under the receiver operating characteristic curve of 0.82 (95% confidence interval = 0.74–0.90) and 0.79 (95% confidence interval = 0.68–0.89) in the training and external sets, respectively. The deep learning model showed good calibration; based on the decision curve analysis, the model's clinical benefit was considered useful. Lower respiratory tract infection was the most important contributing factor, followed by peptide EN and shock. Conclusions: The new prediction model based on deep learning can effectively predict enteral feeding intolerance in intensive care unit patients with sepsis. Simple clinical information such as infection site, nutrient type, and septic shock can be useful in stratifying a septic patient's risk of EN intolerance.

Purpose: Elevated central venous pressure (CVP) plays an important role in the occurrence of acute kidney injury (AKI) and it is also independently associated with the prognosis of critically ill patients. However, the effect of CVP on critically ill AKI patients remains unclear. In this study, we analyzed the relationship between CVP and all-cause mortality of critically ill patients with AKI. Patients and Methods: The clinical data of patients in intensive care unit (ICU) were retrieved from the Medical Information Mart for Intensive Care III (MIMIC-III) database and retrospectively analyzed. The all-cause mortality for up to 90 days was the main observed outcome. We used the minimum CVP value obtained during the first 72 hours after ICU admission for our analysis and patients were grouped according to this parameter. Patients were also analyzed after being further divided according to stages 1, 2 and 3 of AKI. Multiple Cox regression and Kaplan–Meier analyses were used to explore the association between CVP measurements and death of ICU patients with AKI. Results: A total of 1986 ICU patients with AKI were studied. A total of 527 (26.5%) patients died by day 90. The high CVP group (patients with ≥ 10 mmHg) had the lowest 90-day survival rate (P =0.001 by log rank test) when according to Kaplan–Meier analysis. By using Cox regression analysis, high CVP was found to be linked to an increase in mortality (CVP ≥ 10 mmHg versus ≤ 5 mmHg, HR, 1.336, 95% CI, 1.064 to 1.677, P trend=0.014). Furthermore, when using in a multivariate Cox regression analysis with CVP as a continuous variable, the higher CVP levels were still an independent risk factor for 90-day all-cause mortality (per 1 mmHg increase, HR, 1.031, 95% CI, 1.013– 1.049, P=0.001). In subgroup analysis, a similar trend was observed in patients with AKI stages 2 and 3. Conclusion: The minimum CVP level during the first 72h after ICU admission was positively associated with mortality in critically ill patients with AKI and this more marked in cases with severe AKI.

Background Patients with alcohol use disorder (AUD) are common attendees of the intensive care unit (ICU). Early assessment of the prognosis for critically ill patients with AUD is conducive for formulating comprehensive treatment measures and improving survival rates. The purpose of this study was to explore the predictive value of red blood cell distribution width (RDW) for 28‐day mortality in critically ill patients with AUD. Methods 2,884 patients with AUD were recruited retrospectively. Data from the MIMIC‐III database were collected and analyzed. A receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of RDW. The Kaplan‐Meier method and Cox regression models were used to evaluate prognostic factors. Results Of the 2,884 patients there were 344 non‐survivors (11.9%). The non‐survivors had a higher RDW than the survivors (p < 0.001). According to ROC curve analysis, the area under the curve predicted by RDW for 28‐day mortality was 0.728 (95% CI, 0.700‐0.755) and the optimal cutoff value was 15.45% (sensitivity: 67.2%, specificity: 67.3%). Length of stay in ICU, length of stay in hospital, in‐hospital mortality and 28‐day mortality in patients with an RDW > 15.45% were significantly higher than in those with an RDW ≤ 15.45% (p < 0.001). Cox regression analysis showed that an RDW > 15.45% was an independent prognostic indicator for 28‐day mortality in critically ill patients with AUD (HR = 1.964, 95% CI: 1.429‐2.698). Conclusions High RDW was associated with increased short‐term mortality risks in critically ill patients with AUD.

Kidney disease is a significant health concern worldwide. Ineffective treatment can lead to disastrous consequences, such as organ failure and death. Research has turned to cell-based therapy, but has yet to produce an effective and reliable treatment for kidney disease. To address this problem, we examined four datasets of gene expression profiles from diseased and healthy kidney tissue in humans, mice, and rats. Differentially expressed genes (DEGs) were screened and subjected to enrichment analyses. Up-regulated genes in diseased kidney tissue were significantly enriched in pathways associated with regulatory T cells (Tregs). Analysis with the xCell tool showed that Tregs were generally increased in diseased kidney tissue in all species. To validate these results in vivo, kidneys were removed from mice with Adriamycin-induced nephropathy, and histology confirmed increase of Tregs. Furthermore, Tregs were adoptively transferred from healthy mice into mice with kidney injury, restoring normal structure to the damaged kidneys. Treg cells that were co-cultured with M2c macrophages exhibited up-regulation of chemokine receptors CCR2, CCR5, CCR7, CD62L, and CX3CR1. This may be the mechanism by which M2c cells enhance the migration of Tregs to the site of inflammation. We propose that Tregs may be an effective, novel candidate for cell-based therapy in pre-clinical kidney injury models.

The remodeling of the extracellular matrix (ECM) in the parenchyma plays an important role in the development of acute respiratory distress syndrome (ARDS), a disease characterized by lung injury. Although it is clear that TGF‐ β 1 can modulate the expression of the extracellular matrix (ECM) through intracellular signaling molecules such as Smad3, its role as a therapeutic target against ARDS remains unknown. In this study, a rat model was established to mimic ARDS via intratracheal instillation of lipopolysaccharide (LPS). A selective inhibitor of Smad3 (SIS3) was intraperitoneally injected into the disease model, while phosphate‐buffered saline (PBS) was used in the control group. Animal tissues were then evaluated using histological analysis, immunohistochemistry, RT‐qPCR, ELISA, and western blotting. LPS was found to stimulate the expression of RAGE, TGF‐ β 1, MMP2, and MMP9 in the rat model. Moreover, treatment with SIS3 was observed to reverse the expression of these molecules. In addition, pretreatment with SIS3 was shown to partially inhibit the phosphorylation of Smad3 and alleviate symptoms including lung injury and pulmonary edema. These findings indicate that SIS3, or the blocking of TGF‐ β /Smad3 pathways, could influence remodeling of the ECM and this may serve as a therapeutic strategy against ARDS.

In this study, we first analyzed the expression level of fractalkine (FKN) in the serum of patients with lupus nephritis (LN) and the distribution of peripheral blood Treg cells, and explored FKN and Treg cells, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) correlation. Subsequently, we explored the specific role of FKN in tubule interstitial lesions (TILs) and regulatory T (Treg) cells/T helper (Th) 17 cell balance in lupus model mice. Treated with an anti-FKN antibody (aFKN), recombinant FKN (rFKN), or an isotype antibody (IgG) in MRL/MpJ-Faslpr/J and C57BL/6 mice, and then detected TIL level and forkhead box p3 (Foxp3), IL-10, IL-17 and IL-6 expression levels in the kidney and spleen in the proportion of Treg and Th17 cells. Finally, then use aFKN, rFKN, or IgG to intervene in polarized Tregs with IL-6, TGF-beta, IL-23, anti-interferon, and Th17 cells with anti-IL-4 after transforming to transform growth factor (TGF)-beta and interleukin (IL)-2 in isolated mouse spleen lymphocytes. The results showed that the expression level of FKN was positively correlated with SLEDAI-2K and negatively correlated with the distribution of Treg cells. After treatment with aFKN in lupus model mice, kidney damage was delayed, TIL formation was reduced, Foxp3 and IL-10 levels were up-regulated, IL-17 and IL-6 levels were down-regulated in renal tissues, Th17 cell subsets and Treg cell subsets were reduced The increase is in the spleen, and rFKN treatment has the opposite effect in mouse. In addition, after interfering with polarized cells by aFKN, it was found that IL-17 and IL-6 expression levels were down-regulated in Th17 cells, Foxp3 and IL-10 levels in Tregs were up-regulated, and rFKN treatment had the opposite effect in vitro. These results indicate that FKN participates in and promotes SLE target organ damage including: secretion of inflammatory factors and renal TIL, and most importantly, these effects might have been due to modification of the Treg/Th17 cell balance.