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Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine’s protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis.

BackgroundSepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear.MethodsGenetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes.ResultsOur MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype.ConclusionOur MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.

Abstract Background To identify the factors influencing the early encapsulation of peripancreatic fluid/necrosis collections via contrast-enhanced computed tomography (CECT) and to determine the clinical significance of early encapsulation for determining the prognosis of acute pancreatitis (AP) patients. Methods AP patients who underwent CECT between 4 and 10 days after disease onset were enrolled in this study. Early encapsulation was defined as a continuous enhancing wall around peripancreatic fluid/necrosis collections on CECT. Univariate and multivariate logistic regression analyses were performed to assess the associations between the variables and early encapsulation. Clinical outcomes were compared between the non-encapsulation and early encapsulation groups with 1:1 propensity score matching. Results A total of 289 AP patients were enrolled. The intra-observer and inter-observer agreement were considered good (kappa statistics of 0.729 and 0.614, respectively) for identifying early encapsulation on CECT. The ratio of encapsulation increased with time, with a ratio of 12.5% on day 5 to 48.7% on day 9. Multivariate logistic regression analysis revealed that the longer time from onset to CECT examination (OR 1.55, 95% CI 1.23–1.97), high alanine aminotransferase level (OR 0.98, 95% CI 0.97–0.99), and high APACHE II score (OR 0.89, 95% CI 0.81–0.98) were found to be independent factors associated with delayed encapsulation. The incidence of persistent organ failure was significantly lower in the early encapsulation group after matching (22.4% vs 6.1%, p = 0.043). However, there was no difference in the incidence of infected pancreatic necrosis, surgical intervention, or in-hospital mortality. Conclusions AP patients without early encapsulation of peripancreatic fluid/necrosis collections have a greater risk of persistent organ failure. In addition to longer time, the high APACHE II score and elevated alanine aminotransferase level are factors associated with delayed encapsulation.

Abstract Pneumocystis jirovecii pneumonia and invasive pulmonary aspergillosis are both life‐threatening opportunistic fungal infections. There are only few reports of coinfection by these two fungi in the literature, and Aspergillus fumigatus is the predominant Aspergillus species in the coinfection. We report here the first case of coinfection by Aspergillus terreus and P. jirovecii pneumonia and caspofungin can be an appropriate choice for salvage treatment of the coinfection. A 51‐year‐old man with a history of immune thrombocytopenia treated with prednisone over 2 months was admitted to emergency intensive care unit for acute respiratory failure and a cavity was found on chest computed tomography. Therefore, his trachea was immediately intubated. The patient was treated with a large spectrum of antibiotic regimen, consisting initially of imipenem/cilastatin, moxifloxacin and fluconazole followed by fluconazole, imipenem/cilastatin, vancomycin, trimethoprim–sulphamethoxazole (TMP‐SMZ) and azithromycin. When the polymerase chain reaction analysis of the bronchoalveolar lavage sample revealed P. jirovecii and A. terreus, all the antibiotics were stopped except TMP‐SMZ, and voriconazole was added. Two weeks later, the patient showed clinical improvement but radiological deterioration. Consequently, caspofungin was started for salvage therapy, then the patient showed gradual clinical improvement. He was discharged with oral voriconazole and TMP‐SMZ. The antifungal treatment was continued for 6 months until complete radiological absorption. In conclusion, early bronchoscopy with bronchoalveolar lavage fluid should be considered in order to diagnose and treat promptly in those treated with corticosteroids combined with immunocompromised and caspofungin could be an appropriate choice for salvage treatment of coinfection by P. jirovecii and A. terreus.

Abstract Background Antibiotic use in the early stages of acute pancreatitis is controversial. The purpose of this study was to investigate the effect of early antibiotic application on the prognosis of acute pancreatitis (AP). Materials and methods Clinical data of patients with primary AP admitted to our emergency ward within 72 hours of onset were retrospectively collected from January 2016 to December 2020. We classified patients with acute pancreatitis according to etiology and disease severity, and compared the differences in hospital stay, laparotomy rate, and in-hospital mortality among AP patients who received different antibiotic treatment strategies within 72 hours of onset. Results A total of 1134 cases were included, with 681 (60.1%) receiving early antibiotic treatment and 453 (39.9%) not receiving it. There were no significant differences in baseline values and outcomes between the two groups. In subgroup analysis, patients with biliary severe acute pancreatitis (SAP) who received early antibiotics had lower rates of laparotomy and invasive mechanical ventilation, as well as shorter hospital stays compared to those who did not receive antibiotics. In logistic regression analysis, the early administration of carbapenem antibiotics in biliary SAP patients was associated with a lower in-hospital mortality rate. Early antibiotic use in biliary moderate-severe acute pancreatitis (MSAP) reduced hospital stays and in-hospital mortality. Quinolone combined with metronidazole treatment in biliary mild acute pancreatitis (MAP) shortened hospital stays. Early antibiotic use does not benefit patients with non-biliary AP. Conclusion Strategies for antibiotic use in the early stages of AP need to be stratified according to cause and disease severity.

Abstract Background We sought to evaluate the effect of early short-term abdominal paracentesis drainage (APD) in moderately severe and severe acute pancreatitis (MSAP/SAP) with pelvic ascites. Methods A total of 135 MSAP/SAP patients with early pelvic ascites were divided into the Short-term APD group (57 patients) and the Non-APD group (78 patients). The effects, complications, and prognosis of short-term APD patients were evaluated. Results The baseline characteristics in the two groups were similar. The target days of intra-abdominal hypertension relief, half-dose enteral nutrition, duration of mechanical ventilation, length of intensive care unit stay (in days) and total hospitalization (also in days) were all lower in the Short-term APD group than in the Non-APD group (P = 0.002, 0.009, 0.004, 0.006 and 0.019), while the white blood cell count and serum C-reaction protein level decreased significantly more quickly (P

BackgroundAcute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.MethodsEmploying a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.ResultsOur investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis.ConclusionThis study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Background: In addition to excessive inflammation, immunosuppression has been recognized as a contributing factor to poor prognosis of sepsis. Although it has been reported that T cells can become functionally impaired during sepsis, the underlying mechanisms responsible for this phenomenon remain unclear. This study aims to elucidate the mechanisms by which macrophages induce immunosuppression in T cells. Methods: In an in vivo setting, C57BL-6J mice were subjected to cecal ligation and puncture (CLP) with or without depletion of macrophages, and the functions of T cells were assessed. In vitro experiments involved direct co-culture or separate culture of T cells and septic macrophages using a transwell system, followed by analysis of T cell immunity. Additionally, a siRNA targeting CD18 on macrophages was utilized to investigate the role of complement receptor 3 (CR3). Results: Both macrophages and T cells exhibited immunosuppression during sepsis. In the in vivo experiments, the absence of macrophages partially alleviated T cell immunosuppression, as evidenced by restored vitality, increased production of TNF-α and IFN-γ, elevated CD8+ T cell levels, and decreased CD25+ T cell levels. In the in vitro experiments, direct co-culture of T cells with septic macrophages resulted in diminished T cell immunity, which was improved when T cells and macrophages were separated by a chamber wall. The expression of CR3 (CD11b/CD18) was upregulated on septic macrophages, and silencing of CD18 led to decreased TNF-α production by T cells, reduced CD4+ T cell numbers, and increased CD25+ T cell numbers. Conclusion: In sepsis, macrophages induce immunosuppression in T cells through direct cell-cell contact, with the involvement of CR3.

Abstract The application of metagenomic next-generation sequencing (mNGS) has gradually been carried out by clinical practitioner. However, few studies have compared it with blood cultures in patients suffering from suspected bloodstream infections. The purpose of this study was to compare the detection of pathogenic microorganisms by these two assays in patients with suspected bloodstream infection. We retrospectively studied patients with fever, chills, antibiotic use for more than 3 days, suspected bloodstream infection, and admission to the emergency department of Ruijin Hospital from January 2020 to June 2022. All patients had blood drawn on the same day for blood mNGS and blood cultures. Clinical and laboratory parameters were collected on the day blood was drawn. The detection of pathogenic microorganisms by the two methods was compared. Risk factors and in-hospital mortality in patients with bloodstream infections were analysed separately for these two assays. In all 99 patients, the pathogenic microorganisms detection rate in blood mNGS was significantly higher than that in blood culture. Blood mNGS was consistent with blood culture in only 12.00% of all positive bacterial and fungal test results. The level of CRP is related to bacteraemia, fungaemia and viraemia detected by blood mNGS. No clear risk factors could be found in patients with a positive blood culture. In critically ill patients, both tests failed to improve patient outcomes. In patients with suspected bloodstream infection, mNGS is not yet a complete replacement for blood cultures.

ABSTRACTClostridioides difficile is a pathogen contributing to increased morbidity and mortality of patients with inflammatory bowel disease (IBD). To determine how C. difficile affects the severity of colitis, we constructed a dextran sulfate solution-induced colitis model challenged with C. difficile. Without antibiotic administration, C. difficile led to transient colonization in mice with colitis, but still significantly enhanced disease severity as assessed by weight loss, histopathological damages, and inflammatory cytokine concentrations. Because this effect is independent of toxin production as shown by infection with a non-toxigenic strain, we focused on changes in the gut microbiota. The microbiota altered by C.difficile, featured with reduced proportions of g_Prevotellaceae_UCG-001 and g_Muribaculaceae, were confirmed to contribute to disease severity in colitis mice via fecal microbiota transplantations. The inflamed colon showed neutrophil accumulation by flow cytometric analysis and myeloperoxidase immunochemical staining. There was enrichment of upregulated genes in leukocyte chemotaxis or migration as shown by RNA sequencing analysis. The isolated neutrophils from C. difficile-infected mice with colitis showed a robust migratory ability and had enhanced expression of cytokines and chemokines. We observed a detrimental role of neutrophils in the progress of disease by hindering neutrophil recruitment with the CXCR2 inhibitor SB225002. Furthermore, neutrophil recruitment appeared to be regulated by interleukin (IL)-1β, as inhibition of IL-1β production by MCC950 markedly ameliorated inflammation with decreased neutrophil accumulation and neutrophil-derived chemokine expression. In conclusion, our study provides information on the complicated interaction between microbiota and immune responses in C. difficile-induced inflammation in mice with colitis. Our findings could help determine potential therapeutic targets for patients with IBD concurrent with C. difficile infection.

There is no gold standard for the diagnosis of coagulation dysfunction in sepsis, and the use of the current scoring systems is still controversial. The purpose of this study was to assess the performance of sepsis-induced coagulopathy (SIC), the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC), and the International Society on Thrombosis and Haemostasis overt DIC (ISTH overt-DIC). The relationship between each scoring system and 28-day all-cause mortality was examined. Among 452 patients (mean age, 65 [48,76] years), 306 [66.7%] were men, the median SOFA score was 6 [4,9], and the median APACHE II score was 15 [11,22]. A total of 132 patients (29.2%) died within 28 days. Both the diagnosis of SIC (AUROC, 0.779 [95% CI, 0.728–0.830], P

IntroductionAcute pancreatitis is a common gastrointestinal disease. The mortality of patients affected by severe acute pancreatitis (SAP) remains high. It is unclear whether high-dose intravenous vitamin C (HDIVC) therapy could improve the prognosis of these patients. The current prospective, randomized, double-blinded, placebo-controlled study will explore the effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis.Methods and designA total of 418 participants with moderately severe and severe acute pancreatitis who meet the eligible criteria will be randomly assigned in a 1:1 ratio to receive treatment with HDIVC (200 mg/kg/24 h) or placebo (saline) for a period of 7 days. The primary outcome is 28-day mortality in these patients. The secondary outcomes include organ functions and interventions, laboratory tests, healthcare, and 90-day mortality.Ethics and disseminationThis protocol was approved by the institutional ethics board of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Registration Number: 2019-90). The report of the study will be published in peer-reviewed journals and presented at conferences, both nationally and internationally.Clinical trial registrationChinese Clinical Trial Registry (ChiCTR1900022022). Version 1.5.

Abstract Background The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application. Method In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis. Results Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis. Conclusion Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.

BackgroundNonthyroidal illness syndrome (NTIS) is a common endocrine dysfunction predicting unfavorable outcomes in critical illness. The objective of the study is to evaluate the association between different NTIS subtypes with outcomes in septic patients.MethodsSeptic patients in two Chinese academic centers from October 2012 and October 2022 are enrolled in analysis. Multivariable regressions are used to assess associations between NTIS and outcomes. Outcomes include in-hospital mortality, length of stay in hospital (LOS), non-invasive ventilation failure and weaning failure. Patients with NTIS are categorized into 4 types according to the different levels of FT4 and TSH. The association between different NTIS subtypes and mortality are further analyzed. Survival curve is plotted using the Kaplan–Meier method.ResultsAfter screening, a total of 1226 septic patients with complete thyroid hormones result are eventually enrolled. Among them, 520 (42.4%) patients are diagnosed as NTIS. In multivariable regression analysis, NTIS is independently associated with increased 30-days mortality (OR=1.759, CI 1.009-3.104, p=0.047), but has no association with 60-days mortality (OR=1.524, CI 0.893-2.618, p=0.123), 90-days mortality (OR=1.411, CI 0.831-2.408, p=0.203), LOS, non-invasive ventilation failure or weaning failure. In NTIS subtypes, NTIS patients with low FT3 and TSH levels, regardless of the FT4 values, have significantly higher mortality than euthyroid patients (30-days mortality, OR= 6.488, CI 1.546-27.808, p=0.01; 60-days mortality, OR=3.973, CI 1.006-15.579, p=0.046; 90-days mortality, OR=3.849, CI 0.977-15.088, p=0.051). This result is consistent in patients with low FT3 and FT4 levels, regardless of the TSH values (30-days mortality, OR=3.349, CI 1.402-7.957, p=0.006; 60-days mortality, OR= 2.594, CI 1.122-5.930, p=0.024; 90-days mortality, OR=2.55, CI 1.110-5.804, p=0.025). There is no survival difference between NTIS patients with low FT3 only and euthyroid patients. Survival plot shows the worst prognosis is in NTIS patients with low FT3, FT4 and TSH level.ConclusionsNTIS is frequent in sepsis. A reduction of FT3 together with FT4 or TSH, but not FT3 only, is associated with an increased risk of mortality.

Abstract Severe acute pancreatitis (SAP) is a common abdominal disorder contributing to high mortality and open laparotomy rates. The role of exogenous infused albumin in fluid resuscitation or continuous therapy has always been an unanswered question. In early stage after onset, SAP patients with higher serum albumin or prealbumin show a better prognosis. In this study, we tried to disclose the linkage between albumin/prealbumin and SAP prognosis and establish a new goal-directed therapy involving albumin and prealbumin. Pearson’s chi-squared test and the Mann–Whitney U test were used to compare the descriptive data between surviving and non-surviving patients. Three days, 4–7 days, 8–14 days and 15–28 days after SAP onset were defined as stages 1–4. The average concentrations of albumin and prealbumin were calculated, and receiver operating characteristic (ROC) curves were drawn to screen out the best cutoff values associated with poor prognostic outcomes, including laparotomy and failure to survive. Kaplan–Meier survival curves and log-rank tests were used to validate the effect of the cut-off values. A total of 199 admitted patients were enrolled in this study. According to the analysis of the ROC curve, the serum albumin value should be raised to 35, 37, 40 and 42 g/L in the 1–4 stage after onset. Serum prealbumin values should be raised to 108, 180, and 181 g/L in stages 2–4 after onset. The validity of the above data was confirmed by Kaplan–Meier survival curves. Serum albumin and prealbumin levels in the early stage of SAP are significantly relevant to prognosis. Albumin should be infused from the fluid resuscitation stage to continuous therapy in order to reach the targets mentioned above. The increase in prealbumin depends on the early initiation of enteral nutrition and this also helps to ameliorate the prognosis.

Abstract Background The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored. Methods ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups. Discussion ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

BackgroundSenescence is significantly associated with cancer prognosis. This study aimed to construct a senescence-related prognostic model for colorectal cancer (CRC) and to investigate the influence of senescence on the tumor microenvironment.MethodsTranscriptome and clinical data of CRC cases were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Senescence-related prognostic genes detected by univariate Cox regression were included in Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a model. The efficacy of the model was validated using the receiver operating characteristic (ROC) curve and survival analysis. Differentially expressed genes (DEGs) were identified and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. CIBERSORT and Immuno-Oncology Biological Research (IOBR) were used to investigate the features of the tumor microenvironment. Single-cell RNA-seq data were used to investigate the expression levels of model genes in various cell types. Immunofluorescence staining for p21, SPP1, and CD68 was performed with human colon tissues.ResultsA seven-gene (PTGER2, FGF2, IGFBP3, ANGPTL4, DKK1, WNT16 and SPP1) model was finally constructed. Patients were classified as high- or low-risk using the median score as the threshold. The area under the ROC curve (AUC) for the 1-, 2-, and 3-year disease-specific survival (DSS) were 0.731, 0.651, and 0.643, respectively. Survival analysis showed a better 5-year DSS in low-risk patients in the construction and validation cohorts. GO and KEGG analyses revealed that DEGs were enriched in extracellular matrix (ECM)-receptor interactions, focal adhesion, and protein digestion and absorption. CIBERSORT and IOBR analyses revealed an abundance of macrophages and an immunosuppressive environment in the high-risk subgroup. Low-risk patients had higher response rates to immunotherapy than high-risk patients. ScRNA-seq data revealed high expression of SPP1 in a subset of macrophages with strong senescence-associated secretory phenotype (SASP) features. Using CRC tumor tissues, we discovered that SPP1+ macrophages were surrounded by a large number of senescent tumor cells in high-grade tumors.ConclusionOur study presents a novel model based on senescence-related genes that can identify CRC patients with a poor prognosis and an immunosuppressive tumor microenvironment. SPP1+ macrophages may correlate with cell senescence leading to poor prognosis.

Sepsis-induced acute kidney injury (AKI) is one of the important causes of increased mortality in sepsis patients. Long non-coding RNA (lncRNA) is believed to play a vital function in the progression of AKI. However, the mechanism of nuclear enriched abundant transcript 1 (NEAT1) has not been fully elucidated. NEAT1 was overexpressed and miR-22-3p was underexpressed in sepsis patients and lipopolysaccharide (LPS)-induced AKI cell models. Knockdown of NEAT1 could promote viability and suppress apoptosis and the inflammatory response in LPS-induced HK2 cells. MiR-22-3p could be sponged by NEAT1, and its inhibitor reversed the inhibition effect of NEAT1 silencing on LPS-induced HK2 cell injury. CXCL12 could be targeted by miR-22-3p, and its overexpression reversed the suppression effect of miR-22-3p on LPS-induced HK2 cell injury. Silenced NEAT1 could restrain the activity of the NF-B signaling pathway, and miR-22-3p inhibitor or CXCL12 overexpression could reverse this effect. In addition, NEAT1 knockdown alleviated the inflammation response of cecal ligation and puncture (CLP) mouse models. In summary, our data showed that NEAT1 promoted LPS-induced HK2 cell injury via regulating the miR-22-3p/CXCL12/NF-B signaling pathway, suggesting that NEAT1 knockdown might be a potential pathway for alleviating sepsis-induced AKI.

BackgroundAcute pancreatitis (AP) is the most common gastrointestinal disease requiring hospital admission. AP patients are categorized as mild, moderately severe, and severe AP (SAP). For SAP patients, malnutrition increases susceptibility to infection and mortality. The Nutritional Risk Screening 2002 (NRS 2002), the Nutrition Risk in Critically Ill (NUTRIC) score and modified Nutrition Risk in Critically Ill (mNUTRIC) are nutritional risk screening tools of critically ill patients and have not been validated in patients with SAP. It is essential to evaluate the prognostic performance of these nutritional risk screening tools.Materials and methodsA retrospective study was designed to validate the NRS 2002, NUTRIC, and mNUTRIC when applied to SAP patients. Receiver operating characteristic curves were plotted to investigate the predictive ability of clinical outcomes by comparing areas under the curve (AUC). Appropriate cut-offs were calculated by using Youden’s index. Patients were identified as being at high nutritional risk according to the calculated cut-off values. The effects of different scoring systems on mortalities were calculated using the Cox proportional hazards model. Logistic regression was used to assess the association between the energy provision and 28-day mortality.ResultsFrom January 2013 to December 2019, 234 SAP patients were included and analyzed. Patients categorized as high nutritional risk by the NRS 2002 (12.6% versus 1.9% for 28-day and 20.5% versus 3.7% for 90-day), NUTRIC (16.2% versus 0.0% for 28-day and 27.0% versus 0.0% for 90-day), and mNUTRIC (16.4% versus 0.0% for 28-day and 26.4% versus 0.8% for 90-day) had significant higher mortality than those categorized as low nutritional risk. The NUTRIC (AUC: 0.861 for 28-day mortality and 0.871 for 90-day mortality, both cut-off value ≥3) and mNUTRIC (AUC: 0.838 for 28-day and 0.828 for 90-day mortality, both cut-off value ≥3) showed better predictive ability of the 28- and 90-day mortality than the NRS 2002 (AUC: 0.706 for 28-day mortality and 0.695 for 90-day mortality, both cut-off value ≥5).ConclusionThe NRS 2002, NUTRIC, and mNUTRIC scores were predictors for the 28- and 90-day mortalities. The NUTRIC and mNUTRIC showed better predictive ability compared with the NRS 2002 when applied to SAP patients.

Background: How to detect acute pancreatitis (AP) complicated with infection early and how to arrange the treatment time are still the main problems in the world. There are few reports on the potential relationship between extrapancreatic infections and AP. The purpose of this article was to investigate the characteristics, influencing factors and prognosis of extrapancreatic infection in AP patients with modified Marshall score ≥2 on admission. Materials and methods: We retrospectively analyzed AP admitted to emergency intensive care unit of Ruijin hospital within 72 h of onset from September 2019 to December 2021. In addition to the patients' baseline data, sites of infection and microorganisms outside the pancreas were collected. Microbial cultures were used to identify infections of the respiratory tract, blood, abdominal cavity, biliary tract, urinary tract and clostridium difficile in feces. Results: 144 patients with AP were included, of which extrapancreatic infection accounted for 40.28%. C-reactive protein, procalcitonin, blood urea nitrogen, serum creatinine, oxygenation index, modified Marshall score, BISAP score and APACHE II score were significantly increased in the extrapancreatic infection group. The risk factors of extrapancreatic infection included blood urea nitrogen, Modified Marshall score and duration of mechanical ventilation. The positive rates of pathogenic bacteria in sputum culture, blood culture, ascites culture and bile culture were significantly higher than those in the 1–3 days after admission. The infection begins to worsen as early as 4–7 days after the onset of symptoms. Extrapancreatic infection is associated with pancreatic necrosis, the rate of laparotomy, length of hospital stay and in-hospital mortality. Conclusion: Our research has confirmed the need to prevent and monitor extrapancreatic infection in the early stage.

BackgroundEarly recognition of the risk factors is important for acute pancreatitis management. The aim of this study is to investigate the relationship between platelet count and clinical outcomes in patients with acute pancreatitis.MethodsThe data are collected from a university-affiliated hospital between January 2013 and December 2020. A generalized additive model and a two-piecewise linear regression model are used to estimate the association between platelet count and the risks of intra-abdominal infection, surgical intervention, in-hospital mortality, and length of hospital stay.ResultsAmong the 1,363 patients, 99 (7.3%) patients suffered intra-abdominal infection, 190 (13.9%) patients underwent surgical intervention, and 38 (2.8%) patients died in the hospital. The median length of hospital stay is 21 days. Generalized additive model and two-piecewise linear regression analysis show that the risk of intra-abdominal infection decreases as the platelet count increases to 160 × 109/L (OR: 0.991, 95% CI: 0.984–0.998, p = 0.015) and then increases as the platelet count levels up (OR: 1.007, 95% CI: 1.004–1.010, p < 0.001). The trend is similar to the risk of surgical intervention and length of hospital stay. Even though there seems a declining trend in mortality, no significant association is found after adjustment for potential confounders. Further analysis shows that changes in platelet count within the first 3 days after admission have no obvious association with clinical outcomes.ConclusionA platelet count of approximately 160 × 109/L on admission is associated with the lowest risk of intra-abdominal infection, surgical intervention, and shortest hospital stay in patients with acute pancreatitis.

Abstract. Background:. Coronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. We aimed to investigate whether low molecular weight heparin (LMWH) can promote organ function recovery in moderate Covid-19 pneumonia patients. Methods:. We initiated an LMWH protocol in Covid-19 patients with increased D-dimer, body mass index >30 kg/m2 or a history of diabetes from January 18, 2020 at Shanghai Public Health Clinical Center. In this retrospective study, we assigned moderate Covid-19 pneumonia patients admitted between January 18th and April 18, 2020 receiving the LMWH protocol to the LMWH group. Moderate patients who met the inclusion criteria but did not receive LMWH protocol were included in the control group by 1:2 propensity score matching. General clinical information, indicators for renal function, arterial blood gas analyses, arterial blood lactic acid content (mmol/L), and coagulation indexes at 0 day, 3 days, 7 days, and 11 days after admission were recorded and compared between the two groups. Results:. There were 41 patients in the LMWH group and 82 patients in the control group. General information in both groups were similar. Compared to the control group, the arterial blood lactic acid content (mmol/L) at day 11 (1.3 [1.1, 1.7] vs. 1.2 [0.9, 1.3], P = 0.016) was reduced in the LMWH group. The estimated glomerular filtration rate (eGFR) in the LMWH group was higher than that in the control group at day 7 (108.54 [89.11, 128.17] vs. 116.85 [103.39, 133.47], P = 0.039) and day 11 (113.74 [94.49, 126.34] vs. 128.31 [112.75, 144.12], P = 0.003). The serum creatinine levels (Scr) in the LMWH group were lower than that in the control group at day 7 (62.13 [51.47, 77.64] vs. 55.49 [49.50, 65.75], P = 0.038) and day 11 (63.35 [50.17, 75.73] vs. 51.62 [44.62, 61.24], P = 0.005). Conclusions:. LMWH treatment can reduce arterial blood lactic acid levels and improve eGFR in moderate Covid-19 pneumonia patients. Randomized controlled trials are warranted to further investigate this issue. Trial registration:. ChiCTR.org.cn, ChiCTR2000034796.

Abstract Fluid resuscitation via colon (FRVC) is a complementary therapeutic procedure for early-stage cases of severe acute pancreatitis (SAP). The expression of intestinal dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) regulates systemic inflammation. This study aimed to investigate the effect of FRVC on the expression of DC-SIGN in the colon tissue of SAP rats and its effect on the early response of systemic inflammatory and multiple organ injury. SAP was induced in rats via retrograde injection of sodium taurocholate into the biliopancreatic duct. DC-SIGN expression of appeared in the proximal and distal colon. Histological characteristics and inflammatory cytokines were examined to compare the effect of FRVC and intravenous fluid resuscitation (IVFR). The results showed that DC-SIGN expression in the proximal colon increased in a time-dependent manner in the early-stage of SAP rats. FRVC inhibited DC-SIGN expression in the proximal colon. Both FRVC and IVFR alleviated histological injuries of the pancreas and colon. However, FRVC had an advantage over IVFR in alleviating lung injury and reducing serum TNF-α, IL-6 and LPS. These results suggest that FRVC treatment might help suppress systemic inflammation and prevent subsequent organ failure in early-stage SAP rats likely through inhibiting DC-SIGN expression in the proximal colon.

BackgroundSepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis.Methods and designHere, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events.ConclusionThe findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis.Clinical trial registration[http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].

Abstract Severe acute pancreatitis (SAP) is a life-threatening disease. Fluid Resuscitation Via Colon (FRVC) may be a complementary therapy for early controlled fluid resuscitation. But its clinical application has not been reported. This study aims to explore the impact of FRVC on SAP. All SAP patients with the first onset within 72 h admitted to the hospital were included from January 2014 to December 2018 through electronic databases of Ruijin hospital and were divided into FRVC group (n = 103) and non-FRVC group (n = 78). The clinical differences before and after the therapy between the two groups were analyzed. Of the 181 patients included in the analysis, the FRVC group received more fluid volume and reached the endpoint of blood volume expansion ahead of the non-FRVC group. After the early fluid resuscitation, the inflammation indicators in the FRVC group were lower. The rate of mechanical ventilation and the incidence of hypernatremia also decreased significantly. Using pure water for FRVC was more helpful to reduce hypernatremia. However, Kaplan–Meier 90-day survival between the two groups showed no difference. These results suggest that the combination of FRVC might benefit SAP patients in the early stage of fluid resuscitation, but there is no difference between the prognosis of SAP patients and that of conventional fluid resuscitation. Further prospective study is needed to evaluate the effect of FRVC on SAP patients.

Abstract Background Clostridioides difficile infection (CDI) is a leading cause of nosocomial diarrhea. Patients receiving enteral nutrition (EN) in the intensive care unit (ICU) are potentially at high risk of CDI. In the present study, we assessed the risk factors and intestinal microbiome of patients to better understand the occurrence and development of CDI. Methods Patients were screened for C. difficile every week after starting EN, and their clinical records were collected for risk factor identification. Fecal samples were analyzed using 16S rRNA sequencing to evaluate the intestinal microbiota. Results Overall incidence of CDI was 10.7% (18/168 patients). History of cerebral infarction was significantly associated with CDI occurrence (OR, 9.759; 95% CI, 2.140–44.498), and treatment with metronidazole was identified to be protective (OR, 0.287; 95% CI, 0.091–0.902). Patients with EN had lower bacterial richness and diversity, accompanied by a remarkable decrease in the abundance of Bacteroides, Prevotella_9, Ruminococcaceae, and Lachnospiraceae. Of these patients, acquisition of C. difficile resulted in a transient increase in microbial diversity, along with consistent alterations in the proportion of some bacterial taxa, especially Ruminococcaceae and Lachnospiraceae. Upon initiation of EN, patients who were positive for C. difficile later showed an enhanced load of Bacteroides, which was negatively correlated with the abundance of C. difficile when CDI developed. Conclusion ICU patients receiving EN have a high prevalence of CDI and a fragile intestinal microbial environment. History of cerebral infarction and prior treatment with metronidazole are considered as vital risk and protective factors, respectively. We propose that the emergence of CDI could cause a protective alteration of the intestinal microbiota. Additionally, Bacteroides loads seem to be closely related to the occurrence and development of CDI.

Abstract Background Clostridioides difficile is considered the main pathogen responsible for hospital-acquired infections. This prospective study determined the prevalence, molecular epidemiological characteristics, and risk factors for C. difficile infection (CDI) and C. difficile colonization (CDC) among patients in the intensive care unit (ICU) of a large-scale tertiary hospital in China, with the aim of providing strategies for efficient CDI and CDC prevention and control. Methods Stool samples were collected and anaerobically cultured for C. difficile detection. The identified isolates were examined for toxin genes and subjected to multilocus sequence typing. Patients were classified into CDI, CDC, and control groups, and their medical records were analyzed to determine the risk factors for CDI and CDC. Results Of the 800 patients included in the study, 33 (4.12%) and 25 (3.12%) were identified to have CDI and CDC, respectively. Associations with CDI were found for fever (OR = 13.993), metabolic disorder (OR = 7.972), and treatment with fluoroquinolone (OR = 42.696) or combined antibiotics (OR = 2.856). CDC patients were characterized by prolonged hospital stay (OR = 1.137), increased number of comorbidities (OR = 36.509), respiratory diseases (OR = 0.043), and treatment with vancomycin (OR = 18.168). Notably, treatment with metronidazole was found to be a protective factor in both groups (CDI: OR = 0.042; CDC: OR = 0.013). Eighteen sequence types (STs) were identified. In the CDI group, the isolated strains were predominantly toxin A and toxin B positive (A + B+) and the epidemic clone was genotype ST2. In the CDC group, the dominant strains were A + B+ and the epidemic clone was ST81. Conclusions The prevalences of CDC and CDI in our ICU were relatively high, suggesting the importance of routine screening for acquisition of C. difficile. Future prevention and treatment strategies for CDC and CDI should consider hospital stay, enteral nutrition, underlying comorbidities, and use of combined antibiotics. Moreover, metronidazole may be a protective factor for both CDI and CDC, and could be used empirically.

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation.Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender.Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6–7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04).” The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7.Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.

Colorectal cancer (CRC) is a malignant tumor with a high incidence and death rate in the world. Molecular interactions inside cells or tissues during tumor occurrence, development, and drug resistance are important for disease prevention and treatment. The long non-coding RNA SNHG14 has been proven to exert its oncogenic function in multiple cancers. However, there is no study regarding the role of SNHG14 in CRC research. In the present study, we applied RT-qPCR and western blot to determine the gene expression levels. MTT and TUNEL assays were used to detect cell proliferation and apoptosis rate. Cell migration and invasion abilities were determined by wound healing and transwell assays, respectively. StarBase was used to predict the potential binding sites and luciferase reporter assay was applied to confirm the direct interactions. Besides, we conducted a xenograft experiment to detect tumor growth rate in vivo. Our results showed that SNHG14 and ATG14 were both significantly higher in CRC tumor tissues than the normal ones, while miR-186 was decreased. The similar results were also observed in CRC cell lines. We confirmed that SNHG14 could directly interact with miR-186 and inhibited its expression. Meanwhile, miR-186 could directly bind ATG14 to inhibit its expression level. In vitro experiments showed that higher expression of SNHG14 led to higher cell proliferation, migration and invasion, while miR-186 significantly inhibited these tumor phenotypes. Furthermore, overexpression of ATG14 could strongly recover the CRC phenotypes attenuated by shSNHG14 or miR-186 mimics. Interestingly, we constructed cisplatin-resistant CRC cells and found that overexpression of ATG14 significantly enhanced the cell proliferation rate and inhibited cell apoptosis. Our research indicated that the novel axis of SNHG14/miR-186/ATG14 could play a vital role in regulating CRC cell progression. Moreover, this axis showed its clinical potential in regulating cisplatin resistance during CRC treatment.

OBJECTIVE:To determine whether the coexistence of carotid atherosclerosis plaque affects the neurological function of cerebral infarction. METHODS:A total of 1078 patients with acute cerebral infarction were enrolled, all patients were divided into carotid plaque group (n = 702) and non-carotid plaque group (n = 376). Meanwhile, all patients were divided into mild group (n = 624) and moderate to severe group (n = 454). The difference of the incidence of carotid plaque between the mild and moderate to severe group was analyzed. RESULTS:In the 1078 patients with cerebral infarction, the NIHSS score in the carotid plaque group was significantly higher than that in the non-carotid plaque group (P

Abstract Background Polymyxin B (PMB), which is regarded as the ultimate antibacterial treatment against some intractable gram-negative bacteria with its outstanding anti-bacterial activities, inflicts several adverse effects on patients. However, skin hyperpigmentaion (SH) induced by PMB is very rare. Here, we report a case of polymyxin B-induced skin hyperpigmentation (PMB-iSH) in a 21-year-old female. To the best of our knowledge, this is the first case of PMB-iSH in China. Case presentation A 21-year-old female patient with sepsis received the administration of PMB by intravenous injection for the treatment of multi-drug resistant Klebsiella pneumoniae (MDR-KP) infection. She later suffered from a rare adverse drug reaction (ADR), namely PMB-iSH, after 5-day PMB administration during her treatment. There were multiple red rashes spread on the whole body skin at first. With the rashes fading away, SH with dark round spots appeared, associated with no pain or pruritus. The skin of the head and neck was darkened evidently, and dark brown spots were spread on the skin of trunk and limbs. About a month after her admission, urged by the relatives, the patient was transferred back to the local hospital for further treatment in the end, and her skin color didn’t recover to the previous state at that time. Conclusion Both our case and the literature review highlight that PMB can give rise to SH indeed. Clinicians and pharmacists should attach great importance to this rare pigmentary disorder and further investigation is warranted.

Abstract Background Acute pancreatitis (AP) is a life-threatening disease that requires early identification of patients at risk of developing infectious complications. Immunosuppression is an initial event that is key to AP pathogenesis. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system is reported to mediate evasion of host immune surveillance in many diseases; however, the relationship between PD-1/PD-L1 expression and these parameters or infectious complications in AP has not been elucidated. This study was conducted to determine whether PD-1 and PD-L1 are upregulated and to reveal the relationship between PD-1/PD-L1 expression and the development of infectious complications in AP. Methods Sixty-three patients with AP and 32 sex- and age-matched healthy control subjects were prospectively enrolled. On days 1 and 3 after the onset of AP, we measured PD-1 expression in peripheral CD4+ T cells and PD-L1 and human leukocyte antigen-DR (HLA-DR) expression in CD14+ monocytes using flow cytometry. Plasma interleukin (IL)-10 levels were measured by enzyme-linked immunosorbent assay. Results Compared with healthy volunteers, the percentages of PD-1-expressing CD4+ lymphocytes and PD-L1-expressing CD14+ monocytes were increased in patients with AP on days 1 and 3 after onset, especially those with infectious complications. Moreover, increased PD-1/PD-L1 expression was associated with increased occurrence of infectious complications, decreased circulating lymphocytes, and increased plasma IL-10 concentration. Multivariate regression analysis indicated that the increased percentage of PD-L1-expressing CD14+ monocytes was an independent risk factor for infectious complications in AP. Area under the ROC curve analysis showed the combination of Acute Physiology and Chronic Health Evaluation II score and PD-L1 and HLA-DR expression in CD14+ monocytes had high accuracy in predicting infectious complications in patients with AP. Conclusions The PD-1/PD-L1 system plays an essential role in the early immunosuppression of AP. PD-L1 expression in CD14+ monocytes may be a new marker for predicting risk of infectious complications in patients with AP.

INTRODUCTION: Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality. METHODS: We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included. RESULTS: A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027-1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691-4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142-5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141-4.420) were significantly associated with mortality. CONCLUSIONS: Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.

Acute lung injury (ALI) is a devastating human malignancy characterized by excessively uncontrolled inflammation and lung endothelial dysfunction. Noncoding RNAs play essential roles in endothelial protections during the pathological processes of ALI. The precise functions and molecular mechanisms of the lncRNA-NORAD-mediated endothelial protection remain obscure. This study reports NORAD was significantly induced in human pulmonary microvascular endothelial cells (HPMECs) under lipopolysaccharide (LPS) treatment. Silencing NORAD effectively protected HPMECs against the LPS-induced cell dysfunction. In addition, RNA pull-down and luciferase assay validated that NORAD sponged miR30c-5p, which showed reverse functions of NORAD in the LPS-induced cell injury of HPMECs. Furthermore, the glucose metabolism of HPMECs was significantly elevated under LPS stimulation which promoted the glucose consumption and extracellular acidification rate (ECAR) of HPMECs. Inhibiting NORAD or overexpressing miR-30c-5p suppressed glucose metabolism in HPMECs, leading to protective effects on HPMECs under LPS stimulation. The glycolysis key enzyme, lactate dehydrogenase-A (LDHA), was subsequently identified as a direct target of miR-30c-5p. Finally, recovery of miR-30c-5p in NORAD-overexpressing HPMECs effectively overrode the NORAD-promoted glycolysis and impaired endothelial dysfunction under LPS stimulation by targeting LDHA. Summarily, we demonstrated a NORAD-miR-30c-5p-LDHA-glycolysis axis in the LPSinduced HPMECs dysfunction in vitro and in vivo, contributing to the development of anti-ALI therapeutic approaches. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a common gastrointestinal disorder with a high mortality rate. This study evaluated the incidence of and risk factors for reoperation after debridement of AP. This retrospective study included 168 patients diagnosed with AP who had undergone debridement between January 2007 and December 2017 at our hospital. Patients were divided into single-operation and reoperation groups separately. Sixty-eight (40.24%) patients underwent reoperation after AP debridement. The main procedure for reoperation was debridement of necrosis. In univariate analysis, the risk factors for reoperation included younger age; higher admission temperature and heart rate; higher levels of C-reactive protein (CRP), blood urea nitrogen and creatinine; higher Acute Physiology and Chronic Health Evaluation II score and rate of continuous renal replacement therapy; shorter operation interval; lower postoperative albumin level; and high incidence of preoperative and postoperative complications. Multivariate logistic analysis indicated that independent risk factors for reoperation included higher levels of C-reactive protein and creatinine in admission, preoperative percutaneous catheter drainage, and postoperative complications. The general characteristics and clinical procedures of patients with AP after debridement might affect prognosis and reoperation. The identification of risk factors could help clinicians to provide specific treatment, better ward management, and stratification of reoperation risk. [ABSTRACT FROM AUTHOR]