Investigating gut microbiota-blood and urine metabolite correlations in early sepsis-induced acute kidney injury: insights from targeted KEGG analyses.

Background: The interplay between gut microbiota and metabolites in the early stages of sepsis-induced acute kidney injury (SA-AKI) is not yet clearly understood. This study explores the characteristics and interactions of gut microbiota, and blood and urinary metabolites in patients with SA-AKI. Methods: Utilizing a prospective observational approach, we conducted comparative analyses of gut microbiota and metabolites via metabolomics and metagenomics in individuals diagnosed with SA-AKI compared to those without AKI (NCT06197828). Pearson correlations were used to identify associations between microbiota, metabolites, and clinical indicators. The Comprehensive Antibiotic Resistance Database was employed to detect antibiotic resistance genes (ARGs), while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways informed on metabolic processes and microbial resistance patterns. Results: Our study included analysis of four patients with SA-AKI and five without AKI. Significant disparities in bacterial composition were observed, illustrated by diversity indices (Shannon index: 2.0 ± 0.4 vs. 1.4 ± 0.6, P = 0.230; Simpson index: 0.8 ± 0.1 vs. 0.6 ± 0.2, P = 0.494) between the SA-AKI group and the non-AKI group. N6, N6, N6-Trimethyl-L-lysine was detected in both blood and urine metabolites, and also showed significant correlations with specific gut microbiota (Campylobacter hominis and Bacteroides caccae, R > 0, P < 0.05). Both blood and urine metabolites were enriched in the lysine degradation pathway. We also identified the citrate cycle (TCA cycle) as a KEGG pathway enriched in sets of differentially expressed ARGs in the gut microbiota, which exhibits an association with lysine degradation. Conclusions: Significant differences in gut microbiota and metabolites were observed between the SA-AKI and non-AKI groups, uncovering potential biomarkers and metabolic changes linked to SA-AKI. The lysine degradation pathway may serve as a crucial link connecting gut microbiota and metabolites.

Association between prolonged vancomycin infusion and trough concentrations in children. Retrospective study. / Asociación entre infusión prolongada de vancomicina y concentración valle en niños. Estudio retrospectivo.

Introduction: This study investigated the serum concentration of vancomycin during prolonged infusion in children. Population and methods: This retrospective cohort study included pediatric patients who received vancomycin from June 2017 to June 2020 at a tertiary referral hospital. The patients were divided into two groups according to infusion strategy, the SII (standard intermittent infusion) group and the PI (prolonged infusion) group. Demographic details, infusion period, serum creatinine, duration of vancomycin therapy, trough concentration of vancomycin, and pediatric intensive care unit stay were reviewed. Differences of the concentrations were measured. Results: Sixty-eight patients were included: 31 in the SII group and 37 in the PI group. The trough concentration of vancomycin was significantly higher in the PI group than in SII group (11.2 mg/L [5.9-13.7] vs. 7 mg/L [3.5- 9.3]; p = 0.02). The target attainment rate was higher in the PI group than in the SII group (59.4% and 19.3%, respectively; p = 0.001). There were no significant differences between the SII and PI groups regarding the peak concentrations of vancomycin, final creatinine and peak creatinine. There were no differences between the SII and PI groups regarding the failure events, PICU stay and duration of vancomycin therapy. The multivariable analysis showed that PI was significantly associated with higher trough serum concentrations of vancomycin (OR = 2.27; p = 0.005). Conclusion: Compared to the SII strategy, the PI strategy may be an optimized option to children with severe infection, as it can achieve higher trough concentrations and target concentration attainment.

Introducción: Este estudio investigó la concentración plasmática de vancomicina en los niños, durante la infusión prolongada. Población y métodos: Estudio retrospectivo de una cohorte que incluyó pacientes pediátricos tratados con vancomicina desde junio de 2017 hasta junio de 2020, en un hospital de referencia de nivel III. Los pacientes se dividieron en dos grupos sogún el tipo de infusión: el grupo de infusión intermitente estándar (IIE) y el grupo de infusión prolongada (IP). Se registraron detalles demográficos, periodo de infusión, creatinina plasmática, duranción del tratamiento con vancomicina, concentración valle de vancomicina y permanencia en la unidad de cuidados intensivos pediátricos (UCIP). Se midieron las diferencias entre concentraciones. Resultados: Se incluyeron 68 pacientes, 31 en el gruop IIE y 37 en el grupo IP. La concentración valle de vancomicina fue significativamente más alta en el grupo IP en comparación con el grupo IIE (11,2mg/L [5,9-13,7] vs. 7 mg/L [3,5-9,3]; p = 0,02). La tasa de logro del objetivo fue más alta en el grupo IP que en el grupo IIE (59,4 % y 19,3 % repectivamente; p = 0,001). No hubo diferencias significativas entre ambos grupos en las concentraciones pico de vancomicina, valor de creatinina final, pico de creatinina, fracaso terapéutico, duración de la estadía en la UCIP y duración del tratamiento con vancomicina. El análisis multivariado mostró que la IP se asoció en forma significativa con concentraciones valle más altas de vancomicina (OR: 2,27, p = 0,005). Conclusión: En comparación con la estrategia de IIE, la infusión prolongada puede ser una opción optimizada para los niños con infección grave, porque puede alcanzar concentraciones valle más altas y mejorar la obtención de la concentración objetivo.

Pediatric intensive care unit treatment alters the diversity and composition of the gut microbiota and antimicrobial resistance gene expression in critically ill children.

Introduction: Common critical illnesses are a growing economic burden on healthcare worldwide. However, therapies targeting the gut microbiota for critical illnesses have not been developed on a large scale. This study aimed to investigate the changes in the characteristics of the gut microbiota in critically ill children after short-term pediatric intensive care unit (PICU) treatments. Methods: Anal swab samples were prospectively collected from March 2021 to March 2022 from children admitted to the PICU of Xinhua Hospital who received broad-spectrum antibiotics on days 1 (the D1 group) and 7 (the D7 group) of the PICU treatment. The structural and functional characteristics of the gut microbiota of critically ill children were explored using metagenomic next-generation sequencing (mNGS) technology, and a comparative analysis of samples from D1 and D7 was conducted. Results: After 7 days of PICU admission, a significant decrease was noted in the richness of the gut microbiota in critically ill children, while the bacterial diversity and the community structure between groups remained stable to some extent. The relative abundance of Bacilli and Lactobacillales was significantly higher, and that of Campylobacter hominis was significantly lower in the D7 group than in the D1 group. The random forest model revealed that Prevotella coporis and Enterobacter cloacae were bacterial biomarkers between groups. LEfSe revealed that two Gene Ontology entries, GO:0071555 (cell wall organization) and GO:005508 (transmembrane transport), changed significantly after the short-term treatment in the PICU. In addition, 30 KEGG pathways were mainly related to the activity of enzymes and proteins during the processes of metabolism, DNA catabolism and repair, and substance transport. Finally, 31 antimicrobial resistance genes had significantly different levels between the D7 and D1 groups. The top 10 up-regulated genes were Erm(A), ErmX, LptD, eptB, SAT-4, tetO, adeJ, adeF, APH(3')-IIIa, and tetM. Conclusion: The composition, gene function, and resistance genes of gut microbiota of critically ill children can change significantly after short PICU treatments. Our findings provide a substantial basis for a better understanding of the structure and function of gut microbiota and their role in critical illnesses.

Analysis of microRNA expression in rat kidneys after VEGF inhibitor treatment under different degrees of hypoxia.

Previously, we found that the incidence of kidney injury in patients with chronic hypoxia was related to the partial pressure of arterial oxygen. However, at oxygen concentrations that contribute to kidney injury, the changes in the relationship between microRNAs (miRNAs) and the hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) axis and the key miRNAs involved in this process have not been elucidated. Therefore, we elucidated the relationship between VEGF and kidney injury at different oxygen concentrations and the mechanisms mediated by miRNAs. Sprague-Dawley rats were exposed to normobaric hypoxia and categorized into six groups based on the concentration of the oxygen inhaled and injection of the angiogenesis inhibitor bevacizumab, a humanized anti-VEGF monoclonal antibody. Renal tissue samples were processed to determine pathological and morphological changes and HIF-1α, VEGF, and miRNA expression. We performed a clustering analysis of high-risk pathways and key hub genes. The results were validated using two Gene Expression Omnibus datasets (GSE94717 and GSE30718). As inhaled oxygen concentration decreased, destructive changes in the kidney tissues became more severe. Although the kidney possesses a self-protective mechanism under an intermediate degree of hypoxia (10% O2), bevacizumab injections disrupted this mechanism, and VEGF expression was associated with the ability of the kidney to repair itself. rno-miR-124-3p was identified as a crucial miRNA; a key gene target, Mapk14, was identified during this process. VEGF plays an important role in kidney protection from injury under different hypoxia levels. Specific miRNAs and their target genes may serve as biomarkers that provide new insights into kidney injury treatment.NEW & NOTEWORTHY Renal tolerance to hypoxic environments is limited, and the degree of hypoxia does not show a linear relationship with angiogenesis. VEGF plays an important role in the kidney's self-protective mechanism under different levels of hypoxia. miR-124-3p may be particularly important in kidney repair, and it may modulate VEGF expression through the miR-124-3p/Mapk14 signaling pathway. These microRNAs may serve as biomarkers that provide new insights into kidney injury treatment.

Neutrophil CD64 index for diagnosis of infectious disease in the pediatric ICU: a single-center prospective study.

BACKGROUND: Infection is a major cause of death in children, and it is particularly important to identify biological indicators of early infection. Previous studies showed that the neutrophil CD64 (nCD64) index may be a useful biomarker for infection. The purpose of this study was to investigate use of the nCD64 index to identify infection in children from a pediatric ICU (PICU) in China. METHODS: This prospective observational study enrolled 201 children who were admitted to our PICU and were divided into an infection group and a non-infection group. In each patient, C-reactive protein (CRP), nCD64 index, procalcitonin (PCT), and white blood cell count were measured during the first 24 h after admission. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity, specificity, and diagnostic value of the nCD64 index for infection. RESULTS: Among all 201 children, the infection group had greater levels of CRP, nCD64 index, and PCT (all p < 0.05). ROC analysis indicated the nCD64 index had a sensitivity of 68.8%, specificity of 90.7%, accuracy of 80.5%, and an optimal cut-off value of 0.14, which had better diagnostic value than CRP or PCT. For children with postoperative fever, the nCD64 index also distinguished systemic inflammatory response syndrome (SIRS) from infection with accuracy of 79%. CONCLUSIONS: The nCD64 index is a useful biomarker for the diagnosis of early infection in children admitted to the PICU.

Value of Central Venous Pressure Monitoring in the Patients with Sepsis-Associated Acute Kidney Injury.

Background: Although the measurement of central venous pressure (CVP) is a common clinical tool, the role of CVP monitoring in the outcome of sepsis is controversial because threshold values of CVP are uncertain, and there are only limited data on short-term survival of patients with septic acute kidney injury (AKI). Methods: This retrospective cohort study was based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (source of the training dataset). Multivariate regression analysis was performed to clarify the relation between CVP measurement and clinical outcomes, and a univariate regression model after propensity score matching was utilized to validate our findings. A mortality prediction model for septic AKI and a risk stratification scoring approach were developed, and the emergency intensive care unit (eICU) database was used for external validation. Results: Of the 9170 patients in the training set, 2446 (26.7%) underwent CVP measurement. No significant association was found between CVP monitoring and 28-day mortality among patients with septic AKI (odds ratio = 0.479; 95% confidence interval 0.213-1.076, P = 0.075), even after adjustments (propensity score matching; P = 0.178). Length of ICU stay and hospital stay was markedly reduced in patients undergoing CVP measurement within 3 hours (median 6.2 and 10.9 days, respectively, P < 0.001). The addition of the mean perfusion pressure initial, CVP, and the magnitude of the CVP change within 48 hours to the model significantly increased model discrimination (area under the receiver operating characteristic curve: 0.867 and 0.780, respectively, P < 0.001). Conclusions: These findings suggest that CVP measurement alone has little effect on the outcome of septic AKI. Nonetheless, initial CVP levels and the dynamic changes in CVP within the first 48 hours after ICU admission and the mean perfusion pressure initial can improve the accuracy of outcome prediction models.

Contribution of gut microbiota toward renal function in sepsis.

Sepsis most often involves the kidney and is one of the most common causes of acute kidney injury. The prevalence of septic acute kidney injury has increased significantly in recent years. The gut microbiota plays an important role in sepsis. It interacts with the kidney in a complex and multifactorial process, which is not fully understood. Sepsis may lead to gut microbiota alteration, orchestrate gut mucosal injury, and cause gut barrier failure, which further alters the host immunological and metabolic homeostasis. The pattern of gut microbiota alteration also varies with sepsis progression. Changes in intestinal microecology have double-edged effects on renal function, which also affects intestinal homeostasis. This review aimed to clarify the interaction between gut microbiota and renal function during the onset and progression of sepsis. The mechanism of gut-kidney crosstalk may provide potential insights for the development of novel therapeutic strategies for sepsis.

Linear scleroderma in a child with central nervous system involvement: clinical and radiological features.

Linear scleroderma is the most common type of localized scleroderma in children. Lesions rarely involve areas other than the skin, and nervous system involvement is even rare. We reported a case of a 6-year-old girl who was admitted to the hospital with recurrent seizures for 4 weeks. Before that, she had left frontal plaques for more than 1 year. Radiological imaging of the brain showed multiple abnormal lesions and skin biopsy of the plaques indicated scleroderma. After drug therapy, the girl had no recurrence of epilepsy, and no obvious abnormalities were found in the reexamination of neuroimaging. We performed further radiological examination on this patient and reviewed the literatures for this rare case.

Prognostic death factors in secondary hemophagocytic lymphohistiocytosis children with multiple organ dysfunction syndrome receiving continuous renal replacement therapy: A multicenter prospective nested case-control study.

INTRODUCTION: Multiple organ dysfunction syndrome (MODS) with secondary hemophagocytic lymphohistiocytosis (SHLH) causes significant mortality. We aimed to identify the predictor factors for death in pediatric patients with SHLH-associated MODS receiving continuous renal replacement therapy (CRRT). METHODS: This multicentered nested case-control study was conducted from 2016 to 2020. The characteristics were compared between survivors and non-survivors. Logistic regression was applied to identify the risk factors for death. The cutoff values were assessed by receiver operating characteristics curves. RESULTS: Fifty two patients were enrolled in this study. Interleukin-6 level (p = 0.018) and the number of organ dysfunction (p = 0.047) were independent risk factors for death. The cutoff value of 13.12 pg/ml interleukin-6 and three organs dysfunction at CRRT initiation presented a high sensitivity and specificity. CONCLUSION: The number of organ dysfunction and interleukin-6 at CRRT initiation are independent risk factors for death in pediatric patients with SHLH-associated MODS.

Association between early fluid overload and mortality in critically-ill mechanically ventilated children: a single-center retrospective cohort study.

BACKGROUND: Positive fluid overload (FO) may cause adverse effect. This study retrospectively analyzed the relationship between early FO and in-hospital mortality in children with mechanical ventilation (MV) in pediatric intensive care unit (PICU). METHODS: This study retrospectively enrolled 309 children (ages 28 days to 16 years) receiving invasive MV admitted to the PICU of Xinhua Hospital from March 2014 to March 2019. Children receiving MV for less than 48 h were excluded. The FO in the first 3 days of MV was considered to the early FO. Patients were divided into groups according to early FO and survival to evaluate the associations of early FO, percentage FO(%FO) > 10%, and %FO > 20% with in-hospital mortality. RESULTS: A total of 309 patients were included. The mean early FO was 8.83 ± 8.81%, and the mortality in hospital was 26.2% (81/309). There were no significant differences in mortality among different FO groups (P = 0.053) or in early FO between survivors and non-survivors (P = 0.992). Regression analysis demonstrated that use of more vasoactive drugs, the presence of multiple organ dysfunction syndrome, longer duration of MV, and a non-operative reason for PICU admission were related to increased mortality (P < 0.05). Although early FO and %FO > 10% were not associated with in-hospital mortality (ß = 0.030, P = 0.090, 95% CI = 0.995-1.067; ß = 0.479, P = 0.153, 95% CI = 0.837-3.117), %FO > 20% was positively correlated with mortality (ß = 1.057, OR = 2.878, P = 0.029, 95% CI = 1.116-7.418). CONCLUSIONS: The correlation between early FO and mortality was affected by interventions and the severity of the disease, but %FO > 20% was an independent risk factor for in-hospital mortality in critically ill MV-treated children.

Mild Hypoxia Enhances the Expression of HIF and VEGF and Triggers the Response to Injury in Rat Kidneys.

BACKGROUND: Hypoxia contributes to a cascade of inflammatory response mechanisms in kidneys that result in the development of renal interstitial fibrosis and subsequent chronic renal failure. Nonetheless, the kidney possesses a self-protection mechanism under a certain degree of hypoxia and this mechanism its adaptation to hypoxia. As the hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF) axis is a key pathway for neovascularization, the activation of this axis is a target for renal hypoxia therapies. METHODS: Sprague-Dawley rats were exposed to normobaric hypoxia and subdivided into three groups, namely group A (21% O2), group B (10% O2), and group C (7% O2). Renal tissue samples were processed and analyzed to determine pathological morphological changes, the expression of HIF, VEGF, inflammation factor and vascular density. RESULTS: We found that as the duration of hypoxia increased, destructive changes in the kidney tissues became more severe in group C (7% O2). In contrast, the increased duration of hypoxia did not exacerbate kidney damage in group B (10% O2). As the hypoxia was prolonged and the degree of hypoxia increased, the expression of HIF-1α increased gradually. As hypoxia time increased, the expression of VEGF increased gradually, but VEGF expression in group B (10% O2) was the highest. Group C (7% O2) had higher levels of IL-6, IL-10, and TNF-alpha. Additionally, the highest vascular density was observed in group B. CONCLUSION: These findings suggest that activating the HIF-VEGF signaling pathway to regulate angiogenesis after infliction of hypoxic kidney injury may provide clues for the development of novel CKD treatments.

Clinical Factors Influencing End-of-Life Care in a Chinese Pediatric Intensive Care Unit: A Retrospective, post-hoc Study.

Objective: End-of-life(EOL) care decision-making for infants and children is a painful experience. The study aimed to explore the clinical factors influencing the EOL care to withhold/withdraw life-sustaining treatment (WLST) in Chinese pediatric intensive care unit (PICU). Methods: A 14-year retrospective study (2006-2019) for pediatric patients who died in PICU was conducted. Based on the mode of death, patients were classified into WLST group (death after WLST) and fCPR group (death after full intervention, including cardiopulmonary resuscitation). Intergroup differences in the epidemiological and clinical factors were determined. Results: There were 715 patients enrolled in this study. Of these patients, 442 (61.8%) died after WLST and 273 (38.2%) died after fCPR. Patients with previous hospitalizations or those who had been transferred from other hospitals more frequently chose WLST than fCPR (both P < 0.01), and the mean PICU stay duration was significantly longer in the WLST group (P < 0.05). WLST patients were more frequently complicated with chronic underlying disease, especially tumor (P < 0.01). Sepsis, diarrhea, and cardiac attack (all P < 0.05) were more frequent causes of death in the fCPR group, whereas tumor as a direct cause of death was more frequently seen in the WLST group. Logistic regression analysis demonstrated that previous hospitalization and underlying diseases diagnosed before admission were strongly associated with EOL care with WLST decision (OR: 1.6; P < 0.05 and OR: 1.6; P < 0.01, respectively). Conclusions: Pediatric patients with previous hospitalization and underlying diseases diagnosed before admission were associated with the EOL care to WLST.

Nursing care of a boy seriously infected with Steven-Johnson syndrome after treatment with azithromycin: A case report and literature review.

RATIONALE: Stevens-Johnson syndrome (SJS) is an acute blistering disease of the skin and mucous membranes. SJS in children is not common but potentially serious disease. But the epidemiology of SJS in China is not well defined. PATIENT CONCERNS: A 6-year-old boy was initially diagnosed as pneumonia admitted to hospital after admission, and the body appears red rash with blisters, skin damage, lip debaucjed, repeated high fever, and rapid progression. DIAGNOSES: SJS often results from an allergy reaction response to a range of drugs. It is a clinical diagnosis suggested by fever and malaise followed by an extensive painful, nonblanching, macular rash that commonly progresses to blistering or sloughing, and mucositis. INTERVENTIONS: The boy was treated with continuous renal replacement therapy, anti-infection therapy, high-dose glucocorticoid treatment, and symptomatic treatment. OUTCOMES: The patient was recovered after 33 days of treatment. LESSONS: The current treatment is mainly symptomatic treatment, and for the patient, it is important to make skin care related well, included early out blisters at effusion, reducing skin ulceration of the mucosa area, keeping skin clean, removing mucosa secretion and blood clots, doing eye care related, preventing the complications, ensuring adequate intake of nutrition and warm and so on.

Causes of death in hospitalized children younger than 12 years of age in a Chinese hospital: a 10 year study.

BACKGROUND: In China, the majority (77%) of urban children die in hospitals. Hospital-based review could provide insight leading to improvements in clinical practice and increase the survival of critically ill children. The aim of the present study is to identify the trends of immediate causes and chronic underlying diseases associated with deaths of children at one of the largest teaching hospitals in China over a period of 10 years (2006-2015). METHODS: A retrospective analysis of data of all children aged 1 month to 11 years who died at Xinhua Hospital between 2006 and 2015. Demographic details, main causes of deaths, and chronic underlying diseases were reviewed. RESULTS: Case fatality rate was 0.55% (510/93,443) and it represented 0.41-0.80% deaths per year. Overall, the most common immediate causes of deaths in hospitalized children were pneumonia (36.7%), sepsis (13.5%), tumour (11.4%), followed by nontraumatic intracranial or gastrointestinal hemorrhage (10.6%) and cardiac shock (9.6%). Over 70% of the deaths in children were complicated with chronic underlying diseases. Congenital abnormality was the most frequent chronic underlying disease observed in infants (60.3%) and tumour was the main chronic underlying disease in toddlers (31.1%) and older children (44%). CONCLUSIONS: Infectious diseases, especially pneumonia, were the major immediate causes of deaths, and the mortality in the study population decreased with age. Tumour and other noninfectious disease accounted for more deaths in older children. Chronic underlying diseases were found in most deaths of children.

Myxedema coma: A case report of pediatric emergency care.

RAIONALE: Myxedema coma (MC) is extremely rare but lethal in pediatric patients with hypothyroidism leading to altered mental status and hypothermia. But there is no clinical guideline for such cases. PATIENT CONCERNS: A 6-year-old Chinese girl presented with coma and hypothermia preceded by pneumonia. Her lab results were: free thyroxin (T4) 4.18 pmol/L and thyroid-stimulating hormone (TSH) > 150 µIU/mL with extremely elevated anti-thyroid peroxidase (TPO-Ab) and anti-thyroglobulin. Pneumonia, mild pleural, and pericardial effusion were seen on computed tomographic (CT) scan. DIAGNOSES: MC, autoimmune hypothyroidism, pneumonia and sepsis were diagnosed. INTERVENTION: Gastric levothyroxine, intravenous dexamethasone and antibiotics were administered. OUTCOME: Her consciousness was restored and temperature returned to normal 2 days after starting levothyroxine. She was discharged two weeks later. CONCLUSION: MC is rare but may be the initial presentation in pediatric patients with prolonged untreated hypothyroidism. Autoimmune thyroiditis could cause hypothyroidism in children. MC should be suspected in pediatric patients with altered mental status, hypothermia and cardiovascular instability. Treatment with 100 mg/m of gastric levothyroxine is an option for pediatric patients with MC.

Human Umbilical Cord Mesenchymal Stromal Cells Improve Survival and Bacterial Clearance in Neonatal Sepsis in Rats.

Sepsis is the main cause of morbidity and mortality in neonates. Mesenchymal stromal cells (MSCs) are potent immune-modulatory cells. Their effect in neonatal sepsis has never been explored. We hypothesized that human umbilical cord-derived MSCs (hUC-MSCs) improve survival in experimental neonatal sepsis. Sepsis was induced in 3-day-old rats by intravenous injection of Escherichia coli (5 × 105/rat). One hour after infection, rats were treated intravenously with normal saline, hUC-MSCs, or with interferon-γ preconditioned hUC-MSCs (107 cells/kg). Eighteen hours after infection, survival, bacterial counts, lung neutrophil and macrophage influx, phagocytosis and apoptosis of splenocytes plasma, and LL-37 concentration were evaluated. Animals were observed for survival for 72 h after E. coli injection. Treatment with either hUC-MSCs or preconditioned hUC-MSCs significantly increased survival (hUC-MSCs, 81%; preconditioned hUC-MSCs, 89%; saline, 51%; P < 0.05). Both hUC-MSCs and preconditioned hUC-MSCs enhanced bacterial clearance. Lung neutrophil influx was decreased with preconditioned hUC-MSCs. The number of activated macrophages (CD206+) in the spleen was increased with hUC-MSCs and preconditioned hUC-MSCs; preconditioned hUC-MSCs increased the phagocytic activity of CD206+ macrophages. hUC-MSCs and preconditioned hUC-MSCs decreased splenocyte apoptosis in E. coli infected rats. Finally, LL-37 plasma levels were elevated in neonatal rats treated with hUC-MSCs or preconditioned hUC-MSCs. hUC-MSCs enhance survival and bacterial clearance in experimental neonatal sepsis. hUC-MSCs may be an effective adjunct therapy to reduce neonatal sepsis-related morbidity and mortality.