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Biofilm formation is easily found in patients suffered from ventilator-associated pneumonia (VAP) in neonatal intensive care unit (NICU) and makes the VAP infections not only harder to be treated but easier to relapse. In order to find some novel ways to inhibit biofilm formation, this study describe a previously unrecognized role for the human umbilical cord mesenchymal stem cells (hUCMSCs). In addition to multiple differentiation, hUCMSCs have the ability to prevent the biofilms formation in vitro by secreting antibacterial peptides (LL-37 and hBD-2). This occurred while P. aeruginosa PA27853 and hUCMSCs were cocultured, and the filtrated medium, which was the supernatant containing antibacterial peptides (5.9 ng/ml of LL-37, 1.77 ng/ml of hBD-2), and inhibited the growth of the bacterial biofilm on the surface of tracheal tube (2.5#, for preterm infant). Using microarrays, we were able to demonstrate that the antibacterial peptides from hUCMSC affected biofilm formation by downregulating the gene-encoded polysaccharide biosynthesis protein. In addition, in order to find out the most suitable concentration of hUCMSCs, P. aeruginosa was cocultured with eight-level concentrations of hUCMSCs, and we found that the concentration of LL-37 was positively correlated with the concentration of hUCMSCs. Meanwhile, the concentration of LL-37 became stable while the hUCMSC concentration reaches higher than 5 × 10 6 cells / ml . But the concentration of hBD-2 had no significant correlation with hUCMSCs. The collection of these stem cells is not only limited by ethics but also reduces host rejection. This makes it possible to use autologous hUCMSCs to treat neonatal VAP.

Infection is the leading cause of admission and mortality in neonatal intensive care units. Immature immune function and antibiotic resistance make the treatment more difficult. However, there is no effective prevention for it. Recently, more and more researches are focusing on stem cell therapy, especially mesenchymal stem cells (MSCs); their potential paracrine effect confer MSCs with a major advantage to treat the immune and inflammatory disorders associated with neonatal infection. In this review, we summarize the basal properties and preclinical evidence of MSCs and explore the potential mechanisms of paracrine factors of MSCs for neonatal infection.

The investigation on antibiotic stewardship in neonatal intensive care unit in China is scarce. This study aimed to analyze the effect of a comprehensive 2-year antibiotic stewardship in a level 4 NICU. During this baseline period from October 1st 2017 to October 1st 2019, continuation of empirical antibiotic therapy for ruled-out sepsis courses was beyond 72 h and for pneumonia was more than 7 days. Meropenem or vancomycin was used even if they were not the only bacterial sensitive antibiotics. The intervention period was from October 2nd 2019 to August 23rd 2021. Three areas for quality improvement were targeted in our center: discontinuation of antibiotic use in ruled-out sepsis within 72 h, treatment duration for culture-negative pneumonia less than 7 days, and vancomycin or meropenem was not used unless the cultured bacteria was only susceptible to them. The total antibiotic consumption decreased from 791.1 to 466.3 days of therapy per 1000 patient days from baseline to intervention period. Antibiotics were stopped within 72 h for 47.48% patients with rule-out sepsis and within 7 days for 75.70% patients with pneumonia compared with 11.56% and 37.69% during the baseline period respectively. The prevalence of multi-drug resistance bacteria decreased from 67.20 to 48.90%. The total use rate of meropenem or vancomycin decreased from 7.6 to 1.8%. Our quality improvement approach on antibiotic strategy significantly reduced antibiotic use and prevalence of multi-drug resistance bacteria in our NICU.

To investigate histopathological placental lesions and adverse neonatal outcomes by Pre-eclampsia (PE) with Gestational Diabetes Mellitus (GDM).This was a retrospective cohort study of pregnancies with PE delivered between 1 January 2012 to 1 January 2014. Pregnant women with PE were recruited, and divided into PE with GDM (PE + GDM) group (The (PE + GDM) group was significantly associated with high placenta weight (534.8 ± 124.1 vs 519.3 ± 132.3 g,GDM increased the offspring's complication in pregnancy with PE, the potential mechanism might be that GDM increased the placenta inflammation.

Background: Platelets play an important role in the formation of pulmonary blood vessels, and thrombocytopenia is common in patients with pulmonary diseases. However, a few studies have reported on the role of platelets in bronchopulmonary dysplasia.Objective: The objective of the study was to explore the relationship between platelet metabolism and bronchopulmonary dysplasia in premature infants.Methods: A prospective case-control study was performed in a cohort of premature infants (born with a gestational age Results: A total of 252 premature infants were included in this study. Forty-eight premature infants developed BPD, 48 premature infants without BPD in the control group who were matched against the study infants for gestational age, birth weight, and admission diagnosis at the age of postnatal day 28. Compared with the controls, infants with BPD had significantly lower peripheral platelet count [BPD vs. controls: 180.3 (24.2) × 109/L vs. 345.6 (28.5) × 109/L, p = 0.001]. Circulating MK count in the BPD group was significantly more abundant than that in the control group [BPD vs. controls: 30.7 (4.5)/ml vs. 13.3 (2.6)/ml, p = 0.025]. The level of CD62p, CD63, and TPO in BPD group was significantly higher than the control group [29.7 (3.1%) vs. 14.5 (2.5%), 15.4 (2.0%) vs. 5.8 (1.7%), 301.4 (25.9) pg/ml vs. 120.4 (14.2) pg/ml, all p < 0.05]. Furthermore, the concentration of TPO was negatively correlated with platelet count in BPD group with thrombocytopenia.Conclusions: Our findings suggest that platelet metabolism is involved in the development of BPD in preterm infants. The possible mechanism might be through increased platelet activation and promoted TPO production by feedback.

Background: The role of serum LL37 in systemic inflammation has been confirmed, and the influence of it in umbilical cord blood to early-onset sepsis in preterm infants is currently being investigated.Results: The level of LL37 of sepsis group was higher than those of in control group (362.13±46.71 vs 248.13±83.30 ng/ml), the levels of CRP, WBC and MPV in sepsis group were higher than those of in control group (6.25±4.19 vs 2.89±2.77 mg/L; 17.60±12.35 vs 8.24±3.55×109/L; 11.10±1.11 vs 8.93±0.68 fL), the level of PLT was lower than those of in control group (175.20±38.51 vs 245.75±49.85×109/L) (P < 0.05). The expression of LL37 was negatively correlated with PLT (r = -0.9347, P < 0.0001), and positively correlated with MPV ((r =0.9463 , P < 0.0001), the expression of PLT was negatively correlated with MPV (r = -0.9641, P < 0.0001). The area under curve of LL37 for diagnosis of early-onset sepsis was 0.875, the prediction probability was 0.7, the sensitivity was 90.0% and the specificity was 80.0%.Conclusions：The higher level of LL37 in umbilical cord blood was associated with the development of early-onset sepsis in preterm infants.

Objective. ANGPTL7 is a member of the angiogenin-like protein family. Compared to other members, ANGPTL7 is the least known. Recent studies have explored the relationship between ANGPTL7 and multiple pathological processes and diseases. However, there is no research about ANGPTL7 in neonates. This study was designed to investigate the concentration of ANGPTL7 in cord blood of preterm infants. Method. Singleton infants born in November 2017 to June 2019 in the study hospital were enrolled in the study. Maternal and neonatal clinical data were collected. ANGPTL7 levels in cord blood and serum on the third day after birth were measured by an enzyme-linked immunosorbent assay. Result. A total of 182 infants were enrolled in this study. Patients were categorized into two groups by gestational age (102 preterm, 80 full-term). ANGPTL7 levels in preterm infants were significantly higher than that in full-term babies ( t = 15.4 , P < 0.001 ). In multiple line regression analysis, ANGPTL7 levels independently correlated with gestational age ( β = − 0.556 , P < 0.001 ). There is also no correlation between preterm outcomes and ANGPTL7 levels. Cord blood levels of ANGPTL7 were significantly higher than those in serum on the third day after birth ( t = 13.88 , P < 0.001 ). Conclusion. Cord blood ANGPTL7 levels are higher in preterm infants than full-term babies. The levels are independently influenced by gestational ages and attenuated significantly after birth. The underlying mechanism needs to be further studied.

ObjectiveTo investigate the effect of pathological staging of chorioamnionitis (CA) on complications in preterm infants;MethodsA single-center, retrospective study was conducted to choose singleton preterm infants (gestational age ResultsA total of 221 preterm infants were enrolled, including 186 cases in non-amnionitis group and 35 cases in amnionitis group. The gestational age of amnionitis group (32.00 ± 2.71 weeks) was significantly lower than non-amnionitis group (34.14 ± 2.06 weeks), birth weight (1.93 ± 0.64 kg) was significantly lower than that of non-amnionitis group (2.26 ± 0.58 kg), and the hospital stay in amnionitis group was significantly longer (25.71 ± 19.23 days), all of the difference above was statistically significant(P P = 0.002), and the risk of IVH was significantly increased by amnionitis (OR = 3.636, 95%CI: 1.632–8.102); after correction of gestational age, birth weight and thrombocytopenia, the risk of IVH was still significantly increased (OR = 2.471,P = 0.046, 95% CI: 1.015–6.015). And the late-onset IVH was more common (P = 0.009).ConclusionAmnionitis leads to a significant reduction in gestational age and birth weight in preterm infants, and it is an independent risk factor for IVH.

Objective: To explore the relationship between platelet metabolism and bronchopulmonary dysplasia in premature infants. Methods: A prosepective case-control study was performed in a cohort of premature infants (born with a gestational age less than 33 weeks and a birth weight less than 1500 grams) between June 2017 and June 2018. Subjects were stratified into two groups according to the diagnostic of bronchopulmonary dysplasia: with bronchopulmonary dysplasia (BPD group) and without bronchopulmonary dysplasia (control group). Platelet count, circulating megakaryocyte count (MK), platelet activating markers (CD62P and CD63), thrombopoietin (TPO) were recorded and compared in two groups, then, serial thrombopoietin levels and concomitant platelet counts were measured in infants with BPD. Results: A total of 252 premature infants were included in this study. 48 premature infants developed BPD, 48 premature infants in the control group who were matched with 1:1 according to gestational age, birth weight and admission diagnosis at their age of postnatal day 28. Compared to the controls, infants with BPD had significantly lower peripheral platelet count[BPD vs controls: 180.3 (24.2) x 109/L vs 345.6 (28.5) x 109/L, p=0.001], Circulating MK count in the BPD group was significantly more abundant than that in the control group [BPD vs controls: 30.7 (4.5) /mL vs 13.3 (2.6) /mL, p=0.025], The level of CD62p, CD63 and TPO in BPD group were significantly higher in control group ［29.7 (3.1)% vs 14.5 (2.5)%，15.4(2.0)% vs 5.8(1.7)%，301.4 (25.9) pg /mL vs 120.4 (14.2) pg/mL，all P < 0. 05］,furthermore, the concentration of TPO was negatively correlated with platelet count in BPD group with thrombocytopenia. Conclusions: Thrombocytopenia and platelet activation in premature infants with bronchopulmonary dysplasia may be related to lung microvascular endothelial cell injury. Thrombopoietin maybe the major regulator in thrombocytopoiesis and platelet homeostasis of infants with BPD.

Congenital leukemia (CL), defined as manifestations of leukemia within the first 4 weeks of life, is a rare condition with an estimated incidence of only 1 to 5 per million live births. Despite extensive research and the clinical application of new therapies, the prognosis of CL remains poor. Few large-scale studies have investigated the factors affecting the outcomes of infants with CL. Here, we conducted a retrospective study and analysis of CL cases published in the English language from 1 January 2001 to 1 May 2016. Our goal was to provide updated information about this rare disease and to investigate factors that may affect the outcomes of patients with CL.

【Abstact】 Objective: To investigate the effect of pathological staging of chorioamnionitis (CA) on complications in preterm infants; Methods: A single-center, retrospective study was conducted to choose singleton preterm infants in our hospital from December 2016 to December 2017. The basic data and placental pathological results were retrospectively collected. The patients were divided into 4 groups according to the placental pathological results, the incidence of common complications in preterm infants in each group was compared, and analyzed the influence of pathological staging of CA on the complications. Further, CA 0/I phase was combined into non-amnitis group, CA II/III phase was combined into amnitis group, gestational age and birth weight were corrected, logistic regression was used to analyze the effects on complications whether inflammation infiltrated amnion according to odds ratio (OR) value. Results: A total of 221 preterm infants were enrolled, including 84 cases of non-chorioamnionitis(CA0), 102 cases of CAI, 30 cases of CAII, and 5 cases of CAIII. The gestational age of CA II and III groups was lower than CA 0 and I, birth weight was lower than that of CA 0 and I, and the hospital stay in CA II and III was longer (P

Preterm birth and its complications are the leading cause of neonatal death. The main underlying pathological mechanisms for preterm complications are disruption of the normal maturation processes within the target tissues, interrupted by premature birth. Cord blood, as a new and convenient source of stem cells, may provide new, promising options for preventing preterm complications. This prospective, nonrandomized placebo controlled study aimed at investigating the effect of autologous cord blood mononuclear cells (ACBMNC) for preventing preterm associated complications. Preterm infants less than 35 weeks gestational age were assigned to receive ACBMNC (5 × 107 cells/kg) intravenous or normal saline within 8 hours after birth. Preterm complication rates were compared between two groups to demonstrate the effect of ACBMNC infusion in reducing preterm complications. Fifteen preterm infants received ACBMNC infusion, and 16 infants were assigned to the control group. There were no significant differences when comparing mortality and preterm complication rates before discharge. However, ACBMNC infusion demonstrated significant decreases in duration of mechanical ventilation (3.2 days vs 6.41 days, P = .028) and oxygen therapy (5.33 days vs 11.31 days, P = .047). ACBMNC infusion was effective in reducing respiratory support duration in very preterm infants. Due to the limited number of patients enrolled, powered randomized controlled trials are needed to better define its efficacy., Autologous cord blood cells infusion in preterm neonates safely reduces respiratory support duration and potentially preterm complications.

Intrauterine inflammation is the main reason for neonatal adverse outcomes and normal placenta perfusion plays an important role in fetal development. However, whether inflammation will affect placental angiogenesis and the underlying mechanism are still poorly understood. To investigate lipopolysaccharide (LPS)-induced intrauterine inflammation on placenta angiogenesis and Wnt5a-Flt1 expression. LPS-induced intrauterine inflammation rat model was established. Preterm rat outcomes were analyzed and angiogenesis of placenta villi was calculated by immunohistochemistry (IHC) of CD34 staining, and placenta Wnt5a-Flt1 expression was detected by western blot and IHC. Compared to control group, neonatal rats in LPS group showed higher death rate (1.4% vs 10.1%, p

Background. Preterm birth complications are one of the leading causes of death among children under 5 years of age. Despite advances in medical care, many survivors face a lifetime of disability, including mental and physical retardation, and chronic lung disease. More recently, both allogenic and autogenic cord blood cells have been applied in the treatment of neonatal conditions such as hypoxic-ischemic encephalopathy (HIE) and bronchopulmonary dysplasia (BPD). Objective. To assess the safety of autologous, volume- and red blood cell- (RBC-) reduced, noncryopreserved umbilical cord blood (UCB) cell infusion to preterm infants. Method. This study was a phase I, open-label, single-arm, single-center trial to evaluate the safety of autologous, volume- and RBC-reduced, noncryopreserved UCB cell (5 × 107cells/kg) infusion for preterm infants Results. After processing, (22.67 ± 4.05) ml UCB cells in volume, (2.67 ± 2.00) × 108 cells in number, with (22.67 ± 4.05) × 106 CD34+, (3.72 ± 3.25) × 105 colony forming cells (CFU-GM), and (99.7 ± 0.17%) vitality were infused to 15 preterm infants within 8 hours after birth. No adverse effects were noticed during treatment. All fifteen patients who received UCB infusion survived. The duration of hospitalization ranged from 4 to 65 (30 ± 23.6) days. Regarding preterm complications, no BPD, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP) was observed. There were 1/15 (7%) infant with intraventricular hemorrhage (IVH), 5/15 (33.3%) infants with ventilation-associated pneumonia, and 10/15 (66.67%) with anemia, respectively. Conclusions. Collection, preparation, and infusion of fresh autologous UCB cells to preterm infants is feasible and safe. Adequately powered randomized controlled studies are needed.

Rationale: Necrotizing fasciitis (NF) is a life-threatening situation that is rare in children, especially infants, and early diagnosis is challenging. Timely identification and broad-spectrum antibiotic and supportive treatment before surgical debridement are very important for survival and may reduce scar formation. Patient concerns: A previously healthy 4-month-old infant was admitted to our pediatric intensive care unit (PICU) with a history of fever and cough for 5 days and extreme swelling of the scrotum for one day. Necrotic-like tissue without margins appeared on his scrotum and perineum in 24 hours. Diagnosis: NF was suspected, and the patient soon developed shock. The patient underwent surgical debridement after his condition stabilized. Pathological analysis confirmed the diagnosis of NF. Intervention: Broad-spectrum antibiotic, immediate fluid resuscitation, assistant ventilation, and vasoactive drugs were administered. Surgical debridement and autologous split-thickness skin grafting were performed. Outcomes: The wound recovered well after 2 months. Ultrasound revealed normal testicles, and no anorectal injury was found. Lessons: Close clinical monitoring and timely treatment of skin injuries in sick children are very important. Sufficient antibiotic administration and supportive treatment before surgical debridement are crucial for survival from NF.