Case Report: A case report and literature review of hemoglobin variation associated with neonatal cyanosis.

We will discuss a recent case of unexplained neonatal cyanosis, evaluate its origin, clinical presentation, diagnosis, and treatment, and share with you some of our clinical insights. We report a transient cyanosis in a newborn due to a mutation in the globulin gene (HBG2), as well as diagnosis and treatment. Clinically, the infant was in good overall health, and despite low oxygen saturation, the arterial oxygen partial pressure was always normal. Early respiratory support includes mechanical ventilation, nasal tube oxygen, and eventually stopping oxygen therapy. With the above treatment measures, the blood oxygen saturation of the child always fluctuated at 85%, but the arterial blood oxygen partial pressure was up to 306 mmHg. Further improvement of laboratory tests revealed elevated methemoglobin levels, reticulocytosis, mild anemia, and basically normal on chest x-ray and echocardiography. To clarify the etiology, WES testing was performed. The results showed heterozygous variation in HBG2 gene (c.190C>T. p.H64Y). There is heterozygous variation at this site in the proband father, and no variation at this site in the proband mother. Given the age of the affected infants, we hypothesized that the mutation originated in the gamma peptide chain of the head protein. The baby was discharged from the hospital 10 days after birth, with blood oxygen saturation fluctuating around 90%. The cyanosis disappeared 2 months after discharge, and the blood oxygen saturation level returned to normal.

A novel compound heterozygous mutation of the CLCN7 gene is associated with autosomal recessive osteopetrosis.

Osteopetrosis is a genetic condition of the skeleton characterized by increased bone density caused by osteoclast formation and function defects. Osteopetrosis is inherited in the form of autosomal dominant and autosomal recessive manner. We report autosomal recessive osteopetrosis (ARO; OMIM 611490) in a Chinese case with a history of scarce leukocytosis, vision and hearing loss, frequent seizures, and severe intellectual and motor disability. Whole-exome sequencing (WES) followed by Sanger sequencing revealed novel compound heterozygous mutations in the chloride channel 7 (CLCN7) gene [c.982-1G > C and c.1208G > A (p. Arg403Gln)] in the affected individual, and subsequent familial segregation showed that each parent had transmitted a mutation. Our results confirmed that mutations in the CLCN7 gene caused ARO in a Chinese family. Additionally, our study expanded the clinical and allelic spectrum of the CLCN7 gene and enhanced the applications of WES technology in determining the etiology of prenatal diagnoses in fetuses with ultrasound anomalies.

Pollen-Inspired Shell-Core Aerosol Particles Capable of Brownian Motion for Pulmonary Vascularization.

Nebulization is the most widely used respiratory delivery technique with non-invasive properties. However, nebulized drugs often fail to function due to the excretion and immune clearance of the respiratory system. In this work, inspired by pollen in nature, novel shell-core aerosol particles (APs) capable of Brownian motion are constructed for respiratory delivery. Drugs-loaded poly(lactic-co-glycolic acid) nanoparticles are prepared by emulsification to form the inner core, and the membranes of macrophages are extracted to form the outer shell. The optimized size and the shell-core structure endow APs with Brownian motion and atomization stability, thus enabling the APs to reach the bronchi and alveoli deeply for effective deposition. Camouflaging the macrophage membranes equips the APs with immune evasion. In vitro experiments prove that deferoxamine (DFO)-loaded APs (DFO@APs) can promote the angiogenesis of human umbilical vein endothelial cells. A hyperoxia-induced bronchopulmonary dysplasia (BPD) model is constructed to validate the efficiency of DFO@APs. In BPD mice, DFO@APs can release DFO in the alveolar interstitium, thus promoting the reconstruction of microvasculature, ultimately inducing lung development for treating BPD. In conclusion, this study develops "pollen"-inspired shell-core aerosol particles capable of Brownian motion, which provides a novel idea and theoretical basis for respiratory administration.

Discrimination of serum metabolomics profiles in infants with sepsis, based on liquid chromatography-mass spectrometer.

Sepsis is one of the most important problems to be addressed in pediatrics, characterized by insidious onset, rapid progression, and high rates of severe infection and even mortality. Biomarkers with high sensitivity and robustness are urgently required for the early diagnosis of infant sepsis. Serum metabolomic approaches based on liquid chromatography-mass spectrometry were used to analyze the samples from 30 infants with sepsis at an early stage and 30 infants with noninfectious diseases. Multivariate statistical analysis was used to screen for differential metabolites and ROC curves were generated to find potential biomarkers. Six metabolites, including phosphatidic acid (PA (8:0/14:0)), phosphatidyl ethanolamine (PE (16:0/18:2(9Z,12Z))), cytidine 5'-diphosphocholine (CDP-CHO), sphingomyelin (SM (d18:0/16:1(9Z))), prolylhydroxyproline and phosphorylcholine (P-CHO), were identified between the two groups. ROC curve analysis showed that prolylhydroxyproline (AUC = 0.832) had potential diagnostic values for infant sepsis. The AUC value was 0.859 (CI: 0.764, 0.954) in the combined model. Prolylhydroxyproline were found to be correlated with CRP and PCT levels, while PE and CDP-CHO associated with PCT levels. Pathway analysis indicated that glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis and necroptosis pathways played important roles in infant sepsis. Network analysis showed that the differential metabolites were linked to ERK/ MAPK, NF-κB, AMPK, mTOR, and other classical inflammatory and metabolic signaling pathways. This study identified serum metabolite profiles and three metabolites as potential biomarkers in infants with sepsis. The findings will help improve the early diagnosis of sepsis in infants.

[Efficacy and safety of lactase additive in preterm infants with lactose intolerance: a prospective randomized controlled trial].

OBJECTIVE: To study the efficacy and safety of lactase additive in improving lactose intolerance in preterm infants. METHODS: A total of 60 preterm infants with lactose intolerance who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2019 were randomly divided into a lactase treatment group and a control group, with 30 infants in each group. The infants in the lactase treatment group were given 4 drops of lactase additive (180 mg) added into preterm formula or breast milk, and those in the control group were given placebo, oral administration of probiotics (live combined Bifidobacterium, Lactobacillus and Enterococcus powder) at half an hour after feeding (1 g each time, twice a day), and clockwise abdominal massage around the belly button at 1 hour after feeding for 15 minutes each time, 3 times a day. Fecal pH, fecal reducing sugar, growth indicators, symptoms of lactose intolerance, and laboratory markers were measured at the end of the first and second weeks after intervention. RESULTS: Finally 29 infants in the lactase treatment group and 26 infants in the control group completed the trial. At the end of the first week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and gastric retention amount (P < 0.05) and a significantly higher proportion of infants with fecal pH > 5.0 (P < 0.05). At the end of the second week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and 24-hour abdominal circumference difference (P < 0.05) and a significantly higher proportion of infants with the absence of gastric retention, fecal pH > 5.0, or negative reducing sugar in feces (P < 0.05). No adverse reactions associated with the lactase additive or probiotics were observed during the trial. CONCLUSIONS: Lactase additive can safely and effectively improve the clinical symptoms caused by lactose intolerance in preterm infants.

Increased serum levels of IL-33 and soluble ST2 in neonates with human cytomegalovirus infection.

Interleukin 33 (IL-33) and soluble form of ST2 (sST2) are involved in inflammation. This study aimed to assess the role of serum IL-33 and sST2 in neonates with HCMV infection. The concentration of serum IL-33 and sST2 in 20 patients and 16 healthy controls were measure by enzyme-linked immune-sorbent assay (ELISA). The clinical and laboratory data were described. Our results showed serum sST2 and IL-33 levels were significantly higher in the HCMV group than the control group. Significant positive correlation was observed between sST2 and IL-33 (r = 0.518, P = 0.001). Furthermore, there was a positive, moderate, and statistically significant correlation between sST2 and ALT levels in the control and HCMV groups (r = 0.579, P = 0.007; r = 0.66, P = 0.005, respectively). The AUC of sST2 and IL-33 was found to be 0.822 and 0.867 respectively. Further, at a cut-off value of 1823.4 ng/mL, sST2 gave 65% sensitivity and 93.7% specificity. Similarly, IL-33 gave 95% sensitivity and 68.7% specificity at a cut-off value 2.04 pg/mL. The Youden index of sST2 and IL-33 was found to be 0.587 and 0.637, respectively. In conclusion, this study revealed that sST2 and IL-33 have great potential to be used as biomarkers for early screening and indicate liver damage for HCMV patients in future after validation in large cohort study.

Aerosolized deferoxamine administration in mouse model of bronchopulmonary dysplasia improve pulmonary development.

Bronchopulmonary dysplasia (BPD) is the most common complication in preterm newborns. It occurs due to early exposure to high-oxygen and ventilation therapy. The mechanisms of disrupted alveolarization and vascular development associated with BPD were unclear. Deferoxamine (DFO) has been reported to reduce mortality and lung injury in mice after chlorine exposure. The effect of DFO in the treatment of BPD has not been explored. This study aimed to investigate the effect of aerosolized DFO administration in a mouse model of BPD. A mouse model of oxygen-induced BPD was established by postnatal hyperoxia (75% oxygen for 7 days) and DFO [17 mg/(kg·day)] (BPD+D) or aerosolized vehicle (BPD+V) administered for 14 days. The mice were anesthetized and sacrificed after 14 days treatment before removing the lungs for analysis. An exogenous continuous aerosol of DFO exerted a biological effect on BPD mice. The BPD+DFO group showed a better weight gain compared with the BPD+V group. Furthermore, the treatment of DFO exhibited a reduced pathological severity and increase expression of hypoxia-inducible factor (HIF)-1α and CD31, and activated downstream vascular endothelial growth factor (VEGF)-induced angiogenesis. The results showed that C57BL/6 mice exposed to hyperoxic environment and treated with aerosolized of DFO solution, obviously promoted the pulmonary vascularization and alveolarization. The HIF-1α/VEGF signaling pathway mediated this process. The findings indicated that treatment with an exogenous continuous aerosol of DFO might be a potential therapeutic strategy for BPD.

[A 5-year retrospective clinical study of perinatal cytomegalovirus infection].

OBJECTIVE: To investigate the incidence, clinical features, and treatment of perinatal cytomegalovirus (CMV) infection, as well as the factors affecting the therapeutic effect of ganciclovir. METHODS: The clinical data of 237 infants who were hospitalized and diagnosed with perinatal CMV infection from 2008 to 2012 were retrospectively analyzed. RESULTS: The clinical features of infants with perinatal CMV infection and the proportion of such infants in all hospitalized infants showed no significant differences across the five years. In most infants, two or more systems were involved, and CMV hepatitis plus CMV pneumonia was most common (43.1%). The results of pathogen detection showed that the percentage of the infants with positive blood CMV-IgM and blood/urine CMV-DNA was 3.8%, while 90.3% of all infants had positive blood CMV-IgM alone and 5.9% had positive blood/urine CMV-DNA alone. A total of 197 infants were treated with ganciclovir, and the cure rate was 88.3%. An abnormal history of pregnancy (OR=6.191, 95% CI: 1.597-24.002) and liver involvement before medication (OR=3.705, 95% CI: 1.537-8.931) were the independent risk factors affecting the therapeutic effect of ganciclovir in infants with perinatal CMV infection. CONCLUSIONS: The epidemiological characteristics of perinatal CMV infection have remained generally stable for the last 5 years. CMV often involves several organs or systems, especially the liver and lung. Ganciclovir has a significant efficacy in the treatment of perinatal CMV infection, and an abnormal history of pregnancy and liver involvement before medication can increase the risk of ganciclovir resistance in infants with perinatal CMV infection.

High mobility group box 1-mediated autophagy promotes neuroblastoma cell chemoresistance.

Neuroblastoma (NB) is one of the most common tumors in childhood. Unfortunately, the survival outcomes remain unsatisfactory since NB commonly develops multidrug resistance. Recent studies have demonstrated that the high mobility group box 1 (HMGB1)-mediated autophagy promotes chemoresistance in osteosarcoma, lung adenocarcinoma and ovarian cancer, but the exact molecular mechanism underlying HMGB1-mediated autophagy in NB has not been clearly defined. In the present study, we investigated the role of HMGB1 in the development of resistance to anticancer agents in NB. Anticancer agents including doxorubicin, cisplatin and etoposide each induced HMGB1 upregulation, promoted cytosolic HMGB1 translocation and the elevation of autophagic activity in human NB cells. RNA interference-mediated knockdown of HMGB1 restored the chemosensitivity of NB cells. Furthermore, mechanistic investigation revealed that HMGB1 promoted the proliferative activity and invasive potential of NB cells. HMGB1 enhanced drug resistance by inducing Beclin-1-mediated autophagy, an intracellular self-defense mechanism known to confer drug resistance. In addition, we found that HMGB1 facilitated autophagic progression and reduced oxidative stress induced by doxorubicin. Therefore, through its role as a regulator of autophagy, HMGB1 is a critical factor in the development of chemoresistance and tumorigenesis, and it may be a novel target for improving the efficacy of NB therapy.

Integrated measures for prevention of invasive Candida infections in preterm infants in a Chinese neonatal intensive care unit.

BACKGROUND: The increasing incidence of invasive Candida infections (ICIs) in preterm infants in the neonatal intensive care unit (NICU) of Xinhua Hospital aroused our concern. We undertook a retrospective study to evaluate the efficacy of different preventive measures for ICI in preterm infants. METHODS: Preterm infants with gestational age (GA) <33 weeks admitted between 2010 and 2013 were divided into 3 groups according to the preventive measures applied in different periods: the control group (CG), fluconazole group (FG), and integrated measures group (IMG). We analyzed the incidence of ICI and distribution of fungal pathogens in these 3 groups, and also evaluated the efficiency of various measures in preventing ICIs in preterm infants. RESULTS: The study sample comprised 261 preterm infants born at <33 weeks GA, including 94 in the CG, 99 in the FG, and 68 in the IMG. The differences among the groups were not significant at baseline. ICI developed in 41 of the 261 infants (15.7%). The incidence of ICI varied significantly among the groups: 22.3% in the CG (21/94), 18.2% in the FG (18/99), and only 2.9% in the IMG (2/68) (P = .003). ICI was less frequent in the IMG compared with the CG (P <.001) and the FG (P = .003). CONCLUSIONS: The integrated measures approach is meaningful for the prevention of ICIs in preterm infants in NICUs with many patients but inadequate medical resources in some developing countries.

The c-Jun N-terminal kinase inhibitor SP600125 inhibits human cytomegalovirus replication.

Human cytomegalovirus (HCMV) is an opportunistic pathogen that causes severe diseases in congenitally infected newborns and immunocompromised patients. Currently, no vaccine is available to prevent HCMV infection. Anti-viral drugs are limited by their side effects and drug resistance. In this study, by performing a medium-sized, anti-HCMV chemical screening, we identified SP600125, CC-401, and the c-Jun N-terminal kinase (JNK) inhibitor VIII, three structurally different small molecule JNK inhibitors that effectively inhibited HCMV replication in cultured human fibroblasts (HFs). SP600125 showed its potential by inhibiting the viral replication of a HCMV laboratory strain in HFs and a HCMV clinical strain in human retinal pigment epithelial cells. Knockdown of JNK expression by RNA interference significantly impaired HCMV replication, mimicking the effect of the chemical inhibitors on virus infection. Mechanistically, SP600125 affects a very early step of the viral life cycle. Viral binding, entry, and the delivery of viral DNA into the cells were not inhibited by the compound. Instead, it suppressed the transcription of the immediate-early viral genes IE1/2 and the accumulation of their gene products. IE1/2 are among the first genes expressed after viral entry, and they are the master regulators of late phase viral gene expression. Consistent with this notion, the expression of other viral genes was also reduced after SP600125 treatment. We propose that JNK inhibitors have the potential to become a new class of anti-HCMV drug candidates, and JNK is a feasible target for the development of anti-HCMV drugs.

Dried blood spots PCR assays to screen congenital cytomegalovirus infection: a meta-analysis.

The performance of dried blood spots (DBS) polymerase chain reaction (PCR) assays in screening for congenital cytomegalovirus (cCMV) infection varies between different studies. To determine whether the DBS PCR assay has sufficient accuracy to be used as a screening test for cCMV infection, we performed a meta-analysis of 15 studies (n = 26007 neonates) that evaluated the performance of DBS PCR tests in screening for cCMV infection and that met our inclusion criteria. The pooled sensitivity and specificity were 0.844 (95% CI = 0.812-0.872) and 0.999 (95% CI = 0.998-0.999), respectively, and the diagnostic odds ratio was 1362.10 (95%CI = 566.91-3272.60). As sensitivity analysis showed that the results were robust. In conclusion, the performance of DBS PCR assays for testing cCMV was more suitable for retrospective diagnosis than screening.

[Effects of ribavirin aerosol on viral exclusion of patients with hand-foot-mouth disease].

OBJECTIVE: To explore the roles of ribavirin aerosol in the prevention and treatment of hand-foot-mouth disease (HFMD). METHODS: For this prospective, multicenter, randomized, double-blind and placebo-controlled trial, a total of 300 HFMD outpatients from 3 class 3A hospitals from July 2011 to June 2013 were divided into treatment (ribavirin aerosol) and control (placebo) groups (n = 150 each). The age range was 6 months to 6 years. The proportion of male and female was 1.5: 1. Temperature, herpes of mouth and skin rash were observed before and after treatments. Before treatment and 6-7 days after, their specimens of throat swab were collected and the levels of EV71 and CA16 detected with reverse transcription (RT)-PCR. The software SAS 9.2 was used for statistic data analyses. RESULTS: Before treatment, no significant statistical difference existed in parameters between treatment and control groups (all P > 0.05). After treatment, the degree of herpes of mouth and papulovesicle of skin in treatment group was better than that in control group (100.0% (147/147) vs 83.9% (120/143), χ(2) = 109.21, P < 0.01); (100.0% (147/147) vs 95.9% (139/145) , χ(2) = 6.38, P < 0.05) . The virus negative conversion rates had significant inter-group difference (80.0% (102/110) vs 41.8% (41/98) , χ(2) = 37.06, P < 0.01). The temperature, compliance and differences were not significant (all P > 0.05). The effective rate of comprehensive efficacy in treatment group was higher than that in control group (93.9% (122/130) vs 52.0% (64/123), χ(2) = 111.08, P < 0.01). No obvious adverse drug reaction was observed. CONCLUSIONS: Ribavirin aerosol has multiple advantages of lower dose, quicker onset, higher local concentration, better clinical efficacy and fewer side-effects. Its therapeutic effect for local lesion is better than that for systemic lesion. Thus it may shorten the duration of oropharyngeal and skin lesions and lower the number and time of viral release.

[Effects of extensively hydrolyzed protein formula on feeding and growth in preterm infants: a multicenter controlled clinical study].

OBJECTIVE: To study the effects of extensively hydrolyzed protein formula (eHF) on the feeding and growth in preterm infants through a multicenter controlled clinical study. METHODS: Preterm infants admitted to eight upper first-class hospitals in China between February 2012 and December 2013 were randomly selected. They were divided into two observation groups and two control groups. The first observation group consisted of preterm infants with a gestational age of <32 weeks, who were fed with eHF for 10-14 days after birth and then with standard preterm formula (SPF) until discharge. The second observation group consisted of preterm infants with a gestational age of 32-34 weeks, who were fed with SPF after birth, but were switched to eHF (7-14 days) if suffering feeding intolerance at 6-8 days after birth. The two control groups with corresponding gestational ages kept to be fed with SPF after birth. Clinical data were recorded to compare feeding condition, physical growth, blood biochemical indices, and major complications between different groups. RESULTS: A total of 328 preterm infants were enrolled. Preterm infants with a gestational age of <32 weeks in the observation group had a significantly shorter meconium evacuation time than in the corresponding control group (P<0.05). They also had significantly lower levels of serum total bilirubin at weeks 1 and 2 after birth compared with the control group (P<0.05). The observation group needed more time in reaching enteral nutrition (EN) basic energy uptake of 50 kcal/(kg·d), partial parenteral nutrition (PPN), hospitalization, and corrected gestational age at discharge compared with the controlled infants (P<0.05). There was no difference in the incidence of extrauterine growth retardation (EUGR) at discharge between the two groups (P>0.05). Preterm infants with a gestational age of 32-34 weeks in the observation group had significantly lower serum total bilirubin levels at 2 weeks after birth compared with the corresponding control group (P<0.05). They required more time in achieving EN basic energy and PPN than in the control group (P<0.05). There was no difference in the incidence of EUGR at discharge between the two groups (P>0.05). CONCLUSIONS: For preterm infants, eHF can improve gastrointestinal motility, accelerate bilirubin metabolism and excretion and does not increase the incidence of EUGR.

Interleukin-10 blocks in vitro replication of human cytomegalovirus by inhibiting the virus-induced autophagy in MRC5 cells.

BACKGROUND: Interleukin-10 is an important cytokine that regulates immune response. Previous studies have shown that human cytomegalovirus can trigger cell autophagy during the early stages of infection. To our knowledge, whether IL-10 inhibits HCMV-induced autophagy and virus replication has not been studied previously. OBJECTIVES: We investigated whether IL-10 affects cell viability and autophagy under the conditions of starvation and HCMV infection by using the MRC5 cell line. We also explored the role of IL-10-mediated autophagy on HCMV replication. RESULTS: Our data showed that IL-10 inhibited the autophagic flux of the MRC5 cells irrespective of starvation or HCMV infection, and suppressed HCMV replication. The promotion of autophagy with either a pharmacological inducer (rapamycin), or a technique to over-express the BECN1 gene reversed the effect of IL-10 on virus replication. Furthermore, the PI3K/Akt signal pathway was activated when the cells were pretreated with IL-10. CONCLUSIONS: Our results indicated that IL-10 can suppress HCMV replication by inhibiting autophagy in host cells during the early stages of infection.

[Efficacy and safety of ribavirin aerosol in children with hand-foot-mouth disease].

OBJECTIVE: To evaluate the efficacy and safety of ribavirin aerosol in children with hand-foot-mouth disease (HFMD). METHODS: A randomized, double-blind, placebo-controlled trial was performed. A total of 119 children with mild HFMD were randomly divided into an observed group (n=59) and a control group (n=60). In the observed group, ribavirin aerosol was given four times within the first hour, followed by once every other hour for the remaining time of the day and day 2; from days 3 to 7, it was given 4 times per day, with 2-3 sprays every time, for 7 days. In the control group, placebo was given in the same way as in the observed group. Additionally, both groups used oral antiviral liquid. The scores of clinical symptoms including oral ulcer, skin rash, nasal congestion, runny nose, sneezing, cough, and fever before and after treatment were recorded to evaluate treatment outcomes. Throat swabs were taken before treatment and 5-7 days after treatment to measure viral load by RT-PCR and to compare the negative conversion rate between the two groups. RESULTS: Fifty-seven patients in the observed group and 56 patients in the control group were tested according to the original research design. After 5-7 days of treatment, the observed group had a significantly higher overall negative conversion rate of enterovirus than the control group (P<0.01). The overall marked response rate and overall response rate of the observed group were 89% and 89%, respectively, significantly higher than those of the control group (29% and 43%). During treatment, there were no adverse reactions such as dizziness, vomiting, and notable decreases in hemoglobin, white blood cells, and platelets in the two groups. CONCLUSIONS: Ribavirin aerosol can be effectively and safely used for treating mild HFMD. With low dosage and few adverse reactions, it holds promise for clinical application.

Dose-related regulatory effect of intravenous immunoglobulin on dendritic cells-mediated immune response.

CONTEXT: Intravenous immunoglobulin (IVIG) has been successfully applied in immune-related diseases of adults and neonates, such as human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE). OBJECTIVE: This study aims to investigate the distinct impacts of IVIG on cultured dendritic cells (DCs) from newborn and healthy adult. MATERIALS AND METHODS: Blood samples were collected from eight full-term newborns and eight healthy adult volunteers. DCs from cord blood and peripheral blood were both cultured in the RPMI 1640 medium containing 10% fetal calf serum, 50 ng/ml granulocyte/macrophage colony-stimulating factor (GM-CSF) and 10 ng/ml recombinant human interleukin-4 (rhIL-4) for 5 d with therapeutic IVIG (20 mg/ml) or physiological IVIG (10 mg/ml). Lipopolysaccharides (LPSs, 1 µg/ml) were added on the fifth day to induce the maturation of immature DCs. The phagocytosis of monocytes, expression of MR (mannose receptor), CD14, CD1a, CD80, CD83, CD86 and MHC II were examined by flow cytometry. The expression of IL-4 mRNA was detected by RT-PCR, while IFN-γ, IL-12 and IL-10 were analyzed by enzyme-linked immunosorbent assay (ELISA) commercial kits. RESULTS: IVIG of therapeutic dose inhibited the phagocytosis, differentiation and maturation of DCs, whereas physiological dose exhibited an accelerated role in vitro, especially on DCs from neonates, but aroused different effects on cytokine secretion. DISCUSSION AND CONCLUSION: The different responses are generally due to immature immune system of neonate, which has a limit capacity to maintain immunity homeostasis. Modulation of DCs phagocytosis, differentiation, maturation and cytokine secretion by IVIG is of potential relevance to its dosage and immune status of patients.

3C3R modified PBL pediatric teaching of Chinese medical students.

A Content, Context, Connection and Researching, Reasoning, Reflecting (3C3R) model is a conceptual framework for problem-based learning (PBL) problem design. We introduced the 3C3R-PBL method into a pediatric teaching plan, and evaluated its effectiveness and feasibility. The 3C3R model was applied in a pediatric problem design teaching plan "why the lips turn purple when a baby is crying". All students were assigned either into a traditional PBL course or into a 9-step 3C3R model PBL course (3C3R-PBL). The performance outcomes of both groups were compared. For the PBL group, the proportion of students scoring ≥4 for content, context, and problem design connection, was 90.8%, 80.3%, and 64.5% respectively, while for tutors, it was 71.4%, 71.4%, and 28.6%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 81.6%, 55.3%, and 40.8%, while for tutors, it was 71.4%, 100%, and 57.1%. The learning difficulty was not considered high with only 31.6% of students and 42.9% of tutors rating the task as difficult. For the 3C3R-PBL group, the proportion of students scoring content, context, and connection, ≥4 was 100%, 98.4%, and 90.5%, while for tutors it was 100%, 100%, 83.3%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 95.2%, 88.9%, and 76.2%, while for tutors it was 100% for all 3 R components. Students and tutors were convinced by the content, case context, research process and reasoning process of both teaching plans, while scores for connection and reflecting were significantly improved when the PBL plan was amended by a 3C3R model (p<0.05) and the case learning difficulty was statistically increased (p<0.05). The 3C3R model, evaluated for the first time in China, was helpful for effective and reliable problem design in a pediatric PBL teaching plan for Chinese students.

Incidence of brain injuries in premature infants with gestational age ≤ 34 weeks in ten urban hospitals in China.

BACKGROUND: There is a large number (1.5 million per year) of premature births in China. It is necessary to obtain the authentic incidences of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), the common brain injuries, in Chinese premature infants. The present multicenter study aimed to investigate the incidence of brain injuries in premature infants in ten urban hospitals in China. METHODS: The research proposal was designed by the Subspecialty Group of Neonatology of Pediatric Society of the Chinese Medical Association. Ten large-scale urban hospitals voluntarily joined the multicenter investigation. All premature infants with a gestational age ≤ 34 weeks in the ten hospitals were subjected to routine cranial ultrasound within three days after birth, and then to repeated ultrasound every 3-7 days till their discharge from the hospital from January 2005 to August 2006. A uniform data collection sheet was designed to record cases of brain injuries. RESULTS: The incidences of overall IVH and severe IVH were 19.7% (305/1551) and 4.6% (72/1551), respectively with 18.4% (56/305) for grade 1, 58.0% (177/305) for grade 2, 17.7% (54/305) for grade 3 and 5.9% (18/305) for grade 4 in nine hospitals. The incidences of overall PVL and cystic PVL were 5.0% (89/1792) and 0.8% (14/1792) respectively, with 84.3% (75/89) for grade 1, 13.5% (12/89) for grade 2, and 2.2% (2/89) for grade 3 in the ten hospitals. The statistically significant risk factors that might aggravate the severity of IVH were vaginal delivery (OR=1.883, 95% CI: 1.099-3.228, P=0.020) and mechanical ventilation (OR=4.150, 95% CI: 2.384-7.223, P=0.000). The risk factors that might result in the development of cystic PVL was vaginal delivery (OR=21.094, 95% CI: 2.650-167.895, P=0.000). CONCLUSIONS: The investigative report can basically reflect the incidence of brain injuries in premature infants in major big cities of China. Since more than 60% of the Chinese population live in the rural areas of China, it is expected to undertake a further multicenter investigation covering the rural areas in the future.

Suppressive effects of intravenous immunoglobulin (IVIG) on human umbilical cord blood immune cells.

We investigated in vitro immunomodulatory effects of intravenous immunoglobulin (IVIG) on cord blood mononuclear cells (CBMNC), macrophages, dendritic cells and CD3(+) T cells were isolated from umbilical venous blood. Cell proliferation used (3)H-TdR incorporation, culture supernatants were assayed for cytokines using ELISA, and surface marker expressions were determined by flow cytometry. IVIG suppressed CBMNCs and CD3(+) T-cells proliferation, secretions of IL-10, INF-γ and TGF-ß(1), but not IL-4, and PHA-induced expressions of surface molecules (CD25, CD45RA and CD45RO), with more pronounced effects for CBMNCs. IVIG decreased cord blood (CB) macrophage phagocytosis and CD14, HLA-DR and CD86 expressions. IVIG increased CD14 expression and decreased MCH II expression for differentiation-stage CB dendritic cells (DCs) and increased CD14 expression and decreased CD80 and CD83 expressions of mature DCs, suggesting that IVIG intervention inhibited DC differentiation and maturation. In addition to T cells, IVIG immunomodulatory effects on CBMNCs involve a variety of cells and molecules. CB macrophages and CBMNC-DCs are targets of IVIG.