Neonatal-onset primary mitochondrial disease caused by nuclear gene mutations: a report of 4 cases / 中国新生儿科杂志

Objective:To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease (PMD) caused by nuclear gene mutations.Methods:From May 2020 to March 2022, the clinical data, genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results:A total of 4 patients were enrolled, all with hyperlactatemia and metabolic acidosis. In case 1, the fetal cranial MRI showed agenesis of corpus callosum. In case 2, echocardiography after birth indicated hypertrophic cardiomyopathy. Whole exome sequencing found the following mutations: EARS2 nuclear gene c.1294C>T and c.971G>T variants, COA6 nuclear gene c.411_412insAAAG variant, ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants, FOXRED1 nuclear gene c.1054C>T and c.3dup variants. Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities. Cases 1 and 3 died during the neonatal period. Case 2 died at 2-year-and-2-month of age. Case 4 was followed up to 1 year of age with developmental delay.Conclusions:The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia, refractory metabolic acidosis and cardiomyopathy, which have a poor prognosis. Proactive genetic tests are helpful for early diagnosis.

Clinical analysis of different types of neonatal sepsis: a multi-center retrospective study / 中国新生儿科杂志

Objective:To study the clinical characteristics of different types of neonatal sepsis.Methods:From January 2012 to December 2019, neonates with confirmed sepsis from 5 neonatal centers of central-south China were reviewed. The neonates were assigned into early-onset sepsis (EOS) and late-onset sepsis (LOS) group, and the latter was further subgrouped into hospital-acquired LOS (hLOS) group and community-acquired LOS (cLOS) group. The etiological and clinical characteristics were analyzed. SPSS 26.0 was used for statistical analysis.Results:A total of 580 neonates were enrolled, including 286 (49.3%) in the EOS group and 294 (50.7%) in the LOS group. In LOS group, 147 were in hLOS group and 147 were in cLOS group. The gestational age and birth weight of hLOS group were significantly lower than the other two groups [(32.7±3.6) weeks vs. (37.1±3.7) weeks and (37.7±3.0) weeks, (1 810±717) g vs. (2 837±865) g and (3 024±710) g] ( P<0.05). The common pathogens in EOS and cLOS groups were coagulase-negative staphylococci and Escherichia coli, while Klebsiella pneumoniae was common in hLOS group. Carbapenems usage in the hLOS group was significantly higher than the other two groups [62.6% vs. 28.7% and 16.2%] ( P<0.05). Antibiotics duration in the hLOS group was longer than the other two groups [19 (14, 27) d vs. 15 (12, 20) d and 14 (12, 19) d] ( P<0.05). Conclusions:The clinical characteristics of neonatal sepsis vary among different types of infections, and it is necessary to establish appropriate prevention, control, diagnosis and treatment protocols.

Effects of human milk on short-term outcomes of very/extremely low birth weight preterm infants / 中华围产医学杂志

Objective To study the effects of human milk on feeding intolerance, infant growth and development, complications during hospitalization and length of hospital stay in very/extremely low birth weight (VLBW/ELBW) preterm infants. Methods VLBW/ELBW preterm infants admitted to the Division of Neonatology, Children's Medical Center of the Second Xiangya Hospital from May 2015 to April 2018 were enrolled in this retrospective study and were assigned into two groups: human milk group (human milk accounted for at least 50% of total enteral feeding during hospitalization) and formula group (exclusive formula feeding due to breastfeeding contraindication or insufficient human milk supply). Feeding intolerance, neonatal growth, complications and length of hospital stay were compared between the two groups using independent sample t-test, Mann-Whitney U test and Chi-square test (or Fisher's exact probability test). Results A total of 113 VLBW/ELBW infants were enrolled consisting of 52 in the human milk group and 61 in the formula group. The starting time of enteral feeding, duration of minimal enteral feeding and incidence of feeding intolerance were similar between the two groups (all P>0.05). The increasing rate of milk volume was (8.4±1.6) ml/(kg·d) in the human milk group and (7.6±1.4) ml/(kg·d) in the formula group (t=2.853, P<0.05). The length of parenteral nutrition of the human milk group was shorter than that of the formula group [(29.3±7.6) vs (33.0±7.9) d, t=－2.570, P<0.05], so was the time to full enteral feeding [(30.0±7.8) vs (34.9±8.8) d, t=－3.076, P<0.05]. No significant difference was found in the average weight gain, increment in head circumference or body length, the length of regaining birth weight, or the incidence of extrauterine growth restriction between the two groups (all P>0.05). The incidence of neonatal necrotizing enterocolitis (NEC) in the human milk group was lower than that of the formula group [1.9% (1/52) vs 11.5% (7/61), χ2=3.894, P<0.05]. No statistical difference in the incidence of sepsis, cholestasis, anemia, bronchopulmonary dysplasia (BPD), retinopathy of prematurity or periventricular leukomalacia was observed between the two groups (all P>0.05). There were 14 cases (26.9%) of BPD in the human milk group, of which eight were mild and six moderate. While in the formula group, 24 cases (39.3%) had BPD and among them, four, 18 and two infants were mild, moderate and severe BPD, respectively. BPD cases in the human milk group were less severe than those in the formula group (U=－2.645, P<0.05). The length of hospital stay of the human milk group was shorter than that of the formula group [(47.5±14.8) vs (53.9±16.3) d, t= － 2.129, P<0.05)]. Conclusions Human milk for VLBW/ELBW infants may shorten the time to full enteral feeding and the length of hospital stay, reduce the incidence of NEC, decrease the severity of BPD. VLBW/ELBW infants fed with fortified human milk have similar growth rate as those fed with formula milk.

Discussion on Characteristics and Ethical Path of Assisted Reproductive Treatment in Elderly Patients / 中国医学伦理学

Through summarizing and analyzing the characteristics of elderly infertile people,the problems emer-ging in the assisted reproduction process and the possible ethical problems emerging in the assisted reproduction treatment of elderly patients,this paper explored how to build the ethical path which aimed at elderly pregnancy -assisted people and suitable for Reproductive Center in the First Affiliated Hospital of Xinjiang Medical University. And aiming at the possible ethical problems emerging in the process of assisted reproduction treatment of elderly pa-tients,this paper put forward that it should establish normative ethical working path,to be more convenient to fully conduct ethical supervision and examination in the process of assisted reproduction treatment of elderly patients.

A synthetic peptide derived from bactericidal/permeability-increasing protein neutralizes endotoxin in vitro and in vivo.

Lipopolysaccharide (LPS [endotoxin]), a structural component of gram-negative bacteria, is implicated in the pathogenesis of septic shock. Lipid A is an evolutionarily conserved region of LPS that has been identified as the toxic component of LPS. Therapeutic strategies for the treatment of septic shock in humans are currently focused on neutralization of LPS. Here, the anti-endotoxin activity of BNEP, a synthetic peptide derived from the human bactericidal/permeability-increasing protein (BPI; aa 148-161) was investigated in vitro and in experimental animal endotoxemia models in vivo. The ability of BNEP to bind LPS from Escherichia coli O55:B5 and lipid A from Salmonella Re 595 was tested using an affinity sensor assay, and its ability to neutralize LPS was tested using a sensitive Limulus amebocyte lysate (LAL) assay. Polymyxin B (PMB) was used as the positive control in the in vitro experiments and in mouse experiments. We found that BNEP and PMB bound LPS with a similar affinity (Kd values of 25.4 and 25.8 nM, respectively). In contrast, BNEP bound lipid A with a slightly lower affinity than that of PMB (Kd values of 8 and 5.6 nM, respectively). The exact capacity of BNEP binding to LPS was approximately 0.53 microg peptide per 1 ng of LPS, as shown by affinity sensor assay. The LAL test showed that 256 microg of BNEP almost completely neutralized 2 ng LPS. In vivo, mice were randomized, intravenously injected with BNEP (0.5-10 mg/kg) or 1 mg/kg PMB, and then lethally challenged with 20 mg/kg LPS. We found that 5 mg/kg BNEP significantly protected mice from LPS challenge. In an endotoxemia rat model, animals were co-treated with 5 or 10 mg/kg BNEP and 10 mg/kg LPS via cardiac catheter. BNEP treatment resulted in significant reduction of tumor necrosis factor alpha (TNF-alpha) and IL-6, compared with LPS-only control animals. In addition, 10 mg/kg BNEP-treated animals showed a significant decrease in plasma endotoxin levels in comparison to animals treated with LPS alone. These results provide evidence that BNEP effectively neutralizes LPS in vitro and in vivo, and could protect animals from the lethal effects of LPS via decreasing plasma endotoxin and proinflammatory cytokines. Our work suggests that this peptide is worthy of further investigation as a possible novel treatment for septic shock.

Clinical Significance of Nucleosomes Released from Peripheral Blood Mononuclear Cells of Patients with Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To assess the levels of nucleosomes released from peripheral blood mononu-clear cells(PBMC)of patients with systemic lupus erythematosus(SLE),and their relationship with auto-antibodies as well as disease activity.Methods Levels of both nucleosomes released from PBMC and vari-ous auto-antibodies were detected by ELISA in sera from SLE patients.The disease severity was evaluated using SLEDAI(systemic lupus erythematosus disease activity index)system.Results Levels of nucleosomes released from PBMC were significantly higher in patients with active SLE than those of patients with inactive disease and normal controls(39.39?25.70,13.44?8.82,and11.73?7.87IU/mL,respectively).There was a significant positive correlation between nucleosome levels and SLEDAI scores,serum ds-DNA auto-an-tibody levels,and low C3levels.Conclusion Nucleosomes released from apoptotic PBMC of patients with SLE is closely correlated to disease activity,which implies that nucleosomes may play an important role in the pathogenesis of SLE.

AFFINITIES OF PEPTIDE (BNEP) MIMICKING BACTERICIDALITY/PERMEABILITY-INCREASING PROTEIN FOR LIPOPOLYSACCHARIDE AND Lipid A BY BIOSENSOR TECHNOLOGY / 解放军医学杂志

To explore the mechamisms of bactericidal neutralizing endotoxin peptide(BNEP), a synthetic peptide mimicking bactericidality/permeability-increasing protein (BPI). The affinities of BNEP for LPS and Lipid A were determined with biosensor technology, and the ability of BNEP neutralizing LPS in vitro was tested by quantitative limulus amoebocyte lysate assay. The results showed that BNEP had high affinities for both LPS and Lipid A. The Kd value for LPS was at the level between 25.8 and 48.8nmol/L and for Lipid A from 11.8 to 21.8nmol/L. When 8?g/ml of BNEP was used, it could completely neutralize the concentration of 2ng/ml of LPS in vitro. It is concluded that BNEP has high binding affinities for both LPS and Lipid A. Our results also suggest that the binding site of LPS is at the glucosaminyl-?1'-6-glucosamine disaccharide of Lipid A. The binding activity of BNEP for LPS is in accord with its neutralizing activity for LPS.