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.

Objective To analyze the factors influencing early-onset sepsis in preterm infants and construct nomogram model.Methods A total of 124 neonates with premature sepsis admitted to Shanxi Children's Hospital(Shanxi Maternal and Child Health Hos-pital)from January 2020 to December 2021 were collected.According to gestational age,the neonates were divided into premature group(n=33)and full-term group(n=91),and the clinical characteristics of the two groups were compared,and nomogram model was es-tablished to internally validate the predictiveness and accuracy of the model.Results Compared with the full-term group,the proportion of females in premature group was higher(x2=7.147,P＜0.05),the 1min Apgarscore in premature group was lower(x2=-3.398,P＜0.05),the proportion of perinatal mothers with pregnancy complications in premature group was higher(x2=7.846,P＜0.05),the incidence of pneumonia and poor response in preterm infants of premature group were higher(x2=18.210,P＜0.05;x2=14.814,P＜0.05),but the incidence of jaundice in premature group was lower(x2=10.400,P＜0.05).Multivariate Logistic regression analysis showed that female and pneumonia were risk factors for early-onset sepsis in preterm infants(P＜0.05).The results of the nomogram model showed that the C-index of the model was 0.886.The predicted incidence was generally consistent with the actual incidence,the area under the receiver operator characteristic curve was 0.886,and the decision curve showed a high net benefit value at threshold proba-bilities of 4％-100％.Conclusion Female,preterm infants with pneumonia have a higher risk of early-onset sepsis.The nomogram model of premature sepsis constructed in this study has high clinical value and can provide a reference basis for clinical prevention of early-onset sepsis in preterm infants.

Objective:To investigate the effect of quality improvement (QI) project on delayed cord clamping (DCC) implementation in very preterm infants.Methods:This study retrospectively collected the clinical data and assessed the QI indices of very preterm infants born in the Women and Children's Hospital of Chongqing Medical University and transferred to the Neonatology Department from January 2017 to January 2021. The indices for QI assessment included three types: (1) process indices: the implementation rate and timing of DCC; (2) outcome indices: hemoglobin level and hematocrit, etc; (3) balancing indices: the proportion of neonates requiring endotracheal intubation in the delivery room and chest compressions, Apgar score body temperature, and blood pH value on admission, etc. There were four phases for the implementation of QI, the pre-QI period (January to December of 2017), the QI period (January to December of 2018), the post-QI period (January to December of 2019), and the sustained-QI period (January 2020 to January 2021). The QI project was performed since August 2018. Control charts or statistical tests were used for statistical analysis.Results:(1) Process indices: After the implementation of the QI project, the practice of DCC increased from 0 to 82.2%, and the timing of umbilical cord clamping was from 0 s to a delay of 47.1 s. (2) Outcome indices: The levels of hemoglobin in the QI period, the post-QI period, and the sustained-QI period were significantly higher than those in the pre-QI period [(202.22±28.84), (210.10±33.52), (210.52±32.27) g/L vs. (187.94±35.29) g/L; F=8.61, P<0.001]. The hematocrit values in the post-QI period and the sustained-QI period were significantly higher than those in the pre-QI period [(58.99±8.71) %, (60.18±8.06)% vs. (55.41±9.17)%; χ2=5.13, P=0.002]. The other indices showed no statistical differences in different phases. (3) Balancing indices: The proportions of neonates receiving endotracheal intubation in the delivery room in the post-QI period and the sustained-QI period were significantly lower than those in the pre-QI period [16.0% (19/119), 13.2% (25/191) vs. 42.3% (30/71); χ2=29.08, P<0.001]. The body temperature on admission increased gradually through the four periods [pre-QI period: 35.3 ℃ (34.5-36.1 ℃); QI period: 36.0 ℃ (34.0-37.7 ℃); post-QI period: 36.0 ℃ (35.6-37.4 ℃); sustained-QI period: 37.0 ℃ (35.9-38.1 ℃); H=277.88, P<0.001]. The blood pH value on admission in the sustained-QI period [7.32 (6.85-7.50)] was significantly higher than those in the other three periods [7.26 (7.07-7.46), 7.26 (7.04-7.43), and 7.25 (6.91-7.49); H=34.46, P<0.001]. Conclusion:The interventions in this QI project significantly increase the practice of DCC and enable a longer DCC in very preterm infants.

Objective:To study the iodine nutritional status of pregnant women in the third trimester in the Southwest of Shandong Province, analyze its impact on their cardiac electrical activity, and provide a basis for scientific supplementation of iodine during pregnancy.Methods:From January 2021 to June 2022, a cross-sectional survey was conducted using cluster random sampling method. According to the inclusion and exclusion criteria, 200 pregnant women in the third trimester were selected from 3 tertiary hospitals in three cities in the Southwest of Shandong Province, and were divided into the third trimester group ( n = 600), and 100 non-pregnant women were selected as the control group ( n = 300). The urinary iodine content was detected by arsenic-cerium catalytic spectrophotometry, and the pregnant women in the third trimester group were subdivided into iodine deficiency subgroup [G1 subgroup, median urinary iodine (MUIC) < 150 μg/L] based on the MUIC, iodine excess subgroup (G2 subgroup, MUIC≥500 μg/L) and moderate iodine subgroup (G3 subgroup, 150 μg/L≤MUIC < 500 μg/L). Chemiluminescence immunoassay was used to measure the serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT 4) and free triiodothyronine (FT 3). The cardiac electrical indexes were detected by a 12-lead surface electrocardiogram (ECG) machine. Results:There was no statistically significant difference in urinary iodine levels between pregnant women in the third trimester group and non-pregnant women in the control group among the 3 tertiary hospitals in the Southwest of Shandong Province ( H = 3.63, 3.27, P > 0.05). In the third trimester group, the proportion of pregnant women in the G1, G2 and G3 subgroups was 27.67% (166/600), 6.83% (41/600) and 65.50% (393/600), respectively. There was a statistically significant difference in urinary iodine levels between the subgroups and the control group ( H = 11.56, P < 0.001). The serum FT 3 and FT 4 levels in the G2 subgroup were lower than those in the G1 and G3 subgroups ( P < 0.001), but there was no statistically significant difference in serum TSH levels among the three subgroups ( P > 0.05). The normal rates of ECG in the G1, G2, G3 subgroups, and the control group were 38.55% (64/166), 41.46% (17/41), 92.37% (363/393), and 95.33% (286/300), respectively. The difference between the groups were statistically significant (χ 2 = 461.25, P < 0.001), the normal rate of ECG in the G1 and G2 subgroups was lower than that in the control group ( P < 0.001). Short P-R intervals and ST-T changes were the most common abnormal ECG in the third trimester group. Conclusions:The incidence of iodine deficiency, iodine excess, and other abnormal iodine nutritional status in pregnant women in the third trimester of the Southwest of Shandong Province is relatively high. Short P-R intervals, ST-T changes, and other arrhythmia caused by this are more common. It is necessary to strengthen monitoring of iodine nutritional status and ECG during pregnancy, and adjust intervention strategies such as iodine supplementation in a timely manner.

Objective:To explore the clinical therapeutic effect and follow-up prognosis of preterm infants with neonatal respiratory distress syndrome (NRDS) managed by less invasive surfactant administration (LISA) and traditional intubation-surfactant-extubation (INSURE) of pulmonary surfactant (PS).Methods:Data during hospitalization and follow-up period of 187 NRDS preterm infants (gestational age 24 weeks to 31 + 6 weeks, and birth weight <1 500 g) admitted to the Department of Neonatology, the Women and Children′s Hospital of Chongqing Medical University from March 2019 to February 2021 were retrospectively analyzed.NRDS preterm infants who were injected with PS by LISA were included in the LISA group (144 cases), and those who were injected with PS by INSURE were included in the INSURE group (43 cases). The propensity score matching method was used to correct the confounding factors between groups, and the covariate equilibrium samples between groups were obtained (39 cases in each group). Clinical treatment effect and prognosis of physical development, hearing and vision development, nervous system development, respiratory system diseases and other conditions of the two groups of children were compared using the t test, Chi- square test and other statistical analysis methods as appropriate. Results:(1)Compared with that of the INSURE group, the incidence of BPD [12 cases (33.3%) vs.23 cases (63.9%), χ2=6.727, P=0.009] and ROP [13 cases (36.1%) vs.26 cases (72.2%), χ2=9.455, P=0.002] in the LISA group were significantly lower.The incidence of mild BPD [8 cases (22.2%) vs.16 cases (44.4%), χ2=4.000, P=0.046] and stage Ⅰ-Ⅱ ROP [11 cases (30.6%) vs.22 cases (61.1%), χ2=6.769, P=0.009] in the LISA group was significantly lower than that of the INSURE group.There was no significant difference in the incidence of moderate and severe BPD and stageⅢ ROP and above between groups (all P>0.05). (2)There were no statistical differences in the repeated use of PS, mechanical ventilation rate within 72 h, pneumothorax/pulmonary hemorrhage, grade Ⅲ-Ⅳ periventricula-rintraventricular hemorrhage, stage Ⅱ-Ⅲ neonatal necrotizing enterocolitis, sepsis, abnormal amplitude integrated electroencephalogram, mortality in 36 weeks of corrected gestational age, total oxygen inhalation duration and hospitalization duration between the two groups (all P>0.05). (3)Follow-up within 1 year of corrected age after discharge.There were no significant differences in extrauterine body mass, body length and head circumference development, visual development, hearing development, Neonatal Behavioral Neurological Assessment score at corrected gestational age of 40 weeks, Bayley Scales of Infants Development score at corrected gestational age of 6 months and age of 1 year, pneumonia and re-hospitalization due to respiratory diseases between groups (all P>0.05). Conclusions:PS administration with LISA technology can reduce the incidence of mild BPD and stage Ⅰ-Ⅱ ROP in premature infants with NRDS who had the gestational age of 24-31 + 6 weeks and birth weight<1 500 g, without increasing the risk of other complications.The long-term prognosis of them treated with PS administration with LISA and INSURE is similar.

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.

Objective : To investigate the expression of macrophage migration inhibitory factor (MIF) and its effect on autophagy and insulin resistance of ovarian granulosa cells in polycystic ovary syndrome ( PCOS) . Methods: Follicular fluid and ovarian granulosa cells were collected from 40 PCOS patients ( n = 40) and non PCOS patients (control group, n = 20) . PCOS included patients with IR (PCOS with IR, n = 20) and patients without IR (PCOS without IR, n = 20) . The expression of MIF in follicular fluid was detected by ELISA . The ratio of autophagy vacuoles to microtubule⁃associated protein light chain Ⅱ( LC3 Ⅱ) /microtubule⁃associated protein light chain Ⅰ( LC3 Ⅰ)in granulosa cells was observed by transmission electron microscopy and Western blot . Human ovarian granule cell line KNG was cultured in vitro and CCK⁃8 was used to detect the effects of different concentrations of MIF on granule cell activity . KNG cells were divided into four groups: normal culture group ( NC group), MIF group, chloroquine group (CQ group) and MIF + CQ group . The effects of MIF on the expression of autophagy related proteins LC3, autophagy related genes 7(Atg7), ubiquitin binding protein(p62), and insulin signaling pathway related proteins insulin receptor substrate⁃1(ISR⁃1), glucose transporter 4(GLUT4), protein kinase B(Akt) phosphorylation were observed by Western blot, and the effect of MIF on glucose uptake ability of granulosa cells was detected by glucose uptake test . Results : Compared with the control group or PCOS without IR group, MIF expression in follicular fluid and autophagy level of granulosa cells in PCOS with IR group increased (P < 0. 05 or P < 0. 01); In vitro experiments showed that MIF could significantly inhibit the cellular activity of KNG in granulocytes in a concentration⁃dependent manner, in which 100 ng/ml MIF was selected for subsequent relevant experiments; Compared with NC group, LC3Ⅱ/LC3I ratio and Atg7 protein in MIF group and MIF + CQ group increased (P < 0. 05), while p62 protein, IRS⁃1 protein, Akt phosphorylation level, GLUT4 protein expression level and glucose uptake ability decreased ( P < 0. 05 ), while the above autophagy markers in MIF + CQ group were significantly higher than those in MIF group (P < 0. 05), and the protein related to insulin signal transduction and glucose uptake increased (P < 0. 05) . Conclusion MIF may promote IR development in PCOS patients by up⁃regulating the autophagy level of granulosa cells, while inhibiting the autophagy of granulosa cells can improve MIF⁃induced IR.

Objective:To analyze the outcomes of extremely preterm infants (EPIs) after the implementation and quality improvement of an intervention program from the prenatal period to delivery room and the factors influencing the mortality of EPIs.Methods:This was a retrospective study involving 185 EPIs admitted to neonatal intensive care unit (NICU) of Chongqing Health Center for Women and Children from July 1, 2014, to June 30, 2021. The intervention program from the prenatal period to delivery room was implemented in our hospital in January 2018, according to which, EPIs who were admitted before this time were grouped as the historical group ( n=45) and those who were admitted after as the program group ( n=140). The survival rate and morbidity of the two groups were analyzed and compared using t test, Mann Whitney U test, and Chi-square test. The factors influencing the mortality of EPIs were analyzed by univariate screening and logistic regression. Results:(1) The median gestational age of these EPIs was 26 +6 weeks, ranging from 23 +3 to 27 +6 weeks, and the median birth weight was 950 g, ranging from 390 g to 1 290 g. (2) After the intervention, the proportion of patients in whom the neonatologists were involved in prenatal consultation, women who received a full course of antenatal corticosteroid and magnesium sulfate, and cesarean delivery as well as the neonatal temperature on admission to NICU all increased significantly [77.1% (108/140) vs 8.9% (4/45); 67.9% (95/140) vs 35.6% (16/45); 67.1% (94/140) vs 48.9% (22/45); 44.3% (62/140) vs 17.8% (8/45); 36.6 ℃ (36.3-36.9 ℃) vs 35.2 ℃ (35.0-35.3 ℃), respectively, χ2 or Z values were 66.41, 14.81, 4.85, 10.17 and－9.34, respectively, all P<0.05]. Both delayed cord clamping (DCC) and nasal continuous positive airway pressure (nCPAP) were included in the intervention program, with implementation rates from zero before to 67.9% (95/140) and 89.3%(125/140), respectively. Compared to the historical group, the proportion of infants with 1-minute Apgar score ≤3, endotracheal intubation in the delivery room or mechanical ventilation within 72 h after birth were decreased in the program group [7.1% (10/140) vs 17.8% (8/45), 37.1% (52/140) vs 73.3% (33/45), 38.6% (54/140) vs 57.8% (26/45), χ2 values were 4.39, 17.96 and 5.12, respectively. all P<0.05]. (3) After the intervention, the overall survival rate of EPIs and that among those with gestational age from 27 to 27 +6 weeks were significantly improved [72.9% (102/140) vs 53.3% (24/45), OR=2.349, P=0.015; 84.1% (53/63) vs 56.6% (13/23), OR=4.077, P=0.007]. Although the incidence of periventricular and intraventricular hemorrhage, late-onset sepsis, and retinopathy of prematurity showed a downward trend, the differences were not statistically significant (all P>0.05) (4) Multivariate logistic regression analysis showed that 1-minute Apgar score ≤3 ( OR=8.890, 95% CI:2.005-39.412), low 5-minute Apgar score ( OR=1.468, 95% CI:1.103-1.953), and higher rate of mechanical ventilation within 72 h ( OR=7.165, 95% CI:2.942-17.449) were independent risk factors for the mortality of EPIs; and using nCPAP in the delivery room ( OR=0.314, 95% CI:0.137-0.719) and birth weight ( OR=0.996, 95% CI:0.993-0.999) were protective factors. Conclusions:Early interventions for EPIs in the prenatal period or the delivery room, the quality improvement program, including intrapartum temperature management, DCC, and nCPAP, is likely to improve the survival rate and outcome of EPIs.

Objective:To investigate the expression of long non-coding RNA MALAT1, interleukin 6(IL-6) and apoptosis induced factor(AIF) in peripheral venous blood of premature infants with bronchopulmonary dysplasia (BPD) and its clinical significance.Methods:Preterm infants admitted to the Department of Neonatology, Shanghai Children′s Hospital from January 2015 to December 2016 were enrolled.The selection criteria included gestational age (GA) ≥28 weeks and ≤32 weeks, and birth weight (BW) < 1 500 g. According to the diagnosis, they were divided into BPD group (20 cases) and control group (20 cases). The clinical data of the two groups of premature infants were collected and analyzed, and the levels of MALAT1, IL-6 and AIF in the blood of 40 premature infants were detected by real-time polymerase chain reaction (RT-PCR). T test was used to compare gestational age, birth weight, MALAT1, IL-6 and AIF between the two groups. Results:(1)There was no significant differences in sex ( χ2=1.76), gestational age ( t= 0.17) and birth weight ( t=1.25) of premature infants in BPD group, compared with the control group (all P >0.05). (2)Compared with the control group, the expression of MALAT1 in the peripheral blood of premature infants in BPD group were significantly increased (0.273 4±0.067 3 vs. 0.375 5±0.081 9, P<0.05). (3)Compared with the control group, the expression of IL-6 in the peripheral blood of premature infants in BPD group were obviously decreased (1.448 8±0.191 8 vs.4.444 6±0.165 7, P<0.05). (4)Compared with the control group, the expression of AIF in the peripheral blood of premature infants in BPD group were remarkably decreased(0.006 8±0.002 0 vs.0.004 5±0.001 9, P<0.05). Conclusions:MALAT1 and IL-6 levels of long non-coding RNA in BPD and non-BPD preterm infants are different, which may be related to the incidence of BPD.IL-6 may be a predictor of BPD, and MALAT1 may protect premature infants with BPD.

Objective:To understand quality improvement (QI) in resuscitation and its impacts on the outcomes in very low birth weight infants (VLBWI).Methods:This was a retrospective study involving 318 cases of VLBWI born in Chongqing Health Center for Women and Children and transferred to the Neonatal Intensive Care Unit (NICU) in the same hospital from January 1, 2017 to December 31, 2019. All recruited VLBWIs were divided into three groups based on chronological order: pre-QI group (born in 2017, n=83), under-QI group (born in 2018, n=102) and post-QI group (born in 2019, n=133). The implementation and effects of different resuscitation strategies, including body temperature management, delayed cord clamping (DCC), respiratory support [continuous positive airway pressure (CPAP) in the delivery room, positive pressure ventilation or tracheal intubation] and oxygen therapy [initial fraction of inspired oxygen (FiO 2), maximum FiO 2 and pure oxygen resuscitation], and the neonatal outcomes in each year were analyzed and compared by trend Chi-square test, Kruskal-Wallis H test, Wilcoxon rank-sum test, analysis of variance and LSD test. Results:(1) The proportion of antenatal steroid exposure increased gradually during the three years [44.6% (37/83), 47.1% (48/102), 72.2% (96/133); χ2trend=18.218, P<0.001]. (2) From 2017 to 2019, the incidence of hypothermia on admission decreased [100.0% (83/83), 90.2% (92/102), 33.8% (45/133); χ2trend=136.042, P<0.001], without increasing the proportion of hyperthermia [0.0% (0/83), 1.0% (1/102), 0.0% (0/133); χ2trend=2.124, P=0.346]. (3) The proportion of VLBWIs receiving DCC increased annually [0.0% (0/83), 29.4% (30/102), 90.2% (120/133); χ2trend=178.659, P<0.001], and the concentration of capillary hemoglobin within 12-24 h after birth also increased [(190.1±34.8), (202.0±29.7), (213.6±32.3) g/L; LSD test, P<0.05]. The incidence of suspected polycythemia (capillary hematocrit >68%) increased annually[7.2%(6/83), 7.8%(8/102), 17.3(23/133); χ2trend=5.825, P=0.016]; While the incidence of confirmed polycythemia (venous hematocrit >65%) was not increased[1.3%(1/80), 2.0%(2/100), 4.8%(6/126); χ2trend=2.333, P=0.127] after excluding those untested cases. (4) The use of CPAP in delivery room increased annually [0.0% (0/83), 28.4% (29/102), 87.2%(116/133); χ2trend=167.721, P<0.001], while that of positive pressure ventilation [44.6% (37/83), 31.9% (32/102), 28.6% (38/133); χ2trend=5.371, P=0.020], and the proportion of intubation within 1 min after birth [100.0% (31/31), 45.0% (9/20), 35.0%(7/20); χ2trend=37.467, P<0.001] and overall intubation [37.3% (31/83), 19.6% (20/102), 15.0% (20/133); χ2trend=13.566, P<0.001] decreased year by year. There was no difference in the percentage of infants receiving chest compression or epinephrine, or with low Apgar scores during the three years (all P>0.05). (5) The initial inhaled FiO 2 [30%(21%-100%), 30%(21%-100%) vs 40(25%-100%)] as well as the highest FiO 2 [40%(21%-100%), 30%(21%-100%) vs 40%(25%-100%)] were significantly lower in 2018 and 2019 than in 2017(all P<0.017). The proportion of infants receiving pure oxygen resuscitation decreased year by year [13.3% (11/83), 1.0% (1/102), 0.8% (1/133); χ2trend=17.719, P<0.001]. There was no statistical difference in radial artery blood gas analysis, the proportion of infants receiving pulmonary surfactant or mechanical ventilation, the highest value of percutaneous bilirubin, the incidence of hyperbilirubinemia, necrotizing enterocolitis, periventricular intraventricular hemorrhage, bronchopulmonary dysplasia, or mortality during hospitalization (all P>0.05). Conclusions:Resuscitation QI program helps reduce the incidence of hypothermia, increased the hemoglobin level after birth, and lessen the use of positive pressure ventilation and tracheal intubation in VLBWIs, without influencing the resuscitation effect or increasing the risk of short-term adverse outcomes.