Objective:To analyze the risk factors and clinical features of premature infants with bronchopulmonary dysplasia(BPD)at high altitude in Tibet and low altitude in Beijing.Methods:A retrospective case-control study was conducted.The clinical data of children with gestational age ≤32 weeks admitted to the Department of Neonatology of Lhasa People′s Hospital(altitude of 3 600 m)and the Department of Neonatology of Children′s Hospital Affiliated to Capital Institute of Pediatrics(altitude of 50 m)from January 1, 2018 to December 31, 2021 were collected.Cases were divided into BPD group and non-BPD group.Premature infants with BPD were divided into high altitude group and low altitude group according to different altitudes.The clinical characteristics and high risk factors of BPD were analyzed.Results:There were 379 premature infants with gestational age ≤32 weeks, 351 were included in the study, including 110 cases in group and 241 cases in non-BPD group.There were 48 cases in high altitude group and 62 cases in low altitude group.The incidence of BPD in high altitude areas(Lhasa)was 38.7%(48/124), among which mild, moderate and severe BPD accounted for 75.0%(36 cases), 18.8%(9 cases)and 6.3%(3 cases), respectively.The incidence rates of BPD were 100%(2/2), 86.7%(13/15)and 38.7%(33/107) in gestational age <28 weeks, 28 to 29 + 6 weeks and 30 to 32 weeks, respectively.There was a statistically significant difference among different gestational age groups( χ2=19.696, P<0.001). The incidence of BPD in low altitude areas(Beijing)was 27.3%(62/227), among which mild, moderate and severe BPD accounted for 74.2%(46 cases), 4.8%(3 cases)and 21.0%(13 cases), respectively.The incidence rates of BPD in gestational age<28 weeks, 28 to 29 + 6 weeks and 30 to 32 weeks were 100%(15/15), 45.6%(36/79)and 8.3%(11/133), respectively.There was a statistically significant difference among different gestational age groups( χ2=77.474, P<0.001). The incidence of BPD in high altitude areas was significantly higher than that in low altitude areas( χ2=4.841, P=0.028). Multivariate regression analysis showed that high altitude( OR 146.893, 95% CI 19.044-1 133.064), birth weight( OR 0.996, 95% CI 0.993-0.999), asphyxia( OR 4.187, 95% CI 3.020-21.670), non-invasive mechanical ventilation( OR 1.171, 95% CI 1.106-1.240)and invasive mechanical ventilation( OR 1.198, 95% CI 1.065-1.347)were significantly correlated with the occurrence of BPD.The gestational age at birth, small for gestational age infant, the fraction of inspired oxygen and the incidence of pregnancy induced hypertension in pregnant women in high altitude group were higher than those in low altitude group( P<0.05). The incidence of patent ductus arteriosus, the use time of noninvasive and invasive mechanical ventilation, the length of hospital stay, the age of mother, the application of prenatal hormone and the twin ratio in high altitude group were significantly lower than those in low altitude group( P<0.05). Conclusion:High altitude in Tibet is a high-risk factor for the occurrence of BPD in preterm infants.Strengthening maternal health care in high altitude areas of Tibet and doing a good job in asphyxia resuscitation in delivery room may be important measures to reduce BPD in preterm infants.

Objective:To explore the prognostic indicators and influencing factors of neonatal asphyxia in Tibet.Methods:From March 2019 to March 2020, the clinical data of 126 asphyxiated newborns admitted to the neonatology department of Lhasa People's Hospital were retrospectively studied. According to the prognosis, they were divided into good prognosis group and poor prognosis group, and the clinical characteristics of the two groups were compared. The predictive value of Apgar score after birth, arterial blood gas analysis within 6 hours [pH, alkali residue (BE)] and their combined detection on the prognosis of asphyxiated newborns was analyzed. Logistic regression analysis was used to analyze the related factors affecting the prognosis of asphyxiated newborns.Results:31 cases (24.6%) in the poor prognosis group and 95 cases (75.4%) in the good prognosis group. The Apgar score at 1, 5 and 10 minutes after birth and pH and BE within 6 hours in the poor prognosis group were significantly lower than those in the good prognosis group (all P<0.05). The incidence of meconium stained amniotic fluid, fetal intrauterine distress, brain damage, lung damage, myocardial damage, kidney damage, abnormal coagulation function and multiple organ damage after asphyxia in the good prognosis group were significantly higher than those in the good prognosis group (all P<0.05). The Apgar score at the 1, 5 and 10 minutes after birth combined with arterial blood gas analysis (pH and BE) within 6 hours after birth had high predictive value for the prognosis of asphyxiated newborns, with the area under receiver operating characteristic (ROC) curve of 0.79, sensitivity of 68.4% and specificity of 90.3%. Multivariate regression analysis showed that meconium stained amniotic fluid ( OR=4.501, 95% CI: 1.262-16.056), lung damage ( OR=5.004, 95% CI: 1.007-24.866) and brain damage ( OR=10.786, 95% CI: 2.726-42.673) were independent risk factors affecting the prognosis of neonatal asphyxia ( P<0.05). Conclusions:In Tibet, there are many factors affecting the poor prognosis of neonatal asphyxia. High attention and intervention should be given to mothers in perinatal period and asphyxiated newborns in order to reduce the incidence of poor prognosis of neonatal asphyxia.

Objective:To investigate the incidence and risk factors of hypertensive disorders in pregnancy (HDP) in high altitude areas and their influence on maternal and infant outcomes.Methods:This was a retrospective case-control study. A total of 220 newborns were selected as the high altitude group, who were born to 216 mothers with HDP and admitted to the Neonatal Intensive Care Unit of the Lhasa People's Hospital from June 1, 2018, to June 1, 2020. The low altitude group consisted of 235 newborns born to 231 mothers with HDP and admitted to the Department of Neonatology of the Children's Hospital Affiliated to Beijing Capital Institute of Pediatrics from January 1, 2018, to December 31, 2021. Differences in the types of HDP between the two groups and the risk factors for the high incidence of preeclampsia-eclampsia and early-onset preeclampsia in high altitude area were analyzed. The influences of HDP in high and low altitude areas on maternal and infant outcomes were compared. Statistical analysis was performed using t-test, Mann-Whitney U test, Pearson Chi-square test, or continuous correction Chi-square test, and univariate and multivariate logistic regression analysis. Results:Maternal age and the proportions of primiparae and women of advanced age or having irregular prenatal examination were greater in the high altitude group than those in the low altitude group (all P<0.05). Besides, the incidence of early-onset preeclampsia, eclampsia, preeclampsia-eclampsia, and chronic hypertension complicated by preeclampsia were also higher in the high altitude group (all P<0.05). Multivariate logistic regression analysis showed that high altitude was a risk factor for the development of preeclampsia-eclampsia ( OR=4.437, 95% CI:2.582-7.626). Adverse pregnancy history ( OR=2.576, 95% CI:1.217-5.452) and irregular prenatal examination ( OR=2.862, 95% CI:1.412-5.800) were independent risk factors for early-onset preeclampsia in pregnant women in high altitude areas. Twin-pregnancy was a protective factor for early-onset preeclampsia in pregnant women in high altitude areas ( OR=0.183, 95% CI: 0.054-0.623). The incidence of maternal heart failure [7.9% (17/216) vs 0.4% (1/231), χ2=15.98], placental abruption [7.9% (17/216) vs 3.5% (8/231), χ2=4.11], hemolysis, elevated liver function and low platelet count syndrome [14.4% (31/216) vs 1.7% (4/231), χ2=24.64], premature delivery [86.1% (118/216) vs 73.6% (170/231), χ2=10.79], fetal growth restriction [52.3% (115/220) vs 18.7% (44/235), χ2=56.26], fetal distress [18.2% (40/220) vs 8.1% (19/235), χ2=10.26], neonatal asphyxia [29.5% (65/220) vs 11.1% (26/235), χ2=24.26], severe asphyxia [8.6% (19/220) vs 2.6% (6/235), χ2=8.10] and the proportion of neonates requiring mechanical ventilation within 24 h after birth [69.5% (153/220) vs 42.6% (100/235), χ2=33.54] as well as neonatal death within 7 d after birth [5.5% (12/220) vs 1.3% (3/235), χ2=6.22] in the high altitude group were significantly higher than those in the low altitude group (all P<0.05). Conclusion:High altitude is a risk factor for preeclampsia-eclampsia, and the adverse effects of HDP on mothers and infants are more severe in high altitude areas.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.