Invasive fungal infection (IFI) is one of the main causes of death and disability in premature infants.The occurrence of neonatal IFI involves host factors (such as extreme prematurity, very low birth weight, immature immune system, and fungal colonization, etc.) and external factors (such as central venous catheterization, mechanical ventilation, parenteral nutrition, and broad-spectrum antibiotic application, etc.). The clinical manifestations of IFI in neonates are nonspecific, which is easily confused with late-onset bacterial sepsis.Thrombocytopenia and hyperglycemia are important features of IFI.G-test and PCR have certain values in the diagnosis of fungal infection.The neonatal IFI should be mainly focused on its prevention.It is crucial for neonatal IFI to take comprehensive preventive measures such as cutting off transmission routes and strengthening medical management.The incidence of fungal infection and high risk factors in NICU where it is located should be considered when using the fluconazole prophylactically.Empirical antifungal treatment should be commenced promptly when a high degree of suspicion for IFI exists based on the presence of specific clinical features and risk factors.Targeted therapy means administer antifungal drugs on the basis of isolation of fungal.In addition, more attention should be given to the issues regarding central nervous system infection and biofilm in the management of neonatal IFI.

Objective To explore the perinatal risk factors and clinical characteristics of complications of early term neonates.Methods Data of 5 468 live term newborns and their mothers hospitalized in the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2013 were analyzed.Background information,morbidity and complications of the mothers were compared among early,full and late term groups (n=l 933,3 013,412,respectively).And background information and incidence of complications were also investigated among neonates of early,full and late term groups (n=2 033,3 023,412,respectively),and neonates born between 37-37+6 (n=695) and 38-38+6 weeks (n=1 338).One-way analysis of variance,LSD-t test,logistic regression analysis,Chi-square or Fisher exact test,Pearson Chi-square test,corrected Chi-square test were used for statistical analysis.Results 1.Comparison among the early,full and late term group showed that higher proportions of elder gravida [21.1％(407/1 933),10.5％(317/3 013),6.8％(28/412),x2=127.690],multipara [43.7％(844/1 933),23.1％(697/3 013),15.0％(62/412),x2=287.765],scarred uterus [27.9％(539/1 933),8.9％(267/3013),1.5％(6/412),x2=396.521],higher incidence of cesarean section [75.2％(1 453/1 933),56.2％(1 693/3 013),54.1％(223/412),x2=196.348],hypertensive disorder complicating pregnancy [9.2％(178/1 933),3.5％(105/3 013),2.9％(12/412),x2=79.915],multiple pregnancy[5.1％(99/1 933),0.3％(9/3 013),0.0％(0/412),x2=147.860],gravidity＞1[63.1％(1 220/1 933),47.3％(1 425/3 013),39.6％(163/412),x2=147.668],premature rupture of fetal membranes[20.6％(398/l 933),14.2％(428/3 013),10.2％(42/412),x2=47.217],abnormal amniotic fluid[17.8％(344/1 933),12.3％(370/3 013),11.2％(46/412),x2=32.777],gestational diabetes mellitus[11.5％(223/1 933),5.9％(178/3 013),5.1％(21/412),x2=56.169],abnormal presentation [9.5％(184/1 933),5.1％(155/3 013),2.9％(12/412),x2=43.511],abnormal placenta [7.6％(146/1 933),3.1％(92/3 013),2.7％(11/412),x2=57.739],hysteromyoma[4.9％(94/1 933),2.3％(68/3 013),0.7％(3/412),x2=35.062] in the early term group than in the full and late term group,respectively (all P＜0.016).Multivariate logistic analysis showed that multiple pregnancy (OR=21.736,95％CI:10.785-43.806),scarred uterus (OR=3.302,95％CI:2.679-4.071) and hypertensive disorder complicating pregnancy(OR=2.658,95％CI:2.040-3.465) were the leading three perinatal risk factors for early term delivery.2.The incidence of the following neonatal conditions were different among early,full and late term infants (all P＜0.05):hyperbilirubinemia [12.5％(255/2 033),3.9％(119/3 023),4.9％(20/412),x2=138.343],infectious diseases [4.3％(88/2 033),2.0％(59/3 023),1.7％(7/412),x2=27.122],asphyxia[3.0％(60/2 033,1.4％(42/3 023),1.0％(4/412),x2=17.795],brain damage [2.3％(46/2 033),0.5％(15/3,023),10.％(4/412)],respiratory distress syndrome [1.1％(23/2 033),0.2％(7/3 023),0.0％(0/412)],feeding problems [2.0％(41/2 033),0.3％(10/3 023),1.0％ (4/412)],surgical diseases[2.0％(41/2 033),0.9％(28/3 023),1.5％(6/412),x2=0.709],intracranial hemorrhage [1.9％(39/2 033),0.9％(26/3 023),0.5％(2/412),x2=13.263],wet lung [0.9％(19/2 033),0.4％(11/3 023),0.5％(2/412)].Incidences of the above complications in the early term infants were all higher than in the full term infants,but when compared with the later term infants,only that of hyperbilirubinemia and infectious diseases was higher (all P＜0.016).Incidence of admission ot NICU [24.5％(170/695) vs 11.5％(153/1 338),x2=57.729],hyperbilirubinemia [19.0％(132/695) vs 9.2％(123/1 338),x2=40.046],infectious diseases[6.2％(43/695) vs 3.4％(45/1 338),x2=8.807],brain damage[4.0％(28/695) vs 1.3％(18/1 338),x2=14.828],and NRDS[2.0％(14/695) vs 0.5％(9/1 338),x2=7.329],feeding problems [3.2％(22/695) vs 1.5％(20/1 338),x2=6.271],intracranial hemorrhage [3.2％(22/695) vs 1.3％(17/1 338),x2=8.684],wet lung [1.7％(12/695) vs 0.5％(7/1 338),x2=7.049] of the early term infants born at 37-37+6 weeks were all higher than those born at 38-38+6 weeks(all P＜0.05).Conclusions Multiple pregnancy,scarred uterus and hypertensive disorder of pregnancy are the three leading perinatal risk factors of early term delivery.The incidence of neonatal complications among early term infants are higher than those among full term infants,and early term infants are more likely to stay in NICU.We should take preventive measures to decrease the rate of early term delivery and improve the follow-up management of early term infants.

Objective:To study the action mechanism of Rukang oral liquid in rats with hyperplasia of mammary glands. Meth-ods:The rats were randomly divided into six groups:the normal group, the model group, tamoxifen group, low, medium and high dose of Rukang oral liquid groups. The model of hyperplasia of mammary glands was induced by estradiol benzoate injection and progester-one injection. After the administration, ELISA was used to detect the serum concentrations of ER, PR, P53 and Oct4, Western blot was used to detect the expression of ER, PR, P53 and Oct4 in breast tissue, a fluorescence quantitative PCR method was used to de-tect the expression of GnRH, GnRHR, and the expression of telomerase in breast tissue was detected by in situ hybridization. Results:Rukang oral liquid could reduce the expression of ER and PR in serum and breast tissue(P<0. 01), reduce the expression of P53, te-lomerase and Oct4(P<0. 01), and decrease the expression of GnRH in hypothalamus and pituitary, which could reverse the hyperpla-sia of mammary glands and played the role effectively(P<0. 01). Conclusion: Rukang oral Liquid can reduce the expression of ER and PR in serum and breast tissue, and decrease the expression of GnRH in hypothalamus and pituitary to play the role in the treatment of hyperplasia of mammary glands. Rukang oral Liquid may prevent breast hyperplasia from developing into breast cancer through re-ducing the expression of three related markers P53, telomerase and Oct4.

ObjectiveTo investigate the effects of caffeine citrate (CC) on the neuronal proliferation and apoptosis and long-term learning ability in neonatal rats with hypoxia-ischemic brain damage (HIBD).MethodsForty-eight 7-day-old Sprague-Dawley neonatal rats were randomly divided into 3 groups: sham operation group (n=16), HIBD group (n=16), HIBD + caffeine citrate group (CC group,n=16). Rats in HIBD and CC groups received ligation of left common carotid artery followed by 2 hours of hypoxia to establish HIBD model. Rats in CC group were injected intraperitoneally with CC (20 mg/kg) before and at 0 min, 24 h, 48 h, and 72 h after hypoxia-ischemic (HI), and rats in the other two groups were injected intraperitoneally with an equal volume of normal saline at the corresponding time. Meanwhile, from postnatal day 10, each rat was injected intraperitoneally with 5-bromo-2’-de-oxyuridine (BrdU) (50 mg/kg) for 5 consecutive times, once every 12 h. On postnatal day 12, BrdU in the hippocampal dentate gyrus and cleaved caspase-3 in the hippocampal CA1 area were detected by immunohistochemistry, and neuronal apoptosis in hippocampal CA1 area were detected by TUNEL staining. On postnatal day 28, long-term learning and memory ability of rats was tested by Y maze.ResultsThere was signiifcant difference in the number of BrdU-positive cells in brain tissues of rats among three groups (F=101.38,P<0.01). The BrdU-positive cells in HIBD group and CC group were signiifcantly more than those in sham operation group (P<0.05). There was signiifcant difference in the number of cleaved caspase-3-positive cells in hippocampal CA1 area among three groups (F=379.77,P<0.01). The cleaved caspase-3-positive cells in CC group were signiif-cantly fewer than those in HIBD group but signiifcantly more than those in sham operation group (P<0.05). The TUNEL-pos-itive cells in hippocampal CA1 area were signiifcantly different among three groups (F=505.92,P<0.01) which was most in HIBD group and fewest in sham operation group and signiifcant difference was found through multiple comparison (P<0.05). The total learning number of avoiding electric shock tested by Y maze was signiifcantly different among three groups (F=32.05, P<0.01) which was most in HIBD group. Correct response rate was significantly different among three groups (F=24.99, P<0.01) which was lowest in HIBD group.ConclusionsCaffeine citrate can improve the ability of long-term learning and memory in neonatal rats with hypoxia-ischemic brain damage, the mechanism of which may be related to reducing the neuronal apoptosis after hypoxia ischemia.

AIM: To assess the effect of raloxifene, a selective estrogen modulator, on the transcriptional activity of estrogen responsive element (ERE) in vascular endothelial cells. METHODS: Vascular endothelial cells were transfected with ERE-TK-Luc reporter plasmid and PRL-SV40 control plasmid via FuGENE 6. The activities of firefly luciferase and renilla luciferase were measured with dual-luciferase reporter assay system. The transcriptional activity in transfected cells treated with raloxifene was compared with that in untreated cells. Furthermore, raloxifene was used to cotreat the cells with estradiol (E_2) and the influence of raloxifene to the effect of E_2 was assessed. RESULTS: Compared to untreated cells, the luciferase activity in cells treated with raloxifene decreased and showed significance at concentration of 10~(-7)mol/L (P

Objective To investigate the protective effect of caffeine citrate on white matter damage in 2-day-old neonatal rats induced by postnatal infection.Methods Forty-eight 2-day-old SD rats were randomly divided into the control group (group A,n =16),lipopolysaccharide(LPS) infection group (group B,n =16),and caffeine citrate intervention group (group C,n =16) according to the random table method.The newborn rats of group B and C were continuously injected LPS 0.6 mg/kg intraperitoneally for 5 days from 2 days old,and the newborn rats of group A were continuously injected by an equal volume of 9 g/L saline intraperitoneally.Group C was continuously injected by caffeine citrate 10 mg/kg intraperitoneally for 7 days from 4 days old;equal volume of 9 g/L saline was injected into group A and B for 7 days continuously.At 12 days old,8 rats of each group were sacrificed randomly to evaluate the expression of myelin basic protein(MBP) subcortical white matter by immunohistochemical method.Both sides of hippocampus of the rest 8 rats of each group were taken out in ice surface rapidly.The left hippocampus was used to detect the expression of MBP and Caspase-3 by Western blot method,and the right hippocampus was used to evaluate the MBP and Caspase-3 protein level by quantitative real-time PCR(qPCR) method.Results The mean integral optical density (IOD) of subcortical MBP positive expression in group A,group B and group C were 132.64 ± 1.94,102.43 ± 2.12,114.25 ± 2.04,and the difference was statistically significant among 3 groups (F =22.912,P ＜ 0.05).The relative expression levels of MBP mRNA of 3 groups in hippocampus were 0.79 ± 0.01,0.39 ± 0.03,0.55 ± 0.02,and the difference was statistically significant among 3 groups (F =18.584,P ＜ 0.05).The relative expression levels of MBP protein of 3 groups in hippocampus were 0.64 ± 0.03,0.31 ± 0.03,0.51 ± 0.05,and the difference was statistically significant among 3 groups (F =25.780,P ＜ 0.05).The relative expression levels of Caspase-3 mRNA of 3 groups in hippocampus were 0.34 ± 0.02,0.74 ± 0.03,0.57 ± 0.04,and the difference was statistically significant among 3 groups (F =6.105,P ＜ 0.05).The relative expression of Caspase-3 protein of 3 groups in hippocampus were 0.11 ± 0.03,0.36 ± 0.02,0.23 ± 0.03,and the difference was statistically significant among 3 groups (F =40.541,P ＜ 0.05).Conclusions Caffeine citrate has showed protective effect on white matter damage in neonatal rats of 2 days old induced by postnatal infection.The mechanism may be related to inhibition of inflammatory response and reducing apoptosis.

Objective To explore the influence of erythropoietin (EPO) on infection induced neonatal rat brain injury at different starting time and its related mechanism.Methods Postnatal day 2 (P2) newborn SD rats were randomly divided into 4 groups:control group (group A),lipopolysaccharide (LPS) group (group B),the early EPO group(group C)and the later EPO group(group D).Pups in group A,B and C were injected different drugs intraperitoneally(group A for saline,group B for 0.6 mg/kg of LPS,and group C for 0.6 mg/kg of LPS and 5 000 U/kg of EPO) once a day for consecutive 5 days(P2-P6).LPS in group D were injected 0.6 mg/kg of LPS intraperitoneally once a day for consecutive 5 days(P2 P6),and with 5 000 U/kg of EPO once a day for consecutive 5 days(P7-P1 1).Rats in each group were given different drugs starting at corresponding time by intraperitoneal injection for 5 consecutive days.Every 10 newborn rats in group A and B were selected randomly on P2(6 h after intraperitoneal injection of drugs for the first time),P7 and P12,the brains were divided into the left and the right hemispheres marked by sagittal suture,using enzyme-linked immunosorbent assay method to evaluate the erythropoietin receptor(EPOR) protein level with the right cerebral hemisphere and reverse transcription-polymerase chain reaction (RT-PCR) method was used to investigate EPOR mRNA level of the left cerebral hemisphere.Immunohistochemical method was adopted to evaluate the expression of myelin basic protein(MBP),glial fibrillary acidic protein(GFAP) and EPOR at specified time point,and HE dyeing for the pathological changes of brain damage in different groups.Results HE staining of the group A presented the normal structure in the neonatal rat brain.Reduced numbers of hippocampal pyramidal cells,expansion of the lateral ventricles and periventricular leukomalacia were found in group B.No leukomalacia or lateral ventricles's expansion in EPO administrated groups and it was more obvious in group C.The EPOR protein and mRNA of group B was increased compared with the group A.The EPOR protein and mRNA levels had a tendency to decline with the increase of age.The MBP expression of group B(107.46 ±3.65)was significantly reduced compared with the group A(146.78 ± 3.13) (P ＜ 0.05),and the expression of EPO groups increased in contrast to the group B,moreover,the group C (126.25 ± 4.42) increased more obviously than that of group D(117.35 ± 3.42) (P ＜ 0.05).The GFAP expression of group B(141.46 ± 11.92 at P7 and 149.48 ± 13.59 at P12) increased significantly than group A(120.63 ± 13.32 at P7 and 119.74 ± 12.48 at P12) (P ＜0.05),the EPO group expressed lower than group B at the P12,and the group C (134.59 ± 12.19) decreased than the group D(137.27 ± 13.87) (P ＞ 0.05).Conclusions EPO shows a protective effect on the cerebral white matter injury caused by postpartum infection,it is superior to administer EPO at early time than later time.The mechanism of the protective effect may be connected with the fact that the infection can induce the expression of brain EPOR and the EPOR expression level has a tendency to decline with the increase of age.

AIM: To assess the effect of estrogen on the gene expression of caveolin-1 in rat vascular smooth muscle cells (VSMCs). METHODS: Wistar rats were ovariectomized and subjected to subcutaneous implantation of placebo pellets (OVX+V group) or estradiol pellets (OVX+E group). 2 weeks after implantation, the expression of caveolin-1 gene in endothelium-denuded aortic tissue was examined by RT-PCR. Furthermore, Northern blotting was used to analyze the mRNA expression of caveolin-1 in cultured rat VSMCs. RESULTS: RT-PCR showed that expression of caveolin-1 gene was significantly higher in OVX+E group than that in OVX+V group. Northern blot analysis showed that the mRNA expression of caveolin-1 was higher in VSMCs pretreated with 17?-estradiol (17?-E 2) than that in VSMCs without 17?-E 2 pretreatment. CONCLUSION: Estrogen up-regulates the gene expression of caveolin-1 in the vascular wall, partially indicating the cardiovascular effect of estrogen. [

Objective To study the clinical manifestations, risk factors, treatment and prognosis of carbapenem-resistant klebsiella pneumoniae (CRKP) sepsis in premature infants. Method A retrospective analysis was done for the premature infants diagnosed with klebsiella pneumoniae sepsis and admitted to the neonatal wards of the Hospital from April 2015 to March 2018. According to the results of drug sensitive test, the infants was assigned to CRKP group and non-CRKP group. The perinatal factors, clinical manifestations, treatment, and prognosis of the two groups were analyzed. Furthermore, high risk factors for CRKP group were analyzed. Result A total of 39 premature infants with KP sepsis were included in our study. There were 23 cases in the CRKP group and 16 cases in the non-CPAP group. In CPKP group, the gestational age was (29.5 ± 0.6) weeks, the birth weight was (1177 ± 272) g. In non-CRKP group, the gestational age was (30.0 ± 0.5) weeks, the birth weight was (1387 ± 220) g. Univariate Logistic regression analysis showed that low birth weight was a risk factor for CRKP sepsis in premature infants (OR=1.203, 95％CI 1.068～1.355, P=0.002). The proportion of that required combination treatment with antibiotics and the incidence of intracranial hemorrhage after infection in the CPKP group were both higher than that in the non-CRKP group (P<0.05). The proportion and duration of antibiotics used in the first week before the onset of infection in infants with CRKP sepsis and combined antibiotic treatment were significantly higher than those in infants with CPKP sepsis and single antibiotic treatment. The use of antibiotics in the first week before the onset of infection was an independent risk factor for the combined drug treatment of premature infants with CRKP sepsis (OR=10.500, 95％CI 1.015～108.577, P=0.049). In the CRKP group, the improvement rate was 87.0％(20/23), 2 cases were withdrew, and 1 case deceased. In the non-CPKP group, the improvement rate was 87.5％(14/16), and 2 deceased. Conclusion The lower the birth weight, the greater the risk of infection with CRKP sepsis. The proportion of need combination treatment with antibiotics is high in infants with CRKP sepsis. The use of antibiotics in the first week before the onset of infection is a risk factor for combined antibiotic treatment in premature infants with CRKP sepsis .

Objective:To study the neurodevelopmental prognosis and risk factors for adverse outcomes of neonatal seizure.Methods:From December 2019 to November 2020, infants with neonatal seizure diagnosed in our hospital were enrolled in this retrospective study. Based on survival or not, mental development index (MDI), psychomotor development index (PDI) and seizure episodes at the age of 12 months, the infants were assigned into adverse outcome group and normal outcome group. The risk factors for adverse outcomes were statistically analyzed.Results:A total of 75 infants were enrolled,including 39 cases in adverse outcome group and 36 in normal outcome group. 69 cases showed abnormal amplitude-integrated electroencephalogram(aEEG), including 38 mildly abnormal cases,23 moderately abnormal cases and 8 severely abnormal cases, The incidences of adverse outcomes and mortality rates were significantly different ( P<0.05) among infants with different severity levels of aEEG abnormalities and the severity levels of aEEG abnormalities were positively correlated with adverse outcomes ( r=0.367, 0.471, P<0.05).Univariate analysis showed that adverse outcome group had significantly higher incidences of chorioamnionitis, seizure onset age ≤3 d, 5 min Apgar score ≤3, cranial ultrasound abnormalities, brain MR abnormalities and aEEG abnormalities than normal outcome group ( P<0.05).Logistic regression analysis showed that seizure onset age ≤3 d ( OR=3.988, 95% CI 1.376-11.674), abnormal brain MR ( OR=3.296, 95% CI 2.383-17.377) and bilirubin encephalopathy ( OR=3.792,95% CI 2.110-13.216) were independent risk factors for adverse outcomes of neonatal seizure. Conclusions:For neonatal seizure, the infants with more severe abnormal aEEG will have higher incidences of adverse outcomes and mortality. Seizure onset age ≤3 d, brain MR abnormalities and bilirubin encephalopathy were independent risk factors for adverse outcomes of neonatal seizure.