Research progress on the influence of maternal gestational diabetes mellitus on fetal outcomes / 中华实用儿科临床杂志

Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy, which seriously affects the normal development of the fetus.Blood glucose control during pregnancy is associated not only with recent adverse outcomes such as preterm birth, macrosomia, hypoglycemia, neonatal respiratory distress syndrome, electrolyte disorders, heart malformations and intestinal disorders, but also with long-term results such as conti-nued impaired glucose tolerance, obesity, metabolic syndrome, mental illness and eye disease.Correct understanding of adverse effects of GDM on newborn infants in the short and long term and their related mechanisms as well as timely prevention and treatment measures can significantly improve the outcome of pregnancy.This paper will make a summary of these problems.

Correlation between perfusion index and the severity of disease in early neonates / 中国小儿急救医学

Objective:To analyze the role of perfusion index(PI)in assessing the severity of neonatal illnesses.Methods:A total of 502 newborns admitted to the Department of Neonatology within 24 hours of birth at Xinxiang Central Hospital from October 2018 to July 2019 were recruited.Neonatal critical illness score(NCIS)was graded within 24 hours of admission, and newborns were categorized into non-critical(NCIS>90 scores), critical(NCIS 70-90 scores)and extremely critical(NCIS<70 scores). PI was monitored in all newborns within 24 hours of birth in a resting state.A total of 502 PIs were recorded, including 341 cases of non-critical, 110 cases of critical and 51 cases of extremely critical.Results:The medium PI [ M( P25, P75)] of newborns in non-critical, critical and extremely critical groups were 1.80(1.40, 2.60), 0.96(0.74, 1.43)and 0.65(0.41, 1.10), respectively.PI values in extremely critical group was significantly lower than those in critical group and non-critical group( P<0.05). The medium PI [ M( P25, P75)] of full-term newborns, moderate/late preterm newborns and extremely/very preterm newborns were 1.70(1.20, 2.70), 1.60(1.10, 2.30) and 1.35(0.80, 2.30), respectively.PI in full-term newborns was significantly higher than those in moderate/late preterm newborns and extremely/very preterm newborns( P<0.05). PI was moderately positively correlated with NCIS in newborns( r=0.791, P<0.01). The area under the receiver operating characteristic curve of NCIS predicted by PI value was 0.846, and the prediction sensitivity and specificity were 85.0% and 70.8% when PI was 0.56. Conclusion:PI is correlated with NCIS in newborns, which is able to reflect the severity of neonatal illnesses.A low PI indicates severe conditions of neonatal illnesses.

Case report of congenital complete heart block in premature twins and literatures review / 中华实用儿科临床杂志

Objective:To investigate the pathogenesis, precaution and treatment of neonatal congenital complete heart block (CCHB) in twins.Methods:The clinical data of a case of premature twins with neonatal CCHB from the Department of Neonatology, the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed and related literature was reviewed.Results:(1)Case review: the 37-year-old gravida had no symptoms.Fetal ultrasound cardiogram(fUCG)at 23 weeks of gestation indicated bradycardia and CCHB.Then, the mother was diagnosed with undifferentiated connective tissue disease.After treatment with human immunoglobulin, dexamethasone and hydroxychloroquine, fUCG at 31 weeks of gestation still suggested CCHB.An emergency cesarean section was performed on the diagnosis of threatened preterm labor.With weakly positive neonatal antinuclear antibody (ANA), and positive Ro60 and Ro52 autoantibodies, twins were diagnosed with CCHB by 24 hour-Holter monitors.One of the twins was discharged with CCHB (ventricular rate of 80-90 times/min) after systemic therapy, but the weight increased to 2 200 g. The other one of the twins suffered from the sudden decrease of heart rate and blood pressure and finally died of sudden cardiac arrest.(2) Literature search: two cases in Chinese and 9 cases in English were reviewed.Among them, 9 cases were sjogren syndrome type A (SSA)/Ro and sjogren syndrome type B(SSB)/La related CCHB, and 2 cases were idiopathic CCHB.Conclusions:The placental transfer of anti-SSA or anti-SSB is an important mechanism of neonatal CCHB in twins, and other factors may also be involved.Current treatments are unsatisfactory.Most patients need pacemaker implantation.Early diagnosis and prenatal management can improve the prognosis.

Proliferation, migration and apoptosis of acute myeloid leukemia cells regulated by mir-23a-3p targeting SMC1A and the mechanism / 中华肿瘤杂志

Objective@#To investigate the effects of miR-23a-3p on proliferation, migration and apoptosis on human acute myeloid leukemia (AML) cells by targeting SMC1A.@*Methods@#Microarray analysis was used to screen differentially expressed microRNAs and mRNAs in human AML cells. Real-time fluorescence quantitative PCR (RT-qRCR) was used to detect the expressions of miR-23a-3p and SMCA in human AML cell line U937. TargetScan database was used to analyze the correlation between miR-23a-3p and SMC1A. Double luciferase reporter gene was used to detect the interaction between miR-23a-3p and SMC1A. The effect of miR-23a-3p expression on the proliferation of U937 cells was detected by clonal assay. The migration, apoptosis, cell cycle and caspase-3 activity of U937 cells regulated by miR-23a-3p were detected by cell scratch assay and flow cytometry, respectively. Western blot was used to detect the expressions of Bax and Bcl-2 in U937 cells.@*Results@#Compared with human normal monocyte SC group (1.00), the expression of miR-23a-3p in U937 cells was up-regulated (2.56±0.78) (P<0.01), while the expression of SMC1A was down-regulated (0.48±0.56, P<0.01). miR-23a-3p specifically bond to SMC1A 3′UTR and regulated the expression activity of SMC1A. Overexpression of miR-23a-3p promoted the proliferation and migration of U937 cells and inhibited the apoptosis of U937 cells, while up-regulation of SMC1A inhibited the proliferation and migration of U937 cells and promoted the apoptosis of U937 cells. The percentages of G0/G1 phase, G2/M phase and S phase cells in the negative control group were (37.48±0.21)%, (16.78±0.18)% and (45.74±0.15)% respectively, and those in the miR-23a-3p mimics group were (19.96±0.11)%, (41.69±0.24)% and (38.24±0.34)%, respectively. The difference was statistically significant (all P<0.05). The proportions of G0/G1 phase, G2/M phase and S phase cells in the group of miR-23a-3p mimics+ pcDNA3.1-SMC1A were (36.88±0.21)%, (30.44±0.33)% and (32.88±0.16)%, respectively, without significant difference when compared with those of the miR-23a-3p mimics group (P>0.05). The relative expression levels of Bax and Bcl-2 protein in the negative control group were 0.55±0.45 and 0.31±0.54, respectively. Overexpression of miR-23a-3p inhibited the expression of Bax protein in U937 cells (0.23±0.13, P<0.001), promoted the expression of Bcl-2 protein (0.50±0.23, P<0.01), while SMC1A increased the expression of Bax protein in U937 cells (0.40±0.11, P<0.01), and inhibited the expression of Bcl-2 protein (0.37±0.15). In the negative control group, caspase-3 activity was (25.82±0.89)%. Overexpression of miR-23a-3p inhibited caspase-3 activity in U937 cells (3.64±0.56)%, P<0.01, while up-regulation of SMC1A promoted caspase-3 activity in U937 cells (15.29±0.85)%, P<0.01.@*Conclusion@#miR-23a-3p can inhibit the proliferation and migration and promote apoptosis of human AML cells by targeting SMC1A.

Study on the relationship between Toll like receptor 4 expression and apoptosis in periventricular leukomalacia rat model induced by hypoxia-ischemia / 中华实用儿科临床杂志

Objective@#To investigate the correlation between Toll like receptor 4 (TLR4) expression and apoptosis in periventricular leukomalacia (PVL) rat model induced by hypoxia-ischemia.@*Methods@#One hundred and forty three-day-old sprague-dawley (SD) rats, which were divided into experimental group (ischemia-hypo-xia group) and control group (sham operation group) randomly, were used to establish a hypoxic model by ligating the right common carotid artery and inhaling gas mixtures with 60 mL/L oxygen and 940 mL/L nitrogen.The rats were killed 6 h, 12 h, 24 h, 3 d, 7 d after model reproducing and the brain tissues were used for the following experiments.The pathological changes and apoptosis of brain tissues were detected by way of hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (Tunel) assay respectively, and TLR4 expression was detected by adopting immunohistochemistry and reverse-transcription polymerase chain reaction(RT-PCR). The data were analyzed by using the SPSS 19.0 software.@*Results@#TLR4 expression in the modeling rat brain commenced to increase in 6 hours (0.541±0.069, 0.166±0.058)and reached the peak in 3 days(1.932±0.161, 0.300±0.039), and then began to decline in 7 days (1.242±0.109, 0.220±0.025) post hypoxia-ischemia.Compared with the control group, there were statistical significances at 6 h, 12 h, 24 h, 3 d and 7 d (all P<0.05). The apoptosis of brain ti-ssue cells in the modeling rat brain started to increase at 6 hours(21.33±3.50) and reached the peak in 3 days (35.97±4.20), and then began to decline in 7 days (31.02±4.22) post hypoxia-ischemia.Compared with the control group, there were statistical significance at 6 h, 12 h, 24 h, 3 d and 7 d (all P<0.05). The TLR4 expression was positively correlated with cell apoptosis (r=0.774, 0.575, all P<0.05).@*Conclusions@#In the rat model of PVL induced by hypoxia-ischemia, TLR4 is likely to injure the neural cell through apoptosis.

Effect of ω-3 polyunsaturated fatty acids and ω-6 polyunsaturated acids on Toll-like receptor /nuclear fac-tor-κB signaling pathway and the inflammatory cytokines in neonatal rats with brain injury induced by lipopolysaccharide / 中华实用儿科临床杂志

Objective To investigate the effects of ω-3 polyunsaturated fatty acids(ω-3PUFAs)and ω-6 polyunsaturated fatty acids(ω-6PUFAs)on Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway,and the expressions of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β and IL-6 in neonatal rats with brain injury induced by lipopolysaccharide (LPS). Methods Ninety-six neonatal rats were divided into control group,ω-3PUFAs group,ω-6PUFAs group,and LPS group by using random number table method. Intraperitoneal injection of LPS was performed in LPS group,ω-6PUFAs group and ω-3PUFAs group to establish models of rat brain injury. The rats in control group received 9 g/L saline. Twelve newborn rats were killed at 1 d or 5 d after intraperito-neal injection in each group for hippocampus selection. Real -time PCR and Western blot were used to detect the mRNA and protein expression levels of TLR4,NF-κB,TNF-α,IL-1β and IL-6. Results One day after mode-ling,TLR4,NF-κB,TNF-α,IL-1β and IL-6 mRNA expressions in ω-3PUFAs group (10. 63 ± 0. 07,5. 86 ± 1. 05,7. 65 ± 2. 29,5. 23 ± 1. 31,3. 36 ± 0. 72)were lower than those in ω-6PUFAs group (18. 83 ± 2. 10,8. 79 ± 2. 08,11. 95 ± 3. 23,10. 97 ± 2. 24,6. 37 ± 1. 17)and LPS group (15. 76 ± 1. 59,7. 13 ± 1. 10,9. 71 ± 2. 14,7. 83 ± 0. 85,4. 78 ± 0. 51),and the differences were all statistically significant(all P＜0. 05);which in ω-6PUFAs group were higher than those in LPS group,and the differences were all significant (all P＜0. 05). TLR4,NF-κB,TNF-α, IL-1β and IL-6 protein levels in ω-3PUFAs group (1. 57 ± 0. 11,1. 58 ± 0. 09,1. 55 ± 0. 09,1. 63 ± 0. 31,1. 36 ± 0. 12)were lower than those in ω-6PUFAs group (1. 96 ± 0. 17,2. 21 ± 0. 12,1. 95 ± 0. 23,1. 97 ± 0. 24,1. 77 ± 0. 17)and LPS group (1. 73 ± 0. 15,1. 87 ± 0. 10,1. 79 ± 0. 14,1. 83 ± 0. 15,1. 58 ± 0. 11)in 1 d,and the diffe-rences were all significant (all P＜0. 05),and those in ω-6PUFAs group were higher than those in LPS group (all P＜0. 05). Similarly,TLR,NF-κB,TNF-α,IL-1β and IL-6 mRNA and protein expression levels in ω-3PUFAs group (3. 78 ± 0. 88,3. 86 ± 0. 62,6. 26 ± 1. 94,3. 65 ± 1. 44,2. 11 ± 0. 87;1. 15 ± 0. 08,1. 32 ± 0. 10,1. 46 ± 0. 04, 1. 38 ± 0. 14,1. 21 ± 0. 09)were lower than those in ω-6PUFAs group (7. 76 ± 1. 65,5. 51 ± 0. 88,7. 96 ± 2. 13,5. 35 ± 1. 75,4. 88 ± 1. 35;1. 42 ± 0. 15,1. 51 ± 0. 36,1. 65 ± 0. 13,1. 72 ± 0. 23,1. 48 ± 0. 10)and LPS group (6. 21 ± 1. 87, 4. 98 ± 0. 73,7. 11 ± 2. 10,4. 84 ± 1. 75,4. 25 ± 0. 64;1. 35 ± 0. 13,1. 44 ± 0. 22,1. 59 ± 0. 10,1. 61 ± 0. 18,1. 35 ± 0. 07) in 5 d (all P＜0. 05),and which in ω-6PUFAs group were higher than those in LPS group,and the differences were sig-nificant (all P＜0. 05). Conclusion ω-6PUFAs can up-regulate the activity of TLR4,NF-κB,and reduce the re-lease of TNF-α,IL-1β and IL-6;and ω-3PUFAs can down-regulate the activity of TLR4,NF-κB,and reduce the release of TNF-α,IL-1β and IL-6,so it has a neural protective effect in brain injury induced by LPS.

Identification of the long noncoding RNA_ AK096792 in cord blood as a clinical predictor for early diagnosis of bronchopulmonary dysplasia in preterm infants / 中华实用儿科临床杂志

Objective@#To investigate the feasibility of long noncoding RNA (lncRNA)_AK096792 as a clinical predictor of bronchopulmonary dysplasia (BPD) in preterm infants.@*Methods@#All the cord blood(2-5 mL) of very low birth weight (VLBW) preterm infants born in Huai′an First Hospital Affiliated to Nanjing Medical University were collected from December 1, 2015 to December 1, 2017.Moreover, the peripheral blood(2 mL) of those VLBW infants diagnosed with BPD was also collected.A total of 36 infants with BPD were collected.Another 36 cases of premature children with VLBW were chosen as control group according to random number table.The relative content of lncRNA_AK096792 in cord blood and peripheral blood was detected by using real-time quantitative PCR (qPCR). Additionally, the correlation of lncRNA_AK096792 levels between cord and peripheral blood of BPD infants was analyzed.The sensitivity and specificity of lncRNA_AK096792 for BPD were analyzed by using receiver operating curve test.@*Results@#(1)LncRNA_AK096792 was a common, evolutionarily conserved, non-coding RNA present in both mouse and human.(2) The expression level of lncRNA_AK096792 in peripheral blood was significantly higher than that in cord blood in BPD group[(463.3±352.0)% vs.(50.0±37.5)%], and the difference was significant(P<0.001), and they were highly correlated (r=0.825, P<0.001). (3) The level of lncRNA_AK096792 in cord blood in BPD group was signi-ficantly higher than that in non-BPD group [(484.3±280.5)% vs.(101.2±28.6)%], and the difference was significant(P<0.001). (4)When lncRNA_AK096792 served as a clinical predictor for BPD, the specificity was 83.3%, the sensitivity was 75.6%, and an area under the receiver operating characteristic curve was 0.88(P<0.001).@*Conclusions@#LncRNA_AK096792 is highly correlated with the development of BPD.The level of lncRNA_AK096792 in umbilical cord blood of premature infants can be used as an early predictive marker for BPD, it calls for further study.

Effects of discoidin domain receptor1 mediated phosphorylation of protein Tau on hypoxic-ischemic brain damage in neonatal rats / 中华围产医学杂志

Objective To study the effects of discoidin domain receptor 1 (DDR1) mediated phosphorylation of protein Tau on hypoxic-ischemic brain damage (HIBD) in neonatal rats and its possible mechanism.Methods Sixty-four seven-day-old male specific-pathogen-free Wistar rats were randomly divided into four groups with sixteen in each: Sham, HIBD, HIBD with normal saline (HIBD+NS) and HIBD with DDR1 inhibitor (HIBD+DI) groups. A rat model of HIBD was established by subjecting the rats to left common carotid artery ligation, followed by exposing them to hypoxia for two hours. In HIBD+DI group, the inhibitor of DDR1 was immediately injected into lateral cerebroventricles of the rats following modeling. Forty-eight hours after injection, tissues of left cerebral cortex were collected from each rat to evaluate histopathological changes with HE staining. Western-blotting was used to assess the phosphorylation levels of DDR1 and protein Tau. Enzyme-linked immunosorbent assay was performed to detect the concentrations of acetylcholine. Analysis of variance ort test were used for statistical analysis.Results (1) Damages in cerebral cortex: Percentages of abnormal neurons in the rats of HIBD group were higher than those in Sham group [(80.28±4.51)% vs (10.40±2.17)%,t=39.491,P<0.01]. Pyknotic or necrotic neurons in the rats of HIBD+DI group were less than those in HIBD+NS group [(31.91±3.05)% vs (82.01±7.20)%,t=18.123,P<0.01]. (2) Phosphorylation of DDR1 and protein Tau: Levels of phosphorylated DDR1 in the cerebral cortexes of rats in HIBD group were higher than those in Sham group (0.922±0.199 vs 0.095±0.023,t=10.379,P<0.01), and those levels in HIBD+NS group were higher than those in HIBD+DI group (1.200±0.171 vs 0.255±0.111,t=11.901, P<0.01). The phosphorylation of protein Tau was similar to that of DDR1 (0.919±0.228 vs 0.194±0.224 in HIBD and Sham groups,t=7.347; 1.100±0.167 vs 0.291±0.210 in HIBD+NS and HIBD+DI groups,t=9.447;bothP<0.01). (3) Levels of acetylcholine: Levels of acetylcholine in cerebral cortexes of rats in HIBD group were lower than those in Sham group [(3.685±0.472) vs (7.429±0.861) ng/g protein,t=10.781,P<0.01], and that levels in HIBD+DI group were higher than those in HIBD+NS group [(7.058±0.915) vs (2.521±0.723) ng/g protein,t=10.989,P<0.01].Conclusions Activation of DDR1 plays a key role in enhancing the phosphorylation of protein Tau and in reducing the secretion of acetylcholine in cerebral cortexes of rats with HIBD. Inhibitor of DDR1 could protect neonatal rats from HIBD through the decreasing of protein Tau phosphorylation and increasing of acetylcholine release by inhibiting the activation of DDR1.

Expression of NF-κBp65 and TLR4 in neonatal rats with hypoxic-ischemic brain damage / 国际儿科学杂志

Objective To investigate the expression of nuclear factor-kappa Bp65 (NF-κBp65)and Toll-like receptor 4(TLR4)protein in the brain tissues of 7-day-old Sprague-Dawley(SD) rats with cerebral hypoxia-ischemia encephalopathy (HIE) and to explore the role of TLR4 and NF-κBp65 in the pathogenesis of neonatal rats with hypoxic-ischemic brain damage.Methods Seven-day SD rats were randomly divided into the experimental group and the control group.Brain pathological changes were observed in light microscopy at 6 h、12 h、24 h、72 h、7 d after HIE.The expression of TLR4 and NF-κBp65 in brain tissues were analyzed by immunohistochemistry method.Results NF-κBp65 and TLR4 were expressed in the neuron and microglia of control group and experimental group.The expression were most significant at cerebral cortex and hippocamp.However,the expression of NF-κBp65and TLR4 began to increase at HIE 6h:NF-κBp65 (0.219 3 ± 0.024 7,0.215 7 ±0.030 4)and TLR4(0.327 1 ±0.033 3,0.303 9 ±0.037 9),and achieved the hightest at HIE 24h:NF-κBp65 (0.3564±0.0235,0.3365 ±0.023 2)and TLR4(0.434 2 ±0.0428,0.4193 ±0.041 3),then decreased at HIE 72 h:NF-κBp65 (0.289 2 ± 0.032 0,0.260 9 ± 0.021 2) and TLR4 (0.300 5 ± 0.020 9,0.282 0 ± 0.022 6),and HIE 7 d:NF-κBp65(0.247 9 ±0.0340,0.242 1 ±0.025 4) and TLR4(0.274 4 ±0.0288,0.257 1 ±0.027 5).Conclusion There is a positive correlation between NF-κBp65 and TLR4 in rats with HIE.It suggested that they may have the same pathophysiology development in HIE.

Effect of Omega-3 fish oil fat emulsion on the expression of Toll-like receptor 4 and nuclear factor-κB in the neonatal rats hippocampus after hypoxic-ischemic / 中华实用儿科临床杂志

Objective To discuss whether Omega-3 fish oil fat emulsion has the potential protective mechanism for 7-day-old rats with hypoxic-ischemic brain damage (HIBD).Methods One hundred and sixty-eight 7-day-old SD rats were randomly divided into 4 groups:group A (sham group),group B (Omega-3 fish oil fat emulsion group),group C (normal fat emulsion group),group D (model group),and there were 42 cases in each group.Neonatal HIBD was induced by the method of Rice.Rats were sacrificed at 1 d,3 d and 7 d after the surgery.Hippocampus was removed for Real-time PCR and Western blot test to detect Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) mRNA and protein expression.TUNEL staining comparison was done among different groups to observe the number of cellular apoptosis.Results HE staining of hippocampus CA1 area in 3 d showed that brain tissues in group A maintained normal structures;those in group D had much more brain cells with severe edema than other groups;TLR4 and NF-κB mRNA and protein expression levels in group D were higher than those in group A in 1 d (all P ＜0.05);TLR4 and NF-κB expression levels of mRNA and protein in group B (4.89 ± 0.51,9.30 ± 1.53;1.15 ±0.10,1.44 ± 0.14) were lower than those in group C (17.58 ± 2.50,20.13 ± 1.00;2.56 ± 0.10,2.82 ± 0.09) and group D (15.94-± 2.52,26.21 ± 3.00;2.34 ± 0.11,4.51 ± 0.36) in 3 d (all P ＜ 0.05),and compared with group A (6.30 ± 1.52,5.32 ± 1.06;1.32 ± 0.10,2.42 ± 0.14),there was significant difference (all P ＞ 0.05);TLR4 and NF-κB mRNA and protein expression levels in group B were lower than those in group C and group D in 7 d(all P ＜0.05),and compared with group A there was no significant difference (all P ＞ 0.05).The apoptotic cell number of brain tissues in 3 d:group B (13.67 ±2.52) were lower than those in group C (27.67 ±2.52) and group D (41.00 ±3.61) (all P ＜0.05),and compared with the group A (6.00 ±2.00),the difference was not statistically significant (P ＞ 0.05).Conclusions Omega-3 fish oil fat emulsion plays an important role in protecting neonatal rats with HIBD.The mechanisms were likely to reduce TLR4,NF-κB and cell apoptosis levels.

The effect of high-glucose-high-fat diet in male SD rats on methylation of INSR gene in F1 offspring / 中华内分泌代谢杂志

Objective To study the effect of high-glucose-high-fat diet on expression and methylation of insulin receptor ( INSR) gene in F1 offspring. Methods Sixty 5-week-old male SD rats were randomly divided into two groups:normal diet group and high-glucose-high-fat diet group. After rats were fed for three months, all male rats were performed to copulate with normal female rats. The body weight, blood glucose, and blood insulin of neonatal rats of F1 offspring were measured. The genome DNA, total RNA, and total protein were extracted from livers, brains, and muscles of neonatal rats. Relative expression of INSR in both mRNA level and protein level were detected using a realtime PCR test and a Western blot test respectively. Methylation of INSR promoter was analyzed by a methylation specific PCR ( MSP ) . Results Both body weight and fasting glucose were without significant difference in two groups. In high-glucose-high-fat diet group, both the glucose tolerance and insulin tolerance of neonatal rats in F1 offspring were significantly decreased. Except that in brains, the expressions of INSR gene in livers and in muscles of neonatal rats in high-glucose-high-fat diet group were down-regulated in mRNA ( realtime PCR ) and protein levels ( Western blot) compared to the normal diet group. Meanwhile, the methylation of INSR gene in livers and muscles were strengthened in high-glucose-high-fat diet group. Conclusion A high-glucose-high-fat diet fed to male SD rats leads to the decrease in glucose tolerance, insulin tolerance, and the inhibition of expression of hepatic and muscle INSR gene in neonatal offspring. The methylation of INSR gene could be involved in this phenomenon.

Expression and Clinical Significance of PCNA, p53 and Bcl-2 Protein in Bone Marrow Cells in Children with Acute Leukemia / 中国医师杂志

Objective To investigate the relationship between the expressions of proliferating cell nuclear antigen (PCNA), p53 and Bcl-2 protein and clinical chemothreapy, prognosis in bone marrow cells in children with acute leukemia (AL). Methods Immunohistochemical SP method was used to detect the expressions of PCNA, p53 and Bcl-2 in specimens of bone marrow puncture of 59 children with AL and 15 healthy children as control. Results There was a significant difference in the expressions of PCNA, p53 and Bcl-2 proteins between the initially treated patients and healthy subjects, and between the remission patients and non remission ones. There was not a significnat difference in PCNA expression between the refractory patients and healthy subjects, and PCNA expression was related to the chemotherapeutic sensitivity. There was a significant difference in the 6-week remission rate between the patients with and without PCNA expression, but there was no significant difference in the over 3 years survival rate without illness. The expression levels of Bcl-2 and p53 were significantly higher in the refractory patients than those in healthy subjects. The patients with the high expression of p53 and Bcl-2 were resistant to chemotherapy, low in the remission rate and poor in prognosis. Conclusion The AL patients with PCNA expression were higher in remission rate, and PCNA expression was not associated with long-term prognosis. The AL patients with the expression of p53 and Bcl-2 were lower in remission rate, and their expression was associated with long-term prognosis. Both p53 and Bcl-2 protein may serve as a molecular marker to predict chemotherapeutic sensitivity and prognosis. PCNA, p53 and Bcl-2 may be involved in the pathogenesis of child AL by various ways. It is more valuable for predicting prognosis to simultaneously detect the expression of PCNA, p53 and Bcl-2 proteins.