Objective To evaluate the efficacy and safety of Shengmai injection for hypoxic-ischemic encephalopathy (HIE). Methods We searched MEDLINE (1966 to February 2007), EMBASE (1980 to February 2007), CBM (1978 to 2006), CNKI (1979 to February 2007), VIP (1989 to February 2007), and handsearched five Journals on Pediatrics. We evaluated features of quality of included studies, including randomization, blinding, allocation concealment and loss of follow-up. Meta-analyses were performed using The Cochrane Collaboration’s RevMan 4.2.8. Results Seven randomized controlled trials were included. The cure rate on day 5 in the Shengmai injection group was higher than in the control group (RR 1.55, 95%CI 1.25 to 1.93), but this rate was similar on day 10 (RR 0.74, 95%CI 0.43 to 1.29). No significant difference in cure rate was noted between the Shengmai injection group and naloxone group (RR 0.88, 95%CI 0.53 to 1.46). No significant differences were observed in mortality (RR0.44, 95%CI 0.16 to 1.19) and mutilation rate (RR 0.58, 95%CI 0.21 to 1.56) between the Shengmai injection group and the control group. For those babies suffering from HIE combined with myocardial damage, Shengmai injection could speed up the recovery of ECG (WMD=–2.02, 95%CI –2.76 to –1.28) and myocardial enzymogram (CK-MB: WMD= –4.78, 95%CI –6.77 to –2.79; CK-BB: WMD=–2.68, 95%CI –4.58 to –0.78). Significant differences in NBNA score were noted between the Shengmai injection group and the control group on day 5 (WMD=4.05, 95%CI 2.47 to 5.63) and day 10 (WMD=3.50, 95%CI 2.26 to 4.74). No fatal side effects were reported. Conclusions Shengmai injection has certain therapeutic values in treating HIE. Shengmai injection can speed up the recovery ECG, CK-BM and CK-BB of HIE patients, especially in those who have myocardial damage. Shengmai injection can also improve the NBNA score. However, because of the low statistical power and high risks for selection bias, performance bias and measurement bias in the included trials, these conclusions need to be interpreted cautiously.
Objective To investigate the effect of chronic altitude hypoxia exposure on serum lipoprotein levels in healthy subjects and patients with pulmonary hypertension, and whether there is a difference in serum lipoprotein levels between patients with pulmonary hypertension at middle and high altitude. Methods The case data of 245 Han patients with COPD complicated with pulmonary hypertension admitted to the Affiliated Hospital of Qinghai University from January 2018 to September 2022 were retrospectively analyzed. According to the altitude of their long-term residence before onset, the patients were divided into two groups, 119 cases in the middle altitude group (1500 m~2500 m). 126 cases were in the high altitude group of 2500 m~4500 m. In addition, the physical examination data of 50 healthy people in the intermediate and high altitude groups were collected as the control group (the age and gender of the healthy people in the same altitude group were similar to those in the COPD-PH group), a total of 4 groups were collected. The general data, pulmonary artery systolic blood pressure (PASP), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) of the four groups were compared, and the correlation between pulmonary artery systolic blood pressure (PASP) and related variables was analyzed. ResultsThere were no significant differences in age, gender, smoking and drinking between the healthy control group and COPD-PH group (all P>0.05). There were significant differences in body mass index, PASP, TC, TG, HDL-C, LDL-C, TG/HDL-C, HDL-C/LDL-C between the healthy control group and the COPD-PH group (all P<0.05). In the healthy control group, only BMI was significantly different between the high altitude group and the middle altitude group (P<0.05). In the COPD-PH group, PASP, BMI, TC, HDL-C and TG/HDL-C in the high altitude group were significantly different from those in the moderate altitude group (all P<0.05). There were no significant differences in age, gender, smoking, drinking, TG, LDL-C and HDL-C/LDL-C between the two groups (all P>0.05), when gender, age, altitude, body mass index, PASP, smoking and drinking were included in the multi-factor linear regression equation of lipoprotein (TC, TG, HDL-C and LDL-C), it was found that different elevations (middle and higher elevations) only had statistically different effects on HDL-C (b=-0.046, t=-2.209, P=0.028). Correlation analysis showed that PASP was not correlated with age, altitude, body mass index and blood lipids (TC, TG, HDL-C, LDL-C) in the healthy control group (all P>0.05). However, in the COPD-PH group, PASP was negatively correlated with blood lipid indicators (TC, HDL-C and LDL-C). PASP was positively correlated with altitude (a risk factor for hypoxia). ConclusionsHypoxia environment factors characterized by altitude are closely related to the severity of pulmonary artery pressure in patients with COPD-PH, and higher pulmonary artery systolic pressure is closely related to lower levels of TC, HDL-C and LDL-C.
Objective To assess the effectiveness and safety of fructose 1,6-diphosphate （FDP） in the treatment of hypoxic ischemic encephalopathy （HIE）patients. Methods Biomedical databases, including MEDLINE （1977 -2004 ）, EMBASE（1989- 2004） ,Cochrane Injuries Group trials register, Cochrane Controlled Trials Register, CBMdisk and CNKI （1994- 2005 ）were searched. Chnical trials were collecte＆Quality assessments of chnical trials were carried out. Randomized controlled trials （RCTs） with mortality and the incidence of cerebral palsy, epilepsy and mental defect were selected for meta-analysis. Results Nine RCTs were included, and all were done in China. None of the 9 RCTs described the method of randomization or allocation concealment. None of the 9 RCTs mentioned wether blindness was use＆ In Jadad score, 5 trials were scored by 2 and 4 trials were 1. Seven trials were included in the meta-analysis of death, which showed that the obsolute risk （OR） [95% confidence interval （CI）] of death following FDP administration was 0. 50 （95% CI 0. 21 to 1.16）. Five RCTs reported the results of follow-up. When intention to treat （ITT） analysis was adopted, the OR of FDP on cerebral palsy was 0. 36 （95% CI 0. 19 to 0. 89）, on epilepsy was 0.74 （95% CI 0. 29 to 1.88）, and on dementia was 0. 21 （95% CI 0. 06 to 0.70）. We didn＇t conduct sensitivity analysis because no RCTs were of high quality. We didn＇t identify clinical trials compared with adverse reactions between the two groups. Conclusions The quality of RCTs on FDP for HIE is poor. Because there were no RCTs of high quality available, we can＇t draw a conlusion. Well-designed RCTs with economic evaluation are urgently needed to evaluate the value of FDP in the treatment of HIE.
Objective To investigate the protection on the intrahepatic cholangiocyte mediated by hypoxic preconditioning (HP) after liver transplantation and the role of vascular endothelial growth factor (VEGF). Methods The model of autologous liver transplantation was established, and the rats were divided into 3 groups: autologous liver transplantation group, hypoxic preconditioning before operation group (HP group) and sham operation group. At 6, 12, 24, 48 h after operation, blood samples were collected for examination of the serum total bilirubin (TBIL), direct bilirubin (DBIL) and alkaline phosphatase (ALP), and the expression of VEGF was detected by immunohistochemical method. The pathological changes of cholangiocytes were observed by light microscope. Results As compared with autologous liver transplantation group, the levels of seurm TBIL, DBIL and ALP in HP group were lower (P＜0.05), while the expression of VEGF in HP group was higher at the whole process (P＜0.05). The degrees of billiary epithelium damage and inflammatory infiltration in autologous liver transplantation group were more severe than those in HP group. Conclusion HP has protective effect on cholangiocytes after liver transplantation, in which VEGF may play an important role.
ObjectiveTo observe the effect of integrin β8 on the neuronal apoptosis after hypoxia ischemia (HI) in astrocyte/neuron co-culture system. MethodsAstrocytes and neurons were cultured in vitro from cerebral cortex of the P1-3 days Sprague Dawley rats and E16 days fetal rats, respectively. Immunocytochemistry staining was used to identify the purity of cells. Integrin β8 mRNA expression was qualified in the astrocytes at 12 hours, 1 day, and 2 days after HI and reoxygenation (experimental group) and in normal astrocytes (control group) by RT-PCR. Integrin β8 small interering RNA (siRNA) system was established to specifically block astrocyte β8 expression, the efficiency of integrin β8 inhibition was detected by real-time fluorescent PCR. The astrocytes and neurons were co-cultured to established the astrocyte/neuron co-culture system. The neuronal apoptosis was detected with TUNEL in the normal neurons/astrocytes group (co-cultured HI group), the astrocytes infected by integrin β8 siRNA for 2 days/normal neurons group (β8 RNA interference group), and normal neurons in vitro with HI treatment group (HI group) at 1 day after HI and reoxygenation. The normal neurons without treatment as control (control group). ResultsGlial fibrillary acidic protein and neuronal nuclei staining suggested a purity of more than 90% in cultured cells. HI resulted in an increase of integrin β8 mRNA expression at 12 hours after reoxygenation in astrocytes, which peaked at 1 day after reoxygenation, then slowly decreased and remained higher at 2 days, showing significant differences between control group and experimental group and among different time points in experimental group (P<0.05). RNA interference efficiency was most significant at 2 days after astrocytes infected with integrin β8 siRNA (P<0.05). The neuronal apoptosis was significantly increased in HI group, co-cultured HI group, and β8 RNA interference group when compared with control group (P<0.05). But neuronal apoptosis index (AI) was significantly decreased in co-cultured HI group and β8 RNA interference group when compared with HI group (P<0.05). The significant difference of AI was found between co-cultured HI group and β8 RNA interference group (P<0.05). ConclusionIntegrin β8 expression can be induced with hypoxic-ischemic brain damage, leading to decreased AI of neurons and obvious protective effect.
Objective To study the effects of hypoxic preconditioning on the glucose metabol ism of rat BMSCs and its underlying mechanism so as to provide the theoretical basis for the optimization of the stem-cell based therapy. Methods Density gradient centrifugation method was adopted to isolate rat BMSCs from neonatal SD rats (aged 1-3 days). BMSCs were cultured to 4th passage and divided into 4 groups based on different culture conditions: group A in normoxia condition for 24 hours, group B in 1% O2 for 24 hours, group C in 2-methoxyestradiol (20 μmol/L) for 24 hours before hypoxic preconditioning, and group D in hypoxia-inducible factor 1 (HIF-1) specific siRNA (50 μmol/L) for 12 hours before hypoxicpreconditioning. MTT method was appl ied to evaluate the prol iferation of BMSCs. Biochemical analyzer and Real-timefluorescent quantitative PCR were appl ied to detect the glucose uptake, lactate production, and HIF-1α mRNA and Glut-1mRNA levels of BMSCs. Results MTT showed that the absorbance (A) values were 387.67 ± 58.92, 322.50 ± 50.60, 297.00 ± 53.00, and 286.00 ± 41.00 in groups A, B, C, and D, respectively, showing no significant difference among 4 groups (P gt; 0.05). The levels of glucose uptake and lactate production were higher in group B than in groups A, C, and D, showing significant differences (P lt; 0.05); the levels of groups C and D were higher than those of group A, but showing no significant difference (P gt; 0.05). The mRNA expressions of HIF-1α and Glut-1 elevated significantly in group B when compared with those in group A (P lt; 0.05); groups C and D were significantly lower than group B (P lt; 0.05) and were significantly higher than group A (P lt; 0.05). Conclusion Hypoxic preconditioning can stimulate the glucose uptake and metabol ism of rat BMSCs, whose mechanism is probably related to up-regulating the mRNA expressions of HIF-1α and Glut-1.
ObjectiveTo investigate the effects of hypoxic three-dimensional culture microenvironment on the proliferation of bone marrow mesenchymal stem cells and its mechanism. MethodsP5 generation mouse bone marrow mesenchymal stem cells and P (3HB-co-4HB) were co-cultured under normoxic three-dimensional (20%) and hypoxic three-dimensional microenvironment (4%) respectively. After 24 hours, the proliferation of the two groups was determined by CCK-8 method. The expression of HIF-1α gene was detected by real-time quantitative PCR after 12 hours. Western blotting was used to detect the expression of HIF-1α protein after 24 hours. ResultsAfter 24 hours, the CCK-8 method showed that the OD value of the hypoxia group was significantly higher than that of the normoxia group (0.455±0.027 vs. 0.352±0.090, n=12, P<0.05). After 12 hours of hypoxic culture, the expression level of HIF-1α mRNA in the hypoxia group was significantly higher than that in the normoxia group (P<0.05). Compared with the normoxia group (0.47± 0.05), the relative expression level of HIF-1α protein in the hypoxia group (0.63±0.06) significantly increased in the Western blotting after 24 hours (n=3, P<0.05). ConclusionThe hypoxic three-dimensional microenvironment can promote the proliferation of bone marrow mesenchymal stem cells, which may be related to the activation of HIF-1α signaling pathway.
To review the role of hypoxia inducible factor 1α (HIF-1α) in hypoxic-ischemic injury and its repair, and to analyze the possible mechanisms. Methods Recent l iterature on HIF-1α and its role in hypoxic-ischemic injury was reviewed and analyzed. Results HIF-1α was involved in the hypoxic-ischemic injury of various organs or tissues and their repair processes. Conclusion HIF-1α has a potential to treat common cl inical hypoxic-ischemic injuries and has a promisingfuture for appl ication.
Objective To investigate the influence of hypoxic preconditioning on pulmonary structure of rats exposed to simulated high altitude hypoxia and to explore the role of hypoxia inducible factor-1α（HIF-1α）.Methods Fifty-six Wistar rats were randomly divided into 7 groups(n=8 in each group),ie,a normal control group(N group)，an acute hypoxic control group(H0 group)，an acute hypoxic group(H1 group)，a 3 000 m hypoxic preconditioning group(C3.0 group)，a 3 000 m hypoxic preconditioning + acute hypoxic group (C3.1 group)，a 5 000 m hypoxic preconditioning group(C5.0 group)，and a 5 000 m hypoxic preconditioning + acute hypoxic group(C5.1 group).After treated with hypoxic preconditioning，the animals were exposed to simulated altitude of 6 000 m for 24 hours.Then the protein and mRNA expression of HIF-1α in lung of N，H0，C3.0 and C5.0 groups were assessed by Western blot and RT-PCR，respectively.The lung structure in N，H1，C3.1 and C5.1 groups was observed by light microscope and electron microscope.Results Pulmonary interstitial edema was apparently observed in H1 group，while significantly relieved in two hypoxic preconditioning groups.HIF-1α protein was not detected in rat lungs by Western blot analysis.Compared to N group，the levels of HIF-1α mRNA significantly increased in C3.0 group and C5.0 group(both Plt;0.01).Conclusions Hypoxic preconditioning can relieve hypoxic pulmonary interstitial edema and increase HIF-1α mRNA expression in rat lungs.HIF-1 may be involved in the process of hypoxic preconditioning in rat lungs.
Objective To investigate the effects of simvastatin on the collagen synthesis of rat pulmonary arterial smooth muscle cells ( PASMCs ) induced by hypoxia. Methods Under hypoxic condition, rat PASMCs were cultured with different concentrations of simvastatin. Collagen synthesis of PASMCs with or without simvastatin were measured by 3H-proline incorporation assay. The mRNA expression of TGF-β1 and the contents of super oxide dismrtase ( SOD) ,malondialdehyde ( MDA) in mediumwere also measured. Results The incorporation data of 3H-TdR in the hypoxia group was significantly increased as compared with that in the control group ( P lt;0. 01) , and simvastatin significantly reduced the incorporation data of 3H-TdR induced by hypoxia. The expression of TGF-β1 mRNA in the hypoxia group was significantly increased as compared with that in the control group ( P lt; 0. 01 ) , and simvastatin could significantly inhibited hypoxia-induced expression of TGF-β1 mRNA in a dose-dependent manner. Compared with the hypoxia group, the expression of TGF-β1 mRNA decreased by 55% in simvastatin( 10 - 6mol /L) group ( P lt; 0. 01) , and by 70% ( P lt; 0. 01) in simvastatin ( 10 - 5mol /L) group. Compared with the control group, the activity of SOD was reduced and the contents of MDA were increased significantly in the hypoxia group. Simvastatin can increase the activity of SOD and reduced the content of MDA in a dose-dependent manner. Conclusions Simvastatin can decreases collagen synthesis of PASMCs. This effect might be explained that simvastatin can reduce lipid peroxide and expression of TGF-β1 mRNA.