MicroRNA-214 promotes alveolarization in neonatal rat models of bronchopulmonary dysplasia via the PlGF-dependent STAT3 pathway.

BACKGROUND: Recently, the role of several microRNAs (miRNAs or miRs) in pulmonary diseases has been described. The molecular mechanisms by which miR-214 is possibly implicated in bronchopulmonary dysplasia (BPD) have not yet been addressed. Hence, this study aimed to investigate a putative role of miR-214 in alveolarization among preterm neonates with BPD. METHODS: Microarray-based gene expression profiling data from BPD was employed to identify differentially expressed genes. A BPD neonatal rat model was induced by hyperoxia. Pulmonary epithelial cells were isolated from rats and exposed to hyperoxia to establish cell injury models. Gain- and loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were measured using RT-qPCR and Western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene and RIP assays. IL-1ß, TNF-a, IL-6, ICAM-1 and Flt-1 expression in the rat models was measured using ELISA. RESULTS: The lung tissues of neonatal rats with BPD showed decreased miR-214 expression with elevated PlGF expression. PlGF was found to be a target of miR-214, whereby miR-214 downregulated PlGF to inactivate the STAT3 pathway. miR-214 overexpression or PlGF silencing decreased the apoptosis of hyperoxic pulmonary epithelial cells in vitro and restored alveolarization in BPD neonatal rats. CONCLUSION: Overall, the results demonstrated that miR-214 could facilitate alveolarization in preterm neonates with BPD by suppressing the PlGF-dependent STAT3 pathway.

Anti-placental growth factor antibody ameliorates hyperoxia-mediated impairment of lung development in neonatal rats.

This study investigates the effect of the overexpression of the placental growth factor (PGF) and hyperoxia on lung development and determines whether anti-PGF antibody ameliorates hyperoxia-mediated impairment of lung development in newborn rats. After exposure to normoxic conditions for seven days, newborn rats subjected to normoxia were intraperitoneally or intratracheally injected with physiological saline, adenovirus-negative control (Ad-NC), or adenovirus-PGF (Ad-PGF) to create the Normoxia, Normoxia+Ad-NC, and Normoxia+Ad-PGF groups, respectively. Newborn rats subjected to hyperoxia were intraperitoneally injected with physiological saline or anti-PGF antibodies to create the Hyperoxia and Hyperoxia+anti-PGF groups, respectively. Our results revealed significant augmentation in the levels of PGF and its receptor Flt-1 in the lung tissues of newborn rats belonging to the Normoxia+Ad-PGF or Hyperoxia groups. PGF overexpression in these groups caused lung injury in newborn rats, while anti-PGF antibody treatment significantly cured the hyperoxia-induced lung injury. Moreover, PGF overexpression significantly increased TNF-α and Il-6 levels in the bronchoalveolar lavage (BAL) fluid of the Normoxia+Ad-PGF and Hyperoxia groups. However, their levels were significantly reduced in the BAL fluid of the Hyperoxia+anti-PGF group. Immunohistochemical analysis revealed that PGF overexpression and hyperoxia treatment significantly increased the expression of the angiogenesis marker, CD34. However, its expression was significantly decreased upon administration of anti-PGF antibodies (compared to the control group under hyperoxia). In conclusion, PGF overexpression impairs lung development in newborn rats while its inhibition using an anti-PGF antibody ameliorates the same. These results provided new insights for the clinical management of bronchopulmonary dysplasia in premature infants.

Anti-placental growth factor antibody ameliorates hyperoxia-mediated impairment of lung development in neonatal rats

This study investigates the effect of the overexpression of the placental growth factor (PGF) and hyperoxia on lung development and determines whether anti-PGF antibody ameliorates hyperoxia-mediated impairment of lung development in newborn rats. After exposure to normoxic conditions for seven days, newborn rats subjected to normoxia were intraperitoneally or intratracheally injected with physiological saline, adenovirus-negative control (Ad-NC), or adenovirus-PGF (Ad-PGF) to create the Normoxia, Normoxia+Ad-NC, and Normoxia+Ad-PGF groups, respectively. Newborn rats subjected to hyperoxia were intraperitoneally injected with physiological saline or anti-PGF antibodies to create the Hyperoxia and Hyperoxia+anti-PGF groups, respectively. Our results revealed significant augmentation in the levels of PGF and its receptor Flt-1 in the lung tissues of newborn rats belonging to the Normoxia+Ad-PGF or Hyperoxia groups. PGF overexpression in these groups caused lung injury in newborn rats, while anti-PGF antibody treatment significantly cured the hyperoxia-induced lung injury. Moreover, PGF overexpression significantly increased TNF-α and Il-6 levels in the bronchoalveolar lavage (BAL) fluid of the Normoxia+Ad-PGF and Hyperoxia groups. However, their levels were significantly reduced in the BAL fluid of the Hyperoxia+anti-PGF group. Immunohistochemical analysis revealed that PGF overexpression and hyperoxia treatment significantly increased the expression of the angiogenesis marker, CD34. However, its expression was significantly decreased upon administration of anti-PGF antibodies (compared to the control group under hyperoxia). In conclusion, PGF overexpression impairs lung development in newborn rats while its inhibition using an anti-PGF antibody ameliorates the same. These results provided new insights for the clinical management of bronchopulmonary dysplasia in premature infants.

Noninvasive high-frequency oscillatory ventilation as respiratory support in preterm infants: a meta-analysis of randomized controlled trials.

BACKGROUND: Noninvasive high-frequency oscillatory ventilation (nHFOV), a relatively new modality, is gaining popularity despite scarce evidence. This meta-analysis was designed to evaluate the efficacy and safety of nHFOV as respiratory support in premature infants. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from inception of the database to January 2019. All published randomized controlled trials (RCTs) evaluating the effect of nHFOV therapy with nasal continuous positive airway pressure (nCPAP) or biphasic nCPAP (BP-CPAP) in newborns for respiratory support were included. All meta-analyses were performed using Review Manager 5.3. RESULTS: A total of 8 RCTs involving 463 patients were included. The meta-analysis estimated a lower risk of intubation (relative risk = 0.50, 95% confidence interval of 0.36 to 0.70) and more effective clearance of carbon dioxide (weighted mean difference = - 4.61, 95% confidence interval of - 7.94 to - 1.28) in the nHFOV group than in the nCPAP/BP-CPAP group. CONCLUSIONS: Our meta-analysis of RCTs suggests that nHFOV, as respiratory support in preterm infants, significantly remove carbon dioxide and reduce the risk of intubation compared with nCPAP/BP-CPAP. The appropriate parameter settings for different types of noninvasive high-frequency ventilators, the effect of nHFOV in extremely preterm infants, and the long-term safety of nHFOV need to be assessed in large trials.

Upregulation of CASC2 sensitized glioma to temozolomide cytotoxicity through autophagy inhibition by sponging miR-193a-5p and regulating mTOR expression.

OBJECTIVE: Numerous studies suggested autophagy was involved in temozolomide (TMZ) resistance in glioma. Long non-coding RNA (lncRNA) CASC2 was shown to be downregulated in glioma tissues and cell lines, and was related to the TMZ resistance. However, whether CASC2 affects TMZ resistance through regulating autophagy is unknown. The aim of this study was to assess the role and mechanism of CASC2 in TMZ-induced drug resistance in glioma cells. METHODS: Glioma and the adjacent non-cancerous tissues from 32 patients were collected. The expressions of CASC2 and miR-193a-5p were determined by PCR, and their correlation was analyzed. The correlation between CASC2 expression and the clinical characteristics of patients was also studied. Glioma cells were treated with TMZ to acquire the TMZ-resistant cell lines in which the expressions of CASC2, miR-193a-5p, and mTOR were measured. The regulatory roles of CASC2, miR-193a-5p, and mTOR were defined through the loss of function and luciferase reporter assays. Autophagy was inhibited by autophagy inhibitor 3-MA, CASC2 and mTOR overexpression, or miR-193a-5p inhibitor, and the effect of which on cell viability, apoptosis, and migration of TMZ-resistant glioma cells was evaluated. RESULTS: CASC2 downregulation and miR-193a-5p upregulation was found to be associated with advanced clinical stage and TMZ response in patients with glioma. CASC2 negatively regulates miR-193a-5p expression by direct interaction in glioma cells. Overexpression of CASC2 or inhibition of miR-193a-5p reduced TMZ-induced autophagy via mTOR upregulation, which makes the glioma cells become sensitive to TMZ cytotoxicity. CONCLUSION: CASC2 is downregulated in gliomas, resulting in increased miR-193a-5p level and a decrease in mTOR expression, which further induces protective autophagy, leading to TMZ resistance. Inhibition of autophagy helps to increase the efficacy of TMZ.

Airway administration of corticosteroids for prevention of bronchopulmonary dysplasia in premature infants: a meta-analysis with trial sequential analysis.

BACKGROUND: Uncertainly prevails with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. The meta-analysis with sequential analysis was designed to evaluate the efficacy and safety of airway administration (inhalation or instillation) of corticosteroids for preventing bronchopulmonary dysplasia (BPD) in premature infants. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions to February 2017. All published randomized controlled trials (RCTs) evaluating the effect of airway administration of corticosteroids (AACs) vs placebo or systemic corticosteroid in prematurity were included. All meta-analyses were performed using Review Manager 5.3. RESULTS: Twenty five RCTs retrieved (n = 3249) were eligible for further analysis. Meta-analysis and trial sequential analysis corrected the 95% confidence intervals estimated a lower risk of the primary outcome of BPD (relative risk 0.71, adjusted 95% confidence interval 0.57-0.87) and death or BPD (relative risk 0.81, adjusted 95% confidence interval 0.71-0.97) in AACs group than placebo and it is equivalent for preventing BPD than systemic corticosteroids. Moreover, AACs fail to increasing risk of death compared with placebo (relative risk 0.90, adjusted 95% confidence interval 0.40-2.03) or systemic corticosteroids (relative risk 0.81, 95% confidence interval 0.62-1.06). CONCLUSIONS: Our findings suggests that AACs (especially instillation of budesonide using surfactant as a vehicle) are an effective and safe option for preventing BPD in preterm infants. Furthermore, the appropriate dose and duration, inhalation or instillation with surfactant as a vehicle and the long-term safety of airway administration of corticosteroids needs to be assessed in large trials.

MicroRNA-564 is downregulated in glioblastoma and inhibited proliferation and invasion of glioblastoma cells by targeting TGF-ß1.

Increasing evidence has indicated that aberrant expression of miRNAs has been shown to be strongly implicated in the initiation and progression of glioblastoma. Here, we identified a novel tumor suppressive miRNA, miR-564, and investigated its role and therapeutic effect for glioblastoma. We showed that miR-564 was down-regulated in human glioblastoma tissues and cell lines. Introduction of miR-564 dramatically inhibited cell growth and invasion in glioblastoma cells. Subsequent experiments revealed that Transforming growth factor-ß1 (TGF-ß1) was a direct and functional target of miR-564 in glioblastoma cells. Furthermore, overexpression of miR-564 decreased p-SMAD and SMAD4 expression, which are the downstream signaling molecules of TGF-ß. Meanwhile, ectopic of miR-564 reduced the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9. Furthermore, the upregulation of miR-564 suppressed TGF-ß-mediated U87 proliferation and migration. The expression of EGFR and MMP9 was upregulated in glioblastoma tissues compared to their normal tissues. The EGFR and MMP9 expression levels were inverse correlated with the expression of miR-564. miR-564 suppressed the growth of U87-engrafted tumors. These findings reveal that miR-564/TGF-ß1 signaling that may be required for glioblastoma development and may consequently serve as a new therapeutic target for the treatment of glioblastoma.

TNF-α induces vascular endothelial cells apoptosis through overexpressing pregnancy induced noncoding RNA in Kawasaki disease model.

Kawasaki disease (KD) is an autoimmune disease in which the medium-sized blood vessels throughout the body become inflamed. The increased evidences showed that TNF-α was association with vascular inflammation in KD patients. However the detailed mechanism was still unclear. Recent studies indicated abnormal expressed long non-coding RNAs (LncRNAs) involved in many diseases. Thus the purpose of this study is to explore the role of lncRNAs in KD and find out the new target for KD treatment. In this study, firstly we verified the overexpressed TNF-α in KD patients, and found TNF-α was able to induce HUVECs apoptosis and inhibit HUVECs proliferation. After this we screened out pregnancy induced noncoding RNA (PINC) was significantly overexpression in TNF-α treated HUVECs. We also found PINC overexpressed in KD patients. For further study, we designed two siRNA of PINC. After silenced the expression of PINC in HUVECs, we found the Knockdown of PINC enhanced the viability of HUVECs treated with TNF-α, and increased the expression of anti-apoptotic and reduced the expression of apoptotic gene. These results suggest PINC involves in the process of TNF-α induces vascular endothelial cell apoptosis, it may become a new target for KD treatment.

Effects of Vascular Endothelial Growth Factor in Recovery Phase of Acute Lung Injury in Mice.

AIM: To test the hypothesis that exogenous administration of vascular endothelial growth factor (VEGF) promotes lung repair in acute lung injury (ALI). METHODS: ALI was induced by intranasal lipopolysaccharide (LPS) administration in mice, followed by different treatment protocols for 7 days in 3 groups (n = 6, each) including the LPS, the VEGF and the anti-VEGF group. At day 7, peripheral blood and lungs were collected. Lung wet-to-dry (W/D) ratio and lung injury score were measured. Immunohistochemistry assay was employed to detect the number of pulmonary vessels. Circulating endothelial progenitor cells (EPCs) was detected using flow cytometric analysis, and the apoptosis of lung cells was determined by TUNEL staining. RESULTS: VEGF treatment reduced W/D ratio and pulmonary neutrophil infiltration in the VEGF group compared with the LPS group. The treatment of VEGF increased the number of pulmonary vessels, and significantly increased the number of circulating EPC cells. Moreover, administration of VEGF decreased the percentage of apoptotic cells in the VEGF group. CONCLUSIONS: Our results suggest that VEGF may contribute to vascular endothelial repair and function as a protective factor against ALI.

DNA repair gene ERCC1 polymorphisms and glioma susceptibility among Chinese population: a meta-analysis.

BACKGROUND: Excision repair cross complementation group 1 (ERCC1) has been shown to be involved in the progression of glioma susceptibility. However, the results remain conflict. The aim of this study was to systematically review and evaluate the role of ERCC1 C118T and C8092A polymorphisms in glioma risk among Chinese population. METHODS: Related case-control studies were searched in online electronic databases. Odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the extracted data. RESULTS: Total seven articles were retrieved, including 4426 subjects (1926 were glioma patients and 2500 were matched controls). No significant heterogeneity was found between studies (I(2)=0%, P>0.01). Our results demonstrated that A allele and AA genotype of ERCC1 C8092A polymorphism have a positive association with increasing the risk of glioma in the fixed-effect model (A vs. C: OR=1.13, 95% CI=1.02-1.25, P=0.02; AA vs. CC: OR=1.29, 95% CI=1.04-1.61, P=0.02; AA vs. CA+CC: OR=1.25, 95% CI=1.01-1.55, P=0.04). However, no significant relationship was found between C118T variant and glioma susceptibility. CONCLUSIONS: Our results indicated that ERCC1 C8092A, not C118T polymorphism might be a biomarker for patients with glioma among Chinese population. Future studies with more ethnicities are needed to explore the precise association.

Correlation of serum KL-6 and CC16 levels with neurodevelopmental outcome in premature infants at 12 months corrected age.

The aim of this study was to evaluate KL-6 and CC16 levels and their correlation with neurodevelopmental outcome among very low birth weight pre-term infants at 12 months corrected age. This prospective cohort study was performed from 2011 to 2013 by enrolling pre-term neonates of gestational age ≤ 32 weeks and birth weight ≤ 1500 g. Serum KL-6 and CC16 levels were determined 7 days after birth and their correlation with neurodevelopment was evaluated using Gesell Mental Developmental Scales. Of the 86 eligible pre-term infants, 63 completed follow-up, of which 15 had bronchopulmonary dysplasia. At 12 months corrected age, 49 infants had favorable outcomes and 14 infants had poor neurodevelopmental outcome. KL-6 levels were higher and CC16 levels were lower in infants with poor neurodevelopmental outcome compared with those infants who had favourable neurodevelopmental outcome. Serum KL-6 levels less than 90.0 ng/ml and CC16 levels greater than 320.0 pg/ml at 7 days of life were found to be predictive of a favourable outcome at 12 months corrected age. These biological markers could predict neurodevelopmental outcome at 12 months corrected age in very low birth weight premature infants, and help the clinician plan early therapeutic interventions to minimize or avoid poor neurodevelopmental outcome.

A comparison of KL-6 and Clara cell protein as markers for predicting bronchopulmonary dysplasia in preterm infants.

OBJECTIVES: To evaluate the predictive characteristics of KL-6 and CC16 for bronchopulmonary dysplasia (BPD) in preterm infants, either independently or in combination. STUDY DESIGN: This prospective cohort study was performed from 2011 to 2013 with preterm neonates of gestational age ≤32 weeks and birth weight ≤1500 g. Serum KL-6 and CC16 levels were determined 7 and 14 days after birth. RESULTS: Seventy-three preterm infants were studied. BPD was identified in 24 of these infants. After adjusting for potential confounders, serum KL-6 concentrations were found to be elevated in BPD infants at both time points relative to non-BPD infants, while serum CC16 concentrations were lower at 14 days. At both 7 d and 14 d of life the predictive power of KL-6 levels exceeded that of CC16 (area under receiver operating characteristic curve: at 7 d, 0.91 cf. 0.73, P = 0.02; at 14 d, 0.95 cf. 0.85, P = 0.05). The combination of these markers enhanced the sensitivity further. CONCLUSIONS: Serum KL-6 levels higher than 79.26 ng/mL at 14 days postpartum in preterm infants predict the occurrence of BPD. CC16 was less predictive than KL-6 at this time point, but KL-6 and CC16 together enhanced the prediction.

Association between red blood cell transfusion and bronchopulmonary dysplasia in preterm infants.

Anemia and the need for transfusion of packed red blood cells (PRBCs) are common in preterm infants. PRBC transfusion increases the oxygen carrying capacity of hemoglobin and may result in higher rates of organ dysfunction. To determine whether PRBC transfusion in preterm infants is associated with an increased incidence of bronchopulmonary dysplasia (BPD), this retrospective study was performed on neonates with birth weights ≤ 1,500 g or gestational age ≤ 32 weeks admitted from August, 2008 to November, 2013. Infants who received PRBC transfusion before the diagnosis of BPD and those who did not receive PRBC transfusion or received PRBC transfusion after diagnosis of BPD were compared for incidence of BPD and other morbidities. Of 231 preterm infants, 137 received PRBC transfusion before BPD was diagnosed (group 1) and 94 did not (group 2). The incidence of BPD was significantly higher in group 1 than in group 2 (37.2% vs. 2.1%, P < 0.00001). After adjusting for potential risk factors, the adjusted odds ratio for BPD was 9.80 (95% confidence interval, 1.70-56.36; P = 0.01). This study demonstrated an association between PRBC transfusion and BPD in preterm infants. A cautious approach to PRBC transfusion in these infants is warranted.

Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is usually diagnosed in preterm infants at least 28 days after birth. Great interest lies in the potential to identify biomarkers that predict development of the disease and future neurodevelopmental outcomes. We have reviewed the existing literature on early biomarkers as predictors for BPD in preterm infants. METHODS: Two reviewers independently searched the databases of PubMed, EMBASE, and Google Scholar for studies pertaining to biomarkers for BPD. Studies were assessed using Quality Assessment of Diagnostic Accuracy Studies criteria. RESULTS: We identified 46 relevant articles that are summarized in the review. These studies assessed over 30 potential biomarkers. Sensitivity and specificity of biomarkers were reported or could be calculated for only 16 articles, and ranged from 0 to 100 %. Based on the nine highest quality studies, serum KL-6, CC16, neutrophil gelatinase-associated lipocalin, and end-tidal carbon monoxide (etCO) perform extremely well in predicting the early diagnosis of established BPD, highlighting these biomarkers as promising candidates for future research. CONCLUSIONS: Published data from studies on serum biomarkers and etCO suggest that biomarkers may have great potential to predict the subsequent BPD and neurodevelopmental outcomes. These biomarkers need validation in larger studies, and the generalizability of biomarkers for predicting BPD, as well as the neurodevelopmental outcomes, needs to be further explored.

[Effect of zinc deficiency on intestinal mucosal morphology and digestive enzyme activity in growing rat].

OBJECTIVE: In this study, a growing rat model of zinc deficiency was established to investigate the effect of zinc deficiency on intestinal mucosal morphology and digestive enzyme activity as well as to provide a scientific basis for zinc supplementation therapy in patients with diarrhea. METHOD: Three-week-old weaned Sprague-Dawley male rats (n = 30) were randomly divided into 3 groups with 10 in each: rats in the control group (ZA) were fed with a normal diet containing 30 µg/g zinc; rats in the zinc deficient group (ZD) were fed with a zinc-deficient diet containing 0.4 µg/g zinc (refer to AIN-76 formula); and rats in the paired fed group (PF) were fed with a normal diet, but the food intake was limited to intake of rats in ZD group in the previous day. All rats were provided with deionized water for drinking. Their body weight was measured and the food intake during the previous day was recorded early in the morning of the following day. Symptoms of zinc deficiency, such as anorexia, diarrhea, dermatitis, and growth retardation, were observed. Two weeks later, the rats were sacrificed and serum zinc concentration was measured. Jejunal mucosa was taken for biopsy and was stained with hematoxylin and eosin (HE). The height ratio of the jejunal mucosal villi and crypts was measured. In addition, the activity of lactase in the jejunal mucosal brush border, γ-glutamyl peptidase (GGT), and aminopeptidase N (APN) were measured. RESULT: The average weight of the rats in the ZA, ZD, and PF groups at the beginning of the experiment was (67.4 ± 5.3) g, (64.7 ± 4.8) g, and (66.5 ± 4.1) g, respectively, and the average daily food intake was (11.2 ± 1.0) g, (11.6 ± 1.6) g, and (11.2 ± 1.4) g, respectively. The intergroup differences were not significant. On the 7(th) day of experiment, no significant differences in average food intake were observed between the ZD group and the ZA and PF groups, but the average body weight in the ZD group was significantly lower than that in the ZA and PF groups (P < 0.01). At the end of the experiment (2 weeks), the average weight in the ZD group (112.0 ± 11.5) g was significantly lower than that in the ZA (164.0 ± 15.9) g and PF groups (137.5 ± 16.2) g. The average food intake in the ZD group (13.4 ± 5.1) g was significantly lower than that in the ZA group (18.2 ± 2.4) g (P < 0.01). Serum zinc level in the ZD group (733 ± 231) µg/L was significantly lower than that in the ZA (1553 ± 159) µg/L and PF groups (1457 ± 216) µg/L (P < 0.01). The height ratio of jejunal mucosa villus and crypt in the ZA, ZD, and PF groups was 2.98 ± 0.5, 2.77 ± 0.5, and 2.81 ± 0.7, respectively, and lactase activity was (26.1 ± 15.0) U/mg, (27.4 ± 12.8) U/mg, and (40.8 ± 18.5) U/mg, respectively, without significant intergroup differences. The GGT activity in the jejunal mucosa in the ZD group (12.7 ± 6.5) U/g was significantly lower than that in the ZA (19.1 ± 10.4) U/g and PF groups (18.5 ± 7.7) U/g, but the difference was not significant. The activity of APN in the jejunal mucosa in the ZD group (25.5 ± 7.5) U/g was significantly lower than that in the ZA (48.7 ± 16.8) U/g and PF groups (43.9 ± 14.5) U/g (P < 0.01). CONCLUSION: Zinc deficiency can cause loss of appetite, weight loss, and decreased activity of peptidase in the jejunal mucosal brush border. Zinc deficiency has little effect on the height ratio of the villus and crypt and lactase activity, thereby indicating that zinc deficiency may first affect protein digestion and absorption.

[Ambroxol for the prevention of respiratory distress syndrome in preterm infants: a meta analysis].

OBJECTIVE: To evaluate the efficacy and safety of ambroxol in the prevention of respiratory distress syndrome (RDS) in preterm infants. METHODS: Electronic searches were performed in the Cochrane Library, PubMED, EMBASE, Chinese CBM, Chinese VIP Database, Chinese Wanfang Database and Chinese CNKI Database up to the year of 2009 for randomized controlled trials (RCT) on ambroxol for the prevention of RDS in preterm infants. The meeting articles related to the RCT were manually searched in Pediatrics and Pediatric Research. Meta analysis was performed for the results of homogeneous studies by the Cochrane Collaboration's software RevMan 5.0.17. RESULTS: Six RCTs involving 823 preterm infants were included, and the quality assessment for the trials demonstrated 1 article as A class, 1 article as B class and 4 articles as C class. The Meta analysis showed that ambroxol administration significantly reduced the incidence of RDS (OR=0.24, 95%CI: 0.15 - 0.64, P<0.01), bronchopulmonary dysplasis (BPD, OR=0.41, 95%CI: 0.23 - 0.75, P<0.01), intraventricular hemorrhage (IVH, OR=0.39, 95%CI:0.24 - 0.64, P<0.01), patent ductus arteriosus (PDA, OR=0.33, 95%CI: 0.17 - 0.67, P<0.01) and pulmonary infection (OR=0.24, 95%CI:0.14 - 0.38, P<0.01). No adverse events related to the ambroxol treatment were reported. CONCLUSIONS: The current evidence shows that early use of ambroxol can reduce the risk of RDS, BPD, IVH, PDA and pulmonary infection in preterm infants.

Study on the effect of doxorubicin on expressions of genes encoding myocardial sarcoplasmic reticulum Ca2+ transport proteins and the effect of taurine on myocardial protection in rabbits.

To investigate the effect of doxorubicin(DOX) on gene expression of the myocardial sarcoplasmic reticulum (SR) Ca2+ transport proteins and the mechanism of taurine (Tau) protecting cardiac muscle cells, 9 rabbits were injected with DOX, 8 rabbits with DOX and Tau, and 9 rabbits with normal saline. Cardiac function, concentration of calcium in cardiomyocytes (Myo[Ca2+]i), activity of SR Ca(2+)-ATPase (SERCA2a), level of SERCA2a mRNA and Ca2+ released channels (RYR2) mRNA were detected. The left ventricle tissues were observed by electron microscopy. The results showed that cardiac index, left ventricular systolic pressure, activity of SR Ca(2+)-ATPase and level of SERCA2a mRNA decreased, while Myo[Ca2+]i increased in DOX-treated rabbits. DOX could not affect the level of RYR2 mRNA. Tau intervention could alleviate the increase of left ventricular diastolic pressure, Myo[Ca2+]i and the decrease of SERCA2a mRNA induced by doxorubicin. The results suggested that downregulation of SERCA2a gene expression was an important mechanism of DOX-induced cardiomyopathy and that Tau could partially improve the heart function by reducing calcium overload and alleviating downregulation of SERCA2a mRNA.