We investigated the effects of inhibitors of bone resorption (estrogen, raloxifene, and alendronate) on the processes of fracture repair in ovariectomized (OVX) rats. One hundred forty female Sprague-Dawley rats at 3 months of age were either OVX or sham-operated and divided into five groups: sham control, OVX control, estrogen (17␣-ethynyl estradiol [EE2], 0.1 mg/kg), raloxifene (Rlx, 1.0 mg/kg), and alendronate (Aln, 0.01 mg/kg) groups. Treatment began immediately after the surgery. Four weeks postovariectomy, prefracture controls were killed and bilateral osteotomies were performed on the femoral midshafts and fixed with intramedullary wires. Treatment was continued and fracture calluses were excised at 6 weeks and 16 weeks postfracture for evaluation by X-ray radiography, quantitative computed tomography (QCT,) biomechanical testing, and histomorphometry. At 6 weeks postfracture, Aln and OVX had larger calluses than other groups. Sham and OVX had higher ultimate load than EE2 and Rlx, with Aln not different from either control. Aln calluses also contained more mineral (bone mineral content [BMC]) than all other groups. By 16 weeks postfracture, OVX calluses were smaller than at 6 weeks and the dimensions for Aln had not changed. Aln had higher BMC and ultimate load than OVX, EE2, and Rlx. EE2 and Rlx had similar biomechanical properties, which were similar to sham. Interestingly, OVX and Aln animals were heavier than other groups at all time points; therefore, ultimate load was normalized by body weight to show no significant differences in strength of the whole callus between groups at either 6 weeks or 16 weeks postfracture. However, Aln strongly suppressed remodeling of the callus, resulting in the highest content of woven bone, persistent visibility of the original fracture line, and lowest content of lamellar bone, compared with other groups. Therefore, the larger Aln callus appeared to be a remarkable, morphological adaptation to secure the fracture with inferior material. In conclusion, OVX-stimulated bone turnover resulted in the fastest progression of fracture repair that was most delayed with Aln treatment, consistent with marked suppression of bone resorption and formation activity. Estrogen and Rlx had similar effects that were generally similar to sham, indicating that mild suppression of bone turnover with these agents has insignificant effects on the progression of fracture repair. (J Bone Miner Res 2002;17:2237-2246)

Background:With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.Methods:All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.Results:A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.Conclusions:Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

ARDS has a high mortality in these Chinese PICUs, especially in those with pneumonia and sepsis, and adequate management including lung protective ventilation strategy is required.

The predominant factors identified with IFI were third-generation cephalosporin use, peripherally inserted central venous catheter use, intubation > 6 days, any prior abdominal surgery, and neutropenia during first week of life < 1.5 · 109/L.

Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterized by increased medial and adventitial thickness of the lung vasculature. The underlying mechanisms that regulate the cell phenotype alteration during PPHN remodeling are largely unknown. We randomly selected newborn rats that were exposed to hypoxia (10-12%) or room air for 2 weeks and used a microarray to identify the lung tissue microRNAs (miRNAs) involved in PPHN progression. The role of a key miRNA that affects the endothelial-to-mesenchymal transition (EndMT) in primary cultured rat pulmonary microvascular endothelial cells (RPMECs) was investigated. The expression of miR-126a-5p was elevated in the PPHN model according to microarray analysis. The relative expression of miR-126a-5p in RPMECs increased when they were exposed to hypoxia (P<0.05), consistent with the microarray results. Pecam1 expression decreased, whereas alpha-smooth muscle actin (α-SMA) increased in the hypoxic RPMECs. Knockdown of miR-126a-5p in RPMECs followed by treatment with hypoxia for 48 h resulted in a significant increase in the expression of Pecam1 and a reduction in α-SMA expression, with a simultaneous increase in PI3K (p85β) and phosphorylation of AKT at serine 473 compared with the negative control. Finally, the circulating miR-126a-5p concentration was upregulated in the PPHN model compared with healthy neonates. We concluded that hypoxia changed the cell homeostasis and that miR-126a-5p was upregulated in PPHN, which is partly responsible for hypoxia-induced EndMT. The mechanism underlying the upregulation of miR-126a-5p by hypoxia probably acts through the p85-β/p-AKT pathway.

for the Nasal Oscillation Post-Extubation (NASONE) Study Group IMPORTANCE Several respiratory support techniques are available to minimize the use of invasive mechanical ventilation (IMV) in preterm neonates. It is unknown whether noninvasive high-frequency oscillatory ventilation (NHFOV) is more efficacious than nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV) in preterm neonates after their first extubation.OBJECTIVE To test the hypothesis that NHFOV is more efficacious than NCPAP or NIPPV in reducing IMV after extubation and until neonatal intensive care unit discharge among preterm neonates. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, pathophysiology-based, assessor-blinded, 3-group, randomized clinical trial was conducted in 69 tertiary referral neonatal intensive care units in China, recruiting participants from December 1, 2017, to May 31, 2021. Preterm neonates who were between the gestational age of 25 weeks plus 0 days and 32 weeks plus 6 days and were ready to be extubated were randomized to receive NCPAP, NIPPV or NHFOV. Data were analyzed on an intention-to-treat basis. INTERVENTIONSThe NCPAP, NIPPV, or NHFOV treatment was initiated after the first extubation and lasted until discharge.MAIN OUTCOMES AND MEASURES Primary outcomes were total duration of IMV, need for reintubation, and ventilator-free days. These outcomes were chosen to describe the effect of noninvasive ventilation strategy on the general need for IMV.RESULTS A total of 1440 neonates (mean [SD] age at birth, 29.4 [1.8] weeks; 860 boys [59.7%]) were included in the trial. Duration of IMV was longer in NIPPV (mean difference, 1.2; 95% CI, 0.01-2.3 days; P = .04) and NCPAP (mean difference, 1.5 days; 95% CI, 0.3-2.7 days; P = .01) compared with NHFOV. Neonates who were treated with NCPAP needed reintubations more often than those who were treated with NIPPV (risk difference: 8.1%; 95% CI, 2.9%-13.3%; P = .003) and NHFOV (risk difference, 12.5%; 95% CI, 7.5%-17.4%; P < .001). There were fewer ventilator-free days in neonates treated with NCPAP than in those treated with NIPPV (median [25th-75th percentile] difference, −3 [−6 to −1] days; P = .01). There were no differences between secondary efficacy or safety outcomes, except for the use of postnatal corticosteroids (lower in NHFOV than in NCPAP group; risk difference, 7.3%; 95% CI, 2.6%-12%; P = .002), weekly weight gain (higher in NHFOV than in NCPAP group; mean difference, −0.9 g/d; 95% CI, −1.8 to 0 g/d; P = .04), and duration of study intervention (shorter in NHFOV than in NIPPV group; median [25th-75th percentile] difference, −1 [−3 to 0] days; P = .01).CONCLUSIONS AND RELEVANCE Results of this trial indicated that NHFOV, if used after extubation and until discharge, slightly reduced the duration of IMV in preterm neonates, and both NHFOV and NIPPV resulted in a lower risk of reintubation than NCPAP. All 3 respiratory support techniques were equally safe for this patient population.

The new venous tubing with 1.0-cm(2) cross-sectional area improves the drainage in the vast majority of adult patients undergoing CPB and reduces the priming volume (-27 ml/m). Reduced hemodilution can prevent homologous transfusions if a predefined transfusion trigger level is not reached.

The clinical use of DPEJ is increasing. With appropriate care and expertise, DPEJ may prove to be reliable and safe.