Association of antenatal corticosteroids with mortality and morbidities in very preterm infants born to women with hypertensive disorders of pregnancy: a multicenter prospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS. METHODS: This is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge. RESULTS: Among 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient - 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference. CONCLUSIONS: Even partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples.

Development and validation of a model to predict mortality risk among extremely preterm infants during the early postnatal period: a multicentre prospective cohort study.

BACKGROUND: Recently, with the rapid development of the perinatal medical system and related life-saving techniques, both the short-term and long-term prognoses of extremely preterm infants (EPIs) have improved significantly. In rapidly industrialising countries like China, the survival rates of EPIs have notably increased due to the swift socioeconomic development. However, there is still a reasonably lower positive response towards the treatment of EPIs than we expected, and the current situation of withdrawing care is an urgent task for perinatal medical practitioners. OBJECTIVE: To develop and validate a model that is practicable for EPIs as soon as possible after birth by regression analysis, to assess the risk of mortality and chance of survival. METHODS: This multicentre prospective cohort study used datasets from the Sino-Northern Neonatal Network, including 46 neonatal intensive care units (NICUs). Risk factors including maternal and neonatal variables were collected within 1 hour post-childbirth. The training set consisted of data from 41 NICUs located within the Shandong Province of China, while the validation set included data from 5 NICUs outside Shandong Province. A total of 1363 neonates were included in the study. RESULTS: Gestational age, birth weight, pH and lactic acid in blood gas analysis within the first hour of birth, moderate-to-severe hypothermia on admission and adequate antenatal corticosteroids were influencing factors for EPIs' mortality with important predictive ability. The area under the curve values for internal validation of our prediction model and Clinical Risk Index for Babies-II scores were 0.81 and 0.76, and for external validation, 0.80 and 0.51, respectively. Moreover, the Hosmer-Lemeshow test showed that our model has a constant degree of calibration. CONCLUSIONS: There was good predictive accuracy for mortality of EPIs based on influencing factors prenatally and within 1 hour after delivery. Predicting the risk of mortality of EPIs as soon as possible after birth can effectively guide parents to be proactive in treating more EPIs with life-saving value. TRIAL REGISTRATION NUMBER: ChiCTR1900025234.

A Case of Postnatal Aortic Arch Atresia.

Background: Aortic arch atresia is a rare congenital cardiac defect that may occur after birth. Pregnant women with gestational diabetes mellitus may increase the risk of aortic arch atresia in newborns after birth. Case Description: A 16-day-old infant was referred to our hospital on the 15th postnatal day after an interrupted or atretic aortic arch was discovered. No obvious abnormality was detected in the infant during the prenatal ultrasound. Laboratory tests showed elevated inflammatory marker levels. Transthoracic echocardiography showed stenosis of the transverse arch of the aorta and a blind end at the distal end of the left subclavian artery. During surgery, it was found that the isthmus of the aorta was uninterrupted but completely occluded due to inflammation. Conclusion: This case demonstrates that type A interrupted aortic arch and coarctation of the aorta can be acquired after birth, and if coarctation of the aorta is complicated by inflammation or if the pregnant women have gestational diabetes mellitus, it can result in aortic arch atresia as the patient's condition worsens. It is advised to consider aortic arch atresia when imaging reveals type A interrupted aortic arch.

Determining resuscitation threshold for extremely preterm infants based on the survival rates without severe neurological injury.

Background: Published guidelines on decision-making and resuscitation of extremely preterm infants primarily focus on high-income countries. For rapidly industrializing ones like China, there is a lack of population-based data for informing prenatal management and practice guidelines. Methods: The Sino-northern Neonatal Network conducted a prospective multi-centre cohort study between 1 January 2018 and 31 December 2021. Infants with a gestational age (GA) between 22 (postnatal age in days = 0) and 28 (postnatal age in days = 6) admitted to 40 tertiary NICUs in northern China were included and evaluated for death or severe neurological injury before discharge. Results: For all extremely preterm infants (n = 5838), the proportion of admission to the neonatal was 4.1% at 22-24 weeks, 27.2% at 25-26 weeks, and 75.2% at 27 and 28 weeks. Among 2228 infants admitted to the NICU, 216 (11.1%) were still elected for withdrawal of care (WIC) due to non-medical factors. Survival rates without severe neurological injury were 6.7% for infants at 22-23 weeks, 28.0% at 24 weeks, 56.7% at 24 weeks, 61.7% at 25 weeks, 79.9% at 26 weeks, and 84.5% at 27 and 28 weeks. Compared with traditional criterion at 28 weeks, the relative risk for death or severe neurological injury were 1.53 (95% confidence interval (CI) = 1.26-1.86) at 27 weeks, 2.32 (95% CI = 1.73-3.11) at 26 weeks, 3.62 (95% CI = 2.43-5.40) at 25 weeks, and 8.91 (95% CI = 4.69-16.96) at 24 weeks. The NICUs with higher proportion of WIC also had a higher rate of death or severe neurological injury after maximal intensive care (MIC). Conclusions: Compared to the traditional threshold of 28 weeks, more infants received MIC after 25 weeks, leading to significant increases in survival rates without severe neurological injury. Therefore, the resuscitation threshold should be gradually adjusted from 28 to 25 weeks based on reliable capacity. Registration: China Clinical Trials Registry. ID: ChiCTR1900025234.

Curcumol, a major terpenoid from Curcumae Rhizoma, attenuates human uterine leiomyoma cell development via the p38MAPK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age. Curcumae Rhizoma, the main essential oil component of which is curcumol, is widely used for the treatment of phymatosis in China due to its antitumor, anti-inflammatory, antithrombin, anti-tissue fibrosis and anti-oxygen pharmacological activities, but its potential for the treatment of UFs has not been evaluated. AIM OF THE STUDY: This study aimed to investigate the effects and mechanisms of curcumol intervention in human uterine leiomyoma cells (UMCs). MATERIALS AND METHODS: Putative targets of curcumol intervention in UFs were identified using network pharmacology strategies. Molecular docking was performed to assess the binding affinity of curcumol to core targets. A concentration gradient of curcumol (0, 50, 100, 200, 300, 400 and 500 µM) or RU-486 (mifepristone, 0, 10, 20, 40, 50, and 100 µM) was applied to UMCs, and cell viability was detected by the CCK-8 assay. Cell apoptosis and cell cycle were examined by flow cytometry, and cell migration was assessed by a wound-healing assay. Additionally, the mRNA and protein expression levels of critical pathway components were evaluated by RT‒PCR and western blotting. Finally, the actions of curcumol on different tumor cell lines were summarized. RESULTS: Network pharmacology predicted 62 genes with roles in the treatment of UFs with curcumol, and MAPK14 (p38MAPK) displayed a higher interaction degree. GO enrichment and KEGG analyses revealed that the core genes were abundantly enriched in the MAPK signaling pathway. The molecular binding of curcumol to core targets was relatively stable. In UMCs, 200, 300 and 400 µM curcumol treatment for 24 h decreased cell viability compared with that in the control group, and the greatest effect was detected at 48 h and maintained until 72 h. Curcumol arrested cells in the G0/G1 phase and subsequently suppressed mitosis, promoted early apoptosis and reduced the degree of wound healing in a concentration-dependent manner in UMCs. Furthermore, 200 µM curcumol decreased the mRNA and protein expression of p38MAPK, the mRNA expression of NF-κB, and the protein expression of Ki-67 and increased the mRNA and protein expression of Caspase 9. Curcumol (300 and 400 µM) decreased the mRNA and protein expression of p38MAPK, NF-κB, and Ki-67 and increased the protein expression of Caspase 9 in UMCs. Curcumol was demonstrated to treat tumor cell lines, including breast cancer, ovarian cancer, lung cancer, gastric cancer, liver cancer and nasopharyngeal carcinoma, but its effects on benign tumors have not yet been reported. CONCLUSION: Curcumol suppresses cell proliferation and cell migration while arresting the cell cycle in the G0/G1 phase and inducing cell apoptosis in UMCs via a mechanism related to p38MAPK/NF-κB pathway regulation. Curcumol may be a potential therapeutic and preventive agent in the treatment of benign tumors such as UFs.

Longer duration of initial invasive mechanical ventilation is still a crucial risk factor for moderate-to-severe bronchopulmonary dysplasia in very preterm infants: a multicentrer prospective study.

OBJECTIVES: We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA). METHODS: We performed a prospective cohort study involving infants born at 23-31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database. RESULTS: We identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17-41) days, while in the no or mild BPD group, it was 6 (3-10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV [adjusted odds ratio (AOR): 1.97; 95% confidence interval (CI): 1.10-2.67], late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA). CONCLUSION: In this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.

Association between pulmonary hemorrhage and CPAP failure in very preterm infants.

Background: Pulmonary hemorrhage (PH) in neonates is a life-threatening respiratory complication. We aimed to analyze the perinatal risk factors and morbidity with PH among very preterm infants in a large multicenter study. Methods: This was a multicenter case-control study based on a prospective cohort. Participants included 3,680 in-born infants with a gestational age at 24-32 weeks (birth weight <1,500 g) who were admitted between January 1, 2019, and October 31, 2021. All infants were divided into two groups, namely, the PH and no-PH groups, at a ratio of 1:2 according to the following factors: gestational age (GA), birth weight (BW), and the Score for Neonatal Acute Physiology with Perinatal extension II (SNAPPE II). Perinatal factors and outcomes were compared between the two groups by logistic regression analyses. Results: A total of 3,680 infants were included in the study, and the number of identified cases of PH was 262 (7.1%). The incidence was 16.9% (136/806) for neonates with extremely low BW (BW < 1,000 g) infants. The multivariate analysis showed that CPAP failure (OR 2.83, 95% CI 1.57, 5.08) was significantly associated with PH. PH was associated with a high likelihood of death (OR 3.81, 95% CI 2.67, 5.43) and bronchopulmonary dysplasia (BPD) (≥grade II) (OR 1.58, 95% CI 1.00, 2.48). Conclusions: In this multicenter case-control study based on a prospective cohort, PH to be common among VLBW infants. PH is associated with significant morbidity and mortality, and perinatal management, especially CPAP failure. Respiratory management strategies to decrease the risk of PH should be optimized.

A clinical prediction model to estimate the risk for coarctation of the aorta: From fetal to newborn life.

AIM: A prenatal diagnosis of coarctation of the aorta (CoA) is challenging. This study aimed to develop a coarctation probability model incorporating prenatal cardiac sonographic markers to estimate the probability of an antenatal diagnosis of CoA. METHODS: We reviewed 89 fetuses as an investigation cohort with prenatal suspicion for CoA and categorized them into three subgroups: severe CoA: symptomatic CoA and surgery within the first 3 months; mild CoA: surgery within 4 months to 1 year (29); and false-positive CoA: not requiring surgery (45). Logistic regression was used to create a multiparametric model, and a validation cohort of 86 fetuses with suspected CoA was used to validate the model. RESULTS: The prediction model had an optimal criterion >0.25 (sensitivity of 97.7%; specificity of 59.1%), and the area under the receiver operator curve was 0.85. The parameters and their cut-off values were as follows: left common carotid artery to left subclavian artery distance/distal transverse arch (LCCA-LSCA)/DT Index >1.77 (sensitivity 62%, specificity 88%, 95% confidence interval [CI]: 0.6-0.8), and z-score of AAo peak Doppler > -1.7 (sensitivity 77%, specificity 56%, 95% CI: 0.6-0.8). The risk assessment demonstrated that fetuses with a model probability >60% should have inpatient observation for a high risk of CoA, whereas fetuses with a model probability <15% should not undergo clinical follow-up. CONCLUSION: The probability model performs well in predicting CoA outcomes postnatally and can also improve the accuracy of risk assessment. The objectivity of its parameters may allow its implementation in multicenter studies of fetal cardiology.

Implementation of a temperature bundle improves admission hypothermia in very-low-birth-weight infants in China: a multicentre study.

BACKGROUND: Hypothermia is a common problem that is associated with increased mortality and morbidity among preterm infants, especially in China. The objective of this study was to evaluate the efficacy of a targeted quality improvement (QI) project that applied hypothermia prevention measures for very-low-birth-weight (VLBW) infants in three tertiary neonatal intensive care units (NICUs) in China. PROBLEM: Between January 2018 and December 2018, we conducted a prospective analysis and found that the incidence of AH was 88.2% among VLBW infants. METHODS: The study enrolled preterm infants born at less than 32 weeks' gestation with a VLBW of less than 1500 g who were delivered at three academic tertiary-care hospitals between January 2018 and December 2019. The primary outcome measure was the incidence of hypothermia. The outcomes of the pre-QI group (1 January-31 December 2018) were compared with those of the post-QI group (1 January-31 December 2019). INTERVENTIONS: Based on the literature, our preliminary findings and the needs of each unit, a temperature bundle that included a transport incubator, prewarmed hats, polyethylene wrap, team training and education, and temperature documentation and workflows were implemented in consecutive plan-do-study-act cycles. RESULTS: Of the 530 VLBW infants, 235 infants (36.9%) belonged to the pre-QI group, and 295 infants (46.4%) belonged to the post-QI group. The incidence of hypothermia decreased significantly, from 92.3% to 62% (p<0.001), and the mean body temperature on admission to the NICU increased significantly, from 35.5°C to 36°C±0.7°C (p<0.001). There was one case of hyperthermia during the study period. Infants in the post-QI group had a lower mortality rate (16.1% vs 8.8%, p=0.01). CONCLUSIONS: Targeted interventions can dramatically reduce admission hypothermia and improve the outcome of VLBW infants in China. TRIAL REGISTRATION NUMBER: Chi CTR 1900020861.

A standardized implementation of multicenter quality improvement program of very low birth weight newborns could significantly reduce admission hypothermia and improve outcomes.

BACKGROUND: Admission hypothermia (AH, < 36.5℃) remains a major challenge for global neonatal survival, especially in developing countries. Baseline research shows nearly 89.3% of very low birth weight (VLBW, < 1500 g) infants suffer from AH in China. Therefore, a prospective multicentric quality improvement (QI) initiative to reduce regional AH and improve outcomes among VLBW neonates was implemented. METHODS: The study used a sequential Plan-Do-Study-Act (PDSA) approach. Clinical data were collected prospectively from 5 NICUs within the Sino-Northern Neonatal Network (SNN) in China. The hypothermia prevention bundle came into practice on January 1, 2019. The clinical characteristics and outcomes data in the pre-QI phase (January 1, 2018- December 31, 2018) were compared with that from the post-QI phase (January 1, 2019-December 31, 2020). Clinical characteristics and outcomes data were analyzed. RESULTS: A total of 750 in-born VLBW infants were enrolled in the study, 270 in the pre-QI period and 480 in the post- QI period, respectively. There were no significant differences in clinical characteristics of infants between these two phases. Compared with pre-QI period, the incidence of AH was decreased significantly after the QI initiative implementation in the post-QI period (95.9% vs. 71.3%, P < 0.01). Incidence of admission moderate-to-severe hypothermia (AMSH, < 36℃) also decreased significantly, manifesting a reduction to 38.5% in the post-QI (68.5% vs 30%, P < 0.01). Average admission temperature improved from after QI (35.5 [Formula: see text] 0.7℃ vs. 36.0 [Formula: see text] 0.6℃, P < 0.01). There was no increase in proportion the number of infants with a temperature of > 37.5 °C or thermal burns between the two groups. The risk ratio of mortality in infants during the post-QI period was significantly lower in the post-QI period as compared to the pre-QI period [adjusted risk ratio (aRR): 0.26, 95% confidence interval (CI): 0.13-0.50]. The risk ratio of late-onset neonatal sepsis (LOS) also significantly lowered in the post-QI period (aRR: 0.66, 95% CI: 0.50-0.87). CONCLUSION: Implementation of multicentric thermoregulatory QI resulted in a significant reduction in AH and AMSH in VLBW neonates with associated reduction in mortality. We gained a lot from the QI, and successfully aroused the attention of perinatal medical staff to neonatal AH. This provided a premise for continuous quality improvement of AH in the future, and might provide a reference for implementation of similar interventions in developing countries. TRIAL REGISTRATION: Trial registration number: ChiCTR1900020861 . Date of registration: 21 January 2019(21/01/2019). Prospectively registered.

Initial respiratory support modality and outcome in preterm infants with less than 32 weeks of gestation in China: A multicentre retrospective cohort study.

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.

Clinical utiliy of a model-based piperacillin dose in neonates with early-onset sepsis.

AIMS: Early-onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model-based dosing regimen of piperacillin/tazobactam in EOS patients. METHODS: A prospective, single-centre, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg-1 , q8h) was determined based on a previous piperacillin PPK model in young infants using NONMEM v7.4. The pharmacodynamics (PD) target (70%fT > MIC, free drug concentration above MIC during 70% of the dosing interval) attainment was calculated using NONMEM combined with an opportunistic sampling design. The clinical treatment data were collected. RESULTS: A total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14-41.29) weeks. Forty-seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2-305.8) hours and 31 (30, 5-123) days. There were no obvious adverse events and no infection-related deaths occurred in the first month of life. CONCLUSIONS: A model-based dosing regimen of piperacillin/tazobactam was evaluated clinically, was tolerated well and was determined to be effective for EOS treatment.

Treatment status of extremely premature infants with gestational age < 28 weeks in a Chinese perinatal center from 2010 to 2019.

BACKGROUND: There is a paucity of studies conducted in China on the outcomes of all live-birth extremely premature infants (EPIs) and there is no unified recommendation on the active treatment of the minimum gestational age in the field of perinatal medicine in China. We aimed to investigate the current treatment situation of EPIs and to provide evidence for formulating reasonable treatment recommendations. METHODS: We established a real-world ambispective cohort study of all live births in delivery rooms with gestational age (GA) between 24+0 and 27+6 weeks from 2010 to 2019. RESULTS: Of the 1163 EPIs included in our study, 241 (20.7%) survived, while 849 (73.0%) died in the delivery room and 73 (6.3%) died in the neonatal intensive care unit. Among all included EPIs, 862 (74.1%) died from withholding or withdrawal of care. Regardless of stratification according to GA or birth weight, the proportion of total mortality attributable to withdrawal of care is high. For infants with the GA of 24 weeks, active treatment did not extend their survival time (P = 0.224). The survival time without severe morbidity of the active treatment was significantly longer than that of withdrawing care for infants older than 25 weeks (P < 0.001). Over time, the survival rate improved, and the withdrawal of care caused by socioeconomic factors and primary nonintervention were reduced significantly (P < 0.001). CONCLUSIONS: The mortality rate of EPIs is still high. Withdrawal of care is common for EPIs with smaller GA, especially in the delivery room. It is necessary to use a multi-center, large sample of real-world data to find the survival limit of active treatment based on our treatment capabilities.

Panax quinquefolium saponin Optimizes Energy Homeostasis by Modulating AMPK-Activated Metabolic Pathways in Hypoxia-Reperfusion Induced Cardiomyocytes.

OBJECTIVE: To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes. METHODS: The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters. RESULTS: PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05). CONCLUSION: PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.

Association between admission hypothermia and outcomes in very low birth weight infants in China: a multicentre prospective study.

BACKGROUND: The objective of this prospective, multicentre, observational cohort study was to evaluate the association between admission hypothermia and neonatal outcomes in very low-birth weight (VLBW) infants in multiple neonatal intensive care units (NICUs) in China. METHODS: Since January 1, 2018, a neonatal homogeneous cooperative research platform-Shandong Neonatal Network (SNN) has been established. The platform collects clinical data in a prospective manner on preterm infants with birth weights (BWs) < 1500 g and gestational ages (GAs) < 34 weeks born in 28 NICUs in Shandong Province. These infants were divided into normothermia, mild or moderate/severe hypothermia groups according to the World Health Organization (WHO) classifications of hypothermia. Associations between outcomes and hypothermia were tested in a bivariate analysis, followed by a logistic regression analysis. RESULTS: A total of 1247 VLBW infants were included in this analysis, of which 1100 infants (88.2%) were included in the hypothermia group, 554 infants (44.4%) in the mild hypothermia group and 546 infants (43.8%) in the moderate/severe hypothermia group. Small for gestational age (SGA), caesarean section, a low Apgar score at 5 min and intubation in the delivery room (DR) were related to admission hypothermia (AH). Mortality was the lowest when their admission temperature was 36.5 ~ 37.5 °C, and after adjustment for maternal and infant characteristics, mortality was significantly associated with AH. Compared with infants with normothermia (36.5 ~ 37.5 °C), the adjusted ORs of all deaths increased to 4.148 (95% CI 1.505-11.437) and 1.806 (95% CI 0.651-5.009) for infants with moderate/severe hypothermia and mild hypothermia, respectively. AH was also associated with a high likelihood of respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), and late-onset neonatal sepsis (LOS). CONCLUSIONS: AH is still very high in VLBW infants in NICUs in China. SGA, caesarean section, a low Apgar score at 5 min and intubation in the DR were associated with increased odds of hypothermia. Moderate/severe hypothermia was associated with mortality and poor outcomes, such as RDS, IVH, LOS.

Usage of density analysis based on micro-CT for studying lung injury associated with burn-blast combined injury.

BACKGROUND: Burn-blast combined injury is a kind of injury caused by heat and blast at the same time. The lung injury after burn-blast combined injuries is of primary importance, and investigation of lung injury is needed in the clinical care of patients. Computed tomography (CT) is one of the standard tools used to observe the anatomical basis and pathophysiology of acute lung injury. METHODS: We applied a method of fast 3D (three-dimensional) reconstruction to calculate the density value of the lung injury by CT analysis. Blast-injury group (BL group), burn-injury group (B group), burn-blast combined injury group (BBL group), and sham control group (C group) were established. Each group had 16 rats. The three-dimensional images of the lung tissue were obtained at 6h, 24h, and 48h according to the CT value. The average density of the whole lung, left lung, and right lung were measured. The lung tissues were paraffin-embedded and HE stained. Smith scoring was performed according to the pathological findings. RESULTS: In the BBL group, the density of the lung tissue was higher than those of the BL group and B group (P<0.01). The lung tissue density values at 24h after injury were higher than those at 6h and 48h after injury (P<0.01). Pathological results confirmed the changes of density analysis of the lung tissue. CONCLUSION: The results have indicated that density analysis through a CT scan can be used as a way to evaluate lung injury in a burn-blast injury.

Radiological findings of malignant peripheral nerve sheath tumor: reports of six cases and review of literature.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is a kind of rare neurogenic tumor. If associated with neurofibromatosis type 1, MPNST usually has a higher mortality. The aim of the article is to assess the imaging characteristics of MPNST and compare them with those of benign peripheral nerve sheath tumor (BPNST) to characterize this tumor. METHODS: Clinical and imaging data of six cases with MPNST and 28 cases with BPNST in our institution since 2011 were retrospectively reviewed. Thirty-three patients have available MR imaging data, and two patients of MPNST also accepted CT scan. One patient accepted CT scan only. Location, size, shape, signal or density, boundary, bone destruction, relation to adjacent nerve, contrast-enhanced features as well as some other signs were assessed and compared with statistical software. Student's t test was used for comparison of continuous variables. Fisher's exact test was used for analysis of nominal variable. A P value ≤0.05 was considered to be statistically significant. RESULTS: Differences existed between two groups in tumor size ((7.2 ± 3.3)cm in MPNST vs. (3.8 ± 1.4)cm in BPNST), unclear margin (4/6 in MPNST vs. 1/28 in BPNST), eccentricity to the nerve (1/6 in MPNST vs. 21/28 in BPNST), intratumoral lobulation (4/6 in MPNST vs. 2/28 in BPNST), peritumoral edema (3/6 in MPNST vs. 0 in BPNST), and peripheral enhancement (4/6 in MPNST (three of five MR, one CT) vs. 4/28 in BPNST). Bone destruction was observed in one MPNST. CONCLUSIONS: MR imaging is a valuable, non-invasive modality for the diagnosis of MPNST. Peripheral enhancement with non-cystic appearance or remarkable heterogeneous enhancement may be useful for differential diagnosis. Other imaging features such as large size (over 5 cm in diameter), ill-defined margin, intratumoral lobulation, peritumoral edema, and adjacent bone destruction are also supportive of MPNST.

Transdermal permeation of drugs with differing lipophilicity: Effect of penetration enhancer camphor.

The aim of the present study was to investigate the potential application of (+)-camphor as a penetration enhancer for the transdermal delivery of drugs with differing lipophilicity. The skin irritation of camphor was evaluated by in vitro cytotoxicity assays and in vivo transdermal water loss (TEWL) measurements. A series of model drugs with a wide span of lipophilicity (logP value ranging from 3.80 to -0.95), namely indometacin, lidocaine, aspirin, antipyrine, tegafur and 5-fluorouracil, were tested using in vitro transdermal permeation experiments to assess the penetration-enhancing profile of camphor. Meanwhile, the in vivo skin microdialysis was carried out to further investigate the enhancing effect of camphor on the lipophilic and hydrophilic model drugs (i.e. lidocaine and tegafur). SC (stratum corneum)/vehicle partition coefficient and Fourier transform infrared spectroscopy (FTIR) were performed to probe the regulation action of camphor in the skin permeability barrier. It was found that camphor produced a relatively low skin irritation, compared with the frequently-used and standard penetration enhancer laurocapram. In vitro skin permeation studies showed that camphor could significantly facilitate the transdermal absorption of model drugs with differing lipophilicity, and the penetration-enhancing activities were in a parabola curve going downwards with the drug logP values, which displayed the optimal penetration-enhancing efficiency for the weak lipophilic or hydrophilic drugs (an estimated logP value of 0). In vivo skin microdialysis showed that camphor had a similar penetration behavior on transdermal absorption of model drugs. Meanwhile, the partition of lipophilic drugs into SC was increased after treatment with camphor, and camphor also produced a shift of CH2 vibration of SC lipid to higher wavenumbers and decreased the peak area of the CH2 vibration, probably resulting in the alteration of the skin permeability barrier. This suggests that camphor might be a safe and effective penetration enhancer for transdermal drug delivery.

Lipopolysaccharide pretreatment inhibits LPS-induced human umbilical cord mesenchymal stem cell apoptosis via upregulating the expression of cellular FLICE-inhibitory protein.

Mesenchymal stem cell (MSC)-based regenerative therapy is currently regarded as a novel approach with which to repair damaged tissues. However, the efficiency of MSC transplantation is limited due to the low survival rate of engrafted MSCs. Lipopolysaccharide (LPS) production is increased in numerous diseases and serves an essential function in the regulation of apoptosis in a variety of cell types. Previous studies have indicated that low-dose LPS pretreatment contributes to cytoprotection. In the current study, LPS was demonstrated to induce apoptosis in human umbilical cord mesenchymal stem cells (hUCMSCs) via the activation of caspase, in a dose-dependent manner. Low-dose LPS pretreatment may protect hUCMSCs against apoptosis induced by high-dose LPS, by upregulating the expression of cellular FADD-like IL-1ß-converting enzyme-inhibitory protein (c-FLIP). The results of the present study indicate that pretreatment with an appropriate concentration of LPS may alleviate high-dose LPS-induced apoptosis.

[Comparison of different methods for the isolation of human umbilical cord mesenchymal stem cells].

OBJECTIVE: To explore the most appropriate method for the isolation of human umbilical cord mesenchymal stem cells (MSCs) through a comparison of different methods. METHODS: Fifteen umbilical cord specimens from full-term healthy fetus with caesarean birth were completely rinsed with phosphate buffer saline (PBS) and sliced into 1 mm(3) tissue blocks after removal of umbilical vessels and external membrane. These tissue blocks were averagely divided into 4 groups after washing and centrifuge. Then four methods for the isolation of human umbilical cord MSCs were compared: an explant culture and three enzymatic methods of collagenaseII, collagenaseII/trypsin and collagenaseII/hyaluronidase. The count of living cells was evaluated by trypan blue dye exclusion test. Cell morphology was observed under inverted microscope. The expressions of cell surface markers CD105, CD90, CD73, CD31, CD44, CD45, human leukocyte antigen-I (HLA-I) and human leukocyte antigen class IImolecules (HLA-DR) were detected by immunofluorescent staining. Cell proliferation was assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). RESULTS: The human umbilical cord MSCs were successfully isolated by four isolated methods. However the isolation method used profoundly altered the cell number and proliferation capacity of isolated cells. Isolated cells using four methods were counted at (5.44 ± 0.21)×10(5), (4.03 ± 0.24)×10(5), (4.91 ± 0.33)×10(5) and (5.94 ± 0.40)×10(5) respectively. More cells were obtained with collagenaseII/hyaluronidase than other three methods (all P < 0.05). Cells out of tissue blocks were observed at Day 9-11 and cells were observed at Day 2 with three types of enzyme digestion. The fusion time of cells were (18.5 ± 3.5), (8.0 ± 1.0), (7.5 ± 1.5) and (3.5 ± 0.5) days respectively. The fusion time of cells obtained with collagenaseII/hyaluronidase was lower than other methods (all P < 0.05). Cell morphology: polygonal, irregular and of large volume for explant culture; relatively short and small for collagenaseII and collagenaseII/trypsin methods; thin spindle for collagenaseII/hyaluronidase method. Immunofluorescent staining revealed that CD105, CD73, CD90 and CD44 were expressed in all groups while there was no expression of CD31, CD45 or HLA-DR. And the cells obtained with collagenaseII/hyaluronidase method were in a higher cell proliferation rate and activity compared to other methods. CONCLUSION: The collagenaseII/hyaluronidase method is optimal for the isolation of human umbilical cord MSCs than other methods.