Circular RNA hsa_circ_0050386 suppresses non-small cell lung cancer progression via regulating the SRSF3/FN1 axis.

BACKGROUND: Lung cancer is the most prevalent cancer worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all cases. Circular RNAs(circRNA) play crucial roles in regulating the progression of lung cancer. Despite the identification of a large number of circRNAs, their expression patterns, functions, and mechanisms of action in NSCLC development remain unclear.This study aims to investigate the transcriptional expressions, functions, and potential mechanisms of circRNA hsa_circ_0050386 in NSCLC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for the analysis of hsa_circ_0050386 expression. Cell proliferation was detected using the IncuCyte Live Cell Analysis System and clone formation assays. Migration and invasion of NSCLC cells were evaluated through Transwell assays. Flow cytometry was performed to assay cell cycle and apoptosis. Western blot was used to investigate protein expression. Protein binding analysis was conducted by employing pull-down assays, RNA immunoprecipitation (RIP), and mass spectrometry. The role of hsa_circ_0050386 in vivo was evaluated through the use of a xenograft model. RESULTS: The study discovered that hsa_circ_0050386 displayed lower expression levels in NSCLC tissues when compared to adjacent normal tissues. Patients exhibiting lower levels of hsa_circ_0050386 expression exhibited an inverse correlation with the Clinical Stage, T-stage, and M-stage of NSCLC. Functionally, hsa_circ_0050386 suppressed the proliferation and invasion of NSCLC cells both in vitro and in vivo. A comprehensive examination exposed the interaction between hsa_circ_0050386 and RNA binding protein Serine and arginine-rich splicing factor 3 (SRSF3), resulting in the down-regulation of Fibronectin 1 (FN1) expression, which inhibits the progression of NSCLC. CONCLUSIONS: Our study shows that hsa_circ_0050386 suppresses the malignant biological behavior of NSCLC cells by down-regulating the expression of FN1, and may serve as a potential biomarker and therapeutic target for NSCLC treatment.

A protein-protein interaction map reveals that the Coxiella burnetii effector CirB inhibits host proteasome activity.

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91-120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection.

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.

An EMT-related genes signature as a prognostic biomarker for patients with endometrial cancer.

BACKGROUND: The epithelial-mesenchymal transition (EMT) plays an indispensable role in the development and progression of Endometrial cancer (EC). Nevertheless, little evidence is reported to uncover the functionality and application of EMT-related molecules in the prognosis of EC. This study aims to develop novel molecular markers for prognosis prediction in patients with EC. METHODS: RNA sequencing profiles of EC patients obtained from The Cancer Genome Atlas (TCGA) database were used to screen differential expression genes (DEGs) between tumors and normal tissues. The Cox regression model with the LASSO method was utilized to identify survival-related DEGs and to establish a prognostic signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC) and calibration curve. Eventually, functional enrichment analysis and cellular experiments were performed to reveal the roles of prognosis-related genes in EC progression. RESULTS: A total of 540 EMT-related DEGs in EC were screened, and subsequently a four-gene risk signature comprising SIRT2, SIX1, CDKN2A and PGR was established to predict overall survival of EC. This risk signature could serve as a meaningfully independent indicator for EC prognosis via multivariate Cox regression (HR = 2.002, 95%CI = 1.433-2.798; P < 0.001). The nomogram integrating the risk signature and clinical characteristics exhibited robust validity and performance at predicting EC overall survival indicated by ROC and calibration curve. Functional enrichment analysis revealed that the EMT-related genes risk signature was associated with extracellular matrix organization, mesenchymal development and cellular component morphogenesis, suggesting its possible relevance to epithelial-mesenchymal transition and cancer progression. Functionally, we demonstrated that the silencing of SIX1, SIRT2 and CDKN2A expression could accelerate the migratory and invasive capacities of tumor cells, whereas the downregulation of PGR dramatically inhibited cancer cells migration and invasion. CONCLUSIONS: Altogether, a novel four-EMT-related genes signature was a potential biomarker for EC prognosis. These findings might help to ameliorate the individualized prognostication and therapeutic treatment of EC patients.

The potential benefits and mechanisms of protein nutritional intervention on bone health improvement.

Osteoporosis commonly occurs in the older people and severe patients, with the main reason of the imbalance of bone metabolism (the rate of bone resorption exceeding the rate of bone formation), resulting in a decrease in bone mineral density and destruction of bone microstructure and further leading to the increased risk of fragility fracture. Recent studies indicate that protein nutritional support is beneficial for attenuating osteoporosis and improving bone health. This review summarized the classical mechanisms of protein intervention for alleviating osteoporosis on both suppressing bone resorption and regulating bone formation related pathways (promoting osteoblasts generation and proliferation, enhancing calcium absorption, and increasing collagen and mineral deposition), as well as the potential novel mechanisms via activating autophagy of osteoblasts, altering bone related miRNA profiles, regulating muscle-bone axis, and modulating gut microbiota abundance. Protein nutritional intervention is expected to provide novel approaches for the prevention and adjuvant therapy of osteoporosis.

Characterizing the Internal Structure of Chinese Steamed Bread during Storage for Quality Evaluation Using X-ray Computer Tomography.

Chinese steamed bread (CSB) is a traditional food of the Chinese nation, and the preservation of its quality and freshness during storage is very important for its industrial production. Therefore, it is necessary to study the storage characteristics of CSB. Non-destructive CT technology was utilized to characterize and visualize the microstructure of CSB during storage, and also to further study of quality changes. Two-dimensional and three-dimensional images of CSBs were obtained through X-ray scanning and 3D reconstruction. Morphological parameters of the microstructure of CSBs were acquired based on CT image using image processing methods. Additionally, commonly used physicochemical indexes (hardness, flexibility, moisture content) for the quality evaluation of CSBs were analyzed. Moreover, a correlation analysis was conducted based on the three-dimensional morphological parameters and physicochemical indexes of CSBs. The results showed that three-dimensional morphological parameters of CSBs were negatively correlated with moisture content (Pearson correlation coefficient range-0.86~-0.97) and positively correlated with hardness (Pearson correlation coefficient range-0.87~0.99). The results indicate the inspiring capability of CT in the storage quality evaluation of CSB, providing a potential analytical method for the detection of quality and freshness in the industrial production of CSB.

Oat ß-glucan alleviates muscle atrophy via promoting myotube formation and suppressing protein degradation.

BACKGROUND: The dangerous inducers of muscle atrophy are inflammatory reaction, oxidative stress, and cachexia, etc. ß-Glucan, an important food derived active ingredient, has been reported to exert anti-inflammatory effects, however, its effects on regulating myoblast differentiation and protein degradation are unclear. This study is aimed to investigate the mechanism of oat ß-glucan on alleviating muscle atrophy. RESULTS: The results showed that oat ß-glucan treatment reversed tumor necrosis factor-α (TNF-α) induced abnormal myoblast differentiation and reduced muscle atrophy related MuRF-1 and Atrogin-1 protein expression. The similar phenomenon was observed after using MCC950 (NLRP3 specific inhibitor) or AS1842856 (FoxO1 specific inhibitor) to suppress NLRP3 and FoxO1 expression, respectively. Exposure to ß-glucan or AS1842856 also inhibited TNF-α induced the activation of TLR4/NF-κB pathway by inactivating FoxO1, and subsequently suppressed the expression of NLRP3. CONCLUSION: Our results indicate that oat ß-glucan exerts essential roles in promoting myoblast differentiation and alleviating muscle atrophy via inactivating FoxO1 and NLRP3 inflammasome signal pathway. © 2023 Society of Chemical Industry.

Coxiella burnetii Plasmid Effector B Promotes LC3-II Accumulation and Contributes To Bacterial Virulence in a SCID Mouse Model.

Coxiella burnetii, the causative agent of zoonotic Q fever, is characterized by replicating inside the lysosome-derived Coxiella-containing vacuole (CCV) in host cells. Some effector proteins secreted by C. burnetii have been reported to be involved in the manipulation of autophagy to facilitate the development of CCVs and bacterial replication. Here, we found that the Coxiella plasmid effector B (CpeB) localizes on vacuole membrane targeted by LC3 and LAMP1 and promotes LC3-II accumulation. Meanwhile, the C. burnetii strain lacking the QpH1 plasmid induced less LC3-II accumulation, which was accompanied by smaller CCVs and lower bacterial loads in THP-1 cells. Expression of CpeB in the strain lacking QpH1 led to restoration in LC3-II accumulation but had no effect on the smaller CCV phenotype. In the severe combined immune deficiency (SCID) mouse model, infections with the strain expressing CpeB led to significantly higher bacterial burdens in the spleen and liver than its parent strain devoid of QpH1. We also found that CpeB targets Rab11a to promote LC3-II accumulation. Intratracheally inoculated C. burnetii resulted in lower bacterial burdens and milder lung lesions in Rab11a conditional knockout (Rab11a-/- CKO) mice. Collectively, these results suggest that CpeB promotes C. burnetii virulence by inducing LC3-II accumulation via a pathway involving Rab11a.

The classical and potential novel healthy functions of rice bran protein and its hydrolysates.

Rice bran protein (RBP) is a plant protein obtained from rice bran, a byproduct produced during rice milling process. It has been proved to be a high quality protein due to containing all of the essential amino acids and the content closing to the FAO/WHO recommended ideal pattern. Recent studies indicated that RBP and rice bran protein hydrolysates (RBPH) served variety biological functions. In this review, we summarized the classical functions of RBP and RBPH mediating antioxidant activity, chronic diseases prevention (such as antihypertensive effect, anti-diabetic effect, cholesterol-lowering activity), and anti-cancer effect. We also proposed their potential novel functions on anti-obesity effect, attenuating sarcopenia, promoting wound healing. Furthermore, the potential benefit to coronavirus disease 2019 (COVID-19) patients was put forward, which might provide new strategy for development and utilization of RBP and RBPH.

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.

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.

Novel genotypes of Coxiella burnetii circulating in rats in Yunnan Province, China.

BACKGROUND: Coxiella burnetii (Cb) is the causative agent of the zoonotic disease Q fever which is distributed worldwide. Molecular typing of Cb strains is essential to find out the infectious source and prevent Q fever outbreaks, but there has been a lack of typing data for Cb strains in China. The aim of this study was to investigate the genotypes of Cb strains in wild rats in Yunnan Province, China. RESULTS: Eighty-six wild rats (Rattus flavipectus) were collected in Yunnan Province and 8 of the 86 liver samples from the wild rats were positive in Cb-specific quantitative PCR (qPCR). The Cb strains from the 8 rats were then typed into 3 genotypes using 10-spacer multispacer sequence typing (MST), and 2 of the 3 genotypes were recognized as novel ones. Moreover, the Cb strains in the wild rats were all identified as genotype 1 using 6-loci multilocus variable number of tandem repeat analysis (MLVA). CONCLUSIONS: This is the first report of genotypic diversity of Cb strains from wild rats in China. Further studies are needed to explore the presence of more genotypes and to associate the genotypes circulating in the wildlife-livestock interaction with those causing human disease to further expand on the epidemiological aspects of the pathogen.

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.

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.

Ginsenoside Re Preserves Cardiac Function and Ameliorates Left Ventricular Remodeling in a Rat Model of Myocardial Infarction.

Ginsenoside Re, an herbal ingredient from ginseng, has been demonstrated to protect the heart from various cardiovascular diseases. In this study, we investigated the protective effects and mechanisms of ginsenoside Re (Gin-Re) on cardiac function and left ventricular remodeling in a rat model of myocardial infarction (MI). After ligating the left anterior descending coronary artery, Wistar rats were treated with Gin-Re (135 mg/kg) by gavage everyday for 4 weeks. Serological detection showed that Gin-Re significantly inhibited myocardial injury and attenuated oxidative stress in MI rats. Echocardiographic observation showed that Gin-Re significantly improved cardiac function and prevented left ventricular dilatation induced by MI. Pathological observation found that Gin-Re significantly decreased interstitial fibrosis in the left ventricle of MI rats. Compared with the MI group, Gin-Re treatment promoted AMPKα phosphorylation, decreased TGF-ß1 expression, and attenuated Smad2/3 activation. After Gin-Re treatment, the phosphorylation of FAK, PI3K p110α, and Akt was enhanced in MI rats, while PI3K p110ß showed no difference compared with the MI group. These results indicate that Gin-Re may improve MI-induced cardiac dysfunction and mitigate ventricular remodeling through regulation of the AMPK/TGF-ß1/Smad2/3 and FAK/PI3K p110α/Akt signaling 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.

XIAP overexpression promotes bladder cancer invasion in vitro and lung metastasis in vivo via enhancing nucleolin-mediated Rho-GDIß mRNA stability.

Our recent studies demonstrate that X-linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here, we discovered that RhoGDIß was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIß expressions were consistently elevated in BCs of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice in comparison to bladder tissues from vehicle-treated mice and human BCs in comparison to the paired adjacent normal bladder tissues. Knockdown of XIAP attenuated RhoGDIß expression and reduced cancer cell invasion, whereas RhoGDIß expression was attenuated in BBN-treated urothelium of RING-deletion knockin mice. Mechanistically, XIAP stabilized RhoGDIß mRNA by its positively regulating nucleolin mRNA stability via Erks-dependent manner. Moreover, ectopic expression of GFP-RhoGDIß in T24T(shXIAP) cells restored its lung metastasis in nude mice. Our results demonstrate that XIAP-regulated Erks/nucleolin/RhoGDIß axis promoted BC invasion and lung metastasis.

Apoptosis and death receptor signaling in diaphragm of burnt rats.

BACKGROUND: Respiratory dysfunction is a frequent complication after severe burn injury. Respiratory muscle atrophy may induce respiratory dysfunction due to insufficient inspiratory motive power. Accumulated evidence suggests that apoptosis is very important in skeletal muscle atrophy in multiple pathologic conditions. Therefore, we hypothesize that myonuclear apoptosis contributes to diaphragm atrophy induced by burn injury, and death receptor signaling activation plays a role in this process. METHODS: Wistar rats in the burn-injured group were subjected to a full-thickness scald injury around 40% of total body surface area. Diaphragm samples were examined for myonuclear apoptosis by transmission electron microscope, terminal deoxynucleotidyl transferase-mediated nick end labeling assay, and immunohistochemistry for caspase-3. Serum level of apoptotic ligands were assessed by ELISA. Activation of death receptor signaling was examined by Western blotting. RESULTS: Burn injury resulted in significant reductions of diaphragm muscle mass and myofiber cross-section area. Apoptosis in diaphragm appeared from day 1 and peaked on day 4 after injury. The level of soluble TNF-related apoptosis-inducing ligand and the ratio of Fas ligand to soluble Fas in serum significantly increased after burn injury. In diaphragm of burnt animals, the expressions of proapoptotic proteins, such as cleaved caspase-8, cleaved caspase-3, and Bax-to-Bcl-2 ratio were upregulated, whereas expression of pAkt, an antiapoptotic protein, was downregulated. Immunohistochemistry revealed that the most of the caspase-3 was expressed in myofiber nuclei and their surrounding cytoplasm area in tissue sections. CONCLUSIONS: Severe burn injury induces myonuclear apoptosis in diaphragm, which could be a contributor to diaphragm muscle atrophy. Activation of death receptor signaling may be a mechanism of apoptosis in diaphragm.

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.

A new tumour suppression mechanism by p27Kip1: EGFR down-regulation mediated by JNK/c-Jun pathway inhibition.

p27Kip1 is a potent inhibitor of cyclin-dependent kinases that drive G1-to-S cell-cycle transition. Reduced p27Kip1 expression is prevalent in a wide range of human tumours; however, the exact mechanism(s) of p27Kip1-mediated tumour suppression remains obscure. In the present study, we identified a close inverse relationship between p27Kip1 and EGFR (epidermal growth factor receptor) expression: the parental T24 human bladder cancer cells had high p27Kip1 expression but low EGFR expression and, in striking contrast, the metastatic derivative of T24 (T24T) had low p27Kip1 expression but high EGFR expression. This relationship was also found in various human cancer tissues, and was not only just correlative but also causal; depletion of p27Kip1 in MEF (mouse embryonic fibroblast) cells resulted in markedly elevated EGFR expression, a result reproducible with an Egfr promoter-luciferase reporter in both T24 and MEF cells, suggesting transcriptional repression of EGFR by p27Kip1. Indeed, p27Kip1 was found to regulate EGFR expression via the JNK (c-Jun N-terminal kinase)/c-Jun transcription factor: p27Kip1 deficiency activated JNK/c-Jun, whereas inhibition of JNK/c-Jun by dominant-negative mutants dramatically repressed Egfr transcription. Furthermore, the proximal promoter of the Egfr gene was crucial for its transcription, where the recruiting activity of c-Jun was much greater in p27Kip1-/- cells than in p27Kip1+/+ cells. Introduction of GFP-p27Kip1 into T24T cells suppressed JNK/c-Jun activation, EGFR expression and anchorage-independent growth. The results of the present study demonstrate that p27Kip1 suppresses JNK/c-Jun activation and EGFR expression in MEFs and human bladder cancer cells, and the results obtained are consistent with those from human cancer specimens. The present study provides new insights into p27Kip1 suppression of cancer cell growth, migration and metastasis.