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OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS: Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.
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Hiperplasia Suprarrenal Congénita , Criptorquidismo , Trastornos del Desarrollo Sexual , Hipospadias , Masculino , Humanos , Niño , Trastornos del Desarrollo Sexual/genética , Trastornos del Desarrollo Sexual/diagnóstico , Trastornos del Desarrollo Sexual/patología , Hipospadias/genética , Hipospadias/complicaciones , Criptorquidismo/complicaciones , Estudios Retrospectivos , Esteroide 21-HidroxilasaRESUMEN
BackgroundP16 methylation plays an important role in the pathogenesis of hyperoxia-induced lung fibrosis. 5-aza-2'-deoxycytidine (5-aza-CdR) is a major methyltransferase-specific inhibitor. In this study, the effects of 5-aza-CdR on a hyperoxia-induced lung fibrosis in neonatal rats were investigated.MethodsRat pups were exposed to 85% O2 for 21 days of and received intraperitoneal injections of 5-aza-CdR or normal saline (NS) once every other day. Survival rates and lung coefficients were calculated. Hematoxylin-eosin staining was performed to analyze the degree of lung fibrosis. Collagen content and TGF-ß1 levels were determined. A methylation-specific polymerase chain reaction and western blotting were performed to determine P16 methylation status and P16, cyclin D1, and E2F1 protein expression.Results5-aza-CdR treatment during hyperoxia significantly improved the survival rate and weight gain, while it decreases the degree of lung fibrosis and levels of hydroxyproline and TGF-ß1. Hyperoxia induced abnormal P16 methylation and 5-aza-CdR effectively reversed the hypermethylation of P16. Expression of the P16 protein in lung tissues was enhanced, while cyclin D1 and E2F1 protein were reduced by 5-aza-CdR treatment during hyperoxia.ConclusionThese data show that 5-aza-CdR attenuated lung fibrosis in neonatal rats exposed to hyperoxia by lowering hydroxyproline and TGF-ß1 expression and via re-expression of P16 in neonatal rats.
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Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Decitabina/farmacología , Regulación de la Expresión Génica , Hiperoxia/tratamiento farmacológico , Pulmón/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Animales Recién Nacidos , Metilación de ADN/efectos de los fármacos , Femenino , Fibrosis/tratamiento farmacológico , Hidroxiprolina/metabolismo , Pulmón/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Surfactant protein C (SP-C) deficiency is a risk factor for hyperoxia-induced bronchopulmonary dysplasia in newborn infants. However, the role of SP-C deficiency in the process is unclear. Here, using neonatal rat BPD model and MLE-12, mouse alveolar epithelial type II cell, we examined the changes of SP-C levels during hyperoxia. Immunohistochemistry, immunofluorescence, and ELISA analysis showed SP-C accumulation in alveolar epithelial type II cells. Electron microscopy further demonstrated the accumulation of lamellar bodies and the co-localization of lamellar bodies with autophagosomes in the cytoplasm of alveolar epithelial type II cells. The inhibition of autophagy with 3-Methyladenine and knockdown of Atg7 abolished hyperoxia-induced SP-C accumulation in the cytoplasm. Furthermore, inhibition of JNK signaling with SP600125 suppressed hyperoxia-induced Atg7 expression and SP-C accumulation. These findings suggest that hyperoxia triggers autophagy via JNK signaling-mediated Atg7 expression, which promotes the accumulation of SP-C within alveolar epithelial type II cells. Our data provide a potential approach for hyperoxic lung injury therapy by targeted pharmacological inhibition of autophagic pathway.
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Células Epiteliales/citología , Sistema de Señalización de MAP Quinasas , Alveolos Pulmonares/metabolismo , Proteína C Asociada a Surfactante Pulmonar/metabolismo , Enzimas Activadoras de Ubiquitina/metabolismo , Animales , Animales Recién Nacidos , Autofagia , Hipoxia de la Célula , Línea Celular , Ratones , Alveolos Pulmonares/citología , RatasRESUMEN
BACKGROUND: Social anxious individuals show attention bias towards emotional stimuli, this phenomenon is considered to be an important cause of anxiety generation and maintenance. Cognitive-behavioral therapy (CBT) is a standard psychotherapy for social anxiety disorder. CBT decreases attention biases by correcting the maladaptive beliefs of socially anxious individuals, but it is not clear whether CBT alters neurophysiological features of socially anxious individuals at early automatic and/or late cognitive strategy stage of attentional processing. METHOD: To address this knowledge gap, we collected pre-treatment event-related potential data of 22 socially anxious individuals while they performed a dot-probe task. These participants then received eight weeks of CBT, and post-treatment ERP data were collected after completion of CBT treatment. We also included 29 healthy controls and compared them with individuals with social anxiety to determine the neural mechanisms underlying the effectiveness of CBT. RESULTS: Participants' social anxiety level was significantly alleviated with CBT. ERP results revealed that (1) compared to pre-treatment phase, P1 amplitudes induced by probes significantly decreased at post-treatment phase, whereas P3 amplitudes increased at post-treatment phase; the P1 amplitudes induced by probes following happy-neutral face pairs in socially anxious individuals after treatment was significantly different with that in healthy controls; (2) amplitude of components elicited by face pairs did not change significantly between pre-treatment and post-treatment phases; (3) changes of Liebowitz Social Anxiety Scale were positively correlated with changes of P1 amplitude, and negatively correlated with changes of N1 amplitude. LIMITATIONS: Our sample was university students and lacked randomization, which limits the generalizability of the results. CONCLUSION: The present results demonstrated that CBT may adjust cognitive strategies in the later stage of attentional processing, indicating by changed ERPs appeared in probe-presenting stage for social anxiety.
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Terapia Cognitivo-Conductual , Electroencefalografía , Potenciales Evocados , Fobia Social , Humanos , Femenino , Masculino , Terapia Cognitivo-Conductual/métodos , Potenciales Evocados/fisiología , Adulto , Adulto Joven , Fobia Social/fisiopatología , Fobia Social/terapia , Sesgo Atencional/fisiologíaRESUMEN
Accurate interpretation of the emotional information conveyed by others' facial expressions is crucial for social interactions. Event-related alpha power, measured by time-frequency analysis, is a frequently used EEG index of emotional information processing. However, it is still unclear how event-related alpha power varies in emotional information processing in social anxiety groups. In the present study, we recorded event-related potentials (ERPs) while participants from the social anxiety and healthy control groups viewed facial expressions (angry, happy, neutral) preceded by contextual sentences conveying either a positive or negative evaluation of the subject. The impact of context on facial expression processing in both groups of participants was explored by assessing behavioral ratings and event-related alpha power (0-200 ms after expression presentation). In comparison to the healthy control group, the social anxiety group exhibited significantly lower occipital alpha power in response to angry facial expressions in negative contexts and neutral facial expressions in positive contexts. The influence of language context on facial expression processing in individuals with social anxiety may occur at an early stage of processing.
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Expresión Facial , Reconocimiento Facial , Humanos , Electroencefalografía , Reconocimiento Facial/fisiología , Emociones/fisiología , Potenciales Evocados/fisiología , Ansiedad , LenguajeRESUMEN
OBJECTIVE: To determine the dynamic expression of E2F1 in lung of premature rats with hyperoxia-induced chronic lung disease and the relation between E2F1 and pulmonary fibrosis. METHODS: Premature Wistar rats at 21 days gestation were randomly and equally divided into a hyperoxia group and a room air group. The hyperoxia group was continuously exposed to hyperoxia (90%) while the air group in room air. Lung tissues in the 2 groups were obtained at 3, 7 and 14 days after exposing to either room air or hyperoxia. The changes of pulmonary histopathology at different time points were observed by hematoxylin and eosin staining; the severity of pulmonary fibrosis was evaluated; and the expression of E2F1 in lung tissue was detected by immunohistochemistry and Western blot. RESULTS: After 3 days of hyperoxia, no significant interstitial fibrosis was observed; while after 7 days in the hyperoxia group, interstitial fibrosis was observed. These changes became more obvious after 14 days of prolonged hyperoxia exposure. No significant difference in the expressions of E2F1 protein was found between the hyperoxia group and the room air group 3 days postnatally (P>0.05). The expression of E2F1 in the hyperoxia group significantly increased 7 days and 14 days postnatally (P<0.05, P<0.01). CONCLUSION: Abnormality of E2F1 expression is involved in the pathological process of the proliferation of lung fibroblasts in hyperoxia-induced chronic lung disease neonatal rats, and it plays an important role in lung fibrosis.
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Factor de Transcripción E2F1/metabolismo , Hiperoxia/metabolismo , Enfermedades Pulmonares/metabolismo , Pulmón/patología , Animales , Animales Recién Nacidos , Hiperoxia/patología , Inmunohistoquímica , Enfermedades Pulmonares/patología , Fibrosis Pulmonar , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
The Bivalent Fear of Evaluation (BFEO) model posits that the fear of positive evaluation (FPE) is a core feature of social anxiety. As such, high socially anxious individuals may show attention bias when faced with positive stimuli. However, most of the previous studies focused on the negative attention bias of social anxiety, and less on the attention bias of positive stimuli. Meanwhile, the effect of stimulus presentation time on the attention bias pattern was unclear. In order to investigate this question, we used a dot-probe paradigm with facial expressions (happy, fearful, angry, neutral) presented for 100 ms and 500 ms. The ERP results showed: (1) For high socially anxious group, happy faces elicited a larger N1 for valid than for invalid cued probes, whereas for healthy control group, angry faces elicited a larger N1 for valid than for invalid cued probes. (2) When valid cues following happy faces presented for 500 ms, the N1 amplitude was larger than that of invalid cues. However, when valid cues following angry and fear faces presented for 100 ms, the N1 amplitude was larger than that of invalid cues. The results showed difficulty in attention disengagement of high socially anxious individuals from positive stimuli, as reflected by N1, illustrating the positive attention bias in social anxiety. These results prove that FPE may contribute to maintaining social anxiety.
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Sesgo Atencional , Expresión Facial , Humanos , Ansiedad , Ira , MiedoRESUMEN
Previous studies have shown that the perception of ambiguous facial expressions for individuals with social anxiety was influenced by the affective verbal context. However, it is still unknown how emotional facial expressions are perceived by individuals with social anxiety in the context of the verbal context. In this study, we used event-related potentials (ERPs) technology to examine how individuals with social anxiety perceive emotional facial expressions in positive and negative contexts. The results showed that: (1) Within the negative verbal contexts, the amplitude of P1 induced by facial expressions in the social anxiety group was significantly higher than that induced by the healthy control group; The N170 amplitude induced by facial expressions in social anxiety group was less negative than that in the healthy control group, and was not affected by the context. (2) The social anxiety group had significantly higher LPP in negative contexts elicited by angry expressions than by happy expressions. This study proved that the perception of emotional facial expressions was influenced by top-down information in the early and late stages of visual perception for individuals with social anxiety.
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Electroencefalografía , Expresión Facial , Ansiedad , Electroencefalografía/métodos , Emociones/fisiología , Potenciales Evocados/fisiología , Humanos , Percepción Social , Percepción VisualRESUMEN
p16INK4a (p16) inhibits the vital G1 to S phase transition during cell cycle progression through the p16/cyclin D1/CDK4/retinoblastoma(Rb)/E2F1 pathway. Hyperoxia can suppress the G1/S checkpoint and induce more lung fibroblasts (LFs) to transition from the G1 phase to the S phase and undergo cell proliferation. The present study investigated the rate of p16 gene promoter methylation and the protein expression levels of p16, cyclin D1, CDK4, Rb and E2F1 in LFs from the lungs of rats exposed to hyperoxia and normoxia on postnatal days 3, 7 and 14. In the hyperoxia-exposed group, the methylation rate was 50 and 80% on days 7 and 14, respectively. Cyclin D1 and CDK4 overexpression was associated with p16 loss and Rb inactivation by phosphorylation. Rb phosphorylation induced E2F1 release in the G1 phase, which promoted cell proliferation. No methylation was observed in the normoxia-exposed group. These observations suggested that p16 loss may stimulate aberrant LF proliferation via the p16/cyclin D1/CDK4/Rb/E2F1 pathway.
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OBJECTIVE: To investigate the characteristics of gene expression of surfactant protein A in Chinese premature infants and the association between surfactant protein A and the risk of neonatal respiratory distress syndrome (RDS). METHODS: Vein-blood samples (2 mL) from 18 Chinese premature infants with RDS and 28 controls were assayed for SP-A genotypes 6A2, 6A3, 1A0 and 1A1 by SSCP. RESULTS: The frequency of allele distribution of SP-A1 allele 6A2 and 6A3 was 0.50 and 0.056 respectively in the RDS group and was 0.214 and 0.107 in the control group. Compared with the controls, SP-A1 allele 6A2 was over-represented in the RDS group (P<0.05). In contrast, SP-A1 allele 6A3 tended to be under-represented in the RDS group but there was no statistical difference when compared with the controls. The frequency of allele distribution of SP-A2 allele 1A0 and 1A1 was 0.722 and 0.667 respectively in the RDS group and was 0.679 and 0.821 respectively in the control group. There were no significant differences in the distribution frequency of SP-A2 allele 1A0 and 1A1 between the two groups. In the infants born at gestation >32 weeks, SP-A1 allele 6A2 was over-represented in the RDS group compared with the control group (frequency: 0.56 vs 0.15; P<0.05). CONCLUSIONS: The frequency of SP-A1 allele 6A2 and 6A3 was low, in contrast, the frequency of SP-A2 allele 1A0 and 1A1 was high in normal Chinese premature infants. SP-A1 allele 6A2 may be a susceptible gene for RDS.
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Polimorfismo Genético , Proteína A Asociada a Surfactante Pulmonar/genética , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Síndrome de Dificultad Respiratoria del Recién Nacido/etiologíaRESUMEN
RATIONALE: Traumatic hip dislocation is a common joint dislocation. Delayed reduction has been shown to increase the risk of avascular necrosis of the femoral head. Most of the traditional methods must be performed under general anesthesia or spinal anesthesia to relax hip muscles. Anesthesia will prolong the interval between the injury and the reduction. PATIENT CONCERNS: 16 patients presented with hip pain and a leg shortened, flexed, internally rotated and adducted. DIAGNOSES: X-ray and CT-scan showed acute closed posterior dislocation of hip. INTERVENTIONS: Closed reduction of the traumatic posterior-dislocation of hip joint using a novel sitting technique. OUTCOMES: Among these 16 patients, 15 hips were successfully reduced using the Sitting Technique (table 1), indicating the success rate was 93.8%(15/16). A total of 12 patients were followed up, with a mean period of 23.5 months (range, 6-72 months). Among these 12 patients, 10 patients (83.3%) had excellent grade, 2 patients (16.7%) had good grade. LESSONS: Sitting technique for treatment of traumatic posterior dislocation of hip joint does not need anaesthesia, which it shortens the interval between the injury and the reduction and saves valuable time for 6 hours of joint reduction. On the other hand, this method does no harm to the physicians' low back.
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Luxación de la Cadera/terapia , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: As for the association between vitamin D receptor (VDR) gene polymorphisms and osteoporosis, the current results have yielded conflicts. Therefore, we performed a pooled analysis based on Chinese individuals to provide comprehensive data on the association between VDR BsmI, ApaI, Tru9I polymorphisms and osteoporosis risk. METHODS: Studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine databases through to January 2017. Studies were screened according to the predefined inclusion and exclusion criteria. The association between VDR BsmI, ApaI, Tru9I polymorphisms and osteoporosis was evaluated by calculating pooled odds ratios (ORs) based on the individual ORs. The significance of the pooled OR was evaluated by a Z-test. All statistical analyses were conducted using Stata 12.0 software (StataCorp, College Station, TX, USA). RESULTS: A total of 13 studies with 1141 osteoporosis cases and 1263 controls were included in this meta-analysis. It revealed that VDR Tru9I polymorphism was associated with an increased risk of osteoporosis in a common model (OR = 2.67, CI 95% = 1.59-4.49). No significant association was observed between VDR BsmI, ApaI and osteoporosis. CONCLUSION: In conclusion, this meta-analysis suggests that VDR Tru9I polymorphism may be associated with osteoporosis risk in Chinese individuals, while BsmI, ApaI polymorphisms might not be a risk factor for osteoporosis.
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Osteoporosis/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Oportunidad Relativa , Osteoporosis/diagnóstico , Osteoporosis/etnología , Fenotipo , Factores de RiesgoRESUMEN
Lung fibrosis is an ultimate consequence of bronchopulmonary dysplasia (BPD) which shows the excessive proliferation of lung fibroblasts (LFs). To find a better model for studying the role of LFs in hyperoxia-induced lung fibrosis at the cellular level, we isolated LFs from the lung tissue of hyperoxia- and normoxia-exposed rat lungs on postnatal days 7, 14 and 21 for primary culture to study their proliferative behavior. In the present study, the LF predominance was > 95% in our culture method. The LFs isolated from rats exposed to hyperoxia in vivo showed significantly greater proliferation than that from normoxia-exposed rats. Flow cytometry revealed that percentage of LFs in S and G2/M stage increased, and proportion in the G0/G1 stage declined at the same time. A greater presence of myofibroblasts in LFs isolated from rats exposed to hyperoxia compared with those exposed to normoxia. In addition, elevated collagen level, transforming growth factor-ß and connective tissue growth factor protein expression in conditioned medium were also found in hyperoxia LFs. These data demonstrate that hyperoxia promotes LFs proliferation, myofibroblast transdifferentiation and collagen synthesis in a time-dependent manner. The primary culture of LFs from hyperoxia-exposed rats is a feasible method for studying the pathogenesis and treatment of lung fibrosis caused by BPD at the cellular level.
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BACKGROUND: A persistent increase in the number of lung fibroblasts (LFs) is found in the interstitium of the lungs of infants with bronchopulmonary dysplasia (BPD), which leads to lung fibrosis. P16 methylation plays an important role in the pathogenesis of BPD. 5-aza-2'-deoxycytidine (5-aza-CdR) is a major methyltransferase-specific inhibitor. This study investigated the effects of 5-aza-CdR on LFs in vitro from a hyperoxia-induced lung fibrosis model in newborn rats. METHODS: Methylation-specific polymerase chain reaction (PCR) and Western blotting were performed to determine P16 gene methylation status and protein expression after LFs were treated with 0 µmol/L, 0.5 µmol/L, 1.0 µmol/L, and 5.0 µmol/L 5-aza-CdR for 120 hours. Proliferation was assessed by an MTT assay after LFs were treated with 0 µmol/L, 0.5 µmol/L, 1.0 µmol/L, and 5.0 µmol/L 5-aza-CdR for 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours. At the final time point, cells were also analyzed by flow cytometry to identify any change in their cell cycle profiles. RESULTS: A methylated P16 gene promoter was detected in hyperoxia LFs. Following treatment with 5-aza-CdR, partial methylation and demethylation was detected. The expression protein's level of the P16 gene was significantly higher in the 5.0 µmol/L 5-aza-CdR-treated group compared with that in the control group (p < 0.01). The cell growth rate at each tested time point was lower in the 5-aza-CdR-treated group compared with that in the control group after 72 hours (p < 0.01). Flow cytometry revealed that the cells in the 1.0 µmol/L and 5.0 µmol/L 5-aza-CdR-treated groups were apparently arrested in the G0/G1 phase and that the number of cells in the S phase was significantly lower than the control group (p < 0.01). CONCLUSION: 5-aza-CdR inhibits the growth of the LFs in hyperoxia-induced neonatal BPD rats in vitro by demethylating the P16 gene.
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Azacitidina/análogos & derivados , Proliferación Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Fibroblastos/efectos de los fármacos , Pulmón/citología , Animales , Animales Recién Nacidos , Azacitidina/farmacología , Displasia Broncopulmonar/metabolismo , Decitabina , Modelos Animales de Enfermedad , Hiperoxia/complicaciones , Ratas , Ratas Sprague-DawleyRESUMEN
Although supplemental high-level oxygen treatment can promote the survival of premature infants, hyperoxia may adversely induce acute lung injury (ALI) in newborns. Our prior work illustrated that hyperoxic exposure could enhance the release of placental growth factor (PLGF) in the lungs of neonatal rats. We therefore postulated that PLGF contributed to hyperoxic ALI in newborns and evaluated the anti-PLGF treatment mediated by systematic delivery of lentivirus in hyperoxic ALI in this study. Lentivirus particles containing PLGF specific shRNA were injected into neonatal rats prior to hyperoxic exposure (90% oxygen for 72h) to inhibit PLGF expression. Hyperoxia induced oxidative damages in lung tissues as evidenced by the increased malondialdehyde and myeloperoxidase, and the decreased antioxidant superoxide dismutase. Also, hyperoxia caused excessive infiltration of inflammatory cells and overproduction of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1ß and interleukin-6) in rat lung tissue. These pathological alterations were partly reversed by PLGF shRNA delivery. The expression levels and activities of metalloproteinase (MMP)-2 and MMP9 were up-regulated in response to hyperoxia, whereas down-regulated when PLGF was inhibited. Moreover, PLGF shRNA inhibited nuclear factor kappa B (NFκB) signaling delivery in hyperoxic rat lungs. Additionally, exogenous PLGF-induced activation of MMPs in rat RLE-6TN alveolar epithelial cells was suppressed by NFκB inhibitor pyrrolidine dithiocarbamate. These results suggest that therapy targeting PLGF may be beneficial for infants with hyperoxic ALI.