Factors influencing C-reactive protein status on admission in neonates after birth.

OBJECTIVE: To explore the factors influencing C-reactive protein (CRP) status in neonates on admission after birth. METHODS: 820 newborns born and hospitalized at Xiangya Hospital of Central South University from Jan. 2020 to Dec. 2020 were retrospectively analyzed. Maternal medical history and medication use during pregnancy, neonatal demographic information and status at birth were collected through the electronic medical record system. Statistical software was used to analyze the possible relationship between perinatal factors and CRP on admission after birth. RESULTS: A total of 820 neonates were analyzed, including 463 males and 357 females with a mean gestational age (GA) of 36.07 ± 3.30 weeks. (1) Multifactor Logistic regression analysis: larger GA (OR: 1.13, 95%CI: 1.00-1.28, P = 0.042), premature rupture of membranes (PROM) ≥ 18 h (OR: 2.39, 95%CI: 1.35-4.23, P = 0.003) and maternal autoimmune diseases (OR: 5.30, 95%CI: 2.15-13.07, P < 0.001) were independent risk factors for CRP ≥ 8 mg/L. Cesarean delivery (OR 0.40, 95%CI: 0.26-0.60, P < 0.001) was independent protective factor for CRP ≥ 8 mg/L. (2) Threshold effect analysis: A non-linear relationship was found between GA and CRP. When GA is less than 33.9 weeks, the risk of CRP ≥ 8 mg/L was reduced by 28% with one week increased (P < 0.001), and when GA is more than 33.9 weeks, the risk of CRP ≥ 8 mg/L was increased by 61% with one week increased (P < 0.001). CONCLUSIONS: GA, PROM, maternal autoimmune diseases and cesarean delivery were all independent influences neonatal CRP ≥ 8 mg/L on admission, and there was a nonlinear relationship between GA and neonatal CRP ≥ 8 mg/L on admission.

The association between sex and neonatal respiratory distress syndrome.

BACKGROUND: To investigate the association between sex and neonatal respiratory distress syndrome (NRDS). METHODS: Neonates born at our hospital and transferred to the neonatal department within 1 h were retrospectively analyzed. Depending on whether they developed NRDS during their hospital stay, the neonates was divided into NRDS and non-NRDS groups. There were 142 neonates in the NRDS group (95 males and 47 females) and 310 neonates in the non-NRDS group (180 males and 140 females). The neonates' data on gestational age (GA), sex, birth weight, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), total immunoglobulin M (total IgM), gestational diabetes mellitus(GDM), antenatal steroids use, meconium-stained amniotic fluid, and preterm premature rupture of membranes(PPROM) were gathered. RESULTS: 452 neonates (265 males and 187 females) were involved for the purpose of collecting basic characteristic. Multivariate analysis, males had a 1.87 times higher risk of NRDS than females (P < 0.05) after controlling for the confounding effects of GA, birth weight, WBC, PLT, CRP, total IgM, GDM, antenatal steroids use, meconium-stained amniotic fluid, and PPROM. CONCLUSIONS: Sex was associated with NRDS; males had a considerably higher risk of NRDS than females.

[Melatonin alleviates autophagy in cortical neurons of neonatal rats with hypoxic- ischemic brain damage via the PI3K/AKT pathway]. / è¤ªé»‘ç´ é€šè¿‡PI3K/AKTé€šè·¯å‡è½»ç¼ºæ°§ç¼ºè¡€æ€§è„‘æŸä¼¤æ–°ç”Ÿå¤§é¼ å¤§è„‘çš®å±‚ç¥žç»ç»†èƒžè‡ªå™¬çš„ç ”ç©¶.

OBJECTIVES: To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the PI3K/AKT signaling pathway, aiming to provide a basis for the clinical application of melatonin. METHODS: Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group, an HIBD group, and a melatonin group (n=9 each). The neonatal rat HIBD model was established using the classic Rice-Vannucci method. Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining. Autophagy-related protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunofluorescence staining and Western blot analysis. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression levels were measured by immunohistochemistry and Western blot. The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis. RESULTS: Twenty-four hours post-modeling, neurons in the sham operation group displayed normal size and orderly arrangement. In contrast, neurons in the HIBD group showed swelling and disorderly arrangement, while those in the melatonin group had relatively normal morphology and more orderly arrangement. Nissl bodies were normal in the sham operation group but distorted in the HIBD group; however, they remained relatively intact in the melatonin group. The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group, but was reduced in the melatonin group compared to the HIBD group (P<0.05). The number of p-PI3K+ and p-AKT+ cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group (P<0.05). LC3 and Beclin-1 protein expression levels were higher, and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group (P<0.05); however, in the melatonin group, LC3 and Beclin-1 levels decreased, and p-PI3K and p-AKT increased compared to the HIBD group (P<0.05). The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+ and p-AKT+ cells between the two groups (P<0.05). CONCLUSIONS: Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD, thereby alleviating HIBD. This mechanism is associated with the PI3K/AKT pathway.

HD-eXplosion: visualization of hydrogen-deuterium exchange data as chiclet and volcano plots with statistical filtering.

SUMMARY: Hydrogen-Deuterium eXchange coupled to mass spectrometry is a powerful tool for the analysis of protein dynamics and interactions. Bottom-up experiments looking at deuterium uptake differences between various conditions are the most common. These produce multi-dimensional data that can be challenging to depict in a single visual format. Each user must also set significance thresholds to define meaningful differences and make these apparent in data presentation. To assist in this process, we have created HD-eXplosion, an open-source, web-based application for the generation of chiclet and volcano plots with statistical filters. HD-eXplosion fills a void in available software packages and produces customizable plots that are publication quality. AVAILABILITY AND IMPLEMENTATION: The HD-eXplosion application is available at http://hd-explosion.utdallas.edu. The source code can be found at https://github.com/HD-Explosion.

[The TXNIP/Trx-1/GPX4 pathway promotes ferroptosis in hippocampal neurons after hypoxia-ischemia in neonatal rats]. / TXNIP/Trx-1/GPX4é€šè·¯ä¿ƒè¿›æ–°ç”Ÿå¤§é¼ ç¼ºæ°§ç¼ºè¡€åŽæµ·é©¬ç¥žç»å ƒé“æ­»äº¡çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe the change in ferroptosis in hippocampal neurons after hypoxia-ischemia (HI) in neonatal rats and investigate the related mechanism based on the TXNIP/Trx-1/GPX4 signaling pathway. METHODS: Healthy neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into three groups: sham-operation (n=30), hypoxic-ischemic brain damage (HIBD) (n=30) and siRNA (TXNIP siRNA) (n=12). The classic Rice-Vannucci method was used to establish a neonatal rat model of HIBD. At 6 hours, 24 hours, 72 hours, and 7 days after modeling, Western blot was used to measure the protein expression of GPX4 in the hippocampal tissue at the injured side; at 24 hours after modeling, laser speckle imaging combined with hematoxylin-eosin staining was used to determine whether the model was established successfully; NeuN/GPX4 and GFAP/GPX4 immunofluorescence staining combined with Western blot and other methods was used to measure the protein expression of GPX4 and the signal molecules TXNIP and Trx-1 in the hippocampal tissue at the injured side; the kits for determining the content of serum iron and tissue iron were used to measure the change in iron content; quantitative real-time PCR was used to measure the mRNA expression of TXNIP, Trx-1, and GPX4. RESULTS: At 6 hours, 24 hours, 72 hours, and 7 days after modeling, the HIBD group had a significantly lower protein expression level of GPX4 than the sham-operation group (P<0.05). At 24 hours after modeling, the HIBD group had a significantly lower cerebral blood flow of the injured side than the sham-operation group (P<0.05), with loose and disordered arrangement and irregular morphology of hippocampal CA1 neurons at the injured side. Compared with the sham-operation group, the HIBD group had a significantly higher number of TXNIP+ cells and significantly lower numbers of Trx-1+ cells and NeuN+GPX4+/NeuN+ cells in the hippocampal CA1 region at the injured side (P<0.05), with almost no GFAP+GPX4+ cells in the hippocampal CA1 region. Compared with the sham-operation group, the HIBD group and the siRNA group had significantly higher levels of serum iron and tissue iron in the hippocampus at the injured side (P<0.05). Compared with the HIBD group, the siRNA group had significantly lower levels of serum iron and tissue iron in the hippocampus at the injured side (P<0.05). The HIBD group and the siRNA group had significantly higher mRNA and protein expression levels of TXNIP than the sham-operation group (P<0.05), and the siRNA group had significantly lower expression levels than the HIBD group (P<0.05). The HIBD group and the siRNA group had significantly lower mRNA and protein expression levels of Trx-1 and GPX4 in the hippocampus at the injured side than the sham-operation group (P<0.05), and the siRNA group had significantly higher expression levels than the HIBD group (P<0.05). CONCLUSIONS: HI induces ferroptosis of hippocampal neurons in neonatal rats by activating the TXNIP/Trx-1/GPX4 pathway, thereby resulting in HIBD.

[Fetal pleural effusion in the uterus and dyspnea after birth].

Neonatal chylothorax is a common cause of neonatal congenital pleural effusion and is often caused by the accumulation of chylous fluid in the thoracic cavity due to the rupture of the thoracic duct and its branched lymphatic vessels for a variety of reasons. Neonatal chylothorax caused by malignant tumors is extremely rare, and this is the first case of neonatal mediastinal neuroblastoma with chylothorax in China. The boy was found to have pleural effusion in the left thoracic cavity in the uterus, and experienced apnea at birth, as well as dyspnea and cyanosis as the main manifestations after birth. He was diagnosed with left chylothorax based on conventional biochemical analysis of pleural effusion. After the treatment including persistent chest drainage and symptomatic and supportive treatment, the drainage of the left thoracic cavity reached a volume of 90-180 mL per day. Neonatal refractory chylothorax was considered. Chest radiograph on day 13 after birth showed lesions in the upper left lung field, and contrast-enhanced plain CT scan of the chest suggested the possibility of posterior mediastinal neuroblastoma. The autopsy confirmed giant posterior mediastinal neuroblastoma (poorly differentiated), which involved the C7-T6 spinal canal and the nearby erector spinae, with a small amount of tumor tissue in the liver and both adrenal glands. Mediastinal tumor is considered the underlying cause of chylothorax in this case.

[Levels of airway inflammatory mediators in peripheral blood in infants and young children with wheezing].

OBJECTIVE: To examine the levels of airway inflammatory mediators in peripheral blood in infants and young children with wheezing and to study the possible pathogenesis of wheezing from the aspects of T helper cell 1 (Th1)/T helper cell 2 (Th2) imbalance and airway inflammation. METHODS: A total of 50 children aged 1 month to 3 years with an acute wheezing episode were enrolled as the wheezing group, and 25 age-matched healthy infants were enrolled as the healthy control group. According to the number of wheezing episodes, the wheezing group was divided into a first-episode group (n=25) and a recurrent wheezing (number of episodes ≥2) group (n=25). According to the presence or absence of high-risk factors for asthma, the wheezing group was divided into a high-risk factor group (n=22) and a non-high-risk factor group (n=28). According to the results of pathogen detection, the wheezing group was divided into a positive pathogen group (n=23) and a negative pathogen group (n=27). Levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), transforming growth factor-ß1 (TGF-ß1), and total IgE (TIgE) in peripheral blood were measured for each group. For children with wheezing, eosinophil (EOS) count in peripheral blood was measured, and related samples were collected for respiratory pathogen detection. RESULTS: The wheezing group had significantly higher levels of IL-4, IL-5, IL-13, TGF-ß1, and TIgE in peripheral blood than the healthy control group (P<0.05). There were no significant differences in the levels of IL-2, IL-4, IL-5, IL-13, TGF-ß1, and TIgE in peripheral blood between the first-episode and recurrent wheezing groups, between the high-risk factor and non-high-risk factor groups, and between the positive pathogen and negative pathogen groups (P>0.05). The correlation analysis showed that in children with wheezing, EOS count was positively correlated with IL-4 level (P<0.01), IL-4 level was positively correlated with IL-5 and IL-13 levels (P<0.01), IL-5 level was positively correlated with IL-13 level (P<0.01), and IL-2 level was positively correlated with TGF-ß1 level (P<0.05). CONCLUSIONS: Th1/Th2 imbalance with a predominance of Th2 is observed in infants and young children with wheezing. IL-4, IL-5, IL-13, TGF-ß1, and IgE are involved in the pathogenesis of wheezing in these children. Airway inflammation is also observed in these children with wheezing, but it is not associated with the number of wheezing episodes, presence or absence of high-risk factors for asthma, or results of pathogen detection.

SKA1 overexpression is associated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: SKA1, an important mitosis protein, has been indicated in the initiation and progression of several malignancies. However, its clinical significance in hepatocellular carcinoma (HCC) remain to be elucidated. METHODS: mRNA expression of SKA1 was examined in 126 HCC and paired non-neoplastic tissues using real-time PCR and validated in The Cancer Genome Atlas (TCGA) database. SKA1 protein expression was detected using immunohistochemistry in the 126 HCC tissues and its associations with clinicopathological parameters and prognosis were analyzed. Hierarchical cluster analysis and gene set enrichment analysis (GSEA) were performed in selected Gene Expression Omnibus data sets. RESULTS: SKA1 mRNA expression was significantly elevated in HCC tissues from both local hospital and TCGA database. Immunohistochemistry revealed that increased SKA1 expression was present in 65 of the 126 cases and was significantly associated with higher serum alpha-fetoprotein concentration, larger tumor size and higher TNM stage. Patients with positive SKA1 expression showed significantly worse overall and relapse-free survival. Multivariate Cox regression analysis revealed that SKA1 was an independent predictor of patient prognosis. Gene expression profiling analysis of public data showed that high-SKA1 expression HCC tissues had similar gene expression profiles with fetal liver tissues. Moreover, GSEA showed that genes up-regulated in high SKA1 HCC subgroup were significantly enriched in cell cycle pathway, while genes down-regulated were significantly enriched in apoptosis pathway. CONCLUSIONS: Our findings indicate that the oncofetal gene SKA1 might be involved in the progression of the HCC and could serve as a prognostic marker for HCC.

Excessive Activation of NMDA Receptors Induced Neurodevelopmental Brain Damage and Cognitive Deficits in Rats Exposed to Intrauterine Hypoxia.

Intrauterine hypoxia is one of the most common stressors in fetuses, which can lead to abnormal brain development and permanent neurological deficits in adulthood. Neurological disorder excitotoxicity induced by hypoxia or ischemia may involve N-methyl-D-aspartate receptors (NMDARs), which are known to participate in the maturation and plasticity of developmental neurons. Inhibition of NMDARs has been reported to improve neurological outcomes in traumatic brain injuries and Alzheimer's disease. Here, we investigated if antenatal blockade of NMDARs induced by memantine could alleviate neurodevelopmental brain damage and long-term cognitive deficits in intrauterine hypoxia rats. Pregnant rats were assigned to four groups: air control, air + memantine, hypoxia, and hypoxia + memantine. The rats were exposed to hypoxic conditions (FiO2 = 0.095-0.115) for 8 h/day (hypoxia group) or given a daily memantine injection (5 mg/kg, i.p.) before hypoxia exposure from pregnant day 19 (G19) to G20 (hypoxia + memantine group).The influence of NMDARs antenatal blockade by memantine on intrauterine hypoxia-induced brain developmental damage and cognitive function was then studied. Intrauterine hypoxia resulted in decreased fetal body weight, brain weight, cognitive function, hippocampal neuron numbers, and Ki-67 proliferation index in the hippocampus. Memantine preventive treatment in pregnant rats before hypoxia exposure alleviated the aforementioned damage in vivo. Excessive activation of NMDARs contributes to fetal brain developmental damage and cognitive ability impairment induced by intrauterine hypoxia, which could be alleviated by antenatal memantine preventative treatment.

Metformin Attenuates Cognitive Impairments in Hypoxia-Ischemia Neonatal Rats via Improving Remyelination.

Perinatal hypoxia-ischemia (H/I) causes brain injury and myelination damage. Finding efficient methods to restore myelination is critical for the recovery of brain impairments. By applying an H/I rat model, we demonstrate that metformin (Met) treatment significantly ameliorates the loss of locomotor activity and cognition of H/I rat in the Morris water maze and open field task tests. After administration of Met to H/I rat, the proliferation of Olig2+ oligodendrocyte progenitor cells and the expression of myelin basic protein are obviously increased in the corpus callosum. Additionally, the myelin sheaths are more compact and the impairments are evidently attenuated. These data indicate that Met is beneficial for the amelioration of H/I-induced myelination and behavior deficits.

Loss of FOXF2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma Patients.

BACKGROUND: FOXF2 is a member of the forkhead box (FOX) family of transcription factors. FOXF2 plays an important role in several tumors but its expression and role in hepatocellular carcinoma (HCC) remains unknown. METHODS: Using immunohistochemistry, western blot, and real-time polymerase chain reaction, we analyzed FOXF2 expression in 295 clinicopathologically characterized HCC cases. Using RNA interference (RNAi), we investigated the effects of FOXF2 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine associations between FOXF2 levels, tumor features, and patient outcomes. RESULTS: FOXF2 downregulation was observed in HCC tissues (p < 0.001) compared with peritumorous tissues, and its expression levels were closely correlated with overall survival and recurrence-free survival (p = 0.023 and 0.006, respectively) in patients with HCC. RNAi-mediated silencing of the FOXF2 gene in the MHCC-97H cell line significantly promoted proliferation and anti-apoptosis. CONCLUSIONS: The results of the present study indicate that FOXF2 may serve as a prognostic biomarker for HCC and may be a promising target in the treatment of patients with HCC.

N-methyl-D-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats.

BACKGROUND: Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions. METHODS: In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8). The role of NMDAR activation in hyperoxia-induced lung fibroblast proliferation and differentiation was examined in vitro using primary cells derived from the lungs of 8-day-old Sprague-Dawley rats exposed to hyperoxic conditions. RESULTS: Hyperoxia for 3 days induced acute lung injury in newborn rats. The acute injury almost completely disappeared 4 days after cessation of hyperoxia exposure. However, pulmonary fibrosis, impaired alveolarization, and decreased pulmonary compliance were observed on postnatal days 15 and 22. MK-801 treatment during the recovery period was found to alleviate the chronic damage induced by hyperoxia. Four NMDAR 2 s were found to be upregulated in the lung fibroblasts of newborn rats exposed to hyperoxia. In addition, the proliferation and upregulation of alpha-smooth muscle actin and (pro) collagen I in lung fibroblasts were detected in hyperoxia-exposed rats. MK-801 inhibited these changes. CONCLUSIONS: NMDAR activation mediated lung fibroblast proliferation and differentiation and played a role in the development of hyperoxia-induced chronic lung damage in newborn rats.

Genetic variants in genes of tricarboxylic acid cycle key enzymes predict postsurgical overall survival of patients with hepatocellular carcinoma.

BACKGROUND: Metabolic reprogramming is a hallmark of cancer, including the alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes. However, the significance of single nucleotide polymorphisms (SNPs) in genes encoding these key enzymes has not been investigated in hepatocellular carcinoma (HCC). METHODS: In this study, 17 SNPs in seven genes encoding three TCA cycle enzyme families (SDH, FH, and IDH) were genotyped in 492 HCC patients with surgical treatment and their association with overall survival (OS) was analyzed. RESULTS: Five SNPs in four genes were identified to be associated with OS in HCC patients. Among them, rs3935401 in the 3' untranslated region of SDHC exhibited the most significant association (P < 0.001). The unfavorable genotype of these five SNPs showed a significant accumulative effect on the prognosis of HCC patients, with a P for trend of <0.001. Furthermore, the haplotype group consisting of wild type in rs4131826 and variant in rs3935401 was significantly associated with increased risk of death in HCC patients. Survival tree analysis indicated that variant genotype of rs3935401 was the primary risk factor contributing to the prediction of OS in HCC patients. CONCLUSIONS: SNPs in TCA cycle key enzyme genes may serve as potential biomarkers to predict the OS in HCC patients.

New Neuroimaging Findings in Patients with Molybdenum Cofactor Deficiency Type A: A Case Report and Literature Review.

INTRODUCTION: Molybdenum cofactor deficiency (MoCD-A) is an extremely rare autosomal recessive disease that presents with intractable seizures. The diagnosis poses challenges due to the limited number of cases reported worldwide. Magnetic resonance imaging (MRI) is a useful diagnostic tool that can detect brain injury associated with the disorder. The prognosis of MoCD-A is poor partly because most cases are initially misdiagnosed as HIE (hypoxic ischemic encephalopathy), emphasizing the need for an early and accurate diagnosis to improve quality of life and provide adequate genetic counseling to avoid new cases in the future. CASE REPORT: This report presents a case of molybdenum cofactor deficiency type A (MoCD-A) caused by MOCS1 gene mutations. A male newborn was admitted on the 10th day of birth due to uncontrolled seizures and feeding difficulties. Brain MRI showed severe cerebral damage with multiple foci that did not enhance upon contrast administration. The diagnosis was confirmed by genetic analysis and the patient received rehabilitation. His parents also received genetic counseling. To the best of our knowledge, this is the first reported MoCD-A case that had enhanced MR imaging with Gd-DTPA (0.1 mmol/kg). In addition, we reviewed the clinical and neuroimaging features of 25 newborns diagnosed with MoCD-A, as documented in the existing literature. CONCLUSION: MRI is crucial in the diagnosis of MoCD-A. A correct diagnosis can provide the family with timely genetic counseling to prevent future cases.

Prognostic value of blood inflammatory parameters for predicting mortality in neonates with sepsis.

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality in neonates. The diagnosis of neonatal sepsis has been widely explored using blood inflammatory parameters. However, few researches have focused on the predictive significance of blood inflammation parameters for predicting mortality. This study aimed to evaluate the prognostic value of blood inflammatory parameters, including white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet and C-reactive protein (CRP) for predicting mortality in neonates with sepsis. METHODS: Neonates with culture-proven sepsis were enrolled in this study. The clinical characteristics and levels of white blood cell, neutrophil, lymphocyte, monocyte, platelet and CRP were recorded. The receiver-operating characteristic (ROC) curve was applied to calculate the area under the curve (AUC) and determine the optimal cutoff values. Multivariable Cox regression model was used to evaluate the independent prognostic significance of variables. Kaplan-Meier curve was used to assess survival. RESULTS: A total of 188 neonates with culture-proven sepsis were included for analysis. The 7-day mortality rate was 11.2 % (21/188) and the 28-day mortality rate was 13.8 % (26/188). The levels of white blood cell, neutrophil, monocyte and platelet in non-survivors were lower than those in survivors (P < 0.05). Platelet yielded higher AUC values than other parameters for predicting mortality with the best cutoff value of 132 × 109/L, followed by WBC with the optimal cutoff value of 6.15 × 109/L. Multivariable Cox regression analysis showed platelet and WBC were independent prognostic factors for predicting mortality. Low platelet group showed lower survival according to Kaplan-Meier method. CONCLUSIONS: In conclusion, the levels of platelet and WBC on the day of sepsis onset are valuable indicators for predicting mortality in neonates with sepsis.

Superior effect of hypertonic saline over mannitol to attenuate cerebral edema in a rabbit bacterial meningitis model.

OBJECTIVE: Adjunctive therapies that reduce the cerebral edema in bacterial meningitis include osmotic agents. There is a lack of information comparing mannitol vs. hypertonic saline as an osmotic agent for adjunctive therapy of bacterial meningitis. We attempted to elucidate the impact of hypertonic saline in cerebral edema in the setting of bacterial meningitis as well as to explore potential mechanisms of action. DESIGN: Randomized controlled in vivo study. SETTING: University research laboratory. SUBJECTS: Rabbits. INTERVENTIONS: A rabbit model of bacterial meningitis was used comparing 3% hypertonic saline with 20% mannitol as adjunctive therapy. MEASUREMENTS AND MAIN RESULTS: Adjunctive 3% hypertonic saline treatment persistently elevated mean arterial pressure as compared with the model or ampicillin group (p < .01). Although both 20% mannitol and 3% hypertonic saline efficiently elevated serum osmolality for almost 5 hrs (p < .01), 20% mannitol lowered intracranial pressure for only a short time (<2 hrs) and did not elevate cerebral perfusion pressure. Three percent hypertonic saline treatment efficiently lowered intracranial pressure and elevated cerebral perfusion pressure for almost 5 hrs (p < .01). Furthermore, 3% hypertonic saline treatment efficiently elevated serum Na+ concentration for >5 hrs (p < .01). Three percent hypertonic saline treatment was superior to 20% mannitol in lowering leukocyte number and protein content in cerebrospinal fluid (p < .01). Three percent hypertonic saline treatment reduced water content and Evans blue incorporation in the brain (p < .01). Three percent hypertonic saline treatment inhibited aquaporin 4 expression (p < .01) and attenuated pathologic brain damage more efficiently compared with adjuvant 20% mannitol treatment (p < .01). CONCLUSIONS: Adjunctive 3% hypertonic saline treatment significantly elevated mean arterial pressure, reduced intracranial pressure, greatly improved cerebral perfusion pressure, inhibited brain aquaporin 4 expression, reduced cerebral edema, and attenuated brain damage with a superior effect over 20% mannitol in a rabbit bacterial meningitis model.

Endovascular therapy choices for different sites of delayed postoperative arterial hemorrhage after hepatobiliary pancreatic surgery: a retrospective study.

BACKGROUND: Angiography and subsequent endovascular therapy is an effective technique for delayed postoperative arterial hemorrhage (PAH) after hepatobiliary pancreatic surgery. In this research, we aimed to evaluate endovascular therapy choices for different sites of delayed PAH after hepatobiliary pancreatic surgery. METHODS: A total of 85 patients with delayed PAH who underwent endovascular therapy at the Department of Radioactive Intervention of Eastern Hepatobiliary Surgery Hospital were retrospectively enrolled. According to the hemorrhage site, participants were divided into 3 groups, all of whom then received embolization, covered stent placement, or a combination of both. Ongoing or recurrent hemorrhages, intervention times, complications associated with intervention, and mortality rate were documented. The chi-squared (χ2) test was used for statistical analysis. RESULTS: A total of 22 participants with arterial branch hemorrhage underwent superselective embolization. Overall, 81.8% (18/22) of patients underwent embolization once. The successful hemostasis rate was 77.3% (17/22), and the mortality rate was 13.6% (3/22). A total of 53 participants with arterial trunk hemorrhage underwent embolization or covered stent placement. The rate of multi-time intervention, failure to achieve hemostasis, complications associated with intervention, and mortality was lower in the stent group than in the embolization group, and there was a significant difference in complications between the 2 groups (χ2=4.93, P=0.026). Among a total of 10 patients with multisite hemorrhage who underwent embolization, covered stent placement, or a combination, the successful hemostasis rate was 20%; and the mortality rate was 70%. CONCLUSIONS: Superselective embolization is a safe treatment method for arterial branch hemorrhage, and covered stent placement may be a better choice for arterial trunk hemorrhage. Verification of these findings is required via additional large population studies.

Recurrent undifferentiated embryonal sarcoma of the liver in adult patient treated by pembrolizumab: A case report.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a neoplasm that rarely develops in adults. The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy. Here, we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1 (anti-PD-1) treatment. CASE SUMMARY: A 69-year-old woman was admitted for abdominal pain that developed for 1 wk. Computed tomography showed a 16 cm mass in the right lobe of the liver. Right hemihepatectomy and lymphadenectomy were performed, and histological diagnosis was UESL. Six months later, the patient suffered from painless obstructive jaundice, and positron emission tomography-computed tomography revealed multiple metastases. Then, percutaneous transhepatic cholangial drainage was applied to reduce jaundice, and radiofrequency ablation was used to control the lesion near the hepatic hilum. However, the patient suffered from a serious fever caused by the tumor. The patient received treatment with pembrolizumab, and the prescribed dosage was 2 mg/kg every 3 wk. After the seventh dose, positron emission tomography-computed tomography revealed that the multiple metastases had nearly disappeared. Radiologic exam was used to evaluate the disease state, and no new lesions were found. Next-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to pembrolizumab. Tumor mutation burden, microsatellite instability, and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of these biomarkers are detected in a tumor patient, the patient may be a proper candidate for PD-1 antibodies. CONCLUSION: Anti-PD-1 treatment for tumors needs further research to identify indications and proper biomarkers.

[Adenovirus-mediated vascular endothelial growth factor165 gene therapy in treatment of hypoxic-ischemic brain damage: experiment with rats].

OBJECTIVE: To investigate the therapeutical effect of adenovirus-mediated vascular endothelial growth factor (VEGF)165 gene transplantation in treatment of hypoxic-ischemic brain damage. METHODS: Recombinant vector of adenovirus-mediated VEGF165 gene (Ad-VEGF) was constructed by bacterial homologous recombination technology. Sixty 7-day-old Sprague-Dawley rats were randomly divided into 3 equal groups: hypoxic-ischemic brain damage (HIBD) group undergoing ligation of the left common carotid artery and inhalation of 8% oxygen for 2 hours, Ad-VEGF group undergoing injection of Ad-VEGF into the left sensorimotor cortex with the help of stereo-positioner 3 days after hypoxia-ischemia (HI), and sham operation group. Seven days after transplantation, 5 rats from each group were killed with their left brains taken out. The VEGF protein expression was detected by immunohistochemistry, and the neuron apoptosis was detected by terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL). Since the age of 28 days T-maze foraging test was conducted. At the age of 34 days, sensorimotor tests were performed. After the behavioral tests all the rats were killed. The number of neurons in the CA1 region of the hippocampus and cerebral cortex was detected by Nissl's staining. RESULTS: Immunohistochemistry showed that the density levels of VEGF positive cells in cerebral cortex and hippocampus of the Ad-VEGF group were (68.09 +/- 3.37) and (68.37 +/- 3.17) respectively, both significantly higher than those of the HIBD group [(24.65 +/- 3.14) and (25.14 +/- 1.86) respectively, both P < 0.05]. TUNEL showed that the number of apoptotic neurons of the Ad-VEGF group was (151.4 +/- 21.7), significantly lower than that of the HIBD group [(264.4 +/- 16.3), P < 0.05]. Behavioral tests showed the percentages of accuracy on day 4 of the Ad-VEGF and sham operation groups were both significantly higher than that of the HIBD group (both P < 0.01). Nissl's staining showed that the numbers of neurons per unit area in the hippocampal CA1 area and cortex of the Ad-VEGF group were (70.6 +/- 2.3) and (95.1 +/- 2.8) respectively, both significantly higher than those of the HI group [(55.3 +/- 2.1) and (70.1 +/- 2.7) respectively, both P < 0.05]. CONCLUSION: Adenovirus vector-mediated VEGF gene therapy increases the VEGF protein expression, decreases neuron apoptosis, improves the long-term behavioral function after brain damage, and reduces hypoxic ischemic brain injury, thus possessing neuroprotective effects.