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Background Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus causing systemic mycosis. Due to the atypical symptoms and diverse imaging findings, T. marneffei-infected patients may be misdiagnosed thus preventing timely antifungal therapy. Moreover, HIV-negative patients with T. marneffei infection may be congenitally immunocompromised because of the mutation of immune-related genes. Case presentation We describe a case of an HIV-negative child who developed disseminated T. marneffei infection in a nonendemic area. Chest CT showed similar imaging changes of miliary pulmonary tuberculosis, while there was no other evidence of tuberculosis infection, and empirical antituberculosis treatment was not effective. Lymphocyte subset analysis showed reduced natural killer cells, and the immunoglobulin profile showed low levels of IgM, C3 and C4. A bone marrow smear revealed T. marneffei infection, and ascites culture also proved T. marneffei infection. Despite antifungal treatment, the child died of multiple organ failure. Two gene mutations in caspase recruitment domain-containing protein 9 (CARD9) were detected, which had not been reported previously in T. marneffei-infected patients. Conclusions HIV-negative patients with CARD9 mutations may be potential hosts of T. marneffei. Abnormalities in the immunoglobin profile and lymphocyte subset may provide clues for immunocompromised patients, and further genetic testing is advised to identify gene mutations in HIV-negative patients with T. marneffei infection.

Background Coagulopathy in adult patients with traumatic brain injury (TBI) is strongly associated with unfavorable outcomes. However, few reports focus on pediatric TBI-associated coagulopathy. Methods We retrospectively identified children with Glasgow Coma Scale ≤ 13 in a tertiary pediatric hospital from April 2012 to December 2019 to evaluate the impact of admission coagulopathy on their prognosis. A classification and regression tree (CART) analysis using coagulation parameters was performed to stratify the death risk among patients. The importance of these parameters was examined by multivariate logistic regression analysis. Results A total of 281 children with moderate to severe TBI were enrolled. A receiver operating characteristic curve showed that activated partial thromboplastin time (APTT) and fibrinogen were effective predictors of in-hospital mortality. According to the CART analysis, APTT of 39.2 s was identified as the best discriminator, while 120 mg/dL fibrinogen was the second split in the subgroup of APTT ≤ 39.2 s. Patients were stratified into three groups, in which mortality was as follows: 4.5 % (APTT ≤ 39.2 s, fibrinogen > 120 mg/dL), 20.5 % (APTT ≤ 39.2 s and fibrinogen ≤ 120 mg/dL) and 60.8 % (APTT > 39.2 s). Furthermore, length-of-stay in the ICU and duration of mechanical ventilation were significantly prolonged in patients with deteriorated APTT or fibrinogen values. Multiple logistic regression analysis showed that APTT > 39.2 s and fibrinogen ≤ 120 mg/dL was independently associated with mortality in children with moderate to severe TBI. Conclusions We concluded that admission APTT > 39.2 s and fibrinogen ≤ 120 mg/dL were independently associated with mortality in children with moderate to severe TBI. Early identification and intervention of abnormal APTT and fibrinogen in pediatric TBI patients may be beneficial to their prognosis.

Abnormal blood coagulation often occurs in critically ill patients, which seriously affects their prognosis. This retrospective study investigated the implications of changes in blood coagulation in patients with coronavirus disease 2019 (COVID-19). Records were reviewed for patients admitted with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital death. A total of 85 patients were included, of whom 12 died in the hospital. The admission prothrombin time (PT), international normalized ratio (INR), and levels of D-dimer and fibrin/fibrinogen degradation products (FDP) were significantly higher in non-survivors than in survivors, while the reverse was true for prothrombin time activity (PT-act) and PaO2/FiO2. Multivariate logistic regression showed that PT-act < 75% was independently associated with mortality. The area under the receiver operating characteristic curves for PT-act, D-dimer, and FDP at admission could significantly predict mortality. The AUCs for PT-act were larger than those for D-dimer and FDP; however, there was no significant difference. After 2 weeks of treatment, the coagulation parameters of the surviving patients improved. COVID-19 is often accompanied by abnormal coagulation. PT-act at admission is able to predict mortality in patients with COVID-19 as can D-dimer and FDP levels. PT-act < 75% is independently associated with mortality.

IntroductionThis retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with 2019-coronavirus infected disease (COVID-19).MethodsRecords were reviewed of 85 patients with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital mortality at 28 days.ResultsFourteen patients died. The baseline leukocyte count, neutrophil count and hemoglobin was significantly higher in non-survivors compared with survivors, while the reverse was true of lymphocyte count, platelet, PaO2/FiO2, CD3+ count and CD4+ count. The percentage of neutrophil count > 6.3×109/L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count was independently associated with mortality. However, there were not significant difference in IgG, IgM, IgA, C3, C4 and the percentage of IgE > 100 IU/ml between the death group and survival group. Areas under the receiver operating characteristic curves of the following at baseline could significantly predict mortality: leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts.ConclusionsFor patients with COVID-19, lymphocyte, CD3+ and CD4+ counts that marked decrease suggest a poor outcome. A high neutrophil count is independently associated with mortality. At admission, leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts should receive added attention.

BackgroundLactate is used to evaluate the prognosis of adult patients with trauma. However, the prognostic significance of admission serum lactate in the setting of pediatric traumatic brain injury (TBI) is still unclear. We aim to investigate the impact of admission lactate on the outcome in children with moderate to severe TBI.MethodsThis retrospective study was conducted in a tertiary pediatric hospital between May 2012 and Jun 2018 included children with an admission Glasgow Coma Scale (GCS) of ≤13. Two hundred and thirteen patients were included in the analysis and 45 patients died in hospital.ResultsAdmission lactate and glucose were significantly higher in non-survivors than those in survivors (P < 0.05). Admission lactate was positively correlated with admission glucose and negatively correlated with GCS in all patients (n = 213), subgroup of isolated TBI (n = 112) and subgroup of GCS ≤ 8 (n = 133), respectively. AUCs of lactate could significantly predict the mortality and were higher than those of glucose in all patients, subgroup of isolated TBI and subgroup of GCS ≤ 8, respectively. Multivariate logistic regression showed that admission lactate (Adjusted OR = 1.189; 95% CI: 1.002-1.410; P = 0.047) was independently associated with mortality, while admission glucose (Adjusted OR = 1.077; 95% CI: 0.978-1.186; P = 0.133) wasn't an independent risk factor of death. Elevated admission lactate (> 2 mmol/L) was associated with death, reduced 14-day ventilation-free days, 14-day ICU-free days and 28-day hospital-free days.ConclusionsAdmission serum lactate can effectively predict the mortality of children with moderate to severe TBI. Elevated admission lactate is associated with death, reduced ventilator-free, ICU-free, and hospital-free days. Admission serum lactate could be used as a prognostic biomarker of mortality in children with moderate to severe TBI.

The production of reactive oxygen species (ROS) during hyperoxia contribute to alveolar epithelial apoptosis. In the present study, the molecular mechanisms of oxidative stress-induced alveolar epithelial cell apoptosis were investigated. The cytoprotective effects of N-acetylcysteine (NAC) were evaluated. Treatments using 500 muM H(2)O(2) can induce primary alveolar type II epithelial cell apoptosis. During this procedure, c-Jun N-terminal kinase (JNK) was activated. SP600125, a specific inhibitor of JNK, can partially block H(2)O(2)-induced alveolar type II epithelial cells (ATII cells). SP600125 also attenuated Bax protein content and p53 nuclear accumulation induced by H(2)O(2). NAC (5 mM) pretreatment decreased H(2)O(2)-induced ATII cell apoptosis. The high level of intracellular reactive oxygen species (ROS) induced by H(2)O(2) was also attenuated by NAC pretreatment. Taken together, H(2)O(2) can induce primary ATII cells apoptosis and increase JNK phosphorylation. NAC, a precursor of glutathione (GSH) synthesis, can protect ATII cells from H(2)O(2)-induced apoptosis through scavenging ROS.

To investigate the distribution and drug sensitivity of pathogens and risk factors for ventilator-associated pneumonia (VAP) in children with congenial heart disease (CAD) after surgery.According to the occurrence of VAP, 312 children with CAD who received mechanical ventilation after surgery for 48 hours or longer between January 2012 and December 2014 were classified into VAP (n=53) and non-VAP groups (n=259). Sputum samples were collected and cultured for pathogens in children with VAP. The drug sensitivity of pathogens was analyzed. The risk factors for postoperative VAP were identified by multiple logistic regression analysis.The sputum cultures were positive in 51 out of 53 children with VAP, and a total of 63 positive strains were cultured, including 49 strains of Gram-negative bacteria (78%), 9 strains of Gram-positive bacteria (14%) and 5 strains of funqi (8%). The drug sensitivity test showed that Gram-negative bacteria were resistant to amoxicillin, piperacillin, cefotaxime and ceftazidime, with a resistance rate of above 74%, and demonstrated a sensitivity to amikacin, polymyxin and meropenem (resistance rate of 19%-32%). Single factor analysis showed albumin levels, preoperative use of antibiotics, duration of mechanical ventilation, times of tracheal intubation, duration of anesthesia agent use, duration of acrdiopulmonary bypass, duration of aortic occlusion and use of histamin2-receptor blockade were significantly different between the VAP and non-VAP groups (P0.05). The multiple logistic regression showed albumin levels (35 g/L), duration of mechanical ventilation (≥ 7 d), times of tracheal intubation (≥ 3), duration of acrdiopulmonary bypass (≥ 100 minutes) and duation of aortic occlusion (≥ 60 minutes) were independent risk factors for VAP in children with CAD after surgery.Gram-nagative bacteria are main pathogens for VAP in children with CAD after surgery. The antibiotics should be used based on the distribution of pathogens and drug sensitivity test results of pathogens. The effective measures for prevention of VAP should be taken according to the related risk factors for VAP to reduce the morbidity of VAP in children with CAD after surgery.

To explore the expression of α-smooth muscle actin (α-SMA) during the lung injury induced by hyperoxia in infantile rats.Sixty-four male Sprague-Dawley (SD) rats about 3 weeks were randomly assigned into normal control group which exposured to room air [fraction of inspired oxygen (FiO(2)) was 0.21] and hyperoxia exposure group (95%O(2)) according to random digits table. Eight rats in each group were randomly sacrificed at day 1, 7, 14 and 21.Pulmonary tissue remodeling was observed by hematoxylin-eosin (HE) staining. Immunohistochemistry method was performed to evaluate the expression of α-SMA in pulmonary tissue, further Western blotting was also made to determine the expression of α-SMA.The early histopathologic changes after HE were inflammation and edema in pulmonary tissue, while the later changes were interstitial hyperplasia and fibroblast proliferation. The expression of α-SMA was very slight in bronchial epithelium, alveolar epithelium and alveolar interstitium in normal control group, but increased with the time of hyperoxia exposure prolonged and peaked at 21st day. Western blotting detected that the expression of α-SMA after hyperoxia exposure for 1 day and 7 days in hyperoxia exposure group presented no difference compared with normal control group (1.02±0.12 vs. 1.00±0.13, 1.05±0.14 vs. 0.99±0.12, both P0.05), but the expression of α-SMA after hyperoxia exposure for 14 days and 21 days was increased compared with normal control group (1.27±0.21 vs. 1.05±0.15, 2.26±0.28 vs. 1.05±0.14, P0.05 and P0.01).Pulmonary fibrosis remodeling was caused by hyperoxia exposure. The expression of α-SMA in pulmonary tissue in hyperoxia exposure groups obviously increased, and could play an important role in pulmonary fibrosis remodeling.

Some research has shown that p38 mitogen-activated protein kinase (p38MAPK) plays important roles in lung injuries induced by various factors. Its expression and role in hyperoxia-induced lung injury remains unknown. This study investigated the expression and role of p38MAPK in hyperoxia-induced lung injury juvenile rat model.Hyperoxia-induced lung injury rat model was prepared by 90% O(2) exposure. The location and expression of p38MAPK in lung tissues were detected by immunohistochemistry and Western blot respectively. Apoptosis index of lung was evaluated by TUNEL technique. The effect of SB203580, a p38MAPK inhibitor, on the apoptosis index of lung was observed.The expression of phosphor-p38MAPK increased obviously after hyperoxia. Positive phosphor-p38MAPK cells were mainly distributed in the alveolar, airway epithelial cells, pulmonary vascular endothelium cells and infiltrative inflammatory cells. The apoptosis index of lung also significantly elevated. SB203580 inhibited the activation of p38MAPK, and reduced the apoptosis index of lung.The phosphor-p38MAPK increased and was expressed in many kinds of lung cells in lung injury rat model. It may play a role in the induction of apoptosis in hyperoxia-induced lung injury.

To study in vitro the influence of 60% oxygen and the protective effect of calcitonin gene-related peptide (CGRP) on type II alveolar epithelial cells (AEC II) isolated from the lung of premature rat.AEC II were isolated from the lung of 19-day rat fetus, and they were then cultured in six-well plates. The cells were randomly divided into four groups: air group, hyperoxia group, hyperoxia plus CGRP group, hyperoxia plus CGRP and CGRP8-37 (CGRP receptor antagonist) group. Cells of air group and hyperoxia group were exposed to 21% air or 60% oxygen, respectively, while in hyperoxia plus CGRP group CGRP was added, and in hyperoxia plus CGRP and CGRP8-37 group CGRP and CGRP8-37 were added before exposure to 60% oxygen. Cells in four groups were cultured for 24 hours, and then ground into homogenates for detection of malondialdehyde (MDA), total antioxidant capacity (TAOC) and superoxide dismutase (SOD) with ultraviolet spectrophotometer. Reactive oxygen species (ROS) and apoptosis rate of AEC II were analyzed by flow cytometry and the mRNA level of surfactant associated protein C (SPC) was measured by reverse transcription-polymerase chain reaction (RT-PCR).The levels of ROS, MDA and apoptosis rate were increased whereas TAOC, SOD and SPC mRNA expression declined in hyperoxia group compared with those in air group (all P0.01). In contrast, MDA, ROS and apoptosis rate were significantly lower and levels of TAOC, SOD and SPC mRNA expression were significantly higher in hyperoxia plus CGRP group than those in hyperoxia group (all P0.01). The differences in 6 parameters above between hyperoxia group and hyperoxia plus CGRP and CGRP8-37 group were not statistically significant.Exposure of AEC II from immature rat to 60% oxygen for 24 hours may produce oxidative injury, inducing apoptosis and decrease in SPC mRNA level of AEC II of premature rat in vitro, while CGRP may play a protective role against hyperoxic lung injury by its antioxidant property, and also inhibition of AEC II apoptosis and promotion of the SPC mRNA expression.

To investigate the effects of oxidative stress on the survival and apoptosis of alveolar epithelial type II (ATII) cells, as well as the mechanisms of apoptosis.500 mumol/L H(2)O(2) was added into primary ATII cells at different times and cell viability, apoptotic ratio and the expression of Bax and p53 were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry (FCM) and Western blotting analysis, respectively. The change in mitochondrial membrane potential (MMP) was detected by fluorescence microscopy and FCM.The cell viability and MMP were decreased by H(2)O(2) compared with the controls (F(1)=85.211, F(2)=72.453, respectively, both P0.05). The cell apoptotic ratios were increased with the time of the stimulation prolonged compared with the controls (F=54.002, P0.05). H(2)O(2) increased Bax and p53 protein levels (F(1)=28.118, F(2)=43.456, both P0.05).High level of oxidative stress can inhibit ATII cells proliferation, and induce cells apoptosis and decrease the MMP. Up-regulation of the expression of Bax and p53 may contribute to its apoptosis effects.