Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

Hepatocellular carcinoma(HCC)is one of the most common malignancies with high morbidity and mortality rates worldwide.With the advances in molecular biology and tumor immunology,molecular-targeted agents represented by tyrosine kinase inhibitors(such as sorafenib and lenvatinib)and immunotherapy represented by PD-1/PD-L1 monoclonal antibodies have brought hope for patients with advanced HCC.The combination of immunotherapy and anti-angiogenic therapy can further improve the treatment outcome of patients.In addition,the optimization and integration of stereotactic body radiotherapy,local treatment,and systemic treatment may maximize the benefits of patients.In the future,through a deep understanding of the heterogeneity of HCC,the development of precision molecular subtyping and individualized treatment,and the establishment of a multidisciplinary collaborative diagnosis and treatment system,systemic therapy is expected to achieve long-term management of advanced HCC.This article reviews the current status and advances in systemic therapy for advanced HCC.

Objective:To measure the magnetic field correction factor of reference ionization chamber in a 1.5 T magnetic field and to explore the response of the ionization chamber among different angles between magnetic field and ionization chamber axis.Methods:A home-made magnetic compatible one-dimensional water tank was used to measure the response of PTW30013 and IBA FC65-G in 7 MV photon beam of Elekta Unity with and without magnetic field. The ionizing current was collected by PTW UNIDOS Tango electrometer. The effective measurement point of ionization chamber was positioned to the isocenter of MR-linac using electronic portal image device. The influence on water absorbed dose of reference point was obtained by Monte Carlo calculations.Results:The response of ionization chambers in strong magnetic field was related to the angle between chamber axis and magnetic field. The response of ionization chamber was significantly affected in perpendicular magnetic field with a deviation up to 4.54% compared to parallel magnetic field. The deviation between the magnetic field correction factors measured for parallel or reverse-parallel was 0.03%-0.24%. The magnetic field correction factors for PTW30013 and FC65-G measured in parallel magnetic field were 0.9934±0.0077 and 0.9990±0.0076, respectively.Conclusions:This study experimentally verifies that positioning the ionization chamber axis parallel to the magnetic field direction in MR-linac reference dosimetry can minimize the magnetic field impact. The determined magnetic field correction factor and uncertainty in 1.5 T magnetic field can provide necessary data for establishing an MR-linac reference dosimetry protocol.

Objective:To investigate the prognostic value of the ratio of veno-arterial carbon dioxide partial pressure difference to arterio-venous oxygen content difference (Pv-aCO 2/Ca-vO 2) in children with primary peritonitis-related septic shock. Methods:A retrospective study was conducted. Sixty-three children with primary peritonitis-related septic shock admitted to department of intensive care unit of the Children's Hospital Affiliated to Xi'an Jiaotong University from December 2016 to December 2021 were enrolled. The 28-day all-cause mortality was the primary endpoint event. The children were divided into survival group and death group according to the prognosis. The baseline data, blood gas analysis, blood routine, coagulation, inflammatory status, critical score and other related clinical data of the two groups were statistics. The factors affecting the prognosis were analyzed by binary Logistic regression, and the predictability of risk factors were tested by the receiver operator characteristic curve (ROC curve). The risk factors were stratified according to the cut-off, Kaplan-Meier survival curve analysis compared the prognostic differences between the groups.Results:A total of 63 children were enrolled, including 30 males and 33 females, the average age (5.6±4.0) years old, 16 cases died in 28 days, with mortality was 25.4%. There were no significant differences in gender, age, body weight and pathogen distribution between the two groups. The proportion of mechanical ventilation, surgical intervention, vasoactive drug application, and procalcitonin, C-reactive protein, activated partial thromboplastin time, serum lactate (Lac), Pv-aCO 2/Ca-vO 2, pediatric sequential organ failure assessment, pediatric risk of mortality Ⅲ in the death group were higher than those in the survival group. Platelet count, fibrinogen, mean arterial pressure were lower than those in the survival group, and the differences were statistically significant. Binary Logistic regression analysis showed that Lac and Pv-aCO 2/Ca-vO 2 were independent risk factors affecting the prognosis of children [odds ratio ( OR) and 95% confidence interval (95% CI) were 2.01 (1.15-3.21), 2.37 (1.41-3.22), respectively, both P < 0.01]. ROC curve analysis showed that the area under curve (AUC) of Lac, Pv-aCO 2/Ca-vO 2 and their combination were 0.745, 0.876 and 0.923, the sensitivity were 75%, 85% and 88%, and the specificity were 71%, 87% and 91%, respectively. Risk factors were stratified according to cut-off, and Kaplan-Meier survival curve analysis showed that the 28-day cumulative probability of survival of Lac ≥ 4 mmol/L group was lower than that in Lac < 4 mmol/L group [64.29% (18/28) vs. 82.86% (29/35), P < 0.05]. Pv-aCO 2/Ca-vO 2 ≥ 1.6 group 28-day cumulative probability of survival was less than Pv-aCO 2/Ca-vO 2 < 1.6 group [62.07% (18/29) vs. 85.29% (29/34), P < 0.01]. After a hierarchical combination of the two sets of indicator variables, the 28-day cumulative probability of survival of Pv-aCO 2/Ca-vO 2 ≥ 1.6 and Lac ≥ 4 mmol/L group significantly lower than that of the other three groups (Log-rank test, χ2 = 7.910, P = 0.017). Conclusion:Pv-aCO 2/Ca-vO 2 combined with Lac has a good predictive value for the prognosis of children with peritonitis-related septic shock.

OBJECTIVE: To explore the genetic basis for a child featuring global developmental disorder with epilepsy. METHODS: A child who had presented at Guangzhou Women and Children's Medical Center in July 2022 was selected as the study subject. Clinical data was collected. Potential variant was detected by whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a three-year-old ethnic Zhuang Chinese girl, had presented with global developmental disorder and epilepsy, for which rehabilitation therapy was ineffective. Genetic testing revealed that she has harbored a homozygous c.821T>C (p.Leu274Pro) missense variant of the PIGW gene, for which both of her parents and sister were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of uncertain significance. CONCLUSION The homozygous c.821T>C (p.Leu274Pro) variant of the PIGW gene probably underlay the onset of disease in this child. Above finding has enriched the mutational spectrum of the PIGW gene.
Child, Preschool ; Female ; Humans ; Computational Biology ; Developmental Disabilities ; Epilepsy/genetics* ; Genetic Testing ; Homozygote

OBJECTIVE: To explore the genetic basis for a child with optic atrophy and global developmental delay. METHODS: A child who had presented at the Guangzhou Women and Children's Medical Center in January 2022 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a nine-month-old female, had manifested dysopia and global developmental delay. Genetic testing revealed that she has harbored a de novo c.425G>C (p.Arg142Pro) variant of the NR2F1 gene, which has been associated with Bosch-Boonstra-Schaaf syndrome. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PM1+PM2_Supporting+PM5+PP3+PP4). CONCLUSION The c.425G>C (p.Arg142Pro) variant of the NR2F1 gene probably underlay the pathogenesis in this child. Above finding has enriched the genotypic and phenotypic spectrum of the NR2F1 gene.
Female ; Humans ; Infant ; Computational Biology ; COUP Transcription Factor I/genetics* ; Genetic Testing ; Genomics ; Genotype ; Optic Atrophy/genetics*

Objective:A clinical prediction model was constructed based on the related factors affecting neonatal early-onset sepsis (EOS).Methods:A retrospective study was conducted. The patients with EOS amditted to the neonatal intensive care unit of Children′s Hospital Affiliated to Xi′an Jiaotong University from April 2015 to April 2020 were enrolled. The demographic data and the clinical indicators within 8 hours after admission were collected. The death 7 days after admission was taken as the end event. The differences of various indexes between the survival group and the death group were compared. After univariate analysis of the indexes that may have an impact on the prognosis, binary logistic regression analysis was performed; The predictive model was established for the factors that may affect the prognosis; the predictive value of the relevant models was analyzed by recevier operating characteristic (ROC) curve, and the model was verified by independent clinical medical records.Results:A total of 139 children were enrolled, and 41 died within 7 days, with a fatality rate of 29.50%. Compared with the survival group, the dead group had higher white blood cells (WBC), serum procalcitonin (PCT), lactic acid (Lac), creatinine (Scr), D-dimer and Paediatric Risk of Mortality (PRISM) score {WBC(×10 9/L): 24.15[4.36, 29.36] vs 21.21[19.14, 28.36], PCT: (67.32±40.36)ng/L vs (37.76±25.11)ng/L, Lac: (8.69±6.17)mmol/L vs (2.34±1.11)mmol/L, Scr: (239.99±68.46)μmol/L vs (65.31±34.34)μmol/L, D-dimer(mg/L): 5.21[2.06, 21.49] vs 0.34[0.26, 0.45], PRISM Ⅲ: (19.52±6.25)s vs (10.63±2.05)s, all P<0.05}, and lower fibrinogen (Fib), platelet count (PLT) and hemoglobin concentration (Hb) [Fib: (1.48±1.19)g/L vs (2.44±0.83)g/L, PLT: (154±58)×10 9/L vs (189±29)×10 9/L, Hb: (169±49)g/L vs (182±52)g/L, all P<0.05]. The incidence of placental/umbilical cord lesions, amniotic fluid pollution, asphyxia, premature delivery, premature rupture of membranes, positive etiology and maternal infection in the death group were higher than those in the survival group, while the gestational age and weight were lower than those in the survival group (all P<0.05); Binary logistic regression analysis showed that Lac, PCT and premature rupture of membranes were independent risk factors for the prognosis of EOS [odds ratio ( OR) and 95% confidence interval (95% CI): Lac was 1.23(1.00-2.05), PCT was 1.05(1.03-1.85), premature rupture of membranes was 2.59(1.89-3.32), all P<0.05]; ROC curve analysis showed that the area under the curve (AUC) of the prediction model was 0.967; the predicted sensitivity was 88.70%; and the specificity was 78.20% respectively. Conclusions:PCT, Lac and premature rupture of membranes are independent risk factors affecting the prognosis of EOS. The clinical prognosis prediction model constructed by combining PLT, gestational age and weight has good prediction efficiency.

ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg^-1）， a DIO + high-dose tripterine group （1.0 mg·kg^-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg^-1）， and a COM + high-dose tripterine group （1.0 mg·kg^-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg^-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg^-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.

Objective:To investigate the lymphocyte subsets and clinical characteristics of children with abnormal reaction to Bacillus Calmette-Guérin(BCG)vaccination.Methods:A total of 35 children with BCG disease diagnosed in the Children′s Hospital Affiliated to Xi′an Jiaotong University from January 2013 to December 2019 were enrolled retrospectively.Patients with strong local reaction and lymphadenitis after vaccine injection were selected as the localized group, and with lymphadenitis complicated with distant organ involvement were classified as the disseminated group.The differences in clinical infection indicators, demographic data, lymphocyte subsets and prognosis between the two groups were compared.Results:There are 25 cases in the localized group and 10 cases in the disseminated group, male 20 cases and female 15 cases.Compared with the localized group, the incidence of cough, fever and growth retardation all increased in the disseminated group, with statistical significance(all P<0.05). Lymphocyte ratio[(61.14±18.61)% vs.(39.64±31.45)%], T lymphocytes [CD3 + (×10 6/L): (1 821±487)vs.(1 065±539)], helper/inducible T lymphocytes[CD3 + CD4 + (×10 6/L): (1 058±357)vs.(445±140)], double positive T lymphocytes[CD3 + CD4 + CD8 + (×10 6/L): (24.07±7.17)vs.(14.10±8.89)], CD4 + /CD8 + ratio[CD4 + /CD8 + (%): (1.65±0.73)vs.(1.00±0.25)], natural killer cells[CD16 + CD56 + (×10 6/L): (19.70±2.34)vs.(12.76±7.01)]were lower in the disseminated group than those in the localized group and the differences were significant(all P<0.05). In the disseminated group, 6 cases were diagnosed with immunodeficiency disease and 7 cases died during the follow-up period.All the children in the localized group were cured. Conclusion:Most BCG reaction have a good prognosis, while disseminated children combined with primary immune deficiency have worst prognosis.Early lymphocyte subsets analysis is effective for BCG disease screening.