Objective:To explore the value of REG3α,sST2 and TNFR1 in peripheral blood for risk stratification and prognostic evaluation of acute graft-versus-host disease(aGVHD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:From January 2020 to March 2022,70 children with aGVHD after allo-HSCT in the First Affiliated Hospital of Zhengzhou University were selected as the research objects,of which 50 cases were mild aGVHD(grade Ⅰ-Ⅱ)and 20 cases were severe aGVHD(grade Ⅲ-Ⅳ).30 healthy children who underwent physical examinations in our hospital during the same period were selected as the control group.Luminex platform was used to detect the protein expression levels of REG3α,sST2 and TNFR1 during aGVHD occurrence,and the differences between the three groups were analyzed by one-way ANOVA.According to the outcome of aGVHD treatment within 28 days,the patients were divided into a good prognosis group of 58 cases and a poor prognosis group of 12 cases.The ROC curve was used to analyze the value of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD.Results:The peripheral blood levels of REG3α,sST2 and TNFR1 in the mild aGVHD and severe aGVHD groups were significantly higher than those in the control group(P＜0.05),and those in the severe aGVHD group were significantly higher than those in the mild aGVHD group(P＜0.05).Compared with the good prognosis group,the peripheral blood levels of REG3α,sST2 and TNFR1 in the poor prognosis group were significantly higher(t=9.27,3.33,2.97;P＜0.01).ROC curve analysis showed that the area under the curve(AUC),sensitivity and specificity of the combined detection of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD were higher than those of the above indicators detected alone or in pairs.Conclusion:The expression levels of REG3α,sST2 and TNFR1 were related to the severity of aGVHD.The combination of REG3α,sST2 and TNFR1 has a high clinical value in predicting the prognosis of children with aGVHD,which is expected to provide a reliable reference for clinical evaluation of the prognosis of children with aGVHD.

Objective:To analyze the radiographic parameters of shoulder balance that affect the postoperative satisfaction of Lenke type 1 adolescent idiopathic scoliosis (AIS).Methods:A total of 98 patients with AIS who underwent posterior pedicle screw fusion in Xijing Hospital of Air Force Medical University from August 2017 to July 2020 were retrospectively analyzed. There were 26 males and 72 females, aged 15.2±5.3 years (range, 10-24 years). Distribution of upper instrumented vertebrae: T 2 58 cases (59%), T 3 25 cases (26%), T 4 15 cases (15%); Distribution of lower instrumented vertebrae: T 12 63 cases (64%), L 1 28 cases (29%), L 2 4 cases (4%), L 3 3 cases (3%). Clavicle angle (CA), radiographic shoulder height (RSH), and coracoid height difference (CHD), clavicle-rib cage intersection difference (CRID), T 1 tilt angle, first rib tilt angle, clavicle chest angle difference(CCAD) and Scoliosis Research Society-22 (SRS-22) scale were compared before and after operation. Binary logistic regression was used to analyze the radiographic indicators of shoulder balance that affected the postoperative satisfaction of Lenke type 1 AIS. The receiver operating characteristic (ROC) curve was drawn to determine the threshold value of the imaging index. Results:All operations were successfully completed. The operation time was 260±80 min (range, 220-320 min), and the intraoperative blood loss was 360±110 ml (range, 300-700 ml). There was no nerve, dural or vascular injury during operation. RSH, CHD, CRID, T 1 tilt angle, first rib tilt angle, and CCAD at the final follow-up were 4.0 (0, 13.9) mm, 7.0 (0, 12.9) mm, 4.0 (0, 10.0) mm, 4.8° (3.3°, 8.2°), 5.3°±3.9°, and 5.5° (3.0°, 8.9°), respectively, which were less than the preoperative 10.6 (2.0, 20.3) mm, 10.3 (2.5, 15.9) mm, 8.0 (1.0, 15.2) mm, 7.6° (3.5°, 12.2°), 7.5°±6.9°, 8.5° (3.6°, 18.3°), and the difference was statistically significant ( P<0.05). The SRS-22 function, pain, appearance, and psychological scores at the final follow-up were 4.6 (4.0, 4.9), 4.1±0.5, 4.1±0.7, and 4.2 (3.9, 4.8) points, respectively, which were greater than the preoperative scores of 4.2 (3.8, 4.6), 4.0±0.7, 3.5±0.7, and 4.0 (3.5, 4.4) points, the difference was statistically significant ( P<0.05). Binary logistic regression showed that CCAD was an independent radiographic indicator of shoulder balance that affected the satisfaction of AIS patients after orthopaedic surgery ( OR=0.826, P=0.040). ROC curve showed that the area under the curve and 95% CI was 0.726 (0.572, 0.865), and the threshold was 6.6°. Conclusion:CCAD is an independent radiographic parameter of shoulder balance that affects the postoperative satisfaction of AIS. Patients are more likely to achieve a satisfactory outcome when their postoperative CCAD is ≤6.6°, which can be used clinically as a radiographic parameter to assess the efficacy of orthopaedic spine surgery.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Aim To explore the effect of γ-ray on the mRNA,protein expression levels and metabolic activity level of the key drug metabolic enzyme CYP3A1 in rat liver. Methods Wistar rats were randomly divided into control group, 24 h post-radiation group and 72 h post-radiation group. The experimental group was exposed to total body irradiation of single 6 Gy γ-ray. Blood was collected from the orbital venous plexus for blood routine examination and biochemical analysis 24 h and 72 h after irradiation, and liver tissue was prepared for quantifying expression of CYP3A1 mRNA and liver-specific microRNA (miR-122-5p) through RT-PCR. The expression level of CYP3A1 protein was analyzed by Western blot, and the metabolic activity level of CYP3A1 detected by the specific substrate midazolam combined with LC-MS method. Results Com¬pared with the control group, the weights of the rats in the radiation group significantly decreased, and the number of white blood cells was markedly reduced. Simultaneously, the activities of alanine aminotrans-ferase and alkaline phosphatase continuously descended, as well as the levels of total bilirubin and bile acid significantly increased, which indicated that the liver may be damaged after radiation. The relative expression of CYP3A1 mRNA continued to increase significantly 24 h and 72 h after irradiation. CYP3A1 protein expression and metabolic activity levels showed an obvious increasing trend 24 h after irradiation, and rose significantly 72 h after irradiation compared with the control group. At the same time, the expression of miR-122-5p in liver of rats in the 24 h and 72 h post-radiation group continued to decrease rapidly compared with the control group. Conclusions γ-ray radiation may arouse damage effect on liver, which leads to the continuous up-regulation of the mRNA and protein expression levels of the capital metabolic enzyme CYP3A1 in liver tissue, as well as the elevation of the metabolic activity level. The regulatory mechanism might be related to miR-122-5p.

ObjectiveTo observe the lower limb muscle activation strategy of healthy middle-aged and old women during stair ascent and descent with surface electromyography. MethodsFrom August, 2021 to February, 2022, 20 healthy middle-aged and old women were measured the surface electromyography root mean square (RMS) and integrated electromyography (iEMG) of bilateral vastus lateral, rectus femoris, vastus medialis, biceps femoris and semitendinosus during stair ascent and descent, and co-contraction ratio was calculated. ResultsDuring stair ascent, the RMS of bilateral vastus lateral, rectus femoris and vastus medialis was higher at starting stage than at following stage (|t| > 6.650, P < 0.001), while the RMS of biceps femoris and semitendinosus was lower (t > 3.559, P < 0.01); and the co-contraction ratio of hamstrings/quadriceps was lower at starting stage than at following stage (t > 8.185, P < 0.001). During stair descent, the RMS of bilateral vastus lateral, vastus medialis, biceps femoris and semitendinosus was higher at following stage than at starting stage (t > 2.345, P < 0.05), as well as the co-contraction ratio of hamstrings/quadriceps (t > 2.405, P < 0.05). ConclusionThe activities of the muscles around the knees are almost symmetrical during stair ascent and descent for healthy middle-aged and old women. The activation and co-contraction ratio of quadriceps and hamstring are various at starting/following stages.

Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Herpesvirus 4, Human/genetics* ; Mutation ; Epstein-Barr Virus Infections/pathology* ; Hepatitis A Virus Cellular Receptor 2/genetics*

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Objective: To assess the level and trend of varicella-zoster virus (VZV) antibody among healthy population in Beijing in 2017, after the five-year implementation of the two doses varicella vaccination strategy in 2012, and to provide evidence for scientific evaluation of immunization strategy. Methods: A total of 2 144 subjects in ten age groups from 8 districts of Beijing city were recruited in this study using cross-sectional survey based on multi-stage cluster random sampling method. Serum samples were collected and VZV antibody was detected by ELISA. The influencing factors of antibody concentration and positive rate were analyzed and compared with the study in 2012. The antibody concentration and antibody positive rate were analyzed by nonparametric test and χ² test respectively. Results: The ratio of subjects with registered residence in Beijing city to other provinces was 1∶1. The ratio of male to female was 1∶1.08. The median concentration of VZV antibody was 341.4 (78.6, 1 497.8) mIU/ml, and the total antibody positive rate was 71.1% (1 524/2 144). There were significant differences in antibody positive rate (χ²=736.39, P<0.01) and antibody concentration (χ²=740.34, P<0.01) among different age groups. The antibody positive rate generally increased with age (χ²_trend=7.32, P_trend<0.01). Among 862 children under 14 years old, the antibody positive rate of two doses vaccination 72.8% (182/250) was significantly higher than that of one dose vaccination 51.9% (154/297) (χ²=25.14, P<0.01). There was significant difference between 1-4 years old group (χ²=11.71, P<0.01) and 10-14 years old group (χ²=5.95, P=0.02), but not in 5-9 years old group (χ²=3.00, P=0.07). Compared with the study in 2012, the antibody positive rate increased in 5-9 years old group (χ²=14.35, P<0.01) and decreased in 1-4 years old group (χ²=11.51, P=0.01) in 2017. Conclusion: The recommended varicella booster vaccination has significantly improved the VZV antibody level of children in Beijing city. In the future, it is necessary to explore a more optimized two doses varicella vaccination schedule for children in combination with epidemiological evidence.
Adolescent ; Antibodies, Viral ; Chickenpox/prevention & control* ; Chickenpox Vaccine ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Herpesvirus 3, Human ; Humans ; Infant ; Male ; Vaccination

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.
Computational Biology/methods* ; Gene Expression Profiling/methods* ; Gene Regulatory Networks ; Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Protein Interaction Maps/genetics*