Investigation of serum IL-12, IL-16, and IL-17A as diagnostic biomarkers in children with cow’s milk protein allergy

Background Cow’s milk protein allergy (CMPA) is an abnormal immune response caused by milk proteins and is most common in infancy and early childhood. Statistics revealed up to 7.5% of children suffered from milk allergy. Its clinical symptoms were characterized by diversity, non-specificity, and can affect multiple systems, including the digestive tract, skin, and respiratory tract. In this study, we aimed to investigate the effects of IL-12, IL-16, and IL-17A on diagnosing and monitoring CMPA in children for clinical treatment.Methods A total of 158 infants with CMPA and 89 healthy babies were recruited and evaluated. Demographic and clinical information of all participants were recorded. An extensive analysis of inflammatory cytokine levels, including IL-12, IL-16, and IL-17A, was performed in blood samples from 247 infants younger than 9 months. Meanwhile, the serological specificity immunoglobulin E (sIgE) levels were evaluated. In addition, the area under the curve (AUC) values of IL-12, IL-16, and IL-17A in differentiating CMP from healthy babies were measured by receiver operating characteristic analysis. Finally, the correlation between sIgE and IL-12, IL-16, and IL-17A levels were detected using Spearman correlation analysis.Results Compared with healthy control, infants who developed CMPA had decreased IL-12, increased IL-16, and IL-17A. Moreover, a significant correlation between serum IL-12, IL-16, IL-17A and sIgE levels was observed in the CMPA group. In addition, AUC values of IL-12, IL-16, and IL-17A in discriminating CMPA from healthy infants were 0.8425, 0.9196, and 0.8813, respectively. Finally, IL-12 was increased while IL-16 and IL-17A levels were decreased in the CMPA group after three months of milk avoidance treatment.Conclusions We found that IL-12, IL-16, and IL-17A levels in children with CMPA were associated with SCORAD scores, sIgE levels (AU)

Combating the SARS-CoV-2 Omicron variant with non-Omicron neutralizing antibodies

The highly mutated and transmissible Omicron variant has provoked serious concerns over its decreased sensitivity to the current coronavirus disease 2019 (COVID-19) vaccines and evasion from most anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies (NAbs). In this study, we explored the possibility of combatting the Omicron variant by constructing bispecific antibodies based on non-Omicron NAbs. We engineered ten IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and REGN10987 by fusing the single-chain variable fragments (scFvs) of two antibodies through a linker and then connecting them to the Fc region of IgG1. Surprisingly, eight out of ten bispecific antibodies showed high binding affinity to the Omicron receptor-binding domain (RBD) and exhibited extreme breadth and potency against pseudotyped SARS-CoV-2 variants of concern (VOCs) including Omicron, as well as authentic Omicron(+R346K) variants. Six bispecific antibodies containing the cross-NAb GW01 neutralized Omicron variant and retained their abilities to neutralize other sarbecoviruses. Bispecific antibodies inhibited Omicron infection by binding to the ACE2 binding site. A cryo-electron microscopy (cryo-EM) structure study of the representative bispecific antibody FD01 in complex with the Omicron spike (S) revealed 5 distinct trimers and one unique bi-trimer conformation. The structure and mapping analyses of 34 Omicron S variant single mutants elucidated that two scFvs of the bispecific antibody synergistically induced the RBD-down conformation into 3-RBD-up conformation, enlarged the interface area, accommodated the S371L mutation, improved the affinity between a single IgG and the Omicron RBD, and hindered ACE2 binding by forming bi-trimer conformation. Our study offers an important foundation for anti-Omicron NAb design. Engineering bispecific antibodies based on non-Omicron NAbs may provide an efficient solution to combat the Omicron variant.

Dynamic expression of CCAAT enhancer binding protein A and its significance in rat lung development / 中华实用儿科临床杂志

Objective To investigate the role of CCAAT enhancer binding protein A (C/EBPα) in lung development by analyzing the relationship between dynamic expression of C/EBPα protein and cell differentiation in rat lung tissue.Methods According to the histological stages of rat lung development,lung tissues were collected on 15.5 d (the late pseudoglandular period),17.5 d (the canalicular period),19.5 d (the early saccular period) of embryonic age and at 12 h (the middle saccular period),on 4 d (the late saccular period),7 d (the alveolar period,the alveolar stage),14 d (the alveolar period,the equilibrium stage) of postnatal age.The lung morphologic appearance was observed by using HE staining.Western blot was used to detect the expressions of C/EBPα and surfactant Protein (SP)-A,SP-B,SP-C,SP-D.Phosphatidylcholine (PC) assay kit was utilized to analyze the secretion of PC.Periodic acid-schiff (PAS) staining was used to evaluate the amcunt of glycogen in lung tissue.Results (1) C/EBPαt and SP-A began to express on 15.5 d of embryonic age (0.36 ±0.02,0.01 ±0.01),while SP-B,SP-C and SP-D started to express on 17.5 d of embryonic age (0.33 ±0.06,0.01 ±0.01,0.11 ±0.08).All of them increased with the development of lung,and C/EBPα,SP-A,SP-C reached the highest level at 12 h of postnatal age (3.48 ±0.05,3.24 ± 0.19,1.26 ± 0.21),and SP-D on the postnatal 4 d (1.48 ± 0.10),then gradually decreased,while the expression of SP-B continued to rise.The levels of C/EBPα and SPs maintained stable on postnatal 14 d.The C/EBPα protein level was positively correlated with SPs at embryonic age of 15.5 d,17.5 d,19.5 d and postnatal age 12 h (r =0.999,0.991,0.982,0.951,all P ＜ 0.05).(2) The level of PC was very low at embryonic age of day 15.5 [(60.50 ± 1.30) μg/g].With the development of lung,the secretion of PC increased gradually,but there was no significant correlation between the expression of PC and C/EBPoα(all P ＞ 0.05).(3) The level of glycogen was high in the late pseudoglandular stage (15.5 d) (585.50 ± 2.20),the content of glycogen decreased with the development of lung,especially on the canalicular (embryonic day 17.5) and during early saccular period (embryonic day 19.5),and then it became stable during the alveolar period (postnatal age 7 d).The expression of C/EBPα had negative correlation with the content of glycogen in fetal lung(r =-1.000,P ＜ 0.01).Conclusion C/EBPα plays an important role in rat lung development,as it may promote lung maturation by regulating the synthesis and secretionof SPs and PC.

SPECT and CT in Evaluating Preoperative Renal Function of Patients with Unilateral Hydronephrosis / 中国医学影像学杂志

Purpose To analyze the relationships between glomerular filtration rate (GFR) measured by SPECT and renal parenchyma thickness and enhanced CT value measured by CT, and to explore predictive significance of CT in evaluating renal function of patients with hydronephrosis.Materials and Methods One hundred and fifteen patients diagnosed with unilateral hydronephrosis by ultrasound were retrospectively analyzed. GFR% (GFR percentage of affected kidney to the both kidneys) was measured by SPECT. CT% (percentage of affected renal parenchyma thickness to the both kidneys) and enhanced CT% (percentage of enhanced CT value of affected kidney to the both kidneys) were measured by pre- and post-contrast CT scan. According to GFR, the renal function was divided into mild-to-moderate impairment, severely impairment and non-function. Twenty-five volunteers were recruited as control group. CT%, enhanced CT% and GFR%among the four groups were compared, and the correlation of CT% and enhanced CT%with GFR% was analyzed to evaluated CT in predicting renal function.Results CT%, enhanced CT% and GFR% in mild-to-moderate impairment group was significantly greater than those in severely impairment group and non function group (F=20.24, 7.78 and 329.21,P<0.05). GFR% was positive correlated with CT% (r=0.58,P<0.05) and enhanced CT% (r=0.61,P<0.05). Area under curve (AUC) of CT% were 0.54, 0.79 and 0.83 for mild-to-moderate impairment, severely impairment and non-function, with sensitivity of 92.91%, 93.47%, 65.72%, and specificity of 35.33%, 59.47%, and 88.62%, respectively. AUC of enhanced CT% were 0.79, 0.89 and 0.96 for the three groups, with sensitivity of 97.51%, 80.02%, 97.66%, and specificity of 58.14%, 89.82% and 94.27%, respectively.Conclusion There was high correlation between renal function imaging by SPECT and CT in evaluating renal function of hydroneohrosis patients. Pre- and post-contrast CT scan can be used as complements in predicting renal function, and post-contrast CT with high accuracy.

A clinical study on the treatment of mucocele by bleomyin A5 combined with phosphorus-32 colloid / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of bleomyin A5 combined with phosphorus-32 colloid in the treatment of mucocele.</p><p><b>METHODS</b>A total of 214 patients divided into three groups, bleomyin A5 (50 cases), phosphorus-32 colloid (50 cases) and bleomyin A5 combined with phosphorus-32 colloid (114 cases).</p><p><b>RESULTS</b>The efficacy of bleomyin A5 group, phosphorus-32 colloid group, and bleomyin A5 combined with phosphorus-32 colloid group was 84% (42/50), 82% (41/50) and 98% (112/114), respectively. There were significant difference in efficacy among the three groups (P < 0.05). The phosphorus-32 colloid group and the bleomyin A5 group had no significant difference in efficacy (P > 0.05).</p><p><b>CONCLUSIONS</b>The independent use of bleomyin A5 and phosphorus-32 colloid is effective, but the combined use of the two methods is more effective.</p>

A novel 5' splice site mutation in ACTC1 gene may play an important role in congenital ventricular septal defect / 中国组织工程研究

BACKGROUND: As a candidate gene of congenital heart disease, ACTC1 gene is related to congenital atrial septal defect inhumans.OBJECTIVE: To perform a mutation screen of ACTC1 gene in 110 nuclear families of congenital heart disease.METHODS: A case-control study was conducted based on 110 nuclear families of congenital heart disease and 300 normalhuman beings with no reported cardiac malformation. Six fragments in the coding region of ACTC1 gene was amplified by PCR invitro using five primers pairs. PCR products were screened for gene mutations.RESULTS AND CONCLUSION: A novel G-to-A variant was found at the third nucleotide of the intron downstream from exon 5.This mutation existed in a 5-year-old female with an isolated ventricular septal defect and her 30-year-old father, who had noreported cardiac anomalies. This mutation was not detected in 300 normal controls. These findings indicate that the mutation maybe related with congenital ventricular septal defects in humans.

Efficacy of 32P and pinyangmycin injection in combination on maxillofacial hemangioma in infants and children / 中华医学美学美容杂志

Objective To explore and evaluate the effect of 32P and pinyangmycin injected in combination for the treatment of maxillofacial hemangioma. Methods The patients were randomly divided into three groups. The first group of patients was treated with 32P; 100 patients were enrolled in this group, of which 37 were male and 63 female. 32P dosage between 0.37 and 0. 74 MBq per cm3 was prepared together with 0.5 ml of 2 %lidocaine, and appropriate normal saline, and then the mixture was injected into hemangioma every two weeks. The second group was given pinyangmycin, and the third group received both 32P and pinyangmycin. The second group included 30 male and 60 female, and the third group 64 male and 136 female. The dose and frequency were given as the same to the first group. Results 88.5 % of patients were cured using both 32P and pinyangmycin, and the cure rate was 77.0 % and 71.7 % with either 32P or pinyangmycin. Conclusion These results prove that 32P and pinyangmycin injected in combination for the treatment of maxillofacial hemangioma is more effective than either 32P or pinyangmycin alone, and furthermore, the method is easy, safe and has less complications.