Objective To analyze the relationship between umbilical cord blood chemokines regulated upon activation normal T cell expressed and secreted(RANTES),C-X-C motif chemokine ligand 12(CXCL12),C-X-C motif chemokine receptor 4(CXCR4)and neonatal septicemia inflammatory response and outcome.Meth-ods A total of 242 children with neonatal septicemia admitted to a hospital from January 2020 to January 2024 were selected as the study subjects,and were divided into non-critical group(101 cases),critical group(79 cases)and extremely critical group(62 cases)according to neonatal critical case score.According to the prognosis,the subjects were divided into good prognosis group and bad prognosis group.The levels of RAN-TES,CXCL12,CXCR4 and inflammatory factors[C-reactive protein(CRP),interleukin-6,IL-1β]in umbilical cord blood of each group were detected.The correlation between RANTES,CXCL12,CXCR4 and inflammato-ry factors in umbilical cord blood of neonatal septicemia was analyzed by Pearson correlation,and the influen-cing factors of poor prognosis of neonatal septicemia were analyzed by multivariate Logistic regression.Re-ceiver operating characteristic(ROC)curve was drawn to analyze the value of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting the poor prognosis of neonatal septicemia.Results The levels of RAN-TES,CXCL12,CXCR4,CRP,IL-6 and IL-1β in umbilical cord blood of extremely critical group were higher than those of critical group and non-critical group,and the differences were statistically significant(P＜0.05).The levels of RANTES,CXCL12 and CXCR4 in umbilical cord blood of neonatal septicemia were posi-tively correlated with CRP,IL-6 and IL-1β(P＜0.05).Multivariate Logistic regression analysis showed that extremely severe,early-onset septicemia,high RANTES,high CXCL12 and high CXCR4 were risk factors for poor prognosis of neonatal septicemia(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting poor prognosis of neonatal septicemia were 0.810,0.814 and 0.763,respectively,and the AUC of three indicators combined prediction was 0.914,which was higher than that of single prediction.Conclusion The increased levels of RANTES,CX-CL12 and CXCR4 in umbilical cord blood of neonatal septicemia are associated with inflammation,aggravation and poor prognosis,and the combination of RANTES,CXCL12 and CXCR4 can predict the risk of poor prog-nosis of neonatal septicemia.

Objective To evaluate the relationship between renal function and renal tissue oxygenation in type 2diabetes patients with blood oxygenation level dependent MRI(BOLD MRI)and to explore its value in clinical and scientific research.Methods A total of 80diabetic kidney disease patients with type 2diabetes admitted to hospital from April 2023 to August 2024 were selected.According to the the ratio of urinary albumin and creatinine,the patients were divided into normal albuminuria group,microalbuminuria group and mac-roalbuminuria group.All patients were examined by BOLD MRI.R2* values of renal cortex and medulla were measured by two radiolo-gists respectively,and the mean R2*values of renal cortex and medulla,the ratio of the two values(MCR)were obtained.The consis-tency of CR2* and MR2* measured by 2 physicians and the differences of CR2*,MR2* and MCR among 3 groups were compared,and the correlation with clinical indicators were analyzed.Results There were statistically significant differences in serum creatinine and glomerular filtration rate among the three groups(P＜0.05).ACR,urinary microalbumin and urinary N-acetyl-β-D glucosaminase(UANG)were significantly different among the three groups(all P＜0.01).The fasting C-peptide based insulin resistance index(HOMA2-IR)of the three groups was significantly different(P＜0.05).BOLD MRI results showed that the differences of CR2*,MR2* and MCR among the three groups were statistically significant(all P＜0.05).Correlation analysis showed that CR2* and MR2* were positively correlated with creatinine,ACR,urinary microalbumin,UANG and HOMA2-IR,respectively,and negatively correlated with glomerular filtration rate.Conclusion BOLD MRI is a non-invasive method to evaluate oxygenation in diabetic nephrop-athy,and the R2* of cortex and medulla in renal tissue are correlated with different renal function indicators.

Objective To evaluate the relationship between renal function and renal tissue oxygenation in type 2diabetes patients with blood oxygenation level dependent MRI(BOLD MRI)and to explore its value in clinical and scientific research.Methods A total of 80diabetic kidney disease patients with type 2diabetes admitted to hospital from April 2023 to August 2024 were selected.According to the the ratio of urinary albumin and creatinine,the patients were divided into normal albuminuria group,microalbuminuria group and mac-roalbuminuria group.All patients were examined by BOLD MRI.R2* values of renal cortex and medulla were measured by two radiolo-gists respectively,and the mean R2*values of renal cortex and medulla,the ratio of the two values(MCR)were obtained.The consis-tency of CR2* and MR2* measured by 2 physicians and the differences of CR2*,MR2* and MCR among 3 groups were compared,and the correlation with clinical indicators were analyzed.Results There were statistically significant differences in serum creatinine and glomerular filtration rate among the three groups(P＜0.05).ACR,urinary microalbumin and urinary N-acetyl-β-D glucosaminase(UANG)were significantly different among the three groups(all P＜0.01).The fasting C-peptide based insulin resistance index(HOMA2-IR)of the three groups was significantly different(P＜0.05).BOLD MRI results showed that the differences of CR2*,MR2* and MCR among the three groups were statistically significant(all P＜0.05).Correlation analysis showed that CR2* and MR2* were positively correlated with creatinine,ACR,urinary microalbumin,UANG and HOMA2-IR,respectively,and negatively correlated with glomerular filtration rate.Conclusion BOLD MRI is a non-invasive method to evaluate oxygenation in diabetic nephrop-athy,and the R2* of cortex and medulla in renal tissue are correlated with different renal function indicators.

Objective:To explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome (LDS) due to variants of FOXC2 gene. Methods:A retrospective analysis was carried out on the phenotypic information, fetal ultrasound image, and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University. A literature review was also carried out by searching the China National Knowledge Infrastructure (CNKI), Wanfang Database, and PubMed databases dated from January 2010 to June 2024 using keywords "Lymphedema-Distichiasis syndrome" and " FOXC2". This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No.2021-046-01). Results:Neither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb. The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c. 361C>T (p.R121C) variant and a c. 168C>A (p.Y56*) variant of the FOXC2 gene. Both variants were paternally derived. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as pathogenic and likely pathogenic, respectively. Literature search has identified 20 articles, and combined with our cases, a total of 117 patients were identified. Among them, 13 had shown prenatal phenotypes, primarily with increased nuchal translucency (NT) (12/13), urinary abnormalities (5/12), and fetal edema (4/13). Postnatal phenotypes were observed in 110 cases, mainly as distichiasis (87/110) and lymphedema (73/110). Only 6 cases had both prenatal and postnatal phenotypes. A total of 32 genetic variants were identified. Conclusion:The primary prenatal manifestations of LDS include increased NT, fetal edema, pleural and abdominal effusion, and separation of renal collecting system. Postnatal phenotypes are primarily characterized by lymphedema, distichiasis, and spinal extradural arachnoid cysts. Discovery of the c. 168C>A variant has expanded the spectrum of FOXC2 gene mutations in China.

OBJECTIVE: To explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome (LDS) due to variants of FOXC2 gene. METHODS: A retrospective analysis was carried out on the phenotypic information, fetal ultrasound image, and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University. A literature review was also carried out by searching the China National Knowledge Infrastructure (CNKI), Wanfang Database, and PubMed databases dated from January 2010 to June 2024 using keywords "Lymphedema-Distichiasis syndrome " and "FOXC2 ". This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-046-01). RESULTS: Neither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb. The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c.361C>T (p.R121C) variant and a c.168C>A (p.Y56*) variant of the FOXC2 gene. Both variants were paternally derived. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as pathogenic and likely pathogenic, respectively. Literature search has identified 20 articles, and combined with our cases, a total of 117 patients were identified. Among them, 13 had shown prenatal phenotypes, primarily with increased nuchal translucency (NT) (12/13), urinary abnormalities (5/12), and fetal edema (4/13). Postnatal phenotypes were observed in 110 cases, mainly as distichiasis (87/110) and lymphedema (73/110). Only 6 cases had both prenatal and postnatal phenotypes. A total of 32 genetic variants were identified. CONCLUSION The primary prenatal manifestations of LDS include increased NT, fetal edema, pleural and abdominal effusion, and separation of renal collecting system. Postnatal phenotypes are primarily characterized by lymphedema, distichiasis, and spinal extradural arachnoid cysts. Discovery of the c.168C>A variant has expanded the spectrum of FOXC2 gene mutations in China.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; East Asian People/genetics* ; Eyelashes/abnormalities* ; Forkhead Transcription Factors/genetics* ; Genetic Testing ; Lymphedema/genetics* ; Pedigree ; Phenotype ; Retrospective Studies

Objective:To explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome (LDS) due to variants of FOXC2 gene. Methods:A retrospective analysis was carried out on the phenotypic information, fetal ultrasound image, and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University. A literature review was also carried out by searching the China National Knowledge Infrastructure (CNKI), Wanfang Database, and PubMed databases dated from January 2010 to June 2024 using keywords "Lymphedema-Distichiasis syndrome" and " FOXC2". This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No.2021-046-01). Results:Neither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb. The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c. 361C>T (p.R121C) variant and a c. 168C>A (p.Y56*) variant of the FOXC2 gene. Both variants were paternally derived. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as pathogenic and likely pathogenic, respectively. Literature search has identified 20 articles, and combined with our cases, a total of 117 patients were identified. Among them, 13 had shown prenatal phenotypes, primarily with increased nuchal translucency (NT) (12/13), urinary abnormalities (5/12), and fetal edema (4/13). Postnatal phenotypes were observed in 110 cases, mainly as distichiasis (87/110) and lymphedema (73/110). Only 6 cases had both prenatal and postnatal phenotypes. A total of 32 genetic variants were identified. Conclusion:The primary prenatal manifestations of LDS include increased NT, fetal edema, pleural and abdominal effusion, and separation of renal collecting system. Postnatal phenotypes are primarily characterized by lymphedema, distichiasis, and spinal extradural arachnoid cysts. Discovery of the c. 168C>A variant has expanded the spectrum of FOXC2 gene mutations in China.

OBJECTIVE: To explore the clinical phenotype and genetic variants of a fetus with Glutaracidemia type II C (GA II C). METHODS: Clinical data of a 32-year-old pregnant woman and her fetus with GA II C diagnosed at the Third Affiliated Hospital of Zhengzhou University in December 2021 due to the enlargement and enhanced echo of the kidneys and oligohydramnios fluid at 17 weeks were analyzed retrospectively. Amniotic fluid sample of the fetus and peripheral blood samples of the couple were collected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Copy number variation (CNV) was detected by using low-coverage whole genome sequencing (CNV-seq). RESULTS: At 18 weeks' gestation, ultrasound revealed that the fetus had enlargement and enhanced echo of the kidneys along with no echo of renal parenchymal tubular fissure and oligohydramnios. MRI at 22 weeks' gestation confirmed that both kidneys were enlarged with uniformly increased abnormal T2 signal and decreased DWI signal. The volume of both lungs was small, with slightly higher T2 signal. No CNV was detected in the fetus. WES revealed that the fetus has harbored compound heterozygous variants of the ETFDH gene, namely c.1285+1G＞A and c.343_344delTC, which were inherited from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PM2_Supporting+PS3_Supporting; PVS1+PM2_Supporting+PM3). CONCLUSION The c.1285+1G＞A and c.343_344delTC compound heterozygous variants of the ETFDH gene probably underlay the disease in this fetus. Type II C glutaric acidemia may manifest as bilateral kidney enlargement with enhanced echo and oligohydramnios. Discovery of the c.343_344delTC has enriched the spectrum of ETFDH gene variants.
Pregnancy ; Humans ; Female ; Mutation ; DNA Copy Number Variations ; Oligohydramnios/genetics* ; Retrospective Studies ; Phenotype ; Fetus/diagnostic imaging*

OBJECTIVE: To explore the clinical phenotypes and genetic diagnosis of 2 sporadic cases for cleidocranial dysplasia. METHODS: The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16, 2021 and December 9, 2021 were analyzed retrospectively, and the whole exome sequencing (WES), chromosome microarray analysis and copy number variation sequencing were performed. RESULTS: The main ultrasonographic findings of the fetus had included poorly calcified skull bones, budging of parieto-occipital area, compression and deformation of skull, and loss of nasal bone. The infant's clinical phenotypes included delayed closure of anterior fontanelle, recurrent respiratory tract infection, growth retardation, and clavicular hypoplasia. By WES analysis, the fetus was found to harbor a heterozygous c.911_914delinsTTT variant of the RUNX2 gene, whilst the infant was found to harbor a heterozygous c.1008delT variant of the RUNX2 gene. Both variants were verified by Sanger sequencing to have occurred de novo. CONCLUSION For sporadic cases featuring cleidocranial dysplasia, prenatal ultrasonography is particularly important. Hypoplastic clavicle, skull calcification and nasal bone absence are the main features. Diagnosis should also be suspected for infants featuring growth retardation, recurrent respiratory tract infections and clavicular dysplasia. The identification of the c.911_914delinsTTT and c.1008delT variants of the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis, and also expanded the mutational spectrum of the RUNX2 gene.
Female ; Humans ; Pregnancy ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit ; DNA Copy Number Variations ; Growth Disorders ; Retrospective Studies

Objective To explore the pattern of lymph node metastasis and provide guidance for the delineation of clinical target volume for patients diagnosed with hypopharyngeal squamous cell carcinoma (HSCC).Methods A total of 123 patients who were initially diagnosed with HSCC by electrolaryngoscope and computed tomography (CT) of the head and neck in Shandong Tumor Hospital between 2014 and 2017 were recruited in this study.The lymph node metastasis was evaluated based on the diagnostic criteria of CT scan.The lymphatic metastasis ratio (LMR) at each node level was calculated.Analysis of variance (ANOVA) andx2 test were used to analyze the relationship between LMR and primary tumors.Results Among 123 patients,primary tumors were originated from the pyriform sinus (PS) in 101 cases (82.1％),posterior pharyngeal wall (PPW) in 15 (12.2％) and postcricoid (PC) in 7 (5.7％),respectively.The overall LMR was calculated as 84.6％ (n=104),in detail,84.2％ for patients with primary tumors originating from PS,93.3％ for those from PPW and 71.4％ for patients from PC,respectively.For PSderived tumors,the ipsilateral neck LMR at the level Ⅰa,Ⅰb,Ⅱa,Ⅱb,Ⅲ,Ⅳ,Ⅴ,Ⅵa,Ⅵb,and Ⅶ was 0,3.0％,66.3％,42.6％,46.5％,10.9％,5.0％,2.0％,7.9％,and 11.9％,respectively,and 0,0,14.9％,5.0％,3.0％,2.0％,0,0,3.0％,and 2.0％ for the contralateral neck.For PPW tumors,the ipsilateral neck LMR at the level Ⅰa,Ⅰb,Ⅱa,Ⅱb,Ⅲ,Ⅳ,Ⅴ,Ⅵa,Ⅵb,and Ⅶ was 6.7％,6.7％,66.7％,46.7％,46.7％,20.0％,0,13.3％,33.3％,and 60.0％,respectively,and 6.7％,6.7％,33.3％,26.7％,20.0％,20.0％,0,0,13.3％,and 33.3％ for the contralateral neck.For PC tumors,the ipsilateral neck LMR at the level Ⅱa,Ⅱb,Ⅲ,Ⅳ,Ⅴ and Ⅵb was 71.4％,28.6％,14.3％,14.0％,14.0％,and 14.3％,respectively,and the LMR at the level Ⅱa was 14.3％ for the contralateral neck.No lymph node metastasis occurred in other lymph node levels.The mean levels of lymph node metastasis for the T1-T4 stage tumors were 2.4,1.9,2.2,3.3 with statistical significance (P =0.023),and 2.2,4.5 and 1.6 for patients with the tumors originated from PS,PPW and PC (P=0.000).The PPW invasion was significantly correlated with the level Ⅶ metastasis (P=0.000),and PC or esophageal invasion was intimately correlated with the level Ⅵ metastasis (P=0.002 and 0.001).Conclusions The most common lymphatic metastasis includes ipsilateral neck Ⅱa,Ⅲ,and Ⅱb,whereas the level Ⅰ and Ⅴ are rarely observed.For PPW-derived tumors,the LMR at the level Ⅶ is up to 60.0％.The incidence of PC or esophageal invasion enhances the risk of level Ⅵ lymph node metastasis.

Objective To evaluate the treatment outcomes and toxicities of intensity-modulated radiation therapy (IMRT) combined with chemotherapy for children and adolescents with nasopharyngeal carcinoma.Methods Forty-three nasopharyngeal carcinoma patients less than 19 years old were recruited between April 2010 and April 2016.All patients were treated with IMRT (total dose 61.2-76 Gy) combined with cisplatin based chemotherapy.The Kaplan-Meier test was used to calculate overall survival (OS) and progression-free survival (PFS).The patient's clinical characteristics,side effects and longterm effects of treatment were retrospectively analyzed.Results Among 43 patients,there were 29 (67.4％) male and 14 (32.6％) female,and the median age was 14 years old (range,6-18 years).According to AJCC 7thstaging system,2 patients were in stage Ⅱ,26 in stage Ⅲ,7 in stage ⅣA and 8 in stage Ⅳ B.All patients were confirmed as non-keratinizing carcinoma.The positive rates of EB virus VCAIgA was 53.8％ (7/13),and Rta-IgG was 60.0％ (6/10) before treatment.The median radiation dose was 70 Gy (range,61.2-76 Gy) to the primary tumor.Thirty-three (76.7％) patients received neoadjuvant chemotherapy,with 20 (46.5％) and 36 (83.7％) patients treated by concurrent and adjuvant chemotherapy,respectively.With a median follow-up of 24 months (range,3-76 months),the 5-year OS and PFS ratios were 75.3％ and 64.7％,respectively.There were 5 patients (11.6％) occurred to bone metastasis within 2 years after treatment.Hypothyroidism was reported in 47.4％ (9/19) patients after IMRT.Conclusions Nasopharyngeal carcinoma in childhood and adolescence is mostly locally advanced diseases with poor differentiation.IMRT combined with chemotherapy produce a well treatment outcome with good tolerance in children and adolescents patients.The most common treatment failure bone metastasis.Radiation-induced hypothyroidism is common.