This article reported a case of autosomal dominant intellectual developmental disorder type 22 caused by a heterozygous mutation in the ZBTB18 gene. At 24 +4 weeks of gestation, prenatal ultrasound indicated a short outer diameter of the fetal corpus callosum and bilateral ventricular dilatation. Whole-genome copy number variation analysis of the fetus showed no abnormalities. Whole exome sequencing (WES) and Sanger sequencing validation of the family revealed the fetus carried a c.1374_1383del(p.S459*) heterozygous mutation in the ZBTB18 gene (NM_205768.3), which was neither phenotypically present nor genotypically detected in the parents, suggesting a de novo mutation. Based on the clinical manifestations, the fetus was diagnosed with autosomal dominant intellectual developmental disorder type 22. After genetic counseling, the pregnant woman opted for termination of the pregnancy. This case highlights the correlation between prenatal ultrasonic detection of callosal dysgenesis and lateral ventricular enlargement and intellectual developmental disorders caused by gene mutations. Furthermore, it expands the mutation spectrum of the ZBTB18 gene, thereby facilitating prenatal diagnosis and genetic counseling.

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

This article reported a case of autosomal dominant intellectual developmental disorder type 22 caused by a heterozygous mutation in the ZBTB18 gene. At 24 +4 weeks of gestation, prenatal ultrasound indicated a short outer diameter of the fetal corpus callosum and bilateral ventricular dilatation. Whole-genome copy number variation analysis of the fetus showed no abnormalities. Whole exome sequencing (WES) and Sanger sequencing validation of the family revealed the fetus carried a c.1374_1383del(p.S459*) heterozygous mutation in the ZBTB18 gene (NM_205768.3), which was neither phenotypically present nor genotypically detected in the parents, suggesting a de novo mutation. Based on the clinical manifestations, the fetus was diagnosed with autosomal dominant intellectual developmental disorder type 22. After genetic counseling, the pregnant woman opted for termination of the pregnancy. This case highlights the correlation between prenatal ultrasonic detection of callosal dysgenesis and lateral ventricular enlargement and intellectual developmental disorders caused by gene mutations. Furthermore, it expands the mutation spectrum of the ZBTB18 gene, thereby facilitating prenatal diagnosis and genetic counseling.

Objective:To analyze ultrasonographic manifestations and genetic etiology of nine fetuses with 7q11.23 duplication syndrome.Methods:Ultrasonographic finding, pregnancy outcome and follow-up of nine fetuses detected at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2021 were retrospectively analyzed.Results:The fetuses were found to harbor a duplication in the 7q11.23 region by chromosomal microarray analysis (CMA). Among these, five had shown ventriculomegaly, including four syndromic and one non-syndromic. For the remainders, one had ventricular septal defect and mild tricuspid regurgitation, one had echogenic intracardiac focus, whilst another two were normal. Five couples had accepted parental verification, and the results confirmed that the 7q11.23 duplication carried by their fetuses were de novo in origin. Following genetic counseling, seven couples had opted to terminate their pregnancies. Two fetuses were delivered at full term, and follow-up had found no abnormalities. Conclusion:Prenatal ultrasonographic manifestations of fetuses with 7q11.23 duplication syndrome are variable. CMA can provide assistance for their diagnosis and genetic counseling.

Objective:To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). Methods:A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c. 4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+ PS2_Moderate+ PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy for the fetus. Conclusion:The c. 4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

Objective:To investigate the spatial distribution pattern of local tumor progression (LTP) for hepatocellular carcinoma (HCC) ≤5 cm after microwave ablation.Methods:A retrospective analysis was performed on 169 HCCs with matched MRI before and after ablation from December 2009 to December 2019. A tumor MRI was reconstructed using three-dimensional visualization technology. LTP was classified as contact or non-contact, early or late stage, according to whether LTP was in contact with the edge of the ablation zone and the occurrence time (24 months). The tumor-surrounded area was divided into eight quadrants by using the eight-quadrant map method. An analysis was conducted on the spatial correlation between the quadrant where the ablative margin (AM) safety boundary was located and the quadrant where different types of LTP occurred. The t-test, or rank-sum test, was used for the measurement data. 2-test for count data was used to compare the difference between the two groups.Results:The AM quadrant had a distribution of 54.4% LTP, 64.2% early LTP stage, and 69.1% contact LTP, suggesting this quadrant was much more concentrated than the other quadrants ( P ?

Objective This study aims to discuss the research hotspot and development trend in the field of polycystic ovary syndrome(PCOS)through bibliometric statistics and visual analysis of long noncoding RNA(lncRNA)related studies.Methods Utilizing the Web of Science core database as the literature data source,we searched for PCOS lncRNA-related literature from 2015 to 2023.CiteSpace software was used to conduct a visual analysis,including the annual distribution,citation trends,countries,institutions,funding sources and key words,as well as co-occurrence and cluster analysis of key words.Results The visual analysis of 108 PCOS lncRNA literature revealed that China was the country with the highest number of publications.The first contributing institution was the Shandong University.The national natural science fund of China gave the biggest funding.The keyword cluster analysis suggested that PCOS lncRNA signal pathway regulation,related receptor activators,and the expression of regulatory factors were the research hotspots in ovary syndrome lncRNA research.Conclusion LncRNA related regulatory factors,bioinformatics analysis,and gene transcription in PCOS are new targetsfor PCOS treatment,providing valuable insights for clinical therapy and new strategies for the development of PCOS-related pharmaceuticals.

This study was designed to explore whether overexpression of HMBOX1 inhibits COPD-induced infiltration and pulmonary macrophage activation by regulating NF-κB/CCL2 signaling pathway.Forty Wistar rats were randomly divided into control group,chronic obstructive pulmonary disease group(COPD group),COPD+control overexpression group(COPD+ov-NC group)and chronic COPD+HMBOX1 overexpression group(COPD+ov-HMBOX1 group),with 10 rats in each group.The COPD model was established by continuous cigarette incense and intermittent intratracheal injection of lipopolysaccharide,wihle the HMBOX1 overexpression treatmet was carried out by intratracheal instillation of HMBOX1 overexpressing adenovirus.Western blot was used to detect the expression of HMBOX1,p-NF-κB and NF-κB proteins in lung tissue of rats;RT-qPCR was used to detect the mRNA expression of HMBOX1 and CCL2 in rat lung tissue;HE staining was used to observe the pathological changes of lung tissue in rats;ELISA was applied to detect the levels of TNF-α,MIP-2,IL-1β and IL-10 in serum and BALF of rats.Furthermore,the ratio of CD11b+F4/80+cells in lung tissue of rats was detected by immunofluorescence,while the ratio of F4/80+MHC Ⅱ+cells and F4/80+CD80+cells in lung tissue of rats was detected by flow cytometry.In control group,the alveolar structure of rats was intact,and no inflammatory cell infiltration was found.In COPD group and COPD+ov-NC group,a large number of inflammatory cells infiltrated into the lung tissue and alveolar structure was damaged.In COPD+ov-HMBOX1 group,there were fewer inflammatory cells infiltrated in lung tissue,and the damage of alveolar structure was alleviated.Compared with the control group,the mRNA and protein expression of HMBOX1 in lung tissue,the levels of IL-10 in serum and BALF,the levels of TNF-α,MIP-2 and IL-1β in serum and BALF,CD11b+F4/80+cells,F4/80+MHC Ⅱ+cells and F4/80+CD80+cells in lung tissue of rats in COPD and COPD+ov-NC groups were significantly decreased.HMBOX1 overexpression could revers the changes mentioned above in the two COPD groups.Taken together,overexpression of HMBOX1 can alleviate COPD-induced airway inflammation and lung injury,and its mechanism may be related to inhibiting infiltration and abnormal activation of macrophages in lung tissue mediated by activation of NF-κB/CCL2 signaling pathway.

Objective To establish a rat model of chronic obstructive pulmonary disease(COPD),to explore whether berberine can improve the imbalance of Th17/Treg cells induced by COPD by regulating NF-κB/LCN2 signaling pathway.Methods Fifty Wistar rats were randomly divided into Control group(control group),chronic obstructive pulmonary disease group(COPD group),Berberine group(Berberine group),berberine+overexpression control group(Berberine+ov-NC group)and berberine+overexpression LCN2 group(Berberine+ov-LCN2 group),with 10 rats in each group.Western blotting was used to detect the expression of p-NF-κB,LCN2,IL-17 and IL-10 in lung tissue.HE staining was used to observe the pathological changes of lung tissue in rats.The ratio of Th17/Treg cells in peripheral blood of rats was detected by flow cytometry.The levels of IL-17 and IL-10 in serum of rats were detected by ELISA.Results In the control group,the lung tissue structure was intact;compared with the control group,the lung tissue structure of rats in COPD group was damaged,the expressions of p-NF-κB and LCN2 protein in lung tissue were significantly increased,the proportion of Th17 cells in peripheral blood was significantly increased,the proportion of Treg cells was significantly decreased,the level of IL-17 in serum and the expression of IL-17 protein in lung tissue were significantly increased,and the level of IL-10 in serum and the expression of IL-10 protein in lung tissue were significantly decreased(P<0.05).Compared with COPD group,Berberine group and Berberine+ov-NC group improved lung tissue injury,significantly decreased the expression of p-NF-κB and LCN2 proteins in lung tissue,significantly decreased the proportion of Th17 cells in peripheral blood,significantly increased the proportion of Treg cells,significantly decreased the level of IL-17 in serum and the expression of IL-17 protein in lung tissue(P<0.05).Compared with Berberine group and Berberine+ov-NC group,Berberine+ov-LCN2 group has more lung injury,higher expression of LCN2 protein in lung tissue,higher proportion of Th17 cells in peripheral blood,lower proportion of Treg cells,higher levels of IL-17 in serum and IL-17 protein expression in lung tissue,and higher levels of IL-10 in serum and IL-10 protein in lung tissue(P<0.05).Conclusion Berberine treatment can improve lung injury and Th17/Treg cell imbalance in COPD rats by down-regulating the expression of LCN2,and its mechanism may be related to the inhibition of NF-κB/LCN2 signaling pathway.

This study was designed to explore whether overexpression of HMBOX1 inhibits COPD-induced infiltration and pulmonary macrophage activation by regulating NF-κB/CCL2 signaling pathway.Forty Wistar rats were randomly divided into control group,chronic obstructive pulmonary disease group(COPD group),COPD+control overexpression group(COPD+ov-NC group)and chronic COPD+HMBOX1 overexpression group(COPD+ov-HMBOX1 group),with 10 rats in each group.The COPD model was established by continuous cigarette incense and intermittent intratracheal injection of lipopolysaccharide,wihle the HMBOX1 overexpression treatmet was carried out by intratracheal instillation of HMBOX1 overexpressing adenovirus.Western blot was used to detect the expression of HMBOX1,p-NF-κB and NF-κB proteins in lung tissue of rats;RT-qPCR was used to detect the mRNA expression of HMBOX1 and CCL2 in rat lung tissue;HE staining was used to observe the pathological changes of lung tissue in rats;ELISA was applied to detect the levels of TNF-α,MIP-2,IL-1β and IL-10 in serum and BALF of rats.Furthermore,the ratio of CD11b+F4/80+cells in lung tissue of rats was detected by immunofluorescence,while the ratio of F4/80+MHC Ⅱ+cells and F4/80+CD80+cells in lung tissue of rats was detected by flow cytometry.In control group,the alveolar structure of rats was intact,and no inflammatory cell infiltration was found.In COPD group and COPD+ov-NC group,a large number of inflammatory cells infiltrated into the lung tissue and alveolar structure was damaged.In COPD+ov-HMBOX1 group,there were fewer inflammatory cells infiltrated in lung tissue,and the damage of alveolar structure was alleviated.Compared with the control group,the mRNA and protein expression of HMBOX1 in lung tissue,the levels of IL-10 in serum and BALF,the levels of TNF-α,MIP-2 and IL-1β in serum and BALF,CD11b+F4/80+cells,F4/80+MHC Ⅱ+cells and F4/80+CD80+cells in lung tissue of rats in COPD and COPD+ov-NC groups were significantly decreased.HMBOX1 overexpression could revers the changes mentioned above in the two COPD groups.Taken together,overexpression of HMBOX1 can alleviate COPD-induced airway inflammation and lung injury,and its mechanism may be related to inhibiting infiltration and abnormal activation of macrophages in lung tissue mediated by activation of NF-κB/CCL2 signaling pathway.