OBJECTIVE: To explore the clinical manifestations and genetic etiology of a child with Progressive familial intrahepatic cholestasis (PFIC2). METHODS: From April 2024 to June 2024, a child with jaundice, hepatomegaly and abnormal liver function who was repeatedly admitted to the First Department of Pediatrics of Qinzhou Maternal and Child Health Care Hospital was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and her parents. Genomic DNA was extracted for trio-whole exome sequencing, the candidate variant was verified by Sanger sequencing and bioinformatic analysis using REVEL, BLAST/BLAT, Swiss-Model and Swiss-Pdb Viewer software. This study was approved by the Medical Ethics Committee of the Qinzhou Maternal and Child Health Care Hospital (Ethics No.: L20240116). RESULTS: The child was a 1.5-month-old female. Her main clinical manifestations included jaundice, hepatomegaly, brownish urine and earth-like stool. Laboratory examination showed increased levels of bilirubin, mainly direct bilirubin, increased aminotransferase, especially glutamic oxalacetic aminotransferase, accompanied by increased bile acid. Genetic testing revealed that the she has harbored a homozygous c.3410T>G (p.V1137G) variant of the ABCB11 gene, for which both of her parents were heterozygous carriers. The variant was unreported previously, and was predicted to be pathogenic based on REVEL. Prediction with BLAST/BLAT software showed that the amino acids were highly conserved among different species. Swiss-Pdb Viewer software predicted that the variant has resulted in changes in hydrogen bonds between amino acids. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the variant was determined to be likely pathogenic (PM1+PM2_Supporting+PM3_Supporting+PP3_Moderate). CONCLUSION The homozygous variant of the ABCB11 gene may be the genetic cause of this child. Genetic testing is helpful for confirming the diagnosis and enrich the mutational spectrum of the ABCB11 gene.
Humans ; Cholestasis, Intrahepatic/genetics* ; Female ; Infant ; ATP Binding Cassette Transporter, Subfamily B, Member 11/genetics* ; Homozygote ; Mutation

Objective To observe effect of using ambroxol to humidify of airway during mechanical ventilation to treat severe pneumonia in infants,and to explore dynamic changes of respiratory mechanics.Methods Sixty-five infants with severe pneumonia need ventilator treatment according the diagnosis criterion were divided into 2 groups by random digits table method:experimental group (33 cases) and control group (32 cases).Experimental group was used ambroxol and control group was used 0.9％ sodium chloride,each 2 ml intratracheal instillation,and then took the balloon pressurized oxygen 30 s,followed by ventilator,after 24 h.Changes of respiratory mechanics indexes were observed before and after treatment,including:mean airway resistance,lung dynamic compliance,work of breathing,airway plateau pressure.Respiratory mechanics values were recorded before and after treatment.Results After treatment for 24 h,the index in experimental group were better than those in control group.Mean airway resistance were (0.68 ± 0.04) cmH2O/ (L·s) and (0.57 ± 0.05) cmH2O/ (L·s),1 cmH2O =0.098 kPa,lung dynamic compliance were (3.17 ± 0.81) ml/kPa and (2.56 ± 0.69) ml/kPa,work of breathing were (0.54 ± 0.08) J/L and(0.41 ± 0.06) J/L,airway plateau pressure were (2.23 ± 0.58) cmH2O and (2.12 ± 0.63) cmH2O.There were significant differences (P ＜ 0.05).The mechanical ventilation time in experimental group was significantly shorter than that in control group [(64.08 ± 13.92) h vs.(79.57 ± 19.64) h] (P ＜0.05).Conclusion Airway humidification using ambroxol can better treat severe pneumonia,reduce airway resistance and improve alveolar ventilation,shorten time on the machine.