Esophagogastric variceal bleeding is a common complication and the leading cause of death in advanced liver cirrhosis， and endoscopic variceal ligation （EVL） and endoscopic cyanoacrylate injection （ECI） are commonly used treatment strategies. Thrombocytopenia is one of the most common hematological complications in liver cirrhosis， and patients with severe thrombocytopenia have the potential risk of bleeding， which may affect treatment decision-making by clinicians and endoscopists. This article reviews the evolution of guidelines and clinical research advances regarding EVL/ECI in China and globally， in order to provide a basis for decision making among clinicians.

Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

OBJECTIVE: To explore the clinical and genetic characteristics of two children with developmental delay. METHODS: Two children who had presented at the Children's Hospital Affiliated to Shandong University on August 18, 2021 were enrolled as the study subjects. Clinical and laboratory examination, chromosomal karyotyping and high-throughput sequencing were carried out for both children. RESULTS: Both children had a 46,XX karyotype. High-throughput sequencing showed that they have respectively carried a c.489delG (p.Q165Rfs*14) and a c.1157_1158delAT (p.Y386Cfs*22) frameshifting variant of the CTCF gene, both had a de novo origin and were unreported previously. CONCLUSION The CTCF gene variants probably underlay the development delay in the two children. Above discovery has enriched the mutational spectrum of the CTCF gene and has important implications for revealing the genotype-phenotype correlation for similar patients.
Child ; Humans ; Developmental Disabilities/genetics* ; High-Throughput Nucleotide Sequencing ; Intellectual Disability/genetics* ; Karyotyping ; Mutation

OBJECTIVE: To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old. METHODS: A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa. RESULTS: A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%). CONCLUSIONS The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.
Humans ; Infant ; Child ; Prospective Studies ; Bacterial Infections ; C-Reactive Protein ; Hospitals ; Interleukin-6 ; Procalcitonin

OBJECTIVE: To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Citrullinemia type I (CTLN1). METHODS: Three children diagnosed at the Children's Hospital Affiliated to Shandong University from 2017 to 2020 were selected as the study subjects. Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Next generation sequencing (NGS) was carried out to detect pathological variants of the probands. Sanger sequencing was used for validating the candidate variant among the pedigrees. RESULTS: The probands have respectively carried compound heterozygous variants of c.207_209delGGA and c.1168G>A, c.349G>A and c.364-1G>A, c.470G>A and c.970G>A of the ASS1 gene, which were respectively inherited from their parents. CONCLUSION The newly discovered c.207_209delGGA and c.364-1G>A variants have enriched the mutational spectrum of the ASS1 gene. And the mutation spectrum of Chinese CTLN1 patients is heterogeneous.
Child ; Humans ; Argininosuccinate Synthase/genetics* ; Citrullinemia/genetics* ; East Asian People ; Mutation ; Pedigree

OBJECTIVE: To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome. METHODS: An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS). RESULTS: The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother. CONCLUSION The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.
Humans ; Infant ; Male ; alpha-Thalassemia/diagnosis* ; Ataxia Telangiectasia Mutated Proteins/genetics* ; East Asian People ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/diagnosis* ; Pedigree ; X-linked Nuclear Protein/genetics*

This article retrospectively analyzed the clinical data of 8 patients with vesicovaginal fistula after radiotherapy for cervical cancer admitted in our hospital from January 2015 to October 2021. All of them underwent cystostomy under local anesthesia. A single J tube of bilateral ureters was retained under cystoscope, and the single J tube was introduced into the fistula bag through the cystostomy opening. All patients wore diapers for a long time before operation, and used urine pads 0-2 pieces/day after operation. QOL score was 5.3±0.5 points before operation, and 2.5±0.5 points after operation. The patient's body odor basically disappeared. The vesicovaginal fistula can be repaired by surgery, but for patients who cannot be operated or failed repeatedly due to various reasons, a single J tube of bilateral ureters can be drawn out through the cystostomy opening, which can improve the quality of life of patients through minor trauma.

OBJECTIVE: To explore the genetic basis for a neonate featuring developmental delay. METHODS: Clinical examination and laboratory tests were carried out for the patient. Peripheral venous blood samples of the proband and his parents were extracted and subjected to target capture next generation sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The patient, a four-month-old male, has presented with developmental delay and weakness of limbs. Genetic testing revealed that he had harbored a novel c.1432C>T variant of the TNPO3 gene, which was inherited from his mother. The nonsense variant has resulted in premature termination of protein translation and was predicted to be pathogenic by bioinformatics analysis. CONCLUSION The heterozygous c.1432C>T variant of the TNPO3 gene probably underlay the limb-girdle muscular dystrophies form 1F in this patient. Above finding has enriched the variation spectrum of the TNPO3 gene.
Genetic Testing ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Muscular Dystrophies, Limb-Girdle/genetics* ; Mutation ; Phenotype ; beta Karyopherins/genetics*

OBJECTIVE: To carry out clinical and genetic analysis for an infant manifesting perianal lesions, diarrhea and multiple intestinal perforations. METHODS: Genomic DNA of the infant was extracted and subjected to targeted capture exome sequencing. Candidate variants were verified by Sanger sequencing of his family members. RESULTS: The patient was found to harbor c.301C>T and c.188+1G>A compound heterozygous variants of the IL10RA gene, which has suggested the diagnosis of IL10RA-related very early-onset inflammatory bowel disease (VEOIBD). CONCLUSION The patient was diagnosed with IL10RA-related VEOIBD. The newly discovered c.188+1G>A variant has enriched the spectrum of IL10RA gene variations.
Genetic Testing ; Humans ; Infant ; Inflammatory Bowel Diseases/pathology* ; Mutation ; Exome Sequencing

OBJECTIVE: To analyze the clinical and genetic characteristics of a boy featuring unexplained developmental delay, malnutrition and distinct facial appearance. METHODS: Physical examination was carried out for the child. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA and trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The patient had facial dysmorphism including nasal alae aplasia, scalp defect and teeth deformities, in addition with recurrent diarrhea due to pancreatic exocrine insufficiency. DNA sequencing revealed that he has harbored compound heterozygous variants of the UBR1 gene, namely c.3167C>G (p.S1056X) and c.1911+14C>G, which were inherited from his father and mother, respectively. Database search has suggested the c.3167C>G to be a novel nonsense variant and c.1911+14C>G a known splicing variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were predicted to be pathogenic and likely pathogenic, respectively. CONCLUSION The child was diagnosed with Johanson-Blizzard syndrome due to the compound heterozygous variants of the UBR1 gene. Above finding has enriched the mutational spectrum of the UBR1 gene and provided a basis for genetic counseling for this family.
Child ; Humans ; Male ; Ectodermal Dysplasia/genetics* ; Pancreatic Diseases/genetics* ; Ubiquitin-Protein Ligases/genetics*