OBJECTIVE: To explore the genetic etiology of a child with microcephaly-cortical blind syndrome. METHODS: Clinical data of the child was collected. The child and her parents were subjected to whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing. RESULTS: WES revealed that the child has harbored compound heterozygous variants c.1051C>T and c.609delA of the DIAPH1 gene. CONCLUSION The compound heterozygous variation c.1051C>T (p.R351X) and c.609delA (p.E203Efs*19) of the DIAPH1 gene probably underlay the microcephaly-cortical blindness syndrome in this child.
Blindness/genetics* ; Child ; Female ; Formins/genetics* ; Genetic Testing ; Humans ; Microcephaly/genetics* ; Mutation ; Pedigree ; Exome Sequencing

Stenotrophomonas maltophilia is a gram-negative bacillus which widely exists in natural and hospital environment, and it is also one of the common opportunistic pathogens in clinical settings. The virulence and pathogenicity of Stenotrophomonas maltophilia are weak, however, due to resistance to a variety of antibacterial drugs, it can cause bloodstream infections or pneumonia in immunocompromised or critically ill patients, leading to poor prognosis. Moreover, the inherent drug resistance and increasing acquired drug resistance may make the treatment of the first line antibiotics, like trimethoprim-sulfamethoxazole or quinolone ineffective. Therefore, it is important to understand the drug resistance mechanism and the main countermeasures for it. In this article, the research progress on drug resistance mechanism and treatment for Stenotrophomonas maltophilia are reviewed.

Objective:To investigate the effects of turning head to the opposite insertion side on catheter heterotopia and degree of comfort among PICC catheter patients.Methods:The inpatients with PICC catheter in Hepatological Surgery of Changzhi People′s Hospital from January 2018 to December 2019 were collected as research object, patients from January to December 2018 was assignment to the control group, patients from January to December 2018 was assignment to the experimental group, with 174 cases in each group. They were catheterized with turning head to the opposite insertion side and turning head to the PICC insertion side, respectively. The incidence of catheter heterotopia, complications as well as degree of comfort during the placement of PICC were compared between the two groups.Results:The successful cases of one-time delivery tube and occurred catheter heterotopia were 97.1% (169/174) and 1.2% (2/174) in the experimental group, the index mentioned above were 91.4% (159/174) and 7.5% (13/174) in the control group, the differences between the two groups were statistically significant ( χ2=5.30, 8.43, both P<0.05). The results from survival curve analysis demonstrated that the occurred of catheter-related venous thrombosis and catheter-related bloodstream infections were significantly lower in the experimental group compared to the control group ( χ2=15.23, 8.76, both P<0.05). The score of comfort during the placement of PICC was (15.00 ± 2.19) in the experimental group, which was significantly lower than (16.86 ± 1.88) points in the control group ( t=8.49, P<0.05). Conclusions:Adopting turning head to the opposite insertion side method can improve the success rate of one-time delivery tube, reduce the incidence of catheter heterotopia and reduce the discomfort of patients during PICC catheterization.

Objective:To analyze the antigenicity and genetic characteristics of two strains of Eurasian avian H1N1 swine influenza virus (EAS-H1N1) isolated from 2 human cases found in Gansu province to provide scientific reference for disease prevention and control.Methods:Two cases of human infection with EAS-H1N1 discovered in Gansu province since February 2021 were analyzed for antigenicity and genome comparison, and their genome characteristics were analyzed using software such as Mega7.0.Results:Two human infections with EAS-H1N1 had related environmental exposure history. Two strains were obtained: A/Gansu-Xifeng/1143/2021 and A/Gansu-Xifeng/1194/2021. The two strains of HA, NA genes were all from the Eurasian avian H1N1 swine influenza virus, and are closely related to the human infection EAS-H1N1 virus in Hebei and Tianjin and the EAS-H1N1 virus isolated from the mink in Shandong; the HA receptor binding sites of 2 strains E190D and D225E mutations occurred in all spots, and there were no H274Y and N294S mutations in NA protein.Conclusions:Some important molecular mutations occurred in the genome of people infected with EAS-H1N1 virus in Gansu province, which may lead to increased virulence and potential human-to-human transmission. Strengthening the research and analysis of EAS-H1N1 gene characteristics will help to monitor the mutation and mutation of the virus at the molecular level and scientifically prevent and control the epidemic.

OBJECTIVE: To explore the genetic basis for a patient featuring Rotor syndrome. METHODS: Clinical data of the patient was collected. Whole exome sequencing (WES) based on high-throughput sequencing technology was carried out. Long-interspersed element-1 (LINE-1) insertion in intron 5 of the SLCO1B3 gene was detected by using tri-primer single tube PCR. RESULTS: WES revealed that the patient has carried homozygous c.1738C>T nonsense variants of the SLCO1B1 gene. He was also found to harbor a homozygous insertion of LINE-1 in intron 5 of the SLCO1B3 gene, which has caused skipping of exon 5 or exons 5 to 7 and introduced a stop codon in the SLCO1B3 transcript. CONCLUSION The homozygous c.1738C>T variant of the SLCO1B1 gene and homozygous insertion of LINE-1 in intron 5 of the SLCO1B3 gene probably underlay the Rotor syndrome in this patient.
Exons/genetics* ; Homozygote ; Humans ; Hyperbilirubinemia, Hereditary ; Introns/genetics* ; Liver-Specific Organic Anion Transporter 1 ; Male ; Whole Exome Sequencing

Objective:To investigate the effects of pre-existing antibody on seroconversion rate after influenza vaccination.Methods:This study recruited 1 900 healthy volunteers to receive influenza split vaccines in Xinjiang Uygur Autonomous region and Yunnan Province from September 2009 to October 2018. Hemagglutinin agglutination inhibition assay was used to detect the titers of specific antibodies in blood samples collected before vaccination and 28 d after vaccination and the effects of pre-existing antibody on the seroconversion to different influenza vaccine components were analyzed.Results:Trend analysis showed that with the increasing titer of pre-existing antibody, the seroconversion rates to A/H1N1, A/H3N2, B/Victoria and B/Yamagata vaccine components were gradually decreased (χ 2=121.76, P<0.001; χ 2=67.58, P<0.001; χ 2=45.25, P<0.001; χ 2=54.55, P<0.001). After adjusting for factors such as region, gender and age, multivariate logistic regression showed that pre-existing antibody titer equal to or higher than 40 was an independent factor that affected the seroconversion to A/H1N1, A/H3N2 and B/Victoria vaccine components, and the adjusted OR (95%CI) values were 2.50(2.00-3.13)、1.64(1.35-2.00) and 2.50(1.79-3.45), respectively. Conclusions:The seroconversion rate to each vaccine component was negatively correlated with the pre-existing antibody titer. The factor that pre-existing antibody titer equal to or higher than 40 was detrimental to the seroconversion to A/H1N1, A/H3N2 and B/Victoria vaccine components, but had no significant influence on B/Yamagata seroconversion.

Objective:To understand the agglutination characteristics of different subtypes of avian influenza viruses, we selected erythrocytes from different sources to find suitable erythrocytes for influenza environmental sample detection.Methods:Different subtypes of avian influenza viruses, which were isolated from environmental sample between 2009 and 2016 in China, were selected to do hemagglutination assay using 5 animal erythrocytes (chicken, turkey, guinea pig, horse, and sheep). Flow cytometry was used to detect expression level and type of sialic acid receptors of different erythrocytes, and the characteristics of the receptor binding domain (RBD) of the viral hemagglutinin protein were analyzed by amino acid sequence.Results:In this study, a total of 28 strains of avian influenza virus including 14 subtypes were detected. The result showed that all viruses could agglutinate with turkey and guinea pig erythrocytes and the rest three erythrocytes were unable to produce agglutination with some viruses; among them, one H9N2 virus (A/environment/Anhui/43762/2015) did not agglutinate with chicken erythrocytes, one H1N1 virus (A/environment/Shandong/76972/2014) and two H9N2 viruses (A/environment/Chongqing/79449/2014 and A/environment/Anhui/43762/2015) did not agglutinate with horse erythrocytes, two viruses of H9N2 (A/environment/Chongqing/79449/2014 and A/environment/Anhui/43762/2015) and two viruses of H13N8 (A/environment/Qinghai Lake/166/2012 and A/environment/Qinghai Lake/13/2012) did not agglutinate with sheep erythrocytes. The result of flow cytometry showed that two sialic acid receptors, α-2, 3 and α-2, 6, were detected on the surface of erythrocytes of turkey, chicken and guinea pig, but the expression ratios of the two receptors were different. Only the expression of α-2, 3 sialic acid receptors was detected in horse and sheep erythrocytes. Sequence analysis suggested that amino acid substitution in key regions of viral hemagglutinin protein RBD may be an important factor affecting the binding properties of different erythrocytes.Conclusions:Our result suggested that turkey and guinea pig erythrocytes are the most sensitive in the hemagglutination test. Receptor expression and type of erythrocytes from different sources can significantly affect the agglutination reaction of different subtypes of avian influenza virus, and the amino acid changes in key regions of RBD can also affect the result of agglutination reaction.

OBJECTIVE: To explore the genetic basis for a pedigree affected with KBG syndrome. METHODS: Clinical data of three patients from the pedigree (the proband, his mother and sister) was collected. Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing (WES). Suspected variant was verified by Sanger sequencing. RESULTS: The proband was found to harbor a heterozygous c.4398_4401del (p.Glu1467AsnfsTer63) frameshift variant of the ANKRD11 gene by WES. Sanger sequencing confirmed that the same variant was also present in his mother and sister, but not in his father. CONCLUSION The c.4398_4401de (p.Glu1467AsnfsTer63) variation of the ANKRD11 gene probably underlies the KBG syndrome in this pedigree.

Objective:The antigenic and genetic characteristics of influenza A(H1N1)pdm09 virus isolated from the mainland of China during the 2018-2019 influenza surveillance year were analyzed.Methods:Two thousand nine hundred and fifty-eight influenza A(H1N1)pdm09 virus strains in the 2018-2019 influenza surveillance year were analyzed by hemagglutination inhibition test. The hemagglutinin(HA) gene of 279 influenza A(H1N1)pdm09 virus strains was sequenced and analyzed. The representative strains of the dominant clades were performed for antigenic characteristics using post-vaccination human antisera.Results:Two thousand eight hundred and sixty-one (97%, 2 861/2 958) viruses characterized were antigenically similar to A/Michigan/45/2015. All HA gene of the sequenced viruses belonged to 6B.1 clade, and 269(96%, 269/279) viruses belonged to 6B.1A subclade. Compared with the vaccine virus, it had the common amino acid substitutions of S74R, S164T and I295V in the HA protein. There were several small groups with common amino acid substitutions in the 6B.1A subclade, and 51% sequenced viruses had S183P amino acid substitution in this subclade. The result of antigenic analysis using post-vaccination human antiserums showed that most of the representative strains were well inhibited by the sera.Conclusions:The antigenicity of influenza A(H1N1)pdm09 viruses in the mainland of China in 2018-2019 influenza surveillance year matched well with the corresponding vaccine strain, but the HA gene had genetically diverse characteristic.

Objective: We planned to evaluate the effectiveness of moving epidemic method (MEM) in calculating influenza epidemic threshold of 7 climatic zones in China mainland. Methods: The positive rate of influenza virus was obtained from the National Influenza Surveillance Network System from 2010/2011 to 2017/2018. We divided the 31 provinces into 7 climatic zones according to previous literatures and applied MEM to calculate the influenza epidemic threshold of 2018/2019 influenza season for these climatic zones. Sensitivity, specificity, positive predictive value and negative predictive value were calculated to evaluate the effectiveness of MEM. Results: Pre-epidemic threshold (the positive rate of influenza virus) varied from 9.66% (temperate zone) to 16.36% (subtropical zone) for 2018/2019 influenza season. The gap between pre-epidemic and post-epidemic thresholds was less than 5% except for plateau zone. The sensitivity was 86.16% (95CI:66.81%-98.23%), the specificity was 94.92% (95CI: 91.13%-98.41%), the positive predictive value was 89.87% (95%CI: 84.39%-94.38%), the negative predictive value was 92.96% (95%CI: 84.46%-99.17%). Conclusion Overall, moving epidemic Method performs well in calculating influenza epidemic threshold in China, much better than the previous study.