[Clinical and genetic studies of a family with hereditary angioedema].

Objective: To diagnose a large family of patients with hereditary angioedema, and to study its inheritance pattern and gene locus. Methods: A retrospective analysis was carried out from August 2021 to February 2022 in a proband (female, 48 years old) and 12 family members who underwent medical history collection and laboratory examinations in the Department of Otorhinolaryngology and Head and Neck Surgery, the Second Hospital of Shanxi Medical University. The clinical data of members and non-affected members [including 7 males and 5 females, aged 12-78 (median 24) years old], were drawn a family map while confirming the diagnosis. Whole exome sequencing technology was used to detect the genetic sequence of the proband and to verify its family members to map the genetic pedigree of the mutation. Results: The inheritance pattern of the family was autosomal dominant, and 8 members of the family were diagnosed with hereditary angioedema by laboratory examination, including 7 cases of type I and 1 case of type Ⅱ. Whole exome sequencing analysis was performed on 2 patients with 2 phenotypes, and it was found that they both carried the same pathogenic mutation locus, which was c.890-2A>G. The family members were verified by next-generation sequencing, and it was found that all members of the family who had a history of edema contained this mutation site, while the younger brother of the proband who had no history of edema did not have this mutation. Conclusion: Both type Ⅰ and type Ⅱ phenotypes are present in this hereditary angioedema family, and the mutation of SERPING1 gene c.890-2A>G causes the onset of each patient in this family.

[Association of ICOS and CD28 single nucleotide polymorphisms with pulmonary tuberculosis susceptibility].

Objective: To investigate the association of inducible co-stimulator (ICOS) and CD28 gene polymorphisms with pulmonary tuberculosis susceptibility. Methods: In this case-control study, from Mar 2015 to Sep 2016, peripheral venous blood of 100 pulmonary tuberculosis patients (pulmonary tuberculosis group) in the Jintan People's Hospital of Changzhou and 100 community physical examination volunteers (health control group) were collected. A total of 56 single nucleotide polymorphisms (SNP) in ICOS and CD28 sequences were selected and SNP genotype and allele frequency were analyzed using the next-generation sequencing technology. Association of these SNP with pulmonary tuberculosis susceptibility was investigated using linkage disequilibrium (LD) analysis and genetic models. Results: Among these 56 SNP, 23 SNP with Hardy-Weinberg equilibrium P (HWE-P) value<0.001 or minimum allele frequency<0.05 were kicked out. The frequencies of T allele and TT genotype of ICOS gene SNP locus (rs55663036), and GG genotype of CD28 gene locus (rs45620941) in tuberculosis group were significantly higher than those in healthy control group (all P<0.05). There was a strong linkage imbalance between rs45620941 at CD28 locus and rs56262258 (r(2)=0.757). Conclusion: The polymorphisms of rs55663036 of ICOS gene and rs45620941 of CD28 gene are significantly associated with the risk of pulmonary tuberculosis.

Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.

Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients. A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1. In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%. Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85). No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus. The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor. Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P < 0.05). The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses. Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B. These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.

[Association of PD-1, TIM-3 and TREM-1 single nucleotide polymorphisms with pulmonary tuberculosis susceptibility].

Objective: To investigate the association of programmed cell death 1(PD-1), T cell immunoglobulin mucin 3 (TIM-3) and triggering receptor expressed on myeloid cells-1 (TREM-1) genes polymorphisms with pulmonary tuberculosis susceptibility. Methods: In this case-control study, peripheral venous blood of 100 pulmonary tuberculosis patients (pulmonary tuberculosis group) in the Jintan People's Hospital of Changzhou and of community physical examination volunteers (health control group) was collected from Mar 2015 to Sep 2016. A total of 66 single nucleotide polymorphisms (SNP) in PD-1, TIM-3 and TREM1 sequences were selected and SNP genotype and allele frequency were analyzed using the next-generation sequencing technology. Association of these SNP with pulmonary tuberculosis susceptibility was investigated using linkage disequilibrium (LD) analysis and genetic models. Results: Among these 66 SNP, 24 SNP with Hardy-Weinberg equilibrium P (HWE-P) value <0.001 or minimum allele frequency (MAF) <0.05 were kicked out. The remaining 42 SNP were analyzed with LD analysis and genetic models. There was no significant difference in genotype frequencies between pulmonary tuberculosis group and health control group (all P>0.05). Five SNP (rs41435650, rs28539662, rs13023138, rs75565781, rs36084323) in PD-1 were identified in a significant haplotype (TACGC) between pulmonary tuberculosis group and health control group (P=0.014). Among these haplotypes, strong LD was observed between rs28539662 and rs75565781 (r(2)=0.871), as well as rs36084323 (r(2)=0.864). Rs75565781 showed highest correlation with rs36084323 (r(2)=0.966). Conclusion: These SNP in PD-1, TIM-3 and TREM-1 genes are not associated with the susceptibility of pulmonary tuberculosis.

[Clinical observation on aplastic anemia treated with Chinese herbal medicine combined with cord blood infusion].

Forty-eight cases of aplastic anemia (AA) were divided into two groups: the treated group (30 cases) were treated with Chinese herbal medicine and cord blood infusion, the control group (18 cases) were treated with cord blood infusion solely. The total effective rate in the treated group and the control group was 93.3% and 72.2% respectively, the difference between two groups was significant (P < 0.05). Cultures of bone marrow granulocyte-macrophage colony forming units (CFU-GM) in vitro were measured also in both groups. Results showed that 3 months after treatment, the elevation of CFU-GM in the two groups were similar to each other, but after 6 months' treatment, level of CFU-GM in treated group elevated persistently and steadily, while in control group, it decreased slightly as compared with level at 3 months' treatment, suggesting the recovery of bone marrow hematopoiesis of treated group was more stable than that of control group. This study indicated that combined treatment of Chinese herbal medicine and cord blood infusion is an effective method in treating AA.