[A preliminary study on immune adjunctive therapy for multidrug-resistant Mycobacterium tuberculosis infection in animal models].

OBJECTIVE: To investigate the effect of adjunctive therapy by immune agents in mice infected with multidrug-resistant tuberculosis (MDR-TB). METHODS: Sixty-eight adult male BALB/c mice were infected with multidrug-resistant Mycobacterium tuberculosis (MTB) by aerosol route. The mice were randomly divided into a control group, an immuno-treatment group, a drug treatment group and a combination treatment group (drug plus immuno-treatment). In each treatment group, 16 mice were treated at day 21 after infection, and another 4 mice were sacrificed at day 21 after infection (treatment for 0 week) as the blank control group. In the treatment group, 4 mice were sacrificed in turn at the day after treatment for 4, 8, 16 and 20 weeks. Lung and spleen mass index at the day after treatment for 8, 16 and 20 weeks, lung and spleen live bacterial count in each period, serum IFN-γ and IL-10 levels at the day after treatment for 8 weeks were measured. Comparisons of analyzed parameters among groups were performed with the one way ANOVA test, and comparisons of parameters between 2 groups were performed with SNK and Games-Howell test. RESULTS: The lung mass index in the immuno-treatment group (0.66 ± 0.09)%, drug group (0.60 ± 0.07)% and combination therapy group (0.57 ± 0.05)% at the day after treatment for 8 weeks were significantly lower than that of the control group (0.81 ± 0.09)%, (F = 7.364, P < 0.01). Spleen CFU of immuno-treatment group at 16 and 20 weeks [(3.11 ± 0.14) lg CFU and (3.15 ± 0.18) lg CFU] were significantly lower than those of the control group [(3.77 ± 0.35) lg CFU and (4.31 ± 0.06)] (F values were 446.424 and 2107.689, P < 0.01). Spleen tissues of the drug group and the combination therapy group were sterile from 4 weeks. The serum IFN-γ levels of immuno-treatment group, drug group and combination therapy were (5.3 ± 1.9) ng/L, (1.3 ± 0.5) ng/L and (0.9 ± 1.3) ng/L, respectively, being significantly lower than that of the control group (10.3 ± 2.1) ng/L (F = 32.128, P < 0.01). The lung and spleen mass index, lung and spleen CFU, serum IFN-γ and IL-10 between medication group and combination therapy showed no significant differences. CONCLUSIONS: Immuno-treatment could mitigate lung tissue inflammation, reduce the number of MTB in mouse spleen tissues and decrease serum IFN-γ levels in the MDR-TB mouse model. However immuno-treatment failed to reduce the number of MTB in lung tissues. There was no adjunctive effect of immuno treatment for MDR-TB mice in reducing the number of MTB and mitigating inflammation.

Prenatal diagnosis of Cri-du-Chat syndrome with concomitant distal trisomy 10q syndrome in one fetus with ultrasound anomalies.

OBJECTIVE: The aim of this work was to characterize the genetic abnormalities and prenatal diagnosis indications in one fetus with Cri-du-Chat syndrome with codependent 10q24.2-q26.3 duplication in prenatal screening. MATERIALS AND METHODS: A 31-year-old woman had a second trimester serum screening that indicated the fetus was at low risk. During this pregnancy, the woman underwent amniocentesis at 18+4 weeks' gestation because of adverse fertility history and nuchal fold thickening. Cytogenetic analysis and next-generation sequencing analysis were simultaneously performed to provide genetic analysis of fetal amniotic fluid. According to abnormal results, parental chromosome karyotype of peripheral blood was performed to analysis. RESULTS: CNV-seq detected a 14.00 Mb deletion at 5p15.33-p15.2 and a 34.06 Mb duplication at 10q24.2-q26.3 in the fetus. Cytogenetic analysis of the fetus revealed a karyotype of 46, XY, der(5) t(5;10) (p15.2;q26.3). The karyotype of pregnant women was 46,XX,t(5;10) (p15.2;q24.2). The pregnancy was subsequently terminated after sufficient informed consent. CONCLUSION: This is the first study that reports prenatal diagnosis of a Cri-du-Chat syndrome with concomitant 10 q24.2-q26.3 duplication. Adverse pregnancy history has to be as an important indicator for prenatal diagnosis, and the genetic factors of abnormal pregnancy should be identified before next pregnancy. Nuchal fold thickening is closely related to fetal abnormalities. Combined with ultrasonography, the use of CNV-seq will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies.