Molecular Spectrum of α- and ß-Thalassemia among Young Individuals of Marriageable Age in Guangdong Province, China.

Thalassemia is a group of genetically heterogeneous diseases characterized by hemolytic anemia. To investigate molecular characteristics of α- and ß-thalassemia among young individuals of marriageable age in Guangdong Province, 24,788 subjects with suspected thalassemia were genetically tested for α- and ß-thalassemia by Gap-PCR and reverse dot blot during 2018-2019. For suspected rare thalassemia cases, DNA sequencing was performed to identify rare and unknown thalassemia gene mutations. A total of 14,346 thalassemia carriers were detected, including 7,556 cases of α-thalassemia with 25 genotypes and 8 α-gene mutations identified, 5,860 cases of ß-thalassemia with 18 genotypes and 18 ß-gene mutations identified, and 930 cases of compound α/ß-thalassemia. Among them, the frequency of -- SEA deletion was the highest in α-thalassemia (66.01%), followed by -α 3.7 (17.98%) and -α 4.2 (8.22%), and the frequency of CD41-42 (-TCTT) mutation was the highest in ß-thalassemia (38.38%), followed by IVS-II-654 (C > T) (25.67%), -28 (A > G) (15.76%), and CD17 (10.01%). In addition, 5 rare mutations (--THAI and HKαα, CD113, -90, and CD56) were found in the study population. Our results revealed molecular epidemiological background of α- and ß-thalassemia in Guangdong Province, which can support optimization of thalassemia prevention and control strategies. We demonstrated that thalassemia is heterogeneous with significant geographical differences and population specificity.

Effectiveness of Using Mean Corpuscular Volume and Mean Corpuscular Hemoglobin for Beta-thalassemia Carrier Screening in the Guangdong Population of China.

Beta (ß)-thalassemia is one of the most common hemoglobinopathies worldwide, creating major public health problems and social burdens in many regions. Screening for ß-thalassemia carriers is crucial for controlling this condition. To investigate the effectiveness of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) for screening ß-thalassemia, retrospective data were analyzed for 6,779 ß-thalassemia carriers subjected to genetic testing following thalassemia screening in Guangdong province between January 2018 and December 2019. Prevalent mutations observed included CD41/42 (-TTCT) (38.43%), IVS-II-654 (C > T) (25.71%), -28 (A > G) (15.78%), CD17 (AAG > TAG) (10.03%), and ß E (GAG > AAG) (3.13%). In the ß 0, ß +, and HbE groups, MCV values were 63.8 ± 4.2 fL, 67.0 ± 5.5 fL, and 75.8 ± 5.6 fL, while MCH values were 20.1 ± 1.4 pg, 21.2 ± 1.9 pg, and 24.8 ± 2.0 pg, respectively. Among ß-thalassemia carriers, 85 (1.25%) and 28 (0.41%) individuals had MCV ≥ 80 fL and MCH ≥ 27 pg, respectively. Using a combination of MCV and MCH reduced the number of false negative screenings to 15 (0.22%). Therefore, evaluating both MCV and MCH is strongly recommended for screening ß-thalassemia carriers.

SET7 interacts with HDAC6 and suppresses the development of colon cancer through inactivation of HDAC6.

SET7 is the first lysine methyltransferase and plays vital roles in tumorigenesis. This study aims to seek clinical value of SET7 in colorectal cancer (CRC) patients, along with its biological impact on cell proliferation and migration. In patients with CRC, the expression of SET7 in cancer tissue was significantly lower than that in adjacent tissue, and down-regulated SET7 was closely correlated with poor prognosis. Loss-of-function and gain-of-function studies indicated that SET7 inhibited cell proliferation and migration by acting on HDAC6 substrate in colon cancer cells. Besides, the co-immunoprecipitation assay showed that SET7 and HDAC6 can interact reciprocally. The interaction effect between SET7 and HDAC6 could significantly reduce cell viability, scratch healing rate, and migrated cells in colon cancer cells. Instead of acting on each endogenous expression, the results demonstrated that the level of acetylated α-tubulin was greatly decreased in HDAC6 overexpression group, while significantly increased in SET7 overexpressed group. However, changes were partly restored in both SET7 and HDAC6-transfected group. On the contrary, the expression of acetylated α-tubulin protein was significantly increased in HDAC6 knockdown group, but higher in both HDAC6 and SET7 silencing group. These results indicated that SET7 played a role in tumor suppression via increasing levels of acetylated-α-tubulin mediated by HDAC6. In addition, the interaction effect significantly decreased the ratios of p-ERK/ERK, which indicated that it may partly suppress ERK signaling pathway. In conclusion, SET7 is a promising therapeutic target for preventing metastasis and improving prognosis in colon cancer.

Histone deacetylase 6 is overexpressed and promotes tumor growth of colon cancer through regulation of the MAPK/ERK signal pathway.

Purpose: To investigate the expression of histone deacetylase 6 (HDAC6) in colon cancer and its role in colon cancer cell growth and migration. Materials and methods: We detected the expression of HDAC6 in a colon cancer tissue chip using immunochemical staining, and analyzed the difference in HDAC6 expression between cancer and adjacent noncancerous tissues. Then, we explored the relationship between HDAC6 expression and patients' clinicopathological characteristics and prognoses. In adidition, the role of HDAC6 in colon cancer cell growth and migration, as well as its potential related signal pathway, through HDAC6 knockdown was explored. Results: The immunochemical score of HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (4.54 vs 3.08, P<0.005); similarly, as well as the rate of high HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (71.1% vs 40.9%, P<0.001). Patients showing high HDAC6 expression had a shorter overall survival time. Additionally, Cox regression analysis showed that high HDAC6 expression was an independent risk factor for poor prognosis. HDAC6 knockdown decreased cell viability, colony formation, and number of migrated colon cancer cells (HCT116 and HT29); the expression of p-MEK, p-ERK, and p-AKT was also decreased, but had no influence on MEK, ERK, and AKT expression. Conclusion: HDAC6 is highly expressed in colon cancer and associated with a poor prognosis. HDAC6 knockdown inhibits colon cancer cell growth and migration, partly through the MAPK/ERK pathway.

G6PD genotype and its associated enzymatic activity in a Chinese population.

Knowledge of the G6PD genotype and its associated enzyme activity is significant for population genetics, diagnosis of disease, and management of patients. We tested 2,872 unrelated subjects from a Hakka population in China for G6PD activity by the WHO standard method and for genotype by DHPLC and DNA sequencing. Among female heterozygotes, 78.5% had relatively normal enzyme activity. The phenotype frequency of G6PD deficiency is 0.028, and the causal allele frequency is 0.060 in females. The accuracy, sensitivity, and specificity of DHPLC are more than 98% for detecting G6PD-deficient hemizygotes, heterozygotes, and homozygotes. Measuring enzyme activity alone is not sufficient for the diagnosis of heterozygotes. A combination of enzyme activity and DNA analysis should be used.

[Chromosome abnormalities and Y chromosome microdeletions in patients with the azoospermia and cryptozoospermia].

OBJECTIVE: To study the incidence of the chromosome abnormalities and Y chromosome microdeletions in Chinese patients with azoospermia and cryptozoospermia. METHODS: Conventional chromosomal karyotyping was used to analyze the chromosome abnormalities. Genomic DNA was extracted from peripheral blood samples and multiplex polymerase chain reactions (PCR) analyses were performed using specific primers to confirm the presence or absence of Y chromosome microdeletions. A total of 997 patients with azoospermia and cryptozoospermia were enrolled in the study. RESULTS: The incidence of chromosome abnormalities in the patient with azoospermia and cryptozoospermia was 28.4%. The major abnormal karyotypes included 47,XXY, 46,XY (Y>G), 46,XX, chimera and translocations. The incidence of the Y chromosome microdeletions was 17.4%. They were mainly found in the karyotypes of 46,XY and 46,XY (Y>G). CONCLUSION: Chromosome abnormalities were the most common hereditary causes of the patients with azoospermia and cryptozoospermia. The incidence of Y chromosome microdeletion was higher in the patients with karyotype of 46,XY and 46,XY (Y>G). Therefore, detection of the AZF microdeletion in these patients is helpful to determine the etiology and avoid the unnecessary treatment and vertical transmission of the genetic defects.