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Background. Endocrinopathies are common in patients withβ-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism inβ-thalassemia major based on a meta-analysis.Methods. PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) inβ-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients withβ-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted.Results. A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM inβ-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders inβ-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias.Conclusion. High prevalence of endocrine disorders involving abnormal glucose metabolism was detected inβ-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

The fetal-to-adult hemoglobin switch is regulated in a developmental stage-specific manner and reactivation of fetal hemoglobin (HbF) has therapeutic implications for treatment of b-thalassemia and sickle cell anemia, two major global health problems. Although significant progress has been made in our understanding of the molecular mechanism of the fetal-to-adult hemoglobin switch, the mechanism of epigenetic regulation of HbF silencing remains to be fully defined. Here, we performed whole-genome bisulfite sequencing and RNA sequencing analysis of the bone marrow-derived GYPA þ erythroid cells from b-thalassemia-affected individuals with widely varying levels of HbF groups (HbF R 95th percentile or HbF % 5th percentile) to screen epigenetic modulators of HbF and phenotypic diversity of b-thalassemia. We identified an ETS2 repressor factor encoded by ERF, whose promoter hypermethylation and mRNA downregulation are associated with high HbF levels in b-thalassemia. We further observed that hypermethylation of the ERF promoter mediated by enrichment of DNMT3A leads to demethylation of g-globin genes and attenuation of binding of ERF on the HBG promoter and eventually re-activation of HbF in b-thalassemia. We demonstrated that ERF depletion markedly increased HbF production in human CD34 þ erythroid progenitor cells, HUDEP-2 cell lines, and transplanted NCG-Kit-V831M mice. ERF represses g-globin expression by directly binding to two consensus motifs regulating g-globin gene expression. Importantly, ERF depletion did not affect maturation of erythroid cells. Identification of alterations in DNA methylation of ERF as a modulator of HbF synthesis opens up therapeutic targets for b-hemoglobinopathies.

β‐thalassaemia is a prevalent hereditary haematological disease caused by mutations in the human haemoglobin β (HBB) gene. Among them, the HBB IVS2‐654 (C > T) mutation, which is in the intron, creates an aberrant splicing site. Bone marrow transplantation for curing β‐thalassaemia is limited due to the lack of matched donors. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9), as a widely used tool for gene editing, is able to target specific sequence and create double‐strand break (DSB), which can be combined with the single‐stranded oligodeoxynucleotide (ssODN) to correct mutations. In this study, according to two different strategies, the HBB IVS2‐654 mutation was seamlessly corrected in iPSCs by CRISPR/Cas9 system and ssODN. To reduce the occurrence of secondary cleavage, a more efficient strategy was adopted. The corrected iPSCs kept pluripotency and genome stability. Moreover, they could differentiate normally. Through CRISPR/Cas9 system and ssODN, our study provides improved strategies for gene correction of β‐Thalassaemia, and the expression of the HBB gene can be restored, which can be used for gene therapy in the future.

Purpose To evaluate the response and safety of an inactivated vaccine (Sinovac Life Sciences Co., Ltd., Beijing, China) for coronavirus disease 2019 (COVID-19) in liver transplant (LTx) recipients from China. Patients and Methods Thirty-five recipients post LTx from the First Affiliated Hospital of Zhejiang University School of Medicine who received inactivated vaccine from June to October 2021 were screened. Information regarding vaccine side effects and clinical data were collected. Results Thirty-five LTx recipients were enrolled, with a mean age of 46 years, and most patients were male (30, 85.71%). All the participants had a negative history of COVID-19 infection. Predictors for negative response in the recipients were interleukin-2 receptor (IL-2R) induction during LTx, shorter time post LTx and application of a derivative from mycophenolate acid (MPA). No serious adverse events were observed during the progress of vaccination or after the vaccination. Conclusion LTx recipients have a substantially partial immunological response to the inactivated vaccine for COVID-19. IL-2R induction during LTx, a shorter time post LTx and the application of a derivative from MPA seem to be predictors for a negative serological immunoglobulin G (IgG) antibody response in recipients. The findings require booster vaccination in these LTx recipients.