Objective:To explore the clinical phenotypes and hematological characteristics of β-thalassemia combined with α-globin gene triplet.Methods:A retrospective case analysis study was conducted, taking individuals diagnosed with thalassemia who sought for outpatient services in No 1 people′s hospital of Chenzhou affiliated to South China University from August 10, 2021, to December 31, 2023 as study objectives. Among them, there were 8 768 males and 11 707 females, aged 31.5 (23.0, 46.0) years old. Blood analysis were analyzed by hematology analyze.The hemoglobin(Hb) Hb A, HbA 2,Hb F bands were analyzed by Capillary electrophoresis method, and the genotypes of thalassemia were analyzed by high-throughput sequencing technology.Hematological parameters between different genotypes of thalassemia were analyzed using t-tests and calibrated t-tests for data analysis. Results:A total of 27 cases of beta thalassemia combined with alpha globin triplet were detected, The average hemoglobin (Hb) of 11 cases of β Codon41/42 (-CTTT)/β N combined with ααα anti 4.2 (3.7) (92±16)g/L was lower than that of β Codon41/42 (-CTTT)/β N(112±11)g/L, and the difference was statistically significant ( t=3.97, P0.05). The average Hb of 8 cases of β IVS-Ⅱ-654 (CT)/β N combined with ααα anti 4.2 (3.7)(85±21) g/L was lower than that of β IVS-Ⅱ-654 (CT)/β N(116±12) g/L, and the difference was statistically significant ( t=4.05, P0.05). Conclusion:When the mutation site is at Codon41/42 (-CTTT) or IVS-Ⅱ-654 (CT), β-thalassemia combined with alpha globin triplet can make the clinical manifestations of β-thalassemia at this site more pronounced.

Objective:To explore the clinical phenotypes and hematological characteristics of β-thalassemia combined with α-globin gene triplet.Methods:A retrospective case analysis study was conducted, taking individuals diagnosed with thalassemia who sought for outpatient services in No 1 people′s hospital of Chenzhou affiliated to South China University from August 10, 2021, to December 31, 2023 as study objectives. Among them, there were 8 768 males and 11 707 females, aged 31.5 (23.0, 46.0) years old. Blood analysis were analyzed by hematology analyze.The hemoglobin(Hb) Hb A, HbA 2,Hb F bands were analyzed by Capillary electrophoresis method, and the genotypes of thalassemia were analyzed by high-throughput sequencing technology.Hematological parameters between different genotypes of thalassemia were analyzed using t-tests and calibrated t-tests for data analysis. Results:A total of 27 cases of beta thalassemia combined with alpha globin triplet were detected, The average hemoglobin (Hb) of 11 cases of β Codon41/42 (-CTTT)/β N combined with ααα anti 4.2 (3.7) (92±16)g/L was lower than that of β Codon41/42 (-CTTT)/β N(112±11)g/L, and the difference was statistically significant ( t=3.97, P0.05). The average Hb of 8 cases of β IVS-Ⅱ-654 (CT)/β N combined with ααα anti 4.2 (3.7)(85±21) g/L was lower than that of β IVS-Ⅱ-654 (CT)/β N(116±12) g/L, and the difference was statistically significant ( t=4.05, P0.05). Conclusion:When the mutation site is at Codon41/42 (-CTTT) or IVS-Ⅱ-654 (CT), β-thalassemia combined with alpha globin triplet can make the clinical manifestations of β-thalassemia at this site more pronounced.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors not only have good lipid-lowering effects, but also have pleiotropic effects such as improving cardiovascular outcomes, relieving anti-inflammation, relieving oxidative stress and improving vascular endothelium. In recent years, the continuous development of PCSK9 inhibitors provides new ideas for the treatment of cardiovascular diseases. This article reviewed the pleiotropic mechanisms of PCSK9 inhibitors, especially on vascular endothelial function.

Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes (T2DM). Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge. Neutral sphingophospholipase 2 (Smpd3) is downregulated in jawbone-derived bone marrow mesenchymal stem cells (BMSCs) from T2DM patients. Here, we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles. The combined loading of Smpd3-overexpressing stem cell-derived exosomes (Exos-Smpd3) and nanosilver ions (Ns) to construct a hydrogel delivery system (Exos-Smpd3@Ns) promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment, ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro. Mechanistically, Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations. These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations, providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.
Exosomes ; Animals ; Bone Regeneration/drug effects* ; Dogs ; Mesenchymal Stem Cells ; Humans ; Blood Glucose ; Cell Differentiation ; Osteogenesis/drug effects* ; Diabetes Mellitus, Type 2/therapy* ; Diabetes Mellitus, Experimental ; Cells, Cultured ; Hydrogels ; Male

Hypertension heightens the risk of cardiovascular and renal complications in individuals with type 2 diabetes mellitus. Optimal blood pressure (BP) management is crucial for preventing these complications. This review consolidates evidence from clinical trials and major BP management guidelines to shed light on key aspects of hypertension management in diabetes. It addresses BP thresholds to initiate antihypertensive treatment, optimal BP control targets, recommended first-line antihypertensive edications, and BP monitoring plan for the prevention of chronic complications in type 2 diabetes.

Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes(T2DM).Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge.Neutral sphingophospholipase 2(Smpd3)is downregulated in jawbone-derived bone marrow mesenchymal stem cells(BMSCs)from T2DM patients.Here,we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles.The combined loading of Smpd3-overexpressing stem cell-derived exosomes(Exos-Smpd3)and nanosilver ions(Ns)to construct a hydrogel delivery system(Exos-Smpd3@Ns)promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment,ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro.Mechanistically,Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations.These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations,providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.

Objective:To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention.Methods:A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing.Results:A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-Ⅰ-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+ (Aγδβ)0 had typical microcytic hypochromic and β-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50(G>A)heterozygotes of β-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2.Conclusion:Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.
Pregnancy ; Female ; Humans ; DNA Copy Number Variations ; Chromosome Aberrations ; Chromosome Disorders/genetics* ; Aneuploidy ; Fetus

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

OBJECTIVE: To assess the diagnostic value of whole exome sequencing (WES) for patients with intellectual disability (ID) or global developmental delay (GDD). METHODS: 134 individuals with ID or GDD who presented at Chenzhou First People's Hospital between May 2018 and December 2021 were selected as the study subjects. WES was carried out on peripheral blood samples of the patients and their parents, and candidate variants were verified by Sanger sequencing, copy number variation sequencing (CNV-seq) and co-segregation analysis. The pathogenicity of the variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: A total of 46 pathogenic single nucleotide variants (SNVs) and small insertion/deletion (InDel) variants, 11 pathogenic genomic copy number variants (CNVs), and 1 uniparental diploidy (UPD) were detected, which yielded an overall detection rate of 43.28% (58/134). The 46 pathogenic SNV/InDel have involved 62 mutation sites in 40 genes, among which MECP2 was the most frequent (n = 4). The 11 pathogenic CNVs have included 10 deletions and 1 duplication, which have ranged from 0.76 to 15.02 Mb. A loss of heterozygosity (LOH) region of approximately 15.62 Mb was detected in 15q11.2q12 region in a patient, which was validated as paternal UPD based on the result of trio-WES. The patient was ultimately diagnosed as Angelman syndrome. CONCLUSION WES can detect not only SNV/InDel, but also CNV and LOH. By integrating family data, WES can accurately determine the origin of the variants and provide a useful tool for uncovering the genetic etiology of patients with ID or GDD.
Humans ; Exome Sequencing ; Intellectual Disability/genetics* ; DNA Copy Number Variations ; Mutation ; Loss of Heterozygosity