Critically ill children with SARS-COV-2 Omicron infection at a national children medical center, Guangdong, China.

BACKGROUND: SARS-CoV-2 infection is described as asymptomatic, mild, or moderate disease in most children. SARS-CoV-2 infection related death in children and adolescents is rare according to the current reports. COVID-19 cases increased significantly in China during the omicron surge, clinical data regarding pediatric critical patients infected with the omicron variant is limited. In this study, we aim to provide an overview of the clinical characteristics and outcomes of critically ill children admitted to a national children's medical center in Guangdong Province, China, during the outbreak of the omicron variant infection. METHODS: We conducted a retrospective study from November 25, 2022, to February 8, 2023, which included 63 critically ill children, under the age of 18, diagnosed with SARS-CoV-2 infection. The patients were referred from medical institutions of Guangdong province. The medical records of these patients were analyzed and summarized. RESULTS: The median age of patients was 2 years (Interquartile Range, IQR: 1.0-8.0), sex-ratio (male/female) was 1.52. 12 (19%) patients (age ≥ 3 years) were vaccinated. The median length of hospital stay was 14 days (IQR: 6.5-23) in 63 cases, and duration of fever was 5 days (IQR: 3-8.5), pediatric intensive care unit (PICU) stay was 8 days (IQR 4.0-14.0) in 57 cases. 30 (48%) cases had clear contact history with family members who were infected with SARS-CoV-2. Three children who tested positive for SARS-CoV-2 infection did not show any abnormalities on chest imaging examination. Out of the total patients, 33 (52%) had a bacterial co-infection, with Staphylococcus aureus being the most commonly detected bacterial pathogen. Our cohort exhibited respiratory and nervous system involvement as the primary features. Furthermore, fifty (79%) patients required mechanical ventilation, with a median duration of 7 days (IQR 3.75-13.0). Among these patients, 35 (56%) developed respiratory failure, 16 (25%) patients experienced a deteriorating progression of symptoms and ultimately succumbed to the illness, septic shock was the most common condition among these patients (15 cases), followed by multiple organ failure in 12 cases, and encephalopathy identified in 7 cases. CONCLUSION: We present a case series of critically ill children infected with the SARS-CoV-2 omicron variant. While there is evidence suggesting that Omicron may cause less severe symptoms, it is important to continue striving for measures that can minimize the pathogenic impact of SARS-CoV-2 infection in children.

Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

BACKGROUND: Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli by the repetitive recruitment and derecruitment of alveolar units. This study aims to investigate the potential role and mechanism of fibroblast growth factor 21 (FGF21), a metabolic regulator secreted by the liver, in VILI development. METHODS: Serum FGF21 concentrations were determined in patients undergoing mechanical ventilation during general anesthesia and in a mouse VILI model. Lung injury was compared between FGF21-knockout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect. RESULTS: Serum FGF21 levels in patients and mice with VILI were significantly higher than in those without VILI. Additionally, the increment of serum FGF21 in anesthesia patients was positively correlated with the duration of ventilation. VILI was aggravated in FGF21-KO mice compared with WT mice. Conversely, the administration of FGF21 alleviated VILI in both mouse and cell models. FGF21 reduced Caspase-1 activity, suppressed the mRNA levels of Nlrp3, Asc, Il-1ß, Il-18, Hmgb1 and Nf-κb, and decreased the protein levels of NLRP3, ASC, IL-1ß, IL-18, HMGB1 and the cleaved form of GSDMD. CONCLUSIONS: Our findings reveal that endogenous FGF21 signaling is triggered in response to VILI, which protects against VILI by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These results suggest that boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for the treatment of VILI during anesthesia or critical care.

Preparation and tensile conductivity of carbon nanotube/polyurethane nanofiber conductive films based on the centrifugal spinning method.

Flexible conductive thin films have recently become a research area of focus in both academia and industry. In this study, a method of preparing nanofiber conductive films by centrifugal spinning is proposed. Polyurethane (PU) nanofiber films were prepared by centrifugal spinning as the flexible substrate film, and carbon nanotubes (CNTs) were used as the conducting medium, to obtain CNTs/PU nanofiber conductive films with good conductivity and elasticity. The effects of different CNT concentrations on the properties of the nanofiber films were investigated. It was found that the conductivity of the nanofiber conductive films was optimal when an impregnation concentration of 9% CNTs was used in the stretching process. Cyclic tensile resistance tests showed that the nanofiber conductive films have good durability and repeatability. Physical and structural property analysis of the CNT/PU conductive films indicate that the adsorption of the CNTs on the PU surface was successful and the CNTs were evenly dispersed on the surface of the matrix. Moreover, the CNTs improved the thermal stability of the PU membrane. The CNT/PU conductive films were pasted onto a human finger joint, wrist joint, and Adam's apple to test the detection of movement. The results showed that finger bending, wrist bending, and laryngeal prominence movement all caused a change in resistance of the conductive film, with an approximately linear curve. The results indicate that the CNT/PU nanofiber conductive film developed in this study can be used to test the motion of human joints.

UGT1A1 mutation association with increased bilirubin levels and severity of unconjugated hyperbilirubinemia in ABO incompatible newborns of China.

BACKGROUND: Neonatal hyperbilirubinemia causing jaundice is common in East Asian population. Uridine diphosphate glucuronosyltransferase isoenzyme (UGT1A1) glucuronidates bilirubin and converts the toxic form of bilirubin to its nontoxic form. METHOD: A retrospective study was conducted to review clinical information of ABO hemolysis neonates (ABO HDN) admitted to the Department of Neonatology, referred for neonatal hyperbilirubinemia, in a large general hospital of southern China from 2011 to 2017. Variation status of UGT1A1 was determined by direct sequencing or genotype assays. RESULT: Sixty-nine ABO HDNs were included into the final analysis. UGT1A1 c.211 G > A mutation (UGT1A1*6, p.Arg71Gly, rs4148323) was significantly associated with the increased bilirubin level in ABO HDNs, after adjusted by age, sex and feeding method (P = 0.019 for TBIL, P = 0.02 for IBIL). Moreover, heterozygous and/or homozygous UGT1A1 mutations in the coding sequence region were significantly associated with the increased risk of developing hazardous hyperbilirubinemia (as defined by TSB > 427 umol/L) as compared those with a normal UGT1A1 genotype (ORadj = 9.16, 95%CI 1.99-42.08, P = 0.002) in the study cohort. CONCLUSION: UGT1A1 variant in coding region is actively involved in the pathogenesis of ABO hemolysis related neonatal hyperbilirubinemia. Genetic assessment of UGT1A1 may be useful for clinical diagnosis of neonatal unconjugated hyperbilirubinemia.

Co-inheritance of G6PD deficiency and 211 G to a variation of UGT1A1 in neonates with hyperbilirubinemia in eastern Guangdong.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may manifest as neonatal hyperbilirubinemia, is the most prevalent erythrocytic enzyme-related disease in the world. OBJECTIVE: To investigate the association between neonatal hyperbilirubinemia and co-inheritance of G6PD deficiency and 211 G to A variation of UGT1A1 in Chaozhou city of eastern Guangdong province, the effects of G6PD deficiency and UGT1A1 gene variant on the bilirubin level were determined in neonates with hyperbilirubinemia. METHOD: The activity of G6PD was assayed by an auto-bioanalyzer. PCR and flow-through hybridization were used to detect 14 common G6PD mutations in G6PD deficient neonates. 211 G to A variation of UGT1A1 was determined by PCR and sequencing. The data of neonatal bilirubin was collected and analyzed retrospectively. RESULTS: Seventy four cases of the 882 hyperbilirubinemia neonates were G6PD deficiency (8.39%) while 12 cases of the 585 non-hyperbilirubinemia neonates (control group) were G6PD deficiency (2.05%). The rate of G6PD deficiency in the hyperbilirubinemia group was higher than that of the control group. Moreover, the peak bilirubinin of the G6PD-deficient group of hyperbilirubinemia neonates was 334.43 ± 79.27 µmol/L, higher than that of the normal G6PD group of hyperbilirubinemia neonates (300.30 ± 68.62 µmol/L). The most common genotypes of G6PD deficiency were c.1376G > T and c.1388G > A, and the peak bilirubin of neonates with these two variants were 312.60 ± 71.81 µmol/L and 367.88 ± 75.79 µmol/L, respectively. The bilirubin level of c.1388G > A was significantly higher than that of c.1376G > T. Among the 74 hyperbilirubinemia neonates with G6PD deficiency, 6 cases were 211 G to A homozygous mutation (bilirubin levels 369.55 ± 84.51 µmol/L), 27 cases were 211 G to A heterozygous mutation (bilirubin levels 341.50 ± 63.21 µmol/L), and 41 cases were wild genotypes (bilirubin levels 324.63 ± 57.52 µmol/L). CONCLUSION: The rate of G6PD deficiency in hyperbilirubinemia neonates was significantly higher than that of the non-hyperbilirubinemia neonates in Chaozhou. For the hyperbilirubinemia group, neonates with G6PD deficiency had a higher bilirubin level compared to those with normal G6PD. For hyperbilirubinemia neonates with G6PD deficiency, there was a declining trend of bilirubin levels among 211 G to A homozygous mutation, heterozygous mutation, and wild genotype, but there was no significance statistically among the three groups.

[Phenotype and Genotype Analysis in Two Pedigrees with Hereditary Coagulation Factor â ª Deficiency].

OBJECTIVE: To analyze the phenotype and genotype in two pedigrees with hereditary coagulation factor Ⅺ (FⅪ) deficiency, and investigate the molecular mechanisms of FⅪ deficiency. METHODS: Two patients with hereditary coagulation FⅪ deficiency were admitted to Chaozhou Central Hospital in Nov 2014 and Jan 2018. The prothrombin time (PT), activated partial thromboplastin time (APTT), FⅪ activity (FⅪ∶C) and FⅪ antigen (FⅪ∶Ag) were tested for phenotypic diagnosis. All the exons and exon-intron boundaries of FⅪ gene of proband were analyzed by PCR and sequencing. The family members were tested for the mutant site of proband. Then the mRNA of FⅪ in the proband was analyzed with RT-PCR. RESULTS: The proband-1 was a 7-year-old boy, PT was 10.7 s and APTT was 97.4 s (reference range: 9-12.8 s; 24-40 s), FⅪ∶C (0.6%) and FⅪ∶Ag<1% (reference range: 65%-150%; 72.1%-122.3%). The proband-2 was a 30-year-old female, and showed the PT (11.7 s), APTT (71.3 s), FⅪ∶C (0.7%) and FⅪ∶Ag<1%. FⅧ∶C, FⅨ∶C and FⅫ∶C of two proband were within the normal range. DNA sequencing showed that the proband-1 had a combined mutation of c.326-1G>A and c.1107C>A (p.Tyr351X) in exon 10. His grandmother, mother and brother had a heterozygous splicing mutation of c.326-1G>A, his grandmother and father had a homozygous mutation of c.1107C>A. FXI mRNA was undetected in the proband-1. The proband-2 had a homozygous mutation of c.841C>T (p.Gln263X) in exon 8, and this mutation was also found in her father, mother, daughter and son. CONCLUSION: The c.326-1G>A, c.1107C>A(p.Tyr351X) and c.841C>T (p.Gln263X) might be the molecular pathogenesis for two probands with hereditary coagulation factor Ⅺ deficiency.

The analysis of clinical and laboratory data: a large outbreak of dengue fever in Chaozhou, Guangdong province, China.

A large-scale dengue fever (DF) outbreak occurred in Chaozhou, Guangdong province, China 2015. In our study, 528 dengue-positive patient samples were collected for clinical and laboratory data analysis. 491 cases (93.0%) were primary dengue fever (PDF), 22 cases (4.2%) were dengue hemorrhagic fever (DHF) and 15 cases (2.8%) were diagnosed with severe dengue fever (SDF). All cases were infected by dengue virus serotype 2 (DENV-2), and the isolated strains belonged to cosmopolitan genotype, which were grouped closely with Malaysia strains from 2010 to 2014. Moreover, the study showed that laboratory indices have significantly difference in PDF, DHF and SDF patients. A comprehensive analysis of these data could assist and guide the clinical diagnosis for DF, which has an important significance for the control of dengue virus infection.

Facile Preparation of Metal-Organic Framework (MIL-125)/Chitosan Beads for Adsorption of Pb(II) from Aqueous Solutions.

In this study, novel composite titanium-based metal-organic framework (MOF) beads were synthesized from titanium based metal organic framework MIL-125 and chitosan (CS) and used to remove Pb(II) from wastewater. The MIL-125-CS beads were prepared by combining the titanium-based MIL-125 MOF and chitosan using a template-free solvothermal approach under ambient conditions. The surface and elemental properties of these beads were analyzed using scanning electron microscopy, Fourier transform infrared and X-ray photoelectron spectroscopies, as well as thermal gravimetric analysis. Moreover, a series of experiments designed to determine the influences of factors such as initial Pb(II) concentration, pH, reaction time and adsorption temperature was conducted. Notably, it was found that the adsorption of Pb(II) onto the MIL-125-CS beads reached equilibrium in 180 min to a level of 407.50 mg/g at ambient temperature. In addition, kinetic and equilibrium experiments provided data that were fit to the Langmuir isotherm model and pseudo-second-order kinetics. Furthermore, reusability tests showed that MIL-125-CS retained 85% of its Pb(II)-removal capacity after five reuse cycles. All in all, we believe that the developed MIL-125-CS beads are a promising adsorbent material for the remediation of environmental water polluted by heavy metal ions.

Prevalence of HIV and malaria: a cross-sectional study on Bioko Island, Equatorial Guinea.

Malaria and HIV are two of the most severe public health problems in Africa. However, epidemiological data on Bioko Island is scarce. To investigate the prevalence of malaria and HIV infections and assess association of malaria and HIV infections and possible confounding factors, we performed a cross-sectional survey of people of malaria-endemic Bioko Island, Equatorial Guinea. A cross-sectional study of 1 526 subjects was carried out to determine the prevalence of malaria and HIV infection in Malabo region hospital on Bioko Island. Questionnaires were administered and venous blood samples were drawn for malaria parasites and HIV detection. The prevalence of participants infected with malaria and HIV in this area were 13.8% and 6.6% respectively. The average prevalence of co-infection for malaria and HIV was 0.92%. HIV-infection was significantly associated with the age and gender. Malaria infections were significantly associated with the age. This study showed that the prevalence of HIV and malaria on Bioko Island was higher than expected, although the co-infection prevalence of malaria and HIV was low. The results also indicated that malaria and HIV infections lead to more public health risk to youngsters and women.

Clinical validation of a novel real-time human papillomavirus assay for simultaneous detection of 14 high-risk HPV type and genotyping HPV type 16 and 18 in China.

In the present study, we describe the laboratory workflow and the clinical validation of a novel multiplex real-time PCR-based HPV assay in China. The cross-sectional validation analysis showed that this assay worked well for detection of 14 HR-HPV types and identification of HPV 16 and 18 in a single sensitive assay that is suitable for both clinical usage and high-throughput cervical screening purposes. We predict that this accurate, high-throughput and low-cost HPV assay can greatly reduce the heavy economic burden of HPV detection in China.

Pharmacokinetic study of ofloxacin enantiomers in Pagrosomus major by chiral HPLC.

(S)-(-)-Ofloxacin and (R)-(+)-ofloxacin concentrations in the plasma of Pagrosomus major after drug treatment were detected by chiral high-performance liquid chromatography, and various pharmacokinetic parameters were calculated from these data. The elimination half-life of (S)-(-)-ofloxacin was significantly shorter than that of the (R)-(+) enantiomer. (S)-(-)-Ofloxacin also had a significantly lower maximum plasma concentration, area under the concentration-time curve from zero to infinity, and mean residence time than (R)-(+)-ofloxacin. However, the apparent volume of distribution and total body clearance of (S)-(-)-ofloxacin were greater than those of (R)-(+)-ofloxacin. The ratio of the (S)-(-)- to (R)-(+)-ofloxacin plasma concentration was always <1.0. Together, these data suggest that (S)-(-)-ofloxacin was preferentially excreted and (R)-(+)-ofloxacin was preferentially absorbed. Although the difference in pharmacokinetic parameters was small, the metabolic behavior of the ofloxacin enantiomers in P. major was enantioselective.

Molecular Epidemiological Characterization and Health Burden of Thalassemias in the Chaoshan Region, People's Republic of China.

Thalassemia is one of the most prevalent inherited disease in southern China. However, there have been only a few epidemiological studies of thalassemia in the Chaoshan region of Guangdong Province, People's Republic of China (PRC). A total of 6231 unrelated subjects in two main geographical cities of the Chaoshan region was analyzed for thalassemia. Seven hundred and thirty-six cases of suspected thalassemia carriers with microcytosis [mean corpuscular volume (MCV) <82.0 fL] were found by complete blood cell (CBC) count, and were tested by reverse dot-blot gene chip to reveal a total of 331 mutant chromosomes, including 278 α-thalassemia (α-thal) alleles and 53 ß-thalassemia (ß-thal) alleles. The most common α-thal mutations were the Southeast Asian (- -(SEA)), followed by the -α(3.7) (rightward) and -α(4.2) (leftward) deletions. The two most common ß-thal mutations were HBB: c.316-197C>T and HBB: c.126_129delCTTT, accounting for 69.81% of the ß-thal defects in the studied individuals. In addition, a rare mutation, Cap +1 (A>C) (HBB: c.-50A>C) was described for the first time in the Chaoshan region. Our results gave a heterozygote frequency of 5.31% for common α- and ß-thal in the Chaoshan region, and also indicated a higher prevalence of thalassemia with a heterozygote frequency of 6.29% in Chaozhou, followed by Shantou (3.37%). This study provided a detailed prevalence and molecular characterization of thalassemia in the Chaoshan region, and will be valuable for developing a strategy for prevention of thalassemia and reducing excessive health care costs in this area.

Synthesis and Characterization of Magnetic Molecularly Imprinted Polymer for the Enrichment of Ofloxacin Enantiomers in Fish Samples.

A new method for the isolation and enrichment of ofloxacin enantiomers from fish samples was developed using magnetic molecularly imprinted polymers (MMIPs). These polymers can be easily collected and rapidly separated using an external magnetic field, and also exhibit a high specific recognition for ofloxacin enantiomers. The preparation of amino-functionalized MMIPs was carried out via suspension polymerization and a ring-opening reaction using rac-ofloxacin as a template, ethylenediamine as an active group, glycidyl methacrylate and methyl methacrylate as functional monomers, divinylbenzene as a cross-linker, and Fe3O4 nanoparticles as magnetic cores. The characteristics of the MMIPs were assessed using transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) measurements. Furthermore, the adsorption properties were determined using Langmuir and Freundlich isotherm models. The conditions for use of these MMIPs as magnetic solid-phase extraction (MSPE) sorbents, including pH, adsorption time, desorption time, and eluent, were investigated in detail. An extraction method using MMIPs coupled with high performance liquid chromatography (HPLC) was developed for the determination of ofloxacin enantiomers in fish samples. The limits of quantitation (LOQ) for the developed method were 0.059 and 0.067 µg∙mL(-1) for levofloxacin and dextrofloxacin, respectively. The recovery of ofloxacin enantiomers ranged from 79.2% ± 5.6% to 84.4% ± 4.6% and ofloxacin enantiomers had good linear relationships within the concentration range of 0.25-5.0 µg∙mL(-1) (R² > 0.999). The obtained results demonstrate that MSPE-HPLC is a promising approach for preconcentration, purification, and simultaneous separation of ofloxacin enantiomers in biomatrix samples.

Fibroblast growth factor 10 protects neuron against oxygen-glucose deprivation injury through inducing heme oxygenase-1.

Fibroblast growth factors (FGFs) are a family of structurally related heparin-binding proteins with diverse biological functions. FGFs participate in mitogenesis, angiogenesis, cell proliferation, development, differentiation and cell migration. Here, we investigated the potential effect of FGF10, a member of FGFs, on neuron survival in oxygen-glucose deprivation (OGD) model. In primary cultured mouse cortical neurons upon OGD, FGF10 treatment (100 and 1000 ng/ml) attenuated the decrease of cell viability and rescued the LDH release. Tuj-1 immunocytochemistry assay showed that FGF10 promoted neuronal survival. Apoptosis assay with Annexin V+PI by flow cytometry demonstrated that FGF10 treatment reduced apoptotic cell proportion. Moreover, immunoblotting showed that FGF10 alleviated the cleaved caspase-3 upregulation caused by OGD. FGF10 treatment also depressed the OGD-induced increase of caspase-3, -8 and -9 activities. At last, we found FGF10 triggered heme oxygenase-1 (HO-1) protein expression rather than hypoxia-inducible factor-1 (HIF-1), AMP-activated protein kinase (AMPK) signaling and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Knockdown of HO-1 by siRNA partly abolished the neuroprotection of FGF10 in OGD model. In summary, our observations provide the first evidence for the neuroprotective function of FGF10 against ischemic neuronal injury and suggest that FGF10 may be a promising agent for treatment of ischemic stroke.

Dopaminergic facilitation of GABAergic transmission in layer III of rat medial entorhinal cortex.

The medial entorhinal cortex (MEC) receives a dense dopaminergic innervation and expresses dopamine receptors. However, little is known about the effect of dopamine on GABAergic transmission in this region of the brain. In this study, we recorded GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) by using whole-cell patch-clamp technique. Application of dopamine at 10 µM and 100 µM significantly increased the frequency and amplitude of sIPSCs. This effect of dopamine is primarily mediated by acting at D1-like dopamine receptors, but not D2-like and α1 adrenergic receptors, since dopamine-induced increased in frequency and amplitude of the sIPSCs was completely blocked by D1-like, but not D2-like or α1 adrenergic, receptor antagonist. However, application of dopamine did not affect the frequency and amplitude of the mIPSCs, implying that the effect of dopamine on the GABAergic transmission is action potential-dependent. Together, these findings reveal an indirect mechanism by which activation of D1-like receptors could inhibit the excitability of layer III pyramidal neurons in the MEC.

Molecular Epidemiological Investigation of Thalassemia in the Chengdu Region, Sichuan Province, Southwest China.

Thalassemia is the most common inherited disease in southern China. However, this disorder is usually ignored by the health system in the Sichuan Province due to the lack of epidemiological data. To provide basic epidemiological data for thalassemia screening, genetic counseling, and prenatal diagnosis (PND) in the Chengdu region, a total of 3262 healthy subjects were assessed by complete blood count (CBC), reverse dot-blot gene chip, gap-polymerase chain reaction (gap-PCR), and PCR-DNA sequencing. A frequency of heterozygous thalassemia of 3.43% (112/3262) was found, of which 2.21% (72/3262) patients carried α-thalassemia (α-thal), 1.19% (39/3262) ß-thalassemia (ß-thal) and 0.3% (1/3262) hereditary persistence of fetal hemoglobin (Hb) (HPFH)/δß-thalassemia (δß-thal). Four types of α-thal mutations were found, the most prevalent being - -(SEA) (68.06%), followed by -α(3.7) (rightward deletion, 25.0%), Hb Quong Sze (Hb QS; HBA2: c.377 T > C) (4.17%), and -α(4.2) (leftward deletion, 2.78%). The seven ß-thal mutations included: codons 41/42 (-TTCT), HBB: c.126_129delCTTT (13/39, 33.33%); codon 17 (A > T), HBB: c.52 A > T (11/39, 28.95%); IVS-II-654 (C > T), HBB: c.316-197 C > T (9/39, 23.68%); -28 (A > G), HBB: c.-78 A > G (3/39, 7.69%); -29 (A > G), HBB: c.-79 A > G (1/39, 2.56%); codons 27/28 (+C), HBB: c.84_85insC (1/39, 2.56%), and the rare IVS-II-850 (G > T), HBB: c.316-1 G > T (1/39, 2.56%). Only one case of the Southeast Asian HPFH deletion was found. This is the first detailed molecular epidemiological survey of thalassemia in the Chengdu region, Sichuan Province, People's Republic of China (PRC).

Development and clinical validation of a novel detection kit for α-thalassemia in southern Chinese.

Objective: This study aimed to develop and assess a novel reverse dot blot assay for the simultaneous detection of 10 types of α-thalassemia alleles in the Chinese population, including six common variants of-SEA, -α3.7, -α4.2, αCS, αQS, and αWS, and four rare variants of αααanti-4.2, αααanti-3.7, --FIL deletion and--THAI deletion. Methods: The novel thalassemia gene assay utilized a two-tier multiplex polymerase chain reaction amplification system and one round of hybridization. Genomic DNA samples were sourced from three hospitals in southern China. Each clinically validated DNA sample was re-evaluated using the new multiplex polymerase chain reaction/reverse dot blot assay Ⅲ (M-PCR/RDB Ⅲ). Results: The study analyzed a total of 1,148 unrelated participants, consisting of 810 thalassemia patients and 338 healthy control subjects. Valid hybridization results were obtained for 1,147 samples, with one case (thalassemia carrier) being excluded from the study due to the poor quality of DNA. All 1,147 samples, including those with α heterozygous thalassemia, α homozygous thalassemia, α compound heterozygous thalassemia, and control subjects were accurately genotyped, showing 100% concordance with the reference assays. Conclusion: The novel M-PCR/RDB Ⅲ assay proved to be simple, rapid, and precise, indicating its potential for genetic screening and clinical diagnosis of both common and rare α-thalassemia variants in Chinese populations.

Genotype and phenotype analysis of α-thalassemia fusion gene in southern China.

OBJECTIVE: The α-globin fusion gene between the HBA2 and HBAP1 genes, is clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combined with α0 -thalassemia (α0 -thal). In this study, we evaluate the red blood cell parameters of α-thalassemia fusion gene in southern China. METHOD: Study samples suspected of α-thalassemia fusion gene were collected and confirmed by PCR-sequencing from one medical lab center in southern China. Their genotypes and phenotypes were analyzed. RESULTS: A total of 266 cases of α-thalassemia fusion gene were confirmed in our lab from 2017 to 2023, most of them were from Hainan province (169 cases) and Huadu district of Guangzhou (21 cases), the nationality of 143 cases from Hainan was identified, with 71.3% (102/143) being from the Li minority. The Hb, MCV, MCH for αα/(αα)fusion in adult males were 143.5±11.83g/L, 81.51±4.39 fl, and 26.26±1.29 pg, respectively; and in females, they were 126.69±12.89 g/L, 80.10±4.05 fl, 25.8±2.04 pg, respectively. All 12 cases (αα) Fusion/ --SEA showed anemia with decreased Hb, MCV and MCH. CONCLUSION: The carriers of α-globin fusion gene heterozygotes are clinically silent and exhibit an α+ phenotype. Individuals with (αα)Fusion/--SEA show apparent anemia. This α-globin fusion gene is relatively common in southern China, specifically among the Li minority of Hainan province. Therefore, it should be taken into account for genetic counseling purposes.