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Background: Erythrocyte parameter analysis is the important means for diagnosis and treatment of hematological diseases, which are essential for screening of thalassemia in southern China combined with hemoglobin electrophoresis analysis. But little is known regarding the reference intervals (RIs) in healthy pediatrics in these two areas. Methods: 95% RIs of erythrocyte parameters were calculated from 853 healthy preschoolers, aged from 1 days to <6 years, according to the C28‐A3C guidelines of the Institute of Clinical and Laboratory Standards. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using ANOVA. Concurrently, we selected 3814 thalassemia carriers as carriers group and drew receiver operating characteristic (ROC) curves to establish the optimal cut‐off values of hemoglobin electrophoresis parameters, which were used as the upper/lower limits of RIs to efficiently screen thalassemia. Results: All parameters except red blood cell (RBC) required age partitioning, confirmed by SDRage above.4. There was no need for sex partitioning on all parameters, confirmed by SDRsex below.4. The optimal cut‐off value of Hemoglobin A2 (Hb A2) in the four subgroups was <7.8% (Hb A), 2.3%–3.2%, 2.5%–3.6% and 2.6%–3.6%, respectively. Conclusion: In this study, the establishment of RIs improved the diagnostic efficiency of hematological disease (especially thalassaemia) for children in Guangxi. It provides reliable hematological references for the identification and diagnosis, treatment monitoring, and health screening of children's clinical diseases. [ABSTRACT FROM AUTHOR]

Rainwater harvesting has become an important strategy to achieve the goal of sustainable development in urban areas. The latest emerged gravity driven micro-filtration technology can effectively reduce turbidity and bacteria to a very low level but still have disadvantages of low removal of dissolved organic substances and low permeate flux. An innovative gravity driven micro-filtration technique using ceramic flat sheet membrane as filter module was established and introduced to the treatment of rainwater that was harvested from a typical official building in GuangZhou, South China. The performance of this process has been evaluated in terms of pollutants (e.g. pH, turbidity, total dissolved solids (TDS), CODcr, NH3-N, DOC,UV254, total Coliforms and E.coli) removal efficiency, and the permeate flux profiles. Results shows that the removal rates of turbidity, TDS, CODcr, NH3-N, DOC,UV254, Coliforms and E.coli were 92.2%, 91.9%, 65.5%, 42.6%, 76.9%, 61%, 96.9% and 95.5%, respectively. The GDM system can run continuously for 60 days without back washing, and the permeate flux stabilized at 22~45 L/(m2·h) under a constant water head of 20 kPa. Experimental results demonstrated that the GDM system employing a ceramic flat membrane can significantly improve the organics removal in rainwater. [ABSTRACT FROM AUTHOR]

Background: Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. Methods: A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. Results: A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240–1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. Conclusion: Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency. [ABSTRACT FROM AUTHOR]

β-Thalassemia (β-thal) is one of the most common autosomal recessive disorders worldwide. It is caused mainly by point mutations or, more rarely, deletions on the β-globin gene, leading to reduced (β+) or absent (β0) synthesis of the β chains of hemoglobin (Hb). Molecular characterization of β-thal is essential for the prevention of this disease in the population. In China, more than 46 different mutations have been found, while approximately five large deletional types of β-thal have been reported. Here we described a large deletional mutation of the β-globin gene cluster previously unreported in the Chinese population, the 3.5 kb deletion (NC_000011.10: g.5224302-5227791del3490bp) removing the β-globin gene promoter and the whole β-globin gene leading to a β0-thal phenotype. [ABSTRACT FROM AUTHOR]

β-Thalassemia (β-thal) is one of the most common genetic disorders worldwide. Molecular characterization of β-thal is essential for prevention and understanding the biology of the disease. More and more rare and novel mutations are being reported. Here, we report a novel 7 bp deletion at codons 63–65 (HBB: c.189_195delTCATGGC) in exon 2 of the β-globin gene in a family from Guangxi Province, China. This novel mutation causes a shift in the normal reading frame of the β-globin coding sequence and created a stop codon at codon 87 in exon 2, which leads to a β0-thal phenotype. [ABSTRACT FROM AUTHOR]

Background: Cri-du-chat syndrome (CdCS; OMIM#123450) is a classic contiguous gene syndrome caused by chromosome 5p terminal deletion (5p-), which characterized by a high-pitched cat-like cry, developmental delay, severe psychomotor, mental retardation, and dysmorphic features in infancy. Prenatal diagnosis of CdCS is difficult due to the non-specific ultrasound features. And reports using array analysis are rare. This study presented the first retrospective analysis of prenatal series of CdCS fetuses diagnosed by single nucleotide polymorphism (SNP) array in China. Case presentation: A total of 35,233 pregnant women were enrolled from Jan 2014 to April 2019 in our center, there are twelve 5p- cases with abnormal sonographic signs revealed by SNP array, giving an incidence of 0.034% (12/35,233). Clinical information and molecular basis included: maternal demographics, indications for invasive testing, sonographic findings and SNP array results. Among all the 5p- cases revealed, nine cases were diagnosed by both karyotyping and SNP array, three cases were detected only by SNP array. Half of our cases (6/12) had an isolated 5p terminal deletion, which sizes ranged from 9.0 Mb to 30 Mb. The other half of cases (6/12) characterized by unbalanced translocation, with sex ratio 7:5 (female: male), when combine the clinical features observed from this study and available literature, the most frequent anomaly observed in prenatal ultrasound examination of CdCS was cerebral abnormalities, accounted for 44.4% (16/36) of the existing cases. Features that are less consistent included: choroid plexus cyst (13.8%, 5/36), single umbilical artery (13.3%, 4/30), ventricular septal defect (11.1%, 4/36), hydrops fetalis (8.3%, 3/36), ascites (8.3%, 3/36), increased NT/NF (8.3%, 3/36), absent/severely hypoplastic nasal bone (5.5%, 2/36), in order. Conclusion: Prenatal findings such as cerebral abnormalities, absent/hypoplastic nasal bone, hydrops fetalis, ascites or encephalocele may act as suggestive signs of CdCS or other microdeletion/duplication syndromes. Combining typical karyotyping with chromosomal microarray analysis (CMA) is a definitive method for a precise diagnosis of CdCS and provides more accurate results in order to offer genetic counseling to families which need to deal with cryptic aberrations. [ABSTRACT FROM AUTHOR]

Background: Further knowledge about the pubertal development mode of girls with Turner syndrome (TS) who have undergone hormone replacement therapy (HRT) is beneficial to the proposal of an optimal HRT regimen. This study examined the pubertal development mode of girls with TS who underwent HRT and evaluated the characteristics of optimal sex induction therapy in girls with TS. Method: We conducted a retrospective, longitudinal study over the past two decades at The First Affiliated Hospital, Sun Yat-sen University. Patients: Seventy-one patients with TS and two groups of normal Chinese girls. Results: The total investigation time was 3.00 (2.00, 4.66) years. The interval of each stage was significantly longer (P < 0.001) in the girls with TS than that in the normal Chinese girls, except for B2–3 (P = 0.011). The uterine volumes of the girls with TS in stages B2 and 3 were greater than those of the control group (P = 0.046), whereas the uterine volume of the control group was inversely greater than that of the TS group among those who reached stages B4 and 5 (P = 0.034). During HRT, the uterine volume grew significantly from all previous stages except for breast stage 5 (B3 vs.2: Z = − 2.031; P = 0.042; B4 vs. 3: Z = − 2.273; P = 0.023; B5 vs. 4: Z = − 1.368; P = 0.171). The paired data of 27 girls with TS showed that the uterine volume (17.93 ± 9.31 ml vs. 13.75 ± 6.67 ml) and width (2.54 ± 0.66 cm vs. 2.22 ± 0.36 cm) increased significantly during artificial cycles compared with before artificial cycles (t = − 2.79 and − 2.51, P = 0.01 and 0.018). Conclusion: HRT led to normal breast development in girls with TS; half of the girls with TS in our study reached Tanner stage B5, although the uterus ultimately developed suboptimally. The girls' breasts and uteruses grew quickly at the beginning of HRT (stages B2–4). An optimal HRT regimen for girls with TS may specifically focus on Tanner stages B2–4 and artificial cycles. [ABSTRACT FROM AUTHOR]

Background: type 2 diabetes mellitus (T2DM) is a complicated disease that can affect bone health, but the change in bone biochemical markers caused by T2DM was controversial, so the aim of this study was to investigate whether there was a discrepancy in the levels of bone biochemical markers between postmenopausal women with T2DM and non-diabetic women and to explore the relationship between the level of glycosylated hemoglobin A1c (HbA1c) and bone biochemical markers in these subjects. Methods: A total of 237 type 2 diabetic postmenopausal women visiting the First Affiliated Hospital of Anhui Medical University from January 2017 to October 2018 and 93 healthy postmenopausal women were retrospectively enrolled. The differences in the levels of bone biochemical markers between patients and controls were analyzed by one-way ANOVA or chi-square test. The relationship between HbA1c and bone biochemical markers was analyzed by multivariate regression, forest plot and fitted curve. Results: Bone formation markers including N-MID osteocalcin and procollagen type 1 amino-terminal pro-peptide (PINP) were decreased in postmenopausal women with T2DM compared to controls (17.42 ± 9.50 vs 23.67 ± 7.58, p < 0.001; 48.47 ± 27.27 vs 65.86 ± 21.06, p < 0.001, respectively), but the bone resorption markers β-crossLaps (β-CTX) was no difference between the two groups (0.57 ± 0.28 vs 0.55 ± 0.21, p = 0.868). Multivariate regression showed that HbA1c was inversely associated with N-MID osteocalcin and PINP after adjusting for age, BMI, menopause's years, diabetic duration, TC, TG, HDL-c, LDL-c, creatinine, UA and eGFR. The adjusted coefficients for N-MID osteocalcin and PINP per 1% HbA1c decrease were − 0.71 (− 1.19, − 0.22) and − 1.79 (− 3.30, − 0.28), respectively. A segmentation effect was seen in the fitted curve between HbA1c and β-CTX with an inflection point at 7.4% of HbA1c, the highest quartile of β-CTX (> = 0.74 ng/ml) showed a significantly negative with HbA1c. No significant association was seen between HbA1c and other biochemical markers. Conclusions: Our study found that bone formation was inhibited in postmenopausal women with T2DM, but bone resorption was not affected, and poor glycemic control was related to lower levels of bone formation, may increase the risk of bone fracture in postmenopausal women with T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To demonstrate the performance of Hb Bart's Disease prevention in Guangxi Zhuang Autonomous Region, China. Study design: A prenatal control program for Hb Bart's disease was conducted from January 2006 to December 2012. A total of 17,555 pregnant women were screened for α-thalassemia in our prenatal screening program. Pregnancy at-risk for Hb Bart's disease was offered the choice of direct invasive testing or the non-invasive approach with serial ultrasonography. Results: A total of 1425 at-risk couples attended the prenatal diagnosis. Three hundred ninety couples were screened at our own hospital, and the remaining 1035 couples were referred from other hospitals. Two hundred and three pregnant women chose non-invasive approach, and 1122 chose invasive testing. A total of 365 fetuses were diagnosed with Hb Bart's disease. All cases were finally confirmed by fetal DNA analysis. Eighty-two cases (22.4%) were diagnosed by chorionic villous sampling and 194 (53.2%) by amniocentesis samples. The other 89 (24.4%) cases were performed by cordocentesis. All of the affected pregnancies were terminated. Conclusion: Implementation of a prevention and control program accompanying with a referral system for prenatal diagnosis is technically feasible in Guangxi Zhuang Autonomous Region, China. [Copyright &y& Elsevier]

Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) recurred in six Chinese individuals with COXPD21 but was not present in populations of other races. Our findings expanded the mutation spectrum of TARS2 and confirmed that c.470 C > G is a Chinese-specific founder mutation. The novel phenotypes, including reduced fetal movement, eye anomalies and sleep irregularities, observed in our patients enriched the clinical characteristics of COXPD21., (© 2024. The Author(s).)

Several evidence gaps exist regarding the use of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS), particularly studies conducted in real-world settings, with long-term follow-up, involving varied dosing regimens, and in comparison with daily rhGH. The study aimed to evaluate the effectiveness, safety, and adherence of once-weekly PEG-rhGH for catch-up growth in children with prepubertal ISS compared to daily rhGH. A real-world retrospective cohort study was conducted in prepubertal children with ISS in China. Children who voluntarily received once-weekly PEG-rhGH or daily rhGH were included and were followed up for 2 years. Ninety-five children were included, 47 received PEG-rhGH 0.2-0.3 mg/kg weekly and 48 received daily rhGH. Outcome measures included effectiveness in catch-up growth, adverse events, and treatment adherence. Height velocity increased significantly in both groups during rhGH therapy. In children who received PEG-rhGH treatment, height velocity was 10.59 ± 1.37 cm/year and 8.75 ± 0.86 cm/year in the first and second year, respectively, which were significantly more than those who received daily rhGH (9.80 ± 1.05 cm/year, P = 0.002, and 8.03 ± 0.89 cm/year, P < 0.001). The height standard deviation score improved at the end of the second year for all children (P < 0.001). However, children who received PEG-rhGH showed more excellent improvement than those with daily rhGH (1.65 ± 0.38 vs. 1.50 ± 0.36, P = 0.001). In children who received PEG-rhGH, lower missed doses were observed than those with daily rhGH (0.75 ± 1.06 vs. 4.4 ± 2.0, P < 0.001). No serious adverse events were observed., Conclusion: PEG-rhGH demonstrated superior effectiveness and adherence compared to daily rhGH in the treatment of children with ISS. The safety profiles were similar between the two treatments., What Is Known: • Recombinant human growth hormone (rhGH) has been used to increase adult height in children with idiopathic short stature (ISS), and its safety profile is comparable to other indications for growth hormone treatment. • The use of long-acting rhGH in children with ISS is still an area of uncertainty., What Is New: • This 2-year real-world study provides new evidence that PEGylated rhGH (PEG-rhGH) is more effective than daily rhGH in promoting catch-up growth in children with ISS. • PEG-rhGH also demonstrated superior treatment adherence compared to daily rhGH in children with ISS. • The safety profiles of PEG-rhGH and daily rhGH were found to be similar., (© 2024. The Author(s).)

Objective: To reveal the prevalence and molecular characterization of (δβ) 0 -thalassemia [(δβ) 0 -thal] and hereditary persistence of fetal hemoglobin (HPFH) in the Chinese Zhuang population., Methods: A total of 105 subjects with fetal hemoglobin (Hb F) level ≥5% from 14 204 unrelated ones were selected for the study. Multiplex ligation dependent probe amplification was firstly used to analyze dosage changes of the β-globin gene cluster for associated with (δβ) 0 -thal and HPFH mutations. The gap polymerase chain reaction was then performed to identify the deletions using the respective flanking primers. Hematologic data were recorded and correlated with the molecular findings., Results: Twenty-one (0.15%) subjects were diagnosed with Chinese G γ( A γδβ) 0 -thal. Nine (0.06%) were diagnosed with Southeast Asia HPFH (SEA-HPFH) deletion. Seventy-five (0.53%) cases remained uncharacterized. Three genotypes for Chinese G γ( A γδβ) 0 -thal and SEA-HPFH deletion were identified, respectively. The genotype-phenotype relationships were discussed., Conclusion: Our study for the first time demonstrated that (δβ) 0 and HPFH were not rare events, and molecular characterized G γ( A γδβ) 0 -thal and HFPH mutations in the Chinese Zhuang population. The findings in our study will be useful in genetic counseling and prenatal diagnostic service of β-thalassemia in this populations., (© 2017 The Authors Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Hb Q-Thailand [α74(EF3)Asp→His (α1); HBA1: c.223 G>C] is an abnormal hemoglobin (Hb), variant found mainly in China and Southeast Asian countries. The association of the α Q -Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report a hitherto undescribed condition of patients with a double heterozygosity for Hb Q-Thailand with α 0 -thalassemia (α 0 -thal) and in combination with β 0 -thalassemia (β 0 -thal) in a Chinese family. Our study will provide some clinical manifestations, laboratory diagnosis and genetic counseling for complex hemoglobinopathies.

We present the first description of Chinese individuals with the β-thalassemia (β-thal) mutation IVS-I-6 (T > C) (HBB: c.92 + 6T > C). This mutation interferes with mRNA splicing and results in reducing expression of β-globin chains that leads to a β(+)-thal phenotype. The β-globin haplotype anlaysis revealed the IVS-I-6 mutation in our case was linked with haplotype VI [- + + - - - +] and had Mediterranean characteristics.

We present the first description of a Chinese patient with a rare β-thalassemia (β-thal) mutation IVS-I-130 (HBB: c.93-1G > C). This mutation is a splice donor site mutation, and is associated with a β(0)-thal phenotype.

Objective: To analyze the status and genotypes of Hb H disease in GuangXi area., Methods: Human genomic DNA of 50 377 suspected thalassemia patients was extracted from blood, amniotic fluid and chorionic villi by beads. The deletion of α-thalassemia was detected by Gap-PCR, and the gene mutation of α or β-thalassemia was detected by PCR- RDB. Performing multiplex ligationdependent probe amplification detection and gene sequencing in α or β-globin for the specimens in question., Results: There were 1 571 Hb H disease patients in total from 2011 to 2013, and the detection rates were 2.82%, 3.54% and 3.00% respectively. The vast majority of patients had the Southeast Asian deletion (--(SEA)) on one allele. The - α³·⁷ (rightward) deletion was the most common on the other allele, followed by Hb Constant Spring (Hb CS), the -α(4.2) (leftward) deletion, Hb Westmead (Hb WS) and Hb Quong Sze (Hb QS) mutations. There were 33 Hb H disease patients which genotypes was α(CS)α/α (CS)α. Five patients had THAI deletion(--(THAI)) with deletion or point mutation of α-thalassemia. 95 patients had concomitant β-thalassemia (β-thal) heterozygosity. Tere was a novel genotype of --(SEA)/-α²¹·⁹ causing Hb H disease., Conclusion: GuangXi area had a high accidence of Hb H disease, the results reflected the genetic diversity and genetic heterogeneity of Hb H disease, the latter may also occur new mutations or combined β-thalassemia, some effective measures should be taken to strengthen screening efforts to prevent underdiagnosis of Hb H disease.