BACKGROUND AND OBJECTIVE

Nutritional anemia has become a national public health problem, particularly among female workers, who are a high-risk group. Dates can be formulated into functional food to treat anemia in this group. This study aimed to examine the effectiveness of date biscuits formulated with 10% (A1) and 20% (A2) substitutes in treating anemia among female workers in Makassar, Indonesia.

Experimental research design using a Randomized Controlled Trial (RCT) with a pre-test post-test randomized group was used. The population of this study were female workers in Makassar City, with a total sample of 61 participants. The study randomly divided the sample into three groups: the intervention group that received formula A1 date biscuits (10%), the intervention group that received formula A2 date biscuits (20%), and the control group that did not receive any intervention. The researchers administered 20 grams of biscuits for 60 days. Hemoglobin levels were measured twice, at baseline and after the intervention. The study further performed a bivariate test by comparing the hemoglobin examination results before and after the intervention using the paired t-test, and analyzed differences between groups using the ANOVA test. The significance value was set at pRESULTS

The results showed that A1 date biscuits reduced the case of anemia by 23.8%, from 38.1% to 14.3%. Meanwhile, provision of A2 date biscuits reduced the case of anemia by 13.7%, from 36.4% to 22.7%.

The provision of A1 date biscuits is more effective than A2 for women with anemia. Date biscuits should be specifically provided to workers or women with anemia as they are less effective for those with normal hemoglobin levels. To further increase hemoglobin levels, female workers should also be given additional nutrient- rich foods

OBJECTIVE: To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia. METHODS: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People's Hospital of Yangjiang (Ethics No: 20240001). RESULTS: For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A2, whilst another had significantly decreased Hb A and Hb A2, in addition with the appearance of a Hb H band. The content of Hb Bart's in four neonates was ≥ 0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c.2delT, HBA2: c.1A>G, HBA2: c.1A>T, and HBA1: c.2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c.427T>C (Hb CS) and HBA2: c.2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c.1A>G and Southeast Asian type deletion. CONCLUSION Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c.1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.
Humans ; Phenotype ; Codon, Initiator/genetics* ; Female ; Male ; Retrospective Studies ; alpha-Globins/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobin A/genetics* ; Adult ; Mutation

OBJECTIVE: To analyze the hematological characteristics of patients with three common deletional β-thalassemia and concomitant α-thalassemia in Huizhou, Guangdong province. METHODS: A total of 1 335 subjects of childbearing age with hemoglobin F (Hb F) ≥ 5% at the Huizhou First Maternal and Child Health Care Hospital between June 2014 and December 2023 were enrolled as our study cohort. The hematological parameters were determined by blood cell counters and automatic capillary electrophoresis, while liquid phase chip and gap-PCR were employed for the detection of routine thalassemias and the three common deletional β-thalassemia, respectively. The hematological characteristics of patients with the deletional β-thalassemia were analyzed. This study was reviewed and approved by the Ethics Committee of Huizhou First Maternal and Child Health Care Hospital [Ethics No. 20231107(B2)]. RESULTS: A total of 384 cases of the three common deletional β-thalassemia were identified, including 184 cases of Chinese Gγ⁺(Aγδβ)⁰, 191 cases of Southeast Asian hereditary persistence of fetal hemoglobin (SEA-HPFH), and nine cases of Chinese Taiwanese, for a total detection rate of 28.76%. Patients who did not meet the established criteria were excluded from the study, leaving 372 cases. All of which presented with hypochromic microcytic anemia and significantly elevated Hb F. Except for normal or decreasing of Hb A2 levels in patients with Chinese Gγ⁺(Aγδβ)⁰, the levels of Hb A2 in patients with the other two deletional β-thalassemia were increased with different degrees. Differential comparison results showed that significant differences were observed in Hb A2 and Hb F values among the groups of the three common deletional β-thalassemia heterozygotes (P < 0.05). According to the type of gene variation, 180 patients with Chinese Gγ⁺(Aγδβ)⁰ heterozygotes were divided into three groups, including αα/αα, Chinese Gγ⁺(Aγδβ)⁰/β^N (149), -α/αα, Chinese Gγ⁺(Aγδβ)⁰/β^N (14), and --/αα, Chinese Gγ⁺(Aγδβ)⁰/β^N (17). Similarly, 179 patients with SEA-HPFH heterozygotes were divided into three groups, including αα/αα, SEA-HPFH/β^N (150), -α/αα, SEA-HPFH/β^N (12), and --/αα, SEA-HPFH/β^N (17). Differential comparison results showed that the Hb F levels of the Chinese Gγ⁺(Aγδβ)⁰ combined with α⁰-thalassemia group were significantly lower than those of the Chinese Gγ⁺(Aγδβ)⁰ combined with α⁺-thalassemia group and the control group (P < 0.05). The mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and Hb F values of the SEA-HPFH combined with α⁰-thalassemia group were significantly lower than those of the SEA-HPFH combined with α⁺-thalassemia group and the control group (P < 0.05). CONCLUSION The above research results can not only enhance the ability of clinicians to identify deletional β-thalassemia and concomitant α-thal, improve the level of genetic counseling, but also provide data support for the development of deletional β-thalassemia prevention and control programme and the development of prenatal and postnatal care.
Humans ; beta-Thalassemia/complications* ; alpha-Thalassemia/complications* ; Female ; China ; Male ; Adult ; Fetal Hemoglobin/genetics* ; Adolescent ; Young Adult

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

BACKGROUND: Studies on the impact of blood glucose indicators on metabolism remain relatively scarce. The aim of this study was to investigate the associations between blood glucose indicators and metabolic disorders in China. METHODS: Data were from the Thyroid disorders, Iodine status and Diabetes Epidemiological survey (TIDE survey), which randomly selected 31 cities from 31 provinces in the Chinese mainland. A total of 68,383 participants without preexisting diabetes and have complete data on blood glucose, lipids, and blood pressure were included in the analysis. The diabetic population was divided into seven groups based on different types of elevated blood glucose levels, including fasting plasma glucose (FPG), postprandial glucose (PPG), and hemoglobin A1c (HbA1c): FPG ≥7 mmol/L; PPG ≥11.1 mmol/L; HbA1c ≥6.5%; FPG ≥7 mmol/L and PPG ≥11.1 mmol/L; FPG ≥7 mmol/L and HbA1c ≥6.5%; PPG ≥11.1 mmol/L and HbA1c ≥6.5%; FPG ≥7 mmol/L, PPG ≥11.1 mmol/L, and HbA1c ≥6.5%. The effects of each blood glucose indicator on metabolism were investigated separately. Weighted calculation was applied during the analysis, with the weighting coefficient based on the number of people corresponding to the population characteristics of each sample in the 2010 Chinese Census. A logistic regression model with restricted cubic splines (RCS) was employed to characterize the nonlinear associations of age and body mass index (BMI) with the risk of diabetes subtypes defined by distinct blood glucose indicators elevations, as well as the relationships between different blood glucose indicators (FPG, PPG, HbA1c) and the risk of metabolic disorders such as hypertension, hypertriglyceridemia, hypercholesterolemia, high low-density lipoprotein cholesterol (high LDL-C) and low high-density lipoprotein cholesterol (low HDL-C). RESULTS: Among individuals with diabetes, elevated PPG alone was the most common abnormality, affecting 26.96% (1382/5127) of the population. Among the seven groups with only one elevated blood glucose indicator, individuals with elevated PPG alone exhibited the highest mean levels of triglycerides (TG) at 2.11 mmol/L (95% confidence interval [CI]: 1.97-2.25 mmol/L, P = 0.004), total cholesterol (TC) at 5.26 mmol/L (95% CI: 5.18-5.33 mmol/L, P <0.001), and low-density lipoprotein cholesterol (LDL-C) at 3.12 mmol/L, (95% CI: 3.06-3.19 mmol/L, P = 0.001). Individuals with elevated PPG alone showed a high prevalence of hypertension (806/1382, 58.32%), hypertriglyceridemia (676/1382, 48.91%), hypercholesterolemia (694/1382, 50.22%), High LDL-C (525/1382, 37.94%), and Low HDL-C (364/1382, 26.34%). The association of age and BMI with the risk of diabetes revealed that the older the patient, the steeper the RCS curve for the odds ratio (OR) of diabetes with elevated PPG alone (age = 60, OR = 2.79, 95% CI [2.49-3.12], P <0.01). Similarly, as BMI increased, the RCS curve for the OR of diabetes with elevated HbA1c alone also steepened (BMI = 35, OR = 3.75, 95% CI [3.23-4.35], P <0.001). Additionally, the RCS yielded a positive association between blood glucose indicators and metabolic diseases risk. In individuals with diabetes, RCS for both the ORs of metabolic diseases (hypertension, hypertriglyceridemia, hypercholesterolemia, high LDL-C, low HDL-C) and the levels of metabolic indicators (TG, TC, LDL-C, HDL-C) revealed some inflection points within the ranges of FPG 5-6 mmol/L, PPG 6-8 mmol/L, and HbA1c 5.5-6.0%. CONCLUSIONS PPG is more closely related to metabolic disorders than FPG and HbA1c in people with diabetes. For patients with diabetes and metabolic disorders, it may be necessary to monitor blood glucose fluctuations within specific ranges (FPG 5-6 mmol/L, PPG 6-8 mmol/L, and HbA1c 5.5-6.0%).
Humans ; Female ; Cross-Sectional Studies ; Male ; Blood Glucose/metabolism* ; Middle Aged ; Glycated Hemoglobin/metabolism* ; Adult ; Metabolic Diseases/epidemiology* ; Aged ; China ; Diabetes Mellitus/blood* ; East Asian People

Diabetes mellitus (DM) is a major global health issue, with glycated hemoglobin levels serving as the gold standard for evaluating glucose level control in DM patients. However, it has limitations in reflecting glucose oscillations (i.e. glycemic variability, GV). Increasing evidence suggests that GV is closely related to the progression of diabetes complications and patient prognosis. As people realize the importance of avoiding hypoglycemia while achieving target glycated hemoglobin levels in treatment, the clinical significance of GV becomes more obvious. This article systematically reviewed the concept and connotation of GV, summarized the latest research on its role in the complications of diabetes, and revealed the biochemical and pathophysiological abnormalities caused by excessive glycemic oscillation, aiming to provide a theoretical basis for the risk warning and early intervention of DM patients.
Humans ; Blood Glucose/metabolism* ; Diabetes Complications/physiopathology* ; Glycated Hemoglobin/metabolism* ; Hypoglycemia ; Diabetes Mellitus, Type 2/complications*

OBJECTIVE: Recaticimab (SHR-1209) significantly reduces low-density lipoprotein cholesterol levels. However, its effect on glucose metabolism remains unclear. This study aimed to evaluate its effect on glycemic parameters in a Chinese population. METHODS: Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks. Glycated hemoglobin (HbA1c) levels were measured at baseline every 12 weeks. Fasting plasma glucose (FPG) levels were measured at baseline at week 1, 3, 5, 8, 12, 16, 20, and 24. Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels. RESULTS: Among the 81 participants with normal glucose metabolism, HbA1c levels significantly decreased ( F = 4.568, P = 0.036). In the 29 participants with abnormal glucose metabolism, a significant time effect was observed for FPG levels ( F = 2.492, P = 0.016). For participants with normal and abnormal glucose metabolism, no significant group × time interaction effects on FPG or HbA1c levels were identified. CONCLUSION Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism, indicating its safety in patients with or without diabetes.
Humans ; Male ; Female ; Blood Glucose/drug effects* ; Middle Aged ; Double-Blind Method ; Hyperlipidemias/blood* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; PCSK9 Inhibitors ; Glycated Hemoglobin ; Aged ; Adult ; Proprotein Convertase 9

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

Hemoglobin, the principal protein in red blood cells, is crucial for oxygen transport in the bloodstream. The quantification of hemoglobin concentration is indispensable in medical diagnostics and health management, which encompass the diagnosis of anemia and the screening of various blood disorders. Immunological methods, based on antigen-antibody interactions, are distinguished by their high sensitivity and accuracy. Consequently, it is necessary to develop hemoglobin-specific antibodies characterized by high specificity and affinity to enhance detection accuracy. In this study, we immunized a Bactrian camel (Camelus bactrianus) with human hemoglobin and subsequently constructed a nanobody library. Utilizing a solid-phase screening method, we selected nanobodies and evaluated the binding activity of the screened nanobodies to hemoglobin. Initially, human hemoglobin was used to immunize a Bactrian camel. Following four immunization sessions, blood was withdrawn from the jugular vein, and a nanobody library with a capacity of 2.85×10⁸ colony forming units (CFU) was generated. Subsequently, ten hemoglobin-specific nanobody sequences were identified through three rounds of adsorption-elution-enrichment assays, and these nanobodies were subjected to eukaryotic expression. Finally, enzyme-linked immunosorbent assay and biolayer interferometry were employed to evaluate the stability, binding activity, and specificity of these nanobodies. The results demonstrated that the nanobodies maintained robust binding activity within the temperature range of 20-40 ℃ and exhibited the highest binding activity at pH 7.0. Furthermore, the nanobodies were capable of tolerating a 10% methanol solution. Notably, among the nanobodies tested, VHH-12 displayed the highest binding activity to hemoglobin, with a half maximal effective concentration (EC₅₀) of 10.63 nmol/L and a equilibrium dissociation constant (K_D) of 2.94×10^-7 mol/L. VHH-12 exhibited no cross-reactivity with a panel of eight proteins, such as ovalbumin and bovine serum albumin, while demonstrating partial cross-reactivity with hemoglobin derived from porcine, goat, rabbit, and bovine sources. In this study, a hemoglobin-specific high-affinity nanobody was successfully isolated, demonstrating potential applications in disease diagnosis and health monitoring.
Animals ; Camelus/immunology* ; Single-Domain Antibodies/immunology* ; Hemoglobins/immunology* ; Humans ; Peptide Library