Carbon Fiber-Based Vitrimer Composites: A Path toward Current Research That Is High-Performing, Useful, and Sustainable.

In the polymeric material industry, thermosets and related composites have played a substantial role in the production of rubber and plastics. One important subset of these is thermoset composites with carbon reinforcement. The incorporation of carbon fillers and fibers gives polymeric materials improved electrical and mechanical properties, among other benefits. However, the covalently crosslinked network of thermosets presents significant challenges for recycling and reprocessing because of its intractable nature. The introduction of vitrimer materials opens a new avenue to produce biodegradable and recyclable thermosets. Carbon-reinforced vitrimer composites are pursued for high-performance, long-lasting materials with attractive physical properties, the ability to be recycled and processed, and other features that respond uniquely to stimuli. The development of carbon-reinforced vitrimer composites over the last few years is summarized in this article. First, an overview of vitrimers and the methods used to prepare carbon fiber-reinforced vitrimer composites is provided. Because of the vitrimer nature of such composites, reprocessing, healing, and recycling are viable ways to greatly extend their service life; these approaches are thoroughly explained and summarized. The conclusion is our prediction for developing carbon-based vitrimer composites.

Effect of Helicobacter Pylori Infection on Glucose Metabolism, Lipid Metabolism and Inflammatory Cytokines in Nonalcoholic Fatty Liver Disease Patients.

Objective: To probe into the influence of Helicobacter pylori (Hp) infection on glucose metabolism, lipid metabolism, and inflammatory cytokines in patients with nonalcoholic fatty liver disease (MASLD). Methods: A total of 140 MASLD patients admitted to our Hospital between June 2020 and May 2021 were selected as the research objects. Based on the presence or absence of Hp infection, they were divided into the study group (73 cases with infection) and control group (67 cases without infection). Glucose metabolism indicators [fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), fasting insulin (FINS), glycated hemoglobin (HbAlc)], lipid metabolism indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], and inflammatory indicators [interleukin-37 (IL-37), interleukin-18 (IL-18)] were measured and compared between the two groups. Results: In terms of glucose metabolism indicators, the study group exhibited higher levels of FBG (5.84±0.49 vs 5.40±0.51, t=2.535, P=0.012), 2hPG (7.26±1.30 vs 6.50±1.53, t=3.321, P<0.001), and FINS (11.13±4.13 vs 9.12±3.72, t=3.224, P<0.001), and Insulin resistance index (HOMA-IR) (2.97±0.35 VS 2.13±0.54, t=3.761, P<0.001) and a lower level of HbAlc (5.25±0.56 vs 6.12±0.57, t=5.473, P<0.001) compared to the control group. Regarding lipid metabolism indicators, the study group exhibited higher levels of TC (5.64±1.49 vs 5.01±1.32, t=3.332, P<0.001), TG (1.89±0.34 vs 1.32±0.43, t=3.411, P<0.001), and LDL-C (3.31±0.43 vs 2.12±0.29, t=4.142, P<0.001), and a lower level of HDL-C (1.45±0.21 vs 1.78±0.42, t=4.347, P<0.001) compared to the control group. As for the inflammatory indicators, the study group exhibited higher levels of IL-37 (45.56±6.02 vs 34.02±3.28, t=9.332, P<0.001) and IL-18 (73.57±5.82 vs 60.34±4.84, t=10.141, P<0.001) compared to the control group. Conclusion: It is crucial to place appropriate emphasis on the impact of Hp infection on the glucose metabolism, lipid metabolism, and inflammatory response in MASLD patients, warranting careful consideration during the treatment of these patients.

Inhibited Expression of NLRP12 Promotes the Development of Triple-Negative Breast Cancer by Activating the NF-κB Pathway.

NLRP12 can affect the progression of different diseases, including hepatocellular carcinoma. However, no report on triple-negative breast cancer (TNBC) has been found. Thus, this study aimed to explore the role of NLRP12 in TNBC. In our study, immunohistochemistry, real-time quantitative PCR (qPCR), and Western blot assays were used to evaluate NLRP12 expression in TNBC tissues and cells. Then, NLRP12 lentivirus was constructed and infected into MDA-MB-231 and MDA-MB-157 cells with or without PTD-p65-P1 treatment. Next, cells were collected for cell function detection using the following procedures: colony formation assay for proliferation, Transwell for migration and invasion, and Western blot for NF-κB and MAPK pathway-associated proteins. Finally, a xenograft mouse model was applied; the tumor volume and weight were determined, and NLRP12, p-IκBb-α, and p-IκBb-α expressions were evaluated using qPCR and Western blot. Results indicated that NLRP12 was lowly expressed in TNBC tissues and cells. The inhibition of NLRP12 could induce the proliferation, migration, and invasion of TNBC cells, which also could be reversed by inhibiting the NF-κB pathway (PTD-p65-P1). Moreover, silencing of NLRP12 could upregulate p-IκBb-α, while IκBb-α, p-ERK, ERK, p-p38, p38, p-JNK, and JNK expressions remained unchanged, thereby indicating that only the NF-κB pathway could be activated by NLRP12 silencing. Furthermore, the xenograft mouse model confirmed the abovementioned findings. Therefore, the low expression of NLRP12 promoted the proliferation, migration, and invasion in TNBC cells by activating the NF-κB pathway. This study might provide insights into TNBC therapy.

Kaempferol improves acute kidney injury via inhibition of macrophage infiltration in septic mice.

Sepsis contributes to life-threatening circulatory and organ dysfunction by dysregulating the host response to infection in critically ill patients. Treatment in an Intensive Care Unit (ICU) can improve the survival of patients who suffer from severe sepsis, but sepsis-associated acute kidney injury (SAKI) is still one of the main causes of death. The existing treatment is mainly focused on controlling microorganism induced infections by using drugs, such as ulinastatin and glucocorticoid. Also, it is well documented that kaempferol, a flavonoid derived from plant sources, improves septic mouse survival via anti-inflammatory response. However, the mechanism of anti-inflammatory response mediated by this flavonoid compound was little known. This study aims to demonstrate the mechanisms of inflammatory response regulated by kaempferol treatment during sepsis. We perform cecal ligation and puncture (CLP) injury as a sepsis mouse model and evaluate organ injury in sepsis. The molecular (qRT-PCR and Western Blot) and cellular profiling (IHC staining and Flow Cytometry) of the immune responses illustrates that kaempferol decreases the expression of adhesion molecular genes (ICAM-1 and VCAM-1) and monocyte chemoattractant protein-1 (MCP-1), thereby inhibiting F4/80+ macrophages infiltration in CLP-induced acute kidney injury. Our data suggested that kaempferol alleviates acute kidney injury via regulating F4/80+ macrophages infiltration in CLP-induced acute kidney injury.

Expanding role of CXCR2 and therapeutic potential of CXCR2 antagonists in inflammatory diseases and cancers.

C-X-C motif chemokine receptor 2 (CXCR2) is G protein-coupled receptor (GPCR) and plays important roles in various inflammatory diseases and cancers, including chronic obstructive pulmonary disease (COPD), atherosclerosis, asthma, and pancreatic cancer. Upregulation of CXCR2 is closely associated with the migration of neutrophils and monocytes. To date, many small-molecule CXCR2 antagonists have entered clinical trials, showing favorable safety and therapeutic effects. Hence, we provide an overview containing the discovery history, protein structure, signaling pathways, biological functions, structure-activity relationships and clinical significance of CXCR2 antagonists in inflammatory diseases and cancers. According to the latest development and recent clinical progress of CXCR2 small molecule antagonists, we speculated that CXCR2 can be used as a biomarker and a new target for diabetes and that CXCR2 antagonists may also attenuate lung injury in coronavirus disease 2019 (COVID-19).

Evaluation of interference from 16 hemoglobin variants on hemoglobin A1c measurement by five methods.

Hb variants prevalent in China are different from those in other countries. We aimed to assess the interference from Hb variants found in China on HbA1c measurement. All Hb variants were confirmed using Sanger sequencing. HbA1c was measured using a capillary electrophoresis method (Capillarys 3 OCTA), two cation-exchange high-performance liquid chromatography methods (ADAMS HA-8180V and HLC-723 G8 standard mode), an immunoassay (Cobas c501), and a boronate affinity chromatography method (Premier Hb9210). Premier Hb9210 was used as a comparative method. A total of 16 species of Hb variants were identified in 102 variant carriers. The most common variant was Hb E, followed by Hb Q-Thailand, Hb New York and Hb J-Bangkok. Clinically significant interference was observed for the Capillarys 3 OCTA (two Hb variants), ADAMS HA-8180V (seven Hb variants), HLC-723 G8 (14 Hb variants), and Cobas c501 (two Hb variants). The proportion of unacceptable HbA1c results was 13.7% for Capillarys 3 OCTA, 52.9% for HA-8180V, 83.3% for HLC-723 G8, and 3.9% for Cobas c501. Hb variants in China severely affect the accuracy of some commonly used HbA1c methods.

Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis.

Mycobacterium tuberculosis (MTB) utilizes multiple mechanisms to obtain antibiotic resistance during the treatment of infections. In addition, the biofilms, secreted by MTB, can further protect the latter from the contact with drug molecules and immune cells. These self-defending mechanisms lay a formidable challenge to develop effective therapeutic agents against chronic and recurring antibiotic-tolerant MTB infections. Although several inexpensive and effective drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) have been discovered for the treatment regimen, MTB continues to cause considerable morbidity and mortality worldwide. Antibiotic resistance and tolerance remain major global issues, and innovative therapeutic strategies are urgently needed to address the challenges associated with pathogenic bacteria. Gratifyingly, the cell wall synthesis of tubercle bacilli requires the participation of many enzymes which exclusively exist in prokaryotic organisms. These enzymes, absent in human hepatocytes, are recognized as promising targets to develop anti-tuberculosis drug. In this paper, we discussed the critical roles of potential drug targets in regulating cell wall synthesis of MTB. And also, we systematically reviewed the advanced development of novel bioactive compounds or drug leads for inhibition of cell wall synthesis, including their discovery, chemical modification, in vitro and in vivo evaluation.

Systematic Identification of the RNA-Binding Protein STAU2 as a Key Regulator of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer. RNA-binding proteins (RBPs) regulate highly dynamic post-transcriptional processes and perform very important biological functions. Although over 1900 RBPs have been identified, most are considered markers of tumor progression, and further information on their general role in PAAD is not known. Here, we report a bioinformatics analysis that identified five hub RBPs and produced a high-value prognostic model based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Among these, the prognostic signature of the double-stranded RNA binding protein Staufen double-stranded RNA (STAU2) was identified. Firstly, we found that it is a highly expressed critical regulator of PAAD associated with poor clinical outcomes. Accordingly, the knockdown of STAU2 led to a profound decrease in PAAD cell growth, migration, and invasion and induced apoptosis of PAAD cells. Furthermore, through multiple omics analyses, we identified the key target genes of STAU2: Palladin cytoskeletal associated protein (PALLD), Heterogeneous nuclear ribonucleoprotein U (HNRNPU), SERPINE1 mRNA Binding Protein 1 (SERBP1), and DEAD-box polypeptide 3, X-Linked (DDX3X). Finally, we found that a high expression level of STAU2 not only helps PAAD evade the immune response but is also related to chemotherapy drug sensitivity, which implies that STAU2 could serve as a potential target for combinatorial therapy. These findings uncovered a novel role for STAU2 in PAAD aggression and resistance, suggesting that it probably represents a novel therapeutic and drug development target.

Discovery of Novel Phosphoinositide-3-Kinase α Inhibitors with High Selectivity, Excellent Bioavailability, and Long-Acting Efficacy for Gastric Cancer.

Phosphoinositide-3-kinase (PI3K) overexpressed in many tumors is a promising target for cancer therapy. However, due to toxicity from the ubiquitous expression of PI3K in many tissues, the development of PI3K inhibitors with high selectivity and low toxicity has become an urgent need for tumor treatment. Herein, based on the HipHop, we designed and synthesized a series of 6-(4,6-dimorpholino-1,3,5-triazin-2-yl)benzo[d]oxazol-2-amine derivatives as potent, selective, and long-acting PI3Kα inhibitors. Compound 27 was determined with potent PI3Kα inhibitory activity (IC50 = 4.4 nM), which exhibited excellent selectivity for homologous PI3K enzymes and a 370 kinome panel. Meanwhile, 27 featured favorable stability (T1/2 > 10 h) and high bioavailability (130%). Importantly, compound 27 exerted great antigastric cancer activity in vivo when combined with taxol. Collectively, these characteristics suggested 27 to be a promising PI3K agent for cancer treatment.

Targeting dual-specificity tyrosine phosphorylation-regulated kinase 2 with a highly selective inhibitor for the treatment of prostate cancer.

Prostate cancer (PCa) is one of the most prevalent cancers in men worldwide, and hormonal therapy plays a key role in the treatment of PCa. However, the drug resistance of hormonal therapy makes it urgent and necessary to identify novel targets for PCa treatment. Herein, dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) is found and confirmed to be highly expressed in the PCa tissues and cells, and knock-down of DYRK2 remarkably reduces PCa burden in vitro and in vivo. On the base of DYRK2 acting as a promising target, we further discover a highly selective DYRK2 inhibitor YK-2-69, which specifically interacts with Lys-231 and Lys-234 in the co-crystal structure. Especially, YK-2-69 exhibits more potent anti-PCa efficacy than the first-line drug enzalutamide in vivo. Meanwhile, YK-2-69 displays favorable safety properties with a maximal tolerable dose of more than 10,000 mg/kg and pharmacokinetic profiles with 56% bioavailability. In summary, we identify DYRK2 as a potential drug target and verify its critical roles in PCa. Meanwhile, we discover a highly selective DYRK2 inhibitor with favorable druggability for the treatment of PCa.

Microsized Pore Structure Determination in EPDM Rubbers Using High-Pressure 129Xe NMR Techniques.

Microsized pore parameters, such as pore size and distance between pores in a series of model EPDM rubbers, were determined in situ under the pressure of 500 psi using 129Xe nuclear magnetic resonance (NMR) techniques: spin-lattice (T1) and spin-spin (T2) relaxation measurements, pulsed-field gradient (PFG) NMR, and two-dimensional exchange spectroscopy (2D EXSY). The T1/T2 (≫1) ratio for the xenon confined in the pores is larger than that for nonconfined free xenon. This suggests that almost the entire pore surface interacts with xenon atoms like a closed pore. While these pores still connect each other through very narrow diffusion/exchange channels, it is possible to observe the echo decay in PFG-NMR and cross-peaks in 2D EXSY. The results show that both diffusion (Dpore ≈ 2.1 × 10-10 m2/s) and exchange (exchange rate, τexch = a few tens of milliseconds) of xenon between a pore within the material and outer surface are prolonged. The exchange distances (l), which correspond to the xenon gas penetration depth, were estimated to be 70-100 µm based on the measured diffusion coefficients and exchange rate (1/τexch). NMR diffraction analysis reveals that pore size (a) and pore distance (b) are on the order of magnitude of micrometers and tens of micrometers, while the diffusion coefficients of xenon gas in the diffusion channels (Deff) are about 10-8 m2/s. Overall, this study suggests that the pores with a few micrometers connected through very narrow flowing channels with the length of several tens of micrometers are developed 70 to 100 µm below the rubber surface. Furthermore, the overall steady-state diffusion of xenon is slower, approximately 2 orders of magnitudes, than the diffusion in the channel between the pores. The pore and exchange distances correlated with the composition of rubbers showed that the properties of EPDM rubber as a high-pressure gas barrier could be improved by reducing the size of cracks and the depth of gas penetration by the addition of both carbon black and silica fillers.

Clinical Value of PPM1G Gene in Survival Prognosis and Immune Infiltration of Hepatocellular Carcinoma.

OBJECTIVE: Liver cancer is one of the most common malignancies, but its prognosis is still poor. Exploring potential biomarkers is an important direction of tumor research. We intend to use bioinformatics methods to explore potential biomarkers related to survival and prognosis of HCC. METHODS: The mRNA and protein expressions of PPM1G in liver cancer were analyzed by HPA, TIMER, and UALCAN databases, and the effects of PPM1G on the prognosis of liver cancer patients were explored by the GEPIA database. We also explored the correlation between PPM1G expression and liver cancer immune infiltration through the TIMER database and further explored the potential protein interaction network of PPM1G through the STRING database. RESULTS: The mRNA and protein expression of PPM1G gene in hepatocellular carcinoma tissues was lower than that in normal adjacent tissues. Liver cancer patients with high expression of PPM1G have a better prognosis than those with low expression of PPM1G. The expression of PPM1G is positively or negatively correlated with different immune cells of liver cancer, such as CD4+ T lymphocytes, CD8+ T lymphocytes, B cells, macrophages, and neutrophils. CONCLUSION: The liver cancer patients with high expression of PPM1G have a good prognosis, and PPM1G gene may be a potential immunotherapy target and prognostic marker of liver cancer.

PTPN2, A Key Predictor of Prognosis for Pancreatic Adenocarcinoma, Significantly Regulates Cell Cycles, Apoptosis, and Metastasis.

Objective: This study conducted a comprehensive analysis of the members of the PTPN family and emphasized the key role of PTPN2 as a potential therapeutic target and diagnostic biomarker in improving the survival rate of PAAD. Method: Oncomine was used to analyze the pan-cancer expression of the PTPN gene family. The Cancer Genome Atlas (TCGA) data as well as Genotype-Tissue Expression (GTEx) data were downloaded to analyze the expression and prognosis of PTPNs. The diagnosis of PTPNs was evaluated by the experimental ROC curve. The protein-protein interaction (PPI) network was constructed by combining STRING and Cytoscape. The genes of 50 proteins most closely related to PTPN2 were screened and analyzed by GO and KEGG enrichment. The differentially expressed genes of PTPN2 were found by RNA sequencing, and GSEA enrichment analysis was carried out to find the downstream pathways and targets, which were verified by online tools and experiments. Finally, the relationship between PTPN2 and immune cell infiltration in PAAD, and the relationship with immune score and immune checkpoint were studied. Result: The expression patterns and the prognostic value of multiple PTPNs in PAAD have been reported through bioinformatic analyzes. Among these members, PTPN2 is the most important prognostic signature that regulates the progression of PAAD by activating JAK-STAT signaling pathway. Comparison of two PAAD cell lines with normal pancreatic epithelial cell lines revealed that PTPN2 expression was up-regulated as a key regulator of PAAD, which was associated with poor prognosis. Knockdown of PTPN2 caused a profound decrease in PAAD cell growth, migration, invasion, and induced PAAD cell cycle and apoptosis. In addition, we conducted a series of enrichment analyses to investigate the PTPN2-binding proteins and the PTPN2 expression-correlated genes. We suggest that STAT1 and EGFR are the key factors to regulate PTPN2, which are involved in the progression of PAAD. Meanwhile, the silencing of PTPN2 induced the repression of STAT1 and EGFR expression. Conclusion: These findings provide a comprehensive analysis of the PTPN family members, and for PAAD, they also demonstrate that PTPN2 is a diagnostic biomarker and a therapeutic target.

Discovery of Dual CDK6/PIM1 Inhibitors with a Novel Structure, High Potency, and Favorable Druggability for the Treatment of Acute Myeloid Leukemia.

Nowadays, the simultaneous inhibition of two or more pathways plays an increasingly important role in cancer treatment due to the complex and diverse pathogenesis of cancer, and the combination of the cyclin-dependent kinase 6 (CDK6) inhibitor and PIM1 inhibitor was found to generate synergistic effects in acute myeloid leukemia (AML) treatment. Therefore, we discovered a novel lead 1 targeting CDK6/PIM1 via pharmacophore-based and structure-based virtual screening, synthesized five different series of new derivates, and obtained a potent and balanced dual CDK6/PIM1 inhibitor 51, which showed high kinase selectivity. Meanwhile, 51 displayed an excellent safety profile and great pharmacokinetic properties. Furthermore, 51 displayed stronger potency in reducing the burden of AML than palbociclib and SMI-4a in vivo. In summary, we offered a new direction for AML treatment and provided a great lead compound for AML preclinical studies.

Discovery of novel and orally bioavailable CDK 4/6 inhibitors with high kinome selectivity, low toxicity and long-acting stability for the treatment of multiple myeloma.

Multiple myeloma (MM) ranks second in malignant hematopoietic cancers, and the most common anti-MM drugs easily generate resistance. CDK4/6 have been validated to play determinant roles in MM, but no remarkable progress has been obtained from clinical trials of CDK4/6 inhibitors for MM. To discover novel CDK6 inhibitors with better potency and high druggability, structure-based virtual screening was conducted to identify compound 10. Further chemical optimization afforded a better derivative, compound 32, which exhibited strong inhibition of CDK4/6 and showed high selectivity over 360+ kinases, including homologous CDKs. The in vivo evaluation demonstrated that compound 32 possessed low toxicity (LD50 > 10,000 mg/kg), favorable bioavailability (F% = 51%), high metabolic stability (t1/2 > 24 h) and strong anti-MM potency. In summary, we discovered a novel CDK4/6 inhibitor bearing favorable drug-like properties and offered a great candidate for MM preclinical studies.

Design, Synthesis, and Biological Evaluation of Icaritin Derivatives as Novel Putative DEPTOR Inhibitors for Multiple Myeloma Treatment.

Icaritin is an active ingredient in Epimedium, which has a variety of pharmacological activities. However, the low activity of Icaritin and the unclear target greatly limit its application. Therefore, based on the structure of Icaritin, we adopted the strategy of replacing toxic groups and introducing active groups to design and synthesize a series of new analogues. The top compound C3 exhibited better antimultiple myeloma activity with an IC50 of 1.09 µM for RPMI 8226 cells, induced RPMI 8226 apoptosis, and blocked the cell cycle in the S phase. Importantly, transcriptome analysis, cellular thermal shift assay, and microscale thermophoresis assay confirmed that DEPTOR was the target of C3. Moreover, we explored its binding mode with C3. Especially, C3 displayed satisfactory inhibition of tumor growth in RPMI 8226 xenografts without obvious side effects. In summary, C3 was discovered as a novel putative inhibitor of DEPTOR for the treatment of multiple myeloma.

Iodine Capture with Mechanically Robust Heat-Treated Ag-Al-Si-O Xerogel Sorbents.

Various radionuclides are released as gases during reprocessing of used nuclear fuel or during nuclear accidents including iodine-129 (129I) and iodine-131 (131I). These isotopes are of particular concern to the environment and human health as they are environmentally mobile and can cause thyroid cancer. In this work, silver-loaded heat-treated aluminosilicate xerogels (Ag-HTX) were evaluated as sorbents for iodine [I2(g)] capture. After synthesis of the base NaAlSiO4 xerogel, a heat-treatment step was performed to help increase the mechanical integrity of the NaAlSiO4 gels (Na-HTX) prior to Ag-exchanging to create Ag-HTX xerogels. Samples were characterized by powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, Brunauer-Emmett-Teller analysis, gravimetric iodine loading, nanoindentation, and dynamic mechanical analysis. The structural and chemical analyses of Ag-HTX showed uniform distribution of Ag throughout the gel network after Ag-exchange. After I2(g) capture, the AgI crystallites were observed in the sorbent, verifying chemisorption as the primary iodine capture mechanism. Iodine loading of this xerogel was 0.43 g g-1 at 150 °C over 1 day and 0.52 g g-1 at 22 °C over 33 days. The specific surface area of Ag-HTX was 202 m2 g-1 and decreased to 87 m2 g-1 after iodine loading. The hardness of the Na-HTX was >145 times higher than that of the heat-treated aerogel of the same starting composition. The heat-treatment process increased Young's modulus (compressive) value to 40.8 MPa from 7.0 MPa of as-made xerogel, demonstrating the need for this added step in the sample preparation process. These results show that Ag-HTX is a promising sorbent for I2(g) capture with good iodine loading capacity and mechanical stability.

Association of hemoglobin H (HbH) disease with hemoglobin A1c and glycated albumin in diabetic and non-diabetic patients.

OBJECTIVES: Hemoglobin A1c (HbA1c) and glycated albumin (GA) are glycemic control status indicators in patients with diabetes mellitus. Hemoglobin H (HbH) disease is a moderately severe form of α-thalassemia. Here we examine the usefulness of HbA1c and GA in monitoring glycemic control in patients with HbH disease. METHODS: HbA1c, GA, and an oral glucose tolerance test were performed in 85 patients with HbH disease and 130 healthy adults. HbA1c was measured using five methods, including two systems based on cation-exchange high-performance liquid chromatography (Variant II Turbo 2.0 and Bio-Rad D100), a capillary zone electrophoresis method (Capillarys 3 TERA), a boronate affinity HPLC method (Premier Hb9210), and an immunoassay (Cobas c501). RESULTS: Significant lower levels of HbA1c were observed in patients with HbH disease than in healthy adults. In contrast, GA showed no statistically significant differences between participants with and without HbH disease. A considerable number of diabetic patients with HbH disease would be missed if using HbA1c as a diagnostic criterion for diabetes mellitus. CONCLUSIONS: GA but not HbA1c is suitable for monitoring glycemic control in patients with HbH disease that can modify the discriminative ability of HbA1c for diagnosing diabetes.