Pediatric acute myeloid leukemia with t(8;21) and KIT mutation treatment with avapritinib post-stem cell transplantation: a report of four cases.

Acute myeloid leukemia (AML) with t(8;21) (q22;q22), which forms RUNX1::RUNX1T1 fusion gene, is classified as a favorable-risk group. However, the presence of mutations in KIT exon 17 results in an adverse prognosis in this group. Avapritinib, a novel tyrosine kinase inhibitor, was designed to target KIT mutation. We report a retrospective study of four pediatric patients with AML with t(8:21) and KIT exon 17 mutation who were treated with avapritinib, three of them failed to demethylate drugs and donor lymphocyte infusion targeting RUNX1::RUNX1T1-positivity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, all patients with RUNX1::RUNX1T1 positivity had turned negative after 1, 9, 7, 2 months of avapritinib treatment. The common adverse effect of avapritinib is neutropenia, which is well-tolerated. This case series indicates that avapritinib may be effective and safe for preemptive treatment of children with AML with t(8;21) and KIT mutation after allo-HSCT, providing a treatment option for preventing relapse after allo-HSCT.

Size Dependence of Gold Nanorods for Efficient and Rapid Photothermal Therapy.

In recent years, gold nanomaterials have become a hot topic in photothermal tumor therapy due to their unique surface plasmon resonance characteristics. The effectiveness of photothermal therapy is highly dependent on the shape and size of gold nanoparticles. In this work, we investigate the photothermal therapeutic effects of four different sizes of gold nanorods (GNRs). The results show that the uptake of short GNRs with aspect ratios 3.3-3.5 by cells is higher than that of GNRs with aspect ratios 4-5.5. Using a laser with single pulse energy as low as 28 pJ laser for 20 s can induce the death of liver cancer cells co-cultured with short GNRs. Long GNRs required twice the energy to achieve the same therapeutic effect. The dual-temperature model is used to simulate the photothermal response of intracellular clusters irradiated by a laser. It is found that small GNRs are easier to compact because of their morphological characteristics, and the electromagnetic coupling between GNRs is better, which increases the internal field enhancement, resulting in higher local temperature. Compared with a single GNR, GNR clusters are less dependent on polarization and wavelength, which is more conducive to the flexible selection of excitation laser sources.

Cold snare polypectomy compared to cold forceps polypectomy for endoscopic resection of guideline defined diminutive polyps: A systematic review and meta-analysis of randomized trials.

BACKGROUND: International guidelines recommend cold snare polypectomy (CSP) for polyps < 10 mm in size. However, recent randomized clinical trials (RCTs) showed conflicting results for the use of cold forceps polypectomy (CFP) vs. CSP for the resection of diminutive colorectal polyps (DCPs) (≤ 5 mm), especially for polyps ≤ 3 mm. Herein we compared CFP with CSP for patients with DCPs in this meta-analysis of RCTs. METHODS: We systematically searched the Cochrane Library, PubMed and EMBASE databases from inception to November 24, 2022, (Registration number INPLASY2022110135). The primary endpoint was DCP complete resection rate. The secondary endpoints were mean polypectomy time, polyp retrieval rate and complications. RESULTS: Seven RCTs involving 1023 DCPs were included. The complete resection rate (91.6% vs. 94.7%) for CFP was not significantly lower for polyps ≤ 5 mm (relative risk [RR] = 1.03; 95% confidence interval [CI]: 0.98-1.07). Sub-group analysis showed that the complete resection rate (88.7% vs. 92.4%) for CFP was not significantly lower for DCPs > 3 mm (RR = 1.04; 95% CI: 0.97-1.12). Another sub-group analysis showed that the complete resection rate (97.0% vs. 96.3%) was similar for polyps ≤ 3 mm for CFP vs. CSP (RR = 1.00; 95% CI: 0.98-1.03). The mean polypectomy time was not different between CFP and CSP (95% CI: -11.86-10.18). The polyp retrieval rate (100% vs. 96.9%) was not significantly higher for CFP (RR = 1.02; 95% CI: 0.98-1.07). There were no reported complications in the included studies. The overall study quality was moderate except for the removal of polyps ≤ 5 mm (low-quality evidence). CONCLUSION: CFP was comparable to CSP for the resection of polyps ≤ 3 mm; however, caution should be taken for DCPs > 3 mm because of the low complete resection rate (< 90%).

The influence of methotrexate-related transporter and metabolizing enzyme gene polymorphisms on peri-engraftment syndrome and graft-versus-host disease after haplo-hematopoietic stem cell transplantation in pediatric patients with malignant hematological diseases.

Background: Methotrexate (MTX), utilized as a graft-versus-host disease (GvHD) prophylactic agent in allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been proven to effectively decrease the occurrence of the peri-engraftment syndrome (Peri-ES) and acute GvHD (aGvHD). Changes in the pharmacodynamics of MTX are closely associated with gene polymorphisms in genes encoding drug-metabolizing enzymes and transporters. Nevertheless, the current studies mainly concentrate on leukemia or autoimmune diseases, and limited studies on allo-HSCT were reported. Methods: Here, we retrospectively assessed the relationship between MTX-related transporter and metabolizing enzyme gene polymorphisms, clinical characteristics, and outcomes in 57 pediatric patients who received haploid HSCT (haplo-HSCT) with malignant tumors at a single center. Results: We discovered all gene polymorphisms were in the Hardy-Weinberg equilibrium in our cohort. We discovered a significant correlation between platelet recovery time and ABCB1 (1236C>T) (p = 0.042). Compared with patients with SLCO1B1 (1865+4846T>C) TT, patients with SLCO1B1 (1865+4846T>C) TC/CC had an increased incidence of Peri-ES (p = 0.030). Based on the multivariate Cox analysis, we discovered that SLCO1B1 (1865+4846T>C) TT genotype was an independent protective factor for Peri-ES morbidity (hazard ratio (HR) = 0.464, p = 0.031), and the dose of mononuclear cells reinfused was significantly correlated with II-IV aGvHD (HR = 2.604, p = 0.039). Conclusion: In summary, our findings prove that the host's genotypes might modify the risk of developing Peri-ES, contribute to a better understanding of the inter-individual difference in efficacy, and facilitate the development of individualized approaches to GvHD prophylaxis.

The frequencies of lymphocyte subsets on "day 30″ correlate with the clinical outcome of pediatric hematopoietic stem cell transplantation.

We aimed to determine the relationship between lymphocyte subsets on day 30 (D30) and prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. We retrospectively examined the clinical outcomes and lymphocyte subsets on D30 after allo-HSCT in 115 pediatric patients at the Children's Hospital of Soochow University between January 2016 and June 2019. Measurements were performed using flow cytometry on D30. Lymphocyte subsets were compared among the umbilical cord blood (UCB) (n = 22), HLA-matched sibling donor (MSD) (n = 14), haploidentical donor transplantation (HID) (n = 57), and unrelated donor transplantation (UD) (n = 22) groups. The relationships between the frequencies and counts of lymphocyte subsets and clinical outcomes were analyzed. T and B cell counts were the highest in the MSD group compared to the other groups, and natural killer cell counts were the highest in the UCB group. Lymphocyte subsets on D30 after allo-HSCT were correlated with the occurrence of acute (aGVHD) and chronic graft versus host disease (cGVHD). A high frequency of B cells (≥4.65%) was associated with the development of severe aGVHD. High frequencies of CD4+T (≥10.25%) were correlated with extensive cGVHD. Moreover, a high frequency of CD4+T cells (≥9.80%) was correlated with GVHD-free and failure-free survival (GFFS) after allo-HSCT. However, on D30, there were no statistically significant correlations between viral infections and lymphocyte subsets. The frequencies of lymphocyte subsets on D30 after allo-HSCT are good indicators of prognosis after allo-HSCT in children.

Red cell distribution width: A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: Compared with patients with other causes of acute pancreatitis, those with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are more likely to develop persistent organ failure (POF). Therefore, recognizing the individuals at risk of developing POF early in the HTG-AP process is a vital for improving outcomes. Bedside index for severity in acute pancreatitis (BISAP), a simple parameter that is obtained 24 h after admission, is an ideal index to predict HTG-AP severity; however, the suboptimal sensitivity limits its clinical application. Hence, current clinical scoring systems and biochemical parameters are not sufficient for predicting HTG-AP severity. AIM: To elucidate the early predictive value of red cell distribution width (RDW) for POF in HTG-AP. METHODS: In total, 102 patients with HTG-AP were retrospectively enrolled. Demographic and clinical data, including RDW, were collected from all patients on admission. RESULTS: Based on the Revised Atlanta Classification, 37 (33%) of 102 patients with HTG-AP were diagnosed with POF. On admission, RDW was significantly higher in patients with HTG-AP and POF than in those without POF (14.4% vs 12.5%, P < 0.001). The receiver operating characteristic curve demonstrated a good discriminative power of RDW for POF with a cutoff of 13.1%, where the area under the curve (AUC), sensitivity, and specificity were 0.85, 82.4%, and 77.9%, respectively. When the RDW was ≥ 13.1% and one point was added to the original BISAP to obtain a new BISAP score, we achieved a higher AUC, sensitivity, and specificity of 0.89, 91.2%, and 67.6%, respectively. CONCLUSION: RDW is a promising predictor of POF in patients with HTG-AP, and the addition of RDW can promote the sensitivity of BISAP.

Association between haploidentical hematopoietic stem cell transplantation combined with an umbilical cord blood unit and graft-versus-host disease in pediatric patients with acquired severe aplastic anemia.

Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) based on granulocyte colony-stimulating factor plus anti-thymocyte regimens ('Beijing Protocol') provides a salvage treatment for patients of acquired severe aplastic anemia (SAA) in China. However, graft-versus-host disease (GVHD) is a major impediment of haplo-HSCT due to human leukocyte antigen disparity. Recently, haplo-HSCT combined with umbilical cord blood (UCB) (haplo-cord HSCT) is performed in clinical trials to potentially reduce the risk of severe GVHD. Nevertheless, studies comparing GVHD in pediatric patients receiving haplo and haplo-cord HSCT for SAA are limited. Objective: The objective of this study was to investigate the impact of UCB co-infusion on GVHD in pediatric patients receiving haplo-HSCT for SAA. Design: We conducted a retrospective study of 91 consecutive SAA children undergoing haploidentical transplantation based on the 'Beijing Protocol' with or without co-infusion of UCB in our center. Methods: All patients received uniform non-myeloablative conditioning and GVHD prophylaxis. We compared baseline characteristics and transplant outcomes between the haplo (n = 35) and haplo-cord (n = 56) recipients. Results: All 91 patients achieved hematopoietic recovery from haploidentical donors, with a higher incidence of peri-engraftment syndrome observed with the haplo-cord group as compared with the haplo group (75.0% versus 48.6%, p = 0.029). Notably, the haplo-cord group showed a lower incidence of II-IV acute GVHD (aGVHD) than the haplo group (16.1% versus 42.9%, p = 0.002). Observed incidences of chronic GVHD (cGVHD) and moderate to severe cGVHD in the haplo-cord group were also lower than that in the haplo group (25.6% versus 51.3%, p = 0.019; 16.2% versus 41.3%, p = 0.016, respectively). Haplo-cord HSCT was identified as the only factor associated with a lower incidence of II-IV aGVHD and cGVHD in multivariate analysis. However, no differences were observed between the two groups for infections and survival outcomes. Conclusion: Our data indicated that co-infusion of UCB in 'Beijing Protocol'-based haplo-HSCT may be effective for reducing the risk of severe GVHD in SAA children.

A new synthesis approach of hierarchical MoS2 nanoflakes toward hydrogen evolution in both acidic and alkaline media.

Herein, ultrathin MoS2 flakes were prepared using a synergistic liquid phase precipitation method by applying ultrasound and microwave simultaneously. At 10 mA cm2 of electric current density, the MoS2 electrocatalysts' passing points are 176 mV and 154 mV respectively in acidic and alkaline electrolytes. This research provides a new synthetic method and potential opportunity in the design and preparation of multiple synergistic high-efficiency electrocatalysts.

Clonorchis sinensis infection modulates key cytokines for essential immune response impacted by sex.

Infection with helminths can modulate the host immune response, which ultimately shape morbidity and mortality of the associated diseases. We studied key cytokines for essential immune response in sera from 229 southeastern China individuals infected with Clonorchis sinensis and 60 individuals without C. sinensis infection, and measured serum specific IgG and IgE against worms in these people. Individuals infected with C. sinensis had significantly higher antigen-specific IgG and IgE levels, which were positively correlated with egg counts in feces. However, less enhancement of IgE antibody was observed in females when compared to males with similar infection levels. C. sinensis infection caused diminished Th1 cytokines (IL-1ß, IL-2, IL-12p70, IFN-γ and TNF-α), Th2 cytokine (IL-4), as well as Th17 cytokine (IL-17A) in sera, which showed decreasing trend by infection intensity. Notably, these phenotypes were more significant in females than those in males. Although C. sinensis infection is associated with the development of hepatobiliary diseases, there was no significant correlation between the dampened cytokine profiles and the hepatobiliary morbidities. Our study indicates C. sinensis infection is strongly related to the immune suppression in human. Sex differences shape the immune milieus of clonorchiasis. This study provides a better understanding of how worms affect immune responses and cause a long-term immune alternation in humans with C. sinensis infection.

Evaluation of Essential and Toxic Elements in the Blood of 0-14-Year-Old Children in Hunan, China From 2013 to 2019: A Retrospective Analysis.

Objective: The aim was to investigate the distribution and correlation of Ca, Mg, Zn, Cu, Fe, Pb, and Cd in the blood of children aged 0-14 years in Hunan, China, which may serve to provide a basis for clinical guidance on child health. Study Design: A retrospective analysis was carried out. Concentrations of all elements were determined by atomic absorption spectrophotometry. Distributions were analyzed and compared among different age, sex, and year groups by the Kruskal-Wallis test, the chi-square test, and the Fisher's exact test. Spearman's rank correlation coefficient was used to evaluate the association between every pair of elements. Results: A total of 46,951 children were involved in this study from 2013 to 2019. The median blood levels of elements were 13.51 µmol/L (Cu), 58.69 µmol/L (Zn), 1.70 mmol/L (Ca), 1.40 mmol/L (Mg), 7.46 mmol/L (Fe), 35.00 µg/L (Pb), and 1.00 µg/L (Cd). Girls had a higher level of Ca and lower levels of Pb and Cd than boys. Cu and Ca showed an upward trend, and Mg and Pb showed a downward trend by year. Zn and Fe increased and Ca decreased significantly with age. The deficiency rates of Fe and Zn decreased significantly by year, while Ca and Cu increased significantly by year. Cd exposure in this area was relatively low. Conclusion: Most children had normal levels of the essential elements Ca, Cu, and Mg and the toxic elements Pb and Cd. Severe deficiencies in Zn and Fe were observed in the relatively younger children but improved with age. Persistent efforts in reducing Pb exposure might still be needed.

Hierarchical molybdenum-doped NiCoP@carbon microspheres: a highly-efficient electrocatalyst for the hydrogen evolution reaction.

Herein, we present hierarchical Mo-doped NiCoP@carbon microspheres that exhibit a noticeable enhancement in catalytic activity and fast kinetics for hydrogen evolution. An overpotential of 74.6 mV at 10 mA cm-2 and 54.9 mV dec-1 can be achieved. These results demonstrated the excellent electrochemical properties arising from the intrinsic characteristics of elemental doping and morphology control. We believe that this work opens a new avenue to fabricating TMD-based catalysts via the engineering of transition metal compounds.

Cerium substitution in LaCoO3 perovskite oxide as bifunctional electrocatalysts for hydrogen and oxygen evolution reactions.

Perovskite oxides have attracted great attention in electrochemistry due to their compositional and structural flexibility. Herein, microwave/ultrasound assisted hydrothermal procedures were developed to synthesize Ce-doped LaCoO3 perovskite oxide as bifunctional electrocatalysts for OER and HER application, achieving highly efficient bifunctional catalytic performance. The obtained LCC4 exhibited excellent electrocatalytic activity with an overpotential of 380 mV and 305 mV at 10 mA cm-2 toward OER and HER, respectively. The lower Tafel slopes of 80 mV per decade and 144 mV per decade for OER and HER, respectively, indicated the faster reaction kinetics for the improved inherent electrocatalytic activity. The outstanding long-term durability of LCC4 in alkaline conditions was also vital to the practical applications of water electrolysis. The improved bifunctional electrocatalytic activity was attributed to the synergistic effects of excellent conductivity and enriched active sites arising from A-site substitution. This work not only provides an efficient strategy for the development of perovskite oxide-based electrocatalysts but also puts forward a new insight on bifunctional electrocatalysts for overall water splitting.

The updated beta-spectrin mutations in patients with hereditary spherocytosis by targeted next-generation sequencing.

Hereditary spherocytosis (HS) with hemolysis, splenomegaly, and jaundice as the main clinical symptoms varied in different population and SPTB mutated rate is common except for ANK1 in the Chinese population, whereas only a few studies have been reported. Here, 11 Chinese pediatric patients with newly SPTB mutations detected by targeted next generation sequencing technology were included and analyzed in our study. The characteristics of mutation separation were verified among family members by bidirectional Sanger sequencing. The detected 11 mutations were novel, all of which were heterozygotes, including five de novo mutations, five maternal mutations, and one paternal mutation. Meanwhile, the 11 different novel mutation sites distributed on and near the seven exons included four pathogenic sites and seven likely pathogenic sites. The detection of 11 novel mutation sites gene expanded the mutant spectrum of the SPTB gene, and provided corresponding clinical data, which laid a foundation for the subsequent studies on HS in Chinese population, especially in pediatric patients.

Minimally myelosuppressive regimen for remission induction in pediatric AML: long-term results of an observational study.

Treatment refusal and death as a result of toxicity account for most treatment failures among children with acute myeloid leukemia (AML) in resource-constrained settings. We recently reported the results of treating children with AML with a combination of low-dose cytarabine and mitoxantrone or omacetaxine mepesuccinate with concurrent granulocyte colony-stimulating factor (G-CSF) (low-dose chemotherapy [LDC]) for remission induction followed by standard postremission strategies. We have now expanded the initial cohort and have provided long-term follow-up. Eighty-three patients with AML were treated with the LDC regimen. During the study period, another 100 children with AML received a standard-dose chemotherapy (SDC) regimen. Complete remission was attained in 88.8% and 86.4% of patients after induction in the LDC and SDC groups, respectively (P = .436). Twenty-two patients in the LDC group received SDC for the second induction course. Significantly more high-risk AML patients were treated with the SDC regimen (P = .035). There were no significant differences between the LDC and SDC groups in 5-year event-free survival (61.4% ± 8.7% vs 65.2% ± 7.4%, respectively; P = .462), overall survival (72.7% ± 6.9% vs 72.5% ± 6.2%, respectively; P = .933), and incidence of relapse (20.5% ± 4.5% vs 17.6% ± 3.9%, respectively; P = .484). Clearance of mutations based on the average variant allele frequency at complete remission in the LDC and SDC groups was 1.9% vs 0.6% (P < .001) after induction I and 0.17% vs 0.078% (P = .052) after induction II. In conclusion, our study corroborated the high remission rate reported for children with AML who received at least 1 course of LDC. The results, although preliminary, also suggest that long-term survival of these children is comparable to that of children who receive SDC regimens.

Accuracy of angiopoietin-2 for predicting organ failure in patients with acute pancreatitis: a systematic review and meta-analysis.

OBJECTIVE: Our aim was to assess the accuracy of angiopoietin-2 (Ang-2) as a prognostic marker for acute pancreatitis (AP) with organ failure (OF). METHODS: We undertook a systematic search of the PubMed, Cochrane Library, Embase, Chinese Journals Full-text, Wanfang, China Biology Medicine disc, and Weipu databases to identify eligible cohort studies on the predictive value of Ang-2 for AP with OF. The main outcome measures were sensitivity and specificity. The effects were pooled using a bivariate mixed-effects model. RESULTS: Six articles with seven case-control studies (n = 650) were included. Pooled sensitivity, specificity, and positive and negative likelihood ratios with 95% confidence intervals (CI) for AP with OF were 0.93 (95%CI: 0.75-0.99), 0.85 (95%CI: 0.75-0.92), 6.40 (95%CI: 3.36-12.19), and 0.08 (95%CI: 0.02-0.36), respectively. The area under the summary receiver operating characteristic curve was 0.95 (95%CI: 0.92-0.96), and the diagnostic odds ratio was 83.18 (95%CI: 11.50-623.17). Subgroup analysis showed that admission time of AP onset (< or ≥24 hours) was a source of overall heterogeneity. Sensitivity analysis supported this finding. CONCLUSION: Ang-2 had high diagnostic accuracy for AP with OF; the best prediction of Ang-2 may be 24 to 72 hours after onset of AP.

The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin.

The Blm10/PA200 family of proteasome activators modulates the peptidase activity of the core particle (20S CP). They participate in opening the 20S CP gate, thus facilitating the degradation of unstructured proteins such as tau and Dnm1 in a ubiquitin- and ATP-independent manner. Furthermore, PA200 also participates in the degradation of acetylated histones. In our study, we use a combination of yeast and human cell systems to investigate the role of Blm10/PA200 in the degradation of N-terminal Huntingtin fragments (N-Htt). We demonstrate that the human PA200 binds to N-Htt. The loss of Blm10 in yeast or PA200 in human cells results in increased mutant N-Htt aggregate formation and elevated cellular toxicity. Furthermore, Blm10 in vitro accelerates the proteasomal degradation of soluble N-Htt. Collectively, our data suggest N-Htt as a new substrate for Blm10/PA200-proteasomes and point to new approaches in Huntington's disease (HD) research.

A highly thermotolerant laccase produced by Cerrena unicolor strain CGMCC 5.1011 for complete and stable malachite green decolorization.

Laccases are a class of multi-copper oxidases with important industrial values. A thermotolerant laccase produced by a basidiomycete fungal strain Cerrena unicolor CGMCC 5.1011 was studied. With glycerin and peptone as the carbon and nitrogen sources, respectively, a maximal laccase activity of 121.7 U/mL was attained after cultivation in the shaking flask for 15 days. Transcriptomics analysis revealed an expressed laccase gene family of 12 members in C. unicolor strain CGMCC 5.1011, and the gene and cDNA sequences were cloned. A glycosylated laccase was purified from the fermentation broth of Cerrena unicolor CGMCC 5.1011 and corresponded to Lac2 based on MALDI-TOF MS/MS identification. Lac2 was stable at pH 5.0 and above, and was resistant to organic solvents. Lac2 displayed remarkable thermostability, with half-life time of 1.67 h at 70 ºC. Consistently, Lac2 was able to completely decolorize malachite green (MG) at high temperatures, whereas Lac7 from Cerrena sp. HYB07 resulted in accumulation of colored MG transformation intermediates. Molecular dynamics simulation of Lac2 was conducted, and possible mechanisms underlying Lac2 thermostability were discussed. The robustness of C. unicolor CGMCC 5.1011 laccase would not only be useful for industrial applications, but also provide a template for future work to develop thermostable laccases.

Proteomic profiling and bioinformatics analysis identify key regulators during the process from fanconi anemia to acute myeloid leukemia.

Fanconi anemia (FA) is a congenital aplastic anemia, characterized as congenital bone marrow failure, developmental malformation, and the malignant tendency, which may develop into acute myeloid leukemia (AML). However, few studies have been conducted on the progression from FA to AML. In this study, we used proteomic profiling, together with bioinformatics analyses, to explore the molecular mechanisms by which FA progresses to AML. Quantitative proteomic analyses of bone marrow samples identified 168 differentially expressed proteins (DEPs), including 7 upregulated proteins and 161 downregulated proteins in the bone marrow of the FA patient compared with the healthy people. The upregulated proteins were enriched in response to stress, oxygen transport, and hydrogen peroxide catabolic process. The downregulated proteins were enriched in myeloid leukocyte mediated immunity, response to interleukin-12, platelet degranulation and regulation of ATPase activity. Based on these results, we discovered 155 DEPs (142 upregulated and 13 downregulated) in the bone marrow samples between FA and AML patients, of which HIST1H1D, HIST1H3A, PSME1 and THRAP3 may play important roles in the progression of FA to AML and may be used as markers for AML early diagnosis. Finally, cell-line based experiments confirmed that PSME1 had an important effect on the proliferation of leukemia cells.

Proteomic analysis for identifying the differences in molecular profiling between fanconi anaemia and aplastic anaemia.

Treatment and prognosis of Fanconi anaemia (FA) and acquired aplastic anaemia (AA) differ. However, delayed and inappropriate treatments are administered in FA due to its similarities to AA in presentation. The objective of the current study was to elucidate differences between the molecular mechanisms underlying FA and AA as well as to identify biomarkers and pathways associated with FA via bioinformatics analyses. Proteomic data were obtained from bone marrow samples of patients with FA and AA. Gene ontology analysis was performed using a Database for Annotation, Visualization and Integrated Discovery. KEGG pathway enrichment analyses were conducted using the ClueGO plug-in in Cytoscape. A DEP-associated protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. A total of 114 DEPs, including 71 upregulated proteins and 43 downregulated proteins, were present in the FA samples, compared with those in the AA samples. Upregulated proteins were enriched in the nucleosome assembly, canonical glycolysis, glycolytic process, and the glycolysis/gluconeogenesis pathway, whereas downregulated proteins were enriched in relation to immune response, negative regulation of apoptosis, proteolysis and CoA biosynthesis. Eight hub proteins with a high degree of connectivity were obtained as follows: alpha-enolase (ENO1), HSP90AA1, phosphoglycerate kinase 1 (PGK1), HSP90AB1, ACTC1, ACTBL2, EEF1A1 and CFL1. Upregulation of ENO1 and CFL1 in patients with FA was confirmed through a WB experiment, and substantiated by the results of data analyses. Bioinformatics analyses are useful for identification of biomarkers and pathways associated with FA and AA. Some crucial DEPs, such as ENO1, PGK1, ACTC1, ACTBL2, EEF1A1 and CFL1, may play an important role in FA and show potential as serological markers for its early diagnosis.