Luspatercept enhances hemoglobin levels in a Chinese boy with congenital sideroblastic anemia: A case report.

BACKGROUND: Congenital sideroblastic anemia (CSA) is a rare and heterogeneous group of genetic disorders. Conventional treatment include pyridoxine (vitamin B6) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can alleviate anemia in the majority of cases. Nevertheless, some CSA cases remain unresponsive to pyridoxine or are unable to undergo allo-HSCT. Novel management approaches is necessary to be developed. To explore the response of luspatercept in treating congenital sideroblastic anemia. CASE SUMMARY: We share our experience in luspatercept in a 4-year-old male patient with CSA. Luspatercept was administered subcutaneously at doses of 1.0 mg/kg/dose to 1.25 mg/kg/dose every 3 wk, three consecutive doses, evaluating the hematological response. Luspatercept leading to a significant improvement in the patient's anemia. The median hemoglobin during the overall treatment with three doses of luspatercept was 90 (75-101) g/L, the median absolute reticulocyte count was 0.0593 (0.0277-0.1030) × 1012/L, the median serum ferritin was 304.3 (234.4-399) ng/mL, and the median lifespan of mature red blood cells was 80 (57-92) days. Notably, no adverse reactions, such as headaches, dizziness, vomiting, joint pain, or back pain, were observed during the treatment period. CONCLUSION: We believe that luspatercept might emerge as a viable therapeutic option for the maintenance treatment of CSA or as a bridging treatment option before hematopoietic stem cell transplantation.

Divert More Attention to Vision-Language Object Tracking.

Multimodal vision-language (VL) learning has noticeably pushed the tendency toward generic intelligence owing to emerging large foundation models. However, tracking, as a fundamental vision problem, surprisingly enjoys less bonus from recent flourishing VL learning. We argue that the reasons are two-fold: the lack of large-scale vision-language annotated videos and ineffective visionlanguage interaction learning of current works. These nuisances motivate us to design more effective vision-language representation for tracking, meanwhile constructing a large database with language annotation for model learning. Particularly, in this paper, we first propose a general attribute annotation strategy to decorate videos in six popular tracking benchmarks, which contributes a largescale vision-language tracking database with more than 23,000 videos. We then introduce a novel framework to improve tracking by learning a unified-adaptive VL representation, where the cores are the proposed asymmetric architecture search and modality mixer (ModaMixer). To further improve VL representation, we introduce a contrastive loss to align different modalities. To thoroughly evidence the effectiveness of our method, we integrate the proposed framework on three tracking methods with different designs, i.e., the CNNbased SiamCAR [1], the Transformer-based OSTrack [2], and the hybrid structure TransT [3]. The experiments demonstrate that our framework can significantly improve all baselines on six benchmarks. Besides empirical results, we theoretically analyze our approach to show its rationality. By revealing the potential of VL representation, we expect the community to divert more attention to VL tracking and hope to open more possibilities for future tracking with diversified multimodal messages.

SIAH2 is specifically expressed during cervical carcinogenesis, and closely relates to the abnormal proliferation of cervical epithelial cells.

Background: Cervical cancer is one of the most common malignancies in women worldwide. As a RING type ubiquitin ligase, SIAH2 has been reported to promote the progression of a variety of tumors by interacting with and targeting multiple chaperones and substrates. The aim of this study was to further identify the role and the related molecular mechanisms involved of SIAH2 in cervical carcinogenesis. Methods and results: Cellular assays in vitro showed that knockdown of SIAH2 inhibited the proliferation, migration and invasion of human cervical cancer cells C33A and SiHa, induced apoptosis, and increased the sensitivity to cisplatin treatment. Knockdown of SIAH2 also inhibited the epithelial-mesenchymal transition and activation of the Akt/mTOR signaling pathway in cervical cancer cells, which were detected by Western blot. Mechanistically, SIAH2, as a ubiquitin ligase, induced the ubiquitination degradation of GSK3ß degradation by using coIP. The results of complementation experiments further demonstrated that GSK3ß overexpression rescued the increase of cell proliferation and invasion caused by SIAH2 overexpression. Specific expression of SIAH2 appeared in precancerous and cervical cancer tissues compared to inflammatory cervical lesions tissues using immunohistochemical staining. The more SIAH2 was expressed as the degree of cancer progressed. SIAH2 was significantly highly expressed in cervical cancer tissues (44/55, 80 %) compared with precancerous tissues (18/69, 26.1 %). Moreover, the expression level of SIAH2 in cervical cancer tissues was significantly correlated with the degree of cancer differentiation, and cervical cancer tissues with higher SIAH2 expression levels were less differentiated. Conclusion: Targeting SIAH2 may be beneficial to the treatment of cervical cancer.

Construction of Ketoenamine-Based Covalent Organic Frameworks with Electron-Rich Sites for Efficient and Rapid Removal of Iodine from Solution.

Porous covalent organic frameworks (COFs) have been widely used for the efficient removal of iodine from solution due to their abundance of electron-rich sites. In this study, two kinds of ketoenamine-based COFs, TpBD-(OMe)2 and TpBD-Me2, are successfully synthesized via Schiff base reaction under solvothermal conditions using 1, 3, 5-triformylphoroglucinol as aldehyde monomer, o-tolidine and o-dianisidine as amino monomers. The ability of TpBD-(OMe)2 and TpBD-Me2 to adsorb iodine in cyclohexane or aqueous solutions has been quantitatively analyzed and interpreted in terms of adsorption sites. TpBD-Me2 possesses two adsorption sites, -NH- and -C=O, and exhibits an adsorption capacity of 681.67 mg/g in cyclohexane, with an initial adsorption rate of 0.6 g/mol/min with respect to COF unit cell. The adsorption capacity of TpBD-(OMe)2 can be as high as 728.77 mg/g, and the initial adsorption rate of TpBD-(OMe)2 can reach 1.2 g/mol/min in the presence of oxygen atoms between the methyl group and the benzene ring. Compared with TpBD-Me2, the higher adsorption capacity and adsorption rate of TpBD-(OMe)2 towards iodine are not only reflected in organic solvents, but also in aqueous solutions. It is proven through X-ray photoelectron spectroscopy and Raman spectroscopy that iodine exists in the form of I2, I3-, and I5- within TpBD-(OMe)2 and TpBD-Me2 after adsorption. This work not only expands the application of COFs in the field of iodine adsorption, but also provides research ideas and important an experimental basis for the optimization of iodine adsorption sites.

Genotype-degree of hemolysis correlation in hereditary spherocytosis.

BACKGROUND: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation. RESULTS: In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400). CONCLUSION: The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS.

Development and validation of early death risk score model for emergency status prediction in very severe aplastic anemia.

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation cohort results were consistent with those of the training cohort. The area under the receiver operating characteristic curve for the model was 0.835 (0.734,0.936) in the training cohort and 0.862 (0.730,0.994) in the validation cohort. The calibration plots showed high agreement, and decision curve analysis showed good benefit in clinical applications. The VSAA Early Death Risk Score Model can help with early identification of emergency VSAA and optimize treatment strategies. Emergency VSAA with high risk is associated with high early death rate, and alternative donor hematopoietic stem cell transplantation could be a better treatment than IST even without HLA-matching.

Hetrombopag plus porcine ATG and cyclosporine for the treatment of aplastic anaemia: early outcomes of a prospective pilot study.

Hetrombopag, a small molecular thrombopoietin-receptor agonist, has shown encouraging efficiency in immunosuppressive therapy refractory or relapsed severe aplastic anaemia. To investigate the response rate of hetrombopag combined with IST as first-line treatment, we designed a prospective pilot study including 32 patients with SAA treated with anti-human T lymphocyte porcine immunoglobulin (p-ATG), cyclosporine, and hetrombopag. In addition, 96 patients with SAA treated with p-ATG and cyclosporine alone were matched as controls. In total, 21.9% of patients treated with hetrombopag achieved complete response (CR) at 3 months, while 5.2% of patients achieved CR in the control group (P = 0.005). At 6 months, the CR rates were 34.4% in the hetrombopag group and 14.6% in the control group (P = 0.015). The overall response rates at 6 months were 68.7% and 50.0% in the hetrombopag and control groups, respectively. The median time to haematologic response was 56 days and 77 days, and to CR was 96 days and 214 days in the hetrombopag and control groups, respectively. In conclusion, adding hetrombopag to IST as first-line treatment resulted in faster and better haematologic response in SAA.

Antihuman T lymphocyte porcine immunoglobulin combined with cyclosporine as first-line immunosuppressive therapy for severe aplastic anemia in China: a large single-center, 10-year retrospective study.

Background: Antihuman T lymphocyte porcine immunoglobulin (p-ATG) has been the most common ATG preparation in immunosuppressive therapy (IST) in Chinese patients with severe aplastic anemia (SAA) since 2009. Objectives: This study aimed to evaluate the early hematologic response and long-term outcomes of a large cohort of patients with SAA who received p-ATG plus cyclosporine (CsA) as first-line therapy from 2010 to 2019. Design: This is a single-center retrospective study of medical records. Methods: We analyzed the data of 1023 consecutive patients with acquired aplastic anemia (AA) who underwent p-ATG combined with CsA as a first-line IST treatment from 2010 to 2019 at our department. Results: The median age of the patients was 24 (4-75) years, and the median follow-up time was 57.2 months (3 days-137.5 months). There was an early mortality rate of 2.8% with a median death time of 0.9 months (3 days-2.9 months). The overall response rates were 40.6% and 56.1% at 3 and 6 months, respectively. The 5-year cumulative incidences of relapse and clonal evolution were 9.0% [95% confidence interval (CI) = 4.2-16.0%] and 4.5% (95% CI = 1.4-10.6%), respectively. The 5-year overall survival (OS) and event-free survival rates were 83.7% (95% CI = 81.1-86.0%) and 50.4% (95% CI = 47.1-53.5%), respectively. Conclusion: p-ATG combined with CsA for the treatment of AA is effective and safe, and p-ATG can be used as an alternative ATG preparation for the standard IST regimen in areas in which h-ATG is not available.

Deep Generative Mixture Model for Robust Imbalance Classification.

Discovering hidden pattern from imbalanced data is a critical issue in various real-world applications. Existing classification methods usually suffer from the limitation of data especially for minority classes, and result in unstable prediction and low performance. In this paper, a deep generative classifier is proposed to mitigate this issue via both model perturbation and data perturbation. Specially, the proposed generative classifier is derived from a deep latent variable model where two variables are involved. One variable is to capture the essential information of the original data, denoted as latent codes, which are represented by a probability distribution rather than a single fixed value. The learnt distribution aims to enforce the uncertainty of model and implement model perturbation, thus, lead to stable predictions. The other variable is a prior to latent codes so that the codes are restricted to lie on components in Gaussian Mixture Model. As a confounder affecting generative processes of data (feature/label), the latent variables are supposed to capture the discriminative latent distribution and implement data perturbation. Extensive experiments have been conducted on widely-used real imbalanced image datasets. Experimental results demonstrate the superiority of our proposed model by comparing with popular imbalanced classification baselines on imbalance classification task.

Long-term outcomes of aplastic anemia with cytogenetic abnormalities at diagnosis.

OBJECTIVES: To elucidate the clinical characteristics of AA patients with cytogenetic abnormalities. METHODS: We retrospectively screened 30 patients (30/1206, 2.5%) with cytogenetic abnormalities from 1206 patients with severe and very severe AA who received immunosuppressive therapy (IST) during the years 2012-2019. RESULTS: The most common abnormalities were trisomy 8 (+8, 10/30, 33.3%) and loss of Y (-Y, 8/30, 26.7%). The abnormal clones disappeared 6 months after IST in 14 patients and sustained in 12 patients. Patients with sustained abnormal clones had a lower hematologic response at 6 months after IST than the disappeared (33.3% vs. 64.3%, p = .116). The hematologic response after IST, 5-year overall survival, 5-year event-free survival, myelodysplastic syndrome or acute myeloid leukemia transformation in AA patients with cytogenetic abnormalities were not statistically different from those in normal cytogenetic patients. CONCLUSION: For AA patients with chromosome abnormalities but ineligible for hematopoietic stem cell transplant, IST is effective and appropriate as first-line treatment.

Controlled Iodine Phase Transfer of Covalent Organic Framework Membranes for Instant but Sustained Disinfection.

Freestanding membranes of CuCl2-implanted TpPa covalent organic frameworks (COFs) were mechanochemically produced. The resulting membrane had a high I2 adsorption capacity (566.78 g·mol-1) in cyclohexane, which corresponds to 2.2I2 per unit cell with 1.3I2 immobilized on 3Cl- ions (60%) and 0.9 on 3N atoms (40%). Upon being placed in aqueous media, the membrane released 61.1% of its loaded I2 mainly by its Cl- ions within 10 min and the remaining 38.9% mainly from its N atoms within about 5 h. Thanks to that, the COF membranes loaded with 1.5 mg of I2 could be repetitively utilized to kill about 108 CFU/mL E. coli in 0.5-3 min at least five times, after which the membranes could retain their bactericidal activity for 4 h against 108 CFU/mL E. coli. This highlights the promising application of I2-loaded TpPa-CuCl2 COF membranes for instant and sustained disinfection.

Geotechnical Seismic Isolation System Based on Rubber-Sand Mixtures for Rural Residence Buildings: Shaking Table Test.

The anti-seismic problem of rural residential buildings is the weak link of seismic retrofitting in China. Recently, geotechnical seismic isolation (GSI) technology based on rubber-sand mixtures (GSI-RSM) using rubber-sand mixtures (RSM) between the structural foundation and the foundation soil has been proven to have the possibility of potential applications in rural residential buildings. Many theoretical studies exist on the effectiveness of seismic isolation of the GSI-RSM system, but few studies on either the seismic response test of model buildings placed on the RSM layer or the large-scale shaking table test exist. Therefore, this study considers a large shaking table test performed on a 1/4 single-story masonry structure model with and without a GSI-RSM system by selecting a standard input ground motion and varying input acceleration amplitudes. The test results show that the GSI-RSM system can reduce the seismic response of superstructures. The isolation effect of the GSI-RSM system is low in small earthquakes and increases with increasing earthquake magnitude. Overall, the RSM layer can filter part of the high-frequency components of the earthquake to transmit to the superstructure and consume more seismic energy by generating friction slip in the interaction with the structural foundation.

First-line immunosuppressive therapy with rATG and CsA for severe aplastic anemia: 15 years' experience.

Rabbit antithymocyte globulin (rATG) instead of horse ATG has been used for severe aplastic anemia (SAA) patients in China. This study aimed to investigate the hematologic responses and long-term overall survival (OS) outcomes in SAA patients who received rATG and cyclosporine as first-line immunosuppressive therapy. We analyzed data of 542 SAA patients treated with this therapy between 2005 and 2019. The median age was 20 (range, 2-80) years, and the median follow-up time was 45.5 (range, 0.1-191.4) months. The early mortality rate was 3.9%. The overall response rates (ORRs) were 40.2%, 56.1%, and 62.4% at 3, 6, and 12 months, respectively. The 6- and 12-month ORR of patients treated with 3 mg/kg/d of rATG in 2015-2019 seemed higher than that of patients treated with 3.5-3.75 mg/kg/day in 2005-2014 (60.2% vs. 54.9%, P = 0.30 and 69.9% vs. 60.1%, P = 0.049, respectively). The 10-year cumulative incidences of relapse and clonal evolution were 10.6 ± 2.9% and 7.5 ± 1.5%, respectively. The 10-year OS rate and event-free survival rate were 80.1 ± 2.1% and 75.6 ± 3.7%, respectively. Age, disease severity, treatment periods, and the interval from diagnosis to IST were independent predictors of OS. In conclusion, 3 mg/kg/day rATG is effective as first-line treatment for SAA.

Seismic Behavior of Shear Keys Enhanced with Novel Energy Absorption Devices in Immersion Joints Based on Pseudo-Static Tests.

Shear keys are usually installed as crucial shear-resistant members of an immersion joint; thus, the mechanical behavior of the shear keys, especially under earthquake loading, deserves more attention. This paper presents a novel arc-shaped energy absorption device developed for shear keys. In order to verify the seismic performance of shear keys strengthened by the arc-shaped energy absorption devices, a series of pseudo-static tests were conducted, in which different axial pressures (300 kN, 400 kN) were also taken into consideration. The testing results indicated that failure mode of the shear key enhanced by the energy absorption devices was a synthesis of the oblique shear failure of the rubber blankets, the buckling of the energy absorption devices, and the concrete fracture of the shear key. In view of load-displacement hysteretic curves of testing specimens, loops of the reinforced shear keys were plumper than those from a traditional shear key. In addition, the load-bearing capacity (cracking load, yield load, peak load, and failing load) differences of the shear keys with and without energy absorption devices reinforcement under the same axial pressure were 33.0%, 36.7%, 26.0%, and 23.6%, respectively. The maximum equivalent viscous coefficient values of the shear keys with and without energy absorption devices reinforcement were 0.37, 0.38, and 0.32, respectively. The arc-shaped energy absorption devices can contribute to the hysteretic behavior of the shear keys. However, the axial pressure had a positive influence on the load bearing capacity, accumulated energy absorption capacity, and initial stiffness of the shear keys. In contrast to that, the axial pressure had negative influence on ductility ratio of the reinforced shear keys (equivalent viscous coefficient values of two enhanced shear keys were roughly equal). A reasonable stiffness scheme of an energy absorption device should be given attention during the anti-seismic design of an immersion joint. The study can provide scientific support for further study on the seismic responses of immersion joints and promote the application of earthquake control technology in immersed tunnels.

Efficacy of eltrombopag with immunosuppressive therapy for children with acquired aplastic anemia.

Background: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial. Methods: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) by propensity score matching (PSM). Results: There was no difference in the overall response (OR) rate between the EPAG group and IST group (53.3% vs. 46.7% at 3 months, P = 0.655; 66.7% vs. 57.8% at 6 months, P = 0.543), but the complete response (CR) rate was statistically significant (20.0% vs. 4.4% at 3 months, P = 0.094; 46.7% vs. 13.3% at 6 months, P = 0.012). The median time to achieve a hematological response in the EPAG and IST groups was 105 days and 184 days, respectively. No difference was observed in the event-free survival (EFS) or overall survival (OS) rates. Conclusion: Adding EPAG to standard IST as the first-line treatment for children with acquired SAA improved the rapidity of hematological response and the CR rate but did not improve the OR or EFS rates.

Serum circulating free DNA of syncytin-1 as a novel molecular marker for early diagnosis of non-small-cell lung cancer.

Background: Liquid biopsy has been receiving attention as an emerging detection technology in the clinical application of non-small-cell lung cancer (NSCLC). Methods: We quantified serum circulating free DNA (cfDNA) of syncytin-1 in 126 patients and 106 controls, analyzed the correlation of level with pathological parameters and explored diagnostic utility. Results: The cfDNA of syncytin-1 levels in NSCLC patients were higher than healthy controls (p < 0.0001). These levels were associated with smoking history (p = 0.0393). The area under the curve of cfDNA of syncytin-1 was 0.802, and combination of cfDNA of syncytin-1/cytokeratin 19 fragment antigen 21-1/carcinoembryonic antigen markers improved diagnostic efficiency. Conclusion: The cfDNA of syncytin-1 was detected in NSCLC patients and can be used as a novel molecular marker for early diagnosis.

Multisensory Information Facilitates the Categorization of Untrained Stimuli.

Although it has been demonstrated that multisensory information can facilitate object recognition and object memory, it remains unclear whether such facilitation effect exists in category learning. To address this issue, comparable car images and sounds were first selected by a discrimination task in Experiment 1. Then, those selected images and sounds were utilized in a prototype category learning task in Experiments 2 and 3, in which participants were trained with auditory, visual, and audiovisual stimuli, and were tested with trained or untrained stimuli within the same categories presented alone or accompanied with a congruent or incongruent stimulus in the other modality. In Experiment 2, when low-distortion stimuli (more similar to the prototypes) were trained, there was higher accuracy for audiovisual trials than visual trials, but no significant difference between audiovisual and auditory trials. During testing, accuracy was significantly higher for congruent trials than unisensory or incongruent trials, and the congruency effect was larger for untrained high-distortion stimuli than trained low-distortion stimuli. In Experiment 3, when high-distortion stimuli (less similar to the prototypes) were trained, there was higher accuracy for audiovisual trials than visual or auditory trials, and the congruency effect was larger for trained high-distortion stimuli than untrained low-distortion stimuli during testing. These findings demonstrated that higher degree of stimuli distortion resulted in more robust multisensory effect, and the categorization of not only trained but also untrained stimuli in one modality could be influenced by an accompanying stimulus in the other modality.

Comparison of Levitt's CO breath test and the 15 N-glycine labeling technique for measuring the lifespan of human red blood cells.

The red blood cell (RBC) lifespan is an important physiological indicator of clear significance in clinical research, used for the differential diagnosis of various diseases such as anemia, compensatory phase hemolysis, and polycythemia. The 15 N-glycine labeling technique is the gold standard method for determining RBC lifespans. However, the usefulness of this technique in clinical settings is seriously hindered by the several weeks required to complete the analyses. Levitt's CO breath test is another reliable technique for determining RBC lifespans, with a simpler protocol giving much faster results, making it more useful in clinical applications. We compared the CO breath test and 15 N-glycine labeling technique for measuring the human RBC lifespan. We investigated human RBC lifespans where each subject undertook both the 15 N-glycine labeling technique and the CO breath test. The correlation between the results from these two methods was analyzed. Eight of the ten subjects successfully completed the study. The RBC lifespan values obtained by Levitt's CO breath test were lower than those obtained by the 15 N-glycine labeling technique. The RBC lifespan values determined from the 15 N-glycine labeling technique and the CO breath test were significantly correlated, with a Pearson correlation coefficient of R = 0.98 (p < 0.05), while the R2 of the linear regression equation was 0.96. The CO breath test exhibits as good performance as the 15 N-glycine labelling technique in distinguishing healthy subjects from subjects with hemolysis. The result suggests that the CO breath test is a reliable method for quickly determining human RBC lifespans in clinical applications.

Time and residual hematopoiesis are crucial for PNH clones escape in hepatitis-associated aplastic anemia.

The presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in aplastic anemia (AA) suggests immunopathogenesis, but when and how PNH clones emerge and proliferate are unclear. Hepatitis-associated aplastic anemia (HAAA) is a special variant of AA, contrarily to idiopathic AA, in HAAA the trigger for immune activation is clearer and represented by the hepatitis and thus serves as a good model for studying PNH clones. Ninety HAAA patients were enrolled, including 61 males and 29 females (median age 21 years). Four hundred three of idiopathic AA have been included as controls. The median time from hepatitis to cytopenia was 50 days (range 0-180 days) and from cytopenia to AA diagnosis was 26 days (range 2-370 days). PNH clones were detected in 8 HAAA patients (8.9%) at diagnosis and in 73 patients with idiopathic AA (IAA) (18.1%). PNH cells accounted for 4.2% (1.09-12.33%) of red cells and/or granulocytes and were more likely to be detected in patients with longer disease history and less severe disease. During follow-up, the cumulative incidence of PNH clones in HAAA increased to 18.9% (17/90). Nine HAAA patients newly developed PNH clones, including six immunosuppressive therapy (IST) nonresponders. The clone size was mostly stable during follow-up, and only 2 of 14 patients showed increased clone size without proof of hemolysis. In conclusion, PNH clones were infrequent in newly diagnosed HAAA, but their frequency increased to one that was similar to the IAA frequency during follow-up. These results suggest that the PNH clone selection/expansion process is dynamic and takes time to establish, confirming that retesting for PNH clones during follow-up is crucial.