Obesity is associated with poor outcomes of corticosteroid treatment in patients with primary immune thrombocytopenia.

Emerging evidence has demonstrated that obesity impacts multiple immune-related diseases. It remains unclear whether and how obesity alters treatment outcomes in patients with primary immune thrombocytopenia (ITP). Thus, we retrospectively investigated 214 treatment-naïve patients who received standard high-dose dexamethasone therapy in Qilu Hospital. Patients with obesity showed significantly lower overall initial response (underweight vs. normal vs. overweight vs. obese: 85.7% vs. 85.2% vs. 72.0% vs. 52.3%, p = 0.001) and initial complete response ([CR], 71.4% vs. 70.4% vs. 53.3% vs. 27.3%, p < 0.001) rates. The same trend was observed in the 6-month sustained response (63.6% vs. 52.3% vs. 35.6% vs. 22.7%, p = 0.03) and sustained CR (36.4% vs. 44.6% vs. 24.4% vs. 9.1%, p = 0.01). The Kaplan-Meier analysis revealed a shortened duration of remission in the obese group (median duration of remission, not reached vs. 16 months vs. 2 months vs. 1 month, p = 0.002). In multivariate regression analysis, obesity was independently associated with poor initial and sustained responses, and an increased risk for relapse. In conclusion, obesity is a negative predictor for outcomes of corticosteroid treatment. A stratified strategy according to body mass index status may facilitate the precision management of ITP.

Identification of novel NFKB1 and ICOS frameshift variants in patients with CVID.

Common variable immunodeficiency (CVID) is a 'late-onset' primary immunodeficiency characterized by variable manifestations and genetic heterogeneity. A monogenic cause of CVID has been reported in 10% of patients. In this study, we identified two novel pathogenic variants implicated in monogenic CVID by whole exome sequencing (WES) analysis: a heterozygous nuclear factor κB subunit 1 (NFKB1) p.G686fs mutation and a homozygous inducible T-cell co-stimulator (ICOS) p.L96Sfs mutation. The predicted crystal models indicated premature truncation of the two mutated proteins. Both variants were demonstrated as loss-of-function mutations and were associated with overlapped manifestations of respiratory fungal infection and splenomegaly. We further performed a detailed assessment of immunologic phenotypes and impaired lymphocyte functions in patients. Moreover, we discovered an association between monoclonal T-large granular lymphocyte proliferation and ICOS-deficient CVID for the first time. These observations lead to a new perspective on the underlying genetic heterogeneity of CVID.

Preparation of molecularly imprinted polymer with class-specific recognition for determination of 29 sulfonylurea herbicides in agro-products.

Molecularly imprinting polymers with high selectivity toward 29 sulfonylurea herbicides were synthesized by precipitation polymerization, using metsulfuron-methyl and chlorsulfuron as the template molecule, 4-vinylpyridine as the function monomer, divinylbenzene as the crosslinking agent, and acetonitrile as porogen. The imprinted polymers were characterized and measured by scanning electron microscopy (SEM) and equilibrium adsorption experiments. The molecularly imprinted polymers displayed specific recognition for the tested 29 sulfonylurea herbicides, and the maximum apparent binding capacity was found to be 18.81 mg/g. The synthesized polymer was used as a solid-phase extraction (SPE) column coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for determination of the tested analytes in agro-products. Within the range of 2-100 µg/L, the tested analytes have achieved a good linear association with correlation coefficient (R2) > 0.999. The calculated limits of detection (LODs, S/N=3) as along with limits of quantification (LOQs, S/N=10) were in the ranges of 0.005-0.07 µg/L and 0.018-0.23 µg/L, respectively. Under different spiking levels, the recovery rates were ranged from 74.8% - 110.5%, and the relative standard deviation (RSDs) were < 5.3%. Finally, the feasibility of the proposed methodology was successfully applied for detection of sulfonylurea herbicides in crops, vegetables, and oils samples.

An overview on molecular imprinted polymers combined with surface-enhanced Raman spectroscopy chemical sensors toward analytical applications.

Surface-enhanced Raman spectroscopy (SERS) is a powerful and high-speed detection technology. It provides information on molecular fingerprint recognition with ultrahigh sensitive detection. However, it shows poor anti-interference capacity against complex matrices. Molecularly imprinted polymers (MIPs) can achieve specific recognition of targets from complex matrices. Through introducing the MIP separation system, the MIP-SERS chemical sensor can effectively overcome the limitation of complex matrix interference, and further improve the stability of sensors for detection. Herein, the materials and structures of integrated MIP-SERS sensors are systematically reviewed, and its application as a sensor for chemical detection of hazardous substances in environmental and food samples has been addressed as well. To broaden the prospects of application, we have discussed the current challenges and future perspectives that would accelerate the development of versatile MIP-SERS chemical sensors.

Sensitive SERS assay for glyphosate based on the prevention of l-cysteine inhibition of a Au-Pt nanozyme.

Herein, an indirect SERS sensing assay was developed for the determination of glyphosate (Gly) in tap water. The mechanism of detection was based on relieving the inhibitory effect of l-cysteine (l-cys) on a Au-Pt nanozyme by combining Gly with l-cys through divalent copper ions (Cu2+). In this method, a novel nano-chain-like Au-Ag composite with good repeatability was successfully fabricated to detect SERS signals of oxTMB without disturbing TMB Raman signals. Under optimal conditions, the SERS signal intensity of oxTMB (at 1605 cm-1) was proportional to the concentration of Gly. The results showed a good linear response over the concentration ranges of 10 µg L-1 to 1000 mg L-1. The limit of detection and limit of quantitation of Gly were found to be 5 µg L-1 and 10 µg L-1, respectively. In addition, good anti-interference ability against interfering cations and structural analogues deserves to be mentioned. This SERS assay can be used for detection of Gly in tap water that can meet the needs of practical detection.

MLF1IP promotes normal erythroid proliferation and is involved in the pathogenesis of polycythemia vera.

Myelodysplasia/myeloid leukemia factor 1-interacting protein (MLF1IP) appears to be an erythroid lineage-specific gene in mice; however, its role in normal erythropoiesis and erythropoietic disorders have not yet been elucidated. Here, we found that MLF1IP is abundantly expressed in human erythroid progenitor cells and that MLF1IP-deficiency reduces cell proliferation resulting from cell cycle arrest. Moreover, MLF1IP expression is exclusively elevated in CFU-E cells from polycythemia vera (PV) patients, and MLF1IP transgenic mice develop a PV-like disorder. Further analyses revealed that the erythroid progenitors and early-stage erythroblasts from these transgenic mice expand by up-regulating cyclin D2 and down-regulating p27 and p21. Thus, our data demonstrate that MLF1IP promotes erythroid proliferation and is involved in the pathogenesis of PV, suggesting that it might be a novel molecular target for erythropoietic disorders.

A systematic classification of megakaryocytic dysplasia and its impact on prognosis for patients with myelodysplastic syndromes.

BACKGROUND: Dys-megakaryopoiesis is defined as ≥10 % of dysplastic megakaryocytes in bone marrow smears by the World Health Organization. However, concordance rates for dysplastic megakaryocytes between different observers is low and, consequently, evaluation of dysmegakaryopoiesis is also often discordant. RESULTS: We performed CD41 immune staining and proposed a systematic classification of dys-megakaryopoiesis on bone marrow films: (1) micro-megakaryocytes (<12 µm); (2) micro-megakaryocytes (12-40 µm) with 1 nucleus; (3) micro-megakaryocytes (12-40 µm) with 2 nuclei; (4) micro-megakaryocytes (12-40 um) with multiple (more than 2) nuclei; (5) dysplastic megakaryocytes (≥40 µm) with 1 nucleus; (6) dysplastic megakaryocytes (≥40 µm) with 2 nuclei; and (7) dysplastic megakaryocytes (≥40 µm) with multiple (more than 2) nuclei. Further, we evaluated the prognostic impact of micro-megakaryocytes and dysplastic mono-nucleated megakaryocytes on MDS patients. The best discriminator cut-off point for each group was determined by the minimal P value approach. In multivariate analyses micro-megakaryocytes ≥25 % and dysplastic mono-nucleated megakaryocytes ≥30 % were independent adverse prognostic factors (hazard ratio [HR] = 1.58 [95 % confidence interval [CI], 1.11, 2.23]; P = 0.010 and 1.53 [1.09, 2.16]; P = 0.014). CONCLUSIONS: Our data suggest integration of micro-megakaryocytes and dysplastic mono-nucleated megakaryocytes improve predictive accuracy of the international prognostic scoring system-revised (IPSS-R) scoring system.

[Clinical significance of Sokal, Hasford and EUTOS prognostic scoring systems in chronic myeloid leukemia].

OBJECTIVE: To compare the validity of three currently used chronic myeloid leukemia (CML) scoring systems (Sokal CML prognostic scoring system, Hasford prognostic scoring system, and EUTOS prognostic scoring system) in chronic phase CML (CP-CML) patients. METHODS: One hundred and thirteen CP-CML patients taking hydroxyurea, interferon or imatinib were enrolled in this study. All patients were stratified into different groups according to each scoring system and different therapies respectively. And overall survival (OS) rates were observed and compared among different groups. RESULTS: Three scoring systems were effective predictors of OS in CP-CML patients, and EUTOS scoring system may predict more validly. Hasford scoring system was well correlated with Sokal and EUTOS scores (r=0.792, P<0.01 and r=0.624, Plt;0.01). The correlation between Sokal and EUTOS scores was relatively weak (r=0.508, Plt;0.01). Despite imatinib's marked effect in prolonging survival of CML patients, it was incapable of prolonging survival in Sokal, Hasford and EUTOS high- risk patients. CONCLUSION: EUTOS prognostic scoring system may predict better than Sokal and Hasford systems in CML patients. Classification of patients based on the three scoring systems may assist in the choice of appropriate therapy for CML.

Role of spleen tyrosine kinase in the pathogenesis of chronic lymphocytic leukemia.

The antigen-dependent B-cell receptor (BCR) is triggered by binding to external antigens and transmits signals in normal B lymphocytes. Tonic signaling through the BCR plays a crucial role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). Spleen tyrosine kinase (Syk) is a key component of both BCR signals, and regulates multiple physiological functions of B lymphocytes. Studies have defined enhanced gene expression and protein expression of Syk in CLL cells which are closely related to the status of the immunoglobulin heavy chain variable region genes (IgVH). Recently, abrogating the BCR-induced signaling pathway by Syk inhibitors has represented a novel and active therapeutic approach for CLL. Studies of the correlation between Syk and ZAP-70 expression in CLL cells have brought a new perspective to determining the value of Syk in evaluating the effect of therapy and the prognosis of CLL. Therefore, we here review the role of Syk in the pathogenesis of CLL and provide an update of progress in the clinical development of Syk inhibitors.