Efficacy and safety of high dose recombinant human thrombopoietin in the treatment of immune thrombocytopenia.

The conventional dose of recombinant human thrombopoietin (rhTPO) in the treatment of immune thrombocytopenia (ITP) is 300 U/kg per day, but the clinical reaction rate is not satisfactory. Accordingly, we explored the efficacy and safety of increasing rhTPO dose in the treatment of ITP. A retrospective study was conducted to collect the clinical data of 105 ITP patients who were divided into two groups, a low-dose group (15 000 U/day) and a high-dose group (30 000 U/day) according to the dose of rhTPO. The total effective rate of the low-dose group and the high-dose group was 31/44 (70.45%) vs. 56/61 (91.80%) (P = .049), and the average time of using rhTPO in the high-dose group was shorter than that in the low-dose group (7 days vs. 10 days, P = .001). On the 7th and 14th day of treatment, the efficacy of the high-dose group was better than that of the low-dose group [45/61 (73.77%) vs. 17/44 (38.64%), P < .001; 55/60 (91.67%) vs. 30/44 (68.18%), P < .05)]. The incidence of treatment related adverse events in the low-dose group and the high-dose group was 6/44 (13.64%) vs. 6/61 (9.84%) (P > .05), which were mild and transient in nature. In our study, high-dose rhTPO had good efficacy and high safety in the treatment of ITP with the efficacy better than low-dose rhTPO especially at day 7.

What is the context? Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by low platelet counts due to increased platelet destruction and impaired platelet production.The therapy direction of ITP involves promoting platelet generation, reducing excessive platelet destruction, immune regulation and so on.Recombinant human thrombopoietin (rhTPO), a promote platelet production drug, has pharmacological action similar to that of endogenous TPO. It can increase platelet count rapidly and effectively and has immunological regulation effect as well.It is found that rhTPO can rapidly and effectively increase platelet count, which has potential clinical application value in emergency situations.What is new? Traditionally, rhTPO has been recommended at 300 U/kg per day. Although it can greatly improve the treatment effect of ITP, the effect is not very satisfactory. In clinical practice, it has been observed that rhTPO dosage is often relatively insufficient and the therapeutic effect is poor. Therefore, we explored the efficacy and safety of increasing rhTPO dose in the treatment of ITP.Within the efficacy and safety of rhTPO 15 000 U/day and 30 000 U/day in the treatment of ITP, our analyses suggest that:The early response rate of the high-dose group was better than that of the low-dose group.In the high-dose group, the effective rate of rhTPO alone or combined with glucocorticoids was more than 90%.Treatment related adverse events occurred at a low rate and remained mild and transient.What is the impact? Comparing with conventional dose rhTPO, high-dose rhTPO may have better efficacy and safety in the treatment of immune thrombocytopenia and shorter administration time.

Highly Stable and Eco-friendly Marine Self-Charging Power Systems Composed of Conductive Polymer Supercapacitors with Seawater as an Electrolyte.

A self-charging power system harvesting random and low-frequency wave energy into electricity provides a promising strategy for the construction of smart oceans. However, the system faces huge challenges of easy corrosion in the marine environment and the utilization of toxic organic electrolytes in energy storage devices. To address the issues above, a seawater supercapacitor (SWSC) for the marine self-charging power system is rationally proposed by using a conductive polymer, polypyrrole with hollow morphology (h-PPy), to enhance the stability and capacitance while using seawater as an eco-friendly electrolyte to reduce the cost and achieve sustainability. The hollow design provides a shortcut for the ion transportation of seawater into the h-PPy electrode, and the SWSC achieves a high power density of 4.32 kW kg-1 under an energy density of 5.12 W h kg-1. Even after 180 days in seawater, h-PPy still endows a mass retention of 99.9%, enabling the SWSC to maintain a stability of 99.3% after 6000 cycles. More importantly, when combined with a TENG module as the marine self-charging power system to harvest wave energy, the system provides a stable output in water wave to drive electronics and sensors, which shows a competitive potential in the smart ocean and marine internet of things.

Radiomics-based comparison of MRI and CT for differentiating pleomorphic adenomas and Warthin tumors of the parotid gland: a retrospective study.

OBJECTIVE: The objective of this study was to compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) in differentiating pleomorphic adenomas from Warthin tumors using radiomics. STUDY DESIGN: We retrospectively reviewed 626 patients who underwent preoperative MRI or CT for parotid tumor diagnosis. Patient groups were balanced by propensity score matching (PSM) and 123 radiomic features were extracted from tumor images. Radiomic signatures (rad-scores) were generated using a least absolute shrinkage and selection operator logistic regression model. The Canny edge detector was used to define tumor borders (border index). The diagnostic performance of rad-score and border index before and after PSM was evaluated with area under the receiver operating characteristic curve analysis. RESULTS: For differentiation of pleomorphic adenomas and Warthin tumors, rad-score and border index areas under the curve for MRI after PSM were 0.911 (95% confidence interval [CI], 0.871-0.951) and 0.716 (95% CI, 0.646-0.787), respectively; those for CT were 0.876 (95% CI, 0.829-0.923) and 0.608 (95% CI, 0.527-0.690), respectively. Tumor border index on MRI, but not CT, had superior diagnostic performance (P < .05); MRI- and CT-based rad-scores showed similar performance (P >.05). CONCLUSIONS: MRI is superior to CT for tumor margin examination; however, the radiomics features of both modalities showed no difference.

Magnetic resonance image biomarkers improve differentiation of benign and malignant parotid tumors through diagnostic model analysis.

OBJECTIVES: To explore the effectiveness of magnetic resonance image (MRI)-based biomarkers for identifying benign and malignant parotid tumors via diagnostic model analysis. METHODS: This retrospective study included 109 patients (development cohort and validation cohort) who underwent MRI preoperatively, including T1- and T2-weighted images. Parameters based on 2D or 3D texture analysis were extracted from tumor lesions by MaZda software, fisher discriminant and bootstrap method were used to perform parameter reduction, diagnostic models with the selected biomarkers were established along with clinical data, model performance (discrimination and calibration) was furtherly evaluated by internal and external validation, decision curve analysis was applied to measure the improvement of clinical benefits. RESULTS: S(5,5) Entrop, S(0,1) ASM, WavEnHH (s-4), S(1,1,0) Entropy and Perc.10% were significantly associated with the pathological diagnosis of parotid tumor (benign versus malignancy), when adding these biomarkers to the regression analysis, model performance significantly improved in the development cohort (likelihood-ratio-test; p < 0.05, with an increase of AUC from 0.72 (reference model) to 0.85), and these results were maintained in a small external validation cohort. Decision curve analysis indicated that clinical benefit was greater with the application of MRI-based biomarkers. CONCLUSIONS: MRI-based texture analysis is proven to be an effective tool in differentiating benign and malignant parotid tumors, preoperative diagnosis was improved with the selected biomarkers compared to the reference model.

High efficient detoxification of mustard gas surrogate based on nanofibrous fabric.

In recent years, people pay more attention to the protection against chemical warfare agents, due to the increase in the probability of usage of these chemical warfare agents in wars or terrorist attacks. In this work, MgO nanoparticles were in-situ growth on the surface of poly(m-phenylene Isophthalamide) (PMIA) forming a flexible and breathable fabric for the detoxification of mustard gas surrogate. The as-prepared nanofibrous membrane possesses a "flower-like" structure of which endows not only increase the specific surface area of the composite but also prevent the agglomeration of the MgO nanoparticles. The detoxification ability of the PMIA@MgO nanofibrous fabric was demonstrated by gas chromatography-mass spectrometer (GC-MS). It is found that after 20 h of reaction time, 70.56% of the mustard gas surrogate have been decomposed.

[MUC1-2VNTR DNA Vaccine Induces Immune Responses in Mouse Model with Multiple Myeloma].

OBJECTIVE: To investigate the humoral and cellular immune responses induced by MUC1-2VNTR DNA vaccine in multiple myeloma (MM) tumor-bearing mice. METHODS: In vitro, multiple myeloma cells were transfected by plasmid pcDNA3.1-2VNTR/myc-hisB with Lipofectamine2000. The above-mentioned mouse myeloma cells were inoculated subcutaneously into female BALB/c mice for establishing tumor-bearing animal models. These female BALB/c mice were immunized with pcDNA-2VNTR/myc-hisB or pcDNA/myc-hisB. The cytotoxic T lymphocyte (CTL) activity was detected by the LDH method and the spleen lymphocyte proliferation activity was detected by CCK-8 method. RESULTS: After immunization of BALB/c tumor-bearing mice with recombinant plasmid for 25 days, the tumor mass (0.5605 ± 0.2065 g) was significantly lighter than that in the empty plasmid control group (1.521 ± 0.6985 g) (P < 0.01) and the control group (1.5315 ± 0.5425 g) (P < 0.01). The difference of tumor mass was not statislically significant between empty plasmid control group (1.521 ± 0.6985 g) and the control group (1.5315 ± 0.5425 g) (P > 0.05). The CTL and NK cell activity was significantly higher in the group of intramuscular injection with recombinant plasmid than that in control group. The spleen lymphocyte proliferation was statistically significantly increased after being immunized with recombinant plasmid pcDNA3.1-2VNTR/myc-hisB, compared with empty vector (P < 0.01). The results showed that MUC1-2VNTR gene immunization could induce anti-tumor effect in MM tumor-bearing mice. CONCLUSION: MUC1-2VNTR DNA immunization can elicit both humoral and cellular tumor specific immune response to multiple myeloma in MM tumor-bearing mice. It suggested that the MUC1-2VNTR DNA vaccine may be a potential treatment measure for patients with MM.

A unique MUC1-2-VNTR DNA vaccine suppresses tumor growth and prolongs survival in a murine multiple myeloma model.

Multiple myeloma (MM) is a clonal B-cell malignancy charactered by the aberrant proliferation of malignant plasma cells in the bone marrow. MM is still an incurable malignancy. In this regard, novel treatments are urgently required. MUC1 (mucin 1), a type І transmembrane protein, is overexpressed and aberrantly glycosylated in many carcinomas particularly in MM resulting in an antigenically distinct molecule and may be a potential target for specific immunotherapy. In this study, we first designed a unique DNA vaccine, termed MUC1-2-VNTR (various number tandem repeats) to investigate whether the vaccine could specifically suppress tumor growth in a murine multiple myloma model. Our results showed that the constructed DNA vaccine pcDNA3.1-VNTR elicited both humoral and cellular tumor-specific immune responses in the MM mouse model leading to delay in tumor growth and prolonged survival of the mice. Consequently, our study indicates that this DNA vaccine shows promise to be used as a novel strategy for the treatment of MM.

[Construction of eukaryotic expressing vector of multiple myeloma mucin-1 and its expression in COS-7 cells in vitro].

In order to construct an eukaryotic expression vector for gene of multiple myeloma mucin1 (muc1-2vntr) gene and to express it in COS-7 cells in vitro, so to provide the basic material for further research of multiple myeloma DNA vaccine. muc1-2vntr coding gene was used as a research gene and a KOZAK sequence was inserted before the gene Hind III and XbaI restriction sites were inserted before and after the coding gene. Then the whole sequence was synthesized and inserted into pcDNA3.1/myc-his B vector, and the resulted recombinant vector was transformed into E.coil competent cells to get an engineering strain, the recombinant plasmid pcDNA3.1-2vntr/myc-his B identified by restriction analysis and DNA sequencing were transfected into COS-7 cells by liposome-mediated gene transfer method. Finally, fluorescent microscopy was used to assess GFP expression and Western blot analysis using muc1 monoclonal antibody was used to recognize vntr, confirming the expression of vntr. The results showed that the full length of synthesized muc1-2vntr gene, as expected, was 140 bp. Both restriction analysis and DNA sequencing demonstrated that pcDNA3.1-2vntr/myc-his B included the whole translation frame region and muc1-2vntr gene. Furthermore, the fluorescence microscopy proved that the recombinant plasmid had been successfully transfected into COS-7 cells. The expression of mucin-1 protein was observed both in the transfected cell and the cell supernatant by Western blot. It is concluded that the pcDNA3.1-2vntr/myc-his B has been successfully constructed and expressed in COS-7 cells in vitro, which provides the basic material for further researches of mucin-1 function and possible multiple myloma DNA vaccine.