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An ideal bone metastasis animal model is critical and fundamental for mechanistic research and following development of new drug and treatment. Caudal artery (CA) injection allows bone metastasis in the hindlimb, while in-depth targeted and quantitative studies of bone metastasis require a new model to overcome its limitations. Here, we developed a targeted, quantitative, and highly consistent method for the modeling of bone metastasis with cell-based magnetic micro-living-motor (MLM) system created by effectively combining Fe 3 O 4 -PDA-Au with biosafety. The MLM system can achieve efficient migration, target site colonization and control tumorigenesis in bone precisely with the application of a magnetic field. In vivo, day 3 post cell injection, tumor bone metastasis signals were observed locally in the injected femur among 82.76% mice of the MLM group as compared to the 56.82% in the CA group, and the signal intensity was 45.1 and 95.9 times stronger than that in the left and right lower limbs of the CA group, respectively. Post-injection day 28, metastasis in vital organs was reduced by approximately 90% in the MLM group compared to the CA group. Our innovative use of the MLM system in the field of tumor modeling opens a new avenue for exploring the mechanisms of tumor bone metastasis, recurrence and drug resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Rapid and specific detection of virulent bacterial strains is a great challenge for food safety regarding large amounts of contaminated samples. Herein, a dual-mode hydrogel array biosensor was constructed to simultaneously rapidly screen and precisely quantitatively detect virulent Escherichia coli O157:H7 (E. coli O157:H7) based on a novel DNA-modified phage probe. First, E. coli O157:H7 was incubated with alginate to form the E. coli O157:H7/hydrogel premix complex. Subsequently, hydrogel formation by cross-linking upon the addition of calcium ions and phages for E. coli O157:H7 modified with a DNA primer (phage-DNA) was added to the alginate hydrogel. The DNA on the complex could trigger rolling circle amplification (RCA) to form a phage probe containing a long-chain DNA skeleton (phage@RCA-DNA). The RCA-DNA was then hybridized with the complementary DNA (cDNA) to form double-stranded DNA fragments (phage@RCA-dsDNA), which could be stained by the SYBR Green dye to emit visual green fluorescence (FL) and determined by a smartphone for rapid screening. Meanwhile, the unreacted cDNA in the supernatant could be quantitatively detected by microfluidic chip electrophoresis (MCE). The signal decrement was also proportional to the bacterial concentration. The detection limit values of E. coli O157:H7 were 50 CFU mL -1 by the FL signal and 6 CFU mL -1 by the MCE signal. The two results could be mutually corrected to decrease the false-positive results. This assay was also employed to detect virulent Salmonella Typhimurium (S. Typhimurium) using the corresponding S. Typhimurium phage@RCA-DNA probe. All these results demonstrated that the universal bioassay was suitable for simultaneous rapid screening and precisely quantitative detection of virulent bacterial strains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chronic graft-versus-host disease (cGVHD) involves multiple organs, but little is known about bone marrow (BM) alterations caused by cGVHD. In mice and humans, we found that cGVHD is associated with BM fibrosis resulting in T cell infiltration, IgG deposition, and hematopoietic dysfunction. Macrophages and Nestin+ mesenchymal stromal cells (MSCs) participated in the process of BM fibrosis during BM cGVHD development. BM macrophage numbers were significantly increased in mice and humans with BM fibrosis associated with cGVHD. Amplified macrophages produced TGF-β1, which recruited Nestin+ MSCs forming clusters, and Nestin+ MSCs later differentiated into fibroblasts, a process mediated by increased TGF-β/Smad signaling. TLR4/MyD88-mediated activation of endoplasmic reticulum (ER) stress in macrophages is associated with fibrosis by increasing Nestin+ MSC migration and differentiation into fibroblasts. Depletion of macrophages by clodronate-containing liposomes and inhibition of ER stress by 4-phenylbutyric acid reversed BM fibrosis by inhibiting fibroblast differentiation. These studies provide insights into the pathogenesis of BM fibrosis during cGVHD development., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Overexpression of Wilms' tumor ( WT1 ) is frequently observed in myelodysplastic syndrome (MDS), which has been proposed as a prognostic marker. However, the prognostic role of WT1 expression in different contexts remains to be fully elucidated. We retrospectively assessed the relationships between WT1 levels and preexisting prognostic factors to further investigate its prognostic role under different contexts. In our study, WT1 expression was positively correlated with WHO 2016 classification and IPSS-R stratification. Lower WT1 expression was found in relation to TET2 , TP53 , CD101, or SRSF2 mutations, while mutant NPM1 patients possessed higher level. Notably, WT1 overexpression maintained its inferior prognostic effect on overall survival (OS) in TP53 -wild patients but not in TP53 -mutated group. In multivariate analysis, higher WT1 expression was a risk factors for OS in EB patients without TP53 mutations. Overall, WT1 expression was useful to predict prognosis for MDS and its prognostic role was impacted by some gene mutations.

Background Aims: Bone marrow-derived hematopoietic stem cell transplantation/hematopoietic progenitor cell transplantation (HSCT/HPCT) is widely used and one of the most useful treatments in clinical practice. However, the homing rate of hematopoietic stem cells/hematopoietic progenitor cells (HSCs/HPCs) by routine cell transfusion is quite low, influencing hematopoietic reconstitution after HSCT/HPCT., Methods: The authors developed a micro-living motor (MLM) strategy to increase the number of magnetically empowered bone marrow cells (ME-BMCs) homing to the bone marrow of recipient mice., Results: In the in vitro study, migration and retention of ME-BMCs were greatly improved in comparison with non-magnetized bone marrow cells, and the biological characteristics of ME-BMCs were well maintained. Differentially expressed gene analysis indicated that ME-BMCs might function through gene regulation. In the in vivo study, faster hematopoietic reconstitution was observed in ME-BMC mice, which demonstrated a better survival rate and milder symptoms of acute graft-versus-host disease after transplantation of allogeneic ME-BMCs., Conclusions: This study demonstrated that ME-BMCs serving as MLMs facilitated the homing of HSCs/HPCs and eventually contributed to earlier hematopoietic reconstitution in recipients. These data might provide useful information for other kinds of cell therapies., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2022. Published by Elsevier Inc.)

To reveal the adsorption mechanism of sediment to antibiotics with the presence of dissolved organic matter (DOM), batch experiments were carried out by oxytetracycline (OTC) on sediments with decayed plants (PDOM) and composted chicken manure (MDOM), and the zeta potential in the system before and after adsorption was measured. Results showed that the PDOM promoted the adsorption process, while the MDOM inhibited the adsorption. Adding PDOM, the change of zeta potential (Δζ) increased by 40.08% for first terrace sediments (FT) and 63.98% for riverbed sediments (RB), respectively; meanwhile, MDOM decreased by 20.04% for FT and 28.39% for RB, respectively. The results of kinetic fitting models of replacing the adsorption amount with Δζ were consistent with the initial. It indicated that there was a positive correlation between the adsorption amount and Δζ, and the zeta potential can be used to quickly judge the degree of adsorption process. The Derjaguin-Landau-Verwey-Overbeek (DLVO) theory describes the interactions of sediment particles. In terms of adsorption amount, zeta potential (absolute value) and total interaction energy all followed the order: RB > FT, RB-PDOM > FT-PDOM, and RB-MDOM > FT-MDOM. The more negative the zeta potential is, the better the dispersion of the particles is. Stronger repulsion is more conducive to adsorbing positively charged OTC. The site energy distribution theory further explained that the distribution of adsorption site in the various states of sediments increased while adding the PDOM and decreased while adding the MDOM.

Background: Since 1998, China has gradually moved toward voluntary uncompensated blood donation. In some cities, the shortage of platelets has been noticeably severe. Mutual assistance that collects blood from one's family and social networks is a potential solution. The measure, however, turned out problematic. There are donors who choose to donate platelets over whole blood without compensations, and donate platelets directly to blood banks instead of via the mutual assistance system. This study explores reasons behind their choices qualitatively., Methods: This report is based on data conducted from January to February 2018; 25 uncompensated regular platelet donors were interviewed. The blood component donation service team in Guangzhou facilitated the data collection process and referred prospectively eligible blood donors to our research team. The interviews took about 30 min to two hours to complete. The qualitative data were analyzed by using the software ATLAS.ti 8., Results: Platelet donation takes a much long time than whole blood donation and requires complicated processes. It may also cause discomfort as the other blood components are returned to the body, causing physical and psychological distress due to worries about contamination. Thus, platelet donation tends to involve higher time and psychological costs than whole blood donation. Yet, it has short collection intervals that allows for more frequent donations, and urgency of a severer shortage than whole blood. Hence, regular platelet donors may feel higher significance in platelet donation than whole blood donation, with the belief that more lives would be saved. Some whole blood donors thus switched to become platelet donors. Mutual assistance blood donation was not chosen by the participants for platelet donation, because such donations may exert moral pressure to both the donors and recipients. Furthermore, "acquaintance" has been loosely defined; the system has sometimes been manipulated to become profit-making monetary transactions. It hence failed., Conclusions: The practice of platelet donation reinforces the understanding that blood donation is a gift giving process performed among strangers. A safe and sustainable voluntary blood supply can only be secured in the absence of monetary transactions and moral pressure.

Objective The agranulocytosis-associated perianal infection (PI) rate ranges from 60% to 100% among patients with hematopoietic malignancies. In this study, we assessed the efficacy of a quality control circle (QCC) to minimize the PI rate. Methods Among 274 patients with severe immunodeficiency (agranulocytosis of ≥2 weeks) in our bone marrow transplantation center, the PI rate was 17.20%. A QCC was established following the 10 steps of the plan-do-check-act (PDCA) model; this was scientifically supported by culturing the bacterial colony from patients' perianal skin to determine the sanitization effect and interval time. Because a warm aqueous solution of potassium permanganate is recommended for sanitization, the bacterial colony culture was also used to determine the proper drug concentration, water temperature, and soaking time. All procedures were standardized. Patients, hospital staff, and medical students were enrolled into the QCC team based on the patient-hospital-student (PHS) win-win concept. Results After establishment of the PDCA model, the PI rate among 253 patients decreased from 17.20% to 5.93% and remained at 5.25% during the following year. The medical expenses and length of hospital stay consequently decreased. Conclusion The QCC and PHS win-win concept can reduce the PI rate and promote medical quality.

The sludge from the water supply plant was investigated to remove fluoride ions from the water. To improve the adsorption ability, the original sludge sample was treated with fuel oxidation, pyrolysis, hydrochloric acid, and sulphuric acid methods, and hydrochloric acid treatment improved the adsorption capacity of the sludge on the fluoride in water significantly, with a maximum adsorption capacity to 140 mg/kg. The adsorption experimental data was the well fitted pseudo-first-order model and the Langmuir isotherms model. SEM images and XRD patterns of the adsorbent were recorded to get a better insight into the adsorption process. The effect of three variables, hydrochloric acid treated sludge (HWS) dose, pH, and initial fluoride concentration were studied using a Box-Behnken statistical experimental design. The model of the adsorption and optimum conditions was investigated using the response surface methodology. The optimum removal efficiency of fluoride can reach 81.153% under the optimum condition: HWS dose of 14.10 g/L and pH value at 6.12. The effect of co-existing anions and the removal efficiency from the water were also studied. The results suggest that sludge from the water supply plant can be reused as a coagulant for the removal of fluoride from poor quality water.

The treatment of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) has entranced tyrosine kinase inhibitors (TKIs) era. Currently both imatinib and dasatinib are registered as the front-line treatment for Ph+ ALL, and the other 2 nd -generation TKIs are suggested as an alternative for those who failed the first-line treatment. However, it remains unclear who could benefit from the 2 nd -generation TKIs as the first-line treatment for Ph+ ALL. In this study we compared the efficacy and safety of the 1 st and 2 nd -generation TKIs in the front-line treatment of Ph+ ALL and found a trend toward better disease-free survival (DFS) in the 2 nd -generation TKIs group, though no significant difference in early response and long-term survival between the two groups. Furthermore, subgroup analysis showed that if allogeneic hematopoietic stem cell transplantation (allo-HSCT) was incorporated as consolidation, the 2 nd -generation TKIs benefited patients with better DFS and overall survival (OS). The two generation TKIs were well tolerated. Higher incidence of acquiring T315I mutation was observed in the patients relapsed on the 2 nd -generation TKIs. These findings suggested front-line treatment of Ph+ ALL with the 2 nd -generation TKIs might benefit patients with better survival when allo-HSCT was incorporated as consolidation therapy; meanwhile, the higher incidence of T315I mutation in patients relapsed on the 2 nd -generation TKIs deserved further attention., Competing Interests: CONFLICTS OF INTEREST There is no conflicts of interest.

Autoimmune hematological diseases (AHDs) occur more frequently than other autoimmune complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and are often refractory to treatment. This study was to analyze the incidence and risk factors of AHDs as well as their response to treatment . Four hundred and forty-five adult malignant hematopoietic disorders underwent allo-HSCT were enrolled in this retrospective study, including 124 haploidentical donor (HRD), 140 unrelated donor (MUD) and 181 HLA-matched sibling donor (MSD) transplants. Twelve patients developed AHDs, including 6 autoimmune hemolytic anemia and 6 Evans syndrome. Evans syndrome all occurred in HRD transplants. The 3-year cumulative incidence of AHDs was 4.0 ± 1.3%, and HRD had higher incidence than MUD (8.7 ± 3.0% vs 1.8 ± 1.2%, P = 0.012) and MSD (8.7 ± 3.0% vs 3.5 ± 2.6%, P = 0.004 ). The steroids combined with Cyclosporine A were acted as the first line treatment, and the response rate was 73%. No patients experienced recurrence at a median follow up of 313 days after stopping treatment. HRD transplants (vs MUD: HR, 5.87; CI, 1.24 to 27.73; p = 0.026 and vs MSD: HR, 7.70; CI, 1.63 to 36.44; P = 0.010) and concurrent chronic graft versus host disease (HR, 3.76; CI, 1.18 to 11.92; P = 0.025) were risk factors for AHDs.

The major obstacle is leukemia relapse for refractory leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously introduced a strategy of sequential intensified conditioning and early rapid immunosupressant withdrawal for refractory leukemia undergoing allo-HSCT, with 5-year overall survival (OS) and 3-year relapse rate of 44.6% and 33.3%. To reduce leukemia relapse, prophylactic donor lymphocyte infusion (DLI) was administered based on our historical strategy. A total of 153 refractory advanced acute leukemia patients were enrolled in this prospective study. According to the availability of donor lymphocytes and the criteria for DLI, 144 patients surviving day +60 were divided into two groups (80 DLI versus 64 non-DLI). The relapse rate was less and OS was better in patients receiving DLI than in those not receiving DLI (22.7% vs 33.9%, P=0.048; 58.1% vs 54.9%, P=0.043). The non-relapse mortality (NRM) was similar between DLI and non-DLI groups (P=0.104). Overall, the 5-year overall and disease-free survival post-transplantation were 51.1%±5.7% and 49.2%±5.3%. The 5-year relapse rate and NRM were 27.3%±4.4% and 29.7%±5.3%. Multivariate analysis revealed that lower bone marrow blasts on day 0, DLI and chronic graft-versus-host disease were associated with less relapse and better OS. The strategy of sequential intensified conditioning followed by early immunosupressant withdrawal and DLI could reduce relapse of refractory acute leukemia after allo-HSCT and improve survival., Competing Interests: The authors declare no competing financial interests.

In this paper, a novel dispersive solid phase extraction (dSPE) adsorbent based on aptamer-functionalized magnetic metal-organic framework material was developed for selective enrichment of the trace polychlorinated biphenyls (PCBs) from soil sample. Firstly, we developed a simple, versatile synthetic strategy to prepare highly reproducible magnetic amino-functionalized UiO-66 (Fe3O4@PDA@UiO-66-NH2) by using polydopamine (PDA) as covalent linker. Then amino-functionalized aptamers which can recognize 2,3',5,5'-tetrachlorobiphenyl (PCB72), 2',3',4',5,5'-pentachlorobiphenyl (PCB106) were covalent immobilized on UiO-66-NH2 through coupling reagent of glutaraldehyde. Aptamer-functionalized adsorbent (Fe3O4@PDA@UiO-66-Apt) can specifically capture PCBs from complex matrix with high adsorption capacity based on the specific affinity of aptamer towards target. Moreover, the adsorbent can be easily isolated from the solution through magnetic separation after extraction. Afterwards, the detection was carried out with gas chromatography tandem mass spectrometry (GC-MS). The selective dSPE pretreatment coupled with GC-MS possessed high selectivity, good binding capacity, stability, repeatability and reproducibility for the extraction of PCBs. Furthermore, the adsorbent possessed good mechanical stability which can be applied in replicate at least for 60 extraction cycles with recovery over 80%. It provided a linear range of 0.02-400ngmL(-1) with a good correlation coefficient (R(2)=0.9994-0.9996), and the limit of detection was found to be 0.010-0.015ngmL(-1). The method was successfully utilized for the determination of PCBs in soil samples., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To analyze the effect of sorafenib as salvage therapy used before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in refractory relapsed FLT3-positive acute myeloid leukemia (AML)., Methods: A total of 16 patients with refractory relapsed FLT3-positive AML, including 10 refractory relapsed pre-transplantation and 6 relapsed after allo-HSCT, were enrolled in this retrospective study. Sorafenib treatment protocols included sorafenib in combination with chemotherapy inducing remission, and sorafenib monotherapy as mauntenance treatment after complete remission (CR)., Results: Thirteen of the 16 patients achieved CR after one or two courses of induction therapy, including 7 refractory relapsed pre-transplantation and 6 relapsed after allo-HSCT. With a median follow up of 472 (range, 59-1569) days post-transplantation, 12 patients survived and 4 died. Causes of death included leukemia relapse (n=3) and acute graft-versus-host disease (n=1). The 2-year overall and disease-free survival post-transplantation of the 16 patients were (75.0±10.8) % and (50.5±13.7) % respectively. The main side effect of sorafenib was the skin rash. The incidence of rash was lower in the patients used sorafenib pre-transplantation than those post-transplantation (30.0% vs 75.0%, P=0.043)., Conclusion: Sorafenib used as salvage therapy befor and/or after transplantation for refractory relapsed FLT3-positive AML could reduce the relapse rate and improve the survival.

To improve prognosis of post-transplant lymphoproliferative disease (PTLD), a sequential therapeutic strategy that rituximab-based treatments followed by donor lymphocyte infusion (DLI) or autologous EBV-specific cytotoxic T lymphocytes (EBV-CTL) for biopsy-proven EBV-associated PTLD in recipients of allogeneic hematopoietic stem cell transplantation was designed. 84 patients with EBV-PTLD were enrolled in this prospective study. After two cycles of the rituximab-based treatments, 68 of 84 patients (81% [95% CI 71-88]) responded and 52 (62% [51-72]) had CRs. This increased to 73 of 77 patients (95% [87-98]) with completion of sequential cell infusions, and 70 of 77 (91% [82-96]) achieved CRs after DLI or autologous EBV-CTL infusion. 22 patients experienced acute GVHD (aGVHD) (grade I in 5 and grade II in 13, grade III in 4) and 13 chronic GVHD (limited cGVHD in 7 and extensive cGVHD in 6) in 62 patients undergoing a median of three doses of DLI. The incidences of GVHD were similar between DLI and EBV-CTL group (aGVHD 35% vs. 33%, p = 0.876; cGVHD 21% vs. 13%; p = 0.503). EBV-CTL activity after the rituximab-based treatments did not change, while increased after cell infusions and reached its maximum in the 3rd or 6th month after EBV-CTL or DLI treatment, respectively. The 5-y cumulative incidence of PTLD relapse was 4.5% ± 3.3%. The 5-y overall survival (OS) and progression-free survival (PFS) after PTLD were 70.7% ± 5.2% and 68.9% ± 5.3%, respectively. Rituximab-based treatments combined with adoptive cellular immunotherapy might elevate CR rates and reduce relapse of PTLD after allo-HSCT.

The aim of the study is to determine whether HLA-haploidentical-related donor (HRD) transplant can achieve equivalent outcomes and have stronger GVL compared to HLA-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 355 consecutive patients with acute leukemia undergoing allogeneic transplant at our single institute between March 2008 and March 2014 were enrolled in this retrospective investigation. Of the 355 patients, 96 cases received HRD, 153 MSD, and 106 MUD transplants. HRD transplant was associated with higher incidences of grade II to IV aGVHD (40.6%) compared with MSD (23.5%, P = 0.002) and MUD transplants (34.0%, P = 0.049), whereas incidences of grade III to IV aGVHD (11.4%, 7.8%, 10.5%, respectively; P = 0.590) and cGVHD (29.5%, 24.0%, 29.5%, respectively; P = 0.538) did not differ among 3 groups. Five-year relapse rates were 19.2%, 26.8%, and 23.0% in 3 groups, respectively (P = 0.419). However, of 206 high-risk patients, the relapse rate in HRD transplant was lower than in MSD transplant (23.8% vs 41.9%, P = 0.026). Multivariate analysis showed that HRD had beneficial impact on relapse (for MSD: P = 0.006). Five-year transplant-related mortality was lower in MSD transplant compared with those in HRD (17.3% vs 26.4%, P = 0.041) and MUD transplants (17.3% vs 24.1%, P = 0.037). Five-year overall survival were 60.4%, 64.6%, and 61.0%, respectively, in HRD, MSD, and MUD groups (P = 0.371); 5-year disease-free survival were 59.6%, 58.8%, and 54.9%, respectively (P = 0.423). Our results suggest that HRD transplant results in outcomes equivalent to MSD and MUD transplants. HRD might carry a superior GVL effect compared to MSD for high-risk patients.

Introduction: Migratory cells via blood circulation or cells adjacent to the root apex may potentially participate in dental pulp tissue regeneration or renewal. This study investigated whether systemically transplanted bone marrow cells can contribute to pulp regeneration in a chimeric mouse model., Methods: A chimeric mouse model was created through the injection of bone marrow cells from green fluorescent protein (GFP) transgenic C57BL/6 mice into the tail veins of recipient wild-type C57BL/6 mice that had been irradiated with a lethal dose of 8.5 Gy from a high-frequency linear accelerator. These mice were subjected to pulpectomy and pulp revascularization. At 1, 4, and 8 weeks after surgery, in vivo animal imaging and histologic analyses were conducted., Results: In vivo animal imaging showed that the green biofluorescence signal from the transplanted GFP+ cells increased significantly and was maintained at a high level during the first 4 weeks after surgery. Immunofluorescence analyses of tooth specimens collected at 8 weeks postsurgery showed the presence of nestin+/GFP+, α smooth muscle actin (α-SMA)/GFP+, and NeuN/GFP+ cells within the regenerated pulplike tissue., Conclusions: These data confirm that transplanted bone marrow-derived cells can contribute to dental pulp regeneration., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

A novel multiplexed ratiometric biosensor array was fabricated on a homemade screen-printed carbon electrode (SPCE) for near-simultaneous detection of microRNA (miRNA)-21 and miRNA-141 based on electrochemiluminescence (ECL) coupled with cyclic voltammetry (CV) method. In the detection system, the ECL signal tags (Ru-SiO2@PLL-Au) were fabricated using poly-l-lysine (PLL) as bridging agent and co-reactant to connect Ru-SiO2 (Ru(bpy)3(2+)-doped silica) and gold nanoparticles (Au NPs), which were respectively modified on two spatial resolved working electrodes (WE1 and WE2) of SPCE. Then the ferrocene (Fc)-labeled hairpin DNA (Fc-HDNA1 and Fc-HDNA2) as CV signal tags and ECL quenching material were immobilized on Ru-SiO2@PLL-Au. Upon miRNA-21 and miRNA-141 adding, the target miRNAs could hybridize with corresponding Fc-HDNA, which could lead to Fc away from Ru-SiO2@PLL-Au. Such conformational changes could recover the ECL of Ru-SiO2@PLL-Au and decreased the CV current of Fc, respectively. This "signal-on" of ECL and "signal-off" of CV were employed for dual-signal ratiometric readout. With the help of a multiplexed switch, two dual-signals from WE1 and WE2 were used for multiplexed detection of miRNA-21 and miRNA-141 down to 6.3 and 8.6fM, respectively. This approach was used in real sample analysis and has significant potential for miRNA biomarkers detection in a clinical laboratory setting., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To explore the rate of breakthrough invasive pulmonary aspergillosis (IPA) in patients receiving surgical resection of pulmonary aspergillosis lesions prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: A retrospective analysis was conducted between January 2007 and June 2014. A total of 16 patients were enrolled, who had persistent pulmonary lesions including cavity (diameter >2.0 cm) or mass with a history of IPA prior to allo-HSCT in Nanfang Hospital of Southern Medical University. Ten of the 16 patients underwent thoracoscopic surgery before transplantation, i. e. surgery group, the other 6 patients did not have surgery because of primary underlying diseases (non-complete remission) or multiple lesions i. e. non-surgery group. Secondary prophylactic agents were administrated based on treatment response to initial antigual therapy. The 1-year cumulative and breakthrough rate of IPA, the median time of secondary antifungal prophylaxis (SAP) and overall survival were compared between surgery and non-surgery groups., Results: Within a median follow-up of 364 days after transplantation (range 73 to 400 days). The success rate of SAP was 15/16. The 1-year cumulative and breakthrough IPA were 0 and 0 in surgery group, compared with 3/6 and 1/6 in non-surgery group. The median duration of SAP in surgery group and non-surgery group was 95(74-134)days and 192.5 (56-280)days respectively, which was significantly shorter in surgery group (P=0.017). The overall survival between two groups was 8/10 and 4/6 (P=0.534). No discontinuation of SAP happened in both groups due to drug-related adverse events., Conclusions: In patients with persistent pulmonary IPA lesions, surgical resection followed by SAP might be effective to reduce breakthrough IPA after transplantation with short duration of prophylaxis.

A novel type of "dual-potential" electrochemiluminescence (ECL) aptasensor array was fabricated on a homemade screen-printed carbon electrode (SPCE) for simultaneous detection of malachite green (MG) and chloramphenicol (CAP) in one single assay. The SPCE substrate consisted of a common Ag/AgCl reference electrode, carbon counter electrode and two carbon working electrodes (WE1 and WE2). In the system, CdS quantum dots (QDs) were modified on WE1 as cathode ECL emitters and luminol-gold nanoparticles (L-Au NPs) were modified on WE2 as anode ECL emitters. Then the MG aptamer complementary strand (MG cDNA) and CAP aptamer complementary strand (CAP cDNA) were attached on CdS QDs and L-Au NPs, respectively. The cDNA would hybridize with corresponding aptamer that was respectively tagged with cyanine dye (Cy5) (as quenchers of CdS QDs) and chlorogenic acid (CA) (as quenchers of l-Au NPs) using poly(ethylenimine) (PEI) as a bridging agent. PEI could lead to a large number of quenchers on the aptamer, which increased the quenching efficiency. Upon MG and CAP adding, the targets could induce strand release due to the highly affinity of analytes toward aptamers. Meanwhile, it could release the Cy5 and CA, which recovered cathode ECL of CdS QDs and anode ECL of L-Au NPs simultaneously. This "dual-potential" ECL strategy could be used to detect MG and CAP with the linear ranges of 0.1-100 nM and 0.2-150 nM, with detection limits of 0.03 nM and 0.07 nM (at 3sB), respectively. More importantly, this designed method was successfully applied to determine MG and CAP in real fish samples and held great potential in the food analysis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate the value of C-reactive protein (CRP) on transplantation day in predicting early post-transplant infections and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: We retrospectively analyzed the clinical data of 78 recipients undergoing allo-HSCT. The clinical reference value of CRP on transplantation day was determined, and its sensitivity and specificity for diagnosing bacteremia was analyzed using receiver-operating characteristic curve (ROC). The incidence of transplant-related complications, overall survival, and relapse rate of the patients were analyzed with respect to the CRP level., Results: The clinical reference value of CRP for diagnosing bacteremia was 23.3 mg/L (AUC=0.735 [95% CI: 0.623-0.848], P=0.001), which had a diagnostic sensitivity and specificity of 0.793 and 0.592, respectively. Compared with the patients with low CRP levels, the patients with high CRP levels tended to have delayed neutrophil reconstitution and platelet engraftment by 0.71 days (P=0.237) and 4.09 days (P=0.048), respectively, and had a significantly higher incidence of bacteremia (17.1% vs 53.5%, P=0.001) and CMV viremia (37.1% vs 72.1%, P=0.003) within 100 days following the transplantation; the incidences of EBV viremia, pulmonary invasive fungal infection, or acute graft versus host disease (aGVHD) showed no significant difference between the two groups (41.9% vs 22.9%, P=0.094; 14.0% vs 5.7%, P=0.285; 51.2% vs 45.7, P=0.656, respectively). During the follow-up for a median of 318 (7-773) days in high-CRP group and for 299 (78-747) days in low-CRP group, the high-CRP group showed a significantly lower 2-year overall survival than the low-CRP group (42.5% vs 78.4%, P=0.022), and tended to have a higher 2-year cumulative relapse rate (52.3% vs 19.8%, P=0.235). Logistic multivariate analysis identified a high CRP level on transplantation day as the independent risk factor for post-transplant bacteremia within 100 days (OR=5.090 [95% CI: 1.115 -23.229], P=0.036)., Conclusion: A high CRP level on transplantation day can be indicative of a high risk of early post-transplant bacteremia and CMV viremia and also a poor prognosis following allo-HSCT.

Objective: To explore the therapeutic effects of sequential intensified conditioning regimen followed by graft-versus-1eukemia (GVL) induction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory advanced acute myeloid leukemia (AML)., Methods: A total of 72 patients with refractory AML undergoing allo-HSCT from May 2001 to June 2013 were enrolled in this prospective study. Intensified conditioning included fludarabine + cytarabine plus total body irradiation + cyclophosphamide + etoposide. Cyclosporine A was withdrawn rapidly in a stepwise fashion if patients who did not experience acute graft-versus-host disease (aGVHD) at Day + 30 post-transplantation. Donor lymphocytes were infused in patients without grade II or more than grade II aGVHD at Day + 60 post-transplantation., Results: The median follow-up time was 655 (1-4 200) d post-transplantation. Except for one died of infection and one died of regimen-related toxicity (RRT), the other 70 patients achieved complete remission at the time of neutrophil reconstitution. The mortality of RRT was 1.4% (1/72). The 1-year cumulative incidence of aGVHD and 2-year incidence of chronic GVHD (cGVHD) post-transplantation were 60.7% ± 5.0% and 58.5% ± 4.7%. The 5-year cumulative incidence of relapse post-transplantation was 29.6% ± 6.6%. The 5-year non-relapse mortality was 28.8% ± 6.0%. The 5-year overall and disease-free survival were 51.0% ± 6.5% and 49.9% ± 6.4%. Multivariate analysis revealed that donor lymphocyte infusion, cGVHD and bone marrow blasts at Day 0 were independent prognostic factors for relapse (HR (95% CI): 0.042 (0.007-0.688), 0.009 (0.003-0.345), 3.385 (1.451-7.899)) and survival (HR (95% CI): 0.315 (0.146-0.621), 0.416 (0.200-0.866), 1.332 (1.158-1.533))., Conclusion: The strategy of sequential intensified conditioning followed by GVL induction has an acceptable toxicity profile, and could decrease the relapse rate and improve the survival for refractory AML.

A portable and antibody-free sandwich assay was fabricated for determination of chloramphenicol (CAP) in animal-derived food by a personal glucose meter (PGM). The sandwich-type strategy was developed on the basis of magnetic molecularly imprinted probe (m-MIP) nanoparticles and a β-cyclodextrin/invertase-functionalized signal tag. Firstly, the m-MIPs were fabricated using polydopamine molecularly imprinted film modified Fe3O4 nanoparticles with 2,2-dichloroacetamide as a template that could capture the 2,2-dichloroacetamide segment of CAP. Secondly, β-cyclodextrin/invertase polymer bioconjungate was synthesized as a signal tag that could recognize the nitrobenzene segment of CAP through host-guest interaction. The dual-specificity recognition model relies on the formation of a sandwich between m-MIPs, different segments of CAP, and the β-cyclodextrin-functionalized signal tag. The sandwich-type complex formed was then subjected to detection with a PGM. The complexes can hydrolyze sucrose to glucose, which can be used for detection with a PGM through invertase. According to our experiment, the concentration of CAP was proportional to the amount of glucose formed, which could quantitatively assess the CAP with a dynamic range of 0.5-50 ng mL(-1) and a detection limit of 0.16 ng mL(-1) (signal-to-noise ratio of 3). The detection time of the assay was about 1 h, which was obviously shorter than that of competitive ELISA. More importantly, we have successfully applied this on-site assay for CAP screening in animal-derived food.

Objective: We conducted a retrospective single-center study of 106 patients to investigate the impact of prior exposure to imatinib before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on outcome of HSCT for chronic myeloid leukemia (CML) in china., Methods: Patients were divided into imatinib and non-imatinib group according to whether receiving imatinib therapy before transplantation or not. Hematopoietic engraftment, prognosis, congestive heart failure (CHF), hepatic veno-occlusive disease (HVOD), graft versus host disease (GVHD), hemorrhagic cystitis and infections were compared between the two groups in early stage of transplantation (within 100 days after transplantation)., Results: Compared to non-imatinib group, imatinib group neither had a significantly longer engraftment time nor higher incidence of HVOD, GVHD, hemorrhagic cystitis and infections (P > 0.05). However, imatinib group tended to have a statistically higher incidence of CHF (29.6% vs 8.6%, P = 0.037) and a higher 0.5-year transplant-related mortality (TRM) (27.8% vs 5.9%, P = 0.001). The estimated 10-year relapse-free survival (RFS) and 10-year overall survival (OS) were not statistically significant between the two groups (79.6% vs 62.4% P = 0.432, 68.9% vs 55.5% P = 0.086, respectively)., Conclusion: Thus, prior exposure to imatinib before transplantation does not influence the hematopoietic engraftment and incidence of early transplant-related complications. While, imatinib therapy pre-HSCT probably increases the risk of CHF and TRM in early stage of post-HSCT, and this effect can be enhanced in older age patients. However, Imatinib therapy doesn't impact RFS and OS on a long view.

Objective: To compare the clinical efficacy of HLA- mismatched related donor (MRD) and HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies., Methods: 174 patients with hematopoietic malignancies undergoing allogeneic HSCT (allo-HSCT) (82 from MRD and 92 from MUD) between June 2002 and December 2012 were enrolled in this retrospective study. Hematopoietic engraftment, graft versus host disease (GVHD), relapse, overall survival (OS) and disease-free survival (DFS) were compared between MRD and MUD group., Results: There was no significant difference between MRD and MUD group in terms of age, gender, disease type and disease status before transplantation (all P>0.05). The incidence of Ⅰ-IV acute GVHD (aGVHD) was 62.2% and 54.3% in MRD and MUD group (P=0.295); the incidence of III-IV aGVHD between the two groups was 15.9% and 9.8% (P=0.229). The incidence of chronic GVHD (cGVHD) was 28.4% and 45.1% in MRD and MUD group (P=0.036), but there was no significant difference in the incidence of extensive cGVHD between the two groups (9.0% vs 12.2%, P=0.525). The mortality of GVHD was 8.5% and 10.9% in MRD and MUD group (P=0.605). The 10-year OS and DFS were (50.1±6.1)% and (48.8±6.1)% in MRD group, compared with (50.5±6.7)% and (46.3±6.2)% in MUD group (P=0.501, P=0.873, respectively). The 10-year cumulative relapse rate was (21.5±5.7)% and (37.6±7.3)% in MRD and MUD group (P=0.194)., Conclusion: MRD is equivalent to MUD in efficacy and safety. Without HLA- matched related donors, MRD is superior to MUD because donor source is unlimited and transplantation could be made promptly according to disease status.

We performed a prospective study to evaluate the efficacy and safety of secondary antifungal prophylaxis (SAP) for patients with a history of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the prophylactic agents used were chosen based on treatment response to initial antifungal therapy. One hundred and thirty-six patients undergoing allo-HSCT with prior IPA were enrolled in this multicenter study. The agents of SAP included itraconazole in 24, voriconazole in 74, caspofungin in 32, and liposomal amphotericin B in 6. Eighty-eight patients had stable IPA and 48 had active IPA at the time of transplantation. The success rate of SAP was 91.2%. Twelve patients developed breakthrough invasive fungal disease (IFD), and none discontinued antifungal agents because drug-related adverse events. The incidence of breakthrough IFD was neither different among the different antifungal agents (P = .675) nor between patients with active and stable IPA (P = .080). The 1-year cumulative incidence of IFD and IPA relapse was 27.3% ± 4.5% and 24.7% ± 4.4%, respectively. Our data indicate that SAP with antifungal agents based on initial antifungal therapy has favorable efficacy and safety in allo-HSCT recipients with prior IPA. Active IPA might not increase the risk of breakthrough IFD after transplantation., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the impact of courses of intermediate-dose cytarabine (ID-Ara-C) chemotherapy on the efficiency of hematopoietic stem cell mobilization in acute myeloid leukemia (AML) patients with autologous hematopoietic stem cell transplantation (auto-HSCT)., Methods: 90 patients with de novo AML undergoing auto-HSCT between August 1999 and November 2012 were enrolled. All patients received the mobilization regimen of cytarabine and etoposide chemotherapy in combination with recombinant human granulocyte-colony stimulating factor (rhG-CSF). Stem cell apheresis was scheduled when blood leukocyte count recovered greater than 4.0 × 10⁹/L or the proportion of CD34⁺ cells greater than 1% in peripheral blood. The impact of ID-Ara-C courses on the mobilization efficiency was analyzed retrospectively., Results: According to the ID-Ara-C courses, patients were divided into group A (<2 courses), B (2 courses), and C (>2 courses). The median doses of CD34⁺ cells (×10⁶/kg) in three groups were 4.7, 2.7, 2.3, respectively (P=0.003). Of the available 87 patients who could be evaluated, 61 (70.1%) cases had CD34⁺ cells greater than 2.0 × 10⁶/kg, and 26 (29.9%) cases less than 2.0 × 10⁶/kg. Of the 26 patients without satisfactory mobilization efficiency, 7 (15.2%) were in group A, 10 (47.6%) in group B, and 9 (45.0%) in group C (χ²=10.05, P=0.007). In addition, patients with satisfactory mobilization efficiency (CD34⁺ cells ≥ 2.0×10⁶/kg) in groups C needed more times of collection, more volume of blood processed, and even high-dose and longer course of rhG-CSF (P<0.05). In univariate analysis. The ID-Ara-C courses and the cumulative dose were significant correlate with mobilization efficiency. In multivariate analysis, the ID-Ara-C courses was an independent correlation factor for mobilization efficiency (odd ratio=0.623, 95% confidence interval=0.418-0.926, P=0.019). The sex, age, cytogenetic risk, the standard chemotherapy courses did not correlate with mobilization efficiency., Conclusion: The number of ID-Ara-C courses was independent factor for the mobilization efficiency and should be taken seriously in AML patients with auto-HSCT.

Herpesvirus infections of the central nervous system (CNS) are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Herpesvirus-DNA and cerebrospinal fluid (CSF) cells were sampled from 58 recipients with herpesvirus-associated diseases or with unexplainable CNS manifestations. Results showed that 23 patients were diagnosed as herpesvirus-associated CNS diseases, including 15 Epstein-Barr virus (EBV)-associated diseases (4 encephalitis and 11 lymphoproliferative diseases), 5 herpes simplex virus type 1 encephalitis, 2 cytomegalovirus encephalitis/myelitis and 1 varicella zoster virus encephalitis. The median time of diseases onset was 65 (range 22-542) days post-transplantation. The 3-year cumulative incidence of herpesvirus-associated encephalitis/myelitis and post-transplant lymphoproliferative disorder (PTLD) was 6.3% ± 1.9% and 4.1% ± 1.2%, respectively. Of the evaluable cases, CSF cells mainly consisted of CD19(+)CD20(+) B cells (7/11) and had clonal rearrangement of immunoglobulin genes (3/11) in patients with CNS-PTLD. On the contrary, in patients with encephalitis/myelitis, CSF cells were comprised of different cell populations and none of the gene rearrangement was detected. Herpesvirus-associated CNS diseases are common in the early stages of allo-HSCT, wherein EBV is the most frequent causative virus. The immunophenotypic and clonal analysis of CSF cells might be helpful in the differential diagnosis between encephalitis and lymphoproliferative diseases.

The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran-Fe3O4 magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe3O4) for enriching CA 19-9 were synthesized by immobilizing the CA 19-9's first antibody (CA 19-9 Ab1) on magnetic nanoparticles (dextran-Fe3O4). Secondly, the signal probes (CA 19-9 Ab2/CdTe-G), which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2) to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA). The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor.

An ultrasensitive electrochemiluminescent immunoassay (ECLIA) for aflatoxins M1 (ATM1) in milk using magnetic Fe3O4-graphene oxides (Fe-GO) as the absorbent and antibody-labeled cadmium telluride quantum dots (CdTe QDs) as the signal tag is presented. Firstly, Fe3O4 nanoparticles were immobilized on GO to fabricate the magnetic nanocomposites, which were used as absorbent to ATM1. Secondly, aflatoxin M1 antibody (primary antibody, ATM1 Ab1), was attached to the surface of the CdTe QDs-carbon nanotubes nanocomposite to form the signal tag (ATM1 Ab1/CdTe-CNT). The above materials were characterized. The optimal experimental conditions were obtained. Thirdly, Fe-GO was employed for extraction of ATM1 in milk. Results indicated that it can adsorb ATM1 efficiently and selectively within a large extent of pH from 3.0 to 8.0. Adsorption processes reached 95% of the equilibrium within 10 min. Lastly, the ATM1 with a serial of concentrations absorbed on Fe-GO was conjugated with ATM1 Ab1/CdTe-CNT signal tag based on sandwich immunoassay. The immunocomplex can emit a strong ECL signal whose intensity depended linearly on the logarithm of ATM1 concentration from 1.0 to 1.0 × 10(5) pg/mL, with the detection limit (LOD) of 0.3 pg/mL (S/N = 3). The method was more sensitive for ATM1 detection compared to the ELISA method. Finally, ten samples of milk were tested based on the immunoassay. The method is fast and requires very little sample preparation, which was suitable for high-throughput screening of mycotoxins in food.

An ultrasensitive portable electrochemical immunosensor for human immunodeficiency virus p24 (HIV p24) antigen detection has been developed, whereby the detection sensitivity was 1000 times higher than that of the ELISA method. Firstly, a novel HRP enzyme-antibody copolymer (EV-p24 Ab2) was synthesized through an EnVision regent (EV, a dextrin amine skeleton anchoring more than 100 molecules of HRP and 15 molecules of anti IgG), then incubated in the secondary antibody of p24. Secondly, the copolymer was immobilized on the gold nanocolloids (AuNPs) to fabricate a novel signal tag (AuNPs/EV-p24 Ab2). Subsequently, a sandwich-type immunoreaction would take place between the capture probe (silicon dioxide-coated magnetic Fe₃O₄ nanoparticles (MNPs) labeled with the primary p24 antibody (MNPs-p24 Ab1)), p24 (different concentrations) and the signal tag [AuNPs/EV-p24 Ab2)] to form the immunocomplex. Finally, the immunocomplex was absorbed on the surface of screen printed carbon electrode (SPCE) by a magnet and immersed in the o-hydroxyl phenol (HQ) and H₂O₂. The large amounts of HRP on the signal tag can catalyze the oxidation of HQ by H₂O₂, which can induce an amplified reductive current. Moreover, the capture probe could improve the accumulation ability of p24 and facilitate its separation from the substrate through the magnet. Under optimal conditions, the proposed immunoassay exhibited good sensitivity to p24 within a certain concentration range from 0.001 to 10.00 ng/mL, with a detection limit of 0.5 pg/mL (S/N = 3). The proposed method can be used for real-time and early detection of HIV-infected people.

Background: Graft-versus-host disease (GVHD) remains a main complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule exerting multiple immunoregulatory functions. The aim of this study was to explore the relationship between soluble HLA-G (sHLA-G) and GVHD after allo-HSCT., Methods: The sHLA-G levels were examined using enzyme-linked immunosorbent assay in patients with hematological malignancies (n = 106) before transplantation, on days +15 and +30 after transplantation, as well as healthy volunteers (n = 10)., Results: The levels of sHLA-G5, sHLA-G6 and sHLA-G7 in patients on days +15 and +30 after transplantation were all significantly higher than those before transplantation (all p ≤ 0.001). The increased levels of sHLA-G5 on days +15 and +30 after transplantation were both significantly higher in patients with grade 0-I acute GVHD (aGVHD) compared to those with grade II-IV aGVHD (both p < 0.001). The increased levels of sHLA-G5 on days +15 and +30 after transplantation were both negatively correlated with the severity of aGVHD (both p < 0.001)., Conclusion: sHLA-G5 might be a predictor of the occurrence and severity of aGVHD, which may help to establish individual prophylaxis against aGVHD and improve the survival for patients after allo-HSCT., (Copyright © 2013 S. Karger AG, Basel.)

A method for the determination of histamine, 2-phenylethylamine, tryptamine, putrescine, cadaverine, spermidine and spermine in fish using micellar electrokinetic capillary chromatography (MECC) was developed. Seven biogenic amines (BAs) were extracted from a sample with 6% perchloric acid, then derivatized with benzoyl chloride. 0.02 mol/L borate buffer (pH 9.2) containing 0.06 mol/L sodium deoxycholate-methanol (95 : 5, v/v) was used as a running buffer. The detection wavelength was set at 214 nm. The separation was achieved within 12 min. Good linearities were observed from the calibration plots in the concentration ranges. The detection limit of histamine was 15 microg/g and those of the other amines were 5 microg/g. The developed method was successfully employed for the simultaneous determination of 7 BAs in fish sample with satisfactory results.