Outcome after allogeneic hematopoietic stem cell transplantation following Venetoclax-based therapy among AML and MDS patients.

The use of Bcl-2 inhibitor Venetoclax (VEN) combined with hypomethylating agents or chemotherapy has shown efficacy in treating acute myeloid leukemia (AML) as frontline treatment and for relapse, allowing more patients to bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influence of VEN-based therapy on the prognosis of subsequent allogeneic HSCT remains unknown. We retrospectively collected data from patients who proceeded to allo-HSCT between November 2018 and November 2020 after VEN-based therapy at five transplant centers in Zhejiang Province, China. A total of 39 patients were analyzed. Thirty-one patients were diagnosed with AML (28 de novo, 3 secondary to MDS), 6 with MDS, and 2 with CMML. The majority (74.4%) of patients received VEN-based therapy for the treatment of relapse (38.5%) or refractory disease (35.9%); 5 (12.8%) received it as an initial treatment, and 5 (12.8%) patients who were already in complete remission (CR) received VEN for further consolidation or deep remission before HSCT. Twenty-seven (69.2%) patients were in CR at the time of HSCT. Day + 100 cumulative incidences of grade I-IV acute graft-versus-host disease (aGVHD) and grade II-IV aGVHD were 43.6% and 15.4%, respectively. Of 34 evaluable patients, 6.4% and 25.6% developed chronic GVHD at 1 year and 2 years. The 100-day cytomegalovirus (CMV) reactivation occurred in 76.3% of patients and Epstein-Barr virus (EBV) reactivation occurred in 29.7% of patients. With a median follow-up of 14.7 months, overall survival, progression-free survival, relapse, and non-relapse mortality incidence at 1 year were 75.5%, 61.6%, 16.7%, and 21.7%, respectively. Both univariate and multivariate analysis revealed that relapsed/refractory (R/R) disease was associated with inferior PFS (HR 4.849, 95% CI 1.009-23.30; p = 0.049). Prior poor response to VEN was found to be a significant factor predicting higher risk of relapse (HR 4.37, 95% CI 1.130-16.9; p = 0.033). Our results showed that VEN-based regimen therapy followed by allo-HSCT in AML patients is feasible and does not increase the risk of transplant-related mortality and toxicity.

Preemptive low-dose interleukin-2 or DLI for late-onset minimal residual disease in acute leukemia or myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.

Minimal residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) heralds high risk of relapse. Whether preemptive recombinant interleukin-2 (pre-IL2) is effective for patients with late-onset MRD (LMRD) remains unknown. We retrospectively compared the efficacy and safety of pre-IL2 (n = 30) and pre-DLI (n = 25) for LMRD in patients receiving allo-HSCT for acute leukemia or myelodysplastic syndrome. The 1-year overall survival (OS) and disease-free survival (DFS) rates were 86.7% and 78.4% (P = 0.267), 83.3% and 75.6% (P = 0.329), the cumulative incidence of grades III-IV acute graft-versus-host disease (aGVHD) at 100 days post-preemptive intervention was 3.3% and 12.0% (P = 0.226) in the pre-IL2 group and pre-DLI group, respectively. The 1-year cumulative incidence of moderate/severe chronic GVHD (cGVHD), relapse (CIR), and non-relapse mortality (NRM) were 7.7% and 27.9% (P = 0.018), 13.6% and 20.0% (P = 0.561) and 3.3% and 5.5% (P = 0.321) in the two groups, respectively. No remarkable differences in CIR, OS, and DFS between the two intervention groups were found in multivariate analysis. The GVHD-free and relapse-free survival (GRFS) were better in the pre-IL2 group than in the pre-DLI group (HR = 0.31, 95% confidence interval (CI), 0.12-0.76; P = 0.011). In conclusion, preemptive low-dose IL2 and preemptive DLI yield comparable outcomes for patients with LMRD receiving allo-HSCT, in terms of aGVHD, NRM, relapse, OS, and DFS. However, preemptive low-dose IL2 has a lower incidence of moderate/severe cGVHD and a higher CRFS. Preemptive low-dose IL2 may be an alternative method for patients who develop LMRD after allo-HSCT, particularly for patients who cannot receive preemptive DLI.

Antitumor evaluation and multiple analysis on different extracted fractions of the root of Cynanchum auriculatum Royle ex Wight.

The root of Cynanchum auriculatum (C. auriculatum) Royle ex Wight has been shown to possess various pharmacological effects and has recently attracted much attention with respect to its potential role in antitumor activity. The C-21 steroidal glycosides are commonly accepted as the major active ingredients of C. auriculatum. In this study, the antitumor abilities of different extracted fractions of the root bark and the root tuber of C. auriculatum were investigated by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human cancer cell lines HepG2 and SMMC-7721. The results showed that the chloroform and ethyl acetate fractions of the root tuber suppressed tumor cell growth strongly. To identify and characterize the chemical constituents of different active fractions, an ultra high performance liquid chromatography with triple-quadrupole tandem mass spectrometry method was developed for the simultaneous quantitation of eight C-21 steroidal glycosides. The analysis revealed that the C-21 steroidal glycosides were concentrated in the chloroform and ethyl acetate fractions, and the total contents of different fractions in the root tuber were significantly higher than those of corresponding ones in the root bark. Furthermore, the C-21 steroidal glycosides based on different types of aglucones were prone in different medicinal parts of C. auriculatum.

[Study on chitosan-modified tripterygium glycoside nanoparticles and its renal targeting property].

OBJECTIVE: To prepare chitosan-modified tripterygium glycoside nanoparticles (LMWC-TG-PLA-NPs), and assess its renal targeting property in rats. METHOD: Chitosan-modified tripterygium glycoside nanoparticles (LMWC-TG-PLA-NPs) were prepared by modified spontaneous emulsification solvent evaporation method, and modified with 50% deacetylated low molecular weight chitosan (LMWC). The shape of nanoparticles was observed under a transmission electron microscope. The mean diameter of nanoparticles was measured by particle size analyzer. The drug encapsulation efficiency and drug loading were measured by centrifuge method. The in vitro release behavior was studied with dialysis bags. Renal microdialysis technique and renal artery administration technique were combined to study the renal targeting property of nanopartcles. LMWC-TG-PLA-NPs were administrated in rats by tail vein injection (TVI) and renal artery administration (RAA), respectively, with TG-PLA-NPs as the control group. Renal dialysis fluid was regularly collected to determine the drug concentration in the dialysis fluid, map drug concentration-time curves, and calculate AUC ratio in kidneys through the two injection approaches as the renal targeting parameter (RTP), in order to assess the renal targeting property of LMWC-TG-PLA-NPs. RESULTS: The prepared LMWC-TG-PLA-NPs looked smooth and round. Their average diameter, polydispersity index, encapsulation efficiency and drug loading were (207.6 +/- 3.4) nm, (0.078 +/- 0.009)%, (61.83 +/- 2.43)%, and (10.70 +/- 0.37)%, respectively. The pH 7.4 PBS buffer solution containing 20% ethanol showed obvious sustained release behavior. LMWC-TG-PLA-NPs showed a RTP of 71.97%, which was 3.6 times of TG-PLA-NPs of the control group. CONCLUSION: The prepared LMWC-TG-PLA-NPs showed high drug encapsulation efficiency and drug loading, with obvious sustained release characteristics and renal targeting property. LMWC-TG-PLA-NPs are expected to become a new type vector for reducing toxic and side effects of tripterygium glycoside. Meanwhile, a new method is established for assessing renal targeting property with AUC ratio in kidneys after administrated through caudal veins and renal arteries as the renal targeting parameter.

The novel HLA-B*15:644 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*15:644 differs from HLA-B*15:17:01:02 by one nucleotide in exon 4.

Preemptive interferon-α therapy could prevent relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: A real-world analysis.

Introduction: Measurable residual disease (MRD)-directed interferon-a treatment (i.e. preemptive IFN-α treatment) can eliminate the MRD in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, this study aimed to further assess its efficacy in a multicenter retrospective study in a real-world setting. Methods: A total of 247 patientswho received preemptive IFN-α treatment were recruited from 4 hospitals in China. The protocols for MRD monitoring mainly based on quantitative polymerase chain reaction [qPCR] and multiparameter flow cytometry [MFC]. Results: The median duration of IFN-α treatment was 56 days (range, 1-1211 days). The cumulative incidences of all grades acute graft-versus-host disease (aGVHD), all grades chronic graft-versus-host disease (cGVHD), and severe cGVHD at 3 years after IFN-α therapy were 2.0% (95% confidence interval [CI], 0.3-3.8%), 53.2% (95% CI, 46.8-59.7%), and 6.2% (95% CI, 3.1-9.2%), respectively. The cumulative incidence of achieving MRD negative state at 2 years after IFN-α treatment was 78.2% (95% CI, 72.6-83.7%). The 3-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 20.9% (95% CI, 15.5-26.3%) and 4.9% (95%CI, 2.0-7.7%), respectively. The probabilities of leukemia-free survival and overall survival at 3 years following IFN-α therapy were 76.9% (95% CI, 71.5-82.7%) and 84.2% (95% CI, 78.7-90.1%), respectively. Multivariable analysis showed that MRD positive state by qPCR and MFC before IFN-α treatment, high-risk disease risk index before allo-HSCT, and receiving identical sibling donor HSCT were associated with a higher risk of relapse and a poorer leukemia-free survival. Severe cGVHD was associated with an increased risk of non-relapse mortality. Discussion: Thus, real-world data suggest that preemptive IFN-α is effective for treating patients with AML with MRD after allo-HSCT.

A novel risk model for predicting early relapse in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem-cell transplantation.

Relapse remains the leading cause of death in acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem-cell transplantation (allo-HSCT), limiting the efficacy of allo-HSCT. Thus, the ability to identify high-risk patients in a manner that permits early intervention has the potential to improve survival outcomes. We retrospectively enrolled 414 younger patients (aged 14-60 years) with AML who received allo-HSCT between January 2014 and May 2020. From June 2020 to June 2021, 110 consecutive patients were included prospectively in the validation cohort. The primary outcome was early relapse (relapse within 1 year). The cumulative incidence of early relapse after allo-HSCT was 11.8%. The overall survival rate for patients who relapsed within 1-year was 4.1% at 3 years after relapse. After multivariable adjustment, statistically significant associations between primary resistance, pre-transplantation measurable residual disease, DNMT3A mutation, or white blood cell count at diagnosis and early relapse were observed. An early relapse prediction model was developed based on these factors and the model performed well. Patients deemed to have a high risk or a low risk of early relapse had early relapse rates of 26.2% and 6.8%, respectively (P < 0.001). The prediction model could be used to help identify patients at risk for early relapse and to guide personalized relapse prevention.

Repeated lipopolysaccharide stimulation induces cellular senescence in BV2 cells.

BACKGROUND AND AIM: The dual action of microglia in neurodegenerating diseases has been controversial for some time. Recent studies indicate that microglia senescence might be the key determinant. When microglia age, they function abnormally and fail to respond correctly to stimuli, which eventually promotes neurodegeneration. Accumulating evidence has shown a close relationship between inflammation and aging. Since neuroinflammation is characterized by microglia activation, we assessed if the repeated activation of microglia would lead to senescence. METHOD: The microglia cell line BV2 was repeatedly stimulated every 48 h with lipopolysaccharide (LPS; 10 ng/ml) and senescence was evaluated by ß-galactosidase staining and the presence of senescence-associated heterochromatic foci as well as by cell cycle arrest detection by flow cytometry. The senescence-associated protein p53 was also detected by Western blot. RESULTS: ß-galactosidase staining was barely detectable in control cells, while it tended to increase with repeated LPS stimulation and was positive in most cells after stimulation with LPS 6 times. Similarly, senescence-associated heterochromatic foci were most prominent in cells repeatedly stimulated with LPS, while almost undetectable in control cells or cells receiving a single stimulation. p53 expression was highest in the cells that received LPS stimulation 6 times, and the largest number of cells arrested in the G0/G1 phase was observed in this same group. CONCLUSION: Microglial cells tend to undergo senescence after repeated activation, implying that microglia senescence may start after multiple inflammatory challenges.

First report of the complete mitogenome of Tanypus punctipennis Meigen, 1818 (Diptera, Chironomidae) from Hebei Province, China.

Tanypus punctipennis Meigen, 1818 is an important bioindicator for freshwater ecosystems monitoring. Although COI barcode analyses have been performed on T. punctipennis, the mitogenome of this taxon has not been assembled and analyzed. Here, the complete mitogenome of T. punctipennis was sequenced and analyzed to confirm the systematic and phylogenetic history of this species. The mitogenome is 16,215 bp long with high A + T content, and consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a noncoding control region. The phylogenomic analysis supports monophyletic Tanypodinae and close relationship between T. punctipennis and Clinotanypus. Our results indicate that mitogenomes showed strong signals in phylogenetic reconstructions at the genus level of Tanypodinae.

First Report on Mitochondrial Gene Rearrangement in Non-Biting Midges, Revealing a Synapomorphy in Stenochironomus Kieffer (Diptera: Chironomidae).

(1) Background: Gene rearrangement of mitochondrial genome, especially those with phylogenetic signals, has long fascinated evolutionary biologists. The synapomorphic gene rearrangements have been identified across multiple orders and at many different taxonomic levels, supporting the monophyletic or systematic relationships of related lineages. However, mitochondrial gene rearrangement has never been observed in the non-biting midges (Diptera: Chironomidae); (2) methods: in this study, the complete mitogenomes of seven Stenochironomus species were sequenced and analyzed for the first time; (3) results: each mitogenome of Stenochironomus contains 37 typical genes and a control region. The whole mitogenomes of Stenochironomus species exhibit a higher A+T bias than other published chironomid species. The gene order rearranges from trnI-trnQ-trnM to trnI-trnM-trnQ in all the seven mitogenomes of Stenochironomus, which might be act as a synapomorphy of the genus, supporting the monophyletic of Stenochironomus species. In addition, another derived gene cluster: trnA-trnG-ND3-trnR exists in Stenochironomus tobaduodecimus. The derived gene orders described above are the first case of mitochondrial gene rearrangement in Chironomidae. Coupled with published data, phylogenetic relationships were reconstructed within Chironominae, and strongly supported the monophyly of Stenochironomus; (4) conclusions: our study provides new insights into the mitochondrial gene order of Chironomidae, and provides a valuable resource for understanding the synapomorphic gene rearrangements.

Comparative Analysis of Mitogenomes of Chironomus (Diptera: Chironomidae).

(1) Background: Chironomids are biological indicators, playing an important role in monitoring and assessing the changes in water ecosystems. Mitochondrial genomes have been widely applied as a molecular marker to analyze the taxonomy and phylogeny of insects. However, knowledge of the mitogenomes of Chironomus species is scarce at present, which limits our understanding of the evolutionary relationships among Chironomus. (2) Methods: In our study, the mitogenomes and their basic structure of 12 Chironomus species and one Microchironomus species were newly sequenced. Combined with reported mitogenomes, a total of 15 mitogenomes of Chironomus were selected for a comparative mitogenomic analysis and phylogenetic reconstruction of Chironomus. (3) Results: Each mitogenome of the Chironomus species has the typical 37 genes and a control region. The basic structure of the whole mitogenomes of Chironomus species is relatively conservative, and the genetic arrangements stay the same as the ancestral mitogenome. (4) Conclusions: Our study enriches the library of mitogenomes of chironomids and provides a valuable resource for understanding the evolutionary history of Chironomus.

Comparable outcomes in patients with B-cell acute lymphoblastic leukemia receiving haploidentical hematopoietic stem cell transplantation: Pretransplant minimal residual disease-negative complete remission following chimeric antigen receptor T-cell therapy versus chemotherapy.

Introduction: Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy followed by haploidentical hematopoietic stem cell transplantation (haplo-HSCT) markedly improves the long-term survival of patients with refractory/relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Methods: We performed a parallel comparison of transplant outcomes in 168 B-ALL patients undergoing haplo-HSCT after achieving minimal residual disease (MRD)-negative complete remission (CR) from CAR-T therapy (n = 28) or chemotherapy (n = 140) between January 2016 and August 2021. We further divided the chemotherapy group into the first CR group (chemo+CR1, n = 118) and a second or more CR group (chemo+≥CR2, n = 22). Results: With a median follow-up period of 31.0 months, the 2-year overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM), and relapse rates in the CAR-T and chemotherapy groups did not differ significantly (OS, 87.9% vs. 71.5 %; LFS, 72.0% vs. 66.8%; NRM, 3.9% vs. 13.7%; relapse, 24.1% vs. 19.4%). Multivariate analysis confirmed that ≥CR2 at transplantation following chemotherapy was an independent risk factor associated with poor OS (hazard ratio (HR) 4.22 [95% CI, 1.34-13.293], p = 0.014) and LFS (HR 2.57 [95% CI, 1.041-6.343], p = 0.041). The probabilities of OS and LFS at 2 years in the CAR-T group were comparable to those in the chemo+CR1 group but significantly higher than those in the chemo+≥CR2 group (OS, 87.9% vs. 37.8%, p = 0.007; LFS, 72.0% vs. 41.7%, p = 0.043). No significant differences in the incidences of NRM were noted among the three groups. Conclusions: Our results demonstrated that patients with R/R B-ALL receiving haplo-HSCT after CAR-T therapy achieved comparable outcomes to patients transplanted post-chemotherapy-based MRD-negative CR1, without increased risk of transplant-related mortality and toxicity.

[Effects of blocking inhibitory KIR receptors on cytotoxic activity of human NK cells in vitro].

OBJECTIVE: To investigate the effect of blocking the inhibitory receptors KIR2DL1 and KIR2DL2/2DL3 with monoclonal antibody on cytotoxic activity of human NK cells. METHODS: Human peripheral blood NK cells were isolated by Rosettesep NK sorting kit. The cytotoxic activity of NK cells against human leukemia NB4, K-562, Raji cells and allogeneic mature or dendritic cells (DCs) was detected before or after KIR2DL1 and KIR2DL2/2DL3 were blocked. The effect of NK cells on T lymphocyte proliferation was detected by mixed lymphocyte reaction and TGF-ß1 concentration in culture supernatant was measured. RESULTS: The cytotoxicity of NK cells to NB4 cells was augmented with increasing concentration of the antibody. Combination of both antibodies enhanced killing activity of NK cells. NK cells had strong cytotoxicity to K-562 cells, but were not enhanced by the blockade of inhibitory receptors. The cytotoxicity to Raji cells was not evidently augmented. The cytotoxicity of NK cells to mature DC was enhanced remarkably with the increase of concentration of the antibodies (2.20% ±1.10% compared with 37.59% ±5.06%, P<0.05). In mixed lymphocyte reaction, the blockade of two antibodies enhanced the inhibition effect of NK cells on T cell proliferation (77.85% ± 8.31% compared with 43.05% ± 5.95%, P<0.05) and the content of TGF-ß1 in the supernatant was increased. CONCLUSION: The cytotoxic effects of human NK cells against target cells were significantly enhanced with the blockade of inhibitory KIR receptor; and the cytokine TGF-ß1 secreted by NK cells further inhibits T cells proliferation.

[Synergistic cytotoxic effects of rapamycin and idarubicin on human acute T-cell lymphoblastic leukemia Jurkat cells].

OBJECTIVE: To investigate the cytotoxic effects of mTOR inhibitor rapamycin (Rapa) and idarubicin (IDA) on human T-cell acute lymphoblastic leukemia Jurkat cell line. METHODS: The proliferation of Jurkat cells was observed by CCK-8 assay. The combined index was analyzed by Isobologram method. Apoptosis was detected by electron microscopy and flow cytometry with Annexin V/PI staining. Protein expressions of Caspase 3, PARP, Caspase 8, Caspase 9, Akt, p-Akt, P85S6K, p-P85S6K, P70S6K, p-P70S6K, ERK1/2 and p-ERK1/2 were determined by Western blotting. RESULTS: The IC(50) of IDA for Jurkat cells was significantly reduced when combined with 10 nmol/L rapamycin. The combined index was <1. Both electron microscopy and Annexin V/PI staining flow cytometry revealed that rapamycin significantly increased apoptotic sensitivity to IDA. The combination of IDA with rapamycin enhanced the expressions of Caspase 3, PARP, Caspase 8 and Caspase 9. Rapamycin significantly inhibited mTOR signaling upstream Akt and downstream S6K activation triggered by IDA, and the combination of the two agents led to synergistic inhibition of ERK phosphorylation. CONCLUSION: Combination of IDA with rapamycin exerted a synergistic anti-proliferative effect and promoted apoptosis by both extrinsic and intrinsic apoptotic pathways in Jurkat cells. Inhibition of ERK phosphorylation and mTOR signaling by rapamycin may play a certain role in this synergistic effect.

Zanubrutinib Treatment of Central Nervous System Posttransplant Lymphoproliferative Disorder After Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

Posttransplant lymphoproliferative disorder (PTLD) is a rare complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with poor prognosis. We report a patient with PTLD involved central nervous system (CNS) who treated with zanubrutinib, a second-generation Bruton tyrosine kinase (BTK) inhibitor. Our report supports the efficacy of bruton tyrosine kinase inhibitor zanubrutinib in the treatment of CNS-PTLD, which provides a new therapeutic option.

[Polysorbate-80 modified neurotoxin nanoparticle with its transport and cytotoxicity against blood-brain barrier].

This study was aimed at the transport across blood-brain barrier (BBB) of polysorbate-80 modified neurotoxin loaded polybutylcyanoacrylate nanoparticle (P-80-NT-NP) and its cytotoxicity. An in vitro model of BBB using rat brain microvascular endothelial cells (rBMECs) was established. The cytotoxicity of P-80-NT-NP was measured by the MTT assays, where neurotoxin (NT), nanoparticle (NP), neurotoxin nanoparticle (NT-NP) as control, and the permeability of P-80-NT-NP was determined by using of Millicell insert coculture with rBMECs and fluorescence spectrophotometry. MTT results showed that NT, NP, NT-NP and P-80-NT-NP were avirulent to rBMECs when the concentration of NT was lower than 200 ng x mL(-1). But the cytotoxicity of NP, NT-NP and P-80-NT-NP would be augmented accordingly as concentration increased (P < 0.01), causing obvious reductions of cell survival rate, with no significant difference between them (P > 0.05). When the concentration of NT was 150 ng x mL(-1), the permeability on rBMECs of P-80-NT-NP and NT-NP were both significantly higher than that of NT (P < 0.01), and the permeability of P-80-NT-NP was greater than that of NT-NP (P < 0.05). In conclusion, polysorbate-80 modified neurotoxin nanoparticles can transport across the BBB, while concentration of NT is greater than 200 ng x mL(-1), P-80-NT-NP has a little cytotoxicity against rBMECs.

Class C1 decoy oligodeoxynucleotide inhibits profibrotic genes expression in rat hepatic stellate cells.

The aim of the present study was to investigate whether class C1 decoy oligodeoxynucleotides (ODNs) can inhibit the expression of pro­fibrotic genes associated with rat hepatic stellate cell (HSC) activation and hepatic fibrosis. Luciferase reporter assays were performed to test the promoter activities of transforming growth factor (TGF)­ß and its downstream target genes following transfection of decoy ODNs and plasmids into HSC­T6 cells, and western blot assays were performed to measure the protein expression of those genes following decoy ODN transfection. Class C1 decoy ODNs were confirmed to inhibit the promoter activity of TGF­ß and its downstream target genes, such as type 1 collagen (COLI)α1, tissue inhibitor of metalloproteinases (TIMP)1 and α­smooth muscle actin by Gaussia luciferase reporter assay, and to further downregulate the expression of TGF­ß, SMAD3, COLIα1 and TIMP1 by western blotting in activated HSC­T6 cells. In conclusion, class C1 decoy ODNs inhibited pro­fibrotic gene expression in rat HSCS by downregulating TGF­ß signaling.

Different screening frequencies of carbapenem-resistant Enterobacteriaceae in patients undergoing hematopoietic stem cell transplantation: which one is better?

BACKGROUND: A consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI). METHODS: We retrospectively studied the clinical data of 395 consecutive HSCT patients from September 2017 to April 2019. From September 2017 to June 2018 (period 1), 200 patients received single CRE screening before transplantation. From July 2018 to April 2019 (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary. RESULTS: During period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P < 0.001). Of the 21 colonized patients, 4 (19.0%) patients were identified as positive for CRE at the first screening, 5 (23.8%) were identified at the second screening, and the remaining 12 (57.1%) were identified at the third or later screening. The CRE BSI rate decreased to 0.5% (1/195), and there were no CRE-related death. Fifteen colonized patients developed neutropenic fever. Thirteen colonizers were preemptively treated with tigecycline within 24 h of fever onset, and they achieved rapid temperature control. One colonizer received tigecycline later than 48 h after fever onset and ultimately survived due to the addition of polymyxin. The other received tigecycline later than 72 h after fever onset and died of septic shock. CONCLUSION: The increase in screening frequency contributed to the detection of patients with CRE colonization. Targeted managements for these colonized patients may contribute to reducing the incidence and mortality of CRE BSI, therefore improving the prognosis of patients.

[Analysis of Transport and Transformation Characteristics Between Dissolved Phosphorus and Particulate Phosphorus in Water of the Three Gorges Reservoir].

To understand the difference between transport coefficients of water runoff, sand discharge, and phosphorus flux in each subsection of a river, a judgement method for analyzing the characteristics of phosphorus transport and transformation in water of rivers was established in this study. Based on the measured data of water runoff, sand discharge, and phosphorus fraction concentrations in the water of the Three Gorges Reservoir (TGR) in January and July 2015, characteristics of phosphorus transport and transformation in the water were analyzed by using the conceptual method. The results showed that the predominant phosphorus fraction in water of the TGR was total dissolved phosphorus (TDP), which accounted for 51%-96% of total phosphorus in water. The TDP flux relative to runoff in the TGR decreased in January 2015 That was caused by the adsorption of TDP by suspended particles in the dry season. In contrast, TDP flux showed additive effect relative to water runoff in July 2015 due to exogenous water inputs with high TDP concentrations in the wet season. Both sand and total particulate phosphorus (TPP) presence in the water showed obvious sediment and retention characteristics during the two periods. The TPP flux presented an additive effect relative to sand discharge, meaning that the major transformation direction of phosphorus fractions was from TDP to TPP. The subsection between Qingxichang and Wanzhou was the main retention area of water, sand, and phosphorus in the TGR, which can be associated with the enhancement of phosphorus adsorption capacity caused by particle size reduction of suspended particles in the subsection.

Cell cycle dependent telomere regulation by telomerase in human bone marrow mesenchymal stem cells.

Human bone marrow mesenchymal stem cells (hMSCs) are a promising source for clinical stem cell transplantation. However, telomere regulation mechanisms, as one of the possible major mechanisms by which hMSCs sustain their stem cell characteristics, remain unknown. We isolated hMSCs by plastic adhesion and characterized these cells by morphology, immune phenotype and differentiation capacity. Telomerase was found negative in hMSCs, but slightly up-regulated in hMSC-derived adipocytes by the Telomeric Repeat Amplification Protocol (TRAP) assay. Moreover, hMSCs lack the alternative lengthening of telomeres (ALT) mechanism, because the hallmarks of ALT, such as very long and heterogeneous telomeres, extra-chromosome telomere repeat DNA (ECTR), and ALT-associated promyelocytic leukemia bodies (APBs), were not evident. However, when hMSCs were arrested in S phase with a combination of serum deprivation and aphidicolin, previously undetectable telomerase activity became predominantly positive. Meanwhile, the expression level of hTERT protein and mRNA increased, paralleled with the appearance of a large cohort of synchronized hMSCs at S phase. These findings provide a profile of telomere regulation by cell cycle dependent expression of telomerase in hMSCs and may lead to a better understanding of the stem cell nature of these cells.