Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein.

Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.

Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for adolescent and adult Tlymphoblastic leukemia /lymphoma: a large cohort multicenter study in China.

T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70.8%) and 29 partial response (PR) patients (14.8%). Until October 1, 2023, no difference was found in 5-year overall survival (5-OS) and 5-year progression free survival(5-PFS) between allo-HSCT and auto-HSCT (5-OS 57.9% vs. 36.7%, P = 0.139, 5-year PFS 49.4% vs. 28.6%, P = 0.078) for patients who achieved CR, for patients who achieved PR, allo-HSCT recipients had higher 5-OS compared with chemo alone recipients (5-OS 23.8% vs. 0, P = 0.042). For patients undergoing allo-HSCT, minimal residual disease (MRD) negative population showed better 5-OS survival compared with MRD positive patients (67.8% vs. 19.6%, p = 0.000). There were no significant differences between early T-cell precursor (ETP), NON-ETP patients with or without expression of one or more myeloid-associated or stem cell-associated (M/S+) markers (NON-ETP with M/S+, NON-ETP without M/S+) groups in allo-HSCT population for 5-OS. (62.9% vs. 54.5% vs.48.4%, P > 0.05). Notch mutations were more common in patients with non-relapsed/refractory disease than relapsed/refractory disease (χ² =4.293, P = 0.038). In conclusion, Allo-HSCT could be an effective consolidation therapy not just for patients with CR, but also for those who achieved PR. The prognosis is significantly improved by obtaining MRD negative prior to allogeneic transplantation.

AMSCN: A Novel Dual-Task Model for Automatic Modulation Classification and Specific Emitter Identification.

Specific emitter identification (SEI) and automatic modulation classification (AMC) are generally two separate tasks in the field of radio monitoring. Both tasks have similarities in terms of their application scenarios, signal modeling, feature engineering, and classifier design. It is feasible and promising to integrate these two tasks, with the benefit of reducing the overall computational complexity and improving the classification accuracy of each task. In this paper, we propose a dual-task neural network named AMSCN that simultaneously classifies the modulation and the transmitter of the received signal. In the AMSCN, we first use a combination of DenseNet and Transformer as the backbone network to extract the distinguishable features; then, we design a mask-based dual-head classifier (MDHC) to reinforce the joint learning of the two tasks. To train the AMSCN, a multitask cross-entropy loss is proposed, which is the sum of the cross-entropy loss of the AMC and the cross-entropy loss of the SEI. Experimental results show that our method achieves performance gains for the SEI task with the aid of additional information from the AMC task. Compared with the traditional single-task model, our classification accuracy of the AMC is generally consistent with the state-of-the-art performance, while the classification accuracy of the SEI is improved from 52.2% to 54.7%, which demonstrates the effectiveness of the AMSCN.

Internal and external validation of machine learning-assisted prediction models for mechanical ventilation-associated severe acute kidney injury.

BACKGROUND: Currently, very few preventive or therapeutic strategies are used for mechanical ventilation (MV)-associated severe acute kidney injury (AKI). OBJECTIVES: We developed clinical prediction models to detect the onset of severe AKI in the first week of intensive care unit (ICU) stay during the initiation of MV. METHODS: A large ICU database Medical Information Mart for Intensive Care IV (MIMIC-IV) was analysed retrospectively. Data were collected from the clinical information recorded at the time of ICU admission and during the initial 12 h of MV. Using univariate and multivariate analyses, the predictors were selected successively. For model development, two machine learning algorithms were compared. The primary goal was to predict the development of AKI stage 2 or 3 (AKI-23) and AKI stage 3 (AKI-3) in the first week of patients' ICU stay after initial 12 h of MV. The developed models were externally validated using another multicentre ICU database (eICU Collaborative Research Database, eICU) and evaluated in various patient subpopulations. RESULTS: Models were developed using data from the development cohort (MIMIC-IV: 2008-2016; n = 3986); the random forest algorithm outperformed the logistic regression algorithm. In the internal (MIMIC-IV: 2017-2019; n = 1210) and external (eICU; n = 1494) validation cohorts, the incidences of AKI-23 were 154 (12.7%) and 119 (8.0%), respectively, with areas under the receiver operator characteristic curve of 0.78 (95% confidence interval [CI]: 0.74-0.82) and 0.80 (95% CI: 0.76-0.84); the incidences of AKI-3 were 81 (6.7%) and 67 (4.5%), with areas under the receiver operator characteristic curve of 0.81 (95% CI: 0.76-0.87) and 0.80 (95% CI: 0.73-0.86), respectively. CONCLUSIONS: Models driven by machine learning and based on routine clinical data may facilitate the early prediction of MV-associated severe AKI. The validated models can be found at: https://apoet.shinyapps.io/mv_aki_2021_v2/.

Comprehensive Analyses of Four PtoNF-YC Genes from Populus tomentosa and Impacts on Flowering Timing.

Flowering is an important link in the life process of angiosperms, and it is also an important sign of the transformation of plants from vegetative to reproductive growth. Although the flowering regulation network of Arabidopsis is well-understood, there has been little research on the molecular mechanisms of perennial woody plant flower development regulation. Populus tomentosa is a unique Chinese poplar species with fast growth, strong ecological adaptability, and a long lifecycle. However, it has a long juvenile phase, which seriously affects its breeding process. Nuclear factor-Y (NF-Y) is an important type of transcription factor involved in the regulation of plant flowering. However, there are few reports on PtoNF-Y gene flowering regulation, and the members of the PtNF-YC subfamily are unknown. In this study, four key genes were cloned and analyzed for sequence characteristics, gene structure, genetic evolution, expression patterns, and subcellular localization. The plant expression vector was further constructed, and transgenic Arabidopsis and P. tomentosa plants were obtained through genetic transformation and a series of molecular tests. The flowering time and other growth characteristics were analyzed. Finally, the expression level of flowering genes was detected by quantitative PCR, the interaction between PtoNF-YC and PtoCOL proteins was measured using the yeast two-hybrid system to further explain the flowering regulation mechanism, and the molecular mechanisms by which PtNF-YC6 and PtNF-YC8 regulate poplar flowering were discussed. These results lay the foundation for elucidating the molecular regulation mechanism of PtoNF-YC in flowering and furthering the molecular design and breeding of poplar, while providing a reference for other flowering woody plants.

Rational Construction of a N, F Co-doped Mesoporous Cobalt Phosphate with Rich-Oxygen Vacancies for Oxygen Evolution Reaction and Supercapacitors.

Transition-metal phosphates have been widely applied as promising candidates for electrochemical energy storage and conversion. In this study, we report a simple method to prepare a N, F co-doped mesoporous cobalt phosphate with rich-oxygen vacancies by in-situ pyrolysis of a Co-phosphate precursor with NH4 + cations and F- anions. Due to this heteroatom doping, it could achieve a current density of 10 mA/cm2 at lower overpotential of 276 mV and smaller Tafel slope of 57.11 mV dec-1 on glassy carbon. Moreover, it could keep 92 % of initial current density for 35 h, indicating it has an excellent stability and durability. Furthermore, the optimal material applied in supercapacitor displays specific capacitance of 206.3 F g-1 at 1 A ⋅ g-1 and maintains cycling stability with 80 % after 3000 cycles. The excellent electrochemical properties should be attributed to N, F co-doping into this Co-based phosphate, which effectively modulates its electronic structure. In addition, its amorphous structure provides more active sites; moreover, its mesoporous structure should be beneficial to mass transfer and electrolyte diffusion.

Interference Analysis for mmWave Automotive Radar Considering Blockage Effect.

Due to the increasing number of vehicles equipped with millimeter wave (mmWave) radars, interference among automotive radars is becoming a major issue. This paper explores the automotive radar interference in both two-lane and multi-lane scenarios using stochastic geometry. We derive closed-form expressions for mean and variance of interference power considering directional antenna with constant and Gaussian decaying gains. In view of the sensitivity of mmWave radar signals to the blockages, we propose a blockage model including partially and completely blocking, and then calculate the effective number of the interferers. By means of modeling randomness for interferers and blockages as Poisson point process, we characterize the statistics of radar interference under different conditions. We further utilize the interference characterization to estimate the successful ranging probability of automotive radars. These theoretical analyses are verified by using Monte Carlo simulations. The results show that the increasing interfering density and ranging distance largely degrade the radar detection performance, whereas the interference levels decrease as blockage intensity increases.

Investigation of PtSGT1 and PtSGT4 Function in Cellulose Biosynthesis in Populus tomentosa Using CRISPR/Cas9 Technology.

Cellulose synthesis is a complex process in plant cells that is important for wood processing, pulping, and papermaking. Cellulose synthesis begins with the glycosylation of sitosterol by sitosterol glycosyltransferase (SGT) to produce sitosterol-glucoside (SG), which acts as the guiding primer for cellulose production. However, the biological functions of SGTs in Populus tomentosa(P. tomentosa) remain largely unknown. Two full-length PtSGT genes (PtSGT1 and PtSGT4) were previously isolated from P. tomentosa and characterized. In the present study, CRISPR/Cas9 gene-editing technology was used to construct PtSGT1-sgRNA and PtSGT4-sgRNA expression vectors, which were genetically transformed into P. tomentosa using the Agrobacterium-mediated method to obtain transgenic lines. Nucleic acid and amino acid sequencing analysis revealed both base insertions and deletions, in addition to reading frame shifts and early termination of translation in the transgenic lines. Sugar metabolism analysis indicated that sucrose and fructose were significantly downregulated in stems and leaves of mutant PtSGT1-1 and PtSGT4-1. Glucose levels did not change significantly in roots and stems of PtSGT1-1 mutants; however, glucose was significantly upregulated in stems and downregulated in leaves of the PtSGT4-1 mutants. Dissection of the plants revealed disordered and loosely arranged xylem cells in the PtSGT4-1 mutant, which were larger and thinner than those of the wild-type. This work will enhance our understanding of cellulose synthesis in the cell walls of woody plants.

Application of Contrast-Enhanced Real-time 3-Dimensional Ultrasound in Solid Abdominal Organ Trauma.

OBJECTIVES: To determine whether real-time 3-dimensional ultrasound (RT3DUS) could provide additional information on early detection and evaluation in the management of solid abdominal organ trauma based on an animal model. METHODS: Nine bleeding lesions were developed in the livers (n = 3), kidneys (n = 3), and spleens (n = 3) from 9 pigs. An ultrasound contrast agent was administered intravenously (liver, 0.025 mL/kg; kidney, 0.008 mL/kg; and spleen, 0.013 mL/kg) after an unenhanced 2-dimensional ultrasound (2DUS) examination (B-mode and color Doppler). After contrast agent injection, bleeding lesions were imaged by 2DUS and sequentially imaged by 3-dimensional static ultrasound (3DSUS) and RT3DUS to identify active bleeding, observe the relationship between bleeding lesions and peripheral blood vessels, and evaluate the spatial scope of the bleeding lesions in the organs. RESULTS: For the identification of active bleeding, there was no statistical difference in contrast-enhanced 2DUS, 3DSUS, and RT3DUS. For observation of the relationship between bleeding lesions and peripheral blood vessels, RT3DUS performed statistically better than 2DUS (P < .05), as reconstructed RT3DUS could show more information about the relationship. For the evaluation of the spatial scope of the bleeding lesion in the organ, RT3DUS also performed statistically better than 2DUS from the multiplanar observation by postprocessing of the 3-dimensional real-time volumes (P < .05). CONCLUSIONS: Real-time 3-dimensional ultrasound improves early detection and evaluation of solid abdominal organ trauma and provides additional information over the current contrast-enhanced 2DUS.

X-Linked Hyper IgM Syndrome Manifesting as Recurrent Pneumocystis jirovecii Pneumonia: A Case Report.

We reported a Chinese boy with X-linked hyper IgM (XHIGM) syndrome, manifesting as recurrent and severe pneumonia caused by Pneumocystis jirovecii. His parents were healthy and unrelated. In August 2018, the 5-month-old boy manifested as cough and dyspnea, and then in July 2019, he was admitted because of the same symptoms. Immunological results of the two admissions both showed low IgG, low IgA, normal IgM and high levels of 1,3-ß-D-glucan (BDG). Using next-generation sequencing (NGS), great reading counts of P. jirovecii were identified from the deep sputum in both admissions. Caspofungin combined with trimethoprim-sulfamethoxazole were used to anti-infection, and he recovered quickly. Whole-exome sequencing was performed for this family because of immune suppression, the disease-causing gene (exon 10-22 of CD40L) deletion for XHIGM syndrome was identified. NGS is beneficial for etiology diagnosis. Pneumocystis jirovecii pneumonia as an opportunistic infection could be recurrent in patients with XHIGM syndrome.

Spatial Attention Fusion for Obstacle Detection Using MmWave Radar and Vision Sensor.

For autonomous driving, it is important to detect obstacles in all scales accurately for safety consideration. In this paper, we propose a new spatial attention fusion (SAF) method for obstacle detection using mmWave radar and vision sensor, where the sparsity of radar points are considered in the proposed SAF. The proposed fusion method can be embedded in the feature-extraction stage, which leverages the features of mmWave radar and vision sensor effectively. Based on the SAF, an attention weight matrix is generated to fuse the vision features, which is different from the concatenation fusion and element-wise add fusion. Moreover, the proposed SAF can be trained by an end-to-end manner incorporated with the recent deep learning object detection framework. In addition, we build a generation model, which converts radar points to radar images for neural network training. Numerical results suggest that the newly developed fusion method achieves superior performance in public benchmarking. In addition, the source code will be released in the GitHub.

Early local drug therapy for pancreatic contusion and laceration.

OBJECTIVES: To study the therapeutic effect of early local drug therapy on pancreatic contusion and laceration. METHODS: Twenty pigs were divided into 4 groups: model(PL), 1 ml of saline; medical protein glue (EC), 1 ml of medical protein glue; ulinastatin (UL), 50000U of ulinastatin; combined treatment (UE), 1 ml of medical protein glue and 50000U of ulinastatin. 30 min after model establishment, different groups received different local drug treatments. The pancreatic function, peritoneal effusion and pancreatic pathology were observed. RESULTS: The UE group got the best therapeutic effect. The changes of pancreatic function and the peritoneal effusion were compared with PL group as follows. 0-6h: amylase (p < 0.01), lipase (p > 0.05), effusion (p < 0.01); 6-12h: amylase (p > 0.05), lipase (p < 0.01), effusion (p < 0.01); 12-24h: amylase (p < 0.01), lipase (p < 0.01), effusion (p < 0.01). CONCLUSIONS: Early local drug therapy in pancreatic contusion and laceration could effectively control the development of the disease and improve the prognosis.

Therapeutic effect of ultrasound interventional perirenal catheter-assisted early peripancreatic lavage of protease inhibitor on severe acute pancreatitis in miniature pigs.

OBJECTIVES: To study the therapeutic effect of early peripancreatic lavage of ulinastatin on severe acute pancreatitis(SAP). METHODS: Sixteen pigs were divided into 4 groups: model(SAP), saline lavage(SL), ulinastatin lavage(UL), intravenous ulinastatin(IU). UL and SL group were given peripancreatic lavage of ulinastatin by ultrasound-guided perirenal catheterization and IU group was intravenously instilled with ulinastatin. The multi-organ functions and the inflammatory factors were observed. RESULTS: UL group has the best therapeutic effect. The changes of multi-organ functions and the inflammatory factors were compared with SAP group as follows. In time window of treatment: amylase (p < 0.01), lipase (p < 0.01), ALT (p > 0.05), AST (p < 0.05), CR (p < 0.01), UR (p < 0.01), IL-6 (p < 0.01), IL-10 (p < 0.01). In post-treatment phase: amylase (p < 0.01), lipase (p < 0.01), ALT (p < 0.01), AST (p < 0.01), CR (p < 0.05), UR (p > 0.05), IL-6 (p < 0.01), IL-10 (p < 0.01). CONCLUSIONS: Early peripancreatic lavage of ulinastatin in SAP could effectively improve the multi-organ functions and inflammatory response.

Molecular Mechanisms of Mild and Severe Pneumonia: Insights from RNA Sequencing.

BACKGROUND This study aimed to uncover the molecular mechanisms underlying mild and severe pneumonia by use of mRNA sequencing (RNA-seq). MATERIAL AND METHODS RNA was extracted from the peripheral blood of patients with mild pneumonia, severe pneumonia, and healthy controls. Sequencing was performed on the HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differentially expressed genes (DEGs) were identified between the control group and the mild or severe group. A transcription factor-gene network was constructed for each group. Biological process (BP) terms enriched by DEGs in the network were analyzed and these genes were also mapped to the Connectivity map to search for small-molecule drugs. RESULTS A total of 199 and 560 DEGs were identified from the mild group and severe group, respectively. A transcription factor-gene network consisting of 215 nodes and another network consisting of 451 nodes were constructed in the mild group and severe group, respectively, and 54 DEGs (e.g., S100A9 and S100A12) were found to be common, with consistent differential expression changes in the 2 groups. Genes in the transcription factor-gene network for the mild group were mainly enriched in 13 BP terms, especially defense and inflammatory response (e.g., S100A8) and spermatogenesis, while the top BP terms enriched by genes in the severe group include response to oxidative stress (CCL5), wound healing, and regulation of cell differentiation (CCL5), and of the cellular protein metabolic process. CONCLUSIONS S100A9 and S100A12 may have a role in the pathogenesis of pneumonia: S100A9 and CXCL1 may contribute solely in mild pneumonia, and CCL5 and CXCL11 may contribute in severe pneumonia.

Multisensory Competition Is Modulated by Sensory Pathway Interactions with Fronto-Sensorimotor and Default-Mode Network Regions.

Multisensory information competes for preferential access to consciousness. It remains unknown what neural processes cause one particular modality to win multisensory competition and eventually dominate behavior. Thus, in a paradigm in which human participants sought to make simultaneous auditory and visual detection responses, we sought to identify prestimulus and poststimulus neural signals that were associated with auditory and visual dominance on each trial. Behaviorally, visual detection responses preceded auditory responses more frequently than vice versa. Even when visual responses were preceded by auditory responses, they recovered more quickly from previous responses, indicating the dominance of vision over audition. Neurally, visual precedence was associated with increased prestimulus activity in the prefrontal cortex and reduced prestimulus activity in the default-mode network, and increased poststimulus connectivity between the prefrontal cortex and the visual system. Moreover, the dorsal visual stream showed not only increased activity in post-perceptual phases but also enhanced connectivity with the sensorimotor cortex, indicating the functional role of the dorsal visual stream in prioritizing the flow of visual information into the motor system. In contrast, auditory precedence was associated with increased prestimulus activity in the auditory cortex and increased poststimulus neural coupling between the auditory and the sensorimotor cortex. Finally, whenever one modality lost multisensory competition, the corresponding sensory cortex showed enhanced connectivity with the default-mode network. Overall, the outcome of audiovisual competition depended on dynamic interactions between sensory systems and both the fronto-sensorimotor and the default-mode network. Together, these results revealed both the neural causes and the neural consequences of visual and auditory dominance during multisensory competition.

The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation Over Chemotherapy Alone in the Treatment of Acute Myeloid Leukemia Patients with Mixed Lineage Leukemia (MLL) Rearrangements.

BACKGROUND Acute myeloid leukemia (AML) patients with mixed lineage leukemia (MLL) gene rearrangements always had a very poor prognosis. In this study, we report the incidence of MLL rearrangements in AML patients using gene analysis, as well as the clinical significance and prognostic features of these rearrangements. MATERIAL AND METHODS This retrospective study took place from April 2008 to November 2011 in the People's Liberation Army General Hospital. A total 433 AML patients were screened by multiple nested reverse transcription polymerase chain reaction (RT-PCR) to determine the incidence of the 11 MLL gene rearrangements. There were 68 cases of MLL gene rearrangements, for a positive rate of 15.7%. A total of 24 patients underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and 34 patients received at least 4 cycles of chemotherapy. Ten patients were lost to follow-up. RESULTS The median follow-up was 29 months. The complete remission (CR) rate was 85.4%. The overall survival (OS) was 57.4±5.9 months for the Allo-HSCT group and 21.0±2.1 months for the chemotherapy group. The Allo-HSCT group had superior survival compared with the chemotherapy group (5-year OS: 59±17% vs. 13±8%, P<0.01; 5-year disease-free survival [DFS]: 65±10% vs. 40±16%, P>0.05). Multivariate analysis showed that transplantation, platelets >50×10^9/L at onset, and CR are associated with a better OS in MLL rearranged AML patients. Patients with thrombocytopenia and extramedullary involvement were prone to relapse. CONCLUSIONS Our results suggest that Allo-HSCT is superior to chemotherapy alone for treating MLL rearranged AML patients. Patients treated with Allo-HSCT have a better prognosis and a longer survival. CR is an independent prognostic factor for OS, and extramedullary involvement is an independent prognostic factor for DFS. MLL rearranged AML patients with thrombocytopenia at onset <50×10^9 had very bad OS and DFS.

Prognostic Significance of Mixed-Lineage Leukemia (MLL) Gene Detected by Real-Time Fluorescence Quantitative PCR Assay in Acute Myeloid Leukemia.

BACKGROUND The overall prognosis of acute myeloid leukemia (AML) patients with mixed-lineage leukemia (MLL) gene-positivity is unfavorable. In this study, we evaluated the expression levels of the MLL gene in AML patients. MATERIAL AND METHODS We enrolled 68 MLL gene-positive patients out of 433 newly diagnosed AML patients, and 216 bone marrow samples were collected. Real-time fluorescence quantitative PCR (RQ-PCR) was used to precisely detect the expression levels of the MLL gene. RESULTS We divided 41 patients into 2 groups according to the variation of MRD (minimal residual disease) level of the MLL gene. Group 1 (n=22) had a rapid reduction of MRD level to ≤10^-4 in all samples collected in the first 3 chemotherapy cycles, while group 2 (n=19) had MRD levels constantly >10^-4 in all samples collected in the first 3 chemotherapy cycles. Group 1 had a significantly better overall survival (p=0.001) and event-free survival (p=0.001) compared to group 2. Moreover, the patients with >10^-4 MRD level before the start of HSCT (hematopoietic stem cell transplantation) had worse prognosis and higher risk of relapse compared to patients with ≤10^-4 before the start of HSCT. CONCLUSIONS We found that a rapid reduction of MRD level to ≤10^-4 appears to be a prerequisite for better overall survival and event-free survival during the treatment of AML. The MRD levels detected by RQ-PCR were basically in line with the clinical outcome and may be of great importance in guiding early allogeneic HSCT (allo-HSCT) treatment.

Identification of Potential Key Long Non-Coding RNAs and Target Genes Associated with Pneumonia Using Long Non-Coding RNA Sequencing (lncRNA-Seq): A Preliminary Study.

BACKGROUND This study aimed to identify the potential key long non-coding RNAs (lncRNAs) and target genes associated with pneumonia using lncRNA sequencing (lncRNA-seq). MATERIAL AND METHODS A total of 9 peripheral blood samples from patients with mild pneumonia (n=3) and severe pneumonia (n=3), as well as volunteers without pneumonia (n=3), were received for lncRNA-seq. Based on the sequencing data, differentially expressed lncRNAs (DE-lncRNAs) were identified by the limma package. After the functional enrichment analysis, target genes of DE-lncRNAs were predicted, and the regulatory network was constructed. RESULTS In total, 99 DE-lncRNAs (14 upregulated and 85 downregulated ones) were identified in the mild pneumonia group and 85 (72 upregulated and 13 downregulated ones) in the severe pneumonia group, compared with the control group. Among these DE-lncRNAs, 9 lncRNAs were upregulated in both the mild and severe pneumonia groups. A set of 868 genes were predicted to be targeted by these 9 DE-lncRNAs. In the network, RP11-248E9.5 and RP11-456D7.1 targeted the majority of genes. RP11-248E9.5 regulated several genes together with CTD-2300H10.2, such as QRFP and EPS8. Both upregulated RP11-456D7.1 and RP11-96C23.9 regulated several genes, such as PDK2. RP11-456D7.1 also positively regulated CCL21. CONCLUSIONS These novel lncRNAs and their target genes may be closely associated with the progression of pneumonia.

The effect of ferrous-chelating hairtail peptides on iron deficiency and intestinal flora in rats.

BACKGROUND: Chelating agents, such as small peptides, can decrease free iron content and increase iron bioavailability. They may have promising therapeutic potential and may prevent the pro-oxidant effects of low molecular weight iron. Hairtail is a species of fish that is rich in easily digestible proteins. We extended this strategy for iron delivery by using an enzymatic hydrolysate of hairtail as the chelating agent and found that the ferrous-chelating hairtail peptides have anti-anaemic activity in Sprague-Dawley rats with anaemia. RESULTS: The anti-anaemic activity of ferrous-chelating hairtail peptides prepared by enzymatic hydrolysis of the hairtail and ferrous chelation was studied in rat models of iron deficiency anaemia. After the end of the 35 d experiment, we noted significant differences in haemoglobin, mean corpuscular volume, haemoglobin distribution width, and ferritin concentrations between those animals supplemented with ferrous-chelating hairtail peptides and FeSO4 and healthy animals. There were no negative side effects on the animals' growth or behaviour. There was no obvious inflammation in the intestinal mucosa lamina propria and no unbalance of intestinal flora. CONCLUSION: The novel ferrous-chelating hairtail peptides may be a suitable fortificant for improving iron-deficiency status. Our findings demonstrated that this multi-tracer technique has many applications in nutritional research. © 2015 Society of Chemical Industry.