Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who ...were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell's C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.
Granular micro/mesoporous carbon with a ratio of mesopore to total pore volume (V meso/V total) greater than 75% was prepared using coconut shells as a precursor by a one-step thermal treatment, ...i.e., combined pyrolysis and steam activation process. The process variables, such as final activation temperature, time, and water flow rate were studied. The N2 adsorption isotherms of the samples were of type IV, indicating mesoporous characteristics. The mesoporosity of the resultant porous carbons prepared by this method is greater than the one of those prepared by the conventional two separate pyrolysis and activation processes. Experimental results showed that the yield of porous carbon was proportional to the final pyrolysis temperature and activation time. Additionally, with the increase of activation time and water flow rate, the mesoporosity increased considerably. When the activation time and water flow rate were kept constant, the mesoporosity also increased with a rise in the final pyrolysis temperature. Electrochemical tests indicate that with the increase of V meso/V total of the porous carbons, the equivalent series resistance (ESR) decreases and the capacitance retention is of 93% at a high current density of 5 A g–1. Thereinto, the carbon electrode made from sample CS-800-0.12-60 with the highest V meso/V total have a high capacitance of 228 F g–1 in 6.0 mol L–1 KOH electrolyte at 5 mV s–1 and the energy density of 38.5 Wh kg–1 with an ESR of 1.9 Ω at 0.5 A g–1.
We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early‐stage extranodal nasal‐type NK/T‐cell lymphoma (ENKTCL), ...and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new‐regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram‐revised risk index (NRI). A comparative study was performed using propensity score‐matched (PSM) analysis. Adding new‐regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression‐free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate‐risk/high‐risk patients, but not for low‐risk patients. For intermediate‐risk/high‐risk patients, RT + CT and CT + RT resulted in non‐significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk‐based, response‐adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate‐risk/high‐risk early‐stage patients with ENKTCL in the modern treatment era.
Sleep disorder emerges as a common comorbidity in children with autism spectrum disorder (ASD), and the interaction between the core symptoms of ASD and its sleep disorder remains unclear. Repetitive ...transcranial magnetic stimulation (rTMS) was used on the bilateral dorsolateral prefrontal cortex (DLPFC) to investigate the efficacy of rTMS on the core symptoms of ASD and comorbid sleep problems as well as the mediation role of the ASD symptoms between rTMS intervention and sleep improvement. A total of 41 Chinese children with ASD and who met the criteria in the fifth edition of the American Diagnostic and Statistical Manual of Mental Disorders were recruited, and 39 of them (mean age: 9.0 ± 4.4 years old; the male-female ratio was 3.9: 1) completed the study with the stimulating protocol of high frequency on the left DLPFC and low frequency on the right DLPFC. They were all assessed three times (before, at 4 weeks after, and at 8 weeks after the stimulation) by the Children's Sleep Habits Questionnaire (CSHQ), Strengths and Difficulties Questionnaire (SDQ), Childhood Autism Rating Scale, Repetitive Behavior Questionnaire-2, and Short Sensory Profile (SSP). The repeated-measures ANOVA showed that the main effect of "intervention time" of CSHQ (
= 25.103,
< 0.001), SSP (
= 6.345,
= 0.003), and SDQ (
= 9.975,
< 0.001) was statistically significant. By Bayesian mediation analysis, we only found that the total score of SSP mediated the treating efficacy of rTMS on CSHQ (αβ = 5.11 ± 1.51, 95% CI: 2.50-8.41). The percentage of mediation effect in total effect was 37.94%. Our results indicated the treating efficacy of rTMS modulation on bilateral DLPFC for both autistic symptoms and sleep disturbances. The sensory abnormality of ASD mediated the improvement of rTMS on sleep problems of ASD.
Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL ...can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy between 2008 and 2016 in China Lymphoma Collaborative Group multicenter database. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. Median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had similar cure fraction to that of younger patients. Five-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.
Limited evidence supports the use of early endpoints to evaluate the success of initial treatment of extranodal NK/T-cell lymphoma (ENKTCL) in the modern era. We aim to analyze progression-free ...survival at 24 months (PFS24) and subsequent overall survival (OS) in a large-scale multicenter cohort of patients. 1790 patients were included from the China Lymphoma Collaborative Group (CLCG) database. Subsequent OS was defined from the time of PFS24 or progression within 24 months to death. OS was compared with age- and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Patients who did not achieve PFS24 had a median OS of 5.3 months after progression, with 5-year OS rate of 19.2% and the SMR of 71.4 (95% CI, 62.9-81.1). In contrast, 74% patients achieved PFS24, and the SMR after achieving PFS24 was 1.77 (95% CI, 1.34-2.34). The observed OS rate after PFS24 versus expected OS rate at 5 years was 92.2% versus 94.3%. Similarly, superior outcomes following PFS24 were observed in early-stage patients (5-year OS rate, 92.9%). Patients achieving PFS24 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. These marked differences suggest that PFS24 may be used for study design and risk stratification in ENKTCL.
Successful completion of the molting process requires new epidermal growth and ecdysis of the old cuticle in Haemaphysalis longicornis (H. longicornis). MicroRNAs (miRNAs) participate in the ...development of organisms by inhibiting the expression of their target mRNAs. In this study, a novel tick-specific miRNA was identified and denoted hlo-miR-2 that serves as a novel regulator of molting events in H. longicornis nymphs by targeting a cuticular protein. The full length of this cuticular protein was first obtained and named it CPR1. A qRT-PCR analysis showed that hlo-miR-2 and CPR1 exhibit significant tissue and temporal specificity and that their transcription levels are negatively correlated during the molting process. CPR1, as a direct target of hlo-miR-2, was identified by a luciferase reporter assay in vitro. Agomir treatment indicated that the overexpression of hlo-miR-2 significantly reduced the protein expression level of CPR1, decreased the molting rate and delayed the molting time point in H. longicornis nymphs. RNA interference (RNAi) experiments demonstrated that CPR1 was significantly associated with the molting process in H. longicornis nymphs. Phenotypic rescue experiments convincingly showed that hlo-miR-2 participated in molting events by targeting CPR1 in H. longicornis nymphs. In summary, we present evidence demonstrating that miRNAs constitute a novel important regulator of molting events in addition to hormones. The described functional evidence implicating CPR1 in molting events contributes to an improved understanding of the distinct functions of the CPR family in ticks and will aid the development of a promising application of cuticular protein RNAi in tick control.
is a clinically underestimated conditional pathogen in the genus
, the pathogenicity of the infection caused by
remains poorly understood. According to previous studies, Type-VI secretion system ...(T6SS) is a protein secreting device widely existing in Gram-negative bacilli. Valine-glycine repeat protein G (VgrG) is not only an important component of T6SS, but also a virulence factor of many Gram-negative bacilli. In one of our previous studies, a unique T6SS
gene (
gene) was present in a virulent
strain BPM (BPM), but not in the relatively avirulent
strain E264 (E264). Meanwhile, transcriptome analysis of BPM and E264 showed that the
gene was strongly expressed in BPM, but not in E264. Therefore, we identified the function of the
gene by constructing the mutant and complemented strains in this study.
, the
gene was observed to be involved in the interactions with host cells. The animal model experiment showed that the deletion of
gene significantly led to the decrease in the lethality of BPM and impaired its ability to trigger host immune response. In conclusion, our study provides a new perspective for studying the pathogenicity of
and lays the foundation for discovering the potential T6SS effectors.
The Huanghua Depression is located in the north-centre of Bohai Bay Basin, which is a rift basin developed in the Mesozoic over the basement of the Huabei Platform, China. Permo-Carboniferous source ...rocks were formed in the Huanghua Depression, which has experienced multiple complicated tectonic alterations with inhomogeneous uplift, deformation, buried depth and magma effect. As a result, the hydrocarbon generation evolution of Permo-Carboniferous source rocks was characterized by discontinuity and grading. On the basis of a detailed study on tectonic-burial history, the paper worked on the burial history, heating history and hydrocarbon generation history of Permo-Carboniferous source rocks in the Huanghua Depression combined with apatite fission track testing and fluid inclusion analyses using the EASY%Rₒ numerical simulation. The results revealed that their maturity evolved in stages with multiple hydrocarbon generations. In this paper, we clarified the tectonic episode, the strength of hydrocarbon generation and the time–spatial distribution of hydrocarbon regeneration. Finally, an important conclusion was made that the hydrocarbon regeneration of Permo-Carboniferous source rocks occurred in the Late Cenozoic and the subordinate depressions were brought forward as advantage zones for the depth exploration of Permo-Carboniferous oil and gas in the middle-northern part of the Huanghua Depression, Bohai Bay Basin, China.
This study aimed to clarify the benefit of radiotherapy (RT) in patients with early-stage extranodal NK/T-cell lymphoma (NKTCL) who achieve a complete response (CR) after asparaginase-containing ...chemotherapy (CT).
Of 240 patients achieved a CR after asparaginase-containing CT, 202 patients received additional RT (CT + RT), and 38 patients did not (CT alone).
Compared to CT alone, CT + RT significantly improved overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The 5-year OS, DFS and LRC rates were 84.9%, 76.2% and 84.9% for CT + RT, compared to 58.9% (P = 0.006), 43.6% (P = 0.001) and 62.1% (P = 0.026) for CT alone. The 5-year cumulative disease recurrence rate was 18.8% for CT + RT compared to 46.9% (P = 0.003) for CT alone. High-dose RT (≥50 Gy) significantly decreased the risk of locoregional recurrence. The 5-year cumulative locoregional failure rate was 35.5% for patients receiving <50 Gy compared to 8.8% for patients receiving ≥50 Gy (P = 0.028).
For patients with early-stage NKTCL who achieve a CR after asparaginase-containing CT, omission of RT results in frequent locoregional recurrence and a poor prognosis; RT is essential to improve locoregional control and survival.
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