To evaluate internal tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3-ITD-positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic samples from 241 FLT3-ITDmutated patients. All patients were treated on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48 nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized according to functional regions of the FLT3 receptor: juxtamembrane domain (JMD), n ‫؍‬ 148; JMD hinge region, n ‫؍‬ 48; beta1-sheet of the tyrosine kinase domain-1 (TKD1), n ‫؍‬ 73; remaining TKD1 region, n ‫؍‬ 13. ITD length was strongly correlated with functional regions (P < .001). In multivariable analyses, ITD integration site in the beta1-sheet was identified as an unfavorable prognostic factor for achievement of a complete remission (odds ratio, 0.22; P ‫؍‬ .01), relapsefree survival (hazard ratio, 1.86; P < .001), and overall survival (hazard ratio, 1.59; P ‫؍‬ .008). ITD insertion site in the beta1-sheet appears to be an important unfavorable prognostic factor in young adult patients with FLT3-ITD-positive AML.

• More than 90% of the patients with inv (16)

Periodontitis is a common intraoral infection and is inextricably linked to systemic diseases. Recently, the regulation between host immunologic response and periodontal pathogens has become a hotspot to explain the mechanism of periodontitis and related systemic diseases. Since Porphyromonas gingivalis ( P. gingivalis ) was proved as critical periodontal pathogen above all, researches focusing on the mechanism of its virulence factors have received extensive attention. Studies have shown that in the development of periodontitis, in addition to the direct release of virulent factors by periodontal pathogens to destroy periodontal tissues, over-low or over-high intrinsic immune and inflammatory response mediated by Toll-like receptors (TLRs) can lead to more lasting destruction of periodontal tissues. It is very necessary to sort out how various cytopathic factors of P. gingivalis mediate inflammation and immune responses between the host through TLRs so as to help precisely prevent, diagnose, and treat periodontitis in clinic. This review summarizes the role of three most widely studied pathogenic factors produced by P. gingivalis (lipopolysaccharide, gingipains, pili) and their interactions with TLRs at the cellular and molecular level in the progress of periodontitis.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability, and may be beneficial for motor recovery after stroke. However, the neuroplasticity effects of rTMS have not been thoroughly investigated in the early stage after stroke.ObjectiveTo comprehensively assess the effects of high- and low-frequency repetitive transcranial magnetic stimulations on motor recovery in early stroke patients, using a randomized controlled trial based on clinical, neurophysiological and functional imaging assessments.MethodsSixty hospitalized, first-ever ischemic stroke patients (within 2 weeks after stroke) with motor deficits were randomly allocated to receive, in addition to standard physical therapy, five consecutive sessions of either: (1) High-frequency (HF) rTMS at 10 Hz over the ipsilesional primary motor cortex (M1); (2) Low-frequency (LF) rTMS at 1 Hz over the contralesional M1; (3) sham rTMS. The primary outcome measure was a motor impairment score (Upper Extremity Fugl-Meyer) evaluated at baseline, after rTMS intervention, and at 3-month follow-up. Cortical excitability and functional magnetic resonance imaging (fMRI) data were obtained within 24 h before and after rTMS intervention. Analyses of variance were conducted to compare the recovery effects among the three rTMS groups, assessed using clinical, neurophysiological and fMRI tests.ResultsMotor improvement was significantly larger in the two rTMS groups than in the control group. The HF-rTMS group showed significantly increased cortical excitability and motor-evoked fMRI activation in ipsilesional motor areas, whereas the LF-rTMS group had significantly decreased cortical excitability and motor-evoked fMRI activation in contralesional motor areas. Activity in ipsilesional motor cortex significantly correlated with motor function, after intervention as well as at 3-month follow-up.ConclusionHF- and LF-rTMS can both improve motor function by modulating motor cortical activation in the early phase of stroke.