Background Depressive disorder is a well-known chronic, recurrent and disabling mental disease with high direct and indirect costs to society in both western and eastern cultures. Approximately 40% ...of depressed patients show only partial or no response to initial or even multiple antidepressant medications and are usually called treatment-resistant depression （TRD） patients. The present work was to measure the features of sensory gating （SG） P50 in TRD patients with the intent of understanding the characteristics of this disease. Methods In 50 TRD patients, 39 non-treatment-resistant depression （NTRD） patients and 51 healthy controls （HC）, auditory evoked potential P50 was measured using the conditioning/testing paradigm presented with auditory double clicks stimuli, and 36 TRD patients had repeated measurements after an 8-week venlafaxine treatment course. Results All the depressive disorder patients, including the TRD and NTRD groups, showed an increased testing stimulus wave （$2-P50） amplitude compared to controls （P 〈0.01 and P 〈0.05）, but there was no significant difference between the TRD and NTRD groups （P 〉0.05）. There were significant differences in the ratio of testing stimulus （S2） and conditioning stimulus （S1） （S2/S1） and in the value of 100 × （1-S2/S1） among the three groups. Compared to the baseline, TRD patients had no significant changes of features and different expression of P50 after acute treatment （P 〉0.05）. Meanwhile, a statistically significant positive correlation of S2/S1 with the scores of the 17-item Hamilton Rating Scale for Depression （HAMD-17） （P 〈0.01）, and a significantly negative correlation of S1-S2, 100 × （1-S2/S1） with the scores of HAMD-17 （P 〈0.01） were observed in the TRD patients＇ baseline measurement, but there was no correlation after venlafaxine treatment （P 〉0.05）. Conclusions Both the TRD and NTRD patients had obvious SG deficits, with a more severe deficit in TRD patients. Although, with a correlated relationship to the severity of depressive symptoms, SG P50 deficit might be suggested as a trait marker for TRD, and a combination of S2/S1 ratio, S1-S2 and 100 × （1-S2/S1）, was recommended for electrophysiological measurement in TRD patients.
Background： Plasmacytoid dendritic cells （pDCs） and cytokines play an important role in occurrence and recovery of hepatitis B virus （HBV） infection. The aim of this study was to explore the ...frequency and function ofpDC and serum cytokine network profiles in patients with acute or chronic HBV infection. Methods： The healthy individuals （HI group）, hepatitis B envelope antigen （HBeAg）-positive chronic HBV patients in immune tolerance （IT） phase （IT group）, HBeAg-positive chronic HBV patients （CHB group）, and acute HBV patients （AHB group） were enrolled in this study. The frequency of cluster of differentiation antigen 86 （CD86） ＋ pDC and the counts of CD86 molecular expressed on surface ofpDC were tested by flow cytometer. The quantitative determinations ofcytokines, including Fins-like tyrosine kinase 3 ligand （FIt-3L）, interferon （1FN）-α2, IFN-γ, interleukin （IL）-17A, IL-6, IL-10, transforming growth factor （TGF）-β1 and TGF-β2, were performed using Luminex multiplex technology. Results： In this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group （including all patients in IT, CHB and AHB groups） had significantly higher counts of CD86 molecular expressed on the surface ofpDC （4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P 〈 0.001）. The counts of CD86 molecular expressed on the surface of pDC in CriB group （7739.2 ±4125.4） was significantly higher than that of IT group （6393.4 ± 1653.6, P=0.043）. Compared with IT group, the profile of cytokines of FIt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased （P =0.012） in CH B group. The contents of IL-10, TGF-{31, and TGF-132 in AHB group were significantly increased compared with IT and CHB groups （all P 〈 0.05）. Conclusions： This study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in H BV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.
Achieving a periodic domain structure in ferroelectric materials to tailor the macroscopic properties or realize new functions has always been a hot topic. However, methods to construct periodic ...domain structures, such as epitaxial growth, direct writing by scanning tips, and the patterned electrode method, are difficult or inefficient to implement in emerging molecular ferroelectrics, which have the advantages of lightweight, flexibility, biocompatibility, etc. An efficient method for constructing and controlling periodic domain structures is urgently needed to facilitate the development of molecular ferroelectrics in nanoelectronic devices. In this work, it is demonstrated that large‐area, periodic and controllable needle‐like domain structures can be achieved in thin films of the molecular ferroelectric trimethylchloromethyl ammonium trichlorocadmium (TMCM‐CdCl3) upon the application of tensile strain. The domain evolution under various tensile strains can be clearly observed, and such processes are accordingly identified. Furthermore, the domain wall exhibits a superior piezoelectric response, with up to fivefold enhancement compared to that of the pristine samples. Such large‐area tunable periodic domain structure and abnormally strong piezoresponse are not only of great interests in fundamental studies, but also highly important in the future applications in functional molecular materials.
By applying tensile strain to the thin film of molecular ferroelectric trimethylchloromethyl ammonium trichlorocadmium (TMCM‐CdCl3), a large area of highly ordered periodic domain structures can be obtained. The density and width of these periodic domains can be adjusted by the magnitude of strain and the thickness of the film, respectively, and the piezoelectric response at the domain wall is enhanced.
A novel dual-emission fluorescence ratiometric probe of luminol-Tb-GMP CPNPs for highly sensitive and selective detection of ALP and As(v) has been constructed based on the stimulus responsivity of ...luminol. The introduction of luminol as a ligand for Tb
, combined with GMP, leads to a sensor which is more robust, sensitive, and efficient.
Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell ...therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m
. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10
cells/kg range, 0.07 to 2.1 × 10
) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval CI, 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.
ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
Anatomizing mixed‐phases, referring to analyzing the mixing profiles and quantifying the phases’ proportions in a material, which is of great significance in the genuine applications. Here, by using ...second‐harmonic generation (SHG) polarimetry and piezoresponse force microscopy (PFM) techniques, this work elucidates the contributions and distributions of two different symmetric phases mixed in an archetype monoaxial molecular ferroelectric, diisopropylammonium chloride (DIPACl). The two competing phases are preferred in thermodynamics or kinetic process respectively, and this work evidences the switching behavior between the two competing phases facilitated by an external electrical field as opposed to a heating process. This research contributes novel insights into phase engineering in the field of molecular ferroelectrics and is poised to serve as a potent analytical tool for subsequent applications.
This study introduces an advanced molecular ferroelectric with amalgamation of two symmetric phases (phase α and phase γ). The mixing profile, as unveiled by Second Harmonic Generation (SHG) polarimetry, is predominantly at the nanoscale, as opposed to mixed grains. The transition process between the two symmetric phases is facilitated through the application of an external electrical field.
PDF
