Comparison of the Efficacy of Levofloxacin-based Sequential Therapy and Bismuth Quadruple Therapy in the Second Line and Third Line Therapy for Helicobacter Pylori Infection- A Multi-center Randomized Trial
Objectives: Eradication of H. pylori infection could reduce the occurence or recurrence of gastric cancer and peptic ulcer diseases. However, it was estimated that 15-20% of patients would fail from first line standard eradication therapy and need second line rescue therapy. About 15-30% of patient would fail from second line therapy. Bismuth quadruple therapy and triple therapy containing levofloxacin are currently the recommended rescue therapies in the second line and third line treatment. Recently, our pilot study showed that modified sequential therapy containing levofloxacin achieved high eradication rate (95%) in the second line therapy. The regimen includes a PPI plus amoxicillin for 5-7 days, followed by a PPI plus levofloxacin and metronidazole for another 5-7 days. However, whether this modified sequential therapy containing levofloxacin is more effective than bismuth quadruple therapy in the second line and third line treatment remains unknown. Besides, the impact of these regimens on the antibiotic resistance , microbiota of gut flora, and metabolic factors remains unknown. Aims: Therefore, the investigators aimed to compare the eradication rates and long term re-infection rates of sequential therapy containing levofloxacin for 14 days versus bismuth quadruple therapy for 10 days in the second line and third line treatment assess the impact of antibiotic resistance and CYP2C19 polymorphism on the eradication rate of these regimens assess the impact of these eradication regimens on the antibiotic resistance and microbiota of the gut flora assess the impact of eradication therapy on the metabolic factors
The Effects of Play and Competition-Based Cognitive Therapy on Executive Functions and Occupational Routines in Children With Dyslexia
Purpose: The aim of this study was to investigate the effects of play and competition-based cognitive therapy (PCB-CT) on executive function and occupational routines in children with dyslexia. Method: In this randomized control trail, 64 children with dyslexia (between 7-12 ages) were randomly selected from the 162 clients who applied to the clinic. Children were divided randomly into a treatment group and a control group. Children in the intervention group was given cognitive therapy for 10 weeks, 3 days a week for one hour sessions while no therapy was received to the control group. In order to evaluate the cognition of the children Test of Visual Perceptual Skills-3 (TVPS-3) and Dynamic Occupational Therapy Cognitive Assessment (DOTCA-Ch), to evaluate executive functions the Behavior Rating Inventory of Executive Function (BRIEF) and to evaluate occupational routine The Executive Functions and Occupational Routines Scale (EFORTS) were used. The evaluations were done at baseline, after treatment and the end of the 3rd month for both groups.
The role of tonifying kidney decoction and acupuncture in the treatment of Alzheimer's disease: A network meta-analysis.
作者: Xin-Chen Wang ; Chen-Liang Chu ; Kuan Lu ; Xi Chen ; Xiao-Qian Jin ; Shi-Jian Quan
As one of the chronic neurological degenerative diseases with the highest incidence of amnesia and dementia, Alzheimer's disease (AD) carried out the clinical treatment based on the 2 traditional Chinese medicine (TCM) of Chinese herbal compound and acupuncture (AP). With the vigorous development of TCM, doctors are facing the problem of choosing TCM or western medicine in clinical work. Hence there is an urge to make pairwise comparisons among these interventions to provide evidence for clinical practice.
The used efficacy of the 2 TCM methods and combined with donepeziline were compared to compile the best treatment through network meta-analysis.
Patients diagnosed with AD were included in the randomized clinical trial, who were treated with tonifying kidney decoction (TKD) or AP combined with donepezil hydrochloride (DH) as an intervention measure, while the control group was treated with DH. The total effective rate was the primary outcome, and mini-mental state examination (MMSE) score and activities of daily living (ADCS-ADL) scores were the secondary indicators.
Eventually 30 studies reporting 2236 patients underwent TKD or AP combined with DH were enrolled. In terms of total efficiency, compared with TKD and DH, TKD + DH was significantly preferable. In addition, TKD were classified into 2 categories, namely tonifying kidney with reducing phlegm formulas (TKRP) and tonifying kidney with filling lean marrow (TKFLM). Regarding to MMSE score of TKD, of the 3 interventions, only TKRP + DH (standard mean difference [SMD] = 4.84, 95% confidence interval [CI]: 0.86-8.82) and TKFLM + DH (SMD = 3.93, 95% CI: 1.06-6.80) had significant efficacy over TKFLM (SMD = 4.25, 95%CI: -2.58 to 11.08). Although no difference between TKRP and other groups, its effectiveness was higher than TKFLM + DH and TKFLM (surface under the cumulative ranking curve (SUCRA) = 61.5%). For the ADL score, compared with TKFLM + DH and DH, TKRP + DH had more effective (SUCRA = 70.2%). Regarding to the total effective rates, AP + DH was more statistically better than AP, and AP was statistically better than DH.
TKD or AP in combination with DH are significantly superior in treating AD.
2022-01-01·International journal of nanomedicine
Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids.
作者: Akhil K Mohan ; Minsa M ; T R Santhosh Kumar ; G S Vinod Kumar
Peptide-based therapy is a promising strategy for cancer treatment because of its low drug resistance. However, the major challenge is their inability to target cancer cells specifically. So, a targeted nano-delivery system that could deliver therapeutic peptides selectively to cancer cells to stimulate their action is highly desirable. This study aims to deliver the antitumor peptide, Pep5, to breast tumor cells selectively using a targeting peptide functionalised multi-layered PLGA-PEI nanoparticles.
In this study, Pep5 entrapped PLGA-PEI (Pep5-PPN) dual layered nanoparticles were developed. These nanoparticles were decorated with TKD (Pep5-TPPN) on their surface for site-specific delivery of Pep5 to breast tumor cells. The particles were then characterized using various instrumental analyses. In vitro cytotoxicity of the particles was evaluated in estrogen receptor positive (ER+ve) and triple negative breast cancer (TNBC) cells. An ex vivo tumor spheroid model was used to analyze the antitumor activity of the particles.
Uniformly round Pep5-TPPN particles were synthesized with an average diameter of 420.8 ± 14.72 nm. The conjugation of PEI over Pep5-PLGA nanoparticles shifted the zeta potential from -11.6 ± 2.16 mV to +20.01 ± 2.97 mV. In vitro cytotoxicity analysis proved that TKD conjugation to nanoparticles enhanced the antitumor activity of Pep5 in tested breast cancer cells. Pep5-TPPN induced cytoskeletal damage and apoptosis in the tested cells, which showed that the mechanism of action of Pep5 is conserved but potentiated. Active targeting of Pep5 suppressed the tumor growth in ex vivo spheroid models.
A multi-layered nanoparticle functionalized with dual peptide was fabricated for active tumor targeting, which stimulated Pep5 activity to reduce the tumor growth in vitro and ex vivo.
2020-10-15·Clinical Cancer Research1区 · 医学
Targeted natural killer cell-based adoptive immunotherapy for the treatment of patients with NSCLC after radiochemotherapy: a randomized phase II clinical trial
1区 · 医学
作者: Multhoff, Gabriele ; Seier, Sophie ; Stangl, Stefan ; Sievert, Wolfgang ; Shevtsov, Maxim ; Werner, Caroline ; Pockley, A. Graham ; Blankenstein, Christiane ; Hildebrandt, Martin ; Ahrens, Robert Offner Norbert ; Kokowski, Konrad ; Hautmann, Matthias ; Rodel, Claus ; Fietkau, Rainer ; Lubgan, Dorota ; Huber, Rudolf ; Hautmann, Hubert ; Duell, Thomas ; Molls, Michael ; Specht, Hanno ; Haller, Bernhard ; Devecka, Michal ; Sauter, Andreas ; Combs, Stephanie E.
Non-small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo-activated NK cells in patients with NSCLC after radiochemotherapy (RCT).
PATIENTS AND METHODS:
Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60-70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses.
The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%-90%] for the INT arm and 33% (95% CI, 5%-68%) for the CTRL arm (P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood.
Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT.