Successful use of trametinib and dasatinib combined with chemotherapy in the treatment of Ph-positive B-cell acute lymphoblastic leukemia: A case report

Rationale:Relapsed or refractory acute lymphoblastic leukemia poses a significant clinical challenge due to its poor prognosis, showing survival rates of less than a year even with the use of novel therapies. In this report, we describe the safe and effective use of trametinib combined with dasatinib in a patient with acute lymphoblastic leukemia (ALL). To the best of our knowledge, this is the first report on the successful use of 2 targeted drugs such as trametinib and dasatinib in a pediatric patient with Ph+ ALL and recurrent pancreatitis.Patient concerns:A 6-year-old boy with ALL and Philadelphia chromosome (Ph+) who had recurrent asparaginase-associated pancreatitis.Diagnosis:The patient was diagnosed with ALL, based on clinical features, laboratory analyses, bone marrow aspiration evaluation in morphology, immunology, cytogenetics, and molecular.Interventions:The patient was treated with dasatinib combined with an intermediate risk-oriented chemotherapy. However, owing to recurrent asparaginase-associated pancreatitis, the patient has to abandon asparaginase in consolidation. Considering the high risk of relapse, we used trametinib and dasatinib combined with chemotherapy as maintenance chemotherapy.Outcomes:After 6 months, there were no obvious side effects or residual disease.Lessons:We suggest that the combination of trametinib and dasatinib may represent a viable option to treat patients with potential relapsed/refractory Ph+ ALL.     

Wrist-hand extension function recovery in spastic hemiplegia patient by botulinum toxin injection plus surface electromyography biofeedback therapy: A case report

Rationale:Wrist-hand extension function rehabilitation is a vital and difficult part of hand function recovery in spastic stroke patients. Although botulinum toxin type A (BoNTA) injection plus post injection therapy was applied to the wrist-hand rehabilitation in previous reports, conclusion was inconsistent in promoting function. For this phenomenon, proper selection of patients for BoNTA injection and correct choice of post-injection intervention could be the crucial factors for the function recovery.Patient concerns:We reported a 46-year-old male suffered a spastic hemiplegia with wrist- hand extension deficit.Diagnoses:Computed tomography showed cerebral hemorrhage in the left basal ganglia region.Interventions:Four hundred units of BoNTA were injected into the spasticity flexors, and four-week post injection surface electromyography (sEMG) biofeedback therapy was applied to the patient.Outcomes:The patient exhibited post-intervention improvement in wrist-hand extensors performance (strength, range of motion, sEMG signals), the flexors spasticity, and upper extremity function.Lessons:The present case showed that 4-week of BoNTA injection plus sEMG biofeedback exercise improved the performance and function of wrist-hand extensors in the patient for short- and long-term. Proper selection of patients for BoNTA injection and correct choice of post injection exercise could play a vital role in the hand rehabilitation for patient with spastic hemiplegia.     

The exosome of platelet endothelial cell adhesion molecule-1 (PECAM1) protein: A potential risking star in high blood pressure patients (HBPP)

A number of studies have demonstrated that exosomes were involved in important physiological and pathological processes through cell-to-cell communication in cardiovascular disease, which contained nucleic acids, proteins, and lipid contents. In our study, we found that the protein platelet endothelial cell adhesion molecule-1 (PECAM1) was an extracellular vesicle in the blood of high blood pressure patients (HBPP).Isolated the vesicles from the blood of HBPP and health examiners and detected its size and morphology with nanoparticle tracking analysis, then we identified its surface protein CD63, CD81, and the protein expression of PECAM1 in the exosome with western blot. Furthermore, we analyzed the correlation between the expression of PECAM1 and the high blood degree with linear regression analysis.Our results showed that the morphology of extracellular vesicles was more evident in high blood pressure groups than healthy controls, and the protein expression of PECAM1 was also abundant in the vesicles of HBPP, however, there were no extracellular vesicles in the blood samples of healthy controls. Besides, linear regression showed the linear correlation coefficient R = 0.901, P < .01 between the expression of PECAM1 and the systolic blood pressure of the high blood patients. Therefore, the exosome of protein of PECAM1 was a potential risking star in HBPP.     

Anxiety and prognosis of patients with myocardial infarction: A meta‐analysis

Although anxiety is highly prevalent after myocardial infarction (MI), but the association between anxiety and MI is not well established. This study aimed to provide an updated and comprehensive evaluation of the association between anxiety and short‐term and long‐term prognoses in patients with MI. Anxiety is associated with poor short‐term and long‐term prognoses in patients with MI. We performed a systematic search in the PubMed and Cochrane databases (January 2000–October 2020). The study endpoints were complications, all‐cause mortality, cardiac mortality, and/or major adverse cardiac events (MACEs). Pooled data were synthesized using Stata SE12.0 and expressed as risk ratios (RRs) and 95% confidence intervals (CIs). We included 9373 patients with MI from 16 published studies. Pooled analyses indicated a correlation between high anxiety and poor clinical outcomes (RR: 1.19, 95% CI: 1.13–1.26, p < .001), poor short‐term complications (RR: 1.23, 95% CI: 1.09–1.38, p = .001), and poor long‐term prognosis (RR: 1.27, 95% CI: 1.13–1.44, p < .001). Anxiety was also specifically associated with long‐term mortality (RR: 1.16, 95% CI: 1.01–1.33, p = .033) and long‐term MACEs (RR: 1.54, 95% CI: 1.26–1.90, p < .001). This study provided strong evidence that increased anxiety was associated with poor prognosis in patients with MI. Further analysis revealed that MI patients with anxiety had a 23% increased risk of short‐term complications and a 27% increased risk of adverse long‐term prognosis compared to those without anxiety.     

An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases

Aim:

SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases.

Methods:

Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells.

Results:

Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells.

Conclusion:

NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.     

Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models

Aim:

Carbonaceous dots (CDs), which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene glycol-modified CDs (PEG-CDs) were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models.

Methods:

Mice were intravenously treated with CDs (size: 4.9 nm, 5 mg·kg⁻¹·d⁻¹) or PEG-CDs (size: 8.3 nm, 5 mg·kg⁻¹·d⁻¹) for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos'' hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene (clml2) at 48 hpf.

Results:

Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs (20 μg/mL) caused heart development delay, whereas addition of CDs (80 μg/mL) led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments.

Conclusion:

CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.     

The application of the Chinese version of the Body Image Disturbance Questionnaire in patients with systemic lupus erythematosus

This study aimed to translate the Body Image Disturbance Questionnaire (BIDQ) into Chinese and evaluate its reliability and validity in a sample of patients with systemic lupus erythematosus (SLE).Following the translation and revision of the Chinese version of the BIDQ, 169 patients with SLE were chosen as respondents to test the questionnaire''s reliability and validity. We tested the content''s validity through expert group evaluation. It is structural validity was examined through exploratory factor analysis and confirmatory factor analysis, and reliability was evaluated using Cronbach''s α and test-retest reliability.The Chinese version of the BIDQ showed a content validity of .92. A two-factor structure was revealed by exploratory factor analysis, which explained 67.83% of the variance and proved by confirmatory factor analysis. Its overall Cronbach''s α was .82 (P < .001), and the Cronbach''s α for each item ranged from .76 to .83. The test-retest reliability was .82, with the Cronbach''s α for each item ranging from .76 to .84.Thus, adequate reliability and validity of the Chinese version of the BIDQ were demonstrated for use in patients with SLE.     

The role of estrogen receptor-beta gene +1730G/A polymorphisms in recurrent pregnancy loss: A protocol for systematic review and meta-analysis

Objective:To identify the role of estrogen receptor-beta (ER-β) gene +1730G/A (rs4986938) polymorphisms in recurrent pregnancy loss (RPL).Methods:All relevant case-control studies will be systematically searched in multiple databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet (CNKI), Wanfang and Cqvip. Both pooled odds rations (ORs) and 95% confidence intervals (CIs) will be used to assess the association between ER-β gene +1730G/A polymorphisms and RPL risk. The publication bias will be evaluated using Egger test.Results:ER-β gene +1730G/A variation may be associated with a higher risk of RPL in Caucasian population.Conclusions:The findings of this meta-analysis will provide high-quality evidence for the association between ER-β gene +1730G/A polymorphisms and RPL, facilitating clinical practice and further scientific studies.OSF registration number:10.17605/OSF.IO/EW9FB.     

Hormetic effects of noncoplanar PCB exposed to human lung fibroblast cells (HELF) and possible role of oxidative stress

Hormesis, a biphasic dose–response phenomenon, which is characterized by stimulation of an end point at a low‐dose and inhibition at a high‐dose. In the present study we used human lungs fibroblast (HELF) cells as a test model to evaluate the role of oxidative stress (OS) in hormetic effects of non coplanar PCB 101. Results from 3‐(4,5‐dime‐thylthiazol‐2‐yl)‐2,5‐diphenyltetrazo‐lium bromide (MTT) assay indicated that PCB101 at lower concentrations (10^?5 to 10^?1 μg mL^?1) stimulated HELF cell proliferation and inhibited at high concentrations (1, 5, 10, and 20 μg mL^?1) in a dose‐ and time‐dependent manner. Reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) (except 48 h) showed a significant increase at higher concentrations of PCB 101 than those at the lower concentrations with the passage of time. Antioxidant enzymes such as glutathione peroxidase (GSH‐Px) exhibited decreasing trends in dose and time dependent manner. Lipid peroxidation assay resulted in a significant increase (P < 0.05) of MDA level in PCB 101‐treated HELF cells compared with controls, suggesting that OS plays a key role in PCB 101‐induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of PCB 101 exposure compared to lower concentrations. Overall, we found that HELF cell proliferation was higher at low ROS level and vice versa, which revealed activation of cell signaling‐mediated hormetic mechanisms. The results suggested that PCB 101 has hormetic effects to HELF cells and these were associated with oxidative stress. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1385–1392, 2015.     

Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, P_Adj?=?2.75?×?10^?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.