Publications by authors named "Na Xu"

456 Publications

Processed Multiparameter Electroencephalogram-Guided General Anesthesia Management Can Reduce Postoperative Delirium Following Carotid Endarterectomy: A Randomized Clinical Trial.

Front Neurol 2021 12;12:666814. Epub 2021 Jul 12.

Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Patients undergoing carotid endarterectomy (CEA) for severe carotid stenosis are vulnerable to postoperative delirium, a complication frequently associated with poor outcome. This study investigated the impact of processed electroencephalogram (EEG)-guided anesthesia management on the incidence of postoperative delirium in patients undergoing CEA. This single-center, prospective, randomized clinical trial on 255 patients receiving CEA under general anesthesia compared the outcomes of patient state index (PSI) monitoring [SEDLine Brain Function Monitor (Masimo, Inc, Irvine, CA)] (standard group, = 128) with PSI combined with density spectral array(DSA) -guided monitoring (intervention group, = 127) to reduce the risk of intraoperative EEG burst suppression. All patients were monitored by continuous transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to avoid perioperative cerebral hypoperfusion or hyperperfusion. According to the surgical process, EEG suppression time was calculated separately for three stages: S (from anesthesia induction to carotid artery clamping), S (from clamping to declamping), and S (from declamping to the end of surgery). The primary outcome was incidence of postoperative delirium according to the Confusion Assessment Method algorithm during the first 3 days post-surgery, and secondary outcomes were other neurologic complications and length of hospital stay. There were no episodes of cerebral hypoperfusion or hyperperfusion according to TCD and NIRS monitoring in either group during surgery. The incidence of postoperative delirium within 3 days post-surgery was significantly lower in the intervention group than the standard group (7.87 . 28.91%, < 0.01). In the intervention group, the total EEG suppression time and the EEG suppression time during S2 and S3 were shorter (Total, 0 "0" . 0 "1.17" min, = 0.04; S, 0 "0" . 0 "0.1" min, < 0.01; S, 0 "0" . 0 "0" min, = 0.02). There were no group differences in incidence of neurologic complications and length of postoperative hospital stay. Processed electroencephalogram-guided general anesthesia management, consisting of PSI combined with DSA monitoring, can significantly reduce the risk of postoperative delirium in patients undergoing CEA. Patients, especially those exhibiting hemodynamic fluctuations or receiving surgical procedures that disrupt cerebral perfusion, may benefit from the monitoring of multiple EEG parameters during surgery. www.ClinicalTrials.gov, identifier: NCT03622515.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.666814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311024PMC
July 2021

Agomelatine prevents angiotensin II-induced endothelial and mononuclear cell adhesion.

Aging (Albany NY) 2021 Jul 22;13(undefined). Epub 2021 Jul 22.

Department of Stomatology, Tibet Corps Hospital, Chinese People's Armed Police Forces, Lhasa 850000, Tibet Autonomous Region, China.

Agomelatine is a non-selective melatonin receptor agonist and an atypical antidepressant with anti-inflammatory, neuroprotective, and cardioprotective effects. The renin-angiotensin system modulates blood pressure and vascular homeostasis. Angiotensin II (Ang II) and its receptor Ang II type I receptor (ATR) are recognized as contributors to the pathogenesis of cardiovascular and cardiometabolic diseases, including diabetes, obesity, and atherosclerosis. The recruitment and attachment of monocytes to the vascular endothelium is a major event in the early stages of atherosclerosis and other cardiovascular diseases. In the present study, we demonstrate that agomelatine reduced Ang II-induced expression of ATR while significantly inhibiting the attachment of monocytes to endothelial cells induced by Ang II and mediated by ICAM-1 and VCAM-1. Additionally, Ang II inhibited the expression of the chemokines CXCL1, MCP-1, and CCL5, which are critical in the process of immune cell recruitment and invasion. Agomelatine also suppressed the expression of TNF-α, IL-8, and IL-12, which are proinflammatory cytokines that promote endothelial dysfunction and atherogenesis. Importantly, we demonstrate that the inhibitory effect of agomelatine against the expression of adhesion molecules is mediated through the downregulation of Egr-1 signaling. Together, our findings provide evidence of a novel mechanism of agomelatine that may be practicable in the treatment and prevention of cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.203299DOI Listing
July 2021

Presurgical Evaluation of Epilepsy Using Resting-State MEG Functional Connectivity.

Front Hum Neurosci 2021 2;15:649074. Epub 2021 Jul 2.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Epilepsy is caused by abnormal electrical discharges (clinically identified by electrophysiological recording) in a specific part of the brain [originating in only one part of the brain, namely, the epileptogenic zone (EZ)]. Epilepsy is now defined as an archetypical hyperexcited neural network disorder. It can be investigated through the network analysis of interictal discharges, ictal discharges, and resting-state functional connectivity. Currently, there is an increasing interest in embedding resting-state connectivity analysis into the preoperative evaluation of epilepsy. Among the various neuroimaging technologies employed to achieve brain functional networks, magnetoencephalography (MEG) with the excellent temporal resolution is an ideal tool for estimating the resting-state connectivity between brain regions, which can reveal network abnormalities in epilepsy. What value does MEG resting-state functional connectivity offer for epileptic presurgical evaluation? Regarding this topic, this paper introduced the origin of MEG and the workflow of constructing source-space functional connectivity based on MEG signals. Resting-state functional connectivity abnormalities correlate with epileptogenic networks, which are defined by the brain regions involved in the production and propagation of epileptic activities. This paper reviewed the evidence of altered epileptic connectivity based on low- or high-frequency oscillations (HFOs) and the evidence of the advantage of using simultaneous MEG and intracranial electroencephalography (iEEG) recordings. More importantly, this review highlighted that MEG-based resting-state functional connectivity has the potential to predict postsurgical outcomes. In conclusion, resting-state MEG functional connectivity has made a substantial progress toward serving as a candidate biomarker included in epileptic presurgical evaluations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2021.649074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283278PMC
July 2021

Final results of the double-blind placebo-controlled randomized phase 2 LOTUS trial of first-line ipatasertib plus paclitaxel for inoperable locally advanced/metastatic triple-negative breast cancer.

Breast Cancer Res Treat 2021 Jul 15. Epub 2021 Jul 15.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Purpose: In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free survival (PFS; primary endpoint), with an enhanced effect in patients with PIK3CA/AKT1/PTEN-altered tumors (FoundationOne next-generation sequencing [NGS] assay). We report final overall survival (OS) results.

Methods: Eligible patients had measurable previously untreated aTNBC. Patients were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status, and were randomized 1:1 to paclitaxel 80 mg/m (days 1, 8, 15) plus ipatasertib 400 mg or placebo (days 1-21) every 28 days until disease progression or unacceptable toxicity. OS (intent-to-treat [ITT], immunohistochemistry PTEN-low, and PI3K/AKT pathway-activated [NGS PIK3CA/AKT1/PTEN-altered] populations) was a secondary endpoint.

Results: Median follow-up was 19.0 versus 16.0 months in the ipatasertib-paclitaxel versus placebo-paclitaxel arms, respectively. In the ITT population (n = 124), median OS was numerically longer with ipatasertib-paclitaxel than placebo-paclitaxel (hazard ratio 0.80, 95% CI 0.50-1.28; median 25.8 vs 16.9 months, respectively; 1-year OS 83% vs 68%). Likewise, median OS favored ipatasertib-paclitaxel in the PTEN-low (n = 48; 23.1 vs 15.8 months; hazard ratio 0.83) and PIK3CA/AKT1/PTEN-altered (n = 42; 25.8 vs 22.1 months; hazard ratio 1.13) subgroups. The ipatasertib-paclitaxel safety profile was unchanged.

Conclusions: Final OS results show a numerical trend favoring ipatasertib-paclitaxel and median OS exceeding 2 years with ipatasertib-paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-021-06143-5DOI Listing
July 2021

Barriers and facilitators to exercise in haemodialysis patients: A systematic review of qualitative studies.

J Adv Nurs 2021 Jul 14. Epub 2021 Jul 14.

Health Science Center, Xi'an Jiaotong University, Xi'an, Shaan Xi, China.

Aims: The purpose of this systematic review is to synthesize the results of qualitative research and to identify the barriers and facilitators to exercise in haemodialysis patients from the perspectives of haemodialysis patients, caregivers and dialysis staff members.

Design: Systematic review of qualitative studies.

Data Sources: Qualitative studies were extracted from MEDLINE, EMBASE, Web of Science, CINAHL, PsycINFO, PubMed, CBM, CNKI and WanFang Database from inception of each database until July 2020. Qualitative research and mixed method research including barriers and/or facilitators to exercise in haemodialysis patients were included.

Review Methods: The systematic search method SPIDER (sample, phenomenon of interest, design, evaluation, research type) was used. Thematic synthesis of qualitative data was used.

Results: 284 studies were screened and 10 studies published between 2007 and 2020 were finally included in this review. The review included 180 patients, 70 dialysis staff members and seven caregivers. Five analytical themes were identified: disease distress, perception of exercise, environmental restrictions, spirit strength and hospital management. Barriers include disease distress, perception of exercise (security issue), environmental restrictions and hospital management. Facilitators include perception of exercise (exercise being considered beneficial, preference for exercise) and spirit strength (from religious beliefs). It is the spiritual strength (from family and friends, from dialysis staff members) that is both the barrier and the facilitator.

Conclusion: There are many barriers in popularizing exercise among haemodialysis patients. Future intervention measures and health policies should strengthen the facilitators and reduce the barriers, so as to promote the clinical practice of exercise for haemodialysis patients.

Impact: This review summarizes the barriers and facilitators to exercise in haemodialysis patients. The results of this study have an impact on research, practice and health policy setting. The exercise level of haemodialysis patients can be improved by using the facilitators and solving the barriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jan.14960DOI Listing
July 2021

Association Between Measurable Residual Disease in Patients With Intermediate-Risk Acute Myeloid Leukemia and First Remission, Treatment, and Outcomes.

JAMA Netw Open 2021 Jul 1;4(7):e2115991. Epub 2021 Jul 1.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Importance: Measurable residual disease (MRD) is widely used as a therapy-stratification factor for acute myeloid leukemia (AML), but the association of dynamic MRD with postremission treatment (PRT) in patients with intermediate-risk AML (IR-AML) has not been well investigated.

Objective: To investigate PRT choices based on dynamic MRD in patients with IR-AML.

Design, Setting, And Participants: This cohort study examined 549 younger patients with de novo IR-AML in the South China Hematology Alliance database during the period from January 1, 2012, to June 30, 2016, including 154 who received chemotherapy, 116 who received an autologous stem cell transplant (auto-SCT), and 279 who received an allogeneic SCT (allo-SCT). Subgroup analyses were performed according to dynamic MRD after the first, second, and third courses of chemotherapy. The end point of the last follow-up was August 31, 2020. Statistical analysis was performed from December 1, 2019, to September 30, 2020.

Exposures: Receipt of chemotherapy, auto-SCT, or allo-SCT.

Main Outcomes And Measures: The primary end points were 5-year cumulative incidence of relapse and leukemia-free survival.

Results: Subgroup analyses were performed for 549 participants (314 male participants [57.2%]; median age, 37 years [range, 14-60 years]) according to the dynamics of MRD after 1, 2, or 3 courses of chemotherapy. Comparable cumulative incidences of relapse, leukemia-free survival, and overall survival were observed among participants who had no MRD after 1, 2, or 3 courses of chemotherapy. Participants who underwent chemotherapy and those who underwent auto-SCT had better graft-vs-host disease-free, relapse-free survival (GRFS) than those who underwent allo-SCT (chemotherapy: hazard ratio [HR], 0.35 [95% CI, 0.14-0.90]; P = .03; auto-SCT: HR, 0.07 [95% CI, 0.01-0.58]; P = .01). Among participants with MRD after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse (auto-SCT: HR, 0.25 [95% CI, 0.08-0.78]; P = .01; allo-SCT: HR, 0.08 [95% CI, 0.02-0.24]; P < .001), better leukemia-free survival (auto-SCT: HR, 0.26 [95% CI, 0.10-0.64]; P = .004; allo-SCT: HR, 0.21 [95% CI, 0.09-0.46]; P < .001), and overall survival (auto-SCT: HR, 0.22 [95% CI, 0.08-0.64]; P = .005; allo-SCT: HR, 0.25 [95% CI, 0.11-0.59]; P = .001) vs chemotherapy. In addition, auto-SCT showed better GRFS than allo-SCT (HR, 0.45 [95% CI, 0.21-0.98]; P = .04) in this group. Among participants with MRD after 1 or 2 courses of chemotherapy but no MRD after 3 courses, allo-SCT had superior cumulative incidence of relapse (HR, 0.10 [95% CI, 0.06-0.94]; P = .04) and leukemia-free survival (HR, 0.18 [95% CI, 0.05-0.68]; P = .01) compared with chemotherapy, but no advantageous cumulative incidence of relapse (HR, 0.15 [95% CI, 0.02-1.42]; P = .10) and leukemia-free survival (HR, 0.23 [95% CI, 0.05-1.08]; P = .06) compared with auto-SCT. Among participants with MRD after 3 courses of chemotherapy, allo-SCT had superior cumulative incidences of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.16 [95% CI, 0.08-0.33]; P < .001; leukemia-free survival: HR, 0.19 [95% CI, 0.10-0.35]; P < .001; overall survival: HR, 0.29 [95% CI, 0.15-0.55]; P < .001) and auto-SCT (relapse: HR, 0.25 [95% CI, 0.12-0.53]; P < .001; leukemia-free survival: HR, 0.35 [95% CI, 0.18-0.73]; P = .004; overall survival: HR, 0.54 [95% CI, 0.26-0.94]; P = .04). Among participants with recurrent MRD, allo-SCT was also associated with advantageous cumulative incidence of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.12 [95% CI, 0.04-0.33]; P < .001; leukemia-free survival: HR, 0.24 [95% CI, 0.10-0.56]; P = .001; overall survival: HR, 0.31 [95% CI, 0.13-0.75]; P = .01) and auto-SCT (relapse: HR, 0.28 [95% CI, 0.09-0.81]; P = .02; leukemia-free survival: HR, 0.30 [95% CI, 0.12-0.76]; P = .01; overall survival: HR, 0.26 [95% CI, 0.10-0.70]; P = .007).

Conclusions And Relevance: This study suggests that clinical decisions based on dynamic MRD might be associated with improved therapy stratification and optimized PRT for patients with IR-AML. Prospective multicenter trials are needed to further validate these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2021.15991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264648PMC
July 2021

Alveolar Recruitment Maneuver Reduces Cerebral Oxygen Saturation and Cerebral Blood Flow Velocity in Patients During Carotid Endarterectomy.

Med Sci Monit 2021 Jun 20;27:e930617. Epub 2021 Jun 20.

Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China (mainland).

BACKGROUND This study aimed to determine the effects of alveolar recruitment maneuver (RM) on cerebral oxygen saturation and cerebral blood velocity in patients undergoing carotid endarterectomy (CEA) before clamping of the carotid artery. MATERIAL AND METHODS In this crossover exploratory study, all patients were randomized to undergo an RM (30 cmH₂O of continuous airway pressure for 30 s) and a "sham" maneuver (SM; 5 cmH₂O for 30 s), followed by an alternative intervention after a 5-min equilibration period. Near-infrared spectroscopy (NIRS) was used to monitor regional cerebral oxygen saturation (rSO₂), and transcranial Doppler ultrasonography (TCD) to evaluate blood velocity of the middle cerebral artery (V-MCA). Changes in rSO₂, V-MCA, mean arterial pressure (MAP), and heart rate (HR) in response to the 2 interventions were compared. RESULTS A total of 59 patients underwent the study procedure. RM reduced rSO₂, V-MCA, MAP, and HR, but these variables slightly changed during SM. A significant drop in rSO₂ was observed immediately after RM compared with the baseline value (68.51±4.4% vs 64.12±5.15%; P<0.001). The decrease in rSO₂ was higher during the RM than during the SM (-6±4% vs 1±2%; P<0.001). Similarly, change in V-MCA was more significant in response to RM than SM (-26±19% vs 19±16%; P<0.001). The V-MCA value changed from 39 cm/s to 29 cm/s after RM. In addition, V-MCA of the ipsilateral to the surgical side decreased more obviously than the contralateral side (-26±19% vs -20±17%; P=0.001). CONCLUSIONS An RM at 30 cmH₂O of continuous airway pressure for 30 s decreased rSO₂ and V-MCA. In addition, MAP and HR were affected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.930617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223757PMC
June 2021

The gut microbiome of the Sunda pangolin () reveals its adaptation to specialized myrmecophagy.

PeerJ 2021 2;9:e11490. Epub 2021 Jun 2.

School of Life Science, South China Normal University, Guangzhou, Guangdong Province, China.

Background: The gut microbiomes of mammals are closely related to the diets of their hosts. The Sunda pangolin () is a specialized myrmecophage, but its gut microbiome has rarely been studied.

Methods: Using high-throughput Illumina barcoded 16S rRNA amplicons of nine fecal samples from nine captive Sunda pangolins, we investigated their gut microbiomes.

Results: The detected bacteria were classified into 14 phyla, 24 classes, 48 orders, 97 families, and 271 genera. The main bacterial phyla were Firmicutes (73.71%), Proteobacteria (18.42%), Actinobacteria (3.44%), and Bacteroidetes (0.51%). In the PCoA and neighbor-net network (PERMANOVA: pangolins . other diets, weighted UniFrac distance < 0.01, unweighted UniFrac distance < 0.001), the gut microbiomes of the Sunda pangolins were distinct from those of mammals with different diets, but were much closer to other myrmecophages, and to carnivores, while distant from herbivores. We identified some gut microbiomes related to the digestion of chitin, including , , , and species, which confirms that the gut microbiome of pangolins may help them to digest chitin.

Significance: The results will aid studies of extreme dietary adaption and the mechanisms of diet differentiation in mammals, as well as metagenomic studies, captive breeding, and ex situ conservation of pangolins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.11490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179220PMC
June 2021

Activation of Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Channels Promotes Odontogenic Differentiation of Human Dental Pulp Cells.

J Endod 2021 Jun 12. Epub 2021 Jun 12.

Department of Endodontics, College of Stomatology, Tianjin Medical University, Tianjin, China. Electronic address:

Introduction: Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are thermosensitive channels that play an important role in thermal sensation or tooth pain by regulating intracellular Ca concentration that is essential for pulp tissue repair. The aim of this study was to evaluate the role of TRPA1 and TRPV1 channels in the odontogenic differentiation of human dental pulp cells (HDPCs).

Methods: HDPCs were isolated from healthy human intact third molars and cultured in odontogenic differentiation medium. Gene and protein expression levels of TRPA1 and TRPV1 channels during the odontogenic differentiation of HDPCs were evaluated by real-time quantitative polymerase chain reaction and Western blot analysis. HDPCs were then treated with channel agonists or antagonists, and the expression levels of odontogenic markers dentin sialophosphoprotein (DSPP) and osteopontin (OPN) were examined. Alkaline phosphatase activity and alizarin red staining were also conducted to detect mineralization levels.

Results: Consistent with the mineralization degree and DSPP and OPN expression, messenger RNA and protein expression of TRPA1 and TRPV1 channels was up-regulated during the odontogenic differentiation of HDPCs. The application of TRPA1 or TRPV1 agonists increased the mineralized nodules of alizarin red staining and alkaline phosphatase activity and up-regulated the messenger RNA and protein expression of DSPP and OPN, respectively, with the highest values reached on the seventh day (P < .05). On the contrary, the mineralization level and DSPP and OPN expression could be suppressed by using the antagonists of these 2 channels.

Conclusions: TRPA1 and TRPV1 channels not only showed up-regulated expression along with the odontogenic differentiation of HDPCs but also could affect the odontogenic differentiation by regulating intracellular Ca concentration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joen.2021.06.007DOI Listing
June 2021

Monocular central retinal artery occlusion caused by bilateral internal carotid artery hypoplasia complicated with patent foramen ovale: a case report and review of literature.

Eur J Med Res 2021 Jun 13;26(1):55. Epub 2021 Jun 13.

Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, 325027, Zhejiang, China.

Background: Central retinal artery occlusion (CRAO) is an emergent ophthalmic disease which is commonly caused by atherosclerosis, thromboembolism, and arteriospasm. Here, we report a case of CRAO which is caused by extreme rare bilateral internal carotid artery (ICA) hypoplasia complicated with patent foramen ovale (PFO). The cardiogenic emboli blocked central retinal artery through unclosed foramen ovale and specific blood flow pathway.

Case Presentation: This report describes a case of a 46-year-old woman sudden onset with amaurosis fugax for about 20 min and persistent visual impairment of left eye. Fundus fluorescein angiography shows the arm-retinal circulation time of left eye is 25 s, indicating that the occlusion occurs in the pathway from aortic arch to ophthalmic artery. The MRA and CTA examinations reveal the bilateral ICA hypoplasia and variation of Wills circle. Furthermore, transesophageal echocardiography (TEE) confirms the PFO and cardiogenic embolic event.

Conclusions: This work presents a CRAO case caused by rare congenital hypoplasia of ICA complicated with PFO, reminding us every single cause of vascular disease should be investigated carefully and the TOAST typing of cerebrovascular disease can be of great reference to the ocular vascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40001-021-00530-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201921PMC
June 2021

Asystole during onyx embolisation of dural arteriovenous fistula: a case of trigeminal cardiac reflex.

Neurol Neurochir Pol 2021 Jun 11. Epub 2021 Jun 11.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053 Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/PJNNS.a2021.0044DOI Listing
June 2021

[Clinical Characteristics and Prognosis of Elderly Patients with Medium and High risk Myelodysplastic Syndrome].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):840-846

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China,E-mail:

Objective: To investigate the clinical characteristics and prognosis of patients with medium and high risk myelodysplastic syndrome (MDS).

Methods: 97 MDS patients above the age of 60 treated in Nanfang Hospital, Southern Medical University from February 2011 to August 2020 were enrolled. The clinical characteristics and prognosis of the MDS patients with medium risk, high risk or very high risk based on IPSS-R category were retrospectively analyzed. According to the difference of treatment regimes, the patients were divided into the transplantation group, chemotherapy group and other treatment group, and the efficacy among the patients in the 3 groups were analyzed.

Results: MDS with excess blast (MDS-EB) in the elderly patients with medium and high risk MDS were the most common, 47.4% of the patients with abnormal chromosome karyotypes, and 23.7% with complex karyotypes (≥3). 97.3% of the patients showed at least one gene mutation, and TP53 mutations were detected in nearly 20% of the patients with medium and high risk. Multivariate analysis showed that IPSS-R category and treatment regimes were the factors affecting the prognosis of elderly patients with medium and high risk MDS. The median overall survival (OS) time of the patients in the 3 groups showed significant difference (P=0.012), and the median OS of the patients in the transplantation group was significantly longer than that in the chemotherapy group and other group (P=0.003,P=0.014,respectively), while there was no significant difference in median OS between chemotherapy group and other treatment group (P=0.685).

Conclusion: Elderly MDS patients with medium and high risk can benefit from allogeneic hematopoietic stem cell transplantation, which will prolong their OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.029DOI Listing
June 2021

Knowledge, Attitudes, and Practices of Urban Residents Toward COVID-19 in Shaanxi During the Post-lockdown Period.

Front Public Health 2021;9:659797. Epub 2021 May 20.

School of Nursing, Xi'an Medical University, Xi'an, China.

The coronavirus disease 2019 (COVID-19) pandemic in China is essentially under control. Under global scrutiny, China has started reviving the social, cultural, and working lives of its inhabitants. However, localized outbreaks of COVID-19 are occurring, indicating that the country still needs to follow disease prevention and control measures. Previous studies have assessed the knowledge, attitudes, and behaviors of the general public in China regarding COVID-19 during the pandemic. However, little is known about knowledge, attitudes, and practices (KAP) of Chinese residents regarding COVID-19 after periods of lockdown. Therefore, this study was conducted to identify the KAP and other factors among the residents of Shaanxi Province during the post-lockdown period. A cross-sectional, network questionnaire survey was conducted in Shaanxi Province from October 1-30, 2020. A total of 1,175 urban residents were interviewed via Wen Juan Xing, an online questionnaire tool. A self-developed online KAP COVID-19 questionnaire was developed in this study. The questionnaire consisted of four parts: general information, knowledge, attitude, and practice. Descriptive statistics and binomial logistic regression analysis were used in the statistical analysis. The majority of the participants were knowledgeable about COVID-19. They had optimistic attitudes and behaved appropriately toward COVID-19. Education was an associated factor for the knowledge of residents and the knowledge of COVID-19 was high among people with high academic qualifications. Attitudes were more positive in residents who lived with elderly people, women, and children. The score of practice was higher in residents with positive attitudes and high academic qualifications. There was a positive correlation between age and practice. We found that the KAP of residents in Shaanxi was at a relatively high level during the post-lockdown period. Although the lockdown was lifted, the epidemic is not over. Thus, it is necessary to develop targeted health education programs for residents with different demographic characteristics in Shaanxi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2021.659797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172590PMC
June 2021

Adolescents experienced more treatment failure than children with chronic myeloid leukemia receiving imatinib as frontline therapy: a retrospective multicenter study.

Ann Hematol 2021 Jun 5. Epub 2021 Jun 5.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

To explore the differences in the clinical features, treatment responses, and outcomes among children, adolescents, and adults with chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib as first-line therapy. Data from children (0-8 years for girls and 0-10 years for boys), adolescents (9-19 years for girls and 11-19 years for boys), and adults (age ≥ 20 years) with newly diagnosed CML-CP receiving imatinib as first-line therapy between 2006 and 2019 were retrospectively reviewed. In total, 135 children (cohort 1), 189 adolescents (cohort 2), and 658 adults (cohort 3: age 20-39 years, n = 305; cohort 4: age 40-59 years, n = 270; and cohort 5: age 60-83 years, n = 83) were included in this study. When compared with children, adolescents showed a significantly higher white blood cell count (P = 0.033) and basophil percentage in peripheral blood (P = 0.002) and a significantly higher prevalence of splenomegaly (P = 0.004). Both children and adolescents presented with more aggressive clinical features than adults. During median follow-ups of 28 months (range, 3-161 months) in children, 33 months (range, 3-152 months) in adolescents, and 48 months (range, 3-157 months) in adults, multivariate analysis showed that children and adolescents had higher probabilities of achieving complete cytogenetic response, major molecular response, and molecular response. Notably, compared with not only adults (cohort 3 vs. cohort 1: HR = 2.03 [1.03, 3.98], P = 0.040; cohort 4 vs. cohort 1: HR = 2.15 [1.07, 4.33], P = 0.033; cohort 5 vs. cohort 1: HR = 4.22 [1.94, 9.15], P < 0.001) but also adolescents (cohort 2 vs. cohort 1: HR = 2.36 [1.18, 4.72], P = 0.015), children had significantly longer failure-free survival. Age was not associated with progression-free survival or overall survival. Although they exhibited more aggressive clinical features at diagnosis, both children and adolescents achieved superior treatment responses than adults. Adolescents showed even more adverse features and a poor FFS than children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-021-04544-6DOI Listing
June 2021

Geranylgeranyl pyrophosphate-mediated protein geranylgeranylation regulates endothelial cell proliferation and apoptosis during vasculogenesis in mouse embryo.

J Genet Genomics 2021 Apr 27;48(4):300-311. Epub 2021 Apr 27.

Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and School of Medicine, Nanjing University, National Resource Center for Mutant Mice, Nanjing 210093, China. Electronic address:

Vascular development is essential for the establishment of the circulatory system during embryonic development and requires the proliferation of endothelial cells. However, the underpinning regulatory mechanisms are not well understood. Here, we report that geranylgeranyl pyrophosphate (GGPP), a metabolite involved in protein geranylgeranylation, plays an indispensable role in embryonic vascular development. GGPP is synthesized by geranylgeranyl pyrophosphate synthase (GGPPS) in the mevalonate pathway. The selective knockout of Ggpps in endothelial cells led to aberrant vascular development and embryonic lethality, resulting from the decreased proliferation and enhanced apoptosis of endothelial cells during vasculogenesis. The defect in protein geranylgeranylation induced by GGPP depletion inhibited the membrane localization of RhoA and enhanced yes-associated protein (YAP) phosphorylation, thereby prohibiting the entry of YAP into the nucleus and the expression of YAP target genes related to cell proliferation and the antiapoptosis process. Moreover, inhibition of the mevalonate pathway by simvastatin induced endothelial cell proliferation defects and apoptosis, which were ameliorated by GGPP. Geranylgeraniol (GGOH), a precursor of GGPP, ameliorated the harmful effects of simvastatin on vascular development of developing fetuses in pregnant mice. These results indicate that GGPP-mediated protein geranylgeranylation is essential for endothelial cell proliferation and the antiapoptosis process during embryonic vascular development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgg.2021.03.009DOI Listing
April 2021

Biased agonists with less glucagon-like peptide-1 receptor-mediated endocytosis prolong hypoglycaemic effects.

Eur J Pharmacol 2021 May 26;907:174203. Epub 2021 May 26.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:

Receptor endocytic trafficking entails targeting receptors and ligands to endocytic sites, followed by internalization and sorting to recycling or degradative compartments. Thus, membrane receptor-mediated signalling pathways not only contribute to the efficacy of the drugs but also play a crucial role in the metabolic elimination of peptide drugs. Glucagon-like peptide-1 (GLP-1) receptor is the crucial target for type 2 diabetes mellitus. We mainly focused on the characteristics, early evaluation of GLP-1 receptor endocytosis and effects of optimization for endocytosis on druggability. The GLP-1 receptor endocytosis characteristics of agonists were analysed by a multifunction microplate reader, flow cytometer and confocal microscope. The intracellular cyclic adenosine monophosphate (cAMP) activation of agonists was analysed based on a reporter gene assay, and intracellular β-arrestin recruitment detection was detected based on a Tango assay. We established quantitative evaluation methods of endocytosis based on fluorescently labelled agonist and receptor trafficking and used them to screen agonists with less endocytosis. Sprague-Dawley rats were used for pharmacokinetic analyses, and the hypoglycaemic activity was evaluated by intraperitoneal glucose tolerance tests (IPGTT). Our results showed that GLP-1 receptor-mediated endocytosis, as a manner of elimination, was clathrin-dependent. More importantly, we found that agonists biased towards the G protein pathway were less endocytosed by GLP-1 receptor. We screened an analogue of Exendin-4 M4, which was biased toward the G protein pathway with less endocytosis by the GLP-1 receptor. M4, which shows prolonged hypoglycaemic activities and a long half-life, can be used as a lead compound for type 2 diabetes mellitus treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2021.174203DOI Listing
May 2021

Rheumatologists' understanding of refractory gout: a questionnaire survey in China.

J Int Med Res 2021 May;49(5):3000605211016149

Department of General Internal Medicine, 34732Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P.R. China.

Objective: To explore the understanding of refractory gout in Chinese rheumatologists.

Methods: We conducted an anonymous survey of rheumatologists attending an annual national academic conference on rheumatism.

Results: Of the 910 rheumatologists who completed the questionnaire, 751 (82.5%) had received relevant continuing medical education (CME). Of these, 140 (18.6%) rheumatologists did not select xanthine oxidase inhibitors as the first treatment for patients with chronic tophaceous gout. Of all respondents, 113 (12.4%), 251 (27.6%) and 324 (35.6%) prescribed incorrect maximum doses of allopurinol, febuxostat and benzbromarone, respectively; this tendency was more pronounced in the non-CME group. Most rheumatologists agreed that complications and comorbidities increased the difficulty of gout management and considered the term refractory gout to describe those cases with uncontrolled symptoms, unmet treatment targets or non-shrinkage of tophi after standardized drug treatment. Moreover, 62.8% (472/751) of specialists considered that a diagnosis of refractory gout was appropriate for patients whose lifestyle and compliance failed to improve despite adequate education and regular urate-lowering therapy.

Conclusions: Incorrect and inadequate drug therapy may contribute to some cases of refractory gout, especially in physicians without CME. An emphasis on non-drug therapy and the management of comorbidities and complications may reduce cases of refractory gout.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/03000605211016149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161865PMC
May 2021

Elucidating the relationship between nutrition indices and coronary artery calcification in patients undergoing maintenance hemodialysis.

Ther Apher Dial 2021 May 26. Epub 2021 May 26.

Department of Nephrology, the Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou, China.

Cardiovascular diseases (CVD) are common in maintenance hemodialysis (MHD) patients, and vascular calcification is associated with the incidence of CVD. Malnourished MHD patients are particularly prone to CVD events. Thus far, there is no clear explanation for the relationship of nutrition status with vascular calcification; therefore, we investigated the relationship between malnutrition and vascular calcification. One hundred thirty-one patients underwent laboratory testing, assessment of vascular calcification, modified quantitative subjective global assessment (MQSGA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The patients were divided into two groups based on the presence or absence of coronary artery calcification (CAC), and nutritional statuses were compared between the two groups. The MQSGA score was higher in the CAC group (mean 10.9 ± 1.81) than in the no-CAC group (mean 10.2 ± 1.51); in addition, the mean phase angle (PA) value was significantly lower in the CAC group than in the no-CAC group. Stratification according to CAC score showed that age, Kt/V, incidence of valve calcification, incidence of abdominal aortic calcification, MQSGA score, and blood cell mass were related to the severity of CAC. In addition, quartile analysis revealed that MQSGA score and PA value were related to the incidence and severity of vascular calcification. Binary regression analysis showed that MQSGA score, age, hemoglobin level, and high-density lipoprotein level were independent risk factors for dialysis-related CAC. Patients on MHD who exhibited malnutrition were more likely to have vascular calcification, especially CAC. Namely, the higher the MQSGA score, the lower the PA, and the more likely the occurrence of CAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1744-9987.13693DOI Listing
May 2021

Nurses' turnover intention in secondary hospitals in China: A structural equation modelling approach.

J Nurs Manag 2021 May 22. Epub 2021 May 22.

College of Nursing Science, Kyung Hee University, Seoul, Korea.

Aim: To identify the factors affecting nurses' turnover intention.

Background: The shortage of nurses has been a great challenge worldwide, and nurses' turnover may exacerbate the situation.

Methods: A cross-sectional study was conducted among nurses in six secondary hospitals in China. A model was constructed, and structured questionnaires were adopted to measure model variables. Structural equation modelling was used to verify the model.

Results: Totally, 594 valid questionnaires were collected. The final model showed an acceptable fit, and 35.0% of the total variation was explained. Nine of the ten pathways were statistically significant. The model verified the contribution of professional value, nursing practice, job stress and social support to turnover intention and their effects were mediated by job satisfaction and organisational commitment. As hypothesized, there existed a significant effect between job satisfaction and organisational commitment. Unexpectedly, job stress had a greater direct effect on turnover intention than job satisfaction and organisational commitment.

Conclusions: The structural model provided a feasible model that could explain nurses' turnover intention in China.

Implications For Nursing Management: To prevent the turnover of nurses, administrators and managers should advisably prioritize the effect of job stress, especially in hospitals with similar medical context.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jonm.13379DOI Listing
May 2021

Functional ultrasound-triggered phase-shift perfluorocarbon nanodroplets for cancer therapy.

Ultrasound Med Biol 2021 08 13;47(8):2064-2079. Epub 2021 May 13.

Shenyang Pharmaceutical University, Shenyang, China. Electronic address:

In recent years, because of their unique properties, the use of perfluorocarbon nanodroplets (PFC NDs) in ultrasound-mediated tumor theranostics has attracted increasing interest. PFC is one of the most stable organic compounds with high hydrophobicity. Phase-shift PFC NDs can be transformed into highly echogenic microbubbles for ultrasound and photoacoustic imaging by ultrasound and laser light. In addition, in the process of acoustic droplet vaporization, PFC NDs with cavitation nuclei can be combined with a variety of ultrasound technologies to produce cavitation effects for tumor ablation, antivascular therapy and release of therapeutic agents loaded in nanodroplets. Moreover, they can also be used to overcome tumor hypoxia by virtue of high oxygen solubility. In this review, first the preparation and stabilization of PFC NDs are summarized and then the issues and outlook are discussed. More importantly, multifunctional platforms based on PFC NDs for cancer diagnostics, therapy and theranostics are reviewed in detail.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ultrasmedbio.2021.04.003DOI Listing
August 2021

Apelin receptor upregulation in spontaneously hypertensive rat contributes to the enhanced vascular smooth muscle cell proliferation by activating autophagy.

Ann Transl Med 2021 Apr;9(8):627

Department of Geriatric Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Background: Proliferation of vascular smooth muscle cells (VSMCs) plays a vital role in the progression of vascular remodeling and hypertension. Apelin-13 promotes VSMC proliferation of normal rats. This study was designed to investigate the roles of apelin receptor (APJ) and apelin-13 in VSMC proliferation of hypertension rats and underlying mechanisms.

Methods: Primary VSMCs were obtained from aorta of Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). The expressions of apelin and APJ were detected by Western bolt and PCR, as well as immunohistochemistry. VSMC proliferation was evaluated with CCK-8 kit, PCNA protein expression and percentage of EdU-positive cells. Autophagy was determined by the ratio of LC3BII to LC3BI, ATG5 and p62 protein expressions, as well as LC3B immunofluorescence.

Results: APJ expression was increased while apelin expression was reduced in aorta and VSMCs of SHR compared with those of WKY. Exogenous apelin-13 promoted VSMC proliferation and autophagy of both WKY and SHR, which were prevented by APJ antagonist F13A. Blockade of APJ had no significant effects on VSMC proliferation and autophagy of WKY, but attenuated VSMC proliferation and autophagy of SHR. Administration of autophagy inhibitor 3-methyladenine (3-MA) not only attenuated VSMC proliferation of SHR, but prevented apelin-13-induced VSMC proliferation of both WKY and SHR.

Conclusions: Apelin-13 stimulates VSMC proliferation via APJ-mediated enhancement in autophagy. APJ upregulation in SHR contributes to the enhanced VSMC proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-6891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106044PMC
April 2021

Exogenous application of brassinosteroids regulates tobacco leaf size and expansion via modulation of endogenous hormones content and gene expression.

Physiol Mol Biol Plants 2021 Apr 27;27(4):847-860. Epub 2021 Mar 27.

Tobacco Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Tobacco Biology and Processing, Ministry of Agriculture and Rural Affairs, Qingdao, 266101 China.

Brassinosteroids (BR) play diverse roles in the regulation of plant growth and development. BR promotes plant growth by triggering cell division and expansion. However, the effect of exogenous BR application on the leaf size and expansion of tobacco is unknown. Tobacco seedlings are treated with different concentrations of exogenous 2,4-epibrassinolide (EBL) [control (CK, 0 mol L), T1 (0.5 × 10 mol L), and T2 (0.5 × 10 mol L)]. The results show that T1 has 17.29% and T2 has 25.99% more leaf area than control. The epidermal cell area is increased by 24.40% and 17.13% while the number of epidermal cells is 7.06% and 21.06% higher in T1 and T2, respectively, relative to control. So the exogenous EBL application improves the leaf area by increasing cell numbers and cell area. The endogenous BR (7.5 times and 68.4 times), auxin (IAA) (4.03% and 25.29%), and gibberellin (GA) contents (84.42% and 91.76%) are higher in T1 and T2, respectively, in comparison with control. Additionally, , , and are upregulated showing that the brassinosteroid signaling pathway is activated. Furthermore, the expression of the key biosynthesis-related genes of BR (), IAA (), and GA () are all upregulated under EBL application. Finally, the exogenous EBL application also upregulated the expression of cell growth-related genes (, , , , and ). The results reveal that the EBL application increases the leaf size and expansion by promoting the cell expansion and division through higher BR, IAA, and GA contents along with the upregulation of cell growth-related genes. The results of the study provide a scientific basis for the effect of EBL on tobacco leaf growth at morphological, anatomical, biochemical, and molecular levels.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-00971-x.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12298-021-00971-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055801PMC
April 2021

Allogeneic hematopoietic stem cell transplantation overcomes the poor prognosis in MLL-rearranged solid tumor therapy related-acute myeloid leukemia.

Am J Cancer Res 2021 15;11(4):1683-1696. Epub 2021 Apr 15.

Department of Hematology, Nanfang Hospital, Southern Medical University Guangzhou, China.

MLL rearrangement is very common in solid tumor therapy-related acute myeloid leukemia (t-AML). To investigated the prognosis of solid tumor MLL t-AML, 157 patients were divided into 3 groups: non-MLL t-AML (n=41), MLL t-AML (n=18) and MLL de novo AML (n=98). Of the 150 patients underwent anti-leukemia therapy, the complete remission (CR) was similar in MLL t-AML, non-MLL t-AML and MLL de novo AML (P=0.251). 3-years overall survival (OS) was 37.5%, 21.5% and 20.4% (P=0.046), and leukemia-free survival (LFS) was 28.0%, 32.2% and 22.7% (P=0.031), and the incidence of relapse was 30.0%, 50.4% and 53.5% (P=0.382), respectively, in the three groups. Multivariate analysis revealed that MLL t-AML was a risk factor while allo-HSCT was a protective factor for OS, LFS, and relapse (P<0.001, P<0.001 and P=0.005) (P=0.002, P<0.001 and P<0.001, respectively). The 3-years OS was 0%, 17.9% and 2.3% (P=0.038), and LFS was 0%, 23.1% and 3.3% (P=0.017), and relapse was 100%, 53.1% and 74.4% (P=0.001), respectively, among three groups in patients undergoing chemotherapy alone, while OS was 64.3%, 52.7% and 40.7% (P=0.713), LFS was 60.0%, 48.8% and 37.0% (P=0.934), and relapse was 25.0%, 47.4% and 47.5% (P=0.872), respectively, among these groups in patients undergoing allo-HSCT. Intriguingly, MLL t-AML was no longer risk factor for relapse and LFS (P=0.882 and P=0.484, respectively), and it became a favorable factor for OS (P=0.011) in patients undergoing allo-HSCT. In conclusion, MLL t-AML had poor prognosis compared with non-MLL t-AML and MLL de novo AML, but allo-HSCT might overcome the poor prognosis of MLL t-AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085874PMC
April 2021

Allogeneic hematopoietic cell transplant overcomes the poor prognostic value of CDKN2 deletion in adult B-lineage acute lymphoblastic leukemia.

Cancer Lett 2021 Jul 24;510:59-66. Epub 2021 Apr 24.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Emerging evidence suggested that CDKN2 deletion was a poor prognosis predictor in adult B-lineage acute lymphoblastic leukemia (B-ALL). Here, we investigated the effect of allogeneic hematopoietic cell transplant (allo-HCT) on adult B-ALL with CDKN2 deletion. The patients with adult B-ALL underwent more than two courses of chemotherapy were enrolled in the multicenter retrospective study. Relapse and survival were analyzed. A total of 1336 adult B-ALL, including 295 patients with CDKN2 deletion and 1041 wild-type (WT), from five institutes were enrolled. The complete remission (CR) rates were 86.8% and 91.1% (P = 0.229) after two cycles of chemotherapy in patients with CDKN2 deletion and WT, respectively. The 5-year cumulative relapse post-CR were 56% (95% CI, 52-68) and 43% (95% CI, 40-51) (P < 0.001), 5-year disease-free survival (DFS) were 30% (95% CI, 24-36) and 41% (95% CI, 39-46) (P < 0.001), and 5-year overall survival (OS) were 35% (95% CI, 28-39) and 47% (95% CI, 44-49) (P < 0.001) in the two groups, respectively. Subgroup analysis revealed that the 5-year relapse were 89.3% (95% CI, 83.0-96.5) and 68.4% (95% CI, 60.2-72.5) (P < 0.001), 5-year DFS were 4.9% (95% CI, 1.8-10.4) and 22.7% (95% CI, 18.0-27.7) (P < 0.001), and 5-year OS were 6.9% (95% CI, 3.1-12.9) and 23.4% (95% CI, 18.7-28.6) (P < 0.001) in CDKN2 deletion and WT groups undergoing chemotherapy alone, respectively, while there were not different in terms of 5-year relapse (38.1% vs 34.3%, P = 0.211), DFS (48.4% vs 52.2%, P = 0.325) and OS (54.5% vs 56.3%, P = 0.483) between those with CDKN2 deletion and WT undergoing allo-HCT. Multivariate analysis showed that CDKN2 deletion and high-risk stratification both were the risk factors for relapse, DFS and OS, while allo-HCT was a protective factor. CDKN2 deletion might be a poor prognostic predictor of adult B-ALL. Adult B-ALL with CDKN2 deletion might benefit from allo-HCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2021.04.009DOI Listing
July 2021

Upfront transplantation may have better outcomes than pretransplant cytoreductive therapy for treating patients with MDS-EB-1 or MDS-EB-2.

Int J Cancer 2021 Sep 28;149(5):1109-1120. Epub 2021 May 28.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Whether patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefit from pretransplant cytoreductive therapy remains controversial. Our study compared the outcomes of upfront transplantation with those of pretransplant cytoreductive therapy in the patients who received transplantation and those who dropped out due to cytoreductive therapy-related adverse effects. Patients with MDS-EB-1 or MDS-EB-2 were enrolled and divided into three groups based on therapy pretransplantation: upfront transplantation (upfront, n = 54), induction chemotherapy (CT, n = 66) and hypomethylating agents (HMA, n = 37) alone. One hundred fifty-seven patients were enrolled and 124 received allo-HSCT, with 5.6%, 28.8% and 29.7% of drop-out rate of transplantation in upfront, CT and HMA groups (P = .030), respectively. Overall therapy-related mortality (TRM), cytoreductive therapy and transplant-related mortality was 13.0%, 32.4% and 28.4% (P = .028), and 5-year overall survival (OS) was 73.6%, 43.4% and 46.9% (P = .033). Multivariate analysis showed that CT and HMA were risk factors for TRM and OS, and transplantation was a protective factor for OS. In transplant patients, 3-year cumulative incidence of relapse was 10.6%, 20.4% and 20.3% (P = .033), 5-year TRM was 14.5%, 20.0% and 17.6% (P = .651), OS was 77.3%, 64.3% and 68.8% (P = .047) and DFS was 74.0%, 63.0% and 65.8% (P = .042). Multivariate analysis showed that CT was a risk factor for DFS, while CT, HMA and poor karyotype were risk factors for relapse. Results suggested that pretransplant cytoreductive therapy was not associated with better outcomes in the patients who had undergone transplantation. Therefore, upfront transplantation may be preferable for MDS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33608DOI Listing
September 2021

Comparative transcriptome combined with biochemical and physiological analyses provide new insights toward cadmium accumulation with two contrasting Nicotiana species.

Physiol Plant 2021 Apr 20. Epub 2021 Apr 20.

Tobacco Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Tobacco Biology and Processing, Ministry of Agriculture and Rural Affairs, Qingdao, China.

Cadmium (Cd) is known as one of the most hazardous elements in the environment and a persistent soil constraint toxic to all flora and fauna. In this study, we conducted physiological, biochemical, and transcriptomic analyses of Nicotiana rustica (N. rustica) and Nicotiana tabacum (N. tabacum) treated with CdCl to know the underlying molecular mechanisms of Cd accumulation. As a result, N. rustica had more dry weight than N. tabacum. Additionally, N. rustica accumulated higher Cd concentration (69.65 times), Cd influx (1.32-fold), glutathione S-transferases (GST) enzyme activity (2.54 times), GSH/GSSG (oxidized form of GSH) ratio, increase of superoxide dismutase and CAT and a lower H O and superoxide (O ) accumulation in their roots than N. tabacum. Cd mainly distributed in the cytoplasm of both species and N. rustica had a significant proportion in the cell wall. Furthermore, the transcriptomic analysis revealed 173 and 710 differentially expressed genes (DEGs) between control and Cd-stressed plants in the leaves and roots of N. rustica, while 576 and 1543 DEGs were found in the leaves and roots of N. tabacum, respectively. In N. rustica, phenylpropanoid biosynthesis and phenylalanine metabolism were the most enriched pathways, while GSH metabolism, ATP-binding cassette transporters and phenylpropanoid biosynthesis were the most enriched in N. tabacum. Finally, we found that DEGs related to metal influx, sequestration, remobilization, and chelation were responsible for Cd accumulation. These results indicated that N. rustica accumulated higher Cd content than N. tabacum, suggesting that each species utilized different response mechanism under the same Cd stress conditions. The DEGs identified in this study might lead to the identification of genes or pathways related to Cd regulation. This study identifies important regulators related to Cd accumulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ppl.13431DOI Listing
April 2021

Analysis of the microRNA and mRNA expression profile of ricin toxin-treated RAW264.7 cells reveals that miR-155-3p suppresses cell inflammation by targeting GAB2.

Toxicol Lett 2021 Sep 15;347:67-77. Epub 2021 Apr 15.

College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China. Electronic address:

Ricin toxin (RT) is one of the most lethal toxins derived from the seed of castor beans. In addition to its main toxic mechanism of inhibiting the synthesis of cellular proteins, RT can induce the production of inflammatory cytokines. MicroRNAs (miRNAs) play a key role in regulating both innate and adaptive immunity. To elucidate the regulation of miRNAs in RT-induced inflammation injury, the RNA high-throughput sequencing (RNA-Seq) technology was used to analyze the expression profile of miRNAs and mRNAs in RT-treated RAW264.7 cells. Results showed that a total of 323 mRNAs and 19 miRNAs differentially expressed after RT treated. Meanwhile, 713 miRNA-mRNA interaction pairs were identified by bioinformatics analysis. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that those interaction pairs were mainly involved in JAK-STAT, T cell receptor, and MAPK signaling pathways. Moreover, we further predicted and determined the targeting relationship between miR-155-3p and GAB2 through TargetScan and dual-luciferase reporter assay. Mechanically, overexpression of miR-155-3p can reduce the secretion of TNF-α in RAW264.7 cells, revealing a possible mechanism of miR-155-3p regulating RT-induced inflammatory injury. This study provides a new perspective for clarifying the mechanism of RT-induced inflammatory injury and reveals the potential role of miRNAs in innate immune regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2021.04.011DOI Listing
September 2021

Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor.

Nat Commun 2021 04 15;12(1):2263. Epub 2021 Apr 15.

Department of Biochemistry and Molecular Biology, Hunan Province Key Laboratory of Basic and Applied Hematology, Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Xiangya School of Medicine, Central South University, Changsha, China.

Argininosuccinate synthase (ASS1) is a ubiquitous enzyme in mammals that catalyzes the formation of argininosuccinate from citrulline and aspartate. ASS1 genetic deficiency in patients leads to an autosomal recessive urea cycle disorder citrullinemia, while its somatic silence or down-regulation is very common in various human cancers. Here, we show that ASS1 functions as a tumor suppressor in breast cancer, and the pesticide spinosyn A (SPA) and its derivative LM-2I suppress breast tumor cell proliferation and growth by binding to and activating ASS1. The C13-C14 double bond in SPA and LM-2I while the Cys97 (C97) site in ASS1 are critical for the interaction between ASS1 and SPA or LM-2I. SPA and LM-2I treatment results in significant enhancement of ASS1 enzymatic activity in breast cancer cells, particularly in those cancer cells with low ASS1 expression, leading to reduced pyrimidine synthesis and consequently the inhibition of cancer cell proliferation. Thus, our results establish spinosyn A and its derivative LM-2I as potent ASS1 enzymatic activator and tumor inhibitor, which provides a therapeutic avenue for tumors with low ASS1 expression and for those non-tumor diseases caused by down-regulation of ASS1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050083PMC
April 2021

Inhibited effect of an RGD peptide hydrogel on the expression of β1-integrin, FAK, and Akt in Tenon's capsule fibroblasts.

J Biomed Mater Res B Appl Biomater 2021 Apr 13. Epub 2021 Apr 13.

Institute of Biology and Medicine, College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, China.

Tenon's capsule fibroblasts are the main cellular components of filtration tract scar that limit the success rate of glaucoma filtration surgery. Scar formation results from infiltration and proliferation of fibroblasts into damaged areas, meanwhile synthesis of extracellular matrix glycoproteins. Integrins are cell surface receptors for extracellular molecules that mediate cell adhesion, spreading, migration, and invasion. They bind their ligands often through recognition of short amino-acid sequences-arginine-glycine-aspartic acid (RGD). Peptides that contain RGD sequence can compete with RGD containing insoluble matrix proteins for binding to the integrin receptor and thus prevent the downstream signaling pathway. Increasing evidence supports that β1-integrin/focal adhesion kinase (FAK)/Akt signal pathway plays an important role in fibrogenesis and scar formation in different tissues. In consideration of advantages of peptide hydrogel, that is well biocompatibility, gel state, degradability, good drug loading, we designed and fabricated an RGD peptide hydrogel, and hypothesized that it could inhibit the expression of β1-integrin, FAK, and Akt in Tenon's capsule fibroblasts. Rheology results showed that 1% wt Fmoc-FFGGRGD peptide solution could self-assemble into hydrogel. Western blot analysis revealed that there were statistical differences between control group and 1% wt group in β1-integrin/β-actin, FAK/β-actin, Akt/β-actin respectively (*p < .05). The relative mRNA expression of β1-integrin, FAK, Akt in control group and 1% wt group were also statistically different respectively (*p < .05). We proved that 1% wt Fmoc-FFGGRGD self-assembly peptide hydrogel could inhibit the expression of β1-integrin, FAK and Akt in Tenon's capsule fibroblasts. It is a promising way to solve scar formation of glaucoma filter channel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm.b.34847DOI Listing
April 2021
-->