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1.
Neurosci Lett ; : 135429, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069813

RESUMO

BACKGROUND: Bone fracture may subsequently cause chronic postoperative pain after orthopedic surgery, but mechanisms remain elusive. The necessity of caspase-3 in neuroinflammation and synaptic plasticity has been summarized in pathological pain. Leucine-rich repeat transmembrane protein 1 (LRRTM1) mediates synaptic delivery of AMPA receptor and synaptogenesis. This study evaluated whether caspase-3 and LRRTM1 are required for fracture-associated postoperative allodynia. METHODS: A model of tibial fracture with intramedullary pinning in mice was established for the induction of postoperative pain, verified by measurement of mechanical paw withdrawal threshold and cold scores response to acetone. The caspase-3 specific inhibitor, recombinant caspase-3 and LRRTM1 knockdown by shRNA were utilized for the investigation of pathogenesis as well as the prevention of allodynia. Also, the activity of caspase-3 and the expression of LRRTM1 in the spinal dorsal horn were examined by Western blot and RT-qPCR. RESULTS: This study reported that tibial fracture and orthopedic surgery produced long-lasting mechanical allodynia and cold allodynia, along with the up-modulation of spinal caspase-3 activity (but not caspase-3 expression) and LRRTM1 expression. Spinal caspase-3 inhibition prevented fracture-associated behavioral allodynia in a dose-dependent manner. Caspase-3 inhibitor also reduced the spinal increased LRRTM1 level after tibial fracture with pinning. Spinal LRRTM1 deficiency impaired fracture-caused postoperative pain. Intrathecal recombinant caspase-3 facilitated acute pain hypersensitivity and spinal LRRTM1 expression in naïve mice, reversing by LRRTM1 knockdown. CONCLUSION: Our current results demonstrate the spinal up-regulation of LRRTM1 by caspase-3 activation in the development of tibial fracture-associated postoperative pain in mice.

2.
Int J Neurosci ; : 1-8, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33032501

RESUMO

OBJECTIVE: The cerebral ischemia-reperfusion (I/R) model is crucial for the study of cerebral stroke. Chrysophanol (Chry) can protect nerve damage of mice in cerebral ischemia-reperfusion injury. This study aimed at investigating the neuroprotective effects of chrysophanol through mitochondrial autophagy in mice with ischemia-reperfusion injury. MATERIALS AND METHODS: Adult mice were stochastically divided into five groups: sham, I/R (solvent), I/R+Chry (dose, 10.0ml/kg), I/R+Chry (dose, 1.0ml/kg), and I/R+Chry (dose, 0.1ml/kg). The cerebral ischemia-reperfusion model was made in I/R and I/R+Chry groups. The changes in hippocampal formation were observed by hematoxylin and eosin (H&E) staining. The expressions of LC3B-II and LC3B-I protein in hippocampus were demonstrated by western blot (WB). The fluorescence intensities of NIX, LC3B, and mitochondria were detected by immunohistochemistry fluorescent (IF). RESULTS: Comparing with the I/R group, the I/R+Chry groups showed improvements in reducing the damage on the hippocampus, indicated by the reduced ratio of LC3B-II and LC3B-I protein, decreased fluorescence intensity of NIX and LC3B, and increased intensity of mitochondrial fluorescence. CONCLUSION: Our study showed that chrysophanol may regulate mitochondrial autophagy through NIX protein and alleviate the damage of hippocampus through decreasing the level of mitochondrial autophagy.

3.
Mol Reprod Dev ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022126

RESUMO

In eukaryotic cells, RNA polymerase (Pol) I and Pol III are dedicated to the synthesis of ribosomal RNA precursors and a variety of small RNAs, respectively. Although RNA Pol I and Pol III complexes are crucial for the regulation of cell growth and cell cycle in all cell types, many of the components of the Pol I and Pol III complexes have not been functionally characterized in mammals. Here, we provide the first in vivo functional characterization of POLR1D, a subunit shared by RNA Pol I and Pol III, during early mammalian embryo development. Our results show that Polr1d mutant embryos cannot be recovered at E7.5 early post-gastrulation stage, suggesting failed implantation. Although Polr1d mutants can be recovered at E3.5, they exhibit delayed/stalled development with morula morphology rather than differentiation into blastocysts. Even with extended time in culture, mutant embryos fail to form blastocysts and eventually die. Analysis of E3.0 embryos revealed severe DNA damage in Polr1d mutants. Additionally, lineage assessment reveals that trophectoderm specification is compromised in the absence of Polr1d. In summary, these findings demonstrate the essential role of POLR1D during early mammalian embryogenesis and highlight cell-lethal phenotype without Polr1d function.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33000173

RESUMO

CONTEXT: PD-1, CTLA-4, TIM-3, LAG-3 and TIGIT are considered as major immune co-inhibitory receptors (CIRs) and most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in medullary thyroid carcinoma (MTC). OBJECTIVE: We aimed to provide first evidence regarding the expression profiles and clinical significance of CIRs in a large cohort of MTCs. DESIGN AND PATIENTS: In total, 200 MTCs who received initial surgery in our hospital were included. Immunohistochemistry was performed to evaluate CIR expressions in tissue microarrays (TMA). Combined with the results of our previous PD-L1 study, clinicopathologic and prognostic correlations of these proteins were retrospectively analyzed. RESULTS: TIM-3, PD-1, CTLA-4, LAG-3 and TIGIT positivity was detected in 96 (48.0%), 27 (13.5%), 25 (12.5%), 6 (3.0%) and 6 (3.0%) patients, respectively, in which TIM-3, PD-1 and CTLA-4 expressions were positively correlated. Both log-rank tests and multivariate Cox analyses indicated that TIM-3, CTLA-4 expression and PD-1/PD-L1 coexpression were associated with worse structural recurrence-free survival. In addition, among 20 patients who developed advanced disease during follow-up, 12 (60%) showed TIM-3 positivity, wherein 6 cases also had concurrent moderate to strong PD-1, PD-L1 or CTLA-4 expression. CONCLUSIONS: Using the currently largest TMA cohort of this rare cancer, we delineated the CIR expression profiles in MTC, and identified TIM-3, CTLA-4 expression and PD-1/PD-L1 coexpression as promising biomarkers for tumor recurrence. Furthermore, a subset of advanced MTCs are probably immunogenic, for whom single or combined immunotherapy including TIM-3, PD-1, PD-L1 or CTLA-4 blockade may be potential therapeutic approaches in the future.

5.
Cell Death Dis ; 11(9): 753, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934224

RESUMO

HDAC inhibitors are efficacious for treating lymphoma, but display limited efficacy in treating solid tumors. Here, we investigated the relationship between HDAC inhibitor resistance and the tumor immune environment in colorectal cancer. Our data indicated that among the investigated immune factors, B7x expression was enhanced in HDAC inhibitor-resistant colorectal cancer models in vitro and in vivo. In addition, gene manipulation results demonstrated that xenograft mice with tumors derived from a B7x-overexpressing CT-26 colorectal cancer cell line were resistant to HDAC inhibitor treatment. Notably, we found that there is a negative relationship between HDAC and B7x expression in both colorectal cancer cell lines and patients' tumors. Furthermore, our data indicated that elevated expression of B7x was related to a poor prognosis in colorectal tumor patients. Interestingly, treatment with a specific inhibitor or siRNA of HDAC3, but not HDAC2, 6, and 8, resulted in obvious upregulation of B7x expression in colorectal cancer cells. In addition, our data showed that a cell line with high HDAC3 expression and low B7x expression had decreased enrichment of acetylated histone H3 in the promoter region of the gene encoding B7x. This pattern was reversed by addition of HDAC3 inhibitors. Mechanistically, we found that HDAC3 regulated B7x transcription by promoting the binding of the transcription activator C/EBP-α with the B7x promoter region. Importantly, our data indicated that an antibody neutralizing B7x augmented the response to HDAC inhibitor in the colorectal cancer xenograft model and the lung metastasis model by increasing the ratios of both CD4-positive and CD8-positive T cells. In summary, we demonstrated a role of B7x in HDAC inhibitor resistance and identified the mechanism that dysregulates B7x in colorectal cancer. Our work provides a novel strategy to overcome HDAC inhibitor resistance.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32915349

RESUMO

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

7.
Thorac Cancer ; 11(10): 2858-2866, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32875729

RESUMO

BACKGROUND: High expression of monoamine oxidase A (MAOA) in non-small cell lung cancer (NSCLC) is related to epithelial-mesenchymal transition (EMT) and the development of clinicopathological features of NSCLC. Nevertheless, the role of MAOA in drug resistance still remains unclear. Hence, the aim of this article was to evaluate a previously synthesized MAOA inhibitor (G11) on inhibiting paclitaxel-resistant NSCLC metastasis and growth. METHODS: First, MAOA expression level was evaluated in several NSCLC cell lines. An MTT assay was used to validate the inhibitory effect of G11 on NSCLC cells in vitro. Second, gene expression in G11-treated H460/PTX cells was analyzed by microarray gene expression. Third, transwell assay was performed to assess the invasion and metastasis of G11-treated A549/PTX and H460/PTX cells and western blot assay used to analyze vital protein expression level in G11-treated H460/PTX cells. Finally, the antimetastatic effect of G11 was tested in an NSCLC in vivo model. RESULTS: Our data revealed that G11 significantly inhibited the viability of paclitaxel (PTX)-resistant NSCLC cell lines (A549/PTX and H460/PTX). G11 dramatically reduced the expression of MAOA in A549/PTX and H460/PTX cells, which exhibited relatively high MAOA expression levels. Additionally, G11 was found to hinder A549/PTX and H460/PTX cell migration and invasion. Furthermore, the in vivo study indicated that the coadministration of G11 and paclitaxel significantly suppressed tumor metastasis in H460/PTX lung metastasis models. CONCLUSIONS: These findings indicated G11 showed a moderate inhibitory effect on paclitaxel-resistant NSCLC metastasis and growth, and support further investigation on MAOA potentially as a promising therapeutic target for paclitaxel-resistant NSCLC treatment. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Inhibition of MAOA might contribute to the suppression of metastasis and growth in PTX-resistant NSCLC cells. What this study adds This study explored the potential function of MAOA in drug-resistant NSCLC and might consider MAOA as a promising target for the treatment of drug-resistant NSCLC.

8.
Zhongguo Gu Shang ; 33(9): 831-6, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32959570

RESUMO

OBJECTIVE: From the perspective of clinical application to analyze the effectiveness and reliability of CPC/PMMA bone cement in percutaneous kyphoplasty (PKP) for the treatment of elderly patients with osteoporotic thoracolumbar fractures. METHODS: A retrospective analysis was performed on 62 patients with osteoporotic compression fracture of single-vertebral thoracic or lumbar segment who underwent PKP surgery and had a bone density less than or equal to -3.0 SD from February 2016 to December 2016. Among them, 23 patients were in CPC/PMMA group, with an average age of (77.6±2.2) years old, 39 patients in PMMA group, with an average age of (77.1±1.1) years old. The indexes between two groups were compared, including the visual analogue scale (VAS), height ratio of anterior vertebra (AVHR), local Cobb angle, cement leakage, new adjacent vertebral fracture(NAVF). RESULTS: There were no significant difference in gender, age, follow-up time and preoperative VAS, AVHR, local Cobb angle between two groups (P>0.05), at the 1 day after operation, VAS, AVHR, local Cobb angle in all patients got obvious improvement (P<0.05), which was no significant difference at 1 day after operation and final follow-up (P>0.05). At the same time, there was no statistically significant difference in the incidence of new adjacent vertebral fracture and cement leakage (P>0.05). The pain in both groups continued to improve at follow up after operation (P<0.05), the local Cobb angle increased (P<0.05) and AVHR decreased slightly (P<0.05). However, the images of conventional methods (X-ray or CT) could not find signs about CPC degeneration and new bone ingrowth. CONCLUSION: CPC/PMMA composite bone cement is safe and reliablein PKP for treatment of elderly patients with osteoporotic thoracolumbar fractures, which can effectively relieve pain and maintain vertebral body stability. It has the same curative effect as PMMA bone cement. It was worthy to research more in future, although no direct evidences support the CPC/PMMA composite bone cement can reduce the incidence of adjacent vertebral fracture, CPC degeneration or new bone ingrowth.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Idoso , Cimentos para Ossos , Fosfatos de Dinucleosídeos , Humanos , Polimetil Metacrilato , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
9.
Br J Cancer ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32958824

RESUMO

BACKGROUND: The liver is the central organ for cholesterol homoeostasis, and its dysfunction might cause liver pathological alterations including hepatocellular carcinomas (HCCs). 3ß-hydroxysteroid-Δ24 reductase (DHCR24), a crucial enzyme of cholesterol biosynthetic pathway, is involved in lipid rafts formation. Genkwadaphnin (GD) is a daphnane diterpene isolated from the flower buds of Daphne genkwa Siebold et Zuccarini (Thymelaeaceae). METHODS: We evaluated in vitro and in vivo effect of GD using HCC cells and BALB/c nude mice. Microarray assays were used to identify the differential genes by GD. DHCR24 expression and activity, cholesterol level, lipid rafts structure and the role of DHCR24 in human HCC specimens were tested by various molecular biology techniques. RESULTS: High expression of DHCR24 in human HCC specimens was correlated with poor clinical outcome. Interfering DHCR24 altered growth and migration of HCC cells. GD inhibited growth and metastasis of HCC cells both in vivo and in vitro. GD suppressed DHCR24 expression and activity, as well as DHCR24-mediated cholesterol biosynthesis and lipid rafts formation, then further inhibited HCC cell invasion and migration. CONCLUSIONS: Our data suggest that DHCR24-mediated cholesterol metabolism might be an effective therapeutic strategy in HCC, and natural product GD might be a promising agent for HCC therapy.

10.
Intern Med J ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32975880

RESUMO

BACKGROUND: It is recommended that blood pressure should be measured on a bare upper arm with an appropriately sized cuff. However, in practice, it is more convenient to measure blood pressure on sleeved arms. AIMS: We aim to examine the effect of sleeved arms on the accuracy of blood pressure measurement. METHODS: Patients aged 18 years or older were enrolled. Participants underwent three blood pressure measurements in each of the following sleeve conditions in random order (bare arm; arm covered with a single-layer cotton shirt sleeve,1mm; arm covered with two layers sleeve containing a cotton shirt and a polar fabric sweater, 3mm; arm covered with two layers sleeve containing a cotton shirt and a thick cardigan, 4mm). RESULTS: Of the 300 participants, 155 (52%) were men. The mean age was 62.9(10.7)years, and 226 (75%) had hypertension. There were no significant differences in both systolic blood pressure and diastolic blood pressure among the four kinds of sleeve conditions in all the participants (p>0.5), and the mean blood pressure differences between measurements made on the sleeved arms and bare arm were within 1.0mmHg. Blood pressure of sleeved arms was positively correlated with that of the bare arm (p<0.001, r>0.95), and showed good consistency. CONCLUSIONS: In the present study, we concluded that there was no significant effect of sleeved arms on the accuracy of blood pressure measurement by using an electronic oscillometric sphygmomanometer equipped with a conventional cuff. This article is protected by copyright. All rights reserved.

11.
Theriogenology ; 158: 239-249, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32987289

RESUMO

The ovaries, the main female reproductive organs, directly mediate ovulation and reproductive hormone secretion. These complex physiological processes are regulated by multiple genes and pathways. However, there is a lack of research on goat ovaries, and the molecular mechanisms underlying the signaling pathways remain unclear. In this study, Illumina HiSeq 4000 sequencing was used to sequence the transcriptomes of goat ovaries. The expression patterns of differentially expressed mRNAs in goat ovaries at both the follicular and luteal phases were determined by bioinformatics analysis. A total of 1,122, 014, 112 clean reads were obtained, and 3770 differentially expressed mRNAs were identified for further analysis. There were 1727 and 2043 upregulated mRNAs in the luteal phase and follicular phase, respectively. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, some mRNAs that were highly expressed in ovaries during the luteal phase, such as HSD17B7, 3BHSD, and SRD5A2, may be related to the synthesis of progesterone. In addition, some mRNAs that were highly expressed in ovaries during the follicular phase, such as RPL12, RPS13 and RPL10, are related to the growth and maturation of oocytes. Taken together, the findings of this study provide genome-wide mRNA expression profiles for goat ovaries at the follicular and luteal phases and identify mRNAs associated with goat hormone secretion and follicular development. In addition, this study provides a theoretical basis for further investigation of goat reproductive regulation.

12.
J Diabetes ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32935481

RESUMO

OBJECTIVE: To study the associations between heterogeneity of gestational diabetes mellitus (GDM) subtype/prepregnancy body mass index (pre-BMI) and large-for-gestational-age (LGA) infants of Chinese women. METHODS: We performed a retrospective case-control study of 299 women with GDM and 204 women with normal glucose tolerance (NGT), using oral glucose tolerance test-based indices performed at 24-25 weeks of gestation. Women with GDM were classified into the following three physiologic subtypes: GDM with a predominant insulin-secretion defect (GDM-dysfunction), GDM with a predominant insulin-sensitivity defect (GDM-resistance), or GDM with both defects (GDM-mixed). We then used a binary logistic regression model to evaluate the potential associations of GDM subtypes and pre-BMI with newborn macrosomia or LGA. RESULTS: Women with GDM-resistance had a higher pre-BMI (P < 0.001), whereas women in the GDM-dysfunction and GDM-mixed groups had pre-BMIs comparable to the NGT group. In the logistic regression model, women in the GDM-mixed group exhibited an increased risk of bearing newborns with macrosomia and LGA, and women in the GDM-dysfunction group tended to have newborns with LGA after adjusting for pre-BMI and other potential confounders. Women who were overweight or obese prepregnancy manifested an increased risk of having newborns with macrosomia and LGA relative to normal-weight women, regardless of whether values were unadjusted or adjusted for all potential confounders. There was no significant interaction between GDM subtype and pre-BMI for any of the studied outcomes. CONCLUSIONS: Heterogeneity of GDM (GDM-dysfunction and GDM-mixed) and prepregnancy overweight/obesity were independently associated with LGA in Chinese women. There was no significant interaction between GDM subtypes and pre-BMI for LGA.

13.
Genes (Basel) ; 11(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32883034

RESUMO

Novel genetic markers like microhaplotypes and compound markers show promising potential in forensic research. Based on previously reported single nucleotide polymorphism (SNP) and insertion/deletion (InDel) polymorphism loci, 29 genetic markers including 22 microhaplotypes and seven compound markers were identified. Genetic distributions of the 29 loci in five continental populations, Kazak and Mongolian groups in China were investigated. We found that the expected heterozygosity values of these 29 loci were >0.4 in these populations, indicating these loci were relatively high polymorphisms. Population genetic analyses of five continental populations showed that five loci displayed relatively high genetic variations among these continental populations and could be useful markers for ancestry analysis. In summary, the 29 loci displayed relatively high genetic diversities in continental populations and Chinese two groups and could be informative loci for forensic research.

14.
Lipids ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895983

RESUMO

The ratio of monocyte to high-density lipoprotein cholesterol level (MHR) was a newly proposed inflammatory and oxidative stress marker. This study aimed to explore the association between MHR and Brachial-ankle pulse wave velocity (Ba-PWV) in adult Chinese participants. A total of 2029 participants were divided into two groups according to the Ba-PWV: a high Ba-PWV group (Ba-PWV ≥1400 cm/s) and a low Ba-PWV group (Ba-PWV < 1400 cm/s). According to the cut-off points of quartile of MHR, the participants were divided into four groups. The relationship between MHR and Ba-PWV was analyzed. After adjusting for potential confounders, a non-linear relationship between MHR and Ba-PWV was found in the participants, and the inflection point was 7.78 in the non-linear curve. On the left of the inflection point, MHR had a positive correlation with Ba-PWV (OR = 1.17, 95% confidence interval (CI): 1.08 to 1.28, p < 0.01). However, there was no obvious relationship between MHR and Ba-PWV on the right of the inflection point (OR = 0.96, 95% CI: 0.90 to 1.01, p = 0.117). Further demographic analysis demonstrated that the positive relationship between MHR and Ba-PWV was found in the female participants with hypertension family history, but without a current history of hypertension, smoking, or drinking (p < 0.05). An increased MHR is a risk factor of atherosclerosis, which may predict the potential development of atherosclerosis. When the MHR is close to 7.78, it has the highest predictive value for the risk of atherosclerosis occurrence.

15.
Respirology ; 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32954622

RESUMO

BACKGROUND AND OBJECTIVE: The purpose of this study was to report the characteristics and long-term survival of patients with CTEPH treated in three distinct ways: PEA, BPA and medical therapy. METHODS: Patients diagnosed with CTEPH were included in the registry that was set up in 18 centres from August 2009 to July 2018. The characteristics and survival of patients with CTEPH receiving the different treatments were reported. Prognostic factors were evaluated by Cox regression model. RESULTS: A total of 593 patients with CTEPH were included. Eighty-one patients were treated with PEA, 61 with BPA and 451 with drugs. The estimated survival rates at 1, 3, 5 and 8 years were, respectively, 95.2%, 84.6%, 73.4% and 66.6% in all patients; 92.6%, 89.6%, 87.5% and 80.2% in surgical patients; and 95.4%, 88.3%, 71.0% and 64.1% in medically treated patients. The estimated survival rates at 1, 3, 5 and 7 years in patients treated with BPA were 96.7%, 88.1%, 70.0% and 70.0%, respectively. For all patients, PEA was an independent predictor of survival. Other independent risk factors were CHD, cardiac index, PVR, big endothelin-1, APE and 6MWD. CONCLUSION: This is the first multicentre prospective registry reporting baseline characteristics and estimated survival of patients with CTEPH in China. The long-term survival rates are similar to those of patients in the international and Spanish registries. PEA is an independent predictor of survival.

16.
Fertil Steril ; 114(2): 283-284, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32741468
17.
Int J Lab Hematol ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32812335

RESUMO

INTRODUCTION: Patients with mutated and overexpressed p53 have an aggressive course in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Studies on the impact of MYC expression in AML are limited. This is the first study to evaluate MYC expression and p53 status in AML and MDS. METHODS: We identified 214 patients, 101 AML, 79 MDS, and 34 negative control patients. We retrospectively assessed p53 and MYC expression by immunohistochemistry and correlated MYC expression with p53 expression and aberrational status of TP53. RESULTS: The level of both p53 and MYC expression was significantly higher in AML (mean: 9.7%; 12.1%) and MDS (mean: 5.2%; 5.5%) patients compared with control cases (mean: 0.18%; 2.3%; P = .001-0.02). p53 and MYC expression levels were even more elevated in AML when compared to MDS patients (P < .001). MYC expression was significantly associated with p53 expression and TP53 aberration in AML patients but not in MDS patients (P < .001). p53 expression and >20% MYC expression showed an adverse impact on overall survival (OS) (P < .05) in AML patients while p53 but not MYC expression showed an adverse impact on OS in MDS patients. MYC and p53 dual expression, as well as combined MYC expression and TP53 aberration, showed negative impact on OS in AML patients. MDS patients with leukemic transformation revealed an interval increase in expression of both p53 and MYC. CONCLUSION: High-level MYC expression associates with p53 abnormality and poor survival in AML. MYC may provide proliferative advantage for leukemic progression in p53 dependent and independent manner.

18.
J Am Chem Soc ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32786747

RESUMO

Aqueous Al-ion batteries (AAIBs) are the subject of great interest due to the inherent safety and high theoretical capacity of aluminum. The high abundancy and easy accessibility of aluminum raw materials further make AAIBs appealing for grid-scale energy storage. However, the passivating oxide film formation and hydrogen side reactions at the aluminum anode as well as limited availability of the cathode lead to low discharge voltage and poor cycling stability. Here, we proposed a new AAIB system consisting of an AlxMnO2 cathode, a zinc substrate-supported Zn-Al alloy anode, and an Al(OTF)3 aqueous electrolyte. Through the in situ electrochemical activation of MnO, the cathode was synthesized to incorporate a two-electron reaction, thus enabling its high theoretical capacity. The anode was realized by a simple deposition process of Al3+ onto Zn foil substrate. The featured alloy interface layer can effectively alleviate the passivation and suppress the dendrite growth, ensuring ultralong-term stable aluminum stripping/plating. The architected cell delivers a record-high discharge voltage plateau near 1.6 V and specific capacity of 460 mAh g-1 for over 80 cycles. This work provides new opportunities for the development of high-performance and low-cost AAIBs for practical applications.

19.
Eur J Med Res ; 25(1): 36, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843077

RESUMO

BACKGROUND: Percutaneous vertebroplasty (PVP) has been demonstrated to be effective in the treatment of acute osteoporotic vertebral fracture (AOVF). However, bilateral puncture takes more time to accept more X-ray irradiation; some scholars apply unilateral puncture PVP, but the cement cannot be symmetrically distributed in the vertebral body, so we use a flexible cement injector that undergoes PVP through the unilateral pedicle puncture. This research aims to compare the clinical results of PVP for AOVF with unilateral pedicle puncture using a straight bone cement injector and a bendable cement injector, determine the value of a bendable cement injector. METHODS: We undertook a retrospective analysis of patients with thoracic and lumbar compression fracture treated with unilateral pedicle puncture percutaneous vertebroplasty from our institution from June 2013 to July 2015. Operation time, radiation exposure, bone cement injection amount, and the incidence of bone cement leakage were recorded on presentation, the cement leakage was measured by X-ray and computed tomography scan. The patients were followed up postoperatively and were assessed mainly with regard to clinical and radiological outcomes. RESULTS: There was no significant difference in the operation time, radiation exposure time and incidence of bone cement leakage between the two groups. There was significant difference in the amount of bone cement injection and the difference between the two groups. There were no significant differences in VAS and the relative height of the vertebral body and local Cobb angle and QUALEFFO between the two groups at 1 week after PVP, significant difference was observed only 12 months after operation. CONCLUSIONS: Application of flexible cement injector is safe and feasible, compared with the application of straight bone cement injector, without prolonging the operative time, radiation exposure time and the incidence of bone cement leakage; it has the advantages of good long-term effect and low incidence of vertebral fracture recurrence.

20.
Nat Neurosci ; 23(10): 1203-1214, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32807949

RESUMO

Parkinson's disease (PD) pathogenesis may involve the epigenetic control of enhancers that modify neuronal functions. Here, we comprehensively examine DNA methylation at enhancers, genome-wide, in neurons of patients with PD and of control individuals. We find a widespread increase in cytosine modifications at enhancers in PD neurons, which is partly explained by elevated hydroxymethylation levels. In particular, patients with PD exhibit an epigenetic and transcriptional upregulation of TET2, a master-regulator of cytosine modification status. TET2 depletion in a neuronal cell model results in cytosine modification changes that are reciprocal to those observed in PD neurons. Moreover, Tet2 inactivation in mice fully prevents nigral dopaminergic neuronal loss induced by previous inflammation. Tet2 loss also attenuates transcriptional immune responses to an inflammatory trigger. Thus, widespread epigenetic dysregulation of enhancers in PD neurons may, in part, be mediated by increased TET2 expression. Decreased Tet2 activity is neuroprotective, in vivo, and may be a new therapeutic target for PD.

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