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1.
Nucleic Acids Res ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010171

RESUMO

NBS1 is a critical component of the MRN (MRE11/RAD50/NBS1) complex, which regulates ATM- and ATR-mediated DNA damage response (DDR) pathways. Mutations in NBS1 cause the human genomic instability syndrome Nijmegen Breakage Syndrome (NBS), of which neuronal deficits, including microcephaly and intellectual disability, are classical hallmarks. Given its function in the DDR to ensure proper proliferation and prevent death of replicating cells, NBS1 is essential for life. Here we show that, unexpectedly, Nbs1 deletion is dispensable for postmitotic neurons, but compromises their arborization and migration due to dysregulated Notch signaling. We find that Nbs1 interacts with NICD-RBPJ, the effector of Notch signaling, and inhibits Notch activity. Genetic ablation or pharmaceutical inhibition of Notch signaling rescues the maturation and migration defects of Nbs1-deficient neurons in vitro and in vivo. Upregulation of Notch by Nbs1 deletion is independent of the key DDR downstream effector p53 and inactivation of each MRN component produces a different pattern of Notch activity and distinct neuronal defects. These data indicate that neuronal defects and aberrant Notch activity in Nbs1-deficient cells are unlikely to be a direct consequence of loss of MRN-mediated DDR function. This study discloses a novel function of NBS1 in crosstalk with the Notch pathway in neuron development.

2.
J Am Chem Soc ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021791

RESUMO

We report the synthesis and characterization of a two-dimensional (2D) MX2Y2-type (M = metal, X, Y = N, S, O, and X ≠ Y) copper 1,3,5-triamino-2,4,6-benzenetriol metal-organic framework (Cu3(TABTO)2-MOF). The role of oxygen in the synthesis of this MOF was investigated. Copper metal is formed along with the MOF when the synthesis is done in argon as suggested by XRD. When the reaction was exposed to air with vigorous stirring, copper metal was not observed by XRD. However, if there is no stirring, then copper metal is formed, and we learned that this is because oxygen was not allowed to enter the solvent due to the formation of a MOF film at the air/water interface. For the sample synthesized in argon (Cu3(TABTO)2-Ar), an insulating Cu3(TABTO)2-Ar pellet (σ < 10-10 S cm-1) became a metallic conductor with an electrical conductivity of 0.78 S cm-1 at 300 K after exposure to iodine vapor. This work provides further insights into the role of oxygen in the synthesis of redox-active ligand-based MOFs, expands the family of 2D redox-active ligand-based electrically conductive MOFs, and offers more opportunities in sensing, photocatalytic, electronic, and energy-related applications.

3.
Theranostics ; 10(24): 10940-10956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042263

RESUMO

Background: Taxanes are frontline chemotherapeutic drugs for patients with triple-negative breast cancer (TNBC); however, chemoresistance reduces their effectiveness. We hypothesized that the molecular profiling of tumor samples before and after neoadjuvant chemotherapy (NAC) would help identify genes associated with drug resistance. Methods: We sequenced 10 samples by RNA-seq from 8 NAC patients with TNBC: 3 patients with a pathologic complete response (pCR) and the other 5 with non-pCR. Differentially expressed genes that predicted chemotherapy response were selected for in vitro functional screening via a small-scale siRNAs pool. The clinical and functional significance of the gene of interest in TNBC was further investigated in vitro and in vivo, and biochemical assays and imaging analysis were applied to study the mechanisms. Results: Synaptotagmin-like 4 (SYTL4), a Rab effector in vesicle transport, was identified as a leading functional candidate. High SYTL4 expression indicated a poor prognosis in multiple TNBC cohorts, specifically in taxane-treated TNBCs. SYTL4 was identified as a novel chemoresistant gene as validated in TNBC cells, a mouse model and patient-derived organoids. Mechanistically, downregulating SYTL4 stabilized the microtubule network and slowed down microtubule growth rate. Furthermore, SYTL4 colocalized with microtubules and interacted with microtubules through its middle region containing the linker and C2A domain. Finally, we found that SYTL4 was able to bind microtubules and inhibit the in vitro microtubule polymerization. Conclusion: SYTL4 is a novel chemoresistant gene in TNBC and its upregulation indicates poor prognosis in taxane-treated TNBC. Further, SYTL4 directly binds microtubules and decreases microtubule stability.

4.
Theranostics ; 10(24): 11092-11109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042272

RESUMO

Rationale: Paclitaxel resistance is a major concern when treating triple-negative breast cancer (TNBC) patients. We aimed to identify candidates causing paclitaxel resistance and explore their significance in TNBC therapeutics. Methods: A genome-wide CRISPR screening, integrated with transcriptome analyses, was performed to identify candidates involved in paclitaxel-resistant TNBCs. Cell proliferation, cytotoxicity, immunofluorescent staining, and xenograft assays were conducted to verify the phenotypes of paclitaxel resistance induced by candidate genes, both in vitro and in vivo. RNA sequencing, Western blotting, and chromatin immunoprecipitation assays were used to explore the underlying mechanisms. Results: MEF2-interacting transcriptional repressor (MITR), the truncated isoform of histone deacetylase 9 (HDAC9) lacking the deacetylation domain, was enriched in paclitaxel-resistant cells. Elevated MITR expression resulted in increased interleukin-11 (IL11) expression and activation of downstream JAK/STAT3 signaling. Mechanistically, MITR counteracted MEF2A-induced transcriptional suppression of IL11, ultimately causing paclitaxel resistance. By contrast, pharmacological inhibition of JAK1/2 by ruxolitinib reversed paclitaxel resistance both in vitro and in vivo. Conclusion: Our in vitro and in vivo genetic and cellular analyses elucidated the pivotal role of MITR/MEF2A/IL11 axis in paclitaxel resistance and provided a novel therapeutic strategy for TNBC patients to overcome poor chemotherapy responses.

5.
Nat Genet ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020666

RESUMO

Here, we present a joint-tissue imputation (JTI) approach and a Mendelian randomization framework for causal inference, MR-JTI. JTI borrows information across transcriptomes of different tissues, leveraging shared genetic regulation, to improve prediction performance in a tissue-dependent manner. Notably, JTI includes the single-tissue imputation method PrediXcan as a special case and outperforms other single-tissue approaches (the Bayesian sparse linear mixed model and Dirichlet process regression). MR-JTI models variant-level heterogeneity (primarily due to horizontal pleiotropy, addressing a major challenge of transcriptome-wide association study interpretation) and performs causal inference with type I error control. We make explicit the connection between the genetic architecture of gene expression and of complex traits and the suitability of Mendelian randomization as a causal inference strategy for transcriptome-wide association studies. We provide a resource of imputation models generated from GTEx and PsychENCODE panels. Analysis of biobanks and meta-analysis data, and extensive simulations show substantially improved statistical power, replication and causal mapping rate for JTI relative to existing approaches.

6.
J Cardiothorac Surg ; 15(1): 302, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028372

RESUMO

OBJECTIVES: This study aimed to identify the incidence rate of Acute kidney injury (AKI) in our center and predict in-hospital mortality and long-term survival after heart transplantation (HTx). METHODS: This single-center, retrospective study from October 2009 and March 2020 analyzed the pre-, intra-, and postoperative characteristics of 95 patients who underwent HTx. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Risk factors were analyzed by multivariable logistic regression models. The log-rank test was used to compare long-term survival. RESULTS: Thirty-three (34.7%) patients developed AKI. The mortality in hospital in HTx patients with and without AKI were 21.21 and 6.45%, respectively (P < 0.05). Recipients in AKI who required renal replacement therapy (RRT) had a hospital mortality rate of 43.75% compared to 6.45% in those without AKI or RRT (P < 0.0001). A long cardiopulmonary bypass (CPB) time (OR:11.393, 95% CI: 2.183 to 59.465, P = 0.0039) was positively related to the occurrence of AKI. A high intraoperative urine volume (OR: 0.031, 95% CI: 0.005 to 0.212, P = 0.0004) was negatively correlated with AKI. AKI requiring RRT (OR, 11.348; 95% CI, 2.418-53.267, P = 0.002) was a risk factor for mortality in hospital. Overall survival in patients without AKI at 1 and 3 years was not different from that in patients with AKI (P = 0.096). CONCLUSIONS: AKI is common after HTx. AKI requiring RRT could contribute powerful prognostic information to predict mortality in hospital. A long CPB time and low intraoperative urine volume are associated with the occurrence of AKI.

8.
Nat Commun ; 11(1): 5205, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060564

RESUMO

Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR). Malfunction in GHRHR signaling is associated with abnormal growth, making GHRHR an attractive therapeutic target against dwarfism (e.g., isolated growth hormone deficiency, IGHD), gigantism, lipodystrophy and certain cancers. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein at 2.6 Å. This high-resolution structure reveals a characteristic hormone recognition pattern of GHRH by GHRHR, where the α-helical GHRH forms an extensive and continuous network of interactions involving all the extracellular loops (ECLs), all the transmembrane (TM) helices except TM4, and the extracellular domain (ECD) of GHRHR, especially the N-terminus of GHRH that engages a broad set of specific interactions with the receptor. Mutagenesis and molecular dynamics (MD) simulations uncover detailed mechanisms by which IGHD-causing mutations lead to the impairment of GHRHR function. Our findings provide insights into the molecular basis of peptide recognition and receptor activation, thereby facilitating the development of structure-based drug discovery and precision medicine.

9.
Nat Commun ; 11(1): 4968, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009413

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.


Assuntos
Infecções por Coronavirus/diagnóstico , Progressão da Doença , Pneumonia Viral/diagnóstico , Pneumonia , Tomografia Computadorizada por Raios X/métodos , Adulto , Betacoronavirus , China , Técnicas de Laboratório Clínico , Coinfecção , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Feminino , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1440-1444, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067934

RESUMO

OBJECTIVE: To explore the efficacy and adverse reactions of decitabine combined with reduction FLAG regimen on the senile patients with high-risk AML. METHODS: 12 senile patients with high-risk AML received decitabine combined with reduced FLAG regimen (decitabine 20 mg/m2, intravenous drip, qd, d 1-5; fludarabine 30 mg/m2, intravenous drip lasts 30 min, qd, d 3-6; Ara-C 1 g/m2, intravenous drip, qd, d 3-6; and G-CSF 300 µg/d, subcu- taneous injection, d 2 to neutrophils reached the lowest return to>1.0×109/L) in our study. The efficacy and adverse reactions of this regimen were analyzed. RESULTS: 9 patients achieved complete remission(CR) after one course of decitabine combined with reduced FLAG regimen, 2 patients achieved partial remission (PR) and 1 patient reached a stable disease (SD). The overall response rate was 92%. The median follow-up period was 7.4 months ranged from 3 to 12 months. The median survival time for all patients was 6.4 months. The main treatment-related toxicities were myelosuppression and infection due to neutropenia. Severe non-hematologic toxicities were not observed in these patients, and there was no treatment-related mortality. CONCLUSION: Decitabine combined with reduced FLAG regimen has a definite clinical efficacy in the treatment of senile patients with high-risk AML. This regimen, as induction remission regimen, can effectively improve the CR rate and reduce the adverse reactions. Therefore, it may be used as one of the preferred induction remission regimen to treat the senile patients with high-risk AML.


Assuntos
Decitabina , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/uso terapêutico , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Resultado do Tratamento
11.
Gene ; : 145211, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33053422

RESUMO

OBJECTIVE: The purpose of this study was to investigate associations between two single nucleotide polymorphisms (SNPs) rs505922 and rs532436 in ABO gene and the risk of small artery occlusion stroke (SAO) in southern Chinese Han population. METHODS: Our case-control study comprising 121 patients with SAO and 136 controls. All participants were Han population of southern China. IS sub-type was defined on the basis of the TOAST criteria. SAO was strictly diagnosed after a systematic physical examination and neuroimaging via MRI. Genotype analysis was conducted by the snapshot technique. RESULTS: The distribution of rs532436 genotype between these two groups showed a statistically significant difference (P = 0.048) while that of rs505922 genotype showed no significant difference (P = 0.572). SNP rs532436 was significantly associated with SAO in overdominant model (GA vs. GG + AA) after adjusting for age, hypertension history, diabetes history and cigarette smoking (adjusted OR = 2.03, 95% CI: 1.14-3.62, P = 0.016). However, under all genetic models, the rs505922 polymorphism failed to show association with SAO. CONCLUSION: The resultsindicate that rs532436 polymorphism in ABO gene may have association with SAO in southern Chinese Han population.

12.
Medicine (Baltimore) ; 99(42): e22446, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080679

RESUMO

Autoimmune hepatitis (AIH) is a form of liver inflammation in which immune cells target hepatocytes, inducing chronic inflammatory states. Bariatric surgery (BS) was shown to reduce inflammation in severely obese patients. We hypothesize that obese patients with AIH and BS have lower prevalence of liver-related complications and in-patient mortality compared to those without BS.The National Inpatient Sample from 2007 to 2013 was queried for hospitalizations of adults over 18 years of age with a diagnosis of AIH. Of those, hospitalizations with BS were selected as cases and those with morbid obesity as controls. Case-control 1:2 matching was done based on sex, age, race, and comorbidities. Primary outcomes were prevalence of liver-related complications and in-patient mortality. Independent risk factors of in-patient clinical outcomes were identified using multivariate regression analysis.From 137,834 hospitalizations with a diagnosis of AIH, 688 with BS were selected as cases, and 1295 were matched as controls. The prevalence of ascites was higher in the BS group compared to the control (odds ratio 1.73, 95% confidence interval (CI) 1.27-2.36). The prevalence of cirrhosis (36.8% vs 33.2%), portal hypertension (7.4% vs 10.0%), hepatic encephalopathy (10.6% vs 8.7%), and varices and variceal bleeding (3.9% vs 5.5%) was not statistically different from case controls, (P > .05).BS was an independent risk factor for ascites (adjusted odds ratio (aOR) 1.87; 95% CI 1.36-2.56) and hepatic encephalopathy (aOR 1.42; 95% CI 1.03-1.97) but was an independent protective factor against in-patient mortality (aOR 0.21, 95% CI 0.08-0.55) once adjusted for age, sex, race, and comorbidities.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33013687

RESUMO

Background: Serum uric acid levels have been shown to be associated with increased risk of diabetes. However, it remains unclear whether uric acid-lowering therapy (ULT) is associated with improved glycemic status. This study aimed to summarize evidence from randomized controlled trials (RCTs) to investigate whether ULT reduces fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) levels. Methods: PubMed, Embase, and the Cochrane Library were searched from inception until April 10, 2019. Moreover, in order to maximize the search for articles on the same topic, the reference lists of included studies, relevant review articles and systematic reviews were reviewed. Parallel RCTs investigating the effect of ULT on FBG or HbA1c levels were considered for inclusion. An English language restriction was applied. Data were screened and extracted independently by two researchers. Meta-analyses were performed using random-effects models to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Four trials with 314 patients reported the effect of ULT with allopurinol on FBG and 2 trials with 141 patients reported the effect of ULT with allopurinol on HbA1c. Treatment with allopurinol resulted in a significant decrease in FBG (WMD: -0.61 mmol/L, 95% CI: -0.93 to -0.28), but only a trend of reduction in HbA1c (WMD: -0.47%, 95% CI: -1.16 to 0.22). Notably, the subgroup analyses showed that treatment with allopurinol was associated with reduced FBG levels in patients without diabetes (WMD: -0.60 mmol/L, 95% CI: -0.99 to -0.20), but not in patients with diabetes. In addition, the dose of allopurinol treatment ≥200 mg daily resulted in a reduction of FBG levels (WMD: -0.59 mmol/L, 95% CI: -0.95 to -0.23), whereas low-dose allopurinol (<200 mg daily) had no effect on FBG levels. Conclusions: The findings suggest that ULT with allopurinol may be effective at reducing glycemia, but such an improvement does not appear to be observed in patients with diabetes. The findings require confirmation in additional trials with larger sample sizes.

14.
Nat Immunol ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020660

RESUMO

The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a result of decreased mitophagy activity and displayed functional, transcriptomic and epigenetic characteristics of terminally exhausted T cells. Mechanistically, reduced mitochondrial fitness in TILs was induced by the coordination of T cell receptor stimulation, microenvironmental stressors and PD-1 signaling. Enforced accumulation of depolarized mitochondria with pharmacological inhibitors induced epigenetic reprogramming toward terminal exhaustion, indicating that mitochondrial deregulation caused T cell exhaustion. Furthermore, supplementation with nicotinamide riboside enhanced T cell mitochondrial fitness and improved responsiveness to anti-PD-1 treatment. Together, our results reveal insights into how mitochondrial dynamics and quality orchestrate T cell antitumor responses and commitment to the exhaustion program.

15.
Exp Brain Res ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052428

RESUMO

Sepsis-related encephalopathy (SAE), which causes a series of brain injuries and long-term, potentially irreversible cognitive dysfunction, is closely associated with increased morbidity and mortality. Hydrogen (H2) is a new type of medical gas molecule that has been widely used in the treatment of various diseases in recent years. The aim of the present study was to explore the protective effects of H2 inhalation on brain injury and long-term cognitive impairment in an improved chronic septic mouse model. Male C57BL/6J mice were randomized into four groups: Control, Control + H2, SAE and SAE + H2. The SAE and Control models were established by intraperitoneal injection of human stool suspension or saline in mice. H2 (2%) was inhaled for 60 min at 1 h and 6 h after SAE or Control treatment. The survival rates were recorded for 14 days (days 1-14) and the Morris Water Maze was performed for 7 days (days 8-14). To assess the severity of the brain injury, hematoxylin and eosin staining, Nissl staining, Evans blue (EB) extravasation and the wet/dry weight ratio of brain tissue were detected 24 h after SAE or Control treatment. In addition, inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin 6 (IL-6), high-mobility group box 1 (HMGB1), as well as the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), zonula occludens-1 (ZO-1) and Occludin, were measured 6, 12 and 24 h after SAE or Control treatment. The results showed that H2 treatment increased survival rates, mitigated cognitive impairment, reduced hippocampal histological damage, decreased EB and water content, and decreased the levels of TNF-α, IL-6, HMGB1, Nrf2, HO-1, ZO-1 and Occludin, as compared with the SAE group. These data revealed that 2% H2 could suppress brain damage and improve cognitive function in septic mice by inhibiting oxidative stress, inflammatory response and the sepsis-induced blood-brain barrier (BBB) disruption.

16.
BMC Neurol ; 20(1): 377, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076870

RESUMO

BACKGROUND: To evaluate the effects and optimal parameters of repetitive transcranial magnetic stimulation (rTMS) on cognition function of patients with Parkinson's disease (PD) and to estimate which cognitive function may obtain more benefits from rTMS. METHOD: The articles dealing with rTMS on cognitive function of PD patients were retrieved from the databases until April 2019. Outcomes of global cognitive function and different cognitive domains were extracted. The standardized mean differences (SMDs) with 95% confidence interval (CI) of cognitive outcome for different parameters, scales, and cognitive functions were estimated. RESULTS: Fourteen studies involving 173 subjects were included in this meta-analysis. A significant effect size was observed with the mini-mental state examination (MMSE) for the global cognitive outcome based on the evidence of four published articles. Further subtests for different cognitive domains demonstrated prominent effect for the executive function. The significant effect sizes for executive function were found with multiple sessions of high-frequency rTMS over frontal cortex; especially over dorsolateral prefrontal cortex (DLPFC). All of the other cognitive domains, which included memory, attention, and language ability, did not obtain significant effects. CONCLUSIONS: Multiple sessions of high-frequency rTMS over the DLPFC may have positive effect on executive function in PD patients. Further well designed studies with large sample sizes are needed to verify our results and ascertain the long-term effects of rTMS.

17.
Ultramicroscopy ; 219: 113122, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33091708

RESUMO

Electron tomography has achieved higher resolution and quality at reduced doses with recent advances in compressed sensing. Compressed sensing (CS) exploits the inherent sparse signal structure to efficiently reconstruct three-dimensional (3D) volumes at the nanoscale from undersampled measurements. However, the process bottlenecks 3D reconstruction with computation times that run from hours to days. Here we demonstrate a framework for dynamic compressed sensing that produces a 3D specimen structure that updates in real-time as new specimen projections are collected. Researchers can begin interpreting 3D specimens as data is collected to facilitate high-throughput and interactive analysis. Using scanning transmission electron microscopy (STEM), we show that dynamic compressed sensing accelerates the convergence speed by ~3-fold while also reducing its error by 27% for a Au/SrTiO3 nanoparticle specimen. Before a tomography experiment is completed, the 3D tomogram has interpretable structure within ~33% of completion and fine details are visible as early as ~66%. Upon completion of an experiment, a high-fidelity 3D visualization is produced without further delay. Additionally, reconstruction parameters that tune data fidelity can be manipulated throughout the computation without re-running the entire process.

18.
Transplantation ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33093405

RESUMO

BACKGROUND: The worldwide experience of liver transplantation (LT) in the treatment of propionic acidemia (PA) remains limited and fragmented. This review aims to provide a comprehensive and quantitative understanding of post-transplant clinical outcomes in PA patients. METHODS: MEDLINE, Embase and the Cochrane Library databases were searched for studies focusing on PA patients who underwent LT. The pooled estimate rates and 95% confidence intervals (CIs) were calculated using a random-effects model with Freeman-Tukey double arcsine transformation. RESULTS: Twenty-one studies involving 70 individuals were included. The pooled estimate rates were 0.95 (95% CI, 0.80-1.00) for patient survival and 0.91 (95% CI, 0.72-1.00) for allograft survival. The pooled estimate rates were 0.20 (95% CI, 0.05-0.39) for rejection, 0.08 (95% CI, 0.00-0.21) for hepatic artery thrombosis, 0.14 (95% CI, 0.00-0.37) for cytomegalovirus/Epstein-Barr virus infection and 0.03 (95% CI, 0.00-0.15) for biliary complications. The pooled estimate rates were 0.98 (95% CI, 0.88-1.00) for metabolic stability, 1.00 (95% CI, 0.79-1.00) for reversal of pre-existing cardiomyopathy and 0.97 (95% CI, 0.78-1.00) for improvement of neurodevelopmental delay. A large proportion of patients achieved liberalization of protein intake posttransplant [pooled estimate rate 0.66 (95% CI, 0.35-0.93)]. CONCLUSIONS: Despite the risk of transplant-related complications, LT is a viable therapeutic option in PA patients, with satisfactory survival rates and clinical outcomes. Given the diversity in neurological assessment methods and the inconsistency in achievement of dietary protein liberalization across different studies, consensus on neurological evaluation methods and post-transplant protein intake is necessary. Longer-term clinical outcomes of LT for PA warrants further investigation.

19.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(5): 571-575, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-33085244

RESUMO

Low-intensity pulsed ultrasound (LIPUS) is a common physical therapy to accelerate the healing of bone fracture and treat delayed union of bone fracture. Vessels, nerves, and bone tissue are essential constituents of bone system. Recently, increasing evidence has been revealed that LIPUS can not only promote bone regeneration by directly regulating osteoblasts, osteoblasts, mesenchymal stem cells, but also have a positive impact on the repair of bone healing through vessels and nerves. Thus, we reviewed and summarized the latest published literature about the molecular mechanism for the effects of LIPUS on bone regeneration, which might offer a promising therapy for bone-related diseases.


Assuntos
Fraturas Ósseas , Terapia por Ultrassom , Ondas Ultrassônicas , Regeneração Óssea , Consolidação da Fratura , Fraturas Ósseas/terapia , Humanos
20.
Phys Rev Lett ; 125(15): 157002, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33095631

RESUMO

It has long been proposed that doping a chiral spin liquid (CSL) or fractional quantum Hall state can give rise to topological superconductivity. Despite intensive effort, definitive evidences still remain lacking. We address this problem by studying the t-J model supplemented by time-reversal symmetry breaking chiral interaction J_{χ} on the triangular lattice using density-matrix renormalization group with a finite concentration δ of doped holes. It has been established that the undoped, i.e., δ=0, system has a CSL ground state in the parameter region 0.32≤J_{χ}/J≤0.56. Upon light doping, we find that the ground state of the system is consistent with a Luther-Emery liquid with power-law superconducting and charge-density-wave correlations but short-range spin-spin correlations. In particular, the superconducting correlations, whose pairing symmetry is consistent with d±id wave, are dominant at all hole doping concentrations. Our results provide direct evidences that doping the CSL on the triangular lattice can naturally give rise to topological superconductivity.

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