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1.
Talanta ; 251: 123797, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35970122

RESUMO

In situ growth of quasi-superhydrophobic porous NiCo2S4 nanosheet arrays with a one-step electrodeposition method was provided. A calcium ion-selective electrodes (Ca2+-ISE) was subsequently constructed by using the prepared NiCo2S4 as a solid contact layer. The proposed Ca2+-ISE exhibits a good Nernstian slope of 30.7 ± 0.3 mV/dec and a detection limit of 1.6 × 10-7 M. Due to the large redox capacitance of 1.8 mF, the Ca2+-ISE based on NiCo2S4 nanosheet arrays shows a high potential stability of 1.9 ± 0.5 µV/h over 90 h. Excellent reproducibilities for the NiCo2S4-based Ca2+-ISEs can be obtained with the single batch and batch-to-batch E° standard deviations of 0.3 (n = 6) and 0.7 mV (n = 5), respectively. The NiCo2S4 nanosheet arrays have a large contact angle of 148 ± 1.4°, which effectively suppresses the formation of a water layer at the sensing membrane/NiCo2S4 interface.


Assuntos
Cálcio , Eletrodos Seletivos de Íons , Polímeros/química , Água/química
2.
RSC Chem Biol ; 3(11): 1320-1324, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36349223

RESUMO

Post-translational modifications (PTMs) play important roles in modulating the biological functions of proteins. Stoichiometry, which quantifies the modification percentage, is a critical factor for any given PTM. In this work, we developed a chemoproteomic strategy called "STO-MS" to systematically quantify the PTM stoichiometry in complex biological samples. This strategy employs a resolvable mass tag to differentiate proteoforms with different numbers of modifications and utilizes liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques to measure PTM stoichiometry at the proteomic level. As a proof-of-concept, we successfully determined the stoichiometry of 197 proteins modified by 4-hydroxynonenal (HNE), a well-characterized lipid-derived electrophile and biomarker for oxidative stress. Our work expands the toolbox for quantification of PTM stoichiometry and sheds light on understanding the biological significance of PTMs in oxidative stress.

3.
Front Neurol ; 13: 993979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388205

RESUMO

Background and objective: Gait disturbances are common in the elderly and can lead to the loss of functional independence and even death. Enlarged perivascular space (EPVS) and motor performance may be related, but only few studies have explored this relationship. The aim of our study was to investigate the effects of both the severity and location of EPVS on movement disorders. Method: Two hundred and six participants aged between 45 and 85 years old with complete magnetic resonance imaging (MRI) data were included in our analysis. EPVS were divided into basal ganglia (BG) and centrum semiovale (CSO), and their grades were measured. Gait was assessed quantitatively using a 4-m walkway and TUG test as well as semi-quantitatively using the Tinetti and SPPB tests. The function of upper extremities was evaluated by 10-repeat pronation-supination, 10-repeat finger-tapping, and 10-repeat opening and closing of the hands. Results: Both high-grade EPVS, whether in BG and CSO, were independently correlated with gait parameters, the TUG time, Tinetti, and SPPB tests. The EPVS located in BG had a significant association with 10-repeat finger-tapping time (ß = 0.231, P = 0.025) and a similar association was also observed between CSO-EPVS and 10-repeat pronation-supination time (ß = 0.228, P = 0.014). Conclusion: Our results indicated that EPVS was associated with gait disturbances, and a further investigation found that EPVS has an association with upper extremities disorder. EPVS should be considered as a potential target for delaying gait and upper extremities damage since CSVD can be prevented to some extent.

4.
Pediatr Nephrol ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36416954

RESUMO

Fibroblast growth factor 23 (FGF23) is primarily produced in bones and mainly regulates calcium and phosphorus metabolism. The level of circulating FGF23 increases rapidly in the early stage of acute kidney injury (AKI). Recent studies have shown that FGF23 may serve as a biomarker for the diagnosis and poor prognosis of AKI. The mechanism of increased FGF23 in AKI may include increased production of FGF23, decreased renal clearance of FGF23, and some new regulatory factors, such as inflammation and glycerol 3-phosphate. However, the biological effects of elevated FGF23 in AKI are still unclear. It is also not known whether reducing the level of circulating FGF23 could alleviate AKI or its poor prognosis. Here, we review the pathophysiological mechanism and possible regulation of FGF23 in AKI and discuss the possibility of using FGF23 as a therapeutic target.

5.
Blood Cancer J ; 12(11): 158, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36404343

RESUMO

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or better to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation, and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% vs 97%, and 95% vs 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.


Assuntos
Arsenicais , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Trióxido de Arsênio/uso terapêutico , Arsenicais/uso terapêutico , Óxidos/uso terapêutico , Resultado do Tratamento , Tretinoína/uso terapêutico
6.
Front Pharmacol ; 13: 1057949, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408263

RESUMO

Objective: This study was conducted to investigate the safety, tolerability and pharmacokinetics (PK) of WXFL10203614 after single and multiple oral doses in healthy Chinese subjects. Methods: A single-center, randomized, double-blind, placebo-controlled phase Ⅰ study was performed on healthy Chinese subjects. In the single-dose study, Subjects were randomized into 7 dose levels of WXFL10203614 (1 mg group, n = 2; 2, 5, 10, 17, 25 and 33 mg groups with placebo, 8 subjects per group, 2 of them given placebo). In the multiple-dose study, subjects received 5 or 10 mg WXFL10203614 once daily (QD), 5 mg twice daily (BID) or placebo for 7 consecutive days. Safety, tolerability and PK of WXFL10203614 were all assessed. Results: A total of 592 subjects were screened, 50 subjects were enrolled in the single-dose study and 30 in the multiple-dose study. All adverse events (AEs) were mild or moderate and resolved spontaneously. No Serious Adverse Events (SAEs) or deaths were reported during the study. WXFL10203614 was absorbed rapidly after dosing with Tmax of 0.48-0.98 h, Cmax, AUC0-t and AUC0-∞ were all increased in a dose-related manner over the range of 1-33 mg. Renal excretion was the major route of elimination of WXFL10203614. Steady-state PK parameters (Cmax,ss, AUC0-t,ss and AUC0-∞,ss) were elevated after once-daily administration of 5-10 mg WXFL10203614 and non- and weak drug accumulations were observed, whereas moderate drug accumulation occurred in the 5 mg BID group. Conclusion: WXFL10203614 exhibited good safety, tolerability and favorable PK profiles in healthy Chinese subjects, supporting further clinical development in patients with rheumatoid arthritis. Clinical Trials Registration Number: http://www.chinadrugtrials.org.cn/index.html, #CTR20190069 and CTR20200143.

7.
Phys Rev Lett ; 129(18): 187001, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36374687

RESUMO

We present a theory of superconductivity in twisted bilayer graphene in which attraction is generated between electrons on the same honeycomb sublattice when the system is close to a sublattice polarization instability. The resulting Cooper pairs are spin-polarized valley singlets. Because the sublattice polarizability is mainly contributed by interband fluctuations, superconductivity occurs over a wide range of filling fraction. It is suppressed by (i) applying a sublattice polarizing field (generated by an aligned BN substrate) or (ii) changing moiré band filling to favor valley polarization. The enhanced intrasublattice attraction close to sublattice polarization instability is analogous to enhanced like-spin attraction in liquid ^{3}He near the melting curve and the enhanced valley-singlet repulsion close to valley-polarization instabilities is analogous to enhanced spin-singlet repulsion in metals that are close to a ferromagnetic instability. We comment on the relationship between our pseudospin paramagnon model and the rich phenomenology of superconductivity in twisted bilayer and multilayer graphene.

8.
Adv Mater ; : e2208604, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36440601

RESUMO

The charge carriers of single-junction solar cells can be fluently extracted and then collected by electrodes, leading to weak charge carrier accumulation and low energy loss (Eloss ). However, in tandem solar cells (TSCs), it is a considerable challenge to obtain a balance between the densities of the holes and electrons extracted from the two respective subcells to facilitate an efficient recombination in the interconnecting layer (ICL). Herein, a charge-carrier-dynamic management strategy for inorganic perovskite/organic TSCs is proposed, centered on the simultaneous regulation of the defect states of CsPbI1.9 Br1.1 perovskite in front subcell and hole transport ability from the perovskite to ICL. The target hole density on the perovskite surface and the hole loss before reaching the ICL are significantly improved. As a result, the hole/electron density offset in the ICL can be effectively narrowed, leading to a balanced charge carrier recombination, which reduces the Eloss in TSCs. The resulting inorganic perovskite/organic 0.062-cm2 TSC exhibits a remarkable power conversion efficiency (PCE) of 23.17% with an ultrahigh open-circuit voltage (Voc ) of 2.15 V, and the PCE of the 1.004-cm2 device (21.69%) exhibited a weak size-dependence. This charge-carrier-dynamic management strategy can also effectively enhance the operational and ultraviolet-light stabilities of the TSCs. This article is protected by copyright. All rights reserved.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36404278

RESUMO

Bioelectronic sensors that report charge changes of a biomolecule on target binding enable direct and sensitive analyte detection, but remains a big challenge for potentiometric measurement, mainly due to the Debye Length limitations and the need for molecular-level platforms. Here we report on a magneto-controlled potentiometric method to directly and sensitively measure the target-binding induced charge change of DNA aptamer assembled on magnetic beads using a polymeric membrane potentiometric ion sensor. The potentiometric responses of the negatively charged aptamer, serving as a receptor and reporter, were dynamically controlled and modulated by applying a magnetic field. Based on a potentiometric array, this non-equilibrium measurement technique combined with deep learning algorithms allows for rapidly and reliably classifying and quantifying diverse small molecules using antibiotics as models. This potentiometric strategy opens new modalities for sensing applications.

10.
Medicine (Baltimore) ; 101(46): e31586, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401373

RESUMO

OBJECTIVES: Coronary heart disease (CHD) is the most common heart disease and the leading cause of cardiovascular deaths worldwide. Decreased endothelial cell (EC) proliferation, increased apoptosis, inflammation, and vascular dysfunction are considered vital factors in CHD. In this study, we aimed to determine the expression and role of microRNA-195-3p and brain-derived neurotrophic factor (BDNF) in hypoxic-treated human umbilical vein endothelial cells (HUVECs). MEASURES: We induced hypoxia in HUVECs using the "anaerobic tank method." RESULTS: We found that the levels of microRNA-195-3p and BDNF were upregulated and apoptosis was increased. Furthermore, we found that BDNF/P-ERK1/2 regulated the expression of the mitochondrial apoptosis pathway proteins Bcl-2/BAX, which was downregulated under hypoxic conditions. Finally, the microRNA-195-3p inhibitor downregulated BDNF and P-ERK1/2, upregulated the Bcl-2/BAX axis, and partially reversed the effects of hypoxic-induced injury in HUVECs. CONCLUSIONS: Therapeutic intervention using the microRNA-195-3p/BDNF/P-ERK1/2/Bcl-2/BAX axis could maintain EC function under hypoxic conditions, improve cell activity, and serve as a new treatment strategy for CHDs.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , MicroRNAs , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína X Associada a bcl-2 , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Hipóxia/genética , Hipóxia/metabolismo
11.
Front Pharmacol ; 13: 839803, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339616

RESUMO

Background: Protein-energy wasting (PEW) is highly prevalent in hemodialysis (HD) patients, which is associated with poor quality of life, complications, and an increased risk of mortality. A prospective study in HD patients with 2 months of oral energy supplements (OESs) was performed. Methods: A total of 37 HD patients with PEW were finally enrolled in this prospective study and were randomized into the OES group (n = 19), which received oral energy supplementation (300 kcal) and dietary recommendations, while patients in the non-OES group (n = 18) received only dietary recommendations. The study duration was 2 months. The nutritional status of the patients was evaluated by laboratory indexes, body composition parameters, and the modified quantitative subjective global assessment (MQSGA) and malnutrition-inflammation score (MIS). Quality of life was evaluated by the Short Form Health Survey Questionnaire (SF-36). Results: After 2 months of therapy, a significant increase in serum albumin [39.6 (37.6-45.8) vs. 43.4 (39.1-46.7) g/L; p = 0.018], hemoglobin (101.0 ± 13.6 g/L vs. 111.8 ± 11.7 g/L; p = 0.042), and dietary energy intake (29.17 ± 3.22 kcal/kg/day vs. 33.60 ± 2.72 kcal/kg/day, p < 0.001) was observed in the comparisons of baseline in the OES group. Moreover, the OES group demonstrated significant amelioration in MQSGA [9 (8-13) vs. 8 (7-12), p < 0.001] and MIS [5 (3-10) vs. 3 (2-8), p < 0.001], physical functioning (p < 0.001), and mental health (p = 0.046) subsections of SF-36 compared with the baseline. No electrolyte disorders or dyslipidemia were observed in the OES group. Conclusion: OES in HD patients with PEW can significantly ameliorate energy supply, nutritional status, anemia, and quality of life.

12.
Biochem Biophys Res Commun ; 636(Pt 1): 112-120, 2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36332472

RESUMO

Myocytes undergoing hypoxia condition can recruit macrophages and cause pro-inflammation initiation around the injury area. Mitochondrial dysfunction is related to macrophage pyroptosis. Stomatin-like protein-2 (SLP-2) can regulate mitochondrial biogenesis and function. Whether SLP-2 could affect macrophage pyroptosis remains unclear. In this study, bone marrow derived macrophages (BMDMs) were extracted from WT and SLP-2 knocked out mice, then stimulated by LPS/Nigericin. Western blot showed that SLP-2-/- promoted the expression of NLRP3, GSDMD-N, caspase-11 in macrophages, which means the deficiency of SLP-2 augments macrophage pyroptosis. Higher fluorescence intensity of dihydroethidium and TUNEL represented the increased ROS releasing and macrophage programmed death in SLP-2 deficiency groups. The immunofluorescence intensity of MtioTracker Red decreased and that of mitochondrial ROS (mtROS) increased in SLP-2 deletion groups with LPS/Nigericin stimulation, representing the increased mitochondrial damage. The expression level of HIF-1α increased in SLP-2 deletion macrophages with LPS and Nigericin stimulation. The level of Parkin and the ratio of LC3II/I decreased in SLP-2 deficiency macrophages after stimulated by LPS/Nigericin, compared with untreated macrophages. H9c2 cells were cultured in hypoxia condition before being cocultured with macrophage supernatant. The cocultured H9c2 cells were injured due to the serious pyroptosis of SLP-2 deficiency macrophages. According to these results, we suggest that SLP-2 can reduce macrophage pyroptosis and relieve hypoxia H9c2 cells injury through protecting mitochondrial function.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lipopolissacarídeos/metabolismo , Nigericina , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Hipóxia/metabolismo , Inflamassomos/metabolismo
13.
BMC Med Inform Decis Mak ; 22(1): 310, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443738

RESUMO

BACKGROUND: Nursing information systems embedded with standardized nursing language and clinical decision support have been increasingly introduced in health care settings. User experience is key to the adoption of health information technologies. Despite extensive research into the user experience with nursing information systems, few studies have focused on the interaction between user, technology and organizational attributes during its implementation. Guided by the human, organization and technology-fit framework, this study aimed to investigate nurses' perceptions and experiences with transition to a new nursing information system (Care Direct) 2 years after its first introduction. METHODS: This is a mixed-method study using an embedded design. An online survey was launched to collect nurses' self-reported use of the new system, perceived system effectiveness and experience of participation in system optimization. Twenty-two semi structured interviews were conducted with twenty nurses with clinical or administrative roles. The quantitative and qualitative data were merged using the Pillar Integration Process. RESULTS: The average score of system use behavior was 3.76 ± 0.79. Regarding perceived system effectiveness, the score of each dimension ranged 3.07-3.34 out of 5. Despite large variations in approaches to participating in system optimization, nurses had generally positive experiences with management and technical support. Eight main categories emerged from the integrated findings, which were further condensed into three themes: perceptions on system content, structure, and functionality; perceptions on interdisciplinary and cross-level cooperation; and embracing and accepting the change. CONCLUSIONS: Effective collaboration between clinicians, administrators and technical staff is required during system promotion to enhance system usability and user experience. Clear communication of organizational missions to staff and support from top management is needed to smooth the system implementation process and achieve broader system adoption.


Assuntos
Confiabilidade dos Dados , Software , Humanos , Autorrelato , Tecnologia , Sistemas de Informação
14.
Front Psychiatry ; 13: 1022442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440417

RESUMO

Background: Circadian rhythm was involved in the pathogenesis of depression. The detection of circadian genes and white matter (WM) integrity achieved increasing focus for early prediction and diagnosis of major depressive disorder (MDD). This study aimed to explore the effects of PER1 gene polymorphisms (rs7221412), one of the key circadian genes, on the association between depressive level and WM microstructural integrity. Materials and methods: Diffusion tensor imaging scanning and depression assessment (Beck Depression Inventory, BDI) were performed in 77 healthy college students. Participants also underwent PER1 polymorphism detection and were divided into the AG group and AA group. The effects of PER1 genotypes on the association between the WM characteristics and BDI were analyzed using tract-based spatial statistics method. Results: Compared with homozygous form of PER1 gene (AA), more individuals with risk allele G of PER1 gene (AG) were in depression state with BDI cutoff of 14 (χ2 = 7.37, uncorrected p = 0.007). At the level of brain imaging, the WM integrity in corpus callosum, internal capsule, corona radiata and fornix was poorer in AG group compared with AA group. Furthermore, significant interaction effects of genotype × BDI on WM characteristics were observed in several emotion-related WM tracts. To be specific, the significant relationships between BDI and WM characteristics in corpus callosum, internal capsule, corona radiata, fornix, external capsule and sagittal stratum were only found in AG group, but not in AA group. Conclusion: Our findings suggested that the PER1 genotypes and emotion-related WM microstructure may provide more effective measures of depression risk at an early phase.

15.
Curr Neurovasc Res ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36330623

RESUMO

BACKGROUND AND PURPOSE: Most studies of cerebral microbleeds place more emphasis on the elderly, which made it difficult to obtain data on youth, particularly young ischemic stroke patients. Our study sought to investigate the incidence and related risk factors of cerebral microbleeds in young ischemic stroke patients. METHODS: Young ischemic stroke patients who sought medical advice at Beijing Chaoyang Hospital between June 2016 and September 2020 were included in our study. The clinical and imaging data of these patients were collected and assessed. These patients were grouped by cerebral microbleed presence, count, and location. Univariate and multivariate logistic regression analyses were performed to investigate the association between these groups and screen the influencing factors of cerebral microbleeds in young patients with ischemic stroke. RESULTS: Among the 187 young ischemic stroke patients, the prevalence of microbleeds was 16%. The presence of cerebral microbleeds was associated with hypertension (odds ratio [OR] 8.787, 95% confidence interval [CI] 1.016-76.006, P=0.048), lower estimated glomerular filtration rate (OR 0.976, 95%CI 0.957-0.995, P=0.014) and moderate/severe white matter hyperintensity (OR 10.681, 95%CI 3.611-31.595, P<0.001) in young ischemic stroke patients. CONCLUSION: Cerebral microbleeds were common in young ischemic stroke patients and were associated with hypertension, lower estimated glomerular filtration rate, and moderate/severe white matter hyperintensity.

16.
Front Surg ; 9: 950264, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225217

RESUMO

Background: Coronary artery (CA) involvement due to acute aortic dissection (AAD) is a catastrophic cardiovascular disease with high mortality. Two main surgery strategies, local coronary repair and coronary artery bypass grafting (CABG) can be applied to reestablish the blood flow in the aortic repair. This study was to evaluate the operative and long-term outcomes of type A AAD patients, who received aortic dissection repair plus CABG or local coronary repair. Method: We reviewed our database and screened 148 type A AAD patients with CA involvement from January 2001 to December 2021. Local coronary repair or CABG was performed concomitantly on these enrolled patients. Results: At the time of aortic repair, there were 58 patients with concomitant CABG (Group I) and 90 patients with local coronary repair (Group II). The basal characteristics of these two groups had no difference, except for acute myocardial ischemia (AMI) and CA involvement type. 45 patients with AMI in Group I, but none in Group II (P < 0.001). There was a higher frequency of type B and C lesions of CA involvement in Group I than that in Group II (P < 0.001). There was no difference in surgical procedures and complications, except for postoperative acute kidney injury (AKI) (34.5% vs. 8.9%, P < 0.001). Hospital mortality in Group I was higher than that in Group II, but without statistical difference (20.7% vs. 11.1%, P = 0.155). No significant difference was obtained in long-term survival rate between the two groups (82.5 ± 4.8% vs. 81.2 ± 6.9%, P = 0.19). Conclusion: CABG and local coronary repair suits different types of CA involvement, and their effects on perioperative results and long-term survival for type A AAD patients with CA involvement are equal.

17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1577-1585, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36208269

RESUMO

OBJECTIVE: To investigate the clinical outcomes and prognostic factors of refractory/relapsed acute myeloid leukemia (AML) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 80 refractory/relapsed AML patients who received allo-HSCT from December 2013 to June 2020 were retrospectively analyzed, including the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate, incidence of transplant-related mortality (TRM), and the related risk factors were explored. RESULTS: Hematopoietic reconstitution was obtained in all 80 patients after transplantation, the 3-year OS and DFS rates were (48.8±6.3)% and (40.8±6.7)%, respectively. The 3-year cumulative incidence of relapse and TRM were 33.8% (95%CI: 0.254-0.449) and 15.0%(95%CI: 0.114-0.198), respectively. Univariate analysis showed that non-remission (NR) status before transplantation, DNMT3A R882 mutations and grade II-IV acute graft-versus-host disease (aGVHD) had negative effects on OS and DFS. Multivariate analysis indicated that the DNMT3A R882 mutations and grade II-IV aGVHD were independent risk factors for OS (HR=0.253, 95%CI: 0.092-0.695, P=0.008; HR=5.681, 95%CI: 2.101-15.361, P=0.001) and DFS (HR=0.200, 95%CI: 0.071-0.569, P=0.003; HR=7.117, 95%CI: 2.556-19.818, P<0.001). The 3-year cumulative incidence of relapse was 71.4%(95%CI: 0.610-0.836) in genetic high-risk group, which was higher than 23.3%(95%CI: 0.147-0.370) in intermediate-risk group and 23.5%(95%CI: 0.127-0.437) in favorable-risk group (P=0.006). CONCLUSION: Allo-HSCT is an effective and safe choice for refractory/relapsed AML patients. DNMT3A R882 mutations and grade II-IV aGVHD are negative prognostic factors of allo-HSCT for refractory/relapsed AML patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Prognóstico , Recidiva , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos
18.
Gastrointest Endosc ; 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36252870

RESUMO

BACKGROUND AND AIMS: The prevalence of high-risk varices (HRV) is low among compensated cirrhotic patients undergoing esophagogastroduodenoscopy (EGD). Our study aimed to identify a novel machine learning-based model, named ML EGD, for ruling out HRV and avoiding unnecessary EGDs in patients with compensated cirrhosis. METHODS: An international cohort from 17 institutions from China, Singapore, and India were enrolled (CHESS2001, NCT04307264). The variables with the top three importance scores (liver stiffness, platelet count, and total bilirubin) were selected by shapley additive explanation and inputted into light gradient boosting machine algorithm to develop ML EGD for identification of HRV. Furthermore, we built a web-based calculator of ML EGD and it was free with open access at http://www.pan-chess.cn/calculator/MLEGD_score. Spared EGDs and the rates of missed HRV were used to assess the efficacy and safety for varices screening. RESULTS: A total of 2,794 patients were enrolled. Of them, 1,283 patients in a real-world cohort from one university hospital in China were to develop and internally validate the performance of ML EGD for varices screening. They were randomly assigned into the training (n = 1154) and validation (n = 129) cohorts with a ratio of 9:1. In the training cohort, ML EGD spared 607 (52.6%) unnecessary EGDs with a missed HRV rate of 3.6%. In the validation cohort, ML EGD spared 75 (58.1%) EGDs with a missed HRV rate of 1.4%. To externally test the performance of ML EGD, 966 patients from 14 university hospitals in China (test cohort 1) and 545 from two hospitals in Singapore and India (test cohort 2) comprised two test cohorts. In the test cohort 1, ML EGD spared 506 (52.4%) EGDs with a missed HRV rate of 2.8%. In the test cohort 2, ML EGD spared 224 (41.1%) EGDs with a missed HRV rate of 3.1%. Comparing with Baveno VI criteria, ML EGD spared more screening EGDs in all cohorts (training cohort, 52.6% vs 29.4%; validation cohort, 58.1% vs 44.2%; test cohort 1, 52.4% vs 26.5%; test cohort 2, 41.1% vs 21.1%) (p < 0.001). CONCLUSIONS: We identified a novel model based on liver stiffness, platelet count, and total bilirubin, named ML EGD, as a free web-based calculator. ML EGD could efficiently help rule out HRV and avoid unnecessary EGDs in patients with compensated cirrhosis.

19.
Int J Stem Cells ; 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36310024

RESUMO

Background and Objectives: Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation. Methods and Results: Real-time reverse transcription-polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3'-untranscribed region. Conclusions: These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.

20.
Int Immunopharmacol ; 113(Pt A): 109324, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36244218

RESUMO

BACKGROUND: The albumin-to-fibrinogen ratio (AFR), a novel inflammatory marker, has been studied in various diseases. However, whether AFR could act as a prognostic factor for IgAN patients remains unclear. We aimed to investigate the prognostic value of AFR in IgAN. METHODS: A total of 1289 biopsy-confirmed primary IgAN patients from 2008 to 2018 in West China Hospital, Sichuan University, were studied retrospectively. Receiver operating characteristic curve analysis was generated to assess and compare the ability of indicators to predict survival. Based on the cut-off value of AFR, IgAN patients were classified into the low AFR group and the high AFR group. The demographic and clinical-histopathological data were collected. Renal endpoints included eGFR decreased ≥50 % of the baseline level, ESRD, renal transplantation and/or death. Patients were followed up until a composite endpoint. Kaplan-Meier survival curves and Cox proportional hazards models were used to determine independent predictors. RESULTS: The area under the curve (AUC) of AFR was 0.677, with an optimal cut-off value of 12.44. IgAN patients were classified into two groups (low AFR group: AFR < 12.44, n = 541; high AFR group: AFR ≥ 12.44, n = 748) with a median follow-up of 55.3 (36.4-78.6) months. A higher composition of hypertension, worse renal function, higher proteinuria, and more severe pathological lesions were significantly shown in the low AFR group. Further multivariable Cox regression analyses showed that a low AFR was an independent risk factor for renal survival (HR 1.90, 95 % CI 1.29-2.81, p = 0.001). Kaplan-Meier curves showed that the cumulative incidences of both ESRD and composite end point were significantly higher in patients with AFR < 12.44 (both p < 0.001). CONCLUSIONS: Our study demonstrated that a low AFR (<12.44) is an independent prognostic factor of poor renal prognosis in Chinese IgAN patients.

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