Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 887
Filtrar
1.
Biomater Sci ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363155

RESUMO

Correction for 'MnO2/Ce6 microbubble-mediated hypoxia modulation for enhancing sono-photodynamic therapy against triple negative breast cancer' by Ping Li et al., Biomater. Sci., 2024, https://doi.org/10.1039/d3bm00931a.

2.
Biomater Sci ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38318975

RESUMO

Sono-photodynamic therapy (SPDT) has emerged as a promising treatment modality for triple negative breast cancer (TNBC). However, the hypoxic tumor microenvironment hinders the application of SPDT. Herein, in this study, a multifunctional platform (MnO2/Ce6@MBs) was designed to address this issue. A sono-photosensitizer (Ce6) and a hypoxia modulator (MnO2) were loaded into microbubbles and precisely released within tumor tissues under ultrasound irradiation. MnO2in situ reacted with the excess H2O2 and H+ and produced O2 within the TNBC tumor, which alleviated hypoxia and augmented SPDT by increasing ROS generation. Meanwhile, the reaction product Mn2+ was able to achieve T1-weighted MRI for enhanced tumor imaging. Additionally, Ce6 and microbubbles served as a fluorescence imaging contrast agent and a contrast-enhanced ultrasound imaging agent, respectively. In in vivo anti-tumor studies, under the FL/US/MR imaging guidance, MnO2/Ce6@MBs combined with SPDT significantly reversed tumor hypoxia and inhibited tumor growth in 4T1-tumor bearing mice. This work presents a theragnostic system for reversing tumor hypoxia and enhancing TNBC treatment.

3.
Int J Biol Macromol ; 262(Pt 2): 130106, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38346628

RESUMO

An eco-friendly antimicrobial sulfur quantum dot scale inhibitor (CMC-SQDs) synthesized using carboxymethyl cellulose (CMC) showed strong inhibition of calcium sulfate (CaSO4) at a concentration just below 1 mg/L, with an inhibition efficiency exceeding 99 %. However, the precise interaction process between CMC-SQDs and CaSO4 remains unclear. This article investigates the effectiveness of SQDs in inhibiting the formation of CaSO4 and calcium carbonate (CaCO3) scales. Through static scale inhibition tests, molecular dynamics simulations, and quantum chemical calculations, the study aims to elucidate the different impacts of CMC-SQDs on CaSO4 and CaCO3 scale formation. The research focuses on understanding the relationship between the structural activity of CMC-SQDs and their scale-inhibiting performance and delving into the underlying mechanisms of scale inhibition. The findings describe the role of SQDs in a water-based solution, acting as persistent "nanodusts" that interact with calcium (Ca2+) ions and sulfate ions. CMC forms complexes with Ca2+ ions, and the presence of SQDs enhances the van der Waals force, indirectly increasing the resistance of associated ions and the binding energy on the surface of precipitated gypsum. Conversely, SQDs exhibit weak surface stability and have minimal binding energy when interacting with calcite, leading to limited occupation of available adsorption sites.

4.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38343328

RESUMO

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.


Assuntos
Neoplasias Primárias Desconhecidas , Humanos , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/terapia , Medicina de Precisão , Perfilação da Expressão Gênica/métodos , Análise em Microsséries
5.
Sci Adv ; 10(6): eadk8426, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335289

RESUMO

Acute liver failure (ALF) is a critical medical condition defined as the rapid development of hepatic dysfunction. Conventional ultrasound elastography cannot continuously monitor liver stiffness over the course of rapidly changing diseases for early detection due to the requirement of a handheld probe. In this study, we introduce wearable bioadhesive ultrasound elastography (BAUS-E), which can generate acoustic radiation force impulse (ARFI) to induce shear waves for the continuous monitoring of modulus changes. BAUS-E contains 128 channels with a compact design with only 24 mm in the azimuth direction for comfortable wearability. We further used BAUS-E to continuously monitor the stiffness of in vivo rat livers with ALF induced by d-galactosamine over 48 hours, and the stiffness change was observed within the first 6 hours. BAUS-E holds promise for clinical applications, particularly in patients after organ transplantation or postoperative care in the intensive care unit (ICU).


Assuntos
Técnicas de Imagem por Elasticidade , Dispositivos Eletrônicos Vestíveis , Humanos , Ultrassonografia
6.
Indian J Orthop ; 58(2): 151-161, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38312904

RESUMO

Aims: This study aimed to establish a nomogram model for predicting the probability of postoperative deep vein thrombosis (DVT) risk in patients with hip fractures. Methods: 504 patients were randomly assigned to the training set and validation set, and then divided into a DVT group and a non-DVT group. The study analysed the risk factors for DVT using univariate and multivariate analyses. Based on these parameters, a nomogram model was constructed and validated. The predicting performance of nomogram was evaluated by discrimination, calibration, and clinical usefulness. Results: The predictors contained in the nomogram model included age, surgical approach, 1-day postoperative D-dimer value and admission ultrasound diagnosis of the lower limb vein. Furthermore, the area under the ROC curve (AUC) for the specific DVT risk-stratification nomogram model (0.815; 95% CI 0.746-0.884) was significantly higher than the current model (Caprini) (0.659; 95% CI 0.572-0.746, P < 0.05). According to the calibration plots, the prediction and actual observation were in good agreement. In the range of threshold probabilities of 0.2-0.8, the predictive performance of the model on DVT risk could be maximized. Conclusions: The current predictive model could serve as a reliable tool to quantify the possibility of postoperative DVT in hip fractures patients.

7.
Front Neurol ; 15: 1344961, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348167

RESUMO

Background: The current guideline recommended the use of intravenous thrombolysis (IVT) before Endovascular thrombectomy (EVT), but the effectiveness and safety of tenecteplase compare to alteplase in patients before EVT remain uncertain. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library to identify eligible articles from inception until September 16, 2023. The primary outcome was functional independence (mRS 0-2) at 90 days. Secondary outcomes included excellent outcome (mRS 0-1) at 90 days, all-cause mortality at follow-up, successful reperfusion (TICI 2b-3) after the end of EVT, symptomatic intracranial hemorrhage (sICH) or any intracranial hemorrhage (aICH). The PROSPERO registration number is CRD42023470419. Results: Eight randomized controlled trials (RCTs) were included involving 2,836 acute ischemic stroke (AIS) patients. Compared to EVT alone, tenecteplase (0.25 mg/kg and 0.4 mg/kg) + EVT and 0.9 mg/kg alteplase + EVT were significant difference associated with higher successful reperfusion (TICI 2b-3) after the end of EVT (RR = 2.31; 95% CI 1.15-4.63; RR = 2.31; 95% CI 1.00-5.33; RR = 1.05; 95% CI 1.01-1.09). And compared to 0.25 mg/kg tenecteplase + EVT, alteplase (0.6 mg/kg and 0.9 mg/kg) + EVT were significant difference associated with lower successful reperfusion (TICI 2b-3) after the end of EVT (RR = 0.45; 95% CI 0.22-0.90; RR = 0.45; 95% CI 0.23-0.91). The risk of aICH (RR = 1.50; 95% CI 1.07-2.09) was significantly higher for 0.6 mg/kg alteplase + EVT than EVT alone. There was no significant difference in functional independence (mRS 0-2), excellent outcome (mRS 0-1), all-cause mortality or sICH among the different IVT strategies (0.25 mg/kg or 0.4 mg/kg tenecteplase and 0.6 mg/kg or 0.9 mg/kg alteplase) before EVT. Conclusion: The use of alteplase before EVT may potentially improve the successful reperfusion after EVT compared to tenecteplase. Due to the insufficient sample size, more high-quality RCTs are needed to confirm effectiveness and safety of tenecteplase compare to alteplase in patients before EVT. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023470419.

8.
J Autoimmun ; 143: 103163, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38301505

RESUMO

BACKGROUND: In patients with primary biliary cholangitis (PBC) treated with ursodeoxycholic acid (UDCA), the presence of moderate-to-severe interface hepatitis is associated with a higher risk of liver transplantation and death. This highlights the need for novel treatment approaches. In this study, we aimed to investigate whether combination therapy of UDCA and immunosuppressant (IS) was more effective than UDCA monotherapy. METHODS: We conducted a multicenter study involving PBC patients with moderate-to-severe interface hepatitis who underwent paired liver biopsies. Firstly, we compared the efficacy of the combination therapy with UDCA monotherapy on improving biochemistry, histology, survival rates, and prognosis. Subsequently we investigated the predictors of a beneficial response. RESULTS: This retrospective cohort study with prospectively collected data was conducted in China from January 2009 to April 2023. Of the 198 enrolled patients, 32 underwent UDCA monotherapy, while 166 received combination therapy, consisting of UDCA combined with prednisolone, prednisolone plus mycophenolate mofetil (MMF), or prednisolone plus azathioprine (AZA). The monotherapy group was treated for a median duration of 37.6 months (IQR 27.5-58.1), and the combination therapy group had a median treatment duration of 39.3 months (IQR 34.5-48.8). The combination therapy showed a significantly greater efficacy in reducing fibrosis compared to UDCA monotherapy, with an 8.3-fold increase in the regression rate (from 6.3% to 52.4%, P < 0.001). Other parameters, including biochemistry, survival rates, and prognosis, supported its effectiveness. Baseline IgG >1.3 × ULN and ALP <2.4 × ULN were identified as predictors of regression following the combination therapy. A predictive score named FRS, combining these variables, accurately identified individuals achieving fibrosis regression with a cut-off point of ≥ -0.163. The predictive value was validated internally and externally. CONCLUSION: Combination therapy with IS improves outcomes in PBC patients with moderate-to-severe interface hepatitis compared to UDCA monotherapy. Baseline IgG and ALP are the most significant predictors of fibrosis regression. The new predictive score, FRS, incorporating baseline IgG and ALP, can effectively identify individuals who would benefit from the combination therapy.

9.
Platelets ; 35(1): 2306983, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38314765

RESUMO

Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR.


Platelet transfusion is a critical treatment for patients with a severely reduced platelet count and significant bleeding symptoms. However, some patients do not respond to transfused platelets, especially those with repeated transfusions and malignant hematologic disorders, which may increase the burden of disease. In this review article, the authors outline how immunological factors contribute to the failure of platelet transfusions and conventional therapies. Although antibody-mediated platelet removal is often considered the predominant immunological mechanism, studies have shown that CD8+ T cells also play a unique role in platelet clearance. The authors also cover the prospects and challenges of alternative treatment strategies in clinical practice.


Assuntos
Antígenos de Plaquetas Humanas , Trombocitopenia , Humanos , Transfusão de Plaquetas/efeitos adversos , Plaquetas , Trombocitopenia/etiologia , Antígenos HLA
10.
Nat Commun ; 15(1): 1476, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368459

RESUMO

Overexpressed pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-XL can render tumor cells malignant. Leukemia drug venetoclax is currently the only approved selective BCL-2 inhibitor. However, its application has led to an emergence of resistant mutations, calling for drugs with an innovative mechanism of action. Herein we present cyclic peptides (CPs) with nanomolar-level binding affinities to BCL-2 or BCL-XL, and further reveal the structural and functional mechanisms of how these CPs target two proteins in a fashion that is remarkably different from traditional small-molecule inhibitors. In addition, these CPs can bind to the venetoclax-resistant clinical BCL-2 mutants with similar affinities as to the wild-type protein. Furthermore, we identify a single-residue discrepancy between BCL-2 D111 and BCL-XL A104 as a molecular "switch" that can differently engage CPs. Our study suggests that CPs may inhibit BCL-2 or BCL-XL by delicately modulating protein-protein interactions, potentially benefiting the development of next-generation therapeutics.


Assuntos
Antineoplásicos , Peptídeos Cíclicos , Peptídeos Cíclicos/farmacologia , Proteína bcl-X/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Sulfonamidas/farmacologia , Antineoplásicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Apoptose , Linhagem Celular Tumoral
11.
Angew Chem Int Ed Engl ; : e202315273, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217399

RESUMO

Sequential C-H functionalization of molecules containing multiple C-H bonds can efficiently lead to structural diversity. Herein we present the first chelation-assisted sequential α-/ß-C-H functionalization of E-styrenes with simple alkenes and alkynes in excellent regio- and stereo-selectivity. The process involves α C-H functionalization by six-membered exo-cyclopalladation to result in tri- and tetrasubstituted 1,3-dienes and ß C-H functionalization through seven-membered endo-cyclopalladation to produce tetra- and pentasubstituted 1,3,5-trienes in up to 97% yield with up to > 99/1 E/Z selectivity, both enabled by the chelation assistance of pyrazinamide. The protocol is demonstrated to be widely applicable, tolerant to a wide range of functional groups and bioactive fragments, and suitable for gram-scale synthesis as well as one-pot and two step preparation of trienes. Mechanistic experiments and density functional theory (DFT) calculations were performed to elucidate the selectivity and reactivity.

12.
Int J Biol Macromol ; 259(Pt 2): 129334, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38218298

RESUMO

The digestive properties of oat-based food have garnered considerable interest. This study aimed to explore the internal and external factors contributing to different digestion properties of oat flour under actual processing conditions. Analysis of the ordered structure of oat starch revealed that an increase in gelatinization moisture to 60 % led to a decrease in crystallinity, R1047/1022 value, and helical structures content to 0, 0.48 %, and 1.45 %, respectively. Even when the crystal structure was completely destroyed, the short-range structure retained a certain degree of order. Surface structure observations of starch granules and penetration experiments with amylase-sized polysaccharide fluorescence probes indicated that non-starch components and small pores effectively hindered the diffusion of the probes but low-moisture (20 %) gelatinization substantially damaged this barrier. Furthermore, investigations into starch digestibility and starch molecular structure revealed that the ordered structure remaining inside the starch after high gelatinization delayed the digestion rate (0.028 min-1) and did not increase the content of resistant starch (7.10 %). It was concluded that the surface structure and non-starch components of starch granules limited the extent of starch digestion, whereas the spatial barrier of the residual ordered structure affected the starch digestion rate.

13.
Nat Biotechnol ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253880

RESUMO

Realizing the full potential of organoids and assembloids to model neural development and disease will require improved methods for long-term, minimally invasive recording of electrical activity. Current technologies, such as patch clamp, penetrating microelectrodes, planar electrode arrays and substrate-attached flexible electrodes, do not allow chronic recording of organoids in suspension, which is necessary to preserve architecture. Inspired by kirigami art, we developed flexible electronics that transition from a two-dimensional to a three-dimensional basket-like configuration with either spiral or honeycomb patterns to accommodate the long-term culture of organoids in suspension. Here we show that this platform, named kirigami electronics (KiriE), integrates with and enables chronic recording of cortical organoids for up to 120 days while preserving their morphology, cytoarchitecture and cell composition. We demonstrate integration of KiriE with optogenetic and pharmacological manipulation and modeling phenotypes related to a genetic disease. Moreover, KiriE can capture corticostriatal connectivity in assembloids following optogenetic stimulation. Thus, KiriE will enable investigation of disease and activity patterns underlying nervous system assembly.

14.
J Affect Disord ; 349: 394-399, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38211748

RESUMO

BACKGROUND: There have been many studies on the benefits of repeated ketamine infusions on patients' depression but few on the impact of ketamine on patients' long-term quality of life (QoL). This study investigated long-term QoL in individuals with depression, both anxious and nonanxious. METHODS: A total of 107 individuals with a diagnosis of depression were included in the study. The patients were evaluated on Days 0, 13 and 26 and Months 6 and 9, and they received six ketamine infusions over the course of two weeks. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) Scale and the Patient Health Questionnaire-9 (PHQ-9) Scale were used to measure depressive symptoms and QoL. Linear mixed models were used to evaluate depressive symptoms and QoL during ketamine treatment. RESULTS: A total of 67.2 % of patients were diagnosed with anxious depression. In the long term, there were no significant differences in the time-by-group interactions for general QoL (F = 0.510; P = 0.676), physical QoL (F = 2.092; P = 0.102), psychological QoL (F = 0.102; P = 0.959), social QoL (F = 2.180; P = 0.091), or environmental QoL (F = 1.849; P = 0.139) between the two groups. LIMITATIONS: The main limitation of this study is its open-label design. CONCLUSION: The improvement in depression symptoms and QoL following ketamine treatment was not impacted by the presence or absence of anxiety in patients who were depressed prior to treatment. Only occasionally did depressed individuals with anxiety experience a worsening of their quality of life compared to those without anxiety.


Assuntos
Ketamina , Humanos , Ketamina/efeitos adversos , Depressão/tratamento farmacológico , Qualidade de Vida/psicologia , Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Infusões Intravenosas
15.
J Immunother Cancer ; 12(1)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212119

RESUMO

BACKGROUND: Among patients with advanced/metastatic triple-negative breast cancer (TNBC) with high/positive programmed death-ligand 1 (PD-L1) expression, a superior survival outcome has been demonstrated with immune checkpoint inhibitors (ICIs). However, it remains unclear whether ICIs are beneficial for patients with low PD-L1 levels. Here, we derived survival data for subgroups with low PD-L1-expressing and conducted a pooled analysis. METHODS: After a systematic search of Embase, PubMed, MEDLINE, and CENTRAL from inception until May 18, 2023, randomized controlled trials (RCTs) reporting progression-free survival (PFS), overall survival (OS), or duration of response (DOR) for metastatic TNBC treated with ICI-based regimens were included. Kaplan-Meier curves were extracted for the intention-to-treat population and high PD-L1 subgroups. KMSubtraction was used when survival curves were not provided for subgroups with low PD-L1 expression. A pooled analysis of survival data was then conducted. RESULTS: A total of 3022 patients were included in four RCTs: Impassion130, Impassion131, KEYNOTE-119, and KEYNOTE-355. Unreported low PD-L1-expressing subgroups were identified, including PD-L1 immune cell (IC)<1%, combined positive score (CPS)<1, and 1≤CPS<10. Compared with chemotherapy, ICI-chemotherapy combinations did not significantly differ in OS, PFS, or DOR in the Impassion PD-L1<1%, KEYNOTE-355 PD-L1 CPS<1, and KEYNOTE-355 1≤CPS<10 subgroups. In the KEYNOTE-119 CPS<1 subgroup, the risk of tumor progression was increased with pembrolizumab (HR, 2.23; 95% CI, 1.62 to 3.08; p<0.001), as well as in the 1≤CPS<10 subgroup (HR, 1.64; 95% CI, 1.22 to 2.20; p<0.001). A pooled analysis using a scoring system found no significant difference in OS and PFS among the subgroups with an IC of <1% between immunochemotherapy and chemotherapy. OS (HR, 1.07; 95% CI, 0.91 to 1.26), PFS (HR, 0.96; 95% CI, 0.84 to 1.10), and DOR were also not significantly different in pooled analysis of first-line trials for those with low PD-L1 expression. CONCLUSION: ICI-based regimens are not associated with a survival benefit versus chemotherapy in subgroups of advanced/metastatic TNBC that express low PD-L1 levels.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Fluxo de Trabalho , Quimioterapia Combinada , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico
16.
Biol Sex Differ ; 15(1): 12, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287453

RESUMO

BACKGROUND: Patients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression. METHODS: A total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26). RESULTS: Linear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (ß = 0.414, p = 0.009). CONCLUSIONS: Our results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males. Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn.


Depression and low bone mineral density (BMD) are epidemiologically linked and traditional antidepressants may act as a risk factor for BMD. However, it is unclear whether the novel antidepressant, ketamine, has effects on bone markers in patients with depression and whether there are sex differences on these effects. Ketamine infusions may be associated with modulation of bone markers and may exert a positive effect on BMD in patients with depression, which present sex differences. The study results may inform potential strategies for prevention of low BMD during the treatment of depression. Clinicians should be aware of the bone markers because some of them may be associated antidepressant response.


Assuntos
Transtorno Bipolar , Ketamina , Humanos , Feminino , Masculino , Transtorno Bipolar/tratamento farmacológico , Ketamina/uso terapêutico , Ketamina/farmacologia , Leptina/metabolismo , Osteocalcina , Caracteres Sexuais , Antidepressivos/uso terapêutico
17.
J Affect Disord ; 351: 211-219, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38244793

RESUMO

OBJECTIVE: Childhood trauma (CT) is a major environmental risk factor for an adverse course and treatment outcome of major depressive disorder (MDD). Evidence suggests that an altered regional brain activity may play a crucial role in the relationship between CT and MDD. This study aimed to clarify the relationship between CT, regional brain activity, and depression severity. METHODS: In this study, 96 patients with MDD and 82 healthy controls (HCs) participated. Regional brain activity was measured using the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). These measures were compared between the MDD and HC groups, and the values of different brain regions were extracted as moderators. RESULTS: Increased fALFF and ReHo values were observed in the left middle temporal gyrus in the MDD group compared with the HC group (p < 0.001). Furthermore, the fALFF and ReHo values moderated the positive correlation between the Childhood Trauma Questionnaire (CTQ) score, 17-item Hamilton Depression Rating Scale (HAMD-17) total score, and retardation factor score in the MDD group (all, p < 0.05). Finally, as the fALFF and ReHo values increased, the positive correlations between CTQ, HAMD-17 total, and retardation dimension scores became stronger. CONCLUSION: Our study highlighted the crucial role of altered brain function in connecting childhood maltreatment with depressive symptoms. Our findings indicate that an altered regional brain activity could explain the potential neurobiological mechanisms of MDD symptoms, offering the opportunity to function as a powerful diagnostic biomarker.

18.
Nat Commun ; 15(1): 705, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267418

RESUMO

Toxic amyloid-beta (Aß) plaque and harmful inflammation are two leading symptoms of Alzheimer's disease (AD). However, precise AD therapy is unrealizable due to the lack of dual-targeting therapy function, poor BBB penetration, and low imaging sensitivity. Here, we design a near-infrared-II aggregation-induced emission (AIE) nanotheranostic for precise AD therapy. The anti-quenching emission at 1350 nm accurately monitors the in vivo BBB penetration and specifically binding of nanotheranostic with plaques. Triggered by reactive oxygen species (ROS), two encapsulated therapeutic-type AIE molecules are controllably released to activate a self-enhanced therapy program. One specifically inhibits the Aß fibrils formation, degrades Aß fibrils, and prevents the reaggregation via multi-competitive interactions that are verified by computational analysis, which further alleviates the inflammation. Another effectively scavenges ROS and inflammation to remodel the cerebral redox balance and enhances the therapy effect, together reversing the neurotoxicity and achieving effective behavioral and cognitive improvements in the female AD mice model.


Assuntos
Doença de Alzheimer , Feminino , Animais , Camundongos , Doença de Alzheimer/terapia , Espécies Reativas de Oxigênio , Peptídeos beta-Amiloides , Citoesqueleto , Inflamação , Placa Amiloide
19.
J Clin Periodontol ; 2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38246602

RESUMO

AIM: To evaluate the 3- to 8-year outcomes of dental implants placed with lateral sinus floor augmentation (LSFA) and to identify factors affecting implant survival. MATERIALS AND METHODS: This retrospective study was performed by screening all implants placed with LSFA procedures, which were conducted between January 2012 and December 2016. Subantral bone gain (SABG) and apical bone height (ABH) were assessed using panoramic radiographs. The cumulative survival rate of implants was analysed using life-table analysis and Kaplan-Meier survival curves. The influential risk factors affecting survival were assessed using univariate log-rank tests and multivariable mixture cure rate model. Implant complications were recorded. RESULTS: Based on the established criteria, a total of 449 patients (760 implants) were included in this study. In the 3- to 8-year follow-up (mean ± SD, 5.81 ± 1.33 years), 15 implants in 14 patients failed, with a CRS of 96.81% on an implant basis and 95.07% on a patient basis. A history of periodontitis and poor compliance with supportive periodontal treatment was associated with a significantly higher risk of implant failure at both implant and patient levels. Significant decreases in ABH occurred during each yearly interval except for 3 years. A similar trend has been observed for SABG at 1, 2, 6 and 8 years. The total complication rate was 31.84% on implant basis, with peri-implant mucositis (21.58%) being the most frequent biologic complication and porcelain cracking (5.00%) being the most common technical complication. CONCLUSIONS: Implant with LSFA is a reliable treatment option in atrophic maxilla. A history of periodontitis without regular supportive periodontal treatment was identified as a predictor for implant failure. Slight but significant shrinkage of vertically augmented bone can be observed after implant placement.

20.
J Clin Anesth ; 92: 111309, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37922642

RESUMO

STUDY OBJECTIVE: To explore how American Society of Anesthesiologists (ASA) physical status classification affects different machine learning models in hypotension prediction and whether the prediction uncertainty could be quantified. DESIGN: Observational Studies SETTING: UofL health hospital PATIENTS: This study involved 562 hysterectomy surgeries performed on patients (≥ 18 years) between June 2020 and July 2021. INTERVENTIONS: None MEASUREMENTS: Preoperative and intraoperative data is collected. Three parametric machine learning models, including Bayesian generalized linear model (BGLM), Bayesian neural network (BNN), a newly proposed BNN with multivariate mixed responses (BNNMR), and one nonparametric model, Gaussian Process (GP), were explored to predict patients' diastolic and systolic blood pressures (continuous responses) and patients' hypotensive event (binary response) for the next five minutes. Data was separated into American Society of Anesthesiologists (ASA) physical status class 1- 4 before being read in by four machine learning models. Statistical analysis and models' constructions are performed in Python. Sensitivity, specificity, and the confidence/credible intervals were used to evaluate the prediction performance of each model for each ASA physical status class. MAIN RESULTS: ASA physical status classes require distinct models to accurately predict intraoperative blood pressures and hypotensive events. Overall, high sensitivity (above 0.85) and low uncertainty can be achieved by all models for ASA class 4 patients. In contrast, models trained without controlling ASA classes yielded lower sensitivity (below 0.5) and larger uncertainty. Particularly, in terms of predicting binary hypotensive event, for ASA physical status class 1, BNNMR yields the highest sensitivity of 1. For classes 2 and 3, BNN has the highest sensitivity of 0.429 and 0.415, respectively. For class 4, BNNMR and GP are tied with the highest sensitivity of 0.857. On the other hand, the sensitivity is just 0.031, 0.429, 0.165 and 0.305 for BNNMR, BNN, GBLM and GP models respectively, when training data is not divided by ASA physical status classes. In terms of predicting systolic blood pressure, the GP regression yields the lowest root mean squared errors (RMSE) of 2.072, 7.539, 9.214 and 0.295 for ASA physical status classes 1, 2, 3 and 4, respectively, but a RMSE of 126.894 if model is trained without controlling the ASA physical status class. The RMSEs for other models are far higher. RMSEs are 2.175, 13.861, 17.560 and 22.426 for classes 1, 2, 3 and 4 respectively for the BGLM. In terms of predicting diastolic blood pressure, the GP regression yields the lowest RMSEs of 2.152, 6.573, 5.371 and 0.831 for ASA physical status classes 1, 2, 3 and 4, respectively; RMSE of 8.084 if model is trained without controlling the ASA physical status class. The RMSEs for other models are far higher. Finally, in terms of the width of the 95% confidence interval of the mean prediction for systolic and diastolic blood pressures, GP regression gives narrower confidence interval with much smaller margin of error across all four ASA physical status classes. CONCLUSIONS: Different ASA physical status classes present different data distributions, and thus calls for distinct machine learning models to improve prediction accuracy and reduce predictive uncertainty. Uncertainty quantification enabled by Bayesian inference provides valuable information for clinicians as an additional metric to evaluate performance of machine learning models for medical decision making.


Assuntos
Anestesiologistas , Hipotensão , Feminino , Humanos , Teorema de Bayes , Aprendizado de Máquina , Hipotensão/diagnóstico , Hipotensão/etiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...