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1.
Front Nutr ; 11: 1369331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549750

RESUMO

Background: Early-onset sarcopenia refers to the progressive loss of muscle mass and function that occurs at an early age. This condition perpetuates the vicious cycle of muscle loss and is associated with adverse outcomes. It is important to identify the contributing factors for early intervention and prevention. While diet is known to impact muscle mass, the association of B vitamins with early-onset sarcopenia remains unexplored. Objectives: To investigate the association of B vitamins intake with early-onset sarcopenia risk in a cross-sectional study. Methods: We conducted data analysis on a total of 8,711 participants aged between 20 and 59 years who took part in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Early-onset sarcopenia was defined as a SMI measured by DXA that was one standard deviation below the sex-specific mean of the reference population. B vitamins intake (B1, B2, B3, B6, B9, and B12) was assessed by 24-h dietary recall. We used weighted multiple logistic regression and RCS models to estimate the OR and 95% CI of sarcopenia by B vitamins intake, adjusting for demographic, physical, lifestyle, comorbidities, and nutritional covariates. Results: Higher intake of vitamin B1 was associated with a 22% lower sarcopenia risk (OR = 0.78, CI = 0.63-0.97, p = 0.022), and higher intake of vitamin B2 with a 16% lower risk (OR = 0.84, CI = 0.74-0.97, p = 0.012) in both genders. Gender-specific analyses showed a 28% reduction in sarcopenia risk among males with each additional mg of vitamin B1 intake (OR = 0.72, CI = 0.52-0.97, p = 0.038), and a 26% decrease among females with each additional mg of vitamin B2 intake (OR = 0.74, CI = 0.57-0.96, p = 0.021). No significant differences were found between vitamin B2 and males, or between vitamin B1 and females. The RCS model suggested a nonlinear relationship between vitamin B2 intake and sarcopenia risk (POverall = 0.001, PNonlinear = 0.033), with a plateau effect above 3 mg/d. Conclusion: Higher intake of vitamin B1 and B2 may lower the risk of early-onset sarcopenia, with gender differences. This suggests the potential of nutritional intervention by increasing these vitamins intake through diet and supplements. Further research is warranted to elucidate the mechanisms and design targeted interventions.

2.
J Tradit Chin Med ; 44(1): 122-130, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213247

RESUMO

OBJECTIVE: To investigate the potential pharmacological mechanisms of Ganshuang granules (, GSG) in treating non-alcoholic fatty liver (NAFLD). METHODS: All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Protein-Protein interaction network, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD. Then, the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG. The levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot, respectively. RESULTS: Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD. Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD. Further experiments showed that the significantly decreased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment, as well as the expression levels of IL-6 and TNF-α in the liver. Furthermore, drug intervention increased the protein expression levels of phosphorylated-PI3K (P-PI3K) and P-AKT in the liver of the model group mice, and decreased the protein expression level of sterol regulatory element-binding protein 1. CONCLUSION: We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.


Assuntos
Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fator de Necrose Tumoral alfa/genética , Farmacologia em Rede , Interleucina-6 , Fosfatidilinositol 3-Quinases/genética , Colesterol
3.
Biosens Bioelectron ; 246: 115841, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38006701

RESUMO

There is an urgent need to accurately quantify tumor-derived exosomes, which have emerged as promising non-invasive tumor diagnostic biomarkers. Herein, a bispecific-aptamer sandwich-type gold nanoparticle-modified electrochemical aptasensor was developed based on a four-way junction (4-WJ)-triggered dual rolling circle amplification (RCA)-assisted methylene blue (MB)/G-quadruplex strategy for extremely specific and sensitive exosome detection. This aptamer/exosome/aptamer sandwich-type design contained a CD63-specific aptamer and a cancerous mucin-1 (MUC1) protein-specific aptamer. The CD63 aptamer modified on a gold electrode captured exosomes, and then the sandwich-type aptasensor was formed with the addition of the MUC1 aptamer. The MUC1 aptamer's 3'-end sequence facilitated the formation of 4-WJ, assisted by a molecular beacon probe and a binary DNA probe. Subsequently, a dual-RCA reaction was triggered by binding to two cytosine-rich circle DNA templates at both ends of 4-WJ. Ultimately, dual-RCA products containing multiple G-quadruplex conformations were generated with the assistance of K+ to trap abundant MB indicators and amplify electrochemical signals. The aptasensor exhibited high specificity, sensitivity, repeatability, and stability toward MCF-7-derived exosomes, with a detection limit of 20 particles/mL and a linear range of 1 × 102 to 1 × 107 particles/mL. Moreover, it showed excellent applicability in clinical settings to recover exosomes in normal human serum. Our aptasensor is anticipated to serve as a versatile platform for detecting various specific aptamer-based targets in biomedical and bioanalytical applications.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Nanopartículas Metálicas , Neoplasias , Humanos , Exossomos/metabolismo , Ouro/química , Aptâmeros de Nucleotídeos/química , Limite de Detecção , Técnicas Eletroquímicas , DNA/química , Neoplasias/diagnóstico , Neoplasias/metabolismo
4.
Adv Sci (Weinh) ; 11(10): e2307188, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38145350

RESUMO

Without coordinated strategies to balance the population and activity of tumor cells and polarized macrophages, antitumor immunotherapy generally offers limited clinical benefits. Inspired by the "eat me" signal, a smart tumor cell-derived proximity anchored non-linear hybridization chain reaction (Panel-HCR) strategy is established for on-demand regulation of tumor-associated macrophages (TAMs). The Panel-HCR is composed of a recognition-then-assembly module and a release-then-regulation module. Upon recognizing tumor cells, a DNA nano-tree is assembled on the tumor cell surface and byproduct strands loaded with CpG oligodeoxynucleotides (CpG-ODNs) are released depending on the tumor cell concentration. The on-demand release of CpG-ODNs can achieve efficient regulation of M2 TAMs into the M1 phenotype. Throughout the recognition-then-assembly process, tumor cell-targeted bioimaging is implemented in single cells, fixed tissues, and living mice. Afterward, the on-demand release of CpG-ODNs regulate the transformation of M2 TAMs into the M1 phenotype by stimulating toll-like receptor 9 to activate the NF-κB pathway and increasing inflammatory cytokines. This release-then-regulation process is verified to induce strong antitumor immune responses both in vitro and in vivo. Altogether, this proposed strategy holds tremendous promise for on-demand antitumor immunotherapy.


Assuntos
Macrófagos , Neoplasias , Camundongos , Animais , Macrófagos/metabolismo , Citocinas/metabolismo , Neoplasias/patologia , DNA/metabolismo , Imunoterapia
6.
Acta Pharmaceutica Sinica ; (12): 143-151, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005448

RESUMO

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

7.
Acta Pharmaceutica Sinica ; (12): 76-83, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005439

RESUMO

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

8.
Acta Pharmaceutica Sinica ; (12): 43-60, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005438

RESUMO

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

9.
Huan Jing Ke Xue ; 44(11): 6328-6338, 2023 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-37973115

RESUMO

To investigate the effects of leaves and stems on the accumulation and transport of cadmium(Cd) and arsenic(As) in wheat shoots after flowering, a field experiment was conducted in a typical Cd and As co-contaminated agricultural land to explore the distribution and translocation of Cd and As in the different parts of two wheat cultivars after flowering. The results showed that Cd was mainly distributed in the nodes of two varieties, and the translocation factors of Cd from internode 3 to node 2, from internode 2 to node 1, and from sheath 1 to node 1 were markedly higher than those of other aboveground parts during the grain-filling stage. However, Cd was mainly distributed in the leaves, and the translocation factors of Cd from sheath to leaf and from node 1 to rachis was significantly higher than those of other parts at the mature stage. In addition, the transport capacity of Cd from glume to rachis and from rachis to grain in JM22 was significantly lower than that in SN28, which significantly reduced Cd concentrations in the rachis, glume, and grain of JM22 by 22.3%, 40.8%, and 44.4%, respectively. Meanwhile, As was mainly distributed in the wheat leaves from the grain-filling stage to the mature stage, and As concentrations in the glume and grain of JM22 were 25.8% and 33.3% lower than those of SN28, respectively. Additionally, the translocation factors of As from the sheath to the node were significantly 438% and 190% higher than that from leaf to sheath and from node to internode during the whole grain filling stage and mature stage. Moreover, the translocation factors of As from glumes to grains and from rachis to grains in JM22 were 40.6% and 44.4% lower than that in SN28, respectively. In summary, flag leaf, node 1, and the rachis had regulated Cd transport and accumulation in wheat grains, whereas leaf 3, flag leaf, node 1, the glumes, and the rachis were mainly responsible for As transport and accumulation in wheat grains.


Assuntos
Arsênio , Poluentes do Solo , Cádmio/análise , Triticum , Grão Comestível/química , Agricultura , Poluentes do Solo/análise , Solo
10.
Polymers (Basel) ; 15(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37447517

RESUMO

As energy and environmental issues become more prominent, people must find sustainable, green development paths. Bio-based polymeric phase change energy storage materials provide solutions to cope with these problems. Therefore, in this paper, a fully degradable polyethylene glycol (PEG20000)/polylactic acid (PLA)/g-C3N4 composite phase change energy storage material (CPCM) was obtained by confinement. The CPCM was characterized by FTIR and SEM for compatibility, XRD and nanoindentation for mechanical properties and DSC, LFA, and TG for thermal properties. The results showed that the CPCM was physical co-mingling; when PLA: PEG: g-C3N4 was 6:3:1, the consistency was good. PEG destroys the crystallization of PLA and causes the hardness to decrease. When PLA: PEG: g-C3N4 was 6: 3: 1, it had a maximum hardness of 0.137 GPa. The CPCM had a high latent enthalpy, and endothermic and exothermic enthalpies of 106.1 kJ/kg and 80.05 kJ/kg for the PLA: PEG: g-C3N4 of 3: 6: 1. The CPCM showed an increased thermal conductivity compared to PLA, reaching 0.30 W/(m·K),0.32 W/(m·K) when PLA: PEG: g-C3N4 was 6: 3: 1 and when PLA: PEG: g-C3N4 was 3: 6: 1, respectively. Additionally, the CPCM was stable within 250 °C, indicating a wide appliable temperature range. The CPCM can be applied to solar thermal power generation, transportation, and building construction.

11.
Small ; 19(43): e2302914, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37357169

RESUMO

Changes in atomic bonding configuration in carbon from sp3 to sp2 are known to exist in certain structural defects in diamond, such as twin boundaries, grain boundaries, and dislocations, which have a significant impact on many properties of diamond. In this work, the atomic structure of fivefold twinning in detonation synthesized ultra-dispersed diamonds is investigated using a combination of techniques, including spherical aberration-corrected high-resolution electron microscopy (HREM), HREM image simulations, and molecular mechanics (MM) calculations. The experimental HREM images reveal clearly that the fivefold twinning in diamond has two distinct structures. In addition to the concentric fivefold twins, where the core structure is the intersection of five {111} twinning boundaries, a new extended core structure with co-hybridization of bonding is identified and analyzed in fivefold twinning. The atomic structure forming these fivefold twinning boundaries and their respective core structures is proposed to involve both the tetrahedral sp3 and planar graphitic sp2 bonding configurations, in which a co-hybridized planar hexagon of carbon serves as a fundamental structural unit. The presence of this sp2 -bonded planar unit of hexagonal carbon rings in general grain boundaries is also discussed.

12.
Rev. int. med. cienc. act. fis. deporte ; 23(90): 327-338, jun. 2023. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-222619

RESUMO

Objective: Chronic prostatitis belongs to the category of traditional Chinese medicine, is a common disease in the elderly. This article systematically evaluated the efficacy of traditional Chinese medicine in the treatment of chronic prostatitis with kidney-nourishing method, so as to provide evidence-based reference for clinical treatment. Methods: This study searched PubMed, PMC, CNKI, etc., to screen out randomized controlled trials related to traditional Chinese medicine in the treatment of chronic prostatitis. According to the key words, appropriate literature was selected for inclusion and reasonable exclusion. After reading the literature, the literature was screened according to the above criteria. The methodological quality of the literature was evaluated using the Cochrane Collaboration Risk Bias Assessment tool. RevMan5.4.1 software was used for meta-analysis of outcome measures. Results: A total of 17 articles were included in this study, including 1209 cases in the treatment group and 1214 cases in the control group. Among them, 11 studies reported the effectiveness and ineffectiveness of traditional Chinese medicine in the treatment of chronic prostatitis, and 11 studies reported the change of symptom index of traditional Chinese medicine (NIH-CPSI score) in the treatment of chronic prostatitis. Meta-analysis showed effective rate (95%CI (3.83, 8.49), P<0.00001), ineffective rate (95%CI (0.12, 0.26), P<0.00001), NIH-CPSI score (95%CI (-2.55,-1.20), P<0.00001) were statistically significant. Conclusion: According to the effective rate and NIH-CPSI score index, it can be considered that the traditional Chinese medicine related to kidney AIDS clearance method is safe and effective in the treatment of chronic prostatitis. Clinically, it can be used as an effective treatment for chronic prostatitis. (AU)


Assuntos
Humanos , Prostatite/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Doença Crônica , Medicamentos de Ervas Chinesas/uso terapêutico
13.
ACS Appl Mater Interfaces ; 15(19): 23662-23670, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37140536

RESUMO

Bioactive small molecules serve as invaluable biomarkers for recognizing modulated organismal metabolism in correlation with numerous diseases. Therefore, sensitive and specific molecular biosensing and imaging in vitro and in vivo are particularly critical for the diagnosis and treatment of a large group of diseases. Herein, a modular DNA tetrahedron-based nanomachine was engineered for the ultrasensitive detection of intracellular small molecules. The nanomachine was composed of three self-assembled modules: an aptamer for target recognition, an entropy-driven unit for signal reporting, and a tetrahedral oligonucleotide for the transportation of the cargo (e.g., the nanomachine and fluorescent markers). Adenosine triphosphate (ATP) was used as the molecular model. Once the target ATP bonded with the aptamer module, an initiator was released from the aptamer module to activate the entropy-driven module, ultimately activating the ATP-responsive signal output and subsequent signal amplification. The performance of the nanomachine was validated by delivering it to living cells with the aid of the tetrahedral module to demonstrate the possibility of executing intracellular ATP imaging. This innovative nanomachine displays a linear response to ATP in the 1 pM to 10 nM concentration range and demonstrates high sensitivity with a low detection limit of 0.40 pM. Remarkably, our nanomachine successfully executes endogenous ATP imaging and is able to distinguish tumor cells from normal ones based on the ATP level. Overall, the proposed strategy opens up a promising avenue for bioactive small molecule-based detection/diagnostic assays.


Assuntos
Técnicas Biossensoriais , DNA , Oligonucleotídeos , Trifosfato de Adenosina , Técnicas Biossensoriais/métodos , Limite de Detecção
14.
Adv Sci (Weinh) ; 10(19): e2301814, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37085743

RESUMO

MicroRNAs (miRNAs) can act as oncogenes or tumor suppressors, capable of up or down-regulating gene expression during tumorigenesis; they are diagnostic biomarkers or therapeutic targets for tumors. To detect low abundance of intracellular oncogenic miRNAs (onco-miRNAs) and realize synergistic gene therapy of onco-miRNAs and tumor suppressors, a smart nano-theranostic platform based on dual-miRNAs guided self-feedback tetrahedral entropy-driven DNA circuit is created. The platform as a delivery vehicle is a DNA tetrahedral framework, in which the entropy-driven DNA circuit achieves a dual-miRNAs guided self-feedback, between an in situ amplification of the onco-miRNAs and activation of suppressor miRNAs release. To test this platform, dual-miRNAs are selected, miRNA-155, an up-regulated miRNA, as cancer indicators, and miRNA-122, a down-regulated miRNA as therapy targets in hepatocellular carcinoma, respectively. Through the circuit, the platform to detect onco-miRNAs at femtomolar level as well as visualized miRNAs inside cells, fixed tissues, and mice is programmed. Furthermore, triggered by miRNA-155, preloaded miRNA-122 is amplified via the self-feedback and released into target cells; the sudden increase of miRNA-122 and simultaneous decrease of miRNA-155 synergistically served as therapeutic drugs for gene regulation with enhanced antitumor efficacy and superior biosafety. It is envisioned that this nano-theranostic platform will initiate an essential step toward tumor theranostics in personalized/precise medicine.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Medicina de Precisão , Retroalimentação , Entropia , DNA
16.
J Tradit Chin Med ; 43(1): 34-41, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36639993

RESUMO

OBJECTIVE: To investigate the antitumour efficacy of luteolin on gastric cancer (GC) and study the mechanism underpinning the action. METHODS: Effects of luteolin on cell growth inhibition, apoptosis, and cell cycle arrest in MKN45 cells were investigated using the cell counting kit-8 assay. Changes in the mitochondrial membrane potential after luteolin treatment were assessed using 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanineiodi-de (JC-1) staining. To investigate whether apoptotic effect by luteolin is related to the phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) pathway, cells were additionally treated with LY294002, a PI3K/Akt pathway inhibitor. Moreover, the expressions of apoptosis-related proteins, namely B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein (Bax), Akt, p-Akt, caspase-3, and cytochrome C, were detected after luteolin treatment. RESULTS: The study revealed that in MKN45 cells, luteolin could inhibit the cell proliferation in a time- and dose-dependent manner; block the cell cycle in the S-phase; induce apoptosis; reduce the mitochondrial membrane potential; increase the expression of Bax, caspase-3, and cytochrome C; and decrease the expression of Bcl-2 and p-Akt. Luteolin might be involved in the PI3K/Akt signalling pathway, indicating that this pathway could be a therapeutic target for GC treatment. CONCLUSION: Luteolin could inhibit the proliferation of GC cells and block the cell cycle in the S-phase. The mechanism of inducing apoptosis in these cells was related to the PI3K/Akt signalling pathway.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Neoplasias Gástricas , Humanos , Apoptose , Proteína X Associada a bcl-2/metabolismo , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células , Citocromos c , Luteolina/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2 , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
17.
Chinese Journal of Oncology ; (12): 519-524, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984752

RESUMO

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).


Assuntos
Humanos , Antineoplásicos/efeitos adversos , Dose Máxima Tolerável , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Estudos Prospectivos
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-992699

RESUMO

Objective:To investigate the application of artificial intelligence based on the neural network radiation field in repair of soft tissue defects at lower limbs.Methods:A retrospective analysis was performed of the 23 patients who had been admitted to Department of Orthopedic Surgery, Renmin Hospital of Wuhan University from June 2020 to May 2022 for soft tissue defects at lower limbs. There were 14 males and 9 females, aged (38.6±6.7) years. Causes for soft tissue defects: traffic injury in 9 cases, benign or malignant primary soft tissue tumor in 6 cases, mechanical injury in 4 cases, crush injury in 2 cases, and chronic ulcer in 2 cases. Defect locations: the thigh in 3 cases, the lower leg in 7 cases, and the ankle and distal foot in 13 cases. The areas of soft tissue defect ranged from 6.0 cm×3.8 cm to 14.7 cm×12.8 cm. The defects were repaired and reconstructed by transplantation of an anterolateral femoral free flap in 7 cases and a pedicled flap in 16 cases with the assistance of artificial intelligence based on the neural network radiation field, a cutting-edge artificial intelligence algorithm that can quickly construct and process three-dimensional model images through volume rendering under the radiation field. The flap survival rate, aesthetic satisfaction before and after treatment, time for skin flap harvesting and transplantation, functional recovery of lower limbs and incidence of complications were recorded.Results:All the 23 patients were followed up for 32(28, 36) weeks. All the flaps were harvested smoothly and survived. The time for flap harvesting and transplantation was 65.8(50.0, 76.0) min. The aesthetic satisfaction scored (2.3±0.7) points before treatment and (8.4±1.6) points 4 weeks after treatment, showing a statistically significant difference ( P<0.05). The skin flaps healed well with no complications such as hematoma or infection in all but one patient who suffered from superficial necrosis at the distal skin flap due to venous crisis but healed with a scar. On average, the functional recovery of lower limbs scored 23.7(22.0, 25.0) points at 12 weeks after operation according to the Enneking evaluation system, and the functional recovery of lower limbs was 79% (23.7/30.0). Conclusion:Application of artificial intelligence based on the neural network radiation field can achieve ideal results in repair of soft tissue defects at lower limbs, due to its advantages of rapid and accurate surgical procedures, limited damage to the donor site, and a short learning curve.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-992684

RESUMO

Objective:To evaluate the efficacy of arthroscopic minimally invasive reduction in the treatment of talus posterior process fractures.Methods:The clinical data were retrospectively studied of the 42 patients with talus posterior process fracture who had been admitted to Department of Orthopedics, The Fourth Hospital of Wuhan from January 2010 to June 2021. There were 25 males and 17 females, aged from 21 to 60 years (average, 40.5 years). They were assigned into 2 groups according to their different treatments. In the arthroscopic group of 15 cases, arthroscopic reduction and internal fixation (ARIF) were conducted via the posteromedial and posterolateral approaches; in the open reduction group of 27 cases, open reduction and internal fixation (ORIF) were conducted via the posteromedial para-Achilles approach. The 2 groups were compared in terms of operation time, blood loss, hospital stay, fracture clinical healing time, postoperative complications, and the American Society for Foot and Ankle Surgery (AOFAS) ankle-hindfoot score at one year postoperation.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P> 0.05). The arthroscopic group incurred significantly less blood loss [(32.0±11.5) mL], hospital stay [(5.3±1.8) d], and fracture clinical healing time [(4.6±1.0) months], and a significantly lower incidence of postoperative complications [20.0% (3/15)] than the open reduction group did [(80.0±15.2) mL, (8.4±2.4) d, (6.3±2.2) months, and 29.6% (8/27)], but significantly longer operation time [(74.0±8.9) min] than the open reduction group [(62.9±5.1) min] ( P<0.05). The AOFAS ankle-hindfoot scores at one year postoperation in both groups were higher than those before operation. The AOFAS ankle-hindfoot scores in the arthroscopic group [(83.0±13.0) points] were significantly higher than those in the open reduction group [(72.3±16.0) points] ( P<0.05). Conclusion:ARIF is a preferred minimally invasive treatment for talus posterior process fractures, because it leads to a smaller incision, less blood loss, shorter hospital stay, quicker clinical healing, a lower incidence of postoperative complications, and better functional improvement of the ankle and hindfoot than ORIF.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-992171

RESUMO

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

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