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1.
World J Emerg Med ; 15(5): 333-355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290598

RESUMO

In 2009, the World Health Organization included snakebite on the list of neglected tropical diseases, acknowledging it as a common occupational hazard for farmers, plantation workers, and others, causing tens of thousands of deaths and chronic physical disabilities every year. This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims. These recommendations are based on clinical experience and clinical research evidence. This guideline focuses on the following topics: snake venom, clinical manifestations, auxiliary examination, diagnosis, treatments, and prevention.

2.
Int J Ophthalmol ; 17(9): 1606-1613, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296564

RESUMO

AIM: To determine whether etomidate (ET) has a protective effect on retinal ganglion cells (RGCs) injured with hydrogen peroxide (H2O2) and to explore the potential mechanism underlying the antioxidative stress effect of ET. METHODS: Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and Thy1.1. An injury model of H2O2-induced RGCs oxidative stress was established in vitro. Cells were pretreated with different concentrations of ET (1, 5, and 10 µmol/L) for 4h, followed by further exposure to H2O2 at 1000 µmol/L. Cell counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12, 24, and 48h after H2O2 stimulation. The levels of nitric oxide, malondialdehyde, and glutathione in culture media were measured at these time points. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12, 24, and 48h after H2O2 stimulation and in the retina at 12h after optic nerve transection (ONT). RESULTS: The applications of 5 and 10 µmol/L of ET significantly increased the viability of RGCs. Results from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs at 12, 24 and 48h after H2O2 stimulation, as well as in ET-treated retinas at 12h after ONT. Western blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein, along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in vivo. CONCLUSION: ET is a neuroprotective agent in primary cultured RGCs injured by H2O2. The effect of ET is dose-dependent with the greatest effect being at 10 µmol/L. ET plays an antioxidant role by inhibiting iNOS, up-regulating Nrf2/HO-1, decreasing the production of acrolein, and increasing the scavenge of acrolein.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39230437

RESUMO

Objective: This study aimed to predict therapeutic efficacy among diffuse large B-cell lymphoma (DLBCL) after R-CHOP (-like) therapy using baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) radiomics. Methods: A total of 239 patients with DLBCL were enrolled in this study, with 82 patients having refractory/relapsed disease. The radiomics signatures were developed using a stacking ensemble approach. The efficacy of the radiomics signatures, the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), conventional PET parameters model, and their combinations in assessing refractory/relapse risk were evaluated using receiver operating characteristic (ROC) curves, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and decision curve analysis. Results: The stacking model, along with the integrated model that combines stacking with the NCCN-IPI and SDmax (the distance between the two lesions farthest apart, normalized to the patient's body surface area), showed remarkable predictive capabilities with a high area under the curve (AUC), sensitivity, specificity, PPV, NPV, accuracy, and significant net benefit of the AUC (NB-AUC). Although no significant differences were observed between the combined and stacking models in terms of the AUC in either the training cohort (AUC: 0.992 vs. 0.985, p = 0.139) or the testing cohort (AUC: 0.768 vs. 0.781, p = 0.668), the integrated model exhibited higher values for sensitivity, PPV, NPV, accuracy, and NB-AUC than the stacking model. Conclusion: Baseline PET radiomics could predict therapeutic efficacy in DLBCL after R-CHOP (-like) therapy, with improved predictive performance when incorporating clinical features and SDmax.

5.
Clin Transl Oncol ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251494

RESUMO

PURPOSE: This retrospective study was undertaken to assess the predictive efficacy of 18F-FDG PET/CT -derived radiomic features concerning the co-mutation status of epidermal growth factor receptor (EGFR) and TP53 in LUAD. METHODS: A cohort of 150 LUAD patients underwent pretreatment 18F-FDG PET/CT scans with known mutation status of EGFR and TP53 were collected. The feature extraction based on their PET/CT images utilized the Pyradiomics package based on the 3D Slicer. The optimal radiomic features were selected through correlation analysis and the Gradient Boosting Decision Tree (GBDT) algorithm, followed by the construction of the radiomic model. The clinical model incorporated meaningful clinical variables, whereas the complex model integrated both the radiomic and clinical models. The area under the receiver operating characteristic curve (AUC) facilitated the comparison of prediction performance across the three models. The DCA gauged the clinical utility of these models. RESULTS: The patient cohort was randomly allocated into a training set (n = 105) and a validation set (n = 45) in a 7:3 ratio. Eleven PET and eleven CT optimal radiomic features were selected to construct the radiomic model. The model showed a good ability to discriminate the co-occurrence of EGFR and TP53, with AUC equal to 0.850 in the training set, and 0.748 in the validation set, compared with 0.750 and 0.626 for the clinical model. The complex model exhibited the highest AUC values, with 0.880 and 0.794 in both sets, but there were no significant differences compared to the radiomic model. The DCA revealed favorable clinical value.

6.
Front Med (Lausanne) ; 11: 1453421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39175818

RESUMO

Objective: To compare the effectiveness of radiomic features based on 18F-FDG PET/CT images within (intranodular) and around (perinodular) lung nodules/masses in distinguishing between lung adenocarcinoma and pulmonary granulomas. Methods: For this retrospective study, 18F-FDG PET/CT images were collected for 228 patients. Patients diagnosed with lung adenocarcinoma (n = 156) or granulomas (n = 72) were randomly assigned to a training (n = 159) and validation (n = 69) groups. The volume of interest (VOI) of intranodular, perinodular (1-5 voxels, termed Lesion_margin1 to Lesion_margin5) and total area (intra- plus perinodular region, termed Lesion_total1 to Lesion_total5) on PET/CT images were delineated using PETtumor and Marge tool of segmentation editor. A total of 1,037 radiomic features were extracted separately from PET and CT images, and the optimal features were selected to develop radiomic models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Good and acceptable performance was, respectively, observed in the training (AUC = 0.868, p < 0.001) and validation (AUC = 0.715, p = 0.004) sets for the intranodular radiomic model. Among the perinodular models, the Lesion_margin2 model demonstrated the highest AUC in both sets (0.883 and 0.616, p < 0.001 and p = 0.122). Similarly, in terms of total models, Lesion_total2 model was found to outperform others in the training (AUC = 0.879, p < 0.001) and validation (AUC = 0.742, p = 0.001) sets, slightly surpassing the intranodular model. Conclusion: When intra- and perinodular radiomic features extracted from the immediate vicinity of the nodule/mass up to 2 voxels distance on 18F-FDG PET/CT imaging are combined, improved differential diagnostic performance in distinguishing between lung adenocarcinomas and granulomas is achieved compared to the intra- and perinodular radiomic features alone.

7.
Clin Transl Oncol ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083140

RESUMO

PURPOSE: The objective of this investigation is to explore the capability of baseline 18F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI). METHODS: 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index). RESULTS: 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan--Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05). CONCLUSIONS: The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI.

8.
Anal Chim Acta ; 1309: 342685, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772667

RESUMO

The monitoring of heavy metal ions in ocean is crucial for environment protection and assessment of seawater quality. However, the detection of heavy metal ions in seawater with electrochemical sensors, especially for long-term monitoring, always faces challenges due to marine biofouling caused by the nonspecific adsorption of microbial and biomolecules. Herein, an electrochemical aptasensor, integrating both antifouling and antibacterial properties, was developed for the detection of Hg2+ in the ocean. In this electrochemical aptasensor, eco-friendly peptides with superior hydrophilicity served as anti-biofouling materials, preventing nonspecific adsorption on the sensing interface, while silver nanoparticles were employed to eliminate bacteria. Subsequently, a ferrocene-modified aptamer was employed for the specific recognition of Hg2+, leveraging the aptamer's ability to fold into a thymine-Hg2+-thymine (T-Hg2+-T) structure upon interaction, and bringing ferrocene nearer to the sensor surface, significantly amplifying the electrochemical response. The prepared electrochemical aptasensor significantly reduced the nonspecific adsorption in seawater while maintaining sensitive electrochemical response. Furthermore, the biosensor exhibited a linear response range of 0.01-100 nM with a detection limit of 2.30 pM, and realized the accurate monitoring of mercury ions in real marine environment. The research results offer new insights into the preparation of marine antifouling sensing devices, and it is expected that sensors with antifouling and antimicrobial capabilities will find broad applications in the monitoring of marine pollutants.


Assuntos
Antibacterianos , Incrustação Biológica , Técnicas Biossensoriais , Técnicas Eletroquímicas , Mercúrio , Água do Mar , Mercúrio/análise , Água do Mar/química , Água do Mar/microbiologia , Técnicas Eletroquímicas/métodos , Antibacterianos/análise , Antibacterianos/farmacologia , Técnicas Biossensoriais/métodos , Incrustação Biológica/prevenção & controle , Aptâmeros de Nucleotídeos/química , Prata/química , Poluentes Químicos da Água/análise , Nanopartículas Metálicas/química , Limite de Detecção , Compostos Ferrosos/química , Metalocenos
9.
Environ Technol ; : 1-12, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38525909

RESUMO

Heat pump drying is a low-carbon method of sludge drying. The operating temperature of a heat pump is generally not more than 70℃. To improve the drying efficiency of heat pump dryers, the effects of air parameters and additives on sludge drying characteristics at low temperatures were studied. The sludge drying experiments were conducted at an air temperature 50-70℃ and an air velocity of 0.5-1.7 m/s. The experimental results showed that the increase of air temperature, velocity and the addition ratio of additives can accelerate the sludge drying process. The average and maximum drying rates of sludge pre-conditioned by CaO and sawdust increased by 14.23% and 25.71%, respectively, compared with those of pure sludge. The two-way analysis of variance (ANOVA) revealed that the influence of air temperature on the sludge drying was higher than that of air velocity. Five reference models were fitted by the drying experiment data. The Page model has the highest R2, so it is the most suitable model to predict the drying time of sludge at low temperatures.

10.
Life Sci ; 336: 122329, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38052321

RESUMO

A variety of cancer cells exhibit dysregulated lipid metabolism, characterized by excessive intracellular lipid accumulation, and clear cell renal cell carcinoma (ccRCC) is the most typical disease with these characteristics. As the most common malignancy of all renal cell carcinomas (RCCs), ccRCC is typically characterized by a large accumulation of lipids and glycogen in the cytoplasm and a nucleus that is squeezed by the accumulated lipid droplets and localized to the marginal areas within the cytoplasm. This lipid accumulation has been found to be critically involved in the maintenance of malignant features observed in various cancers. Firstly, it maintains the persistent proliferative and metastasis properties of cancer cells. Secondly, it acts as a buffer against lipid peroxidation, preventing lipid peroxidation-induced ferroptosis. Moreover, lipids can diminish the sensitivity of cancer cells to radiotherapy. As ccRCC is a type of cancer with high lipid synthesis, targeting lipid synthesis-related genes in cancer cells may be a promising therapeutic modality for single treatment or in combination with radiotherapy, chemotherapy, and immunotherapy. This may revolutionize the choice of treatment modality for ccRCC patients. In this review, we concentrate on the current status and progress of research on lipid biosynthesis in ccRCC and the potential applications of targeting lipid synthesis to treat ccRCC. At last, we propose perspective and future research directions for targeting inhibition of lipid biosynthesis in combination with conventional therapeutic approaches for the treatment of ccRCC, which will help to evolve the therapeutic model.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Neoplasias Renais/metabolismo , Metabolismo dos Lipídeos , Lipogênese , Lipídeos/uso terapêutico
11.
Poult Sci ; 103(1): 103231, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37980764

RESUMO

The meat production of broilers is crucial to economic benefits of broiler industries, while the slaughter performance of broilers is directly determined by skeletal muscle development. Hence, the broiler breeding for growth traits shows a great importance. As a kind of small noncoding RNA, microRNA (miRNA) can regulate the expression of multiple genes and perform a wide range of regulation in organisms. Currently, more and more studies have confirmed that miRNAs are closely associated with skeletal muscle development of chickens. Based on our previous miR-seq analysis (accession number: PRJNA668199), miR-460b-5p was screened as one of the key miRNAs probably involved in the growth regulation of chickens. However, the regulatory effect of miR-460b-5p on the development of chicken skeletal muscles is still unclear. Therefore, miR-460b-5p was further used for functional validation at the cellular level in this study. The expression pattern of miR-460b-5p was investigated in proliferation and differentiation stages of chicken primary myoblasts. It was showed that the expression level of miR-460b-5p gradually decreased from the proliferation stage (GM 50%) to the lowest at 24 h of differentiation. As differentiation proceeded, miR-460b-5p expression increased significantly, reaching the highest and stabilizing at 72 h and 96 h of differentiation. Through mRNA quantitative analysis of proliferation marker genes, CCK-8 and Edu assays, miR-460b-5p was found to significantly facilitate the transition of myoblasts from G1 to S phase and promote chicken myoblast proliferation. mRNA and protein quantitative analysis of differentiation marker genes, as well as the indirect immunofluorescence results of myotubes, revealed that miR-460b-5p significantly stimulated myotube development and promote chicken myoblast differentiation. In addition, the target relationship was validated for miR-460b-5p according to the dual-luciferase reporter assay and mRNA quantitative analysis, which indicates that miR-460b-5p was able to regulate RBM19 expression by specifically binding to the 3' UTR of RBM19. In summary, miR-460b-5p has positive regulatory effects on the proliferation and differentiation of chicken myoblasts, and RBM19 is a target gene of miR-460b-5p.


Assuntos
Galinhas , MicroRNAs , Animais , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Mioblastos , Regiões 3' não Traduzidas , Diferenciação Celular , Desenvolvimento Muscular/genética
12.
J Am Chem Soc ; 145(49): 26915-26924, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38019775

RESUMO

Exploring bidirectional CO2/HCO2- catalysis holds significant potential in constructing integrated (photo)electrochemical formate fuel cells for energy storage and applications. Herein, we report selective CO2/HCO2- electrochemical interconversion by exploiting the flexible coordination modes and rich redox properties of a versatile iron-thiolate platform, Cp*Fe(II)L (L = 1,2-Ph2PC6H4S-). Upon oxidation, this iron complex undergoes formate binding to generate a diferric formate complex, [(L-)2Fe(III)(µ-HCO2)Fe(III)]+, which exhibits remarkable electrocatalytic performance for the HCO2--to-CO2 transformation with a maximum turnover frequency (TOFmax) ∼103 s-1 and a Faraday efficiency (FE) ∼92(±4)%. Conversely, this iron system also allows for reduction at -1.85 V (vs Fc+/0) and exhibits an impressive FE ∼93 (±3)% for the CO2-to-HCO2- conversion. Mechanism studies revealed that the HCO2--to-CO2 electrocatalysis passes through dicationic [(L2)-•Fe(III)(µ-HCO2)Fe(III)]2+ generated by unconventional oxidation of the diferric formate species taking place at ligand L, while the CO2-to-HCO2- reduction involves a critical intermediate of [Fe(II)-H]- that was independently synthesized and structurally characterized.

14.
Cell Discov ; 9(1): 84, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37550284

RESUMO

Tumor development, involving both cell growth (mass accumulation) and cell proliferation, is a complex process governed by the interplay of multiple signaling pathways. TET2 mainly functions as a DNA dioxygenase, which modulates gene expression and biological functions via oxidation of 5mC in DNA, yet whether it plays a role in regulating cell growth remains unknown. Here we show that TET2 suppresses mTORC1 signaling, a major growth controller, to inhibit cell growth and promote autophagy. Mechanistically, TET2 functions as a 5mC "eraser" by mRNA oxidation, abolishes YBX1-HuR binding and promotes decay of urea cycle enzyme mRNAs, thus negatively regulating urea cycle and arginine production, which suppresses mTORC1 signaling. Therefore, TET2-deficient tumor cells are more sensitive to mTORC1 inhibition. Our results uncover a novel function for TET2 in suppressing mTORC1 signaling and inhibiting cell growth, linking TET2-mediated mRNA oxidation to cell metabolism and cell growth control. These findings demonstrate the potential of mTORC1 inhibition as a possible treatment for TET2-deficient tumors.

15.
Signal Transduct Target Ther ; 8(1): 297, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37563110

RESUMO

Ten-eleven translocation (TET) family proteins (TETs), specifically, TET1, TET2 and TET3, can modify DNA by oxidizing 5-methylcytosine (5mC) iteratively to yield 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxycytosine (5caC), and then two of these intermediates (5fC and 5caC) can be excised and return to unmethylated cytosines by thymine-DNA glycosylase (TDG)-mediated base excision repair. Because DNA methylation and demethylation play an important role in numerous biological processes, including zygote formation, embryogenesis, spatial learning and immune homeostasis, the regulation of TETs functions is complicated, and dysregulation of their functions is implicated in many diseases such as myeloid malignancies. In addition, recent studies have demonstrated that TET2 is able to catalyze the hydroxymethylation of RNA to perform post-transcriptional regulation. Notably, catalytic-independent functions of TETs in certain biological contexts have been identified, further highlighting their multifunctional roles. Interestingly, by reactivating the expression of selected target genes, accumulated evidences support the potential therapeutic use of TETs-based DNA methylation editing tools in disorders associated with epigenetic silencing. In this review, we summarize recent key findings in TETs functions, activity regulators at various levels, technological advances in the detection of 5hmC, the main TETs oxidative product, and TETs emerging applications in epigenetic editing. Furthermore, we discuss existing challenges and future directions in this field.


Assuntos
Dioxigenases , Dioxigenases/genética , Dioxigenases/metabolismo , Epigênese Genética/genética , Metilação de DNA/genética , Regulação da Expressão Gênica , Oxirredução
16.
J Clin Invest ; 133(9)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37115693

RESUMO

How cancer cells evade the therapeutic effects of immune checkpoint blockade is largely unknown. Here, we report that fibrinogen-like protein 1 (FGL1), a newly identified immune checkpoint ligand, was modified by acetylation at Lys 98 in hepatocellular carcinoma (HCC), which targeted it for proteasomal degradation. Sirtuin 2 (SIRT2) deacetylated and stabilized FGL1, thus promoting immune evasion. Notably, the SIRT2 inhibitor 2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide (AGK2) enhanced acetylation of FGL1 and reduced FGL1 protein levels in vitro. The combination of AGK2 and programmed death ligand 1 (PD-L1) blockade effectively suppressed tumor growth and improved overall survival of mice. Furthermore, aspirin, an old drug, could directly acetylate FGL1 at Lys 98 and promote its degradation in vitro. Aspirin enhanced the immunotherapeutic efficacy, induced tumor regression, and extended the lifespan of tumor-bearing mice. Furthermore, the SIRT2/FGL1 axis was expressed in HCC specimens. Collectively, these findings unveil an acetylation-mediated regulation of FGL1, identify a potential target for HCC immunotherapy, and provide therapeutic strategies for the clinical treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Antígeno B7-H1 , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Fibrinogênio/genética , Imunoterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Sirtuína 2
17.
Molecules ; 28(6)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36985709

RESUMO

Due to the stratum corneum barrier, resveratrol is difficult to be absorbed transdermally, limiting its anti-aging and skin-brightening effects. Furthermore, there is a lack of systematic studies on the efficacy of resveratrol in human skin, especially in three-dimensional skin models and clinical trials. To overcome the low transdermal delivery issue, we encapsulated resveratrol into nanoliposomes using the high-pressure homogenization method to develop an efficient transdermal drug delivery system, and systematically evaluated its anti-aging and skin-brightening efficacy via cell line models, a three-dimensional skin model and human skin. The resveratrol nanoliposomes effectively improved the transdermal penetration and retention of resveratrol and enhanced cellular uptake. In addition, compared to free resveratrol, resveratrol nanoliposomes remarkably enhanced the skin-care effects by promoting the antioxidant capacity and collagen synthesis, inhibiting the secretion of matrix metalloproteinases, tyrosine activity and melanin synthesis. Notably, human clinical trials proved the anti-wrinkle and skin-brightening effectiveness of resveratrol nanoliposomes. Three levels of systematic studies indicated that resveratrol nanoliposomes could be a promising transdermal drug delivery system to enhance the anti-aging and skin-brightening effects of resveratrol.


Assuntos
Absorção Cutânea , Pele , Humanos , Resveratrol/farmacologia , Resveratrol/metabolismo , Administração Cutânea , Sistemas de Liberação de Medicamentos/métodos , Envelhecimento
18.
J Orthop Translat ; 38: 117-125, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36381249

RESUMO

Objectives: This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50-85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60 â€‹mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Results: Of the 448 randomized patients, 409 (LY06006, n â€‹= â€‹311; placebo, n â€‹= â€‹98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P â€‹< â€‹0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 â€‹N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs. Conclusion: In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies. The translational potential of this article: In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.

19.
Front Med (Lausanne) ; 10: 1327295, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259858

RESUMO

Background: Peritoneal dialysis (PD) is a common treatment method for patients with renal failure. While peritonitis and tube floating migration are commonly observed complications, visceral perforation caused by PD is relatively rare. We present a case report of a patient undergoing PD due to renal failure, who encountered two instances of visceral perforation. In both occurrences, Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) played a pivotal role in providing accurate diagnoses and precise localization of the perforation sites. This report underscores the paramount significance of SPECT/CT in diagnosing visceral perforations in the context of PD. Case presentation: A 73-year-old elderly male has been undergoing PD for 1 year due to renal failure. Recently, there has been impaired drainage of the PD catheter. The clinical team suspected the occurrence of peritonitis. The patient underwent a 99mTc Sodium Pertechnetate (99mTc-NaTcO4) SPECT/CT examination, which identified intestinal perforation. After 20 days of conservative treatment, a SPECT/CT follow-up examination revealed the resolution of the intestinal perforation, but a new bladder perforation emerged. The dialysis catheter was methodically and gradually withdrawn in stages while simultaneously performing bladder decompression. Following these interventions, the patient remained free from peritonitis and cystitis. Conclusion: The utilization of SPECT/CT proved to be highly valuable in the accurate diagnosis of visceral perforation, a relatively rare complication observed in PD patients.

20.
Medicine (Baltimore) ; 101(43): e31374, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36316948

RESUMO

RATIONALE: Disseminated cryptococcosis is extremely rare and is easily misdiagnosed as a malignant lymphoma. 18F-Fluorodeoxyglucose Positron Emission Tomography (PET)/ computed tomography (CT) may be useful to assess the involvement of disseminated cryptococcosis and to evaluate residual disease after treatment. PATIENT CONCERNS: A 21-years-old man presented with fever and cough for a month, with multiple red nodules scattered on the skin. 18F- Fluorodeoxyglucose PET/CT revealed multiple hypermetabolic lymph nodes in the upper and lower parts of the diaphragmatic region and hypermetabolic nodules in the skin. According to the PET/CT results, malignant lymphoma was considered a possibility, especially T-cell lymphoma involving the skin. DIAGNOSIS: Cryptococcosis was diagnosed using inguinal lymph node biopsy and blood culture. INTERVENTIONS: The patient received two months of amphotericin B, fluconazole, and half a month of meropenem. OUTCOMES: The patient's body temperature returned to normal and the red nodules on the skin disappeared. Most of the hypermetabolic enlarged lymph nodes disappeared, which was confirmed by reexamination with PET/CT. LESSONS: Disseminated cryptococcosis is easily misdiagnosed as malignant lymphoma, especially when the lymph nodes are more involved. When multiple hypermetabolic enlarged lymph nodes appear on PET/CT, except for lymphoma, specific infections should also be considered.


Assuntos
Criptococose , Linfoma , Masculino , Humanos , Adulto Jovem , Adulto , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Linfoma/diagnóstico por imagem , Linfoma/patologia , Linfonodos/patologia , Criptococose/diagnóstico por imagem , Criptococose/tratamento farmacológico , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodos
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