Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
1.
Physiol Mol Biol Plants ; 30(4): 619-631, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38737324

RESUMEN

Bletilla striata (Thunb.) Rchb.f., a medicinal plant in the Orchidaceae family, is mainly found in East Asia and has extensive pharmacological activities. Plant's volatile components are important active ingredients with a wide range of physiological activities, and B. striata has a special odor and unique volatile components. Yet it has received little attention, hindering a full understanding of its phytochemical components. Employing the ultrasonic-assisted extraction method, the volatile components of B. striata's fibrous root, bud, aerial part and tuber were extracted, resulting in yields of 0.06%, 0.64%, 3.38% and 4.47%, respectively. A total of 78 compounds were identified from their chemical profiles using gas chromatography-mass spectrometry (GC-MS), including 45 components with the main compounds of linoleic acid (content accounting for 31.23%), n-hexadecanoic acid (13.53%), and octadecanoic acid (9.5%) from the tuber, 34 components with the main compounds of eicosane, 2-methyl- (28.42%), linoelaidic acid (10.43%), linoleic acid (4.53%), and n-hexadecanoic acid (6.91%) from the fibrous root, 38 components with the main compounds of pentadeca-6,9-dien-1-ol (9.29%), n-hexadecanoic acid (11%), eicosane,2-methyl- (23.43%), and linoleic acid (23.53%) from the bud, and 27 components with the main compounds of linoelaidic acid (5.97%), n-hexadecanoic acid (15.99%), and linolenic acid ethyl ester (18.9%) from the aerial part. Additionally, the growth inhibition activity against colon cancer HCT116 cells was evaluated using sulforhodamine B (SRB) assay and the thiazolyl blue tetrazolium bromide (MTT) assay, and the accumulation of reactive oxygen species (ROS) was determined using dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining and fluorescence intensity analysis. The volatile extracts exhibited significant growth inhibitory efficacy against HCT116 cells, with half-maximal inhibitory concentration (IC50) values of 3.65, 2.32, 2.42 and 3.89 mg/mL in the SRB assay, and 3.55, 2.58, 3.12 and 4.80 mg/mL in the MTT assay for the root, bud, aerial part, and tuber, respectively. Notably, treatment with the aerial part extract caused morphological changes in the cells and significantly raised the intracellular ROS level. In summary, the chemical profiles of the volatile components of B. striata were revealed for the first time, demonstrating a certain tissue specificity. Additionally, it demonstrated for the first time that these volatile extracts possess potent anti-colon cancer activity, highlighting the importance of these volatile components in B. striata's medicinal properties.

2.
World J Urol ; 42(1): 243, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38639784

RESUMEN

PURPOSE: Reducing operative injuries is important in living donor nephrectomy. The robot-assisted transperitoneal approach has some advantages than traditional laparoscopic techniques. However, longer operation time and risks of abdominal complications indicate the need for improved techniques. The aim of this study is to present the robot-assisted laparoscopic retroperitoneal donor nephrectomy and evaluate its safety and feasibility. METHODS: This was a retrospective study. From June 2016 to December 2020, 218 living donors underwent robot-assisted laparoscopic retroperitoneal donor nephrectomy. Perioperative data such as operation time, warm ischemia time, length of stay and complications were collected and analyzed. To evaluate the feasibility of this surgical technique, the cumulative summation method was used to construct a learning curve. RESULTS: There were 60 male and 158 female donors aged 36-72 years, with an average age of 53.1 ± 6.8 years. Three patients (1.4%) were converted to open surgery. The mean operation time was 115.4 ± 41.9 min, the warm ischemia time was 206.6 ± 146.7 s, and the length of stay was 4.1 ± 1.4 days. Complications were reported in 22 patients (10.1%), three of whom (1.4%) had Clavien‒Dindo IIIa complications. No ileus occurred. No donors were readmitted. Four patients had delayed graft function. The cumulative summation curve showed that the number needed to reach proficiency was 33. The operation time and warm ischemia time after technical proficiency were 100.4 ± 21.6 min and 142.5 ± 50.7 s, respectively. CONCLUSION: Robot-assisted laparoscopic retroperitoneal donor nephrectomy is a safe and efficient technique that offers advantages of shorter operation time and no abdominal organ interference.


Asunto(s)
Trasplante de Riñón , Laparoscopía , Robótica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Nefrectomía/métodos , Laparoscopía/métodos , Donadores Vivos
3.
J Mol Med (Berl) ; 102(5): 655-665, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38436712

RESUMEN

NOD-like receptor family CARD domain containing 3 (NLRC3) is the intracellular protein belonging to NLR (NOD-like receptor) family. NLRC3 can negatively regulate inflammatory signal transduction pathways within the adaptive and innate immunocytes. However, studies need to elucidate the biological role of NLRC3 in bone remodeling. Herein, our study proved that NLRC3 prevents bone loss by inhibiting TNFα+ Th17 cell responses. In osteoporosis, NLRC3 attenuated TNFα+ Th17 cell accumulation in the bone marrow. However, osteoporosis (OP) development was aggravated without affecting bone marrow macrophage (BMM) osteoclastogenesis in NLRC3-deficient ovariectomized (OVX) mice. In this study, we transferred the wild-type and NLRC3-/- CD4+ cells into Rag1-/- mice. Consequently, we evidenced the effects of NLRC3 in CD4+ T cells on inhibiting the accumulation of TNFα + Th17 cells, thus restricting bone loss in the OVX mice. Simultaneously, NLRC3-/- CD4+ T cells promoted the recruitment of osteoclast precursors and inflammatory monocytes into the OVX mouse bone marrow. Mechanism-wise, NLRC3 reduced the secretion of TNFα + Th17 cells of RANKL, MIP1α, and MCP1, depending on the T cells. In addition, NLRC3 negatively regulated the Th17 osteoclastogenesis promoting functions via limiting the NF-κB activation. Collectively, this study appreciated the effect of NLRC3 on modulating bone mass via adaptive immunity depending on CD4+ cells. According to findings of this study, NLRC3 may be the candidate anti-OP therapeutic target. KEY MESSAGES: NLRC3 negatively regulated the Th17 osteoclastogenesis promoting functions via limiting the NF-κB activation. NLRC3 may be the candidate anti-OP therapeutic target.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular , Osteoclastos , Osteogénesis , Osteoporosis , Células Th17 , Factor de Necrosis Tumoral alfa , Animales , Células Th17/inmunología , Células Th17/metabolismo , Osteoporosis/metabolismo , Osteoporosis/etiología , Osteoporosis/inmunología , Osteoporosis/genética , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Osteoclastos/metabolismo , Femenino , Ratones Endogámicos C57BL , Ratones Noqueados , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología
4.
Nat Commun ; 15(1): 2098, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459034

RESUMEN

Yutu-2 rover conducted an exciting expedition on the 41st lunar day to investigate a fin-shaped rock at Longji site (45.44°S, 177.56°E) by extending its locomotion margin on perilous peaks. The varied locomotion encountered, especially multi-form wheel slippage, during the journey to the target rock, established unique conditions for a fin-grained lunar regolith analysis regarding bearing, shear and lateral properties based on terramechanics. Here, we show a tri-aspect characterization of lunar regolith and infer the rock's origin using a digital twin. We estimate internal friction angle within 21.5°-42.0° and associated cohesion of 520-3154 Pa in the Chang'E-4 operational site. These findings suggest shear characteristics similar to Apollo 12 mission samples but notably higher cohesion compared to regolith investigated on most nearside lunar missions. We estimate external friction angle in lateral properties to be within 8.3°-16.5°, which fills the gaps of the lateral property estimation of the lunar farside regolith and serves as a foundational parameter for subsequent engineering verifications. Our in-situ spectral investigations of the target rock unveil its composition of iron/magnesium-rich low-calcium pyroxene, linking it to the Zhinyu crater (45.34°S, 176.15°E) ejecta. Our results indicate that the combination of in-situ measurements with robotics technology in planetary exploration reveal the possibility of additional source regions contributing to the local materials at the Chang'E-4 site, implying a more complicated geological history in the vicinity.

5.
Cureus ; 16(2): e53395, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38314382

RESUMEN

BACKGROUND: Hydroxychloroquine (HCQ) influences both toll-like receptor (TLR) signaling and leukocyte activation, which are speculated to play a role in the pathogenesis of IgA nephropathy (IgAN). METHODS: This is a single-centered retrospective study involving 426 IgAN patients diagnosed from May 2016 to August 2020. All patients were matched according to a propensity score matching (PSM) to produce three groups: renin-angiotensin-aldosterone system inhibitors (RAASi) group (RAASi only), corticosteroids group (corticosteroids only or combined with RAASi), and HCQ group (HCQ only or combined with RAASi), consisting of 63 patients for each group. RESULTS: After PSM, the median urine protein/creatinine ratio (UPCR) of overall patients was 0.91 g/g, while their median serum creatinine was 87.00 µmol/L. After the median follow-up period of 11.03 months, the total remission rates of the RAASi group, corticosteroids group, and HCQ groups were 49.21% (n = 31), 74.60% (n = 47), and 52.38% (n = 33), respectively (p = 0.017). Thirteen (6.88%) patients experienced a decline in estimated glomerular filtration rate (eGFR) of more than 25% from baseline, including six (9.52%) patients in the RAASi group, three (4.76%) patients in the corticosteroids group, and four (6.35%) patients in HCQ group (p = 0.677). One (1.59%) patient in the HCQ group had blurred vision and continued to use HCQ after ruling out retinal lesions by ophthalmic examination. CONCLUSION: HCQ is effective in inducing remission and well-tolerated in IgAN patients with mild to moderate proteinuria.

6.
Int Immunopharmacol ; 126: 111135, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37977065

RESUMEN

The limited efficacy of immune checkpoint inhibitors (ICIs) in the treatment of advanced Esophageal Squamous Cell Carcinoma (ESCC) poses a challenge. Recent evidence suggests that tumor cells' insensitivity to cytotoxic T lymphocytes (CTLs) contributes to drug resistance against ICIs. Here, a particular tRNA-derived fragment called tRF-3024b has been identified as playing a significant role in tumor cell resistance to CTLs. Through tRF sequencing (tRF-seq), we observed a high expression of tRF-3024b in ESCC cells that survived co-culture with CTLs. Further in vitro studies demonstrated that tRF-3024b reduced the apoptosis of tumor cells when co-cultured with CTLs. The mechanism behind this resistance involves tRF-3024b promoting the expression of B-cell lymphoma-2 (BCL-2) by sequestering miR-192-5p, a microRNA that would normally inhibit BCL-2 expression. This means that tRF-3024b indirectly enhances the protective effects of BCL-2, reducing apoptosis in tumor cells. Rescue assays confirmed that the suppressive function of tRF-3024b relies on BCL-2. In summary, the tRF-3024b/miR-192-5p/BCL-2 axis sheds light on the crucial role of tRF-3024b in regulating BCL-2 expression. These findings offer valuable insights into strategies to enhance the response of ESCC to CTLs and improve the effectiveness of immunotherapy approaches in treating ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Linfocitos T Citotóxicos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular
8.
PeerJ ; 11: e16306, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37904848

RESUMEN

Background: According to the histopathology, lung adenocarcinoma (LUAD) could be divided into five distinct pathological subtypes, categorized as high-risk (micropapillary and solid) group, intermediate-risk (acinar and papillary) group, and low-risk (lepidic) group. Despite this classification, there is limited knowledge regarding the role of transcription factors (TFs) in the molecular regulation of LUAD histology patterns. Methods: Publish data was mined to explore the candidate TFs associated with high-risk histopathology in LUAD, which was validated in tissue samples. Colony formation, CCK8, EdU, transwell, and matrigel assays were performed to determine the biological function of FAM83A in vitro. Subcutaneous tumor-bearing in BALB/c nude mice and xenograft perivitelline injection in zebrafish were utilized to unreal the function of FAM83A in vivo. We also performed chromatin immunoprecipitation (ChIP), dual-luciferase reporter, and rescue assays to uncover the underline mechanism of FAM83A. Immunohistochemistry (IHC) was performed to confirm the oncogenic role of FAM83A in clinical LUAD tissues. Results: Screening the transcriptional expression data from TCGA-LUAD, we focus on the differentially expressed TFs across the divergent pathological subtypes, and identified that the expression of FAM83A is higher in patients with high-risk groups compared with those with intermediate or low-risk groups. The FAM83A expression is positively correlated with worse overall survival, progression-free survival, and advanced stages. Gain- and loss-of-function assays revealed that FAM83A promoted cell proliferation, invasion, and migration of tumor cell lines both in vivo and in vitro. Pathway enrichment analysis shows that FAM83A expression is significantly enriched in cell cycle-related pathways. The ChIP and luciferase reporter assays revealed that FAM83A hijacks the promoter of FOXM1 to progress the malignant LUAD, and the rescue assay uncovered that the function of FAM83A is partly dependent on FOXM1 regulation. Additionally, patients with high FAM83A expression positively correlated with higher IHC scores of Ki-67 and FOXM1, and patients with active FAM83A/FOXM1 axis had poor prognoses in LUAD. Conclusions: Taken together, our study revealed that the high-risk histological subtype-related FAM83A hijacks FOXM1 transcriptional regulation to promote malignant progression in lung adenocarcinoma, which implies targeting FAM83A/FOXM1 is the therapeutic vulnerability.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Animales , Ratones , Humanos , Neoplasias Pulmonares/genética , Ratones Desnudos , Pez Cebra/genética , Pronóstico , Regulación Neoplásica de la Expresión Génica/genética , Adenocarcinoma del Pulmón/genética , Luciferasas/metabolismo , Proteína Forkhead Box M1/genética , Proteínas de Neoplasias/genética
9.
Artículo en Inglés | MEDLINE | ID: mdl-37190977

RESUMEN

OBJECTIVE: Camrelizumab combination therapy for advanced or metastatic esophageal squamous cell carcinoma (ESCC) has considerable survival benefits. This study investigated the cost-effectiveness of camrelizumab combination therapy versus chemotherapy alone as a first-line treatment for patients with ESCC from the perspective of the Chinese healthcare system. METHODS: A three-state partitioned survival model was developed to estimate total costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) over a 20-year time horizon. Sensitivity and scenario analyses were also performed. RESULTS: Camrelizumab plus chemotherapy increased QALYs by 0.30 (0.43 LYs), with an incremental cost of $9,272. The ICERs for camrelizumab plus chemotherapy vs chemotherapy alone was $31,062/QALY ($21,599/LY), and the INHB was 0.05 QALY at the cost-effective threshold of $37,653/QALY (3 times China's GDP per capita). One-way sensitivity analyses showed that the ICER was the most sensitive to utility values in the PFS state. Probabilistic sensitivity analyses suggested that camrelizumab combination therapy had a probability of 74.04% cost-effectiveness at a threshold of $37,653/QALY. Scenario analyses confirmed that the findings were robust. CONCLUSIONS: Camrelizumab combination therapy is likely to have a cost-effectiveness advantage over chemotherapy alone for previously untreated advanced or metastatic ESCC in China.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Análisis Costo-Beneficio , Neoplasias Esofágicas/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica
10.
IEEE Trans Cybern ; 53(7): 4691-4703, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37224373

RESUMEN

Major challenges of controlling human-robot collaboration (HRC)-oriented modular robot manipulators (MRMs) include the estimation of human motion intention while cooperating with a robot and performance optimization. This article proposes a cooperative game-based approximate optimal control method of MRMs for HRC tasks. A harmonic drive compliance model-based human motion intention estimation method is developed using robot position measurements only, which forms the basis of the MRM dynamic model. Based on the cooperative differential game strategy, the optimal control problem of HRC-oriented MRM systems is transformed into a cooperative game problem of multiple subsystems. By taking advantage of the adaptive dynamic programming (ADP) algorithm, a joint cost function identifier is developed via the critic neural networks, which is implemented for solving the parametric Hamilton-Jacobi-Bellman (HJB) equation and Pareto optimal solutions. The trajectory tracking error under the HRC task of the closed-loop MRM system is proved to be ultimately uniformly bounded (UUB) by the Lyapunov theory. Finally, experiment results are presented, which reveal the advantage of the proposed method.


Asunto(s)
Robótica , Humanos , Dinámicas no Lineales , Redes Neurales de la Computación , Algoritmos
11.
Expert Rev Anti Infect Ther ; 21(2): 203-211, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36573685

RESUMEN

BACKGROUND: Drowned victims possibly obtain various pathogens from drowning sites. Using drowned renal donors to expand the donor pool still lacks consensus due to the potential risk of disease transmission. RESEARCH DESIGN AND METHODS: This retrospective study enrolled 38 drowned donor renal recipients in a large clinical center from August 2012 to February 2021. A 1:2 matched cohort was generated with donor demographics, including age, gender, BMI, and ICU durations. Donor microbiological results, recipient perioperative infections, and early post-transplant and first-year clinical outcomes were analyzed. RESULTS: Compared to the control group, drowned donors had significantly increased positive fungal cultures (36.84% vs.13.15%, p = 0.039). Recipients in the drowned group had significantly higher rates of gram-negative bacteria (GNB) and multidrug-resistant GNB infections (23.68% vs.5.26%, 18.42% vs. 3.95%, both p < 0.05). Other colonization and infections were also numerically more frequent in the drowned group. Drowned donor recipients receiving inadequate antibiotic prophylaxis had more perioperative bloodstream infections, higher DGF incidences, and more first-year respiratory tract infections and recipient loss than those receiving adequate prophylaxis (all p < 0.05). Clinical outcomes were similar between the adequate group and the control group. CONCLUSIONS: Drowned donors could be suitable options under wide-spectrum and adequate antimicrobial prophylaxis.


Asunto(s)
Ahogamiento , Trasplante de Riñón , Trasplante de Hígado , Humanos , Profilaxis Antibiótica/métodos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos
12.
Front Neurorobot ; 17: 1329589, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38322650

RESUMEN

Introduction: In the field of logistics warehousing robots, collaborative operation and coordinated control have always been challenging issues. Although deep learning and reinforcement learning methods have made some progress in solving these problems, however, current research still has shortcomings. In particular, research on adaptive sensing and real-time decision-making of multi-robot swarms has not yet received sufficient attention. Methods: To fill this research gap, we propose a YOLOv5-PPO model based on A3C optimization. This model cleverly combines the target detection capabilities of YOLOv5 and the PPO reinforcement learning algorithm, aiming to improve the efficiency and accuracy of collaborative operations among logistics and warehousing robot groups. Results: Through extensive experimental evaluation on multiple datasets and tasks, the results show that in different scenarios, our model can successfully achieve multi-robot collaborative operation, significantly improve task completion efficiency, and maintain target detection and environment High accuracy of understanding. Discussion: In addition, our model shows excellent robustness and adaptability and can adapt to dynamic changes in the environment and fluctuations in demand, providing an effective method to solve the collaborative operation problem of logistics warehousing robots.

13.
J Clin Med ; 11(22)2022 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-36431337

RESUMEN

PURPOSE: To compare the safety and efficacy of percutaneous paricalcitol injection with intravenously administered paricalcitol in treating parathyroid hyperplasia in patients with secondary hyperparathyroidism (SHPT). METHODS: This study was approved by the Ethics Committee of our institution. We retrospectively collected data on patients who received percutaneous paricalcitol injection (24 patients) and intravenously administered paricalcitol (22 patients) based on their intact parathyroid hormone (iPTH) level. Serum iPTH, calcium, phosphorus, and the volume of the parathyroid gland were measured at several indicated time points after treatment, and adverse events associated with the two treatments were evaluated. RESULTS: After 6 months of follow-up, we found that patients from the percutaneous injection group had significantly decreased levels of iPTH (from 1887.81 ± 726.81 pg/mL to 631.06 ± 393.06 pg/mL), phosphate (from 1.94 ± 0.36 mmol/L to 1.71 ± 0.34 mmol/L), and volume of the parathyroid gland (from 0.87 ± 0.50 cm3 to 0.60 ± 0.36 cm3), with relief from ostealgia within 48-72 h. In the intravenously administered group, the levels of iPTH decreased from 686.87 ± 260.44 pg/mL to 388.47 ± 167.36 pg/mL; while there was no significant change in phosphate levels, the volume of the parathyroid gland and ostealgia relief were observed at the end of follow-up. The serum calcium level did not significantly change, and no severe complications were observed in both groups. In vitro fluorescence-activated single cell sorting (FACS) analysis indicated that paricalcitol induced parathyroid cell apoptosis in a dose-dependent manner. CONCLUSIONS: Percutaneous paricalcitol injection is a selective treatment for SHPT in ESRD.

14.
Entropy (Basel) ; 24(9)2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36141190

RESUMEN

It is important for Mars exploration rovers to achieve autonomous and safe mobility over rough terrain. Terrain classification can help rovers to select a safe terrain to traverse and avoid sinking and/or damaging the vehicle. Mars terrains are often classified using visual methods. However, the accuracy of terrain classification has been less than 90% in read operations. A high-accuracy vision-based method for Mars terrain classification is presented in this paper. By analyzing Mars terrain characteristics, novel image features, including multiscale gray gradient-grade features, multiscale edges strength-grade features, multiscale frequency-domain mean amplitude features, multiscale spectrum symmetry features, and multiscale spectrum amplitude-moment features, are proposed that are specifically targeted for terrain classification. Three classifiers, K-nearest neighbor (KNN), support vector machine (SVM), and random forests (RF), are adopted to classify the terrain using the proposed features. The Mars image dataset MSLNet that was collected by the Mars Science Laboratory (MSL, Curiosity) rover is used to conduct terrain classification experiments. The resolution of Mars images in the dataset is 256 × 256. Experimental results indicate that the RF classifies Mars terrain at the highest level of accuracy of 94.66%.

15.
Front Pharmacol ; 13: 830380, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35614942

RESUMEN

Background: Tislelizumab, a new high-affinity programmed cell death protein-1 (PD-1) inhibitor, significantly prolonged the overall survival in pretreated non-small-cell lung cancer (NSCLC). This study aimed to assess the cost-effectiveness of tislelizumab versus docetaxel for this population in China. Methods: A three-state partitioned survival model was developed to simulate advanced NSCLC. Efficacy and safety data were based on a global phase 3 clinical trial (RATIONALE 303). Utilities were mainly extracted from previously published resources. Costs were calculated from the Chinese healthcare system's perspective, and only direct medical costs were covered. The main outcomes included total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were carried to test the uncertainty of the modeling results. In addition, several scenarios including tislelizumab price before negotiation, different docetaxel price calculation, 50-year time horizon, and alternative utility values were assessed. Results: The model predicted an average gain of 0.62 LYs and 0.51 QALY for tislelizumab vs. docetaxel, at the additional cost of $9,219. The resulting ICER was $15,033.92/LY and $18,122.04/QALY, both below the cost-effective threshold (CET) of three times gross domestic product (GDP) per capita in China. Sensitivity analyses showed that the results are robust over a plausible range for majority of inputs. Utility of progression-free survival (PFS), followed by the price of tislelizumab, had the greatest impact on the ICER. The probability of being cost-effective for tislelizumab was 96.79% at the CET we set. Conclusion: Tislelizumab improves survival, increases QALYs, and can be considered a cost-effective option at current price compared with docetaxel for pretreated advanced NSCLC in China.

16.
FASEB J ; 36(6): e22342, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35524750

RESUMEN

Renal fibrosis is the final common outcome of chronic kidney disease (CKD), which remains a huge challenge due to a lack of targeted treatment. Growing evidence suggests that during the process of CKD, the integrity and function of mitochondria in renal tubular epithelial cells (TECs) are generally impaired and strongly connected with the progression of renal fibrosis. Mitophagy, a selective form of autophagy, could remove aberrant mitochondria to maintain mitochondrial homeostasis. Deficiency of mitophagy has been reported to aggravate renal fibrosis. However, whether induction of mitophagy could alleviate renal fibrosis has not been stated. In this study, we explored the effect of mitophagy activation by UMI-77, a compound recently verified to induce mitophagy, on murine CKD model of unilateral ureteral obstruction (UUO) in vivo and TECs in vitro. In UUO mice, we found the changes of mitochondrial damage, ROS production, transforming growth factor (TGF)-ß1/Smad pathway activation, as well as epithelial-mesenchymal transition phenotype and renal fibrosis, and these changes were ameliorated by mitophagy enhancement using UMI-77. Moreover, TEC apoptosis, nuclear factor (NF)-κB signaling activation, and interstitial inflammation after UUO were significantly mitigated by augmented mitophagy. Then, we found UMI-77 could effectively and safely induce mitophagy in TECs in vitro, and reduced TGF-ß1/Smad signaling and downstream profibrotic responses in TGF-ß1-treated TECs. These changes were restored by a mitophagy inhibitor. In conclusion, we demonstrated that mitophagy activation protected against renal fibrosis through improving mitochondrial fitness, downregulating TGF-ß1/Smad signaling and alleviating TEC injuries and inflammatory infiltration in kidneys.


Asunto(s)
Insuficiencia Renal Crónica , Animales , Células Epiteliales/metabolismo , Fibrosis , Riñón/metabolismo , Ratones , Mitocondrias/metabolismo , Mitofagia , FN-kappa B/metabolismo , Insuficiencia Renal Crónica/metabolismo , Sulfonamidas , Tioglicolatos , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/metabolismo
17.
Comput Intell Neurosci ; 2022: 1008617, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35463281

RESUMEN

The traveling salesman problem is a typical NP hard problem and a typical combinatorial optimization problem. Therefore, an improved artificial cooperative search algorithm is proposed to solve the traveling salesman problem. For the basic artificial collaborative search algorithm, firstly, the sigmoid function is used to construct the scale factor to enhance the global search ability of the algorithm; secondly, in the mutation stage, the DE/rand/1 mutation strategy of differential evolution algorithm is added to carry out secondary mutation to the current population, so as to improve the calculation accuracy of the algorithm and the diversity of the population. Then, in the later stage of the algorithm development, the quasi-reverse learning strategy is introduced to further improve the quality of the solution. Finally, several examples of traveling salesman problem library (TSPLIB) are solved using the improved artificial cooperative search algorithm and compared with the related algorithms. The results show that the proposed algorithm is better than the comparison algorithm in solving the travel salesman problem and has good robustness.


Asunto(s)
Algoritmos , Solución de Problemas , Mutación , Viaje
18.
Sensors (Basel) ; 21(21)2021 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-34770569

RESUMEN

Copper elbows are an important product in industry. They are used to connect pipes for transferring gas, oil, and liquids. Defective copper elbows can lead to serious industrial accidents. In this paper, a novel model named YOT-Net (YOLOv3 combined triplet loss network) is proposed to automatically detect defective copper elbows. To increase the defect detection accuracy, triplet loss function is employed in YOT-Net. The triplet loss function is introduced into the loss module of YOT-Net, which utilizes image similarity to enhance feature extraction ability. The proposed method of YOT-Net shows outstanding performance in copper elbow surface defect detection.


Asunto(s)
Algoritmos , Cobre , Codo
20.
Adv Ther ; 38(10): 5116-5126, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34417989

RESUMEN

INTRODUCTION: The survival of patients with relapsed small cell lung cancer (SCLC) has achieved little progress in the last several decades. ALTER1202 confirmed the efficacy and safety of anlotinib as a third- or further-line option for relapsed SCLC. This study aimed to assess the cost-effectiveness of anlotinib compared with placebo as third- or further-line treatment for advanced SCLC in China. METHODS: A Markov model was developed to simulate the process of advanced SCLC and estimate the incremental cost-effectiveness ratio (ICER) of anlotinib versus placebo. The health outcomes and utilities were derived from the ALTER1202 (NCT03059797) and published sources, respectively. Total costs were calculated from the perspective of Chinese society. One-way and probabilistic sensitivity analyses (PSA) were conducted to explore the model uncertainties. RESULTS: Anlotinib was estimated to result in an additional 0.12 quality-adjusted life-years (QALYs) at an incremental cost of $2131.32, resulting in an ICER of $17,741.94/QALY. The ICER did not exceed the willingness-to-pay (WTP) threshold of $30,833 per QALY, which was three times the gross domestic product (GDP) per capita of China in 2019. One-way sensitivity analysis showed that the cost of anlotinib exerted the maximum influence on the result of the model, followed by the utility of progression-free survival (PFS) state in the anlotinib group and median overall survival (mOS) in the anlotinib group. In PSA, the probability of anlotinib being cost-effective was 26.6% and 78.5% when the WTP threshold was one and three times the GDP per capita, respectively. CONCLUSION: Anlotinib is likely to be a cost-effective option compared with placebo for patients with relapsed SCLC who experience failure of at least two lines of chemotherapy in China.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , China , Análisis Costo-Beneficio , Humanos , Indoles , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Años de Vida Ajustados por Calidad de Vida , Quinolinas , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...