Publications by authors named "Ye Peng"

414 Publications

Therapeutic applications of toll-like receptors (TLRs) agonists in AML.

Clin Transl Oncol 2022 Aug 13. Epub 2022 Aug 13.

Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 58 Shangtang Road, Hangzhou, 310014, Zhejiang, People's Republic of China.

Acute myeloid leukemia (AML) is an aggressive type of blood cancer affecting bone marrow (BM). In AML, hematopoietic precursors are arrested in the early stages of development and are defined as the presence of ≥ 20% blasts (leukemia cells) in the BM. Toll-like receptors (TLR) are major groups of pattern recognition receptors expressed by almost all innate immune cells that enable them to detect a wide range of pathogen-associated molecular patterns and damage-associated molecular patterns to prime immune responses toward adaptive immunity. Because TLRs are commonly expressed on transformed immune system cells (ranging from blasts to memory cells), they can be a potential option for developing efficient clinical alternatives in hematologic tumors. This is because several in vitro and in vivo investigations have demonstrated that TLR signaling increased the immunogenicity of AML cells, making them more vulnerable to T cell-mediated invasion. This study aimed to review the current knowledge in this field and provide some insight into the therapeutic potentials of TLRs in AML.
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http://dx.doi.org/10.1007/s12094-022-02917-5DOI Listing
August 2022

Cost-Effectiveness Analysis of Trastuzumab Deruxtecan versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer in the USA.

Adv Ther 2022 Aug 9. Epub 2022 Aug 9.

Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.

Introduction: Based on data from the DESTINY-Breast03 trial, we performed a cost-effectiveness analysis of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had been previously treated with trastuzumab and a taxane from the US payer perspective.

Methods: We conducted a Markov model to assess the cost-effectiveness of T-DXd versus trastuzumab emtansine (T-DM1). The simulation time horizon for this model was the lifetime of patients. Transition probabilities were based on data from the DESTINY-Breast03 trial. Health utility data were derived from published studies. Outcome measures were costs (in 2022 US$), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses assessed the uncertainty of key model parameters and their joint impact on the base-case results.

Results: The base-case results found that T-DXd provided an improvement of 3.90 QALYs compared with T-DM1, and the ICER was $220,533 per QALY. The one-way sensitivity analysis demonstrated that the utility value of progression-free survival, hazard ratios of T-Dxd versus T-DM1, and cost of T-Dxd contributed substantial uncertainty to the model. Probabilistic sensitivity analysis predicted T-DXd being cost-effective compared to T-DM1 was 0, 1, 16, and 46% at willingness-to-pay of $50,000, $100,000, $150,000, and 200,000 per QALY, respectively.

Conclusion: T-DXd was unlikely to offer a reasonable value for the money spent compared to T-DM1 in a US payer setting.
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http://dx.doi.org/10.1007/s12325-022-02273-4DOI Listing
August 2022

Liquid-cooled modular gas cell system for high-order harmonic generation using high average power laser systems.

Rev Sci Instrum 2022 Jul;93(7):073002

ELI ALPS, ELI-HU Non-Profit Ltd., Wolfgang Sandner utca 3, Szeged H-6728, Hungary.

We present the design and implementation of a new, modular gas target suitable for high-order harmonic generation using high average power lasers. To ensure thermal stability in this high heat load environment, we implement an appropriate liquid cooling system. The system can be used in multiple-cell configurations, allowing us to control the cell length and aperture size. The cell design was optimized with heat and flow simulations for thermal characteristics, vacuum compatibility, and generation medium properties. Finally, the cell system was experimentally validated by conducting high-order harmonic generation measurements using the 100 kHz high average power HR-1 laser system at the Extreme Light Infrastructure Attosecond Light Pulse Source (ELI ALPS) facility. Such a robust, versatile, and stackable gas cell arrangement can easily be adapted to different experimental geometries in both table-top laboratory systems and user-oriented facilities, such as ELI ALPS.
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http://dx.doi.org/10.1063/5.0097788DOI Listing
July 2022

The Conceivable Functions of Protein Ubiquitination and Deubiquitination in Reproduction.

Front Physiol 2022 13;13:886261. Epub 2022 Jul 13.

Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, China.

Protein ubiquitination with general existence in virtually all eukaryotic cells serves as a significant post-translational modification of cellular proteins, which leads to the degradation of proteins via the ubiquitin-proteasome system. Deubiquitinating enzymes (DUBs) can reverse the ubiquitination effect by removing the ubiquitin chain from the target protein. Together, these two processes participate in regulating protein stability, function, and localization, thus modulating cell cycle, DNA repair, autophagy, and transcription regulation. Accumulating evidence indicates that the ubiquitination/deubiquitination system regulates reproductive processes, including the cell cycle, oocyte maturation, oocyte-sperm binding, and early embryonic development, primarily by regulating protein stability. This review summarizes the extensive research concerning the role of ubiquitin and DUBs in gametogenesis and early embryonic development, which helps us to understand human pregnancy further.
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http://dx.doi.org/10.3389/fphys.2022.886261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326170PMC
July 2022

EGFR, HER2, and HER3 protein expression in paired primary tumor and lymph node metastasis of colorectal cancer.

Sci Rep 2022 Jul 28;12(1):12894. Epub 2022 Jul 28.

Department of Anatomy and Histology, School of Preclinical Medicine, Chengdu University, Chengdu, Sichuan Province, People's Republic of China.

Due to the difficulty in sampling of metastatic tumors, patient selection is commonly based on results of primary tumor samples when metastatic samples are not available. However, due to tumor heterogeneity, metastatic tumors may be different from primary tumors in their phenotypes. The aim of this study was to investigate the expression of EGFR, HER2, and HER3 between primary and lymph node metastatic lesions of colorectal cancer. Paired primary tumors and lymph node metastases from 79 patients with colorectal cancer were retrospectively collected and analyzed for EGFR, HER2, and HER3 expression. High EGFR, HER2, and HER3 expression (2+ and 3+) was found in 64.2%, 66.0%, and 85.0% of primary tumors, and 56.8%, 46.0%, and 76.0% of lymph node metastases, respectively. Correlation rates between primary and metastatic lesions were 67.1%, 63.3%, and 74.7% for EGFR, HER2, and HER3, respectively. Stage IV tumors (with distant metastasis) had higher correlation rates of HER2 expression compared to stage III tumors (without distant metastasis) (P = 0.050). Moderate correlation rates in EGFR, HER2, and HER3 expression were observed between primary and metastatic lesions of colorectal cancer. Tumor stage or existence of distant metastasis could serve as potential predictive markers for the correlation of HER2 expression between primary tumors and lymph node metastases of colorectal cancer.
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http://dx.doi.org/10.1038/s41598-022-17210-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334602PMC
July 2022

Testing latent class of subjects with structural zeros in negative binomial models with applications to gut microbiome data.

Stat Methods Med Res 2022 Jul 27:9622802221115881. Epub 2022 Jul 27.

Department of Epidemiology, 25812School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.

Human microbiome research has become a hot-spot in health and medical research in the past decade due to the rapid development of modern high-throughput. Typical data in a microbiome study consisting of the operational taxonomic unit counts may have over-dispersion and/or structural zero issues. In such cases, negative binomial models can be applied to address the over-dispersion issue, while zero-inflated negative binomial models can be applied to address both issues. In practice, it is essential to know if there is zero-inflation in the data before applying negative binomial or zero-inflated negative binomial models because zero-inflated negative binomial models may be unnecessarily complex and difficult to interpret, or may even suffer from convergence issues if there is no zero-inflation in the data. On the other hand, negative binomial models may yield invalid inferences if the data does exhibit excessive zeros. In this paper, we develop a new test for detecting zero-inflation resulting from a latent class of subjects with structural zeros in a negative binomial regression model by directly comparing the amount of observed zeros with what would be expected under the negative binomial regression model. A closed form of the test statistic as well as its asymptotic properties are derived based on estimating equations. Intensive simulation studies are conducted to investigate the performance of the new test and compare it with the classical Wald, likelihood ratio, and score tests. The tests are also applied to human gut microbiome data to test latent class in microbial genera.
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http://dx.doi.org/10.1177/09622802221115881DOI Listing
July 2022

Preparation of oxime compound lipid droplet-specifically labeled fluorescent probe and its application in cell imaging.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Nov 19;281:121648. Epub 2022 Jul 19.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, China.

Fluorescent probes can facilitate our further comprehension of the functional and physiological roles of LDs and thus promote the development of effective therapeutic approaches. Oxime compounds are widely used due to their good crystallinity and high reactivity. However, the majority oximes fluorescent probes are usually employed for the detection of HCIO, and the application of oximes in fluorescently labeled LD is poorly reported. In this paper, three kinds of LDs fluorescent probes (NAP-a, NAP-b and NAP-c) with D-π-A structure were synthesized by simple synthesis method with 1,8-naphthalimide as fluorescent matrix and oxime group as electron donor. These probes were highly sensitive to polarity, and possessed good photostability and low cytotoxicity. Co-staining experiments showed that these probes could target LDs and the fluorescence image was green. These probes NAP-a, NAP-b and NAP-c possessed high Pearson coefficient (HeLa cells: 0.91, 0.95, 0.86) and Manders coefficient (HeLa cells: 0.91, 0.96, 0.86) with Nile Red. Interestingly, the dynamic variations in their size, shape and distribution could be clearly observed in the oleic acid-treated cell model of LDs. Imaging of zebrafish was performed and green fluorescence was collected in zebrafish. These excellent properties make oxime compound fluorescent probes a promising fluorescent probes for studying LDs and metabolic diseases. This study opens up a new way for the preparation of LDs fluorescent probe.
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http://dx.doi.org/10.1016/j.saa.2022.121648DOI Listing
November 2022

International travel, the gut microbiome, and ESBL-E coli carriage.

Lancet Microbe 2022 Jul 21. Epub 2022 Jul 21.

HKU-Pasteur Research Pole, School of Public Health, LKS Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China; JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Microbiota I-Center, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address:

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http://dx.doi.org/10.1016/S2666-5247(22)00201-4DOI Listing
July 2022

Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma.

Nat Commun 2022 Jul 21;13(1):4214. Epub 2022 Jul 21.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergistic therapy. Because our self-assembling NPs are encapsulated in membranes derived from glioma cells, they readily penetrate the blood-brain barrier and target GBM through homotypic recognition. After reaching the tumors, lactate oxidase in the NPs converts LA into pyruvic acid (PA) and hydrogen peroxide (HO). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the HO reacts with the delivered bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate to release energy, which is used by the co-delivered photosensitizer chlorin e6 for the generation of cytotoxic singlet oxygen to kill glioma cells. Such a synergism ensures strong therapeutic effects against both glioma cell-line derived and patient-derived xenograft models.
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http://dx.doi.org/10.1038/s41467-022-31799-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304377PMC
July 2022

Primary malignant melanoma of the right plantar: A case report.

Authors:
Feng Ding Peng Ye

Asian J Surg 2022 Jul 15. Epub 2022 Jul 15.

Wannan Medical College, Wuhu, 241000, Anhui, China.

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http://dx.doi.org/10.1016/j.asjsur.2022.07.024DOI Listing
July 2022

Mulberrin Confers Protection against Doxorubicin-Induced Cardiotoxicity via Regulating AKT Signaling Pathways in Mice.

Oxid Med Cell Longev 2022 7;2022:2967142. Epub 2022 Jul 7.

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Doxorubicin (DOX) is an antitumor anthracycline, but its clinical use was largely limited by its cardiac toxicity. DOX-induced oxidative damage and cardiomyocyte loss have been recognized as the potential causative mechanisms of this cardiac toxicity. Growing interests are raised on mulberrin (Mul) for its wide spectrum of biological activities, including antioxidative and anti-inflammatory properties. The aim of this study was to investigate the effect of Mul on DOX-induced heart injury and to clarify the underlying mechanism. Mice were given daily 60 mg/kg of Mul via gavage for 10 days. Mice received an intraperitoneal injection of DOX to mimic the model of DOX-related acute cardiac injury at the seventh day of Mul treatment. Mul-treated mice had an attenuated cardiac injured response and improved cardiac function after DOX injection. DOX-induced oxidative damage, inflammation accumulation, and myocardial apoptosis were largely attenuated by the treatment of Mul. Activated protein kinase B (AKT) activation was essential for the protective effects of Mul against DOX-induced cardiac toxicity, and AKT inactivation abolished Mul-mediated protective effects against DOX cardiotoxicity. In conclusion, Mul treatment attenuated DOX-induced cardiac toxicity via activation of the AKT signaling pathway. Mul might be a promising therapeutic agent against DOX-induced cardiac toxicity.
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http://dx.doi.org/10.1155/2022/2967142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283020PMC
July 2022

Molecular imaging on ACE2-dependent transocular infection of coronavirus.

J Med Virol 2022 Jun 26. Epub 2022 Jun 26.

Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, China.

A transocular infection has been proved as one of the main approaches that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the body, and angiotensin-converting enzyme 2 (ACE2) plays a key role in this procedure. Dynamic and quantitative details on virus distribution are lacking for virus prevention and drug design. In this study, a radiotraceable pseudovirus packed with an enhanced green fluorescent protein (EGFP) gene, I-CoV, was prepared and inoculated in the unilateral eye of humanized ACE2 (hACE2) mice or ACE2-knockout (ACE2-KO) mice. Single-photon emission computed tomography/computed tomography images were acquired at multiple time points to exhibit ACE2-dependent procedures from invasion to clearance. Positron emission tomography (PET) and western blot were performed to quantify ACE2 expression and verify the factors affecting transocular infection. For the transocular infection of coronavirus (CoV), the renin-angiotensin-aldosterone system (RAAS), lungs, intestines, and genital glands were the main targeted organs. Due to the specific anchor to ACE2-expressed host cells, virus concentrations in genital glands, liver, and lungs ranked the top three most and stabilized at 3.75 ± 0.55, 3.30 ± 0.25, and 2.10 ± 0.55% inoculated dose (ID)/mL at 48 h post treatment. Meanwhile, ACE2-KO mice had already completed the in vivo clearance. In consideration of organ volumes, lungs (14.50 ± 3.75%ID) and liver (10.94 ± 0.71%ID) were the main in-store reservoirs of CoV. However, the inoculated eye (5.52 ± 1.85%ID for hACE2, 5.24 ± 1.45%ID for ACE2-KO, p > 0.05) and the adjacent brain exhibited ACE2-independent virus infection at the end of 72 h observation, and absolute amount of virus played a key role in host cell infection. These observations on CoV infection were further manifested by infection-driven intracellular EGFP expression. ACE2 PET revealed an infection-related systematic upregulation of ACE2 expression in the organs involved in RAAS (e.g., brain, lung, heart, liver, and kidney) and the organ that was of own local renin-angiotensin system (e.g., eye). Transocular infection of CoV is ACE2-dependent and constitutes the cause of disturbed ACE2 expression in the host. The brain, genital glands, and intestines were of the highest unit uptake, potentially accounting for the sequelae. Lungs and liver were of the highest absolute amount, closely related to the respiratory diffusion and in vivo duplication. ACE2 expression was upregulated in the short term after infection with CoV. These visual and quantitative results are helpful to fully understanding the transocular path of SARS-CoV-2 and other CoVs.
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http://dx.doi.org/10.1002/jmv.27958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349515PMC
June 2022

Surface Hydrophilic Modification for Chip of Centrifugal Microfluidic Immunoassay System.

Micromachines (Basel) 2022 May 26;13(6). Epub 2022 May 26.

The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, The College of Laboratory Medicine, Chongqing Medical University, No. 1 Yixueyuan Road, Chongqing 400016, China.

The surface of a centrifugal microfluidic immunoassay system chip such as polymethyl methacrylate (PMMA) is often hydrophobic, which leads to problems such as poor liquid transfer efficiency and easy-to-block siphon channels, leading to bad fluid control. Therefore, surface hydrophilic modification for such chips is necessary to improve the rapidity and sensitivity of the system. Chemical modification is commonly used, but there is little research on the hydrophilic effect of different concentrations of hydrophilic reagents. According to function requirements for different microchannels of the chip (some only need to ensure the liquid can flow into the next chamber, and some also need to ensure the function of "closing the door" during immunoassay incubation), we explored the best combination of hydrophilic reagent and concentration through experiments. Firstly, three hydrophilic reagents were used for modification. Secondly, the hydrophilic effects of different reagents and concentrations were explored by contact angle test, the influence of different modification methods on liquid transfer efficiency was characterized by residual liquid calculation in the chamber. Finally, the effect of different hydrophilic reagents on absorbance was also tested. By experimental results and comprehensively considering the stability of the modification effect and the function requirements, Tween-20 (2.0% /) was chosen as the modifying reagents of the first siphon valve and the second siphon valve, and TritonX-100 (2.0% /) was chosen for the third siphon valve, which effectively reduces the contact angle and improves the liquid transfer efficiency, leading to further improvement of the rapidity and sensitivity of the centrifugal microfluidic immunoassay system by efficient siphoning and high plasma separation efficiency (99%).
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http://dx.doi.org/10.3390/mi13060831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229454PMC
May 2022

Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells.

Biomolecules 2022 06 19;12(6). Epub 2022 Jun 19.

Key Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes and Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou 910095, China.

Cancer stem cells (CSCs) are a subset of highly tumorigenic cells in tumors. They have enhanced self-renewal properties, are usually chemo-radioresistant, and can promote tumor recurrence and metastasis. They can recruit macrophages into the tumor microenvironment and differentiate them into tumor-associated macrophages (TAMs). TAMs maintain CSC stemness and construct niches that are favorable for CSC survival. However, how CSCs and TAMs interact is not completely understood. An understanding on these mechanisms can provide additional targeting strategies for eliminating CSCs. In this review, we comprehensively summarize the reported mechanisms of crosstalk between CSCs and TAMs and update the related signaling pathways involved in tumor progression. In addition, we discuss potential therapies targeting CSC-TAM interaction, including targeting macrophage recruitment and polarization by CSCs and inhibiting the TAM-induced promotion of CSC stemness. This review also provides the perspective on the major challenge for developing potential therapeutic strategies to overcome CSC-TAM crosstalk.
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http://dx.doi.org/10.3390/biom12060850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221070PMC
June 2022

Spatial Bridge Locking Fixator versus Traditional Locking Plates in Treating AO/OTA 32-A3.2 Fracture: Finite Element Analysis and Biomechanical Evaluation.

Orthop Surg 2022 Aug 22;14(8):1638-1648. Epub 2022 Jun 22.

Department of Orthopaedics, First Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing, China.

Objective: To compare the biomechanical behaviors of the spatial bridge locking fixator (SBLF), single locking plate (SP), and double locking plate (DP) for AO/OTA 32-A3.2 fractures using finite element analysis and biomechanical tests.

Methods: Axial loading of 700 N was conducted on the AO/OTA 32-A3.2 model via finite element analysis. The von Mises stress and the interfragmentary movement (IFM) were comparatively analyzed in the three configurations above. On the mechanical tester, axial and torsional loading of 30 synthetic femurs (five specimens of each configuration for each test at random) was performed, and the interfragmentary movement, torsion angle, stiffness, and ultimate load were recorded and analyzed.

Results: The finite element analysis (FEA) results showed that the von Mises stress of the spatial bridge locking fixator (SBLF) was lower than that of the single locking plate (SP) and higher than that of the double locking plate (DP). At 700 N, the axial IFMs were 0.15-0.38 mm (SBLF), 0.03-0.84 mm (SP), and 0.02-0.07 mm (DP). The biomechanical experiment indicated that the axial interfragmentary movements (IFMs) were 0.44 ± 0.23 mm (SBLF), 1.02 ± 0.40 mm (SP), and 0.07 ± 0.07 mm (DP) (p < 0.001). The axial IFM of the SBLF group had the highest probability (79.26%) of falling within the ideal range (0.2-0.8 mm), and the SP and DP groups had probabilities of 27.10% and 3.14%, respectively. The axial stiffness in the SBLF group (1586 ± 130 N/mm) was significantly lower than that in the DP group (10,264 ± 2671 N/mm) (p < 0.001) but greater than that in the SP group (725 ± 178 N/mm) (p = 0.396). The range of axial loads to ultimate failure was 3385-4527 N (SBLF), 3377-4664 N (SP), and 3780-4804 N (DP). The shear motion of the fracture end was 0.35 ± 0.14 mm (SBLF), 0.16 ± 0.10 mm (SP), and 0.08 ± 0.04 mm (DP) (p < 0.001). The torsional stiffness was 1.68 ± 0.14 Nm/degree (SBLF), 2.32 ± 0.29 Nm/degree (SP) (SBLF&SP, p < 0.001), and 3.53 ± 0.73 Nm/degree (DP) (SBLF&DP, p < 0.001).

Conclusions: The SBLF structure may exhibit a better biomechanical performance compared with the SP and DP in providing the best quantity and more symmetrical interfragmentary movement for AO/OTA 32-A3.2 fractures.
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http://dx.doi.org/10.1111/os.13308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363740PMC
August 2022

Therapeutic Benefits of Pomegranate Flower Extract: A Novel Effect That Reduces Oxidative Stress and Significantly Improves Diastolic Relaxation in Hyperglycemic In Vitro in Rats.

Evid Based Complement Alternat Med 2022 8;2022:4158762. Epub 2022 Jun 8.

School of Science, Auckland University of Technology (AUT), 55 Wellesley Street East, Auckland, New Zealand.

The pomegranate flower is an ancient herb in traditional Chinese medicine with multiple properties. Recent studies have shown that pomegranate flower extract is beneficial, especially for hyperglycemia. In this experiment, we investigated the diastolic effect of pomegranate flower polyphenol (PFP) extract on the isolated thoracic aorta of rats in both the absence and presence of high glucose levels. Isotonic contractile forces were recorded from aortic rings (about 3 mm in length) from rats using the BL-420F Biological Function Test System. Tissues were precontracted with 60 mM KCl to obtain maximum tension under 1.0 g load for 1 hour before the balance was achieved, and the fluid was changed every 15 minutes. PFP (700 mg/L-900 mg/L) showed a concentration-dependent relaxant effect on the aortic rings; vasodilation in the endothelium-intact was significantly higher than that in the de-endothelialized segments ( < 0.01). The endothelium-dependent vasorelaxant effect of PFP was partially attenuated by K channel blockers, tetraethylammonium (TEA), glibenclamide (Glib), and BaCl, as well as L-NAME (eNOS inhibitor) on the denuded endothelium artery ring. Concentration-dependent inhibition of PFP on releasing intracellular Ca in the Ca-free solution and vasoconstriction of CaCl in Ca-free buffer plus K (60 mM) was observed. In addition, PFP (0.1-10 mg/L) showed significant inhibition of acetylcholine-induced endothelial-dependent relaxation in the aorta of rats in the presence of high glucose (44 mmol/L). Nevertheless, the vasodilating effect of PFP was inhibited by atropine and L-NAME. The results indicated that PFP-induced vasodilation was most likely related to the antioxidant effects through enhanced NO synthesis, as well as the blocking of K channels and inhibition of extracellular Ca entry. In conclusion, these observations showed that PFP ameliorates vasodilation in hyperglycemic rats. Hence, our results suggest that PFP supplementation may be beneficial for hypertensive patients with diabetes.
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http://dx.doi.org/10.1155/2022/4158762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200500PMC
June 2022

Transcriptome analysis provides insight into deltamethrin-induced fat accumulation in 3T3-L1 adipocytes.

Pestic Biochem Physiol 2022 Jun 6;184:105114. Epub 2022 May 6.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China. Electronic address:

Previously, deltamethrin (a Type-II pyrethroid) has been reported to increase triglyceride (fat) accumulation in adipocytes, while its underlying molecular mechanism is not fully determined. The aim of this study was to further investigate the molecular mechanisms of deltamethrin induced fat accumulation in murine 3T3-L1 adipocytes. Consistent to previous reports, deltamethrin (10 μM) significantly promoted adipogenesis in 3T3-L1 adipocytes. RNA sequencing (RNA-seq) results showed that 721 differentially expressed genes (DEGs) were identified after deltamethrin treatment, involving in 58 Functional groups of Gene Ontology (GO) and 255 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Several key functional groups regulating adipogenesis, such as fat cell differentiation (Igf1, Snai2, Fgf10, and Enpp1) and cytosolic calcium ion concentration (Nos1, Cxcl1, and Ngf) were significantly enriched. Collectively, these results suggest that the promotion of adipogenesis by deltamethrin was attributed to an obesogenic global transcriptomic response, which provides further understanding of the underlying mechanisms of deltamethrin-induced fat accumulation.
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http://dx.doi.org/10.1016/j.pestbp.2022.105114DOI Listing
June 2022

Cost-Effectiveness of Pembrolizumab Plus Chemotherapy as First-Line Therapy for Advanced Oesophageal Cancer.

Front Pharmacol 2022 30;13:881787. Epub 2022 May 30.

Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.

Pembrolizumab plus chemotherapy is recommended as the first-line treatment for advanced oesophageal cancer. The objective of this study is to evaluate the cost-effectiveness of pembrolizumab plus chemotherapy as first-line therapy for advanced oesophageal cancer from the healthcare system perspective in China. Based on the KEYNOTE-590 trial, a Markov model was constructed to estimate the cost and effectiveness of pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. One-way, probabilistic sensitivity analyses (PSA), and subgroup analyses were adapted to test the model robustness. Compared with the placebo group, pembrolizumab group obtained an additional 1.05 QALY, but the cost was also increased by $121,478.76. The ICER was $115,391.84 per QALY gained, which was higher than the willingness-to-pay (WTP) of $31,304.31. The results of One-way sensitivity analyses showed that the ICER was sensitive to the hazard ratio of PFS and per cycle cost of pembrolizumab. At a WTP threshold of $31,304.31, the probability of pembrolizumab plus chemotherapy being cost-effective was 0%. From the perspective of China healthcare system, pembrolizumab plus chemotherapy as first-line treatment is not cost-effective for patients with advanced oesophageal cancer compared with placebo plus chemotherapy.
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http://dx.doi.org/10.3389/fphar.2022.881787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197184PMC
May 2022

Clinical Benefit and Cost Effectiveness of Risk-Stratified Gastric Cancer Screening Strategies in China: A Modeling Study.

Pharmacoeconomics 2022 Jul 15;40(7):725-737. Epub 2022 Jun 15.

Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Background And Objective: A new gastric cancer screening scoring system (NGCS) strategy was recommended for the early gastric cancer (GC) screening process in China. The current study aimed to assess the clinical benefits and the cost effectiveness of the NGCS strategy in GC high-risk areas of China from a societal perspective.

Methods: A Markov microsimulation model was developed to evaluate 30 alternative screening strategies with varying initiation age, including the NGCS strategy, the modified NGCS strategy, and the endoscopic screening strategy with various screening intervals. The primary outcomes included GC mortality, number of endoscopies, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Cost estimates were reported in 2021 USD (US$) and both costs and benefits were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty.

Results: Screening with the NGCS strategy from age 40 years (40-NGCS) reduced the GC incidence by 86.4%, which provided the greatest benefit across strategies. Compared with all strategies, at a willingness-to pay threshold of US$17,922 per QALY, the 40-NGCS strategy was a leading cost-effective strategy, with an ICER of US$15,668 per QALY. Results were robust in univariate and probabilistic sensitivity analyses. The probability of the 40-NGCS strategy being cost effective was 0.863.

Conclusions: The 40-NGCS strategy was an effective and cost-effective strategy to reduce GC incidence and mortality in China. The findings provide important evidence for decision makers to formulate and optimize targeted approaches for GC prevention and control policies in China.
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http://dx.doi.org/10.1007/s40273-022-01160-8DOI Listing
July 2022

Use of Fenestrated Stent Grafts for the Treatment of Anastomotic Pseudoaneurysms in Transplant Renal Arteries.

J Vasc Interv Radiol 2022 Jun 11. Epub 2022 Jun 11.

Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Province, Guangzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.jvir.2022.05.028DOI Listing
June 2022

Effect of Ultrasound-Guided Fascia Iliac Compartment Block with Nalbuphine and Ropivacaine on Preoperative Pain in Older Patients with Hip Fractures: A Multicenter, Triple-Blinded, Randomized, Controlled Trial.

Pain Ther 2022 Sep 8;11(3):923-935. Epub 2022 Jun 8.

Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, No. 134 Dong Street, Fuzhou, 350001, Fujian, China.

Introduction: Pain management for older patients with hip fractures is challenging. This study aimed to investigate the effect of ultrasound-guided fascia iliac compartment block (UGFICB) using different doses of nalbuphine in combination with ropivacaine on preoperative analgesia in older patients with hip fractures.

Methods: In this multicenter randomized controlled trial, 280 elderly patients with hip fracture were randomly allocated into four UGFICB groups (n = 70 in each group): a ropivacaine group (30 mL 0.1% ropivacaine + 0.9% normal saline) and three ropivacaine plus nalbuphine groups (5, 10, and 20 mg nalbuphine, respectively). The primary outcomes were the duration of analgesia at rest and on passive movement. Secondary outcomes included sensory block area, side effects, and vital signs. The doses of rescue analgesia with parecoxib sodium were also analyzed.

Results: The addition of nalbuphine dose-dependently increased the duration of analgesia at rest and on passive movement (P < 0.05) and expanded the area of sensory block (P < 0.05). Compared with the ropivacaine group, the pain scores at rest and on movement at 6 and 8 h after the block were lower in three ropivacaine plus nalbuphine groups (P < 0.05), without between-group differences at 2, 4, and 12 h. The four groups had comparable side effects (nausea and vomiting) and vital signs (P > 0.05).

Conclusions: UGFICB with 5, 10, and 20 mg nalbuphine added to ropivacaine prolonged the analgesia duration, increased sensory block area, reduced pain, and decreased the doses of rescue parecoxib sodium for older patients after hip fracture, without obvious side effects. Among these three doses, nalbuphine 20 mg in combination with ropivacaine provided the longest duration of analgesia and the largest sensory block area.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000029934).
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http://dx.doi.org/10.1007/s40122-022-00397-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314510PMC
September 2022

Therapeutic development for Canavan disease using patient iPSCs introduced with the wild-type gene.

iScience 2022 Jun 11;25(6):104391. Epub 2022 May 11.

Division of Stem Cell Biology Research, Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.

Canavan disease (CD) is a devastating neurological disease that lacks effective therapy. Because CD is caused by mutations of the aspartoacylase () gene, we introduced the wild-type (WT) gene into patient iPSCs through lentiviral transduction or CRISPR/Cas9-mediated gene editing. We then differentiated the WT -expressing patient iPSCs (ASPA-CD iPSCs) into NPCs and showed that the resultant ASPA-CD NPCs exhibited potent ASPA enzymatic activity. The ASPA-CD NPCs were able to survive in brains of transplanted CD mice. The engrafted ASPA-CD NPCs reconstituted ASPA activity in CD mouse brains, reduced the abnormally elevated level of NAA in both brain tissues and cerebrospinal fluid (CSF), and rescued hallmark pathological phenotypes of the disease, including spongy degeneration, myelination defects, and motor function impairment in transplanted CD mice. These genetically modified patient iPSC-derived NPCs represent a promising cell therapy candidate for CD, a disease that has neither a cure nor a standard treatment.
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http://dx.doi.org/10.1016/j.isci.2022.104391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142666PMC
June 2022

Comparing of Frequency Shift and Impedance Analysis Method Based on QCM Sensor for Measuring the Blood Viscosity.

Sensors (Basel) 2022 May 17;22(10). Epub 2022 May 17.

School of Automation Engineering, University of Electronic Science and Technology of China, Chengdu 611731, China.

Blood viscosity measurements are crucial for the diagnosis of cardiovascular and hematological diseases. Traditional blood viscosity measurements have obvious limitations because of their expensive equipment usage and large sample consumption. In this study, blood viscosity was measured by the oscillating circuit method and impedance analysis method based on single QCM. In addition, the effectiveness of two methods with high precision and less sample is proved by the experiments. Moreover, compared to the result from a standard rotational viscometer, the maximum relative errors of the proposed oscillating circuit method and impedance analysis method are ±5.2% and ±1.8%, respectively. A reliability test is performed by repeated measurement (N = 5), and the result shows that the standard deviation about 0.9% of impedance analysis is smaller than that of oscillating circuit method. Therefore, the impedance analysis method is superior. Further, the repeatability of impedance analysis method was evaluated by regression analysis method, and the correlation coefficient R > 0.965 demonstrated that it had excellent reproducibility.
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http://dx.doi.org/10.3390/s22103804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147212PMC
May 2022

Alanine-Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells.

Biomolecules 2022 05 5;12(5). Epub 2022 May 5.

Key Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes and Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou 910095, China.

Liver cancer stem cells (LCSCs) are a small subset of oncogenic cells with a self-renewal ability and drug resistance, and they promote the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanisms regulating LCSCs have not been fully explored. By enriching LCSCs from spheroid cultures and performing transcriptomic analysis, we determined that alanine-glyoxylate aminotransferase (AGXT), which participates in the metabolism of serine and glycine, was significantly upregulated in spheroid cultures, and its function in LCSCs remains unknown. Through the exogenous overexpression or short hairpin RNA knockdown of AGXT in HCC cells, we observed that changes in the AGXT level did not affect the spheroid ability and population of LCSCs. The knockdown of AGXT in LCSCs reduced the number of spheroids and the population of LCSCs; this implies that AGXT is required for the maintenance of cancer stemness rather than as a driver of LCSCs. Mechanistically, AGXT may sustain the self-renewal potential of LCSCs by upregulating the expression of SRY-box transcription factor 2 (SOX2) and octamer-binding transcription factor 4 (OCT4), two well-known master regulators of cancer stemness. Taken together, our study demonstrates the role of AGXT in supporting LCSCs; thus, AGXT merits further exploration.
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http://dx.doi.org/10.3390/biom12050668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138635PMC
May 2022

Secondary esophageal perforation rupture of ascending aorta 16 day accidently-swallowing button battery in a young child: A case report of esophagial foreign body and mini review.

Int J Surg Case Rep 2022 May 4;94:107148. Epub 2022 May 4.

Emergency Department, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China. Electronic address:

Introduction And Importance: Foreign body ingestions often occur in children between the ages of six months and three years. Swallowing button battery can cause serious complications such as gastrointestinal mucosa tissue necrosis and esophageal perforation. Fatal secondary lesions after foreign body removal are rarely reported.

Case Presentation: We reported a case of 18 months old boy who accidently swallowed a button battery (20 mm diameter, 3.2 mm height) which lodged in the esophagus for 3 days before removed by esophagoscope. Secondary esophageal perforation and rupture of ascending aorta resulted in death 13 days after the battery was removed. The autopsy confirmed the rupture and tissue necrosis of the esophagus and ascending aorta.

Clinical Discussion: The button battery incarcerated in the second stricture of the esophagus can cause serious complications and death even after removal due to battery-induced tissue erosion. Great attention should be closely paid to early endoscopic reinspection postoperatively and take comprehensive treatment to avoid similar death.

Conclusion: When the incarceration of button batter occurs in the second stricture of esophagus, the possibility of esophageal perforation and the rupture of main artery should be considered. The comprehensive treatment after operation is as important as taking out the foreign bodies.
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http://dx.doi.org/10.1016/j.ijscr.2022.107148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093002PMC
May 2022

Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations.

J Nanobiotechnology 2022 May 18;20(1):233. Epub 2022 May 18.

Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.

Background: Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal.

Results: Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route.

Conclusions: This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy.
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http://dx.doi.org/10.1186/s12951-022-01431-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118843PMC
May 2022

Cost-Effectiveness Analysis of Hepatic Arterial Infusion Chemotherapy of Infusional Fluorouracil, Leucovorin, and Oxaliplatin Versus Transarterial Chemoembolization in Patients With Large Unresectable Hepatocellular Carcinoma.

Front Pharmacol 2022 26;13:849189. Epub 2022 Apr 26.

Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.

The purpose of this study was to evaluate a cost-effectiveness analysis of hepatic arterial infusion chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX-HAIC) as the first-line treatment for patients with large unresectable hepatocellular carcinoma (HCC) compared with transarterial chemoembolization (TACE). A Markov model was constructed to simulate the first-line treatment, disease recurrence, and survival of patients with large unresectable HCC. Transition probabilities were based on clinical trial data. The costs and health utilities were derived from the public literature. The outputs were total cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICER). One-way and probabilistic sensitivity analyses were performed to examine model uncertainty. We also performed subgroup analyses. The results of the base case analysis found that FOLFOX-HAIC increased overall costs by $9,381 and improved effectiveness by 1.01 QALYs compared with TACE. The one-way sensitivity analysis showed that the hazard ratio of progression-free survival and overall survival for FOLFOX-HAIC relative to TACE had the greatest impact on the ICER. Probabilistic sensitivity analysis found that the probability of FOLFOX-HAIC treatment being cost-effective was 99.54% at the willingness-to-pay threshold of $30,552/QALY. Patients in most subgroups favored FOLFOX-HAIC treatment because it had a more than 50% probability of being cost-effective than TACE, except for patients with negative hepatitis B infection. In conclusion, our study found that the FOLFOX-HAIC was a cost-effective option compared to TACE for patients with large unresectable HCC in China.
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http://dx.doi.org/10.3389/fphar.2022.849189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086423PMC
April 2022

Ni-catalysed deamidative fluorination of amides with electrophilic fluorinating reagents.

Org Biomol Chem 2022 05 26;20(20):4091-4095. Epub 2022 May 26.

Catalytic Hydrogenation Research Center, State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

We describe here a Ni-catalysed deamidative fluorination of diverse amides with electrophilic fluorinating reagents. Different types of amides including aromatic amides and olefinic amides were well compatible, affording the corresponding acyl fluorides in good to excellent yields.
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http://dx.doi.org/10.1039/d2ob00519kDOI Listing
May 2022

Arsenic trioxide induces proteasome dependent TBLR1-RARα degradation to improve leukemia eradication through cell differentiation enhancement.

J Cancer 2022 18;13(7):2301-2311. Epub 2022 Apr 18.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang, China, 310016.

Background: Acute promyelocytic leukemia (APL) mainly harbors PML-RARα fusion gene, which is sensitive to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) treatment. However, APL harboring other RARα fusion genes exhibit different drug sensitivity. Here, we investigated the role and mechanism of TBLR1-RARα, a rare RARα fusion gene, on ATO treatment in leukemia cells.

Methods: By constructing two cell models of leukemia cell line HL-60 and U937 with overexpressed TBLR1-RARα, we detected the cell differentiation in the two cell models after ATO treatment by flow cytometry and Wright staining. Meanwhile, cell viability, colony formation and apoptosis were also determined after ATO treatment.

Results: We found that TBLR1-RARα enhanced ATO-induced apoptosis and cell proliferation inhibition. Besides, TBLR1-RARα also promoted ATO-induced cell differentiation. Furthermore, we found that the mitochondrial caspase pathway was involved in the apoptosis induced by ATO treatment in TBLR1-RARα positive leukemia cells. Moreover, ATO mediated TBLR1-RARα protein degradation via proteasome pathway, which accounts for the transcriptional activation of RARα target gene and is further involved in cell differentiation of TBLR1-RARα positive leukemia cells.

Conclusions: Our study provides evidence that TBLR1-RARα positive APL patients may benefit from ATO treatment, thereby improving the appropriate management in TBLR1-RARα positive APL.
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http://dx.doi.org/10.7150/jca.66175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066217PMC
April 2022

Economic Evaluation of Dapagliflozin in the Treatment of Patients With Heart Failure: A Systematic Review.

Front Pharmacol 2022 14;13:860109. Epub 2022 Apr 14.

Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.

The objective of this study is to systematically review the economic evaluations of dapagliflozin in the treatment of patients with heart failure (HF) and describe their general and methodological features. This systematic review followed the PRISMA guidelines. MEDLINE/PubMed, Website Of Science, Embase, The Cochrane Library, ScienceDirect, CNKI, and Wanfang databases were searched to collect relevant studies, and the retrieval time ended on 31 October 2021. Articles on the economic evaluation of dapagliflozin in the treatment of heart failure were included. Secondary studies, incomplete economic indicators, and non-English-language and non-Chinese-language studies were excluded. Standard drug treatment was selected as the comparison. Basic characteristics, methods, and main results were extracted and analyzed systematically. A total of eight studies were identified, and the overall quality was accepted, which were performed in nine developed countries (Austria, United States, Korea, Japan, Singapore, Spanish, Germany, and United Kingdom) and three developing countries (the Philippines, Thailand, and China). With the exception of the Philippines, the remaining countries considered that dapagliflozin was cost effective. In the analyses of all included studies, the incremental cost-effectiveness ratios were most sensitive to the cost of dapagliflozin, cardiovascular mortality, the duration of dapagliflozin effectiveness, and the probability of HF hospitalization. Dapagliflozin in the treatment of patients with heart failure with reduced ejection fraction was considered cost effective. Further studies are needed to evaluate the comprehensive value of dapagliflozin on HF.
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http://dx.doi.org/10.3389/fphar.2022.860109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046576PMC
April 2022
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