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Per- and polyfluoroalkyl substances (PFASs) can induce a range of adverse health effects, with the precise molecular mechanisms remaining elusive. Extracellular vesicles (EVs) have demonstrated their potential to elucidate unknown molecular mechanisms. Building upon the close alignment of their biological functions with the observed health effects of PFASs, this study innovatively focuses on proteomic insights from EVs into the molecular mechanisms underlying the systemic health effects of PFASs. Through rat exposure experiments and proteomics technology, it not only demonstrated the occurrence of PFASs in EVs but also revealed the alterations in the serum EVs and the expression of their protein cargos following mixed exposure to PFASs, leading to changes in related pathways. These changes encompass various biological processes, including proteasome activity, immune response, cytoskeletal organization, oxidative stress, cell signaling, and nervous system function. Particularly noteworthy is the uncovering of the activation of the proteasome pathway, highlighting significant key contributing proteins. These novel findings provide a new perspective for exploring the molecular mechanism underlying the systemic health effects of PFASs and offer reliable screening for potential biomarkers. Additionally, comparisons with serum confirmed the potential of serum EVs as biological responders and measurable endpoints for evaluating PFASs-induced toxicity.

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Carbendazim (CBZ) is widely used for crop protection and its residues threaten human health and the environment. Therefore, developing an effective electrocatalyst is important for the extremely sensitive detection of CBZ. Lattice-strain engineering is an effective strategy to change its electronic structure and ultimately optimize the catalytic performance of materials, which can be used as a modification method to improve the detection performance of electrochemical sensors. Herein, a NiFeLDH@HsGY-NH2/MWCNTs heterojunction with strain effect is prepared by the electrostatic self-assembly method. The structure, morphology, composition, crystallinity and electrochemical performance of NiFeLDH@HsGY-NH2/MWCNTs are analyzed using various instrumental techniques, in which geometric phase analysis (GPA) and X-ray diffraction (XRD) images confirm the lattice-strain generated in NiFeLDH@HsGY-NH2/MWCNTs. The results indicate that the prepared electrochemical sensor exhibited an excellent response for carbendazim (CBZ) in the linear range of 0.05-50.00 µM with a detection limit of 10.00 nM (S/N = 3) under the optimal detection conditions. By analyzing the reasons for the improvement of the catalytic performance of the composite material, it is found that the composite of MWCNTs not only improves the conductivity of NiFeLDH but also regulates the electronic structure of metal atoms through double effects. This study provides new insights into the design of efficient and low-cost catalysts to facilitate electrochemical sensor applications.

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BACKGROUND: Mushroom poisoning poses a significant global health concern, with high morbidity and mortality rates. The primary lethal toxins responsible for this condition are alpha-amanitin (ɑ-AMA) and beta-amanitin (ß-AMA). As a promising bio-recognition molecules in biosensors, aptamers, have been broadly used in the field of food detection. However, the current SELEX-based methods for screening aptamers for structurally similar small molecules were limited by the labelling or salt ion induction. In this study, we aimed to develop a novel label-free SELEX strategy for the screening of aptamers with high affinity and constructed new aptasensors for the detection of ɑ-AMA and ß-AMA. RESULTS: A novel label-free SELEX strategy based on the positively charged gold nanoparticles (AuNPs) was proposed to simultaneous screening of aptamers for ɑ-AMA and ß-AMA. Only 18 rounds of SELEX were required to obtain new aptamers. The candidate aptamers were analyzed by colloidal gold assay, and the sequences of ɑ-30 and ß-37 displayed great affinity with Kd values of 22.26 nM and 23.32 nM, respectively, without interference from botanical toxins. Notably, the truncated aptamers ɑ-30-2 (50 bp) and ß-37-2 (57 bp) exhibited higher affinity than their original counterpart (79 bp). Subsequently, the selected aptamers were utilized to construct recognition probes for electrochemical aptasensors based on hairpin cyclic cleavage of substrates by Cu2+ dependent DNAzyme and Exo I-triggered recycling cascades. The detection platform showed excellent analytical performance with limits of detection as low as 4.57 pg/mL (ɑ-AMA) and 8.49 pg/mL (ß-AMA). Moreover, the aptasensors exhibited superior performance in mushroom and urine samples. SIGNIFICANCE: This work developed a simple and efficient label-free SELEX method for screening new aptamers for ɑ-AMA and ß-AMA, which employed the positively charged AuNPs as the screening medium, without the need for chemical labelling of libraries or induction of salt ions. Furthermore, two novel electrochemical aptasensors were developed based on our newly obtained aptamers, which offer the new biosensing tool for ultrasensitive detection of the AMA poisoning, showing great potential in practical applications.

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OBJECTIVE: The survival outcomes of Stage IIIC1 in FIGO 2018 showed significant heterogeneity and it seems unreasonable to administer a uniform treatment regimen for Stage IIIC1 patients. This study aimed to assess the survival outcomes among patients with locally advanced cervical cancer based on various lymph node statuses, T-stage classifications, and treatment modalities. METHODS: This is a population-based cohort study utilizing the Surveillance, Epidemiology, and End Results Program from 2004 to 2018. Propensity score-based inverse probability of treatment weighting was used to achieve covariate balance. Women with locally advanced cervical cancer on different lymph node statuses who underwent radical hysterectomy + pelvic lymphadenectomy + chemoradiotherapy, chemoradiotherapy, or radiotherapy alone were examined. Trends, patient characteristics, and survival outcomes were compared across different treatment regimens. RESULTS: Among 8777 patients analyzed, patients with early T-stage and married were identified as independent protective factors for cancer-specific survival regardless of lymph node status. The survival outcomes ranked in descending order as follows: T1N0>T2N0>T1N1 = T2N1>T3N0>T3N1. Therefore, the FIGO Stage IIIC1 was re-stratified into IIC (T1N1+T2N1) and IIIC1(T3N1). Patients who underwent radical hysterectomy combined with adjuvant therapy exhibited superior 5-year cancer-specific survival rates compared to those treated with chemoradiotherapy among IB3, IIA2, and IIC. The therapeutic efficacy of chemoradiotherapy surpassed that of radiotherapy alone in IIIA, IIIB, IIIC1(T3N1), and IVA patients. CONCLUSION: Restratification of Stage IIIC1 based on T-stage effectively discerns patients with divergent prognoses. Radical surgery + chemoradiotherapy is significantly associated with improved survival in early T-stage, regardless of lymph node status in locally advanced cervical cancer.

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BACKGROUND: This study aimed to explore the genetic basis of a fetus with ultrasound indicating a thickening of the nuchal translucency (NT) and a choroid plexus cyst. METHODS: Fetal amniotic fluid and peripheral blood were collected for a G-banding karyotype analysis and single nucleotide polymorphism array (SNP-array) detection. RESULTS: The chromosome karyotypes of the fetus and its parents were normal. SNP-array showed the fetus had carried 277 kb microdeletion at 14q11.2, which was a new mutation. After the induced abortion, the fetus was diagnosed with macrocephaly. CONCLUSIONS: A prenatal diagnosis of a fetus with 14q11.2 microdeletion-induced intrauterine growth retardation was confirmed, which has provided guidance for the subsequent pregnancy.

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Enzyme-free single-molecule sequencing has the potential to significantly expand the application of nanopore technology to DNA, proteins, and saccharides. Despite their advantages over biological nanopores and natural suitability for enzyme-free single-molecule sequencing, conventional solid-state nanopores have not yet achieved single-molecule DNA sequencing. The biggest challenge for the accuracy of single-molecule sequencing using solid-state nanopores lies in the precise control of the pore size and conformity. In this study, we fabricated nanopore devices by covering the tip of a quartz nanopipette with ultrathin two-dimensional (2D) covalent organic framework (COF) nanosheets (pore size ≈ 1.1 nm). The size of the periodically arranged nanopores in COF is comparable to that of protein nanopores, and the structure of each COF nanopore is consistent at the atomic scale. The COF nanopore device could roughly distinguish dAMP, dCMP, dGMP, and dTMP. Furthermore, a certain percentage of the current blockades originating from 150 nucleotides model DNA molecules (13.5% for dA50dC50dA50 and 11.1% for dC50dA50dC50) show distinct DNA sequence-specific concave and convex resistive current patterns. The finite element simulation confirmed that the current blockade pattern of a DNA molecule passing through a COF nanopore is dependent on the relative location of the nanopore with respect to the wall of the nanopipette. Our study is a significant step toward single-molecule DNA sequencing by solid-state nanopores.

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OBJECTIVES: Hypoxia conditions promote the adaptation and progression of non-small-cell lung cancer (NSCLC) via hypoxia-inducible factors (HIF). HIF-1α may regulate estrogen receptor ß (ERß) and promote the progression of NSCLC. The phytochemical homoharringtonine (HHT) exerts strong inhibitory potency on NSCLC, with molecular mechanism under hypoxia being elusive. METHODS: The effects of HHT on NSCLC growth were determined by cell viability assay, colony formation, flow cytometry, and H460 xenograft models. Western blotting, molecular docking program, site-directed mutagenesis assay, immunohistochemical assay, and immunofluorescence assay were performed to explore the underlying mechanisms of HHT-induced growth inhibition in NSCLC. KEY FINDINGS: HIF-1α/ERß signaling-related E2F1 is highly expressed and contributes to unfavorable survival and tumor growth. The findings in hypoxic cells, HIF-1α overexpressing cells, as well as ERß- or E2F1-overexpressed and knockdown cells suggest that the HIF-1α/ERß/E2F1 feedforward loop promotes NSCLC cell growth. HHT suppresses HIF-1α/ERß/E2F1 signaling via the ubiquitin-proteasome pathway, which is dependent on the inhibition of the protein expression of HIF-1α and ERß. Molecular docking and site-directed mutagenesis revealed that HHT binds to the GLU305 site of ERß. HHT inhibits cell proliferation and colony formation and promotes apoptosis in both NSCLC cells and xenograft models. CONCLUSION: The formation of the HIF-1α/ERß/E2F1 feedforward loop promotes NSCLC growth and reveals a novel molecular mechanism by which HHT induces cell death in NSCLC.

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Hepatocyte growth factor (HGF) plays a critical role in promoting tumor migration, invasion, and metastasis, partly by upregulating integrins. The molecular mechanisms behind how HGF facilitates integrin-mediated tumorigenesis are not fully understood. In this study, we demonstrate that the ubiquitin-specific peptidase 22 (USP22) is essential for HGF-induced melanoma metastasis. HGF treatment dramatically increased the expression of both USP22 and multiple integrin family members in particular ITGAV, ITGB3, and ITGA1. An unbiased analysis of the TCGA database reveals integrins as common downstream targets of both USP22 and HGF across multiple human cancer types. Notably, CRISPR-mediated deletion of USP22 completely eliminates HGF-induced integrin expression in melanoma cells. At the molecular level, USP22 acts as a bona fide deubiquitinase for Sp1, a transcription factor for the ITGAV, ITGB3, and ITGA1 genes. USP22 interacts with and inhibits Sp1 ubiquitination, protecting against Sp1 proteasomal degradation. Supporting this, immunohistology analysis detects a positive correlation among USP22, Sp1, and integrin αv in human melanoma tissues. This study identifies the death from the signature gene USP22 as a critical positive regulator for HGF-induced integrin expression by deubiquitinating the Sp1 transcription factor during melanoma metastasis.

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In this study, novel chitosan/polyethylene oxide/Ti3C2Tx 2D MXene nanosheets (CS/PEO/Ti3C2Tx) nanofibers were successfully prepared by a continuous electrospinning process. During the electrospinning process, induced by the syringe tip capillary effects and electric field force, the Ti3C2Tx nanosheets were aligned along the direction of the nanofiber formation to occur a highly oriented structure. This well-ordered arrangement of the inorganic Ti3C2Tx nanosheets within the organic polymer matrix nanofiber was similar with nacre-like 'brick-and-motar' structure to some extent, resulting in a marked increase in thermal stability and mechanical properties of the resultant CS/PEO/Ti3C2Tx nanofiber. As 4 wt% of Ti3C2Tx nanosheets loaded, the highest tensile strength of the CS/PEO/Ti3C2Tx nanofiber mats was achieved as 31.7 MPa, about two times that of neat CS/PEO nanofibers. Uniformly dispersed Pd nanoparticles in size of about 1.6 nm have been successfully immobilized on the composite nanofiber with a solution impregnation process. With a loading as low as 0.2 mol% of Pd, the resultant Pd@CS/PEO/Ti3C2Tx composite nanofiber catalysts were highly active for both Heck and Sonogashira coupling reactions with broad reactants application scope, and could be recycled 15 runs without significant loss of activities.

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Low back pain (LBP) is a highly prevalent disease. Among the various causes of LBP, one of the most frequent is myofascial pain syndrome (MPS) which affects the spinal stabilizer muscles. The aims of this study were to compare the differences in muscular electrical activity and biomechanical properties between the painful and non-painful sides in patients with unilateral MPS and to verify the feasibility of surface electromyography (sEMG) and MyotonPRO for assisting in MPS assessment. Forty patients with unilateral lumbar MPS were recruited via the Department of Rehabilitation Medicine Center of West China Hospital Sichuan University from October 2022 to October 2023. The electrical properties of the bilateral erector spinae muscles were characterized by sEMG signals during a trunk extension task. The following four time-domain features of sEMG were extracted: root mean square (RMS), mean absolute value (MAV), integrated EMG (iEMG), and waveform length (WL). And two frequency domain features were extracted: the median frequency (MDF) and mean power frequency (MPF). The mechanical properties of the muscles were assessed by MyotonPRO at rest. The following biomechanical parameters were acquired: oscillation frequency [Hz], dynamic stiffness [N/m], logarithmic decrement, relaxation time [ms], and Creep. The visual analog scale (VAS) was used to evaluate the pain severity, and the Oswestry Disability Index (ODI) was used to evaluate the severity of disability and disruption to lifestyle activities caused by LBP pain. The outcome measures were obtained prior to the Platelet-rich plasma (PRP) treatment and repeated two weeks after treatment. (1) Prior to the PRP treatment, all sEMG time-domain features on the painful side were significantly higher than those on the non-painful side (RMS, p < 0.001; MAV, p < 0.001; iEMG, p < 0.001; WL, p = 0.001). However, there was no significant difference in the sEMG frequency-domain features (MPF, p = 0.478; MDF, p = 0.758). On the mechanical side, there were significant differences in oscillation frequency (p = 0.041) and logarithmic decrement (p = 0.022) between the painful side and non-painful side, but no significant differences in dynamic stiffness, relaxation time, and creep (both p > 0.05). (2) Two weeks after the PRP treatment, statistically significant decreases were observed in both post-treatment VAS (p < 0.001) and ODI scales (p < 0.001), indicating the PRP treatment clinically significantly reduced the level of. MPS. This change coincided with all sEMG time-domain features, in which the values at the painful side decreased significantly (RMS, p = 0.001; MAV, p = 0.001; iEMG, p = 0.001; WL, p = 0.001). However, no significant difference in the sEMG frequency-domain features (MPF, p = 0.620; MDF, p = 0.850) was found. On the mechanical side, only logarithmic decrement on the painful side increased significantly (p < 0.001). Our combined MyotonPRO and sEMG results indicated that MPS likely leads to increased muscle tone and decreased muscle elasticity, manifested by abnormal time-domain features of sEMG and biomechanical properties. The changes in these objective measurements were agreed with the changes in subjective outcome measures of pain and function currently assessed in the patients with MPS. A single PRP treatment may alleviate muscle dysfunction caused by MPS. These preliminary results demonstrated the potential feasibility of using sEMG and MyotonPRO as tools for assessing the neuromuscular function of MPS.

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A 35-year-old woman was initially misdiagnosed with a muscular ventricular septal defect but was later correctly diagnosed with a double-chambered left ventricle following evaluation by echocardiography and cardiac computed tomography.

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The inhomogeneous plating/stripping of Zn anode, attributed to dendrite growth and parasitic reactions at the electrode/electrolyte interface, severely restricts its cycling life-span. Here, trace zwitterions (trifluoroacetate pyridine, TFAPD) are introduced into the aqueous electrolyte to construct a multifunctional interface that enhances the reversibility of Zn anode. The TFA- anions with strong specific adsorption adhere onto the Zn surface to reconstruct the inner Helmholtz plane (IHP), preventing the hydrogen evolution and corrosion side reactions caused by free H2O. The Py+ cations accumulate on the outer Helmholtz plane (OHP) of Zn anode with the force of electric field during Zn2+ plating, forming a shielding layer to uniformize the deposition of Zn2+. Besides, the adsorbed TFA- and Py+ promote the desolvation process of Zn2+ resulting in fast reaction kinetics. Thus, the Zn||Zn cells present an outstanding cycling performance of more than 10000 hours. And even at 85% utilization rate of Zn, it can stably cycle for over 200 hours at 10 mA cm-2 and 10 mAh cm-2. The Zn||I2 full cell exhibits a capacity retention of over 95% even after 30000 cycles. Remarkably, the Zn||I2 pouch cells (95 mAh) deliver a high-capacity retention of 99% after 750 cycles.

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Objective: This paper utilizes data from the China Family Panel Studies (CFPS) to evaluate the impact of the "4 + 7" National Centralized Drug Procurement (NCDP) on Per Capita Household Health Care Expenditure (PCHHCE). Methods: The study applies the Differences-in-Differences (DID) methodology to analyze the effects of NCDP. Various robustness tests were conducted, including the Permutation test, Propensity Score Matching, alterations in regression methodologies, and consideration of individual fixed effects. Results: Research indicates that the implementation of NCDP led to a reduction of 10.6% in PCHHCE. The results remained consistent across all robustness tests. Additionally, the research identifies diversity in NCDP effects among various household characteristics, with a more significant impact on households residing in rural regions of China, enrolled in Basic Medical Insurance for urban and rural residents and urban workers, and having an income bracket of 25-75%. Conclusion: These findings carry policy implications for the future expansion and advancement of NCDP in China. The study highlights the effectiveness of NCDP in reducing healthcare expenditures and suggests potential areas for policy improvement and further research.

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Antibodies against N-methyl-D-aspartate receptors (NMDARs) are most frequently detected in persons with autoimmune encephalitis (AE) and used as diagnostic biomarkers. Elucidating the structural basis of monoclonal antibody (mAb) binding to NMDARs would facilitate the development of targeted therapy for AE. Here, we reconstructed nanodiscs containing green fluorescent protein-fused NMDARs to label and sort individual immune B cells from persons with AE and further cloned and identified mAbs against NMDARs. This allowed cryo-electron microscopy analysis of NMDAR-Fab complexes, revealing that autoantibodies bind to the R1 lobe of the N-terminal domain of the GluN1 subunit. Small-angle X-ray scattering studies demonstrated NMDAR-mAb stoichiometry of 2:1 or 1:2, structurally suitable for mAb-induced clustering and endocytosis of NMDARs. Importantly, these mAbs reduced the surface NMDARs and NMDAR-mediated currents, without tonically affecting NMDAR channel gating. These structural and functional findings imply that the design of neutralizing antibody binding to the R1 lobe of NMDARs represents a potential therapy for AE treatment.

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Allergen-crosslinked IgE triggers allergy by interacting with its receptor on basophils and mast cells. The anti-IgE monoclonal antibody omalizumab can alleviate allergy by competing with the receptor for IgE binding. However, along with neutralization, omalizumab also inhibits IgE degradation, which is clinically associated with high dose and total IgE accumulation problems. In this study, we have developed an IgE-eliminating antibody on the basis of omalizumab, which has pH-dependent Fabs and an Fc with high affinity for FcγRIIb. In mice, the antibody rapidly eliminated total serum IgE to baseline levels and caused lower free IgE levels than omalizumab. At low dosages, the antibody also exhibited favorable IgE elimination effects. In addition, the antibody can degrade the corresponding allergen with the removal of IgE, addressing the allergy from its source. Introduction of the M252Y/S254T/T256E (YTE) mutation into this antibody prolongs its serum half-life without reducing potency. Thus, this engineered antibody holds a promising therapeutic option for allergy patients. Mechanistic insights are also included in this study.

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BACKGROUND: Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome (ARDS) patients. Mesenchymal stromal cell-derived microvesicles (MSC-MVs) have been shown to exert antifibrotic effects in lung diseases. AIM: To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models. METHODS: MSC-MVs with low hepatocyte growth factor (HGF) expression (siHGF-MSC-MVs) were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model. Following intubation, respiratory mechanics-related indicators were measured via an experimental small animal lung function tester. Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging. Immunohistochemical, western blotting, ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators. RESULTS: The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice. Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores. However, low expression of HGF (siHGF-MSC-MVs) significantly inhibited the effects of MSC-MVs (P < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expression of type I collagen antigen, type III collagen antigen, and the proteins transforming growth factor-ß and α-smooth muscle actin, whereas the siHGF-MVs group exhibited significantly increased expression of these proteins. In addition, pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group, and the effects of the MSC-MVs were significantly inhibited by low HGF expression (all P < 0.05). CONCLUSION: MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

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We assessed the diversity, composition, and distribution of bird species in patches of semi-humid evergreen broad-leaved forest by selecting eight natural forest communities in the central Yunnan Plateau, which is a representative distribution area of semi-humid broad-leaved evergreen forest. Field observations were conducted from April to August 2023 by the sample line and sample point method, and eight survey routes of 3-4 km in length were established. The results showed that 1) A total of 1286 birds were recorded, belonging to 102 species in 7 orders and 30 families. The three most abundant families were Muscicapidae (14 species), Leiothrichidae (9 species), and Phylloscopidae (7 species); 2) Species of Oriental origin, Palaearctic origin, and widespread species accounted for 81.4%, 4.9%, and 13.7% of observations, respectively; 3) The average number of bird species surveyed in forest patches was 32.0±3.5; the Shannon index of birds was lower in secondary, semi-humid evergreen broad-leaved forests (1.536±0.110) than in primary forest communities (2.037±0.100); 4) Species composition exhibited considerable variation between patches, with the presence of dominant and common species, and the difference in rare species; 5) Considering the ecological groups of birds based on diet, invertebrate-eating and omnivorous birds, herbivorous birds, and carnivorous birds accounted for 84.3%, 11.8%, and 3.9%, respectively. The coexistence of birds with similar diets was maintained by diluting interspecific competition, mainly through partitioning of the vertical feeding space. For the conservation of bird species diversity and rare species, all patches of native semi-humid evergreenbroad-leaved forest are of conservation value.

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We analyzed age structure and dynamics, spatial distribution patterns, and reproductive capabilities of four Rosa persica populations in Xinjiang, to evaluate the survival status of the species and explore the reasons behind its endangerment. The results showed that the populations had fewer individuals in the youngest (Ⅰ) and oldest (Ⅵ-Ⅷ) age classes, with a predominance of middle-aged individuals, resulting in an irregular pyramid-shaped distribution, described as "high in the middle, low on both sides". The populations were generally growing, but were susceptible to external environmental disturbances (Vpi'＞0, Pmax＞0). The mortality rate (qx) and vanish rate (Kx) peaked at age Ⅴ, leading to a sharp decline in plant abundance. The life expectancy (ex) decreased progressively with the increases of age class, reaching its lowest at age Ⅷ, which indicated minimal vitality at this stage. A time sequence analysis predicted a future dominance of individuals at age Ⅴ-Ⅷ, suggesting an aging trend. Spatially, the four populations were predominantly clumped, with the intensity of clumping ranked from highest to lowest as P4, P3, P1, and P2. P3 and P4 exhibited better reproductive capabilities than P1 and P2. There was a significant positive correlation between hundred-fruit weight and plant height and crown width, and between total seed number and crown width and hundred-fruit weight.

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BACKGROUND: Alternating sequential administration of drugs may be a promising approach to overcome chemotherapy resistance in advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: This study was an open-label, single-arm, and prospective trial included patients with untreated advanced PDAC. They received 2 cycles of NS regimen (nab-paclitaxel:125 mg/m2, intravenously injected on days 1 and 8, plus S-1:40-60 mg, orally twice per day for 1-14 days) followed by 2 cycles of GemOx regimen (gemcitabine, intravenously injected on days 1 and 8, and oxaliplatin: 130 mg/m2, intravenously injected on day 1). The primary efficacy endpoint was a progression-free survival rate at 6 months (PFSR-6m). The secondary efficacy endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Specific mRNA transcripts were used to explore survival associated genes. RESULTS: Forty-two patients received a minimum of one treatment cycle, and of these, 30 patients completed one alternating treatment consisting of 4 cycles. The PFSR-6m was 71% (95% CI = 58%-87%). The median PFS and OS were 6.53 months (95% CI = 6.03-8.43) and 11.4 months (95% CI = 9.8-14.4), respectively. Common grades 3-4 hematological AEs included neutropenia 30.9%, leukopenia 26.2%, anemia 2.4%, and thrombocytopenia in 11.9%. Patients with OS > 10 months showed high expression of HLA-DQA2 while melanoma-associated antigen genes (MAGE) were notably upregulated in patients with OS < 10 months. CONCLUSION: The alternating sequential administration of the NS and GemOx regimens may be a novel approach for first-line chemotherapy in patients with advanced PDAC requiring further study (ClinicalTrials.gov Identifier: ChiCTR1900024867).