Size-dependent reactivity of VnO+ (n = 1-9) clusters with ethane.

Cost-effective and readily accessible 3d transition metals (TMs) have been considered as promising candidates for alkane activation while 3d TMs especially the early TMs are usually not very reactive with light alkanes. In this study, the reactivity of Vn+ and VnO+ (n = 1-9) cluster cations towards ethane under thermal collision conditions has been investigated using mass spectrometry and density functional theory calculations. Among Vn+ (n = 1-9) clusters, only V3-5+ can react with C2H6 to generate dehydrogenation products and the reaction rate constants are below 10-13 cm3 molecule-1 s-1. In contrast, the reaction rate constants for all VnO+ (n = 1-9) with C2H6 significantly increase by about 2-4 orders of magnitude. Theoretical analysis evidences that the addition of ligand O affects the charge distribution of the metal centers, resulting in a significant increase in the cluster reactivity. The analysis of frontier orbitals indicates that the agostic interaction determines the size-dependent reactivity of VnO+ cluster cations. This study provides a novel approach for improving the reactivity of early 3d TMs.

[Multi-scenario Simulation of Construction Land Expansion and Its Impact on Ecosystem Carbon Storage in Beijing-Tianjin-Hebei Urban Agglomeration].

It is of great practical significance for regional sustainable development and ecological construction to quantitatively analyze the impact of construction land expansion on terrestrial ecosystem carbon storage and to explore the optimization scheme of simulating construction land expansion to improve future ecosystem carbon storage. Based on the land use and cover change (LUCC) and other geospatial data of the Beijing-Tianjin-Hebei Urban Agglomeration from 2000 to 2020, this study utilized the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model and the patch-generating land-use simulation (PLUS) model to assess and analyze the changes in ecosystem carbon stocks and spatial patterns regionally. In this study, we performed linear regression analysis to investigate the relationship between urban land expansion and changes in ecosystem carbon stocks for varying urban land proportion levels during two distinct time intervals, 2000-2010 and 2010-2020, which was conducted at a spatial resolution of 2 km. Three distinct urban land expansion scenarios were subjected to simulation to forecast the prospective land use pattern by 2030. Subsequently, we quantified the ramifications of these scenarios on ecosystem carbon stocks during the period from 2020 to 2030. The results were as follows:① In the Beijing-Tianjin-Hebei Urban Agglomeration, the ecosystem carbon stocks exhibited notable variations over the study period, with values of 2 088.02, 2 106.78, and 2 121.25 Tg recorded for the years 2000, 2010, and 2020, respectively, resulting in a cumulative carbon sequestration of 33.23 Tg C during the study duration. It is noteworthy that forest carbon storage emerged as the dominant contributor, with an increase from 1 010.17 Tg in 2000 to 1 136.53 Tg in 2020. Throughout the study period, the spatial distribution of carbon stocks displayed relative stability. Regions characterized by lower carbon content were concentrated in the vicinity of the Bohai Rim region and in proximity to cities such as Beijing, Tianjin, and Shijiazhuang, as well as rural settlements. In contrast, grid units with moderate and high carbon stocks were predominantly situated in the western Taihang Mountain and the northern Yanshan Mountain. Additionally, there was a tendency of increasing carbon stocks in the Taihang Mountain and Yanshan Mountain region, whereas those surrounding major urban centers such as Beijing, Tianjin, Shijiazhuang, and Tangshan experienced a notable decline in carbon stocks. Such reductions were most pronounced in regions undergoing urban land expansion during the study period. ② In grid units with an urban land proportion exceeding 10% at each level, a strong correlation was observed between urban land expansion and changes in carbon stocks during both the 2000-2010 and 2010-2020 periods. The changes in urban land proportion adequately explained the variations in carbon stocks. However, the explanatory power of urban land on carbon stocks decreased during the 2010-2020 period, indicating that other factors played a more substantial role in influencing carbon stocks during this time. The regression coefficients for both periods exhibited a fluctuating upward trend. In comparison to that during the 2000-2010 period, the impact of urban land expansion on carbon stocks was relatively smaller during 2010-2020, indicating a weakening influence. ③ In light of three distinct development scenarios, namely natural development (Scenario Ⅰ), a 15% reduction in the rate of urban land expansion (Scenario Ⅱ), and a 30% reduction in the rate of urban land expansion (Scenario Ⅲ), the projected ecosystem carbon stocks for the Beijing-Tianjin-Hebei Urban Agglomeration in the year 2030 were estimated to be 2 129.12, 2 133.55, and 2 139.10 Tg, respectively. These projections indicated an increase of 7.88, 12.30, and 17.85 Tg in comparison to the current carbon stocks. All scenarios demonstrated that the terrestrial ecosystem would play a role of carbon sink, particularly with the greatest carbon sink observed in the scenario with a 30% reduction in urban land expansion. The fit performance between urban land expansion and carbon stock changes during the 2020-2030 period was significantly better than that during the 2000-2010 and 2010-2020 periods, and the regression coefficients showed a fluctuating increase with an increase in urban land proportion. Across grid units with different urban land proportion levels, the regression coefficients exhibited the order of Scenario Ⅰ < Scenario Ⅱ < Scenario Ⅲ. In pursuit of the carbon peaking and carbon neutrality goals, the Beijing-Tianjin-Hebei Urban Agglomeration should prioritize scenarios with reduced rates of urban land expansion, especially in regions with higher urban land proportions.

Machine Learning for Experimental Reactivity of a Set of Metal Clusters toward C-H Activation.

Understanding the mechanisms of C-H activation of alkanes is a very important research topic. The reactions of metal clusters with alkanes have been extensively studied to reveal the electronic features governing C-H activation, while the experimental cluster reactivity was qualitatively interpreted case by case in the literature. Herein, we prepared and mass-selected over 100 rhodium-based clusters (RhxVyOz- and RhxCoyOz-) to react with light alkanes, enabling the determination of reaction rate constants spanning six orders of magnitude. A satisfactory model being able to quantitatively describe the rate data in terms of multiple cluster electronic features (average electron occupancy of valence s orbitals, the minimum natural charge on the metal atom, cluster polarizability, and energy gap involved in the agostic interaction) has been constructed through a machine learning approach. This study demonstrates that the general mechanisms governing the very important process of C-H activation by diverse metal centers can be discovered by interpreting experimental data with artificial intelligence.

Thermal Reactions of NiAl3O6+ and Al4O6+ with Methane: Reactivity Enhancement by Doping.

Investigation of the reactivity of heteronuclear metal oxide clusters is an important way to uncover the molecular-level mechanisms of the doping effect. Herein, we performed a comparative study on the reactions of CH4 with NiAl3O6+ and Al4O6+ cluster cations at room temperature to understand the role of Ni during the activation and transformation of methane. Mass spectrometric experiments identify that both NiAl3O6+ and Al4O6+ could bring about hydrogen atom abstraction reaction to generate CH3• radical; however, only NiAl3O6+ has the potential to stabilize [CH3] moiety and then transform [CH3] to CH2O. Density functional theory calculations demonstrate that the terminal oxygen radicals (Ot-•) bound to Al act as the reactive sites for the two clusters to activate the first C-H bond. Although the Ni atom cannot directly participate in methane activation, it can manipulate the electronic environment of the surrounding bridging oxygen atoms (Ob) and enable such Ob to function as an electron reservoir to help Ot-• oxidize CH4 to [H-O-CH3]. The facile reduction of Ni3+ to Ni+ also facilitates the subsequent step of activating the second C-H bond by the bridging "lattice oxygen" (Ob2-), finally enabling the oxidation of methane into formaldehyde. The important role of the dopant Ni played in improving the product selectivity of CH2O for methane conversion discovered in this study allows us to have a possible molecule-level understanding of the excellent performance of the catalysts doping with nickel.

Activation of Methane by Rhodium Clusters on a Model Support C20H10.

Supported metals represent an important family of catalysts for the transformation of the most stable alkane, methane, under mild conditions. Here, using state-of-the-art mass spectrometry coupled with a newly designed double ion trap reactor that can run at high temperatures, we successfully immobilize a series of Rhn- (n = 4-8) cluster anions on a model support C20H10. Reactivity measurements at room temperature identify a significantly enhanced performance of large-sized Rh7,8C20H10- toward methane activation compared to that of free Rh7,8-. The "support" acting as an "electron sponge" is emphasized as the key factor to improve the reactivity of large-sized clusters, for which the high electron-withdrawing capability of C20H10 dramatically shifts the active Rh atom from the apex position in free Rh7- to the edge position in "supported" Rh7- to enhance CH4 adsorption, while the flexibility of C20H10 to release electrons further promotes subsequent C-H activation. The Rh atoms in direct contact with the support serve as electron-relay stations for electron transfer between C20H10 and the active Rh atom. This work not only establishes a novel approach to prepare and measure the reactivity of "supported" metal clusters in isolated gas phase but provides useful atomic-scale insights for understanding the chemical behavior of carbon (e.g., graphene)-supported metals in heterogeneous catalysis.

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer.

BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC). METHODS: For this integrated analysis, from inception to January 2, 2023, we searched PubMed, Web of Science, Embase, and Cochrane library databases for prospective studies that evaluated SC in RM-TNBC patients. Primary endpoints were survival outcomes and responses. Secondary endpoints were all grade and grade ≥ 3 toxicities. RESULTS: Six hundred potentially relevant records were screened. Our analysis included 3 trials (412 patients). Median overall survival was 12.9 months (95% confidence interval [CI], 11.5-14.4), progression-free survival was 5.7 months (5% CI, 5.1-6.3), and duration of objective response was 7.4 months (5% CI, 5.8-9.0). The objective response rate was 34%, and the disease control rate was 71%. Key grade ≥ 3 toxicities (in over 10% of the patients) included neutropenia (46%), leukopenia (12%), febrile neutropenia (11%), diarrhea (11%), and anemia (10%). Four treatment-related deaths were reported. CONCLUSION: SG was associated with effectiveness in patients with RM-TNBC. Myelosuppression and diarrhea were the primary treatment-related adverse events.

High-temperature reactivity of vanadium oxide clusters in methane activation: Vibrational degrees of freedom matter.

Understanding the properties of small particles working under high-temperature conditions at the atomistic scale is imperative for exact control of related processes, but it is quite challenging to achieve experimentally. Herein, benefitting from state-of-the-art mass spectrometry and by using our newly designed high-temperature reactor, the activity of atomically precise particles of negatively charged vanadium oxide clusters toward hydrogen atom abstraction (HAA) from methane, the most stable alkane molecule, has been measured at elevated temperatures up to 873 K. We discovered the positive correlation between the reaction rate and cluster size that larger clusters possessing greater vibrational degrees of freedom can carry more vibrational energies to enhance the HAA reactivity at high temperature, in contrast with the electronic and geometric issues that control the activity at room temperature. This finding opens up a new dimension, vibrational degrees of freedom, for the simulation or design of particle reactions under high-temperature conditions.

C-H Activation by Iron-Vanadium Bimetallic Oxide Cluster Anions FeV3 O10 - and FeV5 O15 - : A Comparison with Scandium-Vanadium Oxide Clusters.

Late transition metal-bonded atomic oxygen radicals (LTM-O⋅- ) have been frequently proposed as important active sites to selectively activate and transform inert alkane molecules. However, it is extremely challenging to characterize the LTM-O⋅- -mediated elementary reactions for clarifying the underlying mechanisms limited by the low activity of LTM-O⋅- radicals that is inaccessible by the traditional experimental methods. Herein, benefiting from our newly-designed ship-lock type reactor, the reactivity of iron-vanadium bimetallic oxide cluster anions FeV3 O10 - and FeV5 O15 - featuring with Fe-O⋅- radicals to abstract a hydrogen atom from C2 -C4 alkanes has been experimentally characterized at 298 K, and the rate constants are determined in the orders of magnitude of 10-14 to 10-16  cm3 molecule-1 s-1 , which are four orders of magnitude slower than the values of counterpart ScV3 O10 - and ScV5 O15 - clusters bearing Sc-O⋅- radicals. Theoretical results reveal that the rearrangements of the electronic and geometric structures during the reaction process function to modulate the activity of Fe-O⋅- . This study not only quantitatively characterizes the elementary reactions of LTM-O⋅- radicals with alkanes, but also provides new insights into structure-activity relationship of M-O⋅- radicals.

Methane activation by vanadium oxide cluster anions (V2O5)NO- (N = 1-18).

The reactivity of vanadium oxide cluster anions (V2O5)NO- (N = 1-18) that feature with vanadium oxyl radicals (V-O⋅-) toward the most stable alkane, methane, at 273 K has been characterized by employing a newly home-made ship-lock type reactor coupled with a time-of-flight mass spectrometer. The rate constants were determined in the orders of magnitude of 10-16-10-18 cm3 molecule-1 s-1, which significantly breaks the detection limit of predecessors that the reactivity of metal-oxyl radicals (Mn+-O⋅-) with rate constants higher than 10-14 cm3 molecule-1 s-1 could usually be measured. The dynamic structural rearrangement of the cluster skeleton has been proposed to account for the size-dependent reactivity of (V2O5)1-5O- clusters, which may also function in tuning the reactivity of large-sized (V2O5)6-18O- clusters. This work provides new insights into the mechanism of Mn+-O⋅--mediated C-H activation of methane at a strictly molecular level and expands the activity landscape of Mn+-O⋅- radicals.

Tyrosine Kinase Inhibitors for Pediatric Leukemia: History and Current Status.

Tyrosine kinase inhibitors (TKIs) block the activity of tyrosine kinases by competitive inhibition of ATP at the catalytic tyrosine kinase binding site and inhibit oncogenic signaling. One important target of TKIs is BCR-ABL1, which is constitutively activated in leukemia cells. In this review, we briefly describe the development of TKIs from the first generation to the third generation, and summarize their use in the treatment of chronic myeloid leukemia and acute lymphoblastic leukemia in children. We highlight several future directions in the development of TKIs for pediatric leukemia therapy. In conclusion, we focus on chronic myeloid leukemia and acute lymphoblastic leukemia as the examples of pediatric blood cancer that significantly benefit from TKIs-based target therapy. Further development of TKIs will allow us to better manage pediatric leukemia.

Pyrolysis of mass-selected (V2O5)NO- (N = 1-6) clusters in a high-temperature linear ion trap reactor.

A high-temperature linear ion trap that can stably run up to 873 K was newly designed and installed into a homemade reflectron time-of-flight mass spectrometer coupled with a laser ablation cluster source and a quadrupole mass filter. The instrument was used to study the pyrolysis behavior of mass-selected (V2O5)NO- (N = 1-6) cluster anions and the dissociation channels were clarified with atomistic precision. Similar to the dissociation behavior of the heated metal oxide cluster cations reported in literature, the desorption of either atomic oxygen atom or molecular O2 prevailed for the (V2O5)NO- clusters with N = 2-5 at 873 K. However, novel dissociation channels involving fragmentation of (V2O5)NO- to small-sized VxOy - anions concurrent with the release of neutral vanadium oxide species were identified for the clusters with N = 3-6. Significant variations in branching ratios for different dissociation channels were observed as a function of cluster size. Kinetic studies indicated that the dissociation rates of (V2O5)NO- monotonically increased with the increase in cluster size. The internal energies carried by the (V2O5)NO- clusters at 873 K as well as the energetics data for dissociation channels have been theoretically calculated to rationalize the experimental observations. The decomposition behavior of vanadium oxide clusters from this study can provide new insights into the pyrolysis mechanism of metal oxide nanoparticles that are widely used in high temperature catalysis.

Fluorescent Talarolactones from Talaromyces sp.

(+)-Talarolactone C (1), Talarolactone A (2), Talarolactone B (3, sulfoxide derivative), and Talarolactone D (4, sulfone derivative) were isolated from Talaromyces sp. which was cultured in rice medium with sodium butyrate. The structures of talarolactone analogs above were characterized by a combination of spectroscopic, X-ray crystallographic, and computational methods. These talarolactones and Talarolactone A sodium (5) with the same carbon skeleton showed different fluorescence characteristics.

Conversion of CH4 Catalyzed by Gas Phase Ions Containing Metals.

Methane is an abundant and cheap feedstock to produce valuable chemicals. The catalytic reaction of methane conversion generally requires the participation of multiple molecules (such as two or three CH4 molecules, O2 , CO2 , etc.). Such complex process includes the cleavage of original chemical bonds, formation of new chemical bonds, and desorption of products. The gas phase study provides a unique arena to gain molecular-level insights into the detailed mechanisms of bond-breaking and bond-forming involved in complicated catalytic reactions. In this Review, we introduce the methane conversion catalyzed by gas phase ions containing metals and three topics will be discussed: (1) the direct coupling of methane molecules, (2) the conversion of CH4 with O2 , O3 and N2 O, and (3) the conversion of CH4 with CO2 and H2 O. The obtained mechanistic aspects may provide new clues for rational design of better-performing catalysts for conversion of methane to value-added products.

Conversion of Methane with Oxygen to Produce Hydrogen Catalyzed by Triatomic Rh3 - Cluster Anion.

Metal catalysts, especially noble metals, have frequently been prepared upon downsizing from nanoparticles to subnanoclusters to catalyze the important reaction of partial oxidation of methane (POM) in order to optimize the catalytic performance and conserve metal resources. Here, benefiting from mass spectrometric experiments in conjunction with photoelectron spectroscopy and quantum chemical calculations, we successfully determine that metal cluster anions composed of only three Rh atoms (Rh3 -) can catalyze the POM reaction with O2 to produce 2H2 + CO2 under thermal collision conditions (∼300 K). The interdependence between CH4 and O2 to protect Rh3 - from collapse and to promote conversion of CH4 → 2H2 has been clarified. This study not only provides a promising metal cluster displaying good catalytic behavior in POM reaction under mild conditions but also reveals a strictly molecular-level mechanism of direct partial oxidation for the production of hydrogen, a promising renewable energy source in the 21st century.

Methane Activation by (MoO3 )5 O- Cluster Anions: The Importance of Orbital Orientation.

The reactivity of the molybdenum oxide cluster anion (MoO3 )5 O- , bearing an unpaired electron at a bridging oxygen atom (Ob .- ), towards methane under thermal collision conditions has been studied by mass spectrometry and density functional theory calculations. This reaction follows the mechanism of hydrogen atom transfer (HAT) and is facilitated by the Ob .- radical center. The reactivity of (MoO3 )5 O- can be traced back to the appropriate orientation of the lowest unoccupied molecular orbitals (LUMO) that is essentially the 2p orbital of the Ob .- atom. This study not only makes up the blank of thermal methane activation by the Ob .- radical on negatively charged clusters but also yields new insights into methane activation by the atomic oxygen radical anions.

Rhodium chemistry: A gas phase cluster study.

Due to the extraordinary catalytic activity in redox reactions, the noble metal, rhodium, has substantial industrial and laboratory applications in the production of value-added chemicals, synthesis of biomedicine, removal of automotive exhaust gas, and so on. The main drawback of rhodium catalysts is its high-cost, so it is of great importance to maximize the atomic efficiency of the precious metal by recognizing the structure-activity relationship of catalytically active sites and clarifying the root cause of the exceptional performance. This Perspective concerns the significant progress on the fundamental understanding of rhodium chemistry at a strictly molecular level by the joint experimental and computational study of the reactivity of isolated Rh-based gas phase clusters that can serve as ideal models for the active sites of condensed-phase catalysts. The substrates cover the important organic and inorganic molecules including CH4, CO, NO, N2, and H2. The electronic origin for the reactivity evolution of bare Rhx q clusters as a function of size is revealed. The doping effect and support effect as well as the synergistic effect among heteroatoms on the reactivity and product selectivity of Rh-containing species are discussed. The ingenious employment of diverse experimental techniques to assist the Rh1- and Rh2-doped clusters in catalyzing the challenging endothermic reactions is also emphasized. It turns out that the chemical behavior of Rh identified from the gas phase cluster study parallels the performance of condensed-phase rhodium catalysts. The mechanistic aspects derived from Rh-based cluster systems may provide new clues for the design of better performing rhodium catalysts including the single Rh atom catalysts.

Catalytic Co-Conversion of CH4 and CO2 Mediated by Rhodium-Titanium Oxide Anions RhTiO2.

Catalytic co-conversion of methane with carbon dioxide to produce syngas (2 H2 +2 CO) involves complicated elementary steps and almost all the elementary reactions are performed at the same high temperature conditions in practical thermocatalysis. Here, we demonstrate by mass spectrometric experiments that RhTiO2 - promotes the co-conversion of CH4 and CO2 to free 2 H2 +CO and an adsorbed CO (COads ) at room temperature; the only elementary step that requires the input of external energy is desorption of COads from the RhTiO2 CO- to reform RhTiO2 - . This study not only identifies a promising active species for dry (CO2 ) reforming of methane to syngas, but also emphasizes the importance of temperature control over elementary steps in practical catalysis, which may significantly alleviate the carbon deposition originating from the pyrolysis of methane.

6 versus 12 months of adjuvant trastuzumab in HER2+ early breast cancer: A systematic review and meta-analysis.

BACKGROUND: Adjuvant trastuzumab improves survival outcomes of human epidermal receptor 2 positive early breast cancer patients. Currently, administration of 12 months adjuvant trastuzumab is the standard therapy. However, whether 6 months treatment is non-inferior to the standard 12 months treatment remains controversial. METHODS: Relevant records were searched in PubMed, Cochrane Library, Web of Science, and EMBASE through Jan 14, 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were meta-analyzed. The primary endpoint was DFS with a non-inferiority hazard margin of 1.2 and the second was OS with 1.43. RESULTS: Three randomized clinical studies met the inclusion criteria, including 3974 patients in 6 months group and 3976 in 12 months group. HR for DFS was 1.18 (95% CI 0.97-1.44, P = .09), with the non-inferiority margin comprised in the 95% CI. HR for OS was 1.14 (95% CI 0.98-1.32, P= .08), whereas the upper limit of 95% CI did not exceed the non-inferiority hazard margin. CONCLUSION: Our analysis failed to show that 6 months treatment was non-inferior to 12 months treatment in improving the DFS. Although the non-inferiority of the 6-month adjuvant trastuzumab treatment was found for OS, considering that breast cancer patients should receive additional systematic therapies when disease progression or relapse happens, we suggest that 12 months adjuvant trastuzumab treatment should remain the standard therapeutic strategy for patients with early human epidermal receptor 2 positive breast cancer.

Photooxidation of Isoprene by Titanium Oxide Cluster Anions with Dimensions up to a Nanosize.

Titania (TiO2) nanoparticles are active photocatalysts, and isoprene (C5H8) is a biogenic volatile organic compound that contributes crucially to global particulate matter generation. Herein, the direct photooxidation of isoprene by titanium oxide cluster anions with dimensions up to a nanosize by both ultraviolet (UV) and visible (Vis) light excitations has been successfully identified through mass spectrometric experiments combined with quantum chemistry calculations. The potential role of "dry" titania in atmospheric isoprene oxidation has been revealed, and a clear picture of the photooxidation mechanism on titanium oxide nanoparticles has been provided explicitly at the molecular level. The adsorption of isoprene on the atomic oxygen radicals (O•-) of titanium oxide clusters leads to the formation of the crucial interfacial state (IS) within the band gap of titanium oxides. This IS is demonstrated to be the significant factor in delivering the electron from the π orbital of C5H8 to the Ti3d orbital in the photooxidation process (C5H8 + Ti4+-O•- → C5H8O + Ti3+) and creating photoactivity in the Vis region. It is revealed that after the photogeneration of the O•- radicals by UV excitation on the TiO2 particle surface, the subsequent reactions can be induced by Vis excitation through the IS. This multicolor strategy in both the UV and Vis regions can enhance the efficiency of solar energy harvesting and improve the product yield of the photocatalysis on TiO2 nanoparticles. New insights have been provided into both the atmospheric chemistry of isoprene and the photochemistry of TiO2 nanoparticles.

Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia.

AIMS: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS: A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS: The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.