PTX-RPPR, a conjugate of paclitaxel and NRP-1 peptide inhibitor to prevent tumor growth and metastasis.

Paclitaxel, a potent anti-tumor drug widely recognized for its therapeutic efficacy, has faced limitations in clinical application due to its poor solubility. The use of Cremophor EL (CrEL) as a cosolvent in paclitaxel injections has been associated with hypersensitivity reactions in some patients. To overcome these challenges, we have developed a novel conjugate by linking a neuropilin-1 targeting peptide, RPPR, to paclitaxel, resulting in PTX-RPPR. This innovative approach has significantly enhanced the solubility of paclitaxel, achieving a 3.8 mg/mL concentration, a remarkable 90-fold increase over the native drug. PTX-RPPR has shown potent anti-tumor activity, inhibiting tumor cell proliferation with an IC50 ranging from 0.26 to 1.64 µM and effectively suppressing migration, invasion, and angiogenesis at a concentration of 75 nM. Notably, in a 4T1 mammary carcinoma model, PTX-RPPR administered at a dose of 0.7 µmol/kg exhibited tumor growth inhibition comparable to that of paclitaxel at a higher dose of 3.5 µmol/kg, with superior efficacy in preventing lung metastasis. Furthermore, PTX-RPPR effectively reduced NRP-1 expression in both tumors and lungs post-treatment. In contrast to paclitaxel formulated with CrEL, PTX-RPPR did not induce IL-6 expression, suggesting a safer profile in terms of immunological response. Characterized by a particle size of 200 nm and a zeta potential of +30 mV, the nano-formulation of PTX-RPPR demonstrated remarkable stability over seven days. This study introduced PTX-RPPR as a promising peptide-drug conjugate that addresses the solubility and hypersensitivity issues associated with paclitaxel, offering a safer therapeutic strategy for cancer treatment.

Experimental Investigations and MD Simulation on Nanoparticle-Enhanced CO2-Responsive Foam (NECRF): Implications on CO2-EOR.

CO2-responsive foam (CRF) is a highly promising candidate for CO2-enhanced oil recovery (CO2-EOR) because it displays higher stability than the surfactant-stabilized foam owing to the formation of robust wormlike micelles (WLMs) upon exposure to CO2. In this work, the nanoparticle-enhanced CO2-responsive foam (NECRF) was properly prepared using lauryl ether sulfate sodium (LES)/diethylenetriamine/nano-SiO2, and its interfacial properties and EOR potential were experimentally and numerically assessed, aiming to explore the feasibility and effectiveness of NECRF as a novel CO2-EOR technique. It was found that the interfacial expansion elastic modulus increased 6-fold after CO2 stimulation. The modulus continued to increase with the introduction of nano-SiO2 owing to the pronounced synergistic effect of WLMs and nanoparticles. In addition to increasing the viscosity of the foaming liquid, WLMs and nano-SiO2 enhanced the shearing resistance of the NECRF as well. Calculations demonstrated that both the coarsening rate and the size distribution uniformity coefficient of NECRF were markedly lower than that of the LES foam, which subsequently inhibited NECRF decay and greatly improved its dynamic stability. Besides, molecular dynamics simulation revealed that adding inorganic salts to NECRF could notably enhance the foaming performance due to the intensified hydration of surfactant head groups and reduced binding energy of neighboring molecules. Nuclear magnetic resonance-assisted core flooding experiments validated the exceptional capacity of NECRF to sweep the low-permeability region and improve the conformance profile. Overall, these findings may provide valuable insights into the development and application of novel materials and strategies for the CO2-EOR.

A novel prediction model for the probability of aggressive behavior in patients with mood disorders: Based on a cohort study.

BACKGROUND: Accurately predicting the probability of aggressive behavior is crucial for guiding early intervention in patients with mood disorders. METHODS: Cox stepwise regression was conducted to identify potential influencing factors. Nomogram prediction models were constructed to predict the probabilities of aggressive behavior in patients with mood disorders, and their performance was assessed using consistency index (C-index) and calibration plots. RESULTS: Research findings on 321 patients with mood disorders indicated that being older (HR = 0.92, 95% CI: 0.86-0.98), single (HR = 0.11, 95% CI: 0.02-0.68), having children (one child, HR = 0.07, 95%CI: 0.01-0.87; more than one child, HR = 0.33, 95%CI: 0.04-2.48), living in dormitory (HR = 0.25, 95%CI: 0.08-0.77), non-student (employee, HR = 0.24, 95% CI: 0.07-0.88; non-employee, HR = 0.09, 95% CI: 0.02-0.35), and higher scores in subjective support (HR = 0.90, 95% CI: 0.82-0.99) were protective factors. On the contrary, minorities (HR = 5.26, 95% CI: 1.23-22.48), living alone (HR = 4.37, 95% CI: 1.60-11.94), having suicide history (HR = 2.51, 95% CI: 1.06-5.95), and having higher scores in EPQ-E (HR = 1.04, 95% CI: 1.00-1.08) and EPQ-P (HR = 1.03, 95% CI: 1.00-1.07) were identified as independent risk factors for aggressive behavior in patients with mood disorders. The nomogram prediction model demonstrated high discrimination and goodness-of-fit. CONCLUSIONS: A novel nomogram prediction model for the probability of aggressive behavior in patients with mood disorders was developed, effective in identifying at-risk populations and offering valuable insights for early intervention and proactive measures.

Design of a Social Justice Curriculum to Expand Critical Consciousness Among Resident Trainees.

BACKGROUND: Health equity curricula emphasizing critical pedagogy and centering perspectives of those with marginalized identities, both in curriculum design and execution, have yet to be described in interdisciplinary graduate medical education settings. AIM: The application of public health critical race praxis (PHCRP) in the redesign and evaluation of a social medicine immersion month (SMIM) curriculum. SETTING: A mandatory, 4-week course within the Residency Program for Social Medicine in the Bronx, NY. PARTICIPANTS: First-year residents in internal medicine, family medicine, pediatrics, and clinical psychology fellows between 2019 and 2020. PROGRAM DESCRIPTION: Residents and faculty underrepresented in medicine employed PHCRP to ground SMIM in critical pedagogy and structural competency with the goals of increasing critical consciousness, sensitizing trainees to structural barriers faced by patients, and promoting meaningful engagement in advocacy. PROGRAM EVALUATION: SMIM was evaluated pre- and post-curriculum using a validated critical consciousness and intersectionality survey, with additional questions to assess competency and behaviors. Participants also provided course feedback. Participants demonstrated significant increases across all domains of the measure (Racism + 1.62 (p < .01), Classism + 1.62 (p < .05), Heterosexism + 1.06 (p < .05)). Participant feedback was positive. DISCUSSION: PHCRP is a valuable model for designing health equity curriculum. SMIM provides insights for incorporating this framework into GME curricula.

Deciphering the Role of Necroptosis-Related Long Non-coding RNAs in Hepatocellular Carcinoma: A Necroptosis-Related lncRNA-Based Signature to Predict the Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, characterized by a high morbidity rate. Long non-coding RNAs (lncRNAs) play an important role in regulating various cellular processes and diseases, including cancer. However, their specific roles and mechanisms in HCC are not fully understood. This study used a multi-cohort design to investigate necroptosis-related lncRNAs (NRLs) in patients with HCC. We curated a list of 1095 NRLs and 838 genes showing differential expression between tumor and normal tissues. Among them, we found 105 NRLs closely associated with the prognosis of HCC patients. The 10 lncRNAs (AC100803.3, AC027237.2, AL158166.1, LINC02870, AC026412.3, LINC02159, AC027097.1, AC139887.4, AC007405.1, AL023583.1) generated by LASSO-Cox regression analysis were used to create a prognostic risk model for HCC and group patients into groups based on risk. The KEGG analysis revealed distinct pathway enrichments in high-risk (H-R) and low-risk (L-R) subgroups. According to GO analysis, this study identified 230 differentially expressed genes (DEGs) that were significantly enriched in specific biological processes. Comparison of immune checkpoint-related genes (MCPGs) between H-R and L-R patients revealed significant differences. Moreover, we established a correlation between the risk scores of patients with liver cancer and their sensitivity to 16 chemotherapeutic agents. Employing protein-protein interaction (PPI) analysis, we identified 10 hub genes that potentially regulate the molecular networks involved in HCC development. This study is a pioneering effort to investigate the roles of NRLs in HCC. It opens a new avenue for potential targeted therapies and provides insights into the molecular mechanisms of HCC.

Stereoselective benzylic C(sp3)-H alkenylation enabled by metallaphotoredox catalysis.

Selective activation of the benzylic C(sp3)-H bond is pivotal for the construction of complex organic frameworks. Achieving precise selectivity among C-H bonds with comparable energetic and steric profiles remains a profound synthetic challenge. Herein, we unveil a site- and stereoselective benzylic C(sp3)-H alkenylation utilizing metallaphotoredox catalysis. Various linear and cyclic (Z)-all-carbon tri- and tetrasubstituted olefins can be smoothly obtained. This strategy can be applied to complex substrates with multiple benzylic sites, previously deemed unsuitable due to the uncontrollable site-selectivity. In addition, sensitive functional groups such as terminal alkenyl and TMS groups are compatible under the mild conditions. The exceptional site-selectivity and broad substrate compatibility are attributed to the visible-light catalyzed relay electron transfer-proton transfer process. More importantly, we have extended this methodology to achieve enantioselective benzylic C(sp3)-H alkenylation, producing highly enantioenriched products. The applicability and scalability of our protocol are further validated through late-stage functionalization of complex structures and gram-scale operations, underscoring its practicality and robustness.

Cysteine sulfenylation contributes to liver fibrosis via the regulation of EphB2-mediated signaling.

Sulfenylation is a reversible oxidative posttranslational modification (PTM) of proteins on cysteine residues. Despite the dissection of various biological functions of cysteine sulfenylation, its roles in hepatic fibrosis remain elusive. Here, we report that EphB2, a receptor tyrosine kinase previously implicated in liver fibrosis, is regulated by cysteine sulfenylation during the fibrotic progression of liver. Specifically, EphB2 is sulfenylated at the residues of Cys636 and Cys862 in activated hepatic stellate cells (HSCs), leading to the elevation of tyrosine kinase activity and protein stability of EphB2 and stronger interactions with focal adhesion kinase for the activation of downstream mitogen-activated protein kinase signaling. The inhibitions of both EphB2 kinase activity and cysteine sulfenylation by idebenone (IDE), a marketed drug with potent antioxidant activity, can markedly suppress the activation of HSCs and ameliorate hepatic injury in two well-recognized mouse models of liver fibrosis. Collectively, this study reveals cysteine sulfenylation as a new type of PTM for EphB2 and sheds a light on the therapeutic potential of IDE for the treatment of liver fibrosis.

M2 macrophage-derived extracellular vesicles ameliorate Benzalkonium Chloride-induced dry eye.

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.

Renin-angiotensin system inhibitors and risk of hepatocellular carcinoma among patients with hepatitis B virus infection.

BACKGROUND: Hepatitis B virus (HBV) infection is a common cause of liver-related morbidity and mortality. Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) decrease liver fibrosis, an intermediate step between liver injury and hepatocellular carcinoma (HCC). Our aim was to investigate the association between the use of ACEIs and ARBs on incident HCC and liver-related mortality among patients with HBV infection. METHODS: We conducted a population-based study on a new-user cohort of patients seen at 24 hospitals across China. We included adult patients with HBV infection who started ACEIs or ARBs (ACEIs/ARBs), or calcium channel blockers or thiazide diuretics (CCBs/THZs) from January 2012 to December 2022. The primary outcome was incident HCC; secondary outcomes were liver-related mortality and new-onset cirrhosis. We used propensity score matching and Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of study outcomes. RESULTS: Among 32 692 eligible patients (median age 58 [interquartile range (IQR) 48-68] yr, and 18 804 male [57.5%]), we matched 9946 pairs of patients starting ACEIs/ARBs or CCBs/THZs. During a mean follow-up of 2.3 years, the incidence rate of HCC per 1000 person-years was 4.11 and 5.94 among patients who started ACEIs/ARBs and CCBs/THZs, respectively, in the matched cohort. Use of ACEIs/ARBs was associated with lower risks of incident HCC (HR 0.66, 95% CI 0.50-0.86), liver-related mortality (HR 0.77, 95% CI 0.64-0.93), and new-onset cirrhosis (HR 0.81, 95% CI 0.70-0.94). INTERPRETATION: In this cohort of patients with HBV infection, new users of ACEIs/ARBs had a lower risk of incident HCC, liver-related mortality, and new-onset cirrhosis than new users of CCBs/THZs.

SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure.

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

Distinct roles of Kif6 and Kif9 in mammalian ciliary trafficking and motility.

Ciliary beat and intraflagellar transport depend on dynein and kinesin motors. The kinesin-9 family members Kif6 and Kif9 are implicated in motile cilia motilities across protists and mammals. How they function and whether they act redundantly, however, remain unclear. Here, we show that Kif6 and Kif9 play distinct roles in mammals. Kif6 forms puncta that move bidirectionally along axonemes, whereas Kif9 appears to oscillate regionally on the ciliary central apparatus. Consistently, only Kif6 displays microtubule-based motor activity in vitro, and its ciliary localization requires its ATPase activity. Kif6 deficiency in mice disrupts coordinated ciliary beat across ependymal tissues and impairs cerebrospinal fluid flow, resulting in severe hydrocephalus and high mortality. Kif9 deficiency causes mild hydrocephalus without obviously affecting the ciliary beat or the lifespan. Kif6-/- and Kif9-/- males are infertile but exhibit oligozoospermia with poor sperm motility and defective forward motion of sperms, respectively. These results suggest Kif6 as a motor for cargo transport and Kif9 as a central apparatus regulator.

Characterization and Dissolution Mechanism of Low-Molecular-Weight Organic Acids or Inorganic Mesoporous Particle-Based Piperine Amorphous Solid Dispersions.

The objective of the current study is to prepare amorphous solid dispersions (ASDs) containing piperine (PIP) by utilizing organic acid glycyrrhizic acid (GA) and inorganic disordered mesoporous silica 244FP (MSN/244FP) as carriers and to investigate their dissolution mechanism. The physicochemical properties of ASDs were characterized with scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) and one-dimensional proton nuclear magnetic resonance (1H NMR) studies collectively proved that strong hydrogen-bonding interactions formed between PIP and the carriers in ASDs. Additionally, molecular dynamic (MD) simulation was conducted to simulate and predict the physical stability and dissolution mechanisms of the ASDs. Interestingly, it revealed a significant increase in the dissolution of amorphous PIP in ASDs in in vitro dissolution studies. Rapid dissolution of GA in pH 6.8 medium resulted in the immediate release of PIP drugs into a supersaturated state, acting as a dissolution-control mechanism. This exhibited a high degree of fitting with the pseudo-second-order dynamic model, with an R2 value of 0.9996. Conversely, the silanol groups on the outer surface of the MSN and its porous nanostructures enabled PIP to display a unique two-step drug release curve, indicating a diffusion-controlled mechanism. This curve conformed to the Ritger-Peppas model, with an R2 > 0.9. The results obtained provide a clear evidence of the proposed transition of dissolution mechanism within the same ASD system, induced by changes in the properties of carriers in a solution medium of varying pH levels.

The structure of the γ-TuRC at the microtubule minus end - not just one solution.

In cells, microtubules (MTs) assemble from α/ß-tubulin subunits at nucleation sites containing the γ-tubulin ring complex (γ-TuRC). Within the γ-TuRC, exposed γ-tubulin molecules act as templates for MT assembly by interacting with α/ß-tubulin. The vertebrate γ-TuRC is scaffolded by γ-tubulin-interacting proteins GCP2-6 arranged in a specific order. Interestingly, the γ-tubulin molecules in the γ-TuRC deviate from the cylindrical geometry of MTs, raising the question of how the γ-TuRC structure changes during MT nucleation. Recent studies on the structure of the vertebrate γ-TuRC attached to the end of MTs came to varying conclusions. In vitro assembly of MTs, facilitated by an α-tubulin mutant, resulted in a closed, cylindrical γ-TuRC showing canonical interactions between all γ-tubulin molecules and α/ß-tubulin subunits. Conversely, native MTs formed in a frog extract were capped by a partially closed γ-TuRC, with some γ-tubulin molecules failing to align with α/ß-tubulin. This review discusses these outcomes, along with the broader implications.

Rapid isolation method for extracellular vesicles based on Fe3O4@ZrO2.

Extracellular vesicles (EVs) are pivotal in intercellular communication, disease mechanisms. Despite numerous methods for EVs isolation, challenges persist in yield, purity, reproducibility, cost, time, and automation. We introduce a EVs isolation technique using Fe3O4@ZrO2 beads, leveraging ZrO2-phosphate interaction. The results indicated that EVs were efficiently separated from large volumes of samples in 30 minutes without preconcentration. Our method demonstrated capture efficiency (74%-78%) compared to ultracentrifugation, purity (97%), and reproducibility (0.3%-0.5%), with excellent linearity (R2 > 0.99). EVs from urine samples showed altered expression of miRNAs. The logistic regression model achieved an AUC of 0.961, sensitivity of 0.92, and specificity of 0.94. With potential for automation, this magnetic bead-based method holds promise for clinical applications, offering an efficient and reliable tool for EVs research and clinical studies.

Steady Output Triboelectric-Electromagnetic Hybrid Generator with Variable Drag Turbine Blades for Natural Wind Energy Harvesting.

In recent years, the triboelectric-electromagnetic hybrid generator (TEHG) has been widely studied. However, the problems of unsteady output and high starting wind speed of traditional TEHG in the wind energy environment have not been effectively solved. This work introduces an innovative solution in the form of a steady output triboelectric-electromagnetic hybrid generator (SO-TEHG) with variable drag turbine blades. The SO-TEHG integrates the energy management circuit to output steady electric energy under random wind conditions. In addition, the integration of variable drag turbine blades with the triboelectric nanogenerator (TENG) reduces the wind speed threshold required for SO-TEHG activation. In comparison to the traditional turbine blades, which necessitate a minimum wind speed of 3 m/s, the SO-TEHG's innovative design allows it to commence power generation at a lower 2 m/s wind speed, producing an additional output of 50 V. This enhanced starting capability in mild breezes positions the SO-TEHG as an ideal power source for applications. In practical farmland settings, experimental results conclusively demonstrate the SO-TEHG's ability to successfully activate soil hygrothermographs and hydrogen sensors. As a steady power source driven by gentle winds, the SO-TEHG holds tremendous promise for advancing smart agriculture.

Polytypic B cells, monotypic/monoclonal B-cell proliferations, and neoplastic T cells diverge from TET2-/DNMT3A-mutant clonal hematopoiesis in follicular helper T-cell lymphomas.

Not available.

A Pedigree Investigation of H-antigen Deletion Caused by Mutation of 658 C to T in the FUT1 Gene.

H-antigen deletion is often caused by FUT1 gene mutation, which is a very rare blood group. In this case, the H-antigen phenotype, FUT1, FUT2 sequences, and family genetic investigation of a 26-year-old patient (proband) and her three family members were studied. The results showed that the proband and little her brother were H-deficient phenotype, their ABO genotype of both was A/O1, her father was A/B, and her mother was O1/O1. The proband and her little brother's FUT1 phenotype were both h3|h3, with a homozygous mutation 658C > T in their FUT1 gene, and the FUT1 phenotype of their parents' were H|h3, with a heterozygous mutation (658C > T) in their FUT1 gene. The result of whole gene sequencing showed that the father of the proband had a deletion of CHR19.49,255,178-49,257,177 in the FUT1 gene (hg19 was used as the reference). The results of the family investigation showed that the mutation of site 658 in the FUT1 gene between offspring and parents was consistent with Mendelian inheritance law.

Intratumoral T-cell composition predicts epcoritamab-based treatment efficacy in B-cell non-Hodgkin lymphomas.

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.

Clinical Characteristics and Outcomes of Hyperphosphatemia in patients with CKD Stages 1 to 2.

INTRODUCTION: There was limited research on the epidemiology of hyperphosphatemia in early-stage chronic kidney disease (CKD) patients. We aimed to explore the clinical characteristics and prognostic value of hyperphosphatemia in patients with CKD stages 1-2. METHODS: We enrolled adult patients with CKD stages 1-2 from 24 regional central hospitals across China. Hyperphosphatemia was defined as a serum phosphate level exceeding 1.45 mmol/L. The study outcomes included all-cause and cardiovascular (CV) mortality. Cox proportional hazard models were used to investigate the association of hyperphosphatemia with all-cause and CV mortality. RESULTS: Among 99,266 patients with CKD stages 1-2 across China, the prevalence of hyperphosphatemia was 8.3%. The prevalence of hyperphosphatemia was increased with the level of urinary protein and was higher in younger and female patients. Among 63,121 patients with survival information, during a median of 5.2 years follow-up period, there were 436 (8.0%) and 4,695 (8.1%) deaths in those with and without hyperphosphatemia, respectively. After adjusting for potential confounders, compared with patients without hyperphosphatemia, patients with hyperphosphatemia was associated with a higher risk of all-cause mortality (HR, 1.28, 95% CI, 1.16-1.41). Although nearly 60.3% of hyperphosphatemia could be relieved without phosphate-lowering drug therapy among patients with CKD stages 1-2, transient hyperphosphatemia was also associated with an increased risk of all-cause mortality (P=0.048). CONCLUSIONS: Hyperphosphatemia was not rare in patients with CKD stages 1-2 and was associated with an increased risk of mortality. Clinicians should closely monitor serum phosphorus levels in patients with CKD, even in those with normal kidney function.