Copper homeostasis and cuproptosis in cancer immunity and therapy.

Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), which correlates to the mitochondrial tricarboxylic acid (TCA) cycle, resulting in proteotoxic stress and eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts an indispensable role in cancer progression, which is considered a promising strategy for cancer therapy. Cancer immunotherapy has gained extensive attention owing to breakthroughs in immune checkpoint blockade; furthermore, cuproptosis is strongly connected to the modulation of antitumor immunity. Thus, a thorough recognition concerning the mechanisms involved in the modulation of copper metabolism and cuproptosis may facilitate improvement in cancer management. This review outlines the cellular and molecular mechanisms and characteristics of cuproptosis and the links of the novel regulated cell death modality with human cancers. We also review the current knowledge on the complex effects of cuproptosis on antitumor immunity and immune response. Furthermore, potential agents that elicit cuproptosis pathways are summarized. Lastly, we discuss the influence of cuproptosis induction on the tumor microenvironment as well as the challenges of adding cuproptosis regulators to therapeutic strategies beyond traditional therapy.

Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation.

Cilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body (BB) and plays critical roles in the initiation of ciliogenesis and TZ assembly. How Cep290 is maintained at BB and whether axonemal and ciliary membrane localized cues converge to determine the localization of Cep290 remain unknown. Here, we report that the Cep131-Cep162 module near the axoneme and the Cby-Fam92 module close to the membrane synergistically control the BB localization of Cep290 and the subsequent initiation of ciliogenesis in Drosophila. Concurrent deletion of any protein of the Cep131-Cep162 module and of the Cby-Fam92 module leads to a complete loss of Cep290 from BB and blocks ciliogenesis at its initiation stage. Our results reveal that the first step of ciliogenesis strictly depends on cooperative and retroactive interactions between Cep131-Cep162, Cby-Fam92 and Cep290, which may contribute to the complex pathogenesis of Cep290-related ciliopathies.

A multiomic study uncovers a bZIP23-PER1A-mediated detoxification pathway to enhance seed vigor in rice.

Seed vigor in crops is important in terms of improving grain quality and germplasm conservation; however, little is known about its regulatory mechanisms through the encoded proteome and gene network. Comparative analyses of transcriptome (RNA sequencing [RNA-seq]) and broadly targeted metabolic profiling of two subspecific rice cultivars with distinct seed vigor during accelerated aging revealed various biological pathways and metabolic processes as key influences explaining trait differences. RNA-seq coexpression regulatory network analyses identified several transcription factors, including bZIP23 and bZIP42, that act as nodes in the gene network. Importantly, transgenic seeds of overexpression of bZIP23 enhanced seed vigor, whereas its gene knockout reduced seed vigor, suggesting that the protein it encodes functions as a positive regulator. Similarly, overexpression and knockout of PER1A that encodes a key player in the detoxification pathway enhanced and decreased seed vigor, respectively. We further demonstrated a direct interaction of the PER1A promoter with bZIP23 in seeds, which activates the expression of PER1A, and the genetic evidence suggested that bZIP23 most likely functions in a common pathway with and acts upstream of PER1A to modulate seed vigor. In addition, the control of seed vigor by the bZIP23-PER1A module was connected with that of the abscisic acid signaling pathway. Collectively, we revealed the genetic architecture of variation in seed vigor and uncovered the bZIP23-PER1A-mediated detoxification pathway that enhances the trait in rice.

Epigenetic regulation of H3K27me3 in laying hens with fatty liver hemorrhagic syndrome induced by high-energy and low-protein diets.

BACKGROUND: Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics. RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways. CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.

METTL3/16-mediated m6A modification of ZNNT1 promotes hepatocellular carcinoma progression by activating ZNNT1/osteopontin/S100A9 positive feedback loop-mediated crosstalk between macrophages and tumour cells.

Macrophages are the major components of tumour microenvironment, which play critical roles in tumour development. N6-methyladenosine (m6A) also contributes to tumour progression. However, the potential roles of m6A in modulating macrophages in hepatocellular carcinoma (HCC) are poorly understood. Here, we identified ZNNT1 as an HCC-related m6A modification target, which was upregulated and associated with poor prognosis of HCC. METTL3 and METTL16-mediated m6A modification contributed to ZNNT1 upregulation through stabilizing ZNNT1 transcript. ZNNT1 exerted oncogenic roles in HCC. Furthermore, ZNNT1 recruited and induced M2 polarization of macrophages via up-regulating osteopontin (OPN) expression and secretion. M2 Macrophages-recruited by ZNNT1-overexpressed HCC cells secreted S100A9, which further upregulated ZNNT1 expression in HCC cells via AGER/NF-κB signaling. Thus, this study demonstrates that m6A modification activated the ZNNT1/OPN/S100A9 positive feedback loop, which promoted macrophages recruitment and M2 polarization, and enhanced malignant features of HCC cells. m6A modification-triggered ZNNT1/OPN/S100A9 feedback loop represents potential therapeutic target for HCC.

Apatinib Plus Toripalimab (Anti-PD1 Therapy) as Second-Line Therapy in Patients With Advanced Gastric or Esophagogastric Junction Cancer: Results From a Randomized, Open-Label Phase II Study.

BACKGROUND: This study aimed to assess the activity of apatinib plus toripalimab in the second line for patients with advanced gastric or esophagogastric junction cancer (GC/EGJC). METHODS: In this open-label, phase II, randomized trial, patients with advanced GC/EGJC who progressed after first-line chemotherapy were enrolled and received 250 mg apatinib per day plus 240 mg toripalimab on day 1 per 3 weeks (arm A) or physician's choice of chemotherapy (PC, arm B). The primary endpoint of this study was the 1-year survival rate. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed as secondary endpoints. RESULTS: Twenty-five patients received apatinib plus toripalimab while 26 were enrolled in arm B. The 1-year survival rates of the 2 groups were 43.3% and 42.3%, respectively (P = .903). The PFS was 2.77 versus 2.33 months (P = .660). The OS was 8.30 versus 9.88 months (P = .539). An objective response was reported in 20.0% of patients in arm A compared to 26.9% in arm B (P = .368), respectively. A total of 6 (24.0%) patients experienced adverse events of grade ≥ 3 in arm A, while 9 (34.6%) patients suffered from adverse events of grade ≥ 3 in arm B. No drug-related deaths occurred in either group. CONCLUSION: Toripalimab plus apatinib treatment in second-line therapy of advanced GC/EGJC showed manageable toxicity but did not improve clinical outcomes relative to PC treatment (ClinicalTrials.gov Identifier: NCT04190745).

Rapid Construction of Double Crystalline Prussian Blue Analogue Hetero-Superstructure.

The controllable construction of complex metal-organic coordination polymers (CPs) merits untold scientific and technological potential, yet remains a grand challenge of one-step construction and modulating simultaneously valence states of metals and topological morphology. Here, a thiocyanuric acid (TCA)-triggered strategy is presented to one-step rapid synthesis a double-crystalline Prussian blue analogue hetero-superstructure (PBA-hs) that comprises a Co3[Fe(CN)6]2 cube overcoated with a KCo[Fe(CN)6] shell, followed by eight self-assembled small cubes on vertices. Unlike common directing surfactants, TCA not only acts as a trigger for the fast growth of KCo[Fe(CN)6] on the Co3[Fe(CN)6]2 phase resulting in a PBA-on-PBA hetero-superstructure, but also serves as a flange-like bridge between them. By combining experiments with simulations, a deprotonation-induced electron transfer (DIET) mechanism is proposed for formation of second phase in PBA-hs, differing from thermally and photo-induced electron transfer processes. To prove utility, the calcined PBA-hs exhibits enhanced oxygen evolution reaction performance. This work provides a new method to design of novel CPs for enriching chemistry and material science. This work offers a practical approach to design novel CPs for enriching chemistry and material science.

The ubiquitin-interacting motif-type ubiquitin receptor HDR3 interacts with and stabilizes the histone acetyltransferase GW6a to control the grain size in rice.

For grain crops such as rice (Oryza sativa), grain size substantially affects yield. The histone acetyltransferase GRAIN WEIGHT 6a (GW6a) determines grain size and yield in rice. However, the gene regulatory network underlying GW6a-mediated regulation of grain size has remained elusive. In this study, we show that GW6a interacts with HOMOLOG OF DA1 ON RICE CHROMOSOME 3 (HDR3), a ubiquitin-interacting motif-containing ubiquitin receptor. Transgenic rice plants overexpressing HDR3 produced larger grains, whereas HDR3 knockout lines produce smaller grains compared to the control. Cytological data suggest that HDR3 modulates grain size in a similar manner to GW6a, by altering cell proliferation in spikelet hulls. Mechanistically, HDR3 physically interacts with and stabilizes GW6a in an ubiquitin-dependent manner, delaying protein degradation by the 26S proteasome. The delay in GW6a degradation results in dramatic enhancement of the local acetylation of H3 and H4 histones. Furthermore, RNA sequencing analysis and chromatin immunoprecipitation assays reveal that HDR3 and GW6a bind to the promoters of and modulate a common set of downstream genes. In addition, genetic analysis demonstrates that HDR3 functions in the same genetic pathway as GW6a to regulate the grain size. Therefore, we identified the grain size regulatory module HDR3-GW6a as a potential target for crop yield improvement.

Acute myeloid leukemia with mast cell differentiation is characterized by interstitial mast cells, complex karyotype, TP53 alterations and poor prognosis.

Not available.

MiR-24-3p regulates the differentiation of adipose-derived stem cells toward pericytes and promotes fat grafting vascularization.

Adipose-derived stem cells (ADSCs) enhance fat graft survival by promoting neovascularization. The mechanism that promotes ADSCs differentiation toward pericytes was not known. We treated ADSCs with conditional medium (CM) from endothelial cells (ECs) or human recombinant transforming growth factor ß (TGF-ß) to induce differentiation into pericytes. Pericytes markers, including platelet-derived growth factor receptor ß (PDGFRß), alpha-smooth muscle actin (α-SMA), and desmin, were examined. Pericytes differentiation markers, migration, and their association with ECs were examined in ADSCs transfected with miR-24-3p mimics and inhibitors. Bioinformatics target prediction platforms and luciferase assays were used to investigate whether PDGFRß was directly targeted by miR-24-3p. In vivo, fat mixed with ADSCs transfected with miR-24-3p mimics or inhibitors was implanted subcutaneously on the lower back region of nude mice. Fat grafts were harvested and analyzed at 2, 4, 6, and 8 weeks. Results showed that endogenous TGF-ß derived from CM from EC or human recombinant TGF-ß promoted migration, association with ECs, and induced expression of pericyte markers (PDGFRß, α-SMA, Desmin) in ADSCs. MiR-24-3p directly targeted PDGFRß in ADSCs by lucifer reporter assays. Inhibition of miR-24-3p promoted pericytes differentiation, migration, and association with ECs in ADSCs. Inhibition of miR-24-3p in ADSCs promoted survival, integrity, adipocyte viability, vascularization, pericytes association with ECs, and reduced fibrosis, whereas overexpression of miR-24-3p in ADSCs yielded the opposite results. Collectively, TGF-ß released by ECs induced ADSCs differentiation toward pericytes through miR-24-3p. Downregulation of miR-24-3p in ADSCs induced survival, integrity, adipocyte viability, vascularization, pericytes association with ECs, and reduced fibrosis after fat grafting.

A novel long non-coding RNA linc-93.2 participates in bisphenol induced oxidative stress and macrophage polarization in red common carp (Cyprinus carpio).

Previous studies show that bisphenol A (BPA) and its analogs induce oxidative stress and promote inflammatory response. However, the key molecules in regulating this process remain unclear. Here, we report significant inductive effects of BPA and bisphenol AF (BPAF) on a newly found long non-coding RNA linc-93.2 accompanied by oxidative stress and activation of pro-inflammatory pathways in treated fish and fish primary macrophages. Silencing linc-93.2 in fish primary macrophages in vitro or fish in vivo significantly promotes the expression of anti-oxidative stress-related genes and anti-inflammatory cytokines. This inhibition of pro-inflammatory cytokine expression, showing cell status disruption towards to M2 polarization. Followed by exposure to BPA or BPAF, silencing linc-93.2 in vitro or in vivo significantly attenuates the increased production of reactive oxygen species and malondialdehyde level aroused by bisphenol treatment, possibly owing to the enhancement of total antioxidant capacity observed in cells and tissue after linc-93.2 knockdown. RNA-sequencing further revealed regulation of nuclear factor-kappa b (NF-κB) in linc-93.2's downstream network, combining with our previous observation on the upstream regulation of linc-93.2 via NF-κB, which together suggest a critical role of linc-93.2 in promoting NF-κB positive feedback loop that may be an important molecular event initiating the immunotoxicity of bisphenols.

E3 ubiquitin ligase HECTD3 is a tumor suppressor and mediates the polyubiquitination of SLC7A11 to promote ferroptosis in colon cancer.

Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3) has been reported to play an essential role in biological processes, including drug resistance, metastasis or apoptosis. However, the relationships between HECTD3 and Colorectal cancer (CRC) remain to be unclear. In this study, we discovered that HECTD3 expressed lowly in CRC compared with normal tissues and patients with low HECTD3 suffered from poorer survival outcomes relative to those with high HECTD3 levels. HECTD3 inhibition could significantly enhance proliferative, clone abilities and self-renewal capacities of CRC cells in vitro and in vivo. Mechanistically, our findings revealed that HECTD3 had endogenous interactions with SLC7A11 proteins. HECTD3 promoted the polyubiquitination of SLC7A11 to trigger the degradation of SLC7A11 proteins. Targeting HECTD3 could notably prolong the half-life period of SLC7A11 proteins, thereby promoting its stability. However, the cysteine mutation at amino acid 823 (ubiquitinase active site) of HECTD3 impaired the polyubiquitination of SLC7A11. HECTD3 deficiency depended on accumulated SLC7A11 proteins to accelerate malignant progression of CRC in vitro and in vivo. Thus, HECTD3 could suppress SLC7A11 levels to attenuate the SLC7A11-mediated cystine uptake, leading to enhanced CRC ferroptosis. SLC7A11 inhibition through polyubiquitination by HECTD3 increased ferroptosis, thereby inhibiting CRC tumor growth. Taken together, these results showed that HECTD3 controlled the stability of SLC7A11 and uncovered the function of HECTD3/SLC7A11 axis in regulating CRC progression.

Empirical analysis of lead neurotoxicity mode of action and its application in health risk assessment.

The mode of action (MOA) framework is proposed to inform a biological link between chemical exposures and adverse health effects. Despite a significant increase in knowledge and awareness, the application of MOA in human health risk assessment (RA) remains limited. This study aims to discuss the adoption of MOA for health RA within a regulatory context, taking our previously proposed but not yet validated MOA for lead neurotoxicity as an example. We first conducted a quantitative weight of evidence (qWOE) assessment, which revealed that the MOA has a moderate confidence. Then, targeted bioassays were performed within an in vitro blood-brain barrier (BBB) model to quantitatively validate the scientific validity of key events (KEs) in terms of essentiality and concordance of empirical support (dose/temporal concordance), which increases confidence in utilizing the MOA for RA. Building upon the quantitative validation data, we further conducted benchmark dose (BMD) analysis to map dose-response relationships for the critical toxicity pathways, and the lower limit of BMD at a 5% response (BMDL5) was identified as the point of departure (POD) value for adverse health effects. Notably, perturbation of the Aryl Hydrocarbon Receptor (AHR) signaling pathway exhibited the lowest POD value, measured at 0.0062 µM. Considering bioavailability, we further calculated a provisional health-based guidance value (HBGV) for children's lead intake, determining it to be 2.56 µg/day. Finally, the health risk associated with the HBGV was assessed using the hazard quotient (HQ) approach, which indicated that the HBGV established in this study is a relative safe reference value for lead intake. In summary, our study described the procedure for utilizing MOA in health RA and set an example for MOA-based human health risk regulation.

Streptococcus suis meningoencephalitis diagnosed with metagenomic next-generation sequencing: A case report with literature review.

Streptococcus suis is a pathogen of emerging zoonotic diseases and meningoencephalitis is the most frequent clinical symptom of S. suis infection in humans. Rapid diagnosis of S. suis meningoencephalitis is critical for the treatment of the disease. While the current routine microbiological tests including bacterial culture and gram staining are poorly sensitive, diagnosis of S. suis meningoencephalitis by metagenomic next-generation sequencing (mNGS) has been rarely reported. Here, we report a 52-year-old female pork food producer with a broken finger developed S. suis meningoencephalitis. After her admission, no pathogenic bacteria were detected through bacterial culture and Gram staining microscopy in the cerebrospinal fluid obtained via lumbar puncture. However, mNGS identified the presence of S. suis in the sample. mNGS is a promising diagnostic tool for rapid diagnosis of rare infectious diseases in the central nervous system.

Nomogram for predicting venous thromboembolism after spinal surgery.

PURPOSE: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery. METHODS: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally. RESULTS: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1. CONCLUSION: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.

DYF-4 regulates patched-related/DAF-6-mediated sensory compartment formation in C. elegans.

Coordination of neurite extension with surrounding glia development is critical for neuronal function, but the underlying molecular mechanisms remain poorly understood. Through a genome-wide mutagenesis screen in C. elegans, we identified dyf-4 and daf-6 as two mutants sharing similar defects in dendrite extension. DAF-6 encodes a glia-specific patched-related membrane protein that plays vital roles in glial morphogenesis. We cloned dyf-4 and found that DYF-4 encodes a glia-secreted protein. Further investigations revealed that DYF-4 interacts with DAF-6 and functions in a same pathway as DAF-6 to regulate sensory compartment formation. Furthermore, we demonstrated that reported glial suppressors of daf-6 could also restore dendrite elongation and ciliogenesis in both dyf-4 and daf-6 mutants. Collectively, our data reveal that DYF-4 is a regulator for DAF-6 which promotes the proper formation of the glial channel and indirectly affects neurite extension and ciliogenesis.

From the archives of MD Anderson Cancer Center. Mesothelial/monocytic incidental cardiac excrescence with a review of the literature.

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign lesion composed of monocytes and mesothelial cells that is most often encountered during cardiothoracic surgery. We describe a case in a 71-year-old man with known aortic valve stenosis who presented with gradual onset dyspnea over a few weeks, made worse with minimal exertion. A transesophageal echocardiogram revealed severe aortic stenosis and mild pericardial effusion. The patient underwent aortic valve replacement, coronary artery bypass, and amputation of the left atrial appendage. Histological examination of a 0.8 cm blood clot received along with the atrial appendage showed an aggregation of bland cells with features of monocytes associated with small strands and nodules of mesothelial cells, fat cells, fibrin and a minute fragment of bone. Immunohistochemical analysis showed that the monocytic cells were positive for CD4 and CD68 (strong) and negative for calretinin and keratin. By contrast, the mesothelial cells were positive for calretinin and keratin and negative for all other markers. In sum, the morphologic and immunohistochemical findings support the diagnosis of MICE. Based on our review of the literature, about 60 cases of MICE have been reported previously which we have tabulated. We also discuss the differential diagnosis.

From the archives of MD Anderson Cancer Center: Monomorphic epitheliotropic intestinal T-cell lymphoma: A case with an unusual immunophenotype and discussion of differential diagnosis.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive T-cell neoplasm associated with poor survival. We report a case of MEITL that presented as an ulcerated mass in the jejunum with perforation. Microscopic examination showed that the neoplasm involved the full thickness of the intestinal wall, extended into the mesentery, and was composed of monomorphic, small to medium-size cells. Immunohistochemical analysis showed that the neoplastic cells were positive for T-cell receptor (TCR) delta, CD3, CD7, CD8 (small subset), BCL-2 and TIA-1, and negative for TCR beta, CD4, CD5, CD10, CD20, CD30, CD34, CD56, CD57, CD99, ALK, cyclin D1, granzyme B, MUM1/IRF4, and TdT. The Ki-67 proliferation index was approximately 50 %. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER ISH) was negative. Next-generation sequencing (NGS) analysis showed mutations involving SETD2 and STAT5B. The patient was treated with aggressive chemotherapy and consolidative autologous stem cell transplant and had clinical remission, but relapsed after about one year. Retreatment led to another one-year interval of clinical remission, but at last follow up the patient has relapsed disease involving the ileum and colon. We also discuss the differential diagnosis of MEITL.

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis.

BACKGROUND: Arteriovenous fistula (AVF) dysfunction is a common complication in patients undergoing maintenance hemodialysis (MHD). Elevated serum levels of fibroblast growth factor 21 (FGF21) are associated with atherosclerosis and cardiovascular mortality. However, its association with vascular access outcomes remains elusive. The present study evaluated the relationship of serum FGF21 levels with AVF dysfunction and all-cause mortality in patients undergoing MHD. METHODS: We included patients undergoing MHD using AVF from January 2018 to December 2019. FGF21 concentration was detected using enzyme-linked immunosorbent assay. Patients were followed up to record two clinical outcomes, AVF functional patency loss and all-cause mortality. The follow-up period ended on April 30, 2022. RESULTS: Among 147 patients, the mean age was 58.49 ± 14.41 years, and the median serum level of FGF21 was 150.15 (70.57-318.01) pg/mL. During the median follow-up period of 40.83 months, the serum level of FGF21 was an independent risk factor for AVF functional patency loss (per 1 pg/mL increase, HR 1.002 [95% CI: 1.001-1.003, p = 0.003]). Patients with higher serum levels of FGF21 were more likely to suffer from all-cause mortality (per 1 pg/mL increase, HR 1.002 [95% CI: 1.000-1.003, p = 0.014]). The optimal cutoffs for FGF21 to predict AVF functional patency loss and all-cause mortality in patients undergoing MHD were 149.98 pg/mL and 146.43 pg/mL, with AUCs of 0.701 (95% CI: 0.606-0.796, p < 0.001) and 0.677 (95% CI: 0.595-0.752, p = 0.002), respectively. CONCLUSIONS: Serum FGF21 levels were an independent risk factor and predictor for AVF functional patency loss and all-cause mortality in patients undergoing MHD.

[Differences in the Elderly Care Service Demand,Preference,and Tendency Between Urban and Rural Areas in the Pearl River Delta].

Objective To understand the differences in the demand,preference,and tendency for elderly care services between urban and rural areas in the Pearl River Delta (PRD),and to provide reference for the planning and balanced allocation of elderly care resources in urban and rural areas. Methods Using the multi-stage stratified random sampling method,we selected 7 community health service centers in 2 prefecture-level cities in the PRD and conducted a questionnaire survey on the elderly care service demand,preference,and tendency among 1919 regular residents aged 60 years and above who attended the centers. Results A total of 641 urban elderly residents (33.4%) and 1278 rural elderly residents (66.6%) were surveyed in the PRD.The urban and rural elderly residents showed differences in the child number (χ2=43.379,P<0.001),willingness to purchase socialized elderly care services (χ2=104.141,P<0.001),and attitudes to the concept of raising child to avoid elderly hardship (χ2=65.632,P<0.001).The proportion (71.8%) of rural elderly residents who prefer family-based elderly care was higher than that (57.1%) of urban elderly residents (χ2=41.373,P<0.001).The proportion (62.2%) of urban elderly residents clearly expressing their willingness to choose institutions for elderly care was higher than that (44.0%) of rural elderly residents (χ2=57.007,P<0.001).Compared with family-based elderly care,the willingness to choose institutional or community-based in-house elderly care was low among the urban elderly residents with surplus monthly household income or balanced income and expenditure;urban males,those with college education background or above,and those who purchased socialized elderly care services tended to prefer community-based in-house elderly care.In rural areas,the elderly residents who had local household registry were prone to choose institutional or community-based in-house elderly care,while those who had more than one child and those who were satisfied with the current living conditions were less willing to choose community-based in-house elderly care. Conclusions It is suggested that the urban-rural differences in the elderly care service demand,preference and tendency should be fully considered in the planning and allocation of urban and rural elderly care resources.Efforts remain to be made to develop diversified social elderly care services tailored to the characteristics of urban and rural areas.