Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Metabolomics-based understanding of the olanzapine-induced weight gain in female first-episode drug-naïve patients with schizophrenia.

Previous studies have demonstrated that patients with schizophrenia (SZ) have greater rate of metabolic disorder as compared with the control population, which likely be the consequence of use of atypical antipsychotics. Olanzapine is a widely used antipsychotic, which increases the weight of SZ patients. However, the underlying mechanism remains poorly understood. Here we report the metabolomics-based understanding of the weight gain induced by olanzapine. 57 first-episode drug-naïve patients (FEDN) were recruited, of whom 27 patients completed a 4-week clinical trial. We then profiled the metabolomes of their plasma with the LC-MS-based nontargeted metabolomics approach at the baseline and after olanzapine monotherapy for 4 weeks. We observed that the plasma of the olanzapine-treated patient had significantly higher lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lower carnitine as compared with that of the baseline plasma samples. Moreover, regression analyses indicated that the change of LysoPC(14:0) level was an independent contributor to the olanzapine-induced weight gain. Our study suggests that the metabolomics-based approach may facilitate the identification of biomarkers associated with the metabolic disorder causing by antipsychotic in schizophrenia patients.

HIF-1α Alleviates High-Glucose-Induced Renal Tubular Cell Injury by Promoting Parkin/PINK1-Mediated Mitophagy.

It is well-established that mitophagy leads to Diabetic Nephropathy (DN) and renal failure. Mitophagy mediated by a Hypoxia-inducible factor-1α (HIF-1α) plays a beneficial role in many diseases. Nevertheless, the mechanisms underlying HIF-1α-mediated mitophagy in DN remain unclear. This study defines the role of HIF-1α mediated mitophagy in DN. The expression of HIF-1α was upregulated in HK-2 cells in an High-Glucose (HG) environment, and the YC-1 (a specific inhibitor of HIF-1α) further exacerbated the hypoxia-induced mitochondrial dysfunction. Conversely, the HIF-1α-mediated protective effect was strengthened by scavenger N-acetylcysteine (NAC), a type of reactive oxygen species. Moreover, HIF-1α-Parkin/PINK1-mediated mitophagy prevented apoptosis and ROS production in HK-2 cells subjected to HG exposure. In summary, HIF-1α mediated mitophagy on HK-2 cells under HG conditions could alleviate DN, suggesting that it has huge prospects for DN treatment.

Cross-sectional study for the clinical application of extracorporeal membrane oxygenation in Mainland China, 2018.

BACKGROUND: To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. METHODS: Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. RESULTS: The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. CONCLUSIONS: Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.

[Effects of different carbon sources on growth and active component contents in Salvia miltiorrhiza and S. castanea f. tomentosa hairy roots].

Salvia miltiorrhiza(Sm) and Salvia castanea f. tomentosa(Sc) hairy roots were used as experimental materials to study the effects of six different carbon sources, galactose, fructose, lactose, glucose, arabinose and sucrose(control), on fresh weight, dry weight, contents and yields of salvianolic acids and tanshinones. The results showed that galactose was most beneficial to the growth of two kinds of hairy roots, while lactose and arabinose were not conducive to their growth. As for Sm hairy roots, fructose significantly promoted the accumulation of salvianolic acid B, and the content increased by 5.801 times and 10.151 times compared with the control group, respectively. Glucose significantly promoted the accumulation of salvianolic acids. The content and yield of rosmarinic acid were 7.674 times and 9.260 times of that of the control group, and the content and yield of salvianolic acid B were 5.532 times and 6.675 times of the control group. For the hairy roots of Sc, galactose significantly increased the content and yield of rosmarinic acid, reaching 7.820 times and 9.944 times of the control group, respectively. Fructose promoted the increase of the content and yield of cryptotanshinone, reaching 9.242 times and 6.609 times of the control group, respectively. The study confirmed the optimal carbon source for the hairy root culture of Sm and Sc, and provided theoretical guidance for large-scale production of Sm drug-derived components and the utilization of Sc.

Serum Ferritin Independently Predicts the Incidence of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

AIM: This study aimed to determine whether serum ferritin (SF) is an independent risk factor of the incidence of chronic kidney disease (CKD) and rapid renal function decline (RFD) in male Tibetan patients with type 2 diabetes mellitus (T2DM). METHODS: We performed a retrospective cohort study that included 191 male Tibetan patients with T2DM without CKD. Patients were divided into three groups according to the level of SF. The following outcomes were measured: cumulative incidence of chronic kidney disease [i.e. estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 and/or urinary albumin/creatine ratio (ACR) ≥30 mg/g] and RFD (i.e. decrease in eGFR of ≥25% from baseline or a decline rate of ≥3 mL/min per 1.73 m2 annually). RESULTS: In total, over a median follow-up period of 23 months, 30 (15.7%) and 89 patients (46.6%) developed CKD and RFD. In multivariable Cox models, a 100 ng/mL increment in SF was associated with a 1.12-fold (95% CI: 1.02-1.24) higher adjusted risk for incidence of CKD. The adjusted-HR of CKD was 1.31 (95% CI: 0.38-4.53) and 2.92 (95% CI: 0.87-9.77) for those in tertile 2 and tertile 3, respectively, compared with the patients in tertile 1. However, SF was not significantly associated with RFD (adjusted-HR: 1.06, 95% CI: 0.99-1.14). CONCLUSION: Serum ferritin independently predicts the incidence of CKD in male Tibetan patients with T2DM. High levels of serum ferritin may play a role in the pathogenesis leading to the development of CKD in T2DM.

[Analysis of HFE and Non-HFE Mutations in a Tibet Cohort with Iron Overload].

OBJECTIVE: The explore the molecular basis of iron-overload in Tibet nationality population of Tibet. METHODS: The inpatients with iron-overload in our department from Dec. 1st 2014 to Jul.31st 2016 were enrolled in this study. Abdominal MRI and the mutation sites C282Y and H63D in HFE exon were examined. For HFE mutation-negative patients, the non-HFE mutation was detected, including 5 HJV mutations of G320V, p.Q312X, p.D249H, p.I281T, p.C321X and 2 TFR2 mutations: (Y250X, I238M), and 2 SLC40A1 mutations: (V162del, N144H). RESULTS: Among 113 iron overload patients, only one showed homozygous p.H63D mutation, and one showed heterozygosis p.H63D mutation. In 73 patients accepted non-HFE gene detection, only one was heterozygosis p.D249N mutation in HJV, and one was heterozygosis p.I238M mutation in TFR2. CONCLUSION: Currently, the pathogenic gene for Tibetan iron-overload has not yet been found.

Low concentration of formononetin promotes proliferation of estrogen receptor-positive cells through an ERα-miR-375-PTEN-ERK1/2-bcl-2 pathway.

A low dose of formononetin accelerates the proliferation of nasopharyngeal carcinoma cells in vitro; however, the underlying mechanism remains unknown. Here, we investigated the molecular mechanism of formononetin in CNE2 cell proliferation. CNE2 cells were treated with 0 to 1 µM formononetin. To inhibit mitogen activated protein kinase / extracellular regulate kinase (MAPK/ERK) kinase (MEK) and microRNA (miR)-375, cells were pretreated with either PD98059 or a miR-375 inhibitor, respectively, followed by co-treatment with formononetin (0.3 µM) plus an inhibitor. Female rats were ovariectomized (OVX), and some OVX rats received formononetin or estrogen (E2) injections. Sham operated animals were used as controls. Compared to control, 0.3 µM formononetin accelerated proliferation and decreased late apoptosis of CNE2 cells. However, formononetin-induced pro-growth and anti-apoptosis activity was abolished by PD98059 and the miR-375 inhibitor. In addition, 0.1 and 0.3 µM formononetin significantly increased estrogen receptor-α (ERα) and bcl-2, but decreased protein-phosphatase and tensin homologue (PTEN) protein expression, all of which was reversed by the miR-375 inhibitor. Additionally, formononetin treatment resulted in a transient upregulation of phosphorylated (p)-ERK1/2. In vivo studies indicated that formononetin significantly increased endometrium thickness and down-regulated ERα expression in OVX rats. Taken together, our study demonstrates that a low concentration of formononetin can promote growth of CNE2 cells and uterine tissues, possibly through regulating the ERα-miR-375-PTEN-ERK1/2-bcl-2 signaling pathway.

Low concentration of formononetin stimulates the proliferation of nasopharyngeal carcinoma cell line CNE2 by upregulating bcl-2 and p-ERK1/2 expression.

Context Formononetin is a typical phytoestrogen, which is a bioactive component found in red clover plants. Previous studies have shown that formononetin inhibits the proliferation of several types of cancer cells, including prostate cancer and osteosarcoma. However, how formononetin affects the proliferation of CNE2 is not clear. Objective The objective of this study is to investigate the effects of formononetin on nasopharyngeal carcinoma cells in vitro, along with the underlying mechanism. Materials and methods CNE2 cells were incubated with various concentrations of formononetin (0, 0.1, 0.2, 0.3 and 1 µM) for 48 h. Cell proliferation was measured by [3-(4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay, while the rate of apoptosis was measured by flow cytometry. Bcl-2 and bax mRNA expression levels were determined by real time polymerase chain reaction (RT-PCR), while p-ERK1/2 and bcl-2 protein expression levels were quantified by Western blotting. Results Formononetin promoted the proliferation of CNE2 cells at low concentrations (0, 0.05, 0.1, 0.2, 0.5, 1, 2 and 5 µM), OD values increased from 0.27 ± 0.01 to 0.30 ± 0.01, 0.30 ± 0.01,0.36 ± 0.01, 0.35 ± 0.01, 0.34 ± 0.01, 0.34 ± 0.01 and 0.32 ± 0.01, respectively. The percentage of late apoptosis declined from 6.77% ± 0.73% (0 µM group) to 6.2% ± 0.4% (0.1 µM group), 3.83% ± 0.71% (0.3 µM group) and 5.1% ± 0.52% (1M group). The mRNA levels of bax and bcl-2 were down- and upregulated, respectively, by formononetin. Bcl-2 and p-ERK1/2 protein levels were also upregulated. Conclusions Formononetin stimulates CNE2 cell proliferation and has an inhibitory effect on CNE2 cells apoptosis, which is mediated by the activation of the ERK1/2 signaling pathways.

The molecular characterization and RNAi silencing of SjZFP1 in Schistosoma japonicum.

During development, Schistosoma japonicum undergoes many morphological and physiological transformations as a result of profound changes in gene expression. Proteins containing zinc finger motifs usually play an important role in DNA recognition, RNA packaging, and transcriptional activation. In our current study, we cloned the open reading frame (ORF) of SjZFP1 of S. japonicum, which encodes a zinc finger protein. We analyzed the complementary DNA (cDNA) sequence of SjZFP1 and examined the expression of SjZFP1 messenger RNA (mRNA) at various developmental stages. We also tested the effects of RNA interference (RNAi) silencing on worm burden, spawning, and egg hatching. The ORF in the SjZFP1 cDNA was 1017 bp in length and was predicted to encode a 338-aa protein with a molecular mass of approximately 38.5 kDa and theoretical isoelectric point (pI) of 7.08. Several conserved regions, including a B-box-type zinc-binding domain, two bipartite nuclear localization signal domains, a paired amphipathic helix repeat, and overlapping RING and PHD finger domains, were identified in the predicted amino acid sequence of SjZFP1. Using real-time PCR, we showed that the SjZFP1 mRNA was expressed across all of the developmental stages of the parasite and that the level of transcription was highest in the cercariae, eggs, schistosomula, and mature adult worms. The level of SjZFP1 mRNA expression in cultured schistosomula treated with one of two SjZFP1-specific small interfering RNAs (siRNAs; AY770 and AY546) was reduced by over 80 %, compared with that in the controls. In RNAi experiments in BALB/c mice, the level of SjZFP1 mRNA increased significantly when the mice were treated with the same SjZFP1-specific siRNAs during the early stages of infection. By contrast, the level of SjZFP1 mRNA decreased significantly when the mice were treated with the SjZFP1-specific siRNAs during the middle to late stages of infection. In four independent experiments, fewer worms were recovered from mice treated with the SjZFP1-specific siRNAs, compared with the number of worms recovered from the control mice. Both the average number and hatching rates of liver eggs recovered from mice treated with the SjZFP1-specific siRNAs during the middle to late stages of infection were significantly lower than those of the liver eggs recovered from the control mice. Our results suggest that the SjZFP1 gene might be important for parasite development, spawning in the vertebrate host, and egg hatching.

[Optimal cut-off value of phalangeal radiographic absorptiometry to identify osteoporosis in postmenopausal women].

OBJECTIVE: To study the optimal cut-off value of phalangeal radiographic absorptiometry (RA) to identify osteoporosis in postmenopausal women. METHODS: A total of 650 postmenopausal women were recruited in this study. Bone mineral density (BMD) at lumbar spine and left proximal femur neck was measured by dual-energy X-ray absorptiometry (DXA) as the standard method to identify postmenopausal osteoprosis. Phalangeal bone density was estimated by the use of RA. Optimal cut-off value of phalangeal RA was determined using a ROC curve for screening the ostreoporosis cases. RESULTS: When the cut-off value of phalangeal RA was T score < or = -2.5, the sensitivity was 74.2%, the specificity was 72.9%. When the cut-off value was T score < or = -2.21, the sensitivity was 81.4%, the specificity was 62.0%. CONCLUSION: The cut-off value of phalangeal RA as T score -2.21. which has higher sensitivity could be optimal to identify postmenopausal osteoporosis.

4-Phenylbutyric acid suppresses inflammation through regulation of endoplasmic reticulum stress of endothelial cells stimulated by uremic serum.

AIMS: Endoplasmic reticulum (ER) stress is involved in the pathogenesis of atherosclerosis (AS). Endothelial cell (EC) dysfunction and monocyte migration to the subendothelium are considered to be essential manifestations of AS. We conducted this study to determine whether ER stress was involved in uremic serum-induced EC dysfunction and whether the regulation of ER stress using a chemical chaperone 4-phenylbutyric acid (4-PBA) had a preventative effect. MAIN METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into 4 groups: a control serum group (C.S), a uremic serum group (U.S), a uremic serum plus 4-PBA (5mM) treatment group (4-PBA), and a uremic serum plus pyrrolidine dithiocarbamate (PDTC:50 µM) treatment group (PDTC). KEY FINDINGS: Lower concentrations of uremic serum (<10%) facilitated the proliferation of HUVECs. In contrast, the proliferative capability of HUVECs was gradually decreased when we continuously increased the concentration of uremic serum. Compared with C.S, HUVEC incubation with uremic serum had high expression levels of GRP78, p-PERK, NF-κB, MCP-1, and VEGF. THP-1 migration was markedly higher than C.S over the indicated time. These alterations were inhibited by the administration of 4-PBA. SIGNIFICANCE: These findings suggest that regulation of ER stress coupled with inflammatory activation by 4-PBA would be a promising therapy to reverse the process and development of uremic serum-induced EC dysfunction.

[Risk factors of acute-phase response following the first-dose administration of zoledronic acid in the treatment of osteoporosis].

OBJECTIVE: To explore the risk factors of acute-phase response (APR) following the first-dose administration of zoledronic acid in the treatment of osteoporosis. METHODS: We reviewed the clinical data of the patients receiving the first use of zoledronic acid 5 mg treatment of osteoporosis from January 2009 to November 2012, and divided the patients into acute phase response group (APR+) and no response group (APR-). The age, body mass index (BMI), concomitant medications, comorbidities, laboratory parameters between the two groups were compared and analyzed. RESULTS: A total of 178 patients were eligible for inclusion in the study, of which 108 patients experienced APR. In APR group, there were 80 (44. 9%) patients developed fever, 14 (9. 6%) chills, 48 (27.0%) musculoskeletal pain, 19 (10.7%) gastrointestinal symptoms, 10 (5.6%) headache and dizziness, 7 (3.9%) palpitation,and 3 (1.7%) rash. APR was more common in the patients with higher baseline tartrate-resistant acid phosphatase 5b (TRACP-5b) and new-onset vertebral compression fractures (new-onset VCF). Stepwise logistic regression showed that the odds ratio (OR) of APR in higher baseline TRACP-5b and new VCF was 3. 3 and 2. 5 respectively. CONCLUSION: The first use of zoledronic acid in the treatment of osteoporosis appears high incidence of APR. High TRACP-5b levels and new vertebral fracture are risk factors for APR.

[Responses of tomato leaf photosynthesis to rapid water stress].

By using polyethylene glycol (PEG-6000) solution to regulate the water potential of tomato (Lycopersicon esculentum) rhizosphere to simulate water stress, this paper studied the dynamic changes of net photosynthetic rate, dark respiratory rate and CO2 compensatory concentration of detached tomato leaves in the process of photosynthetic induction. Under 1000 micromol m-2 s-1 of light induction, the time required to reach the maximum net photosynthetic rate of water-stressed tomato leaves was shortened by 1/3, while the stomatal conductance was increased by 1.5 times, as compared to the non-stress control. Also, the light saturation point (LSP) of water-stressed tomato leaves was lowered by 65% to 85%, and the light compensation point (LCP) was increased by 75% to 100%, suggesting that the effective range of light utilized by tomato leaves was reduced. Furthermore, water stress decreased the maximum photosynthetic capacity of tomato leaves by 40%, but increased the dark respiration rate by about 45% . It was suggested that rapid water stress made the stomata of tomato leaves quickly opened, without initial photosynthetic induction stage. In conclusion, water stress could induce the decrease of plant light-energy use efficiency and potential, being the main reason for the decrease of plant productivity, and stomatal regulation could be the main physiological mechanism of tomato plants to adapt to rapid water stress.

Functional implications of microRNA-215 in TGF-ß1-induced phenotypic transition of mesangial cells by targeting CTNNBIP1.

Mesangial cell (MC) phenotypic transition is crucial for the progression of diabetic nephropathy. A major stimulus mediating high glucose-induced MC phenotypic transition is TGF-ß1. Our current study focuses on microRNA-215 (miR-215) and investigates its role in TGF-ß1-mediated MC phenotypic transition. Using real-time quantitative PCR (qRT-PCR) and northern blotting, we determined that the miR-192/215 family is dramatically upregulated under diabetic conditions both in vitro and in vivo. Gain- and loss-of-function approaches demonstrated that miR-215 inhibition significantly inhibited TGF-ß1-induced mouse mesangial cell (MMC) phenotypic transition, whereas miR-215 upregulation promoted MMC phenotypic transition. Interestingly, these changes were not detected in cells that were treated with TGF-ß1 and miR-192 mimics or inhibitors. These results suggest that miR-215 participates in TGF-ß1-induced MMC phenotypic transition. Luciferase reporter assays were used to identify whether catenin-beta interacting protein 1 (CTNNBIP1) is a direct target of miR-215, which was predicted by bioinformatic analysis. Mechanistic studies revealed that CTNNBIP1 suppresses Wnt/ß-catenin signaling and that miR-215 promotes ß-catenin activation and upregulates α-SMA and fibronectin expression in TGF-ß1-treated MMCs by targeting CTNNBIP1. In addition, in vivo miR-215 silencing with a specific antagomir significantly increased CTNNBIP1 protein expression, resulting in reduced ß-catenin activity and decreased α-SMA and fibronectin expression in db/db mouse kidney glomeruli. Taken together, our findings indicate that miR-215 plays an essential role in MC phenotypic transition by regulating the CTNNBIP1/ß-catenin pathway, which is related to the pathogenesis of diabetic nephropathy.

Uraemic serum induces dysfunction of vascular endothelial cells: role of ubiquitin-proteasome pathway.

The ubiquitin-proteasome pathway (UPP) has been indicated to contribute to dysfunction of endothelial cells (ECs). Nevertheless, the relationship between UPP and vascular complications of uraemia remains unknown. We aimed to determine whether the UPP is activated in vascular ECs when cultured with uraemic serum, and to examine the role of the UPP on dysfunction of ECs in uraemia. Rabbit aortic endothelial cells (RAECs) were cultured with normal serum or different concentrations of uraemic serum. The expression of the ubiquitin-activating enzyme (E1), an indicator of the UPP, was detected by real-time RT-PCR and Western blot; proteasome activity was determined by fluorescence spectrophotometry; and nuclear factor-κB (NF-κB) activity and expression, as well as tumour necrosis factor-α (TNF-α) expression, were also detected. We found that the expression of E1 and the activities of three kinds of proteasomes were increased significantly in RAECs after incubation with uraemic serum. Proliferation of RAECs was increased significantly by incubation with 3-15% uraemic serum but decreased markedly when incubated with uraemic serum above 15% (increased apoptosis). Incubation of RAECs with uraemic serum induced increased NF-B DNA-binding activity and nuclear translocation of NF-κB, decreased nitric oxide production and increased expression of TNF-α, which is the final effector of inflammatory activation of cells. All of these responses in RAECs were suppressed by the specific proteasome inhibitor, MG132. The inhibition of inflammatory responses by MG132 was further supported by a parallel experiment with pyrrolidine dithiocarbamate, a specific inhibitor of κNF-B. These findings suggest that the UPP was activated in RAECs by administration of uraemic serum, and played a pivotal role in the dysfunction of vascular ECs, such as inflammatory activation.