Energetically Favored 2D to 3D Transition: Why Silicene Cannot Be Grown on Ag(111).

Silicene, a two-dimensional (2D) Si monolayer with properties similar to those of graphene, has attracted considerable attention because of its compatibility with existing technology. Most growth efforts to date have focused on the Ag(111) substrate, with a 3 × 3 phase widely reported below one monolayer (ML). As the coverage increases, a √3 × âˆš3 pattern frequently emerges, which has been proposed by various experimental investigations as a Si(111)-3×3-Ag reconstructed structure. We report first-principles calculations to understand this series of observations. A major finding from our energetics studies is that Si growth on Ag(111) beyond one ML will switch to the Volmer-Weber mode, forming three-dimensional sp3 films. Combining with the condition that the 3 × 3 monolayer on Ag(111) does not have the correct buckling pattern of freestanding silicene, we conclude that silicene cannot be grown on Ag(111) and that a 2D to 3D transition is energetically favored beyond one ML.

Surufatinib combined camrelizumab as a valuable third-line rescue therapy for a patient with extensive-stage for small-cell lung cancer: a case report and literature review.

Lung cancer is one of the most common malignant tumors with the highest incidence. Gene mutations are rare in small-cell lung carcinoma (SCLC), resulting in targeted therapy being only a third-line recommendation. Surufatinib (Sulanda) is an oral angio-immune kinase inhibitor used to treat solid tumors. We report a case of SCLC treated with surufatinib combined with camrelizumab, with good therapeutic results in our department. The patient experienced over 18 months of progression-free survival and over 28 months of overall survival. This suggests that surufatinib combined with camrelizumab is an effective third-line treatment for SCLC patients. However, the response rate to surufatinib treatment in all patients with SCLC remains unknown and needs to be determined in a large population.

Association of seafood consumption with cardiovascular disease among adults in Qingdao, China.

BACKGROUND AND AIMS: The relationship between seafood consumption and cardiovascular disease (CVD) is controversial, and studies have not considered competing risk events. Our study examined the association between a full range of seafood consumption and CVD incidence and mortality based on the Qingdao Diabetes Prevention Program. METHODS AND RESULTS: We followed up 5285 participants without CVD at baseline until December 31, 2021. CVD cases and deaths were identified through record linkage with the Qingdao CVD Surveillance System and the Qingdao Death Surveillance System, respectively. Information on seafood consumption was obtained using a food frequency questionnaire. We used the Cox proportional hazard model and the competing risk model to evaluate the association between all types of seafood consumption and CVD incidence and mortality. During a median follow-up of 11.4 years, 122 CVD cases and 75 deaths occurred. After adjustment for potential confounders, compared with nonconsumers, seafood consumption of 300-500 and > 500 g/week was associated with a lower risk of CVD incidence [hazards ratio and 95 % confidence interval (CI): 0.54 (0.29-0.99) and 0.49 (0.26-0.91), respectively]. However, seafood consumption of >500 g/week had a significantly lower risk of CVD mortality [subdistribution hazard ratio and 95 % CI: 0.40 (0.17-0.95)], but it was insignificant in other groups. CONCLUSION: Seafood consumption of 300-500 g/week and >500 g/week was associated with a lower CVD incidence and mortality. Our findings provide evidence of the recommendations of the 2022 Dietary Guidelines for Chinese residents and may guide the promotion of strategies for CVD prevention.

NMDA receptor within nucleus accumbens shell regulates propofol self-administration through D1R/ERK/CREB signalling pathway.

Addictive properties of propofol have been demonstrated in both humans and animals. The nucleus accumbens (NAc) shell (NAsh) in the brain, along with the interactions between N-methyl-D-aspartate receptor (NMDAR) and the dopamine D1 receptor (D1R), as well as their downstream ERK/CREB signalling pathway in the NAc, are integral in regulating reward-seeking behaviour. Nevertheless, it remains unclear whether NMDARs and the NMDAR-D1R/ERK/CREB signalling pathway in the NAsh are involved in mediating propofol addiction. To investigate it, we conducted experiments with adult male Sprague-Dawley rats to establish a model of propofol self-administration behaviour. Subsequently, we microinjected D-AP5 (a competitive antagonist of NMDARs, 1.0-4.0 µg/0.3 µL/site) or vehicle into bilateral NAsh in rats that had previously self-administered propofol to examine the impact of NMDARs within the NAsh on propofol self-administration behaviour. Additionally, we examined the protein expressions of NR2A and NR2B subunits, and the D1R/ERK/CREB signalling pathways within the NAc. The results revealed that propofol administration behaviour was enhanced by D-AP5 pretreatment in NAsh, accompanied by elevated expressions of phosphorylation of NR2A (Tyr1246) and NR2B (Tyr1472) subunits. There were statistically significant increases in the expressions of D1Rs, as well as in the phosphorylated ERK1/2 (p-ERK1/2) and CREB (p-CREB). This evidence substantiates a pivotal role of NMDARs in the NAsh, with a particular emphasis on the NR2A and NR2B subunits, in mediating propofol self-administration behaviour. Furthermore, it suggests that this central reward processing mechanism may operate through the NMDAR-D1R/ERK/CREB signal transduction pathway.

Association between famine exposure during infancy and childhood and the risk of chronic kidney disease in adulthood.

BACKGROUND: Famine exposure in childhood is proven to be associated with multiple chornic disease in adult but has not been studied with chronic kidney disease (CKD). AIMS: This study was conducted to identify the relationship between famine exposure during infancy and childhood - specifically, the Chinese famine of 1959-1961 - and the risk of adult-onset chronic kidney disease (CKD) among Chinese individuals. METHODS: This study included 2937 individuals from the Qingdao Diabetes Prevention Program. They were stratified by birth year into infancy-exposed (1956-1958), childhood-exposed (1950-1955) and unexposed (1963-1971) groups. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR of <90 mL/min/1.73 m2 . RESULTS: The mean eGFR values for the infancy-exposed and childhood-exposed groups were 107.23 ± 12.53 and 103.23 ± 12.44 mL/min/1.73 m2 , respectively, both of which were lower than that of the unexposed group (114.82 ± 13.39 mL/min/1.73 m2 ; P < 0.05). In the crude model, the odds ratio (OR) for CKD was 2.00 (95% confidence interval (CI): 1.39-2.88) in the infancy-exposed group and 2.92 (95% CI: 2.17-3.93) in the childhood-exposed group. Further adjustments for urban/rural residence, body mass index, age, current smoking, type 2 diabetes, systolic blood pressure, diastolic blood pressure and total cholesterol did not significantly alter the association between famine exposure and CKD. The corresponding ORs were 1.71 (95% CI: 1.17-2.50) and 2.48 (95% CI: 1.81-3.40) for the infancy-exposed and childhood-exposed groups respectively. CONCLUSIONS: Famine exposure during infancy and childhood is associated with a long-term decline in eGFR and an increased adult-onset CKD risk. Early intervention for high-risk individuals may mitigate the risk of adult-onset CKD.

[Brain Fog: A Concept Analysis].

Brain fog is a symptom that has gained increasing attention worldwide since the start of the COVID-19 pandemic, as patients affected by COVID-19 may experience cognitive dysfunction, colloquially known as brain fog, for a period of time after recovery. Brain fog affects activities of daily living and work performance and has the potential to negatively impact society and the economy. However, a clear definition and concept analysis of brain fog is lacking in the literature. In this article, a concept analysis of brain fog is conducted using Walker and Avant's concept analysis steps to verify the source and definition of brain fog, clarify related concepts similar to brain fog, and establish the defining attributes, antecedents, and consequences of this condition. Model, borderline, contrary, and related cases are listed to illustrate and provide related empirical references in the literature. The authors hope this article will provide a clearer understanding of brain fog, which then may be applied in nursing clinical practice and future research to develop strategies and care methods for improving brain fog symptoms.

The excitatory transmission from basolateral nuclues of amygdala to nucleus accumbens shell regulates propofol self-administration through AMPA receptors.

Propofol addictive properties have been demonstrated in humans and rats. The glutamatergic transmission from basolateral nucleus of amygdala (BLA) to the nucleus accumbens (NAc) modulates reward-seeking behaviour; especially, NAc shell (NAsh) is implicated in reward-seeking response. Previous studies indicated the interactions between AMPA receptors (AMPARs) and dopamine D1 receptor (D1R) in NAc mediated drug addiction, but whether the circuit of BLA-to-NAsh and AMPARs regulate propofol addiction remains unclear. We trained adult male Sprague-Dawley rats for propofol self-administration to examine the changes of action potentials (APs) and spontaneous excitatory postsynaptic currents (sEPSCs) in the NAsh. Thereafter, optogenetic stimulation with adeno-associated viral vectors microinjections in BLA was used to explore the effect of BLA-to-NAsh on propofol self-administration behaviour (1.7 mg/kg/injection). The pretreatment effects with NBQX (0.25-1.0 µg/0.3 µl/site) or vehicle in the NAsh on propofol self-administration behaviour, the expressions of AMPARs subunits and D1R/ERK/CREB signalling pathway in the NAc were detected. The results showed that the number of APs, amplitude and frequency of sEPSCs were enhanced in propofol self-administrated rats. Propofol self-administration was inhibited in the NpHR3.0-EYFP group, but in the ChR2-EYFP group, there was a promoting effect, which could be weakened by NBQX pretreatment. NBQX pretreatment also significantly decreased the expressions of GluA2 subunit and D1R in the NAc but did not change the expressions of GluA1 and ERK/CREB signalling pathway. The evidence supports a vital role of BLA-to-NAsh circuit in regulating propofol self-administration and suggests this central reward processing may function through the interaction between AMPARs and D1R in the NAsh.

Prediction of Intradialytic Blood Pressure Variation Based on Big Data.

INTRODUCTION: Cardiovascular (CV) events are the major cause of morbidity and mortality associated with blood pressure (BP) in hemodialysis (HD) patients. BP varies significantly during HD treatment, and the dramatic variation in BP is a well-recognized risk factor for increased mortality. The development of an intelligent system capable of predicting BP profiles for real-time monitoring is important. Our aim was to build a web-based system to predict changes in systolic BP (SBP) during HD. METHODS: In this study, dialysis equipment connected to the Vital Info Portal gateway collected HD parameters that were linked to demographic data stored in the hospital information system. There were 3 types of patients: training, test, and new. A multiple linear regression model was built using the training group with SBP change as the dependent variable and dialysis parameters as the independent variables. We tested the model's performance on test and new patient groups using coverage rates with different thresholds. The model's performance was visualized using a web-based interactive system. RESULTS: A total of 542,424 BP records were used for model building. The accuracy was greater than 80% in the prediction error range of 15%, and 20 mm Hg of true SBP in the test and new patient groups for the model of SBP changes suggested the good performance of our prediction model. In the analysis of absolute SBP values (5, 10, 15, 20, and 25 mm Hg), the accuracy of the SBP prediction increased as the threshold value increased. DISCUSSION: This databae supported our prediction model in reducing the frequency of intradialytic SBP variability, which may help in clinical decision-making when a new patient receives HD treatment. Further investigations are needed to determine whether the introduction of the intelligent SBP prediction system decreases the incidence of CV events in HD patients.

Preoperative combination score of neutrophils, monocytes, and lymphocytes as a predictor for locally advanced rectal cancer.

OBJECTIVE: The aim of this study was to investigate the prognostic value of baseline peripheral blood neutrophils, monocytes, and lymphocytes on locally advanced rectal cancer (LARC) patients. METHODS: Clinicopathologic data of 317 LARC patients during July 2010 and October 2016 were retrospectively gathered. X-tile software was used to acquire the optimal cutoff values of neutrophils, monocytes, and lymphocytes. Peripheral blood immune score (PBIS) system was proposed and built based on neutrophils, monocytes, and lymphocytes. The Cox model was used to analyze the associations between clinicopathological characteristics and potential outcomes. C-index was used to assess model performance. A nomogram was constructed to predict prognosis, and a calibration plot was used to verify the accuracy of the nomogram prediction model. RESULTS: Cutoff values of neutrophils, lymphocytes, and monocytes were 4.46 (× 109/L), 1.66 (× 109/L), and 0.39 (× 109/L), respectively. PBIS was related to sex (P < 0.001), tumor length (P = 0.003), and tumor thickness (P = 0.014). Multivariate Cox regression analysis revealed that PBIS (HR = 0.707, 95% CI: 0.549-0.912, P = 0.008) was an independent predictor of DFS. High PBIS (HR = 0.697, 95% CI: 0.492-0.988, P = 0.043) and high lymphocyte count (HR = 0.511, 95%CI: 0.273-0.958, P = 0.036) were favorable factors of OS. Both C-index (0.74, 95% CI: 0.549-0.912) and the calibration plot showed good prediction ability of the nomogram for DFS. CONCLUSION: PBIS, composed of baseline peripheral blood neutrophils, monocytes, and lymphocytes, is an independent predictor of the prognosis of LARC. Combination of PBIS and ypTNM stage may be a promising marker to guide adjuvant therapy after the operation.

MiR-370-5p inhibits the progression of breast cancer via targeting LUC7L3.

Breast cancer is one of the most common malignancies and one of the leading causes of cancer-induced mortality among women. Over the past decades, the occurrence of breast cancer has been a significant increase. As documented in numerous researches, microRNAs (miRNAs) play vital roles in a wide range of biological processes associated with the occurrence and development of breast cancer. Nevertheless, the role of miR-370-5p in breast cancer remains obscure, and the possible molecular regulatory mechanism needs to be further explored. In this study, our results delineated that miR-370-5p was downregulated in breast cancer tissues and cell lines. Besides, miR-370-5p overexpression suppressed cell proliferation and invasion in breast cancer. MiR-370-5p downregulation exerted an opposite result. In addition, LUC7L3 was identified as a target gene for miR-370-5p. Similar with the results induced by miR-370-5p overexpression, LUC7L3 knockdown attenuated the proliferation and invasion ability of breast cancer cells. Moreover, the alternation of LUC7L3 expression reversed the regulatory effects of miR-370-5p on cell phenotypes in breast cancer. Overall, miR-370-5p may exert antitumor effect on breast cancer. Hence, miR-370-5p may serve as a novel therapeutic marker for the treatment of patients with breast cancer.

Oxidative storm in a patient with acute rotenone-containing plant poisoning.

A 64-year-old woman presented with coma, seizure, and lactic acidosis after ingesting 80 yam bean seeds. This rotenone-containing seeds cause cellular asphyxia via blockage of the mitochondrial electron transport. Subsequent oxidative stress results in the formation of lipid peroxidation (LPO). Rotenone analysis via liquid chromatography mass spectrometry revealed the following: 31,590 ng/mL in cooked yam bean seed and 100 ng/mL in the blood. We attempted to use N-acetylcysteine to alleviate oxidative stress and documented the continuous decline in the plasma concentration of LPO.

Downregulation of SIRT1 signaling underlies hepatic autophagy impairment in glycogen storage disease type Ia.

A deficiency in glucose-6-phosphatase-α (G6Pase-α) in glycogen storage disease type Ia (GSD-Ia) leads to impaired glucose homeostasis and metabolic manifestations including hepatomegaly caused by increased glycogen and neutral fat accumulation. A recent report showed that G6Pase-α deficiency causes impairment in autophagy, a recycling process important for cellular metabolism. However, the molecular mechanism underlying defective autophagy is unclear. Here we show that in mice, liver-specific knockout of G6Pase-α (L-G6pc-/-) leads to downregulation of sirtuin 1 (SIRT1) signaling that activates autophagy via deacetylation of autophagy-related (ATG) proteins and forkhead box O (FoxO) family of transcriptional factors which transactivate autophagy genes. Consistently, defective autophagy in G6Pase-α-deficient liver is characterized by attenuated expressions of autophagy components, increased acetylation of ATG5 and ATG7, decreased conjugation of ATG5 and ATG12, and reduced autophagic flux. We further show that hepatic G6Pase-α deficiency results in activation of carbohydrate response element-binding protein, a lipogenic transcription factor, increased expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), a lipid regulator, and suppressed expression of PPAR-α, a master regulator of fatty acid ß-oxidation, all contributing to hepatic steatosis and downregulation of SIRT1 expression. An adenovirus vector-mediated increase in hepatic SIRT1 expression corrects autophagy defects but does not rectify metabolic abnormalities associated with G6Pase-α deficiency. Importantly, a recombinant adeno-associated virus (rAAV) vector-mediated restoration of hepatic G6Pase-α expression corrects metabolic abnormalities, restores SIRT1-FoxO signaling, and normalizes defective autophagy. Taken together, these data show that hepatic G6Pase-α deficiency-mediated down-regulation of SIRT1 signaling underlies defective hepatic autophagy in GSD-Ia.

Vascularized Bone-Mimetic Hydrogel Constructs by 3D Bioprinting to Promote Osteogenesis and Angiogenesis.

Bone is a highly vascularized tissue with a unique and complex structure. Long bone consists of a peripheral cortical shell containing a network of channels for vascular penetration and an inner highly vascularized bone marrow space. Bioprinting is a powerful tool to enable rapid and precise spatial patterning of cells and biomaterials. Here we developed a two-step digital light processing technique to fabricate a bone-mimetic 3D hydrogel construct based on octacalcium phosphate (OCP), spheroids of human umbilical vein endothelial cells (HUVEC), and gelatin methacrylate (GelMA) hydrogels. The bone-mimetic 3D hydrogel construct was designed to consist of a peripheral OCP-containing GelMA ring to mimic the cortical shell, and a central GelMA ring containing HUVEC spheroids to mimic the bone marrow space. We further demonstrate that OCP, which is evenly embedded in the GelMA, stimulates the osteoblastic differentiation of mesenchymal stem cells. We refined the design of a spheroid culture device to facilitate the rapid formation of a large number of HUVEC spheroids, which were embedded into different concentrations of GelMA hydrogels. It is shown that the concentration of GelMA modulates the extent of formation of the capillary-like structures originating from the HUVEC spheroids. This cell-loaded hydrogel-based bone construct with a biomimetic dual ring structure can be potentially used for bone tissue engineering.

Results of Fabry Disease Screening in Male Pre-End Stage Renal Disease Patients with Unknown Etiology Found Through the Platform of a Chronic Kidney Disease Education Program in a Northern Taiwan Medical Center.

BACKGROUND/AIMS: Fabry disease (FD), a rare x-lined genetic disorder is a cause of renal deterioration. The phenotype of FD is highly variable and nonspecific, and correct diagnosis has always been delayed. We aimed to explore the prevalence and clinical presentation of FD in this high-risk male population in a Northern Taiwan medical center. METHODS: This is the first study to survey the incidence of FD in this high-risk population through the platform of a chronic kidney disease (CKD) education program in Asia. A total of 1,012 male patients with unknown CKD causes were screened using an assay of alpha-galactosidase A activity (α-Gal A) by dried blood spots (DBS). A final GLA gene analysis was also done for those with low enzyme activity. RESULTS: We identified two new patients with classic FD and four patients with late-onset FD. One novel GLA mutation with c.413 G>A was found in one classic FD patient (index 5). The prevalence of FD is about 0.59 % (6 in 1,012) in the high-risk population group with CKD. The clinical symptoms of FD patients are nonspecific except in those with various degrees of renal failure. Those patients' correct diagnosis was delayed, taking years and even decades. Three patients received enzyme replacement therapy and one started regular hemodialysis due to persistent renal function deterioration. Another two patients were found from family screening through a new index. In addition, a false negative result occurred in one patient who was proved to have FD by his kidney pathology as determined by this screening. CONCLUSION: FD is not such as rare a disease and its prevalence is greater in this high-risk male population. Clinicians need to be aware that FD should be included in the differential diagnosis in CKD with unknown etiology.

Intelligent system to predict intradialytic hypotension in chronic hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication and a major risk factor of increased mortality during hemodialysis (HD). However, predicting the occurrence of intradialytic blood pressure (BP) fluctuations clinically is difficult. This study aimed to develop an intelligent system with capability of predicting IDH. METHODS: In developing and training the prediction models in the intelligent system, we used a database of 653 HD outpatients who underwent 55,516 HD treatment sessions, resulting in 285,705 valid BP records. We built models to predict IDH at the next BP check by applying time-dependent logistic regression analyses. RESULTS: Our results showed the sensitivity of 86% and specificity of 81% for both nadir systolic BP (SBP) of <90 mmHg and <100 mmHg, suggesting good performance of our prediction models. We obtained similar results in validating via test data and data of newly enrolled patients (new-patient data), which is important for simulating prospective situations wherein dialysis staff are unfamiliar with new patients. This compensates for the retrospective nature of the BP records used in our study. CONCLUSION: The use of this validated intelligent system can identify patients who are at risk of IDH in advance, which may facilitate well-timed personalized management and intervention.

Mice expressing reduced levels of hepatic glucose-6-phosphatase-α activity do not develop age-related insulin resistance or obesity.

Glycogen storage disease type-Ia (GSD-Ia) is caused by a lack of glucose-6-phosphatase-α (G6Pase-α or G6PC) activity. We have shown that gene therapy mediated by a recombinant adeno-associated virus (rAAV) vector expressing human G6Pase-α normalizes blood glucose homeostasis in the global G6pc knockout (G6pc(-/-)) mice for 70-90 weeks. The treated G6pc(-/-) mice expressing 3-63% of normal hepatic G6Pase-α activity (AAV mice) produce endogenous hepatic glucose levels 61-68% of wild-type littermates, have a leaner phenotype and exhibit fasting blood insulin levels more typical of young adult mice. We now show that unlike wild-type mice, the lean AAV mice have increased caloric intake and do not develop age-related obesity or insulin resistance. Pathway analysis shows that signaling by hepatic carbohydrate response element binding protein that improves glucose tolerance and insulin signaling is activated in AAV mice. In addition, several longevity factors in the calorie restriction pathway, including the NADH shuttle systems, NAD(+) concentrations and the AMP-activated protein kinase/sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway are upregulated in the livers of AAV mice. The finding that partial restoration of hepatic G6Pase-α activity in GSD-Ia mice not only attenuates the phenotype of hepatic G6Pase-α deficiency but also prevents the development of age-related obesity and insulin resistance seen in wild-type mice may suggest relevance of the G6Pase-α enzyme to obesity and diabetes.

Glycogen storage disease type Ia mice with less than 2% of normal hepatic glucose-6-phosphatase-α activity restored are at risk of developing hepatic tumors.

Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA) and carcinoma (HCC), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). We have previously shown that G6pc-/- mice receiving gene transfer mediated by rAAV-G6PC, a recombinant adeno-associated virus (rAAV) vector expressing G6Pase-α, and expressing 3-63% of normal hepatic G6Pase-α activity maintain glucose homeostasis and do not develop HCA/HCC. However, the threshold of hepatic G6Pase-α activity required to prevent tumor formation remained unknown. In this study, we constructed rAAV-co-G6PC, a rAAV vector expressing a codon-optimized (co) G6Pase-α and showed that rAAV-co-G6PC was more efficacious than rAAV-G6PC in directing hepatic G6Pase-α expression. Over an 88-week study, we showed that both rAAV-G6PC- and rAAV-co-G6PC-treated G6pc-/- mice expressing 3-33% of normal hepatic G6Pase-α activity (AAV mice) maintained glucose homeostasis, lacked HCA/HCC, and were protected against age-related obesity and insulin resistance. Of the eleven rAAV-G6PC/rAAV-co-G6PC-treated G6pc-/- mice harboring 0.9-2.4% of normal hepatic G6Pase-α activity (AAV-low mice), 3 expressing 0.9-1.3% of normal hepatic G6Pase-α activity developed HCA/HCC, while 8 did not (AAV-low-NT). Finally, we showed that the AAV-low-NT mice exhibited a phenotype indistinguishable from that of AAV mice expressing ≥3% of normal hepatic G6Pase-α activity. The results establish the threshold of hepatic G6Pase-α activity required to prevent HCA/HCC and show that GSD-Ia mice harboring <2% of normal hepatic G6Pase-α activity are at risk of tumor development.

Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. METHODS: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. RESULTS: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. CONCLUSIONS: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

Interferon-α reduces the gefitinib sensitivity of human non-small cell lung cancer.

AIM OF THE STUDY: Many studies have shown that interferon-α (IFN-α) enhances the antiproliferative effect of gefitinib in some solid tumours. We aimed to determine the effect of combining IFN-α with gefitinib in human non-small cell lung cancer (NSCLC) cell lines (A549, H1299, HCC827) with different EGFR and K-Ras gene statuses. MATERIAL AND METHODS: An MTT assay was used to assess cell proliferation. Apoptosis was detected by an Annexin V/propidium iodide assay using flow cytometry, and western blotting was used to determine the expression of epidermal growth factor receptor/phosphorylated epidermal growth factor receptor (EGFR/p-EGFR) and signal transducers and activators of transcription 3/phosphorylated signal transducers and activators of transcription 3 (STAT3/p-STAT3). RESULTS: There was an additive interaction when gefitinib was combined with IFN-α in all cell lines; however, there was antagonism when gefitinib followed IFN-α pretreatment in three cell lines. Notably, IFN-α pretreatment significantly reduced the gefitinib sensitivity of HCC827 cells. Surprisingly, while IFN-α inhibited STAT3 phosphorylation in cell lines, gefitinib could do so. CONCLUSIONS: The results might confirm the hypothesis that IFN-α induces gefitinib sensitivity of NSCLC, and IFN-α inhibits phosphorylation of STAT3, which may be dependent on EGFR signal activation playing a role in the reduction of gefitinib sensitivity after IFN-α treatment in NSCLC cell lines.