Preoperative platelet distribution width predicts bone metastasis in patients with breast cancer.

PURPOSE: Bone metastases occur in 50-70% of patients with breast cancer (BC) and result in high mortality. Platelet distribution width (PDW), a commonly used parameter of activated platelets, has been associated with a poor prognosis in BC. We aim to investigate the prognostic role of PDW for bone metastasis in BC patients. METHODS: 515 patients who received BC surgery in the Harbin Medical University Cancer Hospital from July 1, 2016, to December 31, 2017, were reviewed. Patients' characteristics and platelet indices upon enrollment in this study were collected. The Kaplan-Meier method was used to estimate the 5-year bone metastasis incidence. The univariate and multivariate Cox regression analyses were utilized to identify risk factors associated with bone metastasis. RESULTS: The patients with bone metastases exhibited lower PDW levels than the patients without bone metastases. Moreover, decreased PDW was significantly correlated with histologic type, multifocal disease, and lymph node status. In addition, the patients with reduced PDW levels were more likely to develop bone metastasis. Multivariate analysis showed that PDW was an independent predictor for bone metastasis. CONCLUSION: PDW is an independent predictor of bone metastasis in BC. Further research is warranted.

Remodeling the Electronic Structure of Metallic Nickel and Ruthenium via Alloying in a Molecular Template for Sustainable Hydrogen Evolution.

The reasonably constructed high-performance electrocatalyst is crucial to achieve sustainable electrocatalytic water splitting. Alloying is a prospective approach to effectively boost the activity of metal electrocatalysts. However, it is a difficult subject for the controllable synthesis of small alloying nanostructures with high dispersion and robustness, preventing further application of alloy catalysts. Herein, we propose a well-defined molecular template to fabricate a highly dispersed NiRu alloy with ultrasmall size. The catalyst presents superior alkaline hydrogen evolution reaction (HER) performance featuring an overpotential as low as 20.6 ± 0.9 mV at 10 mA·cm-2. Particularly, it can work steadily for long periods of time at industrial-grade current densities of 0.5 and 1.0 A·cm-2 merely demanding low overpotentials of 65.7 ± 2.1 and 127.3 ± 4.3 mV, respectively. Spectral experiments and theoretical calculations revealed that alloying can change the d-band center of both Ni and Ru by remodeling the electron distribution and then optimizing the adsorption of intermediates to decrease the water dissociation energy barrier. Our research not only demonstrates the tremendous potential of molecular templates in architecting highly active ultrafine nanoalloy but also deepens the understanding of water electrolysis mechanism on alloy catalysts.

Preoperative PDW levels predict pulmonary metastasis in patients with hepatocellular carcinoma.

BACKGROUND: In hepatocellular carcinoma (HCC), pulmonary metastasis (PM) after hepatectomy is associated with poor clinical outcomes. The crucial phases of tumour cell proliferation, angiogenesis, and metastasis all entail platelet activation. In HCC, platelet distribution width (PDW) suggests platelet size changes and predicts a worse prognosis. The aim of this study was to assess the association between PDW and PMs in HCC patients receiving hepatectomy. MATERIAL/METHODS: From January 2013 to December 2015, a cohort of patients who underwent hepatectomy for HCC at the Harbin Medical University Cancer Hospital in China were retrospectively evaluated. The relationship between PDW levels and clinical and demographic parameters was examined. To investigate the relationships between predicted factors and PM, a competing risk model was used. From January 2016 to December 2018, a validation cohort of 109 patients from the First Affiliated Hospital of Harbin Medical University was studied independently. RESULTS: In the primary cohort, 19 out of 214 patients had postoperative PMs. In HCC patients with PM, PDW levels were lower than in those without PM. There was a significant difference in the cumulative incidence of 2-year PM between the high-PDW and low-PDW groups after controlling for competing risk events (death prior to the development of PM) (p < 0.001). In addition, PDW was also found to be an independent predictor for PM in a multivariable competing risk analysis. The results were externally validated in another cohort. CONCLUSIONS: In HCC, preoperative PDW is significantly associated with PM. PDW could be a biomarker for post-operative PM in HCC patients.

Utility of mean platelet volume in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer. HCC and ICC differ in treatment and prognosis, warranting an effective differential diagnosis between them. This study aimed to explore the clinical value of mean platelet volume (MPV) to discriminate between HCC and ICC. MATERIAL/METHODS: We performed a retrospective analysis of ICC and HCC patients who were from the Harbin Medical University Cancer Hospital, China. Logistic regression analysis was used to identify the independent factors for the differentiation of HCC and ICC. A receiver operating characteristic curve was built to evaluate the diagnostic performance of the potential model. An independent validation study was performed to validate the diagnostic ability. RESULTS: ICC patients were detected in 146 out of 348 patients in the primary cohort. MPV levels were decreased in ICC patients compared with those in HCC patients. Logistic regression analysis revealed that MPV was an independent factor in distinguishing HCC from ICC. A combination of sex, hepatitis B surface antigen, MPV, alpha-fetoprotein, and carbohydrate antigen 19-9 demonstrated a good capability to differentiate HCC from ICC. Similar results were achieved in the validation cohort. CONCLUSIONS: MPV may be a new marker to help distinguish ICC from HCC. Further validation studies are required.

[Bioinformatics analysis and expression pattern of NAC transcription factor family of Angelica dahurica var. formosana from Sichuan province].

NAC(NAM/ATAF/CUC) protein plays an important role in plant growth and development, secondary cell wall formation and stress response. In this study, based on the sequencing data of Angelica dahurica, the NAC family was systematically analyzed using bioinformatics methods and its expression pattern was analyzed. Studies showed that 75 candidate genes had been selected from the NAC transcription factor family of A. dahurica, with the protein size of 148-641, all of which were unstable hydrophilic proteins. Most NAC proteins were localized in the nucleus, and had complete NAC domain. Phylogenetic analysis of NAC family proteins of A.dahurica and Arabidopsis thaliana showed that among the 17 subfamilies, NAC members were unevenly distributed in each subfamily, indicating that the evolution of species is developing in multiple directions. Among them, ANAC063 subfamily contained no NAC sequence of A. dahurica, which might be due to the functional evolution of the species. Analysis of protein transmembrane structure and signal peptide showed that NAC transcription factor could carry out transmembrane transportation, but its signal peptide function had not been found. Expression analysis showed that most transcription factors responded to abiotic stress and hormones to varying degrees, and the effects of hormones were obvious, especially ABA and IAA. In different organs of A. dahurica, most members of the NAC family had higher expression in root phloem, followed by root xylem. This study lays a foundation for further research on the function of A. dahurica NAC transcription factor and for solving the biological problems of A. dahurica.

Association between apoptosis inhibitor of macrophage and microsatellite instability status in colorectal cancer.

BACKGROUND: The microsatellite instability (MSI) in colorectal cancer (CRC) has a more favorable clinical outcome and is characterized by highly upregulated expression of various immunological checkpoints than microsatellite stable (MSS) tumors. Apoptosis inhibitor of macrophage (AIM) is a circulating protein and circulates throughout the body to remove cellular debris. The aim of this study was to evaluate the association between MSI status and AIM levels in CRC patients. METHODS: In this study, we evaluated the levels of AIM by Enzyme Linked Immuno-Sorbent Assay (ELISA) in serum of 430 CRC patients. All patients' clinical and laboratory characteristics at initial diagnosis were collected. The relationship between AIM levels and MSI status was examined. RESULTS: 64 patients (14.9%) were identified as having MSI-H (high-frequency MSI) and 366 casess (85.1%) having MSS. Patients with an MSI-H phenotype had lower AIM levels compared with MSS patients. Moreover, AIM levels were correlated with histological type and MSI status. Logistic regression analysis revealed that decreased AIM levels were independently associated with MSI-H phenotype after adjusting confounding factors. CONCLUSION: Reduced AIM levels are associated with MSI-H subtyping of CRC. Further research on the involvement of AIM in MSI-H CRC is needed.

Genetics insight into the amyotrophic lateral sclerosis/frontotemporal dementia spectrum.

Recent genetic discoveries have dramatically changed our understanding of two major neurodegenerative conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are common, devastating diseases of the brain. For decades, ALS and FTD were classified as movement and cognitive disorders, respectively, due to their distinct clinical phenotypes. The recent identification of chromosome 9 open reading frame 72 (C9orf72) as the major gene causative of familial forms of ALS and FTD uncovered a new reality of a continuous FTD/ALS spectrum. The finding that up to 50% of all patients present some degree of ALS and FTD phenotypes supports this ALS/FTD continuum. Now >100 genes are known to contribute to ALS/FTD, with a few major contributors that are reviewed below. The low penetrance of C9orf72 mutations, its contribution to sporadic cases, and its combination with other genes support an oligogenic model where two or more genes contribute to disease risk, onset, progression and phenotype: from 'pure' ALS or FTD to combined ALS/FTD. These advances in the genetics of ALS/FTD will soon lead to a better mechanistic understanding of the pathobiology of the disease, which should result in the development of effective therapies in the near future.

IL-10 deficiency increases renal ischemia-reperfusion injury.

BACKGROUND: Renal ischemia-reperfusion (IR) injury is a frequent cause of acute kidney injury, which results in high morbidity and mortality. Inflammation is an important factor that is involved in kidney repair after renal IR injury. IL-10 is a potent anti-inflammatory cytokine that inhibits inflammatory pathways, but the role of IL-10 in repairing renal IR injury is not known. Here, we investigated the role of IL-10 in kidney repair after renal IR injury. METHODS: We used an IL-10(-/-) mouse model and examined the serologic and histomorphology of kidney after IR injury. We also measured ki67, TNF-α, IL-6, and macrophages with immunohistochemistry or Western blotting. RESULTS: There was a greater increase in serum creatinine in IL-10(-/-) mice than in wild-type (WT) mice. And compared with WT mice, IL-10(-/-) mice had increased histologic renal injury and decreased proliferation. Moreover, the expression of TNF-α, IL-6 and macrophages was clearly increased in IL-10(-/-) mice compared with the WT mice. CONCLUSION: These data reveal an important role for IL-10 in the improvement of renal IR injury, acting through suppression of inflammatory mediators, and that IL-10 would be a crucial target for the treatment of IR injury.

Structure-based discovery of novel piperidine-biphenyl-DAPY derivatives as non-nucleoside reverse transcriptase inhibitors featuring improved potency, safety, and selectivity: From piperazine-biphenyl-DAPYs to piperidine-biphenyl-DAPYs.

Starting from our previously reported nonnucleoside reverse transcriptase inhibitor (NNRTI, 3), continuous efforts were made to enhance its potency and safety through a structure-based drug design strategy. This led to the discovery of a series of novel piperidine-biphenyl-diarylpyrimidines (DAPYs). Compound 10p, the most active compound in this series, exhibited an EC50 value of 6 nM against wide-type HIV-1 strain, which was approximately 560-fold more potent than the initial compound 3 (EC50 = 3.36 µM). Furthermore, significant improvements were observed in cytotoxicity and selectivity (CC50 > 202.17 µM, SI > 33144) compared to compound 3 (CC50 = 14.84 µM, SI = 4). Additionally, compound 10p demonstrated increased inhibitory activity against clinically mutant virus strains (EC50 = 7-63 nM). Further toxicity evaluation revealed that compound 10p exhibited minimal CYP enzyme and hERG inhibition. Importantly, single-dose acute toxicity testing did not result in any fatalities or noticeable pathological damage in mice. Therefore, compound 10p can be regarded as a lead candidate for guiding further development of biphenyl-diarylpyrimidine NNRTIs with favorable druggability for HIV therapy.

Preoperative glucose-to-lymphocyte ratio predicts survival in cancer.

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.

Development of novel S-N3-DABO derivatives as potent non-nucleoside reverse transcriptase inhibitors with improved potency and selectivity.

Following on our initial discovery of S-CN-DABOs as non-nucleoside reverse transcriptase inhibitors (NNRTIs), a series of novel S-N3-DABO derivatives F1-F31 were developed by substituting the cyano group of S-CN-DABOs with azide group. Some of these compounds were conferred significantly increased potency against wild-type HIV-1 and clinically observed mutant strains. Remarkably, the best compound F10 exerted a 7-fold improvement in potency (EC50 = 0.053 µM) and 12.5-fold higher selectivity (SI = 6818) in MT-4 cells infected with wild-type HIV-1, compared to that of the parent compound B1 (EC50 = 370 nM, SI = 547). The anti-HIV-1 activity of F10 against the tested mutant strains was prominently enhanced. For wild-type reverse transcriptase, it was approximately 19-fold more potent (IC50 = 0.080 µM) than B1 (IC50 = 1.51 µM). It was not found that this analog had significant inhibition of hERG, CYP, and acute toxicity after a single dose of F10 (1.0 g/kg).

Lower subcutaneous fat index predicts bone metastasis in breast cancer.

BACKGROUND: Bone metastases affect 50% to 70% of breast cancer (BC) patients and have a high mortality rate. Adipose tissue loss plays a pivotal role in the progression of cancer. OBJECTIVE: This study aims to evaluate the prognostic value of adipose tissue for bone metastasis in BC patients. METHODS: 517 BC patients were studied retrospectively. Patients' characteristics before the surgery were collected. Quantitative measurements of the subcutaneous fat index (SFI) were performed at the level of the eleventh thoracic vertebra. In order to adjust for the heterogeneity between the low SFI and high SFI groups, propensity score matching (PSM) was used. The Kaplan-Meier method was used to estimate the 5-year bone metastatic incidence. The prognostic analysis was performed with the Cox regression models. RESULTS: Compared with the patients without bone metastasis, the patients with bone metastasis had reduced SFI levels. In addition, Kaplan-Meier analysis revealed that patients with low SFI were more likely to develop bone metastases. The independent predictive value of SFI for bone metastases was confirmed by Cox regression analysis. The survival analysis was repeated after PSM with a 1:1 ratio, yielding similar results (P< 0.05). CONCLUSIONS: SFI is an independent predictor of bone metastasis in BC patients.

Albumin-bilirubin score predicts trastuzumab resistance in HER2-positive breast cancer.

BACKGROUND: The albumin-bilirubin (ALBI) score is a novel indicator of liver function. Some studies showed that the ALBI score was a predictive marker for the prognosis and efficacy of drug therapy in malignancies. We aimed to assess the predicted role of ALBI score in the sensitivity to therapy with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). The clinical data of 226 HER2-positive BC patients at the Harbin Medical University Cancer Hospital from January 2017 and December 2018 were retrospectively collected. The ALBI score was calculated with serum albumin and bilirubin before diagnosis. The associations between ALBI score and trastuzumab resistance were analyzed by logistic regression analyses. The patients with trastuzumab resistance had higher ALBI scores compared with the patients without trastuzumab resistance. Moreover, there were weak correlations between the ALBI score and lymph node status (P= 0.093). In addition, multivariate analysis revealed that the ALBI score was an independent prognostic factor for trastuzumab resistance in HER2-positive BC. High ALBI score is associated with trastuzumab resistance in HER2-positive BC. Future studies are needed.

Strong oxygen-content dependence of the magnetic excitations in antiferromagnetic NiO nanoparticles: A Raman probe.

Nanostructured antiferromagnetic (AFM) NiO has attracted much attention from both the fundamental and applied perspectives. Understanding the two-magnon (2 M) is of great significance in NiO applications such as spin valves and next-generation magnetic random access memories (MRAM). We investigated the phonon modes and antiferromagnetically ordered states of NiO nanoparticles prepared by empirically controlled measurements. An intensity enhancement of the 2 M mode was observed by Raman spectroscopy as the NiO nanoparticles were vacuum annealed at 650 ℃. The increased 2 M peak intensity in NiO nanoparticles is explained by the local symmetry conversions from NiO5 to NiO6 configurations due to the oxygen redistribution during the vacuum annealing. The change of the splitting of anisotropic transverse optical (TO) phonon with different oxygen contents was also revealed by the Raman spectroscopy. We have shown that the changes in the oxygen environment underlie both the change in the 2 M intensity and the splitting of TO phonon in the NiO nanoparticles. Our work offers an efficient avenue to strengthen the AFM ordering and emphasizes the effect of vacuum annealing of the NiO nanoparticles, opening the interesting possibility of individual parameter control in practical applications.

Physical activity alleviates negative effects of bedroom light pollution on blood pressure and hypertension in Chinese young adults.

Excessive exposure to light at night (LAN) has become a serious public health concern. However, little is known about the impact of indoor LAN exposure on blood pressure, particularly among young adults. We aimed to investigate the effects of bedroom individual-level LAN exposure in real-world environment on blood pressure and hypertension among vulnerable young adults, and to evaluate the possible buffering effect of physical activity. In this cross-sectional study, a total of 400 healthy young adults aged 16-22 years were included. Bedroom LAN exposure was recorded at 1-min intervals for two consecutive nights using a TES-1339 R illuminance meter. Blood pressure was measured three times (8-11 a.m. in the physical examination day) in the seated position using an Omron HEM-7121 digital sphygmomanometer. A wrist-worn triaxial accelerometer (ActiGraph GT3X-BT) was used to assess physical activity for seven consecutive days. Each 1 lx increase of bedroom LAN intensity was associated with 0.55 mmHg-increase in SBP (95% CI: 0.15, 0.95), 0.30 mmHg-increase in DBP (95% CI: 0.06, 0.54), and 0.38 mmHg-increase in MAP (95% CI: 0.12, 0.65). Higher levels of LAN exposure were associated with increased risk of hypertension (LAN ≥ 3lx vs. LAN < 3lx: OR = 3.30, 95%CI = 1.19-9.19; LAN ≥ 5lx vs. LAN < 5lx: OR = 3.87, 95%CI = 1.37-10.98). However, these detrimental effects of bedroom LAN exposure on blood pressure and hypertension were not observed among young adults with high MVPA (≥2 h/day) level. MVPA can alleviate negative effects of bedroom LAN exposure on blood pressure and hypertension. Maintaining bedroom settings darkness at night may be an important strategy for reducing the risk of hypertension. Furthermore, for individuals living with high levels of indoor LAN exposure, regular physical activity may be a good option for preventing cardiovascular disease and hypertension.

Structure-Based Discovery of Novel NH2-Biphenyl-Diarylpyrimidines as Potent Non-Nucleoside Reverse Transcriptase Inhibitors with Significantly Improved Safety: From NH2-Naphthyl-Diarylpyrimidine to NH2-Biphenyl-Diarylpyrimidine.

Results from recently completed studies suggested that the NH2-naphthyl-diarylpyrimidine JX-7 displayed remarkable inhibitory activity against wild-type HIV-1 (EC50 = 5 nM) and numerous clinically observed variants in MT-4 cells; however, its high cytotoxicity (CC50 = 19 µM) precluded its further development as a clinical candidate. One approach we took to improve the safety involved replacing the naphthyl of JX-7 with biphenyl to provide a series of novel NH2-biphenyl-DAPYs. Investigation of the structure-activity relationships (SARs) led to the identification of 4ab, a potent NNRTI with significantly reduced cytotoxicity (CC50 = 120 µM), approximately 6-fold lower than JX-7, which maintained remarkable anti-HIV-1 activity against wild-type HIV-1 (EC50 = 1.9 nM) and multiple mutant strains simultaneously. Also, 4ab displayed weak CYP sensitivity, little inhibition of hERG, and no apparent in vivo acute toxicity. These promising results demonstrate that 4ab can be used as a drug candidate for HIV-1 therapy.

Preoperative Pectoralis Muscle Index Predicts Distant Metastasis-Free Survival in Breast Cancer Patients.

Background: Breast cancer is one of the most commonly diagnosed cancers, and the fourth leading cause of cancer deaths in females worldwide. Sarcopenia is related to adverse clinical outcomes in patients with malignancies. Muscle index is a key parameter in evaluating sarcopenia. However, there is no data investigating the association between muscle index and distant metastasis in breast cancer. The aim of this study was to explore whether muscle index can effectively predict distant metastasis and death outcomes in breast cancer patients. Study Design: The clinical data of 493 breast cancer patients at the Harbin Medical University Cancer Hospital between January 2014 and December 2015 were retrospectively analyzed. Quantitative measurements of pectoralis muscle area and skeletal muscle area were performed at the level of the fourth thoracic vertebra (T4) and the eleventh thoracic vertebra (T11) of the chest computed tomography image, respectively. The pectoralis muscle index (PMI) and skeletal muscle index (SMI) were assessed by the normalized muscle area (area/the square of height). Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. Result: The patients with metastases had lower PMI at T4 level (PMI/T4) and SMI at T11 level (SMI/T11) compared with the patients without metastases. Moreover, there were significant correlations between PMI/T4 and lymphovascular invasion, Ki67 expression, multifocal disease, and molecular subtype. In addition, multivariate analysis revealed that PMI/T4, not SMI/T11, was an independent prognostic factor for distant metastasis-free survival (DMFS) and overall survival (OS) in breast cancer patients. Conclusions: Low PMI/T4 is associated with worse DMFS and OS in breast cancer patients. Future prospective studies are needed.

Two-dimensional correlation spectroscopy analysis of Raman spectra of NiO nanoparticles.

We report two-dimensional correlation spectroscopy (2D-COS) analyses of the Raman spectra of NiO nanoparticles over a temperature range from 100 to 300 K. 2D-Raman correlation spectra suggest strong correlation of the phonon spectral intensity variation with the magnetic ordering in NiO nanoparticles. It is revealed that the antiferromagnetic ordering affects the TO phonon anisotropy in NiO nanoparticles. We elucidate the complex spectral features of two-magnon (2 M) bands by performing appropriate 2D-COS model simulations. Significant spin-phonon coupling in NiO nanoparticles is supported by our results. High energy magnon-magnon interaction tails are also found to be involved in the spin-phonon coupling. 2D-COS analyses provide rich information regarding the nature of the phonon and magnon excitations of NiO nanoparticles.

Deficiency of IKKα in Macrophages Mitigates Fibrosis Progression in the Kidney after Renal Ischemia-Reperfusion Injury.

Aims. Acute kidney injury (AKI) can lead to chronic kidney disease (CKD), and macrophages play a key role in this process. The aim of this study was to discover the role of IκB kinase α (IKKα) in macrophages in the process of AKI-to-CKD transition. Main Methods. We crossed lyz2-Cre mice with IKKα-floxed mice to generate mice with IKKα ablation in macrophages (Mac IKKα-/-). A mouse renal ischemia/reperfusion injury (IRI) model was induced by clamping the renal artery for 45 minutes. Treated mice were evaluated for blood biochemistry, tissue histopathology, and fibrosis markers. Macrophages were isolated from the peritoneal cavity for coculturing with tubular epithelial cells (TECs) and flow cytometry analysis. Key Findings. We found that fibrosis and kidney function loss after IRI were significantly alleviated in Mac IKKα-/- mice compared with wild-type (WT) mice. The expression of fibrosis markers and the infiltration of M2 macrophages were decreased in the kidneys of Mac IKKα-/- mice after IRI. The in vitro experiment showed that the IRI TECs cocultured with IKKα-/- macrophages (KO MΦs) downregulated the fibrosis markers accompanied by a downregulation of Wnt/ß-catenin signaling. Significance. These data support the hypothesis that IKKα is involved in mediating macrophage polarization and increasing the expression of fibrosis-promoting inflammatory factors in macrophages. Therefore, knockdown of IKKα in macrophages may be a potential method that can be used to alleviate the AKI-to-CKD transition after IRI.

Significant difference of c-type lectin-like receptor 2 between colorectal cancer and polyp subgroups.

BACKGROUND: Platelets play a key role in tumor progression and metastasis. C-type lectin-like receptor 2 (CLEC-2) is the receptor expressed on platelets and the marker of platelet activation. OBJECTIVE: This study aims to determine whether soluble CLEC-2 levels differ between patients with benign colorectal polyps and those with colorectal cancer (CRC). METHODS: We measured plasma soluble CLEC-2 by enzyme-linked immunosorbent assay in 150 patients with colorectal polyps, 150 CRC patients without metastasis, 150 CRC liver metastasis, and 150 control subjects. RESULTS: The CRC patients had higher soluble CLEC-2 levels than patients with colorectal polyps (p< 0.001). Moreover, CRC patients with liver metastases displayed higher CLEC-2 levels than those in CRC patients without metastases (p< 0.001). In the CRC patients, CLEC-2 levels were correlated with lymph node metastasis and advanced stage. In the patients with polyps, there was a significant difference in CLEC-2 levels among patients with hyperplastic polyp, sessile serrated adenoma, and traditional serrated adenoma (p< 0.001). The ROC curve analysis revealed CLEC-2 had an optimal sensitivity of 77.3% and specificity of 94.6% for the screening of CRC, and sensitivity of 71.0% and specificity of 76.7% for the differential diagnosis of colorectal polyps and CRC. CONCLUSIONS: CRC patients have higher CLEC-2 levels than patients with colorectal polyps and healthy controls. Moreover, there is a significant difference in CLEC-2 levels among polyp subtypes. Further research is warranted.