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Abstract 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.

Abstract Background Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. Methods This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. Results The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p

BackgroundSystemic 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.MethodsWe 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.ResultsThe 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.ConclusionElevated 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.

Abstract Background As a transmembrane protein, C-type lectin-like receptor 2 (CLEC-2) is mainly expressed on platelets and released into plasma after platelet activation. Activated platelets participate in the regulation of innate immune cells. Patients with different microsatellite statuses have distinct immune profiles. This study aimed to investigate the association of plasma CLEC-2 levels with microsatellite status among colorectal cancer (CRC) patients. Methods A cross-sectional analysis of 430 CRC patients from Harbin Medical University Cancer Hospital was conducted. CLEC-2 levels were measured with fasting venous blood samples drawn from each participant before any treatment. The microsatellite status was evaluated with DNA obtained from fresh frozen tumor tissue samples. The other clinical data were collected and recorded based on the medical system records. Results CLEC-2 levels were significantly higher among patients with high microsatellite instability phenotype than the stable microsatellite group, adjusting for other confounding variables. Conclusions The increased CLEC-2 is associated with the high microsatellite instability subtype of CRC.

Abstract 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.

Abstract 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

Abstract 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.

Abstract Background Type 2 diabetes mellitus (T2DM) increased the risk of developing pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease originating from the pancreas. Increasing evidence indicates that platelets activation plays a prominent role in tumor and T2DM. Mean platelet volume (MPV) is an indicator of activated platelets and is altered in several cancers. The current study aimed to evaluate the prognostic role of MPV in resectable PDAC patients with T2DM. Methods Eight hundred and three patients with PDAC were included in this retrospective study. We determined the optimal cutoff value of MPV for 5-year overall survival (OS) using the receiver operating characteristic (ROC) method. The associations between MPV levels and clinical characteristics were analyzed. Kaplan-Meier survival analysis and Cox’s proportional hazard regression model were used to evaluate the prognostic value of MPV for OS. Results Compared to the PDAC patients without T2DM, MPV levels were significantly higher in the PDAC patients with T2DM. Moreover, MPV was significantly associated with the differentiation between T2DM and non-T2DM. In addition, Kaplan-Meier analysis found that patients with low MPV levels had a poorer 5-year OS than patients with high MPV levels in diabetic patients. Multivariate analyses revealed that MPV was an independent prognostic factor for OS in patients with T2DM. However, the independent prognostic role of MPV was not observed in patients without T2DM. Conclusion MPV independently predicts poor survival in PDAC patients with T2DM. Prospective studies are required to confirm the role of MPV in PDAC.

BackgroundBreast 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 DesignThe 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.ResultThe 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.ConclusionsLow PMI/T4 is associated with worse DMFS and OS in breast cancer patients. Future prospective studies are needed.

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. [ABSTRACT FROM AUTHOR]

Background. Elevated platelet volume is the risk factor for the development and poor overall survival of colorectal cancer (CRC) patients. Both microsatellite status and platelet glycoprotein Ibα (GPIbα) are related to platelet volume in CRC patients. This study aimed to investigate platelet GPIbα ectodomain (termed glycocalicin) levels among CRC patients and the association between the glycocalicin levels and microsatellite status in CRC. Methods. The clinical and laboratory data of 430 CRC patients between January 2018 and December 2018 in Harbin Medical University Cancer Hospital were collected. The microsatellite status was determined with a polymerase chain reaction. The participants were separated into high microsatellite instability (MSI-H) and microsatellite stable (MSS) groups according to microsatellite status. The glycocalicin levels were measured with an enzyme-linked immunosorbent assay, and the cut-off point was determined with the receiver-operating characteristics curve. The clinical and pathological characteristics were collected via electronic medical records. Logistic regression was used to explore the association between glycocalicin and microsatellite status. Results. Among the 430 CRC patients enrolled, 64 patients (14.9%) were identified as MSI-H and others as MSS CRC. Glycocalicin levels were significantly reduced in patients with MSI-H than those with MSS. After controlling for potential confounders, logistic regression analysis revealed that glycocalicin levels were independently associated with MSI-H CRC. Conclusions. Reduced glycocalicin levels are associated with the MSI-H subtype of CRC. Further research is needed to elucidate the mechanisms of the association between glycocalicin and MSI-H in CRC patients.

Research on clinical data sets of Alzheimer’s disease can predict and develop early intervention treatment. Missing data is a common problem in medical research. Failure to deal with more missing data will reduce the efficiency of the test, resulting in information loss and result bias. To address these issues, this paper designs and implements the missing data interpolation method of mixed interpolation according to columns by combining the four methods of mean interpolation, regression interpolation, support vector machine (SVM) interpolation, and multiple interpolation. By comparing the effects of the mixed interpolation method with the above four interpolation methods and giving the comparison results, the experiment shows that the results of the mixed interpolation method under different data missing rates have better performance in terms of root mean square error (RMSE), mean absolute error (MSE), and error rate, which proves the effectiveness of the interpolation mechanism. The characteristics of different variables might lead to different interpolation strategy choices, and column-by-column mixed interpolation can dynamically select the best method according to the difference of features. To a certain extent, it selects the best method suitable for each feature and improves the interpolation effect of the data set as a whole, which is beneficial to the clinical study of Alzheimer’s disease. In addition, in the processing of missing data, a combination of deletion method and interpolation method is adopted with reference to expert knowledge. Compared with the direct interpolation method, the data set obtained by this method is more accurate.

Abstract Altered mean platelet volume (MPV) is found in several malignancies. Remarkably, there is little consensus on using the value of MPV in the prognostic evaluations of renal cell carcinoma (RCC). The aim of this study is to examine the feasibility of MPV value as a prognostic indicator of RCC. The retrospective study recruited 306 consecutive RCC patients between January 2009 and December 2009. The relationships between MPV and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of MPV. Of the 306 RCC patients, low MPV levels were detected in 61 (19.9%) patients. Reduced MPV was associated with histology types, T classification, UCLA Integrated Scoring System (UISS) category, and Mayo clinic stage, size, grade, and necrosis score (SSIGN) category (P

Abstract Activated platelets promote cancer progression and metastasis. Nevertheless, the prognostic value of platelet indices in melanoma had been rarely reported. The aim of this study was to investigate the predictive significance of platelet indices in melanoma. A total of 220 consecutive patients with melanoma were retrospectively enrolled between January 2009 and December 2009. The relationship between PDW and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of PDW. Of the 220 patients, high platelet distribution width (PDW) levels were observed in 63 (28.6%) patients. Increased PDW was associated with tumor subtype (P

Abstract Platelets play a multifaceted role in cancer progression and metastasis. Mean platelet volume (MPV) and platelet distribution width (PDW) are commonly used platelet parameters from routine blood test. The aim of the present study was to investigate the correlation between platelet indices and prognosis in patients with non-small cell lung cancer (NSCLC). A total of 270 patients who were diagnosed with NSCLC between January 2009 and December 2009 were retrospectively analyzed. Patients’ characteristics and hematologic tests data at initial diagnosis were collected. The overall survival rate was estimated using Kaplan-Meier method. The prognostic analysis was carried out with univariate and multivariate Cox regressions model. Reduced PDW was significantly correlated with T stage, N stage, TNM stage, and histological type of the disease. Moreover, survival analysis showed that the overall survival of patients with PDW ≥ 16.3% was significantly longer than that of those with PDW

The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance are blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism.

Objective: Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation – including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined. Methods: In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP neurons which express LepRs for patch-clamp electrophysiology experiments. Results: We found that leptin and adiponectin synergistically activated melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were inhibited in response to adiponectin. The adiponectin-induced depolarization of arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K) signaling, independent of 5′ AMP-activated protein kinase (AMPK) activity. Adiponectin also activated melanocortin neurons at various physiological glucose levels. Conclusions: Our results demonstrate a requirement for PI3K signaling in the acute adiponectin-induced effects on the cellular activity of arcuate melanocortin neurons. Moreover, these data provide evidence for PI3K as a substrate for both leptin and adiponectin to regulate energy balance and glucose metabolism via melanocortin activity. Author Video: Author Video Watch what authors say about their articles Keywords: Melanocortin, Obesity, Diabetes, Energy balance, Patch-clamp, Electrophysiology

Aims. Liver metastases occur in approximately 25% of colorectal cancer (CRC) patients and cause more than 90% of deaths in CRC. Platelets play a crucial role in cancer progression and metastases. We aimed to investigate the relationship between platelet indices and CRC with synchronous liver metastases. Methods. We conducted a retrospective clinical study including 206 CRC patients without metastases and 200 CRC patients with synchronous liver metastases from January 1, 2015, to December 31, 2017. Data of the patients’ clinicopathological characteristics were collected. Results. Platelet distribution width (PDW) was decreased in CRC patients with liver metastases compared with CRC patients without liver metastases. In addition, the prevalence of liver metastases reduced as PDW quartiles increased. After adjusting for other risk factors, the odds ratios (95% confidence intervals) for CRC liver metastases according to PDW quartiles were 1.000, 0.289 (0.156-0.535), 0.482 (0.271-0.860), and 0.190 (0.101-0.358). Conclusions. Compared with CRC patients without metastases, PDW is reduced in CRC patients with liver metastases. Moreover, PDW was independently associated with the presence of CRC liver metastases.

Background: To compare the clinicopathological features and prognosis between younger and aged patients with hepatocellular carcinoma (HCC). Methods: We analyzed the outcome of 451 HCC patients underwent liver resection, transcatheter arterial chemoembolization and radiofrequency ablation, respectively. Then risk factors for aged and younger patients′ survival were evaluated by multivariate analysis, respectively. Results: The patients who were older than 55 years old were defined as the older group. The overall survival for aged patients was significantly worse than those younger patients. The younger patients had similar liver functional reserve but more aggressive tumor factors than aged patients. Cox regression analysis showed that the elevated levels of aspartate aminotransferase (AST) (Wald χ2 = 3.963, P = 0.047, hazard ratio [HR] =1.453, 95% confidence interval [CI]: 1.006-2.098), lower albumin (Wald χ2 = 12.213, P < 0.001, HR = 1.982, 95% CI: 1.351-2.910), tumor size (Wald χ2 = 8.179, P = 0.004, HR = 1.841, 95% CI: 1.212-2.797), and higher alpha-fetoprotein level (Wald χ2 = 4.044, P = 0.044, HR = 1.465, 95% CI: 1.010-2.126) were independent prognostic factors for aged patients, while only elevated levels of AST (Wald χ2 = 14.491, P < 0.001, HR = 2.285, 95% CI: 1.493-3.496) and tumor size (Wald χ2 = 21.662, P < 0.001, HR = 2.928, 95% CI: 1.863-4.604) were independent prognostic factors for younger patients. Conclusions: Age is a risk factor to determine the prognosis of patients with HCC. Aged patients who have good liver functional reserve are still encouraged to receive curative therapy.

Whether neuronal inositol-requiring enzyme 1 (Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin (Pomc)-specific deficiency of Ire1α accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as "beiging" of white adipose tissue. We also demonstrate that loss of Ire1α in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion of Ire1α in Pomc neurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposed Pomc neurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions that Ire1α-Xbp1s and associated molecular targets link ER stress in arcuate Pomc neurons to aspects of normal energy and glucose homeostasis. [ABSTRACT FROM AUTHOR]

We present the case of a 66-year-old woman with a huge gastrointestinal stromal tumor of the stomach that traversed her upper abdomen. The predominant abdominal sign was a huge, palpable mass, but there were no other distinctive findings in her physical examination or her routine blood workup, including biochemical markers. It was difficult to judge the origin of the mass upon imaging. Furthermore, radiological findings revealed that the mass had a complex relationship with many major blood vessels. An exploratory laparotomy revealed a huge tumor protruding from the anterior wall of the stomach fundus, on the lesser curvature of the stomach, measuring approximately 21 × 34 × 11 cm in diameter and weighing 5.5 kg. A complete resection was performed and the tumor was characterized on immunohistochemistry as a gastrointestinal stromal tumor of the stomach. Preoperative diagnosis of gastrointestinal stromal tumors can be difficult, and we hope that the presentation of this rare case and literature review will benefit other diagnosing clinicians having similar problems. [ABSTRACT FROM AUTHOR]

AbstractAim:To investigate the effects of small interfering RNA (siRNA) knockdown of forkhead box M1 (FoxM1) on the proliferation and invasion capacities of human hepatocellular carcinoma MHCC-97H cells in vitro.Methods:The expression levels of FoxM1 in human hepatocellular carcinoma samples, adjacent non-hepatocellular carcinoma liver samples and MHCC-97 cell lines were detected by RT-PCR and Western blotting. FoxM1 siRNA was transfected into MHCC-97H cells with Lipofectamine 2000. Cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle analysis was performed by flow cytometry. Protein expression levels were evaluated by Western blotting. Anchorage-independent growth and the invasive potency of MHCC-97H cells were measured by soft agar colony formation and a transwell cell invasion assay, respectively.Results:FoxM1 was over-expressed in hepatocellular carcinoma samples compared to adjacent non-hepatocellular carcinoma liver samples. FoxM1 siRNA was successfully transfected into MHCC-97H cells, resulting in the significant inhibition of FoxM1 mRNA and protein expression. Down-regulation of FoxM1 inhibited cell proliferation, caused cell cycle arrest, and decreased invasion of MHCC-97H cells. Compared with control and mock groups, the FoxM1 siRNA transfected cells showed decreased protein expressions of cyclin B1 and cyclin D1, whereas p27 protein expression was increased. Down-regulation of FoxM1 reduced the expression of matrix metalloproteinase-2 (MMP-2) and urokinase plasminogen activator (uPA).Conclusion:FoxM1 is functionally involved in hepatocellular carcinoma cell proliferation and invasion and is a potential target for hepatocellular carcinoma therapy. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation is related to disease progression in asthma. The brachialankle pulse wave velocity (baPWV) is a marker for early atherosclerotic changes. The aim of this study is to evaluate the baPWV levels in patients with stable and severe asthma. Methods: We examined baPWV, high sensitivity C-reactive protein (CRP), lung function parameters, and arterial blood gas analysis in patients with asthma and control subjects. 85 stable asthma patients and 85 severe asthmatics were investigated. 85 control subjects matched for age, gender, body mass index (BMI) and smoking status were recruited. Results: The patients with severe asthma had increased baPWV and CRP compared with the patients with stable asthma and control subjects. Furthermore, baPWV was elevated in stable asthma compared with control subjects. There was a negative correlation between baPWV and forced expiratory volume in 1 s (FEV1), after adjusting age, gender, BMI and smoking status (r = -0.414, p < 0.001). Similarly, baPWV was negatively correlated with FEV1/forced vital capacity (FVC) (r = -0.431, p < 0.001). Although there was no correlation between CRP and baPWV in patients with stable asthma, CRP was positively correlated with baPWV in patients with severe asthma (r = 0.229, p = 0.039). Conclusions: baPWV tends to increase as pathogenic condition aggravated in asthma. In addition, elevated baPWV correlates with impaired lung function. Our observation suggests that baPWV is useful for early detection of subclinical atherosclerosis in asthma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. Methods: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. Results: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. Conclusion: RDW is associated with sarcopenia risk in early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Rui-Tao Wang, Yang Zhao, An-Lei Wang, Yu-Ting Wang, Zhong-Ping Yin, Kai Chen Department of Oncology, Tianjin Fourth Central Hospital, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Kai ChenDepartment of Oncology, Tianjin Fourth Central Hospital, Tianjin, 300060, People’s Republic of ChinaTel +86 22-2624-9182Email chenkai5103@sina.comBackground: Present study was condeucted to investigate the efficacy and safety of regorafenib for patients with previously treated metastatic colorectal cancer (mCRC) in a Chinese population and the prognostic implications of adverse reactions.Methods: This retrospective study a total of 96 consecutive patients with mCRC who had failed standard chemotherapy regimens from June 2017 to December 2020. Patients received regorafenib at an initial dosage of 160 mg or 120 mg. The primary end point was progression-free survival (PFS), and secondary end points objective response rate (ORR), disease-control rate (DCR), overall survival (OS), safety, and associations between prognosis and adverse-reaction status.Results: There were three patients with partial response, 49 with stable disease, and 44 with progressive disease. Consequently, the ORR and DCR of the 96 patients were 3.1% (95% CI 0.6%– 8.9%) and 54.2% (95% CI 43.7– 64.4%), respectively. Prognosis results showed that median PFS of the 96 patients was 2.5 (95% CI 1.98– 3.02) months and median OS 9.8 (95% CI 7.02– 12.59) months. Additionally, the most frequent adverse reactions during regorafenib treatment were hand–foot syndrome (HFS; 52.1%), hypertension (38.5%), and fatigue (33.3%). Interestingly, the relevance of prognosis to adverse-reaction status exhibited that median PFS of patients with HFS and patients without HFS was 3.3 months and 2.0 months, respectively (P=0.013). Similarly, median PFS of patients with hypertension and without hypertension was 3.6 months and 2.2 months, respectively (P=0.023).Conclusion: Potential clinical benefit of regorafenib monotherapy was observed for patients with mCRC who had failed standard chemotherapy regimens. Hypertension and HFS induced by regorafenib therapy could be used as valuable biomarkers to predict the prognosis of regorafenib.Keywords: colorectal cancer, regorafenib, efficacy, safety, biomarker

Background: As a transmembrane protein, C-type lectin-like receptor 2 (CLEC-2) is mainly expressed on platelets and released into plasma after platelet activation. Activated platelets participate in the regulation of innate immune cells. Patients with different microsatellite statuses have distinct immune profiles. This study aimed to investigate the association of plasma CLEC-2 levels with microsatellite status among colorectal cancer (CRC) patients.Methods: A cross-sectional analysis of 430 CRC patients from Harbin Medical University Cancer Hospital was conducted. CLEC-2 levels were measured with fasting venous blood samples drawn from each participant before any treatment. The microsatellite status was evaluated with DNA obtained from fresh frozen tumor tissue samples. The other clinical data were collected and recorded based on the medical system records.Results: CLEC-2 levels were significantly higher among patients with high microsatellite instability phenotype than the stable microsatellite group, adjusting for other confounding variables.Conclusions: The increased CLEC-2 is associated with the high microsatellite instability subtype of CRC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Elevated platelet volume is the risk factor for the development and poor overall survival of colorectal cancer (CRC) patients. Both microsatellite status and platelet glycoprotein Ibα (GPIbα) are related to platelet volume in CRC patients. This study aimed to investigate platelet GPIbα ectodomain (termed glycocalicin) levels among CRC patients and the association between the glycocalicin levels and microsatellite status in CRC. Methods. The clinical and laboratory data of 430 CRC patients between January 2018 and December 2018 in Harbin Medical University Cancer Hospital were collected. The microsatellite status was determined with a polymerase chain reaction. The participants were separated into high microsatellite instability (MSI-H) and microsatellite stable (MSS) groups according to microsatellite status. The glycocalicin levels were measured with an enzyme-linked immunosorbent assay, and the cut-off point was determined with the receiver-operating characteristics curve. The clinical and pathological characteristics were collected via electronic medical records. Logistic regression was used to explore the association between glycocalicin and microsatellite status. Results. Among the 430 CRC patients enrolled, 64 patients (14.9%) were identified as MSI-H and others as MSS CRC. Glycocalicin levels were significantly reduced in patients with MSI-H than those with MSS. After controlling for potential confounders, logistic regression analysis revealed that glycocalicin levels were independently associated with MSI-H CRC. Conclusions. Reduced glycocalicin levels are associated with the MSI-H subtype of CRC. Further research is needed to elucidate the mechanisms of the association between glycocalicin and MSI-H in CRC patients. [ABSTRACT FROM AUTHOR]

Research on clinical data sets of Alzheimer's disease can predict and develop early intervention treatment. Missing data is a common problem in medical research. Failure to deal with more missing data will reduce the efficiency of the test, resulting in information loss and result bias. To address these issues, this paper designs and implements the missing data interpolation method of mixed interpolation according to columns by combining the four methods of mean interpolation, regression interpolation, support vector machine (SVM) interpolation, and multiple interpolation. By comparing the effects of the mixed interpolation method with the above four interpolation methods and giving the comparison results, the experiment shows that the results of the mixed interpolation method under different data missing rates have better performance in terms of root mean square error (RMSE), mean absolute error (MSE), and error rate, which proves the effectiveness of the interpolation mechanism. The characteristics of different variables might lead to different interpolation strategy choices, and column-by-column mixed interpolation can dynamically select the best method according to the difference of features. To a certain extent, it selects the best method suitable for each feature and improves the interpolation effect of the data set as a whole, which is beneficial to the clinical study of Alzheimer's disease. In addition, in the processing of missing data, a combination of deletion method and interpolation method is adopted with reference to expert knowledge. Compared with the direct interpolation method, the data set obtained by this method is more accurate. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) increased the risk of developing pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease originating from the pancreas. Increasing evidence indicates that platelets activation plays a prominent role in tumor and T2DM. Mean platelet volume (MPV) is an indicator of activated platelets and is altered in several cancers. The current study aimed to evaluate the prognostic role of MPV in resectable PDAC patients with T2DM.Methods: Eight hundred and three patients with PDAC were included in this retrospective study. We determined the optimal cutoff value of MPV for 5-year overall survival (OS) using the receiver operating characteristic (ROC) method. The associations between MPV levels and clinical characteristics were analyzed. Kaplan-Meier survival analysis and Cox's proportional hazard regression model were used to evaluate the prognostic value of MPV for OS.Results: Compared to the PDAC patients without T2DM, MPV levels were significantly higher in the PDAC patients with T2DM. Moreover, MPV was significantly associated with the differentiation between T2DM and non-T2DM. In addition, Kaplan-Meier analysis found that patients with low MPV levels had a poorer 5-year OS than patients with high MPV levels in diabetic patients. Multivariate analyses revealed that MPV was an independent prognostic factor for OS in patients with T2DM. However, the independent prognostic role of MPV was not observed in patients without T2DM.Conclusion: MPV independently predicts poor survival in PDAC patients with T2DM. Prospective studies are required to confirm the role of MPV in PDAC. [ABSTRACT FROM AUTHOR]